initial commit

.gitignore

@@ -0,0 +1,5 @@
+data/
+resources.txt
+*.pdf
+__pycache__/
+.env

README.md

@@ -1,11 +1,12 @@
 ---
-title: Y2clutch
-emoji: 🔥
-colorFrom: red
-colorTo: red
+title: Brainandbehaviour
+emoji: 💩
+colorFrom: purple
+colorTo: yellow
 sdk: gradio
 sdk_version: 3.24.1
 app_file: app.py
+python_version: 3.9.1
 pinned: false
 ---
 

app.py

@@ -0,0 +1,251 @@
+from langchain import OpenAI, LLMChain, PromptTemplate
+from langchain.chat_models import ChatOpenAI
+from langchain.chains.qa_with_sources import load_qa_with_sources_chain
+from langchain.vectorstores import Chroma
+from langchain.chains import ConversationalRetrievalChain
+from langchain.embeddings.openai import OpenAIEmbeddings
+from langchain.chains.conversational_retrieval.prompts import CONDENSE_QUESTION_PROMPT
+
+from prompts import VANILLA_PROMPT
+
+import os
+
+import gradio as gr
+
+
+class Chatbot():
+
+    def __init__(
+            self,
+    ):
+        
+        self.models = ['gpt3', 'gpt4']
+
+        # vectorstore
+        self.vectorstore = Chroma(persist_directory='./chroma', embedding_function=OpenAIEmbeddings())
+        self.vectordbkwargs = {"search_distance": 0.9, 'k' : 4}
+        self.modules = list(set([d['module'] for d in self.vectorstore._collection.get(include=['metadatas'])['metadatas']]))
+        print(f"Found modules: {self.modules}")
+
+
+    """ Initialise bots """
+    def _get_llm(self, model):
+        assert model in self.models
+
+        if model == 'gpt3':
+            return OpenAI()
+        
+        if model == 'gpt4':
+            return ChatOpenAI(model='gpt-4')
+
+
+    def _initialise_augmented_chatbot(self, model):
+
+        #doc_chain = load_qa_with_sources_chain(self._get_llm(model), chain_type="map_reduce")
+        #question_generator = LLMChain(llm=self._get_llm(model), prompt=CONDENSE_QUESTION_PROMPT)
+
+        chain = ConversationalRetrievalChain.from_llm(
+            self._get_llm(model),
+            retriever=self.vectorstore.as_retriever(),
+            #combine_docs_chain=doc_chain,
+            #question_generator=question_generator,
+            return_source_documents=True
+            )
+            
+        return chain
+    
+    def _initialise_vanilla_chatbot(self, model):
+        # vanilla gpt
+        template = VANILLA_PROMPT
+        prompt = PromptTemplate(template=template, input_variables=["human_input", "history"])
+        chain = LLMChain(llm=self._get_llm(model), prompt=prompt)
+
+        return chain
+
+
+    """ Format """
+
+    def _format_chat_history(self, history):
+        res = []
+        for human, ai in history:
+            res.append(f"Human:{human}\nAI:{ai}")
+        return "\n".join(res)
+
+    def _format_search_source_documents(self, documents):
+        # add page if none
+        for d in documents:
+            try:
+                d.metadata['page']
+            except:
+                d.metadata['page'] = ''
+
+        output = ' '.join([
+            f'SOURCE {i}\n' + d.page_content + '\n\nSource: ' + d.metadata['source'] + '\nPage: ' + str(d.metadata['page']) + '\n\n\n'
+            for i, d in enumerate(documents)
+        ])
+
+        return output
+    
+    def _format_chat_source_docments(self, documents):
+        # add page if none
+        for d in documents:
+            try:
+                d.metadata['page']
+            except:
+                d.metadata['page'] = 0
+
+
+        # get unique sources
+        unique_sources = list(set([d.metadata['source'] for d in documents]))
+        # get unique pages for each source
+        unique_dict = {s : list(set([d.metadata['page'] for d in documents if d.metadata['source'] == s])) for s in unique_sources}
+
+        output = '\n'.join([
+            f"{k}, pages: " + ', '.join([str(i) for i in v])
+            for k, v in unique_dict.items()
+        ])
+
+        return '\n\n' + 'SOURCES:\n' + output
+
+
+    """ Main Functions """
+    def search(
+            self,
+            inp,
+            history,
+            module,
+    ):
+        history = history or []
+
+        output_raw = self.vectorstore.similarity_search(inp, filter=dict(module=module), k=4)
+        output = self._format_search_source_documents(output_raw)
+
+        history.append((inp, output))
+
+        return history, history
+
+    def chat(
+            self,
+            inp: str,
+            history,
+            module,
+            model,
+        ):
+
+        """Method for integration with gradio Chatbot"""
+        if model == None:
+            model = 'gpt4'
+
+        history = history or []
+        
+        chain = self._initialise_augmented_chatbot(model=model)
+        output_raw = chain(
+            {
+                "question": inp,
+                "chat_history": history,
+                "vectordbkwargs":
+                self.vectordbkwargs | {"filter" : {"module" : module}}
+            }
+        )
+
+        output = output_raw["answer"] + self._format_chat_source_docments(output_raw["source_documents"])
+
+        history.append((inp, output))
+        
+        return history, history#, ""
+    
+    def chat_vanilla(
+            self,
+            inp: str,
+            history,
+            model,
+    ):
+        """ Vanilla GPT 4"""
+
+        if model == None:
+            model = 'gpt4'
+
+        history = history or []
+
+        chain = self._initialise_vanilla_chatbot(model=model)
+        history_formatted = self._format_chat_history(history)
+        output = chain({"human_input": inp, "history": history_formatted})['text']
+
+        history.append((inp, output))
+
+        return history, history
+
+
+    """ Interface """
+    def launch_app(self):
+
+        block = gr.Blocks(css=".gradio-container {background-color: lightgray}")
+
+        with block:
+            
+            with gr.Row():
+                gr.Markdown("<h3><center>y2clutch</center></h3>")
+
+
+            with gr.Tab("Augmented GPT"):
+                
+
+                with gr.Row():
+                    chatbot = gr.Chatbot()
+
+                
+                with gr.Row():
+                    message = gr.Textbox(
+                        lines=1,
+                    )
+                    submit = gr.Button(value="Send", variant="secondary").style(full_width=False)
+                    
+                state = gr.State()
+                module = gr.Dropdown(self.modules, label="Select a module *Required*")
+                model = gr.Dropdown(self.models, label="Select a model *Required*")
+
+                submit.click(self.chat, inputs=[message, state, module, model], outputs=[chatbot, state])
+                message.submit(self.chat, inputs=[message, state, module, model], outputs=[chatbot, state])
+                
+            
+            with gr.Tab("Search"):
+
+                with gr.Row():
+                    search = gr.Chatbot()
+
+                with gr.Row():
+                    message = gr.Textbox(
+                        lines=1,
+                    )
+                    submit = gr.Button(value="Send", variant="secondary").style(full_width=False)
+
+                search_state = gr.State()
+                module = gr.Dropdown(self.modules, label="Select a module *Required*")
+
+                submit.click(self.search, inputs=[message, search_state, module], outputs=[search, search_state])
+                message.submit(self.search, inputs=[message, search_state, module], outputs=[search, search_state])
+
+
+            with gr.Tab("Vanilla GPT"):
+
+                with gr.Row():
+                    vanilla_chatbot = gr.Chatbot()
+
+                with gr.Row():
+                    message = gr.Textbox(
+                        lines=1,
+                    )
+                    submit = gr.Button(value="Send", variant="secondary").style(full_width=False)
+
+                vanilla_state = gr.State()
+                model = gr.Dropdown(self.models, label="Select a model *Required*")
+
+                submit.click(self.chat_vanilla, inputs=[message, vanilla_state, model], outputs=[vanilla_chatbot, vanilla_state])
+                message.submit(self.chat_vanilla, inputs=[message, vanilla_state, model], outputs=[vanilla_chatbot, vanilla_state])
+
+
+        block.launch(debug=True, share=False)
+        
+
+if __name__ == '__main__':
+    Chatbot().launch_app()

chroma/chroma-collections.parquet

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chroma/chroma-embeddings.parquet

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chroma/index/id_to_uuid_48820301-4b52-46b2-8746-e343bf602b95.pkl

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chroma/index/index_48820301-4b52-46b2-8746-e343bf602b95.bin

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chroma/index/index_metadata_48820301-4b52-46b2-8746-e343bf602b95.pkl

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chroma/index/uuid_to_id_48820301-4b52-46b2-8746-e343bf602b95.pkl

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+size 2828

ingest.py

@@ -0,0 +1,87 @@
+import argparse
+
+import os
+
+from langchain.document_loaders import PyPDFLoader
+from langchain.text_splitter import CharacterTextSplitter
+from langchain.embeddings.openai import OpenAIEmbeddings
+from langchain.vectorstores import Chroma
+from langchain.schema import Document
+
+
+
+# parse arguments
+parser = argparse.ArgumentParser()
+parser.add_argument("folder", help="The folder to be ingested", type=str)
+parser.add_argument("--chunk_size", help="Chunk size", type=int, default=1500)
+parser.add_argument('--chunk_overlap', help='Chunk overlap', type=int, default=400)
+parser.add_argument('--separator', help='Separator', type=str, default='\n')
+
+args = parser.parse_args()
+
+FOLDER = args.folder
+CHUNK_SIZE = args.chunk_size
+CHUNK_OVERLAP = args.chunk_overlap
+SEPARATOR = args.separator
+
+
+class Ingest():
+
+    def __init__(
+            self,
+            folder,
+            chunk_size,
+            separator,
+            chunk_overlap,
+    ):
+        self.folder = folder
+        self.chunk_size = chunk_size
+
+        self.data_path = os.path.join('./data', self.folder)
+
+        self.splitter = CharacterTextSplitter(        
+            separator = separator,
+            chunk_size = chunk_size,
+            chunk_overlap  = chunk_overlap,
+            length_function = len,
+        )
+
+
+    def ingest(self):
+        # find all .pdf files in the data folder
+
+        documents = []
+        # pdfs
+        pdffiles = [os.path.join(self.data_path, f) for f in os.listdir(self.data_path) if f.endswith(".pdf")]
+        for f in pdffiles:
+            loader = PyPDFLoader(f)
+            docs = loader.load()
+            for i in docs: i.metadata['source'] = os.path.basename(f).split(".")[0]
+            documents.extend(docs)
+        
+        #txts
+        txtfiles = [f for f in os.listdir(os.path.join('./data', self.folder)) if f.endswith(".txt")]
+        for t in txtfiles:
+            with open(os.path.join('./data', os.path.join(self.folder, t)), "r") as f:
+                documents.append(Document(page_content=f.read(), metadata={"source": os.path.basename(t).split(".")[0] + ' transcript'}))
+
+        for i in documents:
+            i.metadata['module'] = self.folder
+
+        # split texts into chunks
+        print("Splitting texts into chunks...")
+        chunks = self.splitter.split_documents(documents)
+        #[chunks.extend(self.splitter.split_documents(i)) for i in documents]
+        embeddings = OpenAIEmbeddings()
+        # create store
+        print("Embedding chunks...")
+        Chroma.from_documents(chunks, embeddings, persist_directory='./chroma')
+
+if __name__ == "__main__":
+    ingest = Ingest(
+        folder = FOLDER,
+        chunk_size = CHUNK_SIZE,
+        separator = SEPARATOR,
+        chunk_overlap = CHUNK_OVERLAP,
+    )
+    ingest.ingest()

prompts.py

@@ -0,0 +1,15 @@
+VANILLA_PROMPT = """
+
+Assistant is a large language model trained by X to help you clutch y2 exams.
+
+Assistant is designed to be able to assist with a wide range of tasks, from answering simple questions to providing in-depth explanations and discussions on a wide range of topics. As a language model, Assistant is able to generate human-like text based on the input it receives, allowing it to engage in natural-sounding conversations and provide responses that are coherent and relevant to the topic at hand.
+
+Assistant is constantly learning and improving, and its capabilities are constantly evolving. It is able to process and understand large amounts of text, and can use this knowledge to provide accurate and informative responses to a wide range of questions. Additionally, Assistant is able to generate its own text based on the input it receives, allowing it to engage in discussions and provide explanations and descriptions on a wide range of topics.
+
+Overall, Assistant is a powerful tool that can help with a wide range of tasks and provide valuable insights and information on a wide range of topics. Whether you need help with a specific question or just want to have a conversation about a particular topic, Assistant is here to assist.
+
+{history}
+Human: {human_input}
+Assistant:
+
+"""

raw_transcripts/lecture_1.txt

@@ -0,0 +1,2304 @@
+Good morning.
+
+Just checking the mic works.
+
+Yeah.
+
+You can hear me.
+
+Okay.
+
+Okay.
+
+We're going to get going with our lecture now.
+
+It's 5 minutes past the hour.
+
+So welcome to our first lecture in brain and behaviour.
+
+Probably your first lecture, this academic term for these lectures.
+
+We're in this chemistry auditorium, and it's very difficult as
+
+you find, to come in and out.
+
+So we will make some efforts to create a path
+
+for the students.
+
+It is very exciting to be back lecturing you.
+
+I hope you were excited to be back in person.
+
+We've got 20 of these lectures of this course.
+
+I'm Professor Hugo Speers.
+
+It's my details, it's my email address, my lab and
+
+the title of today's lecture was very much looking forward
+
+to teaching you on Moodle.
+
+I'll just show you the the team briefly as myself
+
+as Sam Solomon, who's a professor in psychology, a new
+
+lecturer, Professor Stephen Fleming, Professor Daniel Bender, Paul Burgess, who's
+
+mysteriously Hidden Valley Academy, who will teach you research methods.
+
+And amongst them we have a team of experts who
+
+are coming in to teach you today, and I'm the
+
+first one up and I run.
+
+I'm the convenor for this module.
+
+All the lectures will be lecture cost.
+
+If something goes wrong with those, we have an entire
+
+back catalogue of carefully recorded lectures that are almost identical
+
+to these.
+
+So please do attend.
+
+We hope the idea of these lectures that are starting
+
+today are to kind of be there in person to
+
+speak to you, hopefully inspire you to go and read
+
+the things and have a voice, someone you're actually physically
+
+talking to you.
+
+So without further ado, I'll head into my first slide.
+
+So human brain, there's a picture of the human brain.
+
+There's this sequence of 20 lectures.
+
+A brain in behaviour is all about this one object.
+
+It's by far the most complicated object in the entire
+
+universe, human brain.
+
+It's capable of all the people being here.
+
+Me talking to you now, all the discoveries, all the
+
+history, everything humanity has ever done in terms of what
+
+it's produced has come from the faculties of this brain
+
+over other species.
+
+It's an absolutely remarkable thing.
+
+The beginning of today's lecture on our 20 lectures diving
+
+into topics in brain of behaviour.
+
+It's to take a step back and think, Wow, sitting
+
+inside your head, behind your eyes, looking at me.
+
+Now, next between your ears, listening to me now is
+
+this object.
+
+It looks quite attractive in this well, relatively in this
+
+picture.
+
+But if you were to see a real brain, if
+
+someone was to have it, you know, accidentally removed in
+
+front of us, it would be disgusting.
+
+It's full of blood.
+
+It's vastly for the blood vessels.
+
+It's a really squidgy, pretty disgusting thing.
+
+And for thousands of years in our prehistory millennia, people
+
+weren't very aware of what it was doing.
+
+So today's journey is let's take a look at the
+
+brain history of the scientists.
+
+This study, that is a way.
+
+And if you do get into the brain and slice
+
+it up, as I said, pretty disgusting.
+
+You don't see very much.
+
+The brain is just like this dull kind of, you
+
+know, beige colour.
+
+It's more disgusting than not when it's fresh.
+
+But the scientists discovered over 200 years ago, if you
+
+take something like silver nitrate, you can make dark stains
+
+happen in stuff.
+
+Most of the time you don't want to stain things,
+
+but if you're looking down a microscope that's been developed
+
+and you put a stain into a brain section, an
+
+entire world opens to your eyes the early microscope, people
+
+using microscopes.
+
+There's early microscopist looking down with stain sections, discovered an
+
+amazing world.
+
+Here's a single brain cell in one and one of
+
+these early sections.
+
+If you look even closer, you can see these brain
+
+cells take on these weird, strange forms.
+
+Now, I'm a biased scientist.
+
+I find these B cells that are just quite dramatic
+
+to look at.
+
+But there's not just individual cells.
+
+There's whole collections of networks of these cells.
+
+Here's some examples.
+
+They're they're arranged in the most beautiful ways inside your
+
+head as you're listening to me in how carefully arranged
+
+neurones are doing important work of allowing you to understand
+
+what I'm saying.
+
+Take notes, think about what I'm saying as well.
+
+If we cut through on the lowest bit, is your
+
+body behind your neck and you look into the spinal
+
+cord, you will see this object.
+
+This is a cut through the spinal cord.
+
+You could cut through a bat, a rat, a durable,
+
+a human.
+
+And it would very similar to this.
+
+And again, the early this is hundreds of years old,
+
+this picture drawn by these early anatomists, Peking duck microscopes.
+
+If you look really close, these things look a bit
+
+like sort of strange alien creatures with these incredible fibres,
+
+connections, nerve cells are the neurones are very complicated and
+
+take all sorts of forms and shapes and they're quite
+
+incredible pictures to look at to start your journey into
+
+brain in behaviour, the neurones you're going to be looking
+
+at in a lot of the pictures of the science
+
+today are quite boring.
+
+We've reduced them down to simplicity.
+
+I won't be showing exciting pictures like this through the
+
+rest of the lectures, but I just want to start
+
+with the beauty that exists in the topic we're looking
+
+at.
+
+Here's a particularly beautiful drawing one individual cell and a
+
+sort of climbing block network of fibres from another cell
+
+winding their way round that cell.
+
+And all of those drawings I've just taken you through
+
+step by step were drawn by one anatomist, Santiago Ramon
+
+Cajal, the Spanish Year, an optimist who won the Nobel
+
+Prize.
+
+That discovery, he was the person who who argued.
+
+First of all, I think they're brain cells.
+
+It was a controversial idea.
+
+There were brain cells and we'll come onto that in
+
+a moment.
+
+Reproduced all those beautiful images.
+
+It was arrested in Oxford, actually, for trying to draw
+
+pictures of the local community buildings because they just couldn't
+
+believe he was really a scientist travelling Oxford.
+
+They put him in jail, had to be let out
+
+of jail.
+
+But he's written incredible books about his life experience winning
+
+the Nobel Prize and what you need to do as
+
+a scientist.
+
+Come back to him before we come back to the
+
+scientists that made the stories behind this, I just want
+
+to highlight you.
+
+You are UCL student sitting in one of the world's
+
+top universities for this topic.
+
+We are kind of the top research institute in the
+
+whole of Europe for neuroscience and the topics we're talking
+
+about today.
+
+That means excessive amounts of money coming into UCL around
+
+this excessive amount of scientists have gone in, a number
+
+of Nobel prizes have been made here.
+
+There are lots of fellows the Royal Society in this
+
+topic.
+
+The story keeps going on.
+
+So we're ranked second in the world was slightly behind
+
+Harvard and M.I.T. If you put those two together, they
+
+have a slightly higher number of Nobel Prize winners and
+
+money have a lot more money.
+
+Anyway.
+
+What are we here to learn?
+
+So every lecture we're going to get, you try and
+
+get what are the objectives?
+
+So today's objective of this lecture are two things I
+
+want you to come away with.
+
+Once you acquire the key and knowledge of the key
+
+developments in our historical understanding of brain and behaviour.
+
+My lectures in this course in the others are not
+
+just about the structure of the brain for its own
+
+sake, or how so receptors work.
+
+We're absolutely obsessed in this course by behaviour.
+
+This is the links between how the brain gives rise
+
+to behaviour.
+
+We also want you in this course to learn about
+
+some of the key historical figures.
+
+So if you were to pass in some wisdom, who
+
+was who?
+
+Who developed the ideas behind the brain?
+
+So you would have an idea of who these celebrities
+
+are that would run through maybe a few snippets of
+
+facts about.
+
+When you come to sit exams, the course will kind
+
+of throw up and things.
+
+So right from the get go, I want you to
+
+think thinking about if we were to put up an
+
+exam question after this lecture, what's the kind of exam
+
+question we want to ask?
+
+And you can put that in your head what you're
+
+thinking through doing, How would I get to that?
+
+And it might be something like how has her understanding
+
+of the brain changed since the ancient times?
+
+So what did the ancient people know and what do
+
+we do now?
+
+And I'll be teaching that in this lecture today.
+
+We also run an MQ multiple choice exam for this
+
+lecture, which is extremely easy last year, where we improving
+
+that a little bit, but we'll be giving you lots
+
+of help to make sure that you're absolutely up to
+
+speed with the MQ.
+
+I'm sure you'll nail it as long as you're students
+
+that.
+
+So an example question might be which ancient culture first
+
+is first thought to have a specific word for brain
+
+in the written text?
+
+Greeks, Babylonians, Egyptians.
+
+Persians.
+
+If you go down to the British Museum and ask
+
+the answer to that question, you'll find out in a
+
+moment and give The answer is the ancient Egyptians.
+
+So it's example of a kind of level of question
+
+will be asking.
+
+Let's start right back.
+
+Not with the ancient Egyptians.
+
+Let's go far back in time before those giant pyramids
+
+were built and racing was even invented back to skulls
+
+around 7000 years ago.
+
+This one is it pretty looks like a sort of
+
+Halloween type of skull.
+
+It's quite intense.
+
+But there's a key feature I'm sure you've all noticed
+
+about this skull as a cut mark in the top
+
+of his head.
+
+A lot, a lot of historical skull was dug up
+
+in 7000 years ago, have holes in them through axes,
+
+spears in a brutal life 7000 years ago.
+
+What's really creepy about this one is that the bone
+
+had been cut and healed.
+
+This person walked around living with this whole cold, carefully
+
+cart, not cut with an axe or something in their
+
+head.
+
+And so scientists as well, archaeologists and palaeontologists have argued
+
+that this cutting into the head happening was found 7000
+
+years ago.
+
+And we think we don't know.
+
+There's no written text, but it was used for medical
+
+treatment.
+
+Perhaps this person had epilepsy or some other condition they
+
+would.
+
+They thought maybe if we open up the skull we'll
+
+get the demons out.
+
+What's interesting about this is that they thought that cutting
+
+into the skull, into the head may be doing something
+
+we don't fully understand, that we have no real way
+
+of knowing.
+
+But this is the earliest kind of thinking about humans
+
+might be aware of the brain and doing something to
+
+to medically approach it.
+
+So we come now three and 4000 years forwards.
+
+When the great Pyramids were built in ancient Egypt and
+
+this incredible moment in civilisation when people were writing out
+
+these hieroglyphic texts, which until, you know, a couple hundred
+
+years ago were indecipherable and suddenly through the Rosetta Stone
+
+in a British museum, they were able to decipher and
+
+work out what was written in this hieroglyphics.
+
+And what they discovered was that in these ancient texts
+
+they were able to find from ancient burial sites was
+
+that the ancient Egyptians, in fact, did write about treatments
+
+for brain damage.
+
+What to do if you're a medical doctor and someone
+
+has damage to the head.
+
+These are some of the things one might do.
+
+Critically impressive things have been 5000 years ago it was
+
+the ancient Egyptians discover that if someone hits like a
+
+spear or some axe hits the right side of your
+
+head, you lose the ability to move with the left
+
+side of your body.
+
+And if you smash into the left side of the
+
+head, you'll lose the ability to move or say on
+
+the right side of your body.
+
+So this is known as this contralateral movement sensation.
+
+So when I say contralateral, we'll get into that on
+
+Friday's lecture about what we mean by these anatomical terms
+
+that are quite remarkable.
+
+This is sitting unknown for thousands of years in transcripts,
+
+and it critically had this word brain.
+
+You can see the hieroglyphics of the word brain.
+
+But one fact is that they when they mummified the
+
+ancient Egyptian bodies, most of you be aware of this,
+
+they would put them into these tombs.
+
+It's hard not to know about this, but they obviously
+
+save parts of the body and put them into these
+
+special jars like the intestines and the heart, particularly the
+
+heart.
+
+I just threw away the brain.
+
+I thought it was not something to be preserved into
+
+the afterlife.
+
+So they clearly had some insights.
+
+But then the cultural practice of burial didn't really follow
+
+through.
+
+We now move forward.
+
+We're going to go through individual people.
+
+These are the first person hypocrisies we'll go through with
+
+all the way through it.
+
+A lot of bearded men, a lot of white men
+
+will eventually end on a female scientist passing through a
+
+critical Persian scientist.
+
+So we'll begin with this chap.
+
+Hypocrisies.
+
+Now he is the first person who people wrote about
+
+mentioning his his followers wrote about him, saying, Here's all
+
+the incredible things, hypocrisies.
+
+We know when he lived, when he died.
+
+We can date now.
+
+We have evidence of his existence.
+
+And why he's up here is that he is the
+
+first person named, we can say, as far as we're
+
+aware, to argue that the brain that was what we're
+
+going to teach you in this course.
+
+Brain supports the mind, supports your behaviour.
+
+He argued this because he's he he was he was
+
+really argues to be the first physician, the first doctor
+
+who went round gathering information, building on knowledge and systematising
+
+it to treat people so that doctors will take the
+
+Hippocratic oath.
+
+Do no harm to my patients.
+
+You know, you might be treating someone you really don't
+
+like, but as a Hippocratic Oath, you treat them nonetheless.
+
+And this is where the Hippocratic Oath comes from.
+
+Hypocrisy is arguing medicine should be for treatment above all
+
+other things.
+
+Critically, for today, he stands out as the person who
+
+argued that your behaviour, all the movements you're making are
+
+fundamentally coming from systems in your brain.
+
+But he didn't know how.
+
+He couldn't get much into it beyond that cool fact.
+
+And that was a great advance.
+
+It was held back by two very, very clever people.
+
+This is Plato and Aristotle who came after hypocrisies.
+
+This is the painting Leonardo da Vinci in the Vatican,
+
+and we don't have any current pictures of them from
+
+the time.
+
+So they were they were philosophers that argued in and
+
+really thinking about things, using your mind to mull over
+
+and weigh up the natural philosophy to get into what
+
+the state of the world really is.
+
+They weren't so obsessed with doing experiments, looking at things
+
+that came much later.
+
+What they argue.
+
+Plato in particular argued that reason in perception was in
+
+the head.
+
+So we do have this kind of sense from Plato
+
+that some of the head might not be the brain
+
+is this may not be the brain tissue itself, it
+
+could be something else is what we might perceive the
+
+world.
+
+But all the passions, all your emotions, everything that drives
+
+you, it's not to do with your brain.
+
+It's in your heart.
+
+We still have the idea of like, you know, we
+
+do these heart emojis on your phone.
+
+You will send hearts to say you care about somebody.
+
+This goes back to those early ancient Greek times.
+
+Aristotle even argued further, and he said he didn't think
+
+that the brain was in charge of the body's movements
+
+and the heart and foot.
+
+And Aristotle actually went and did dissections.
+
+He would get into lakes and take out fish and
+
+cut into the fish and see what happens if you
+
+cut into a brain, the animal, the main nervous system,
+
+the had, you can still see a lot of movement
+
+from the animal.
+
+Its spine will still carry on doing things.
+
+But if you cut it and stop the animal's heart,
+
+the animal will die.
+
+Stop doing any movement.
+
+And Aristotle thought this is better evidence.
+
+I can also see through Aristotle with his eye.
+
+The blood vessels go everywhere.
+
+The blood vessels permeate everything.
+
+In this living being, the heart must be the sight
+
+which controls that he couldn't see in the detail.
+
+The nerve fibres that we know now exist or what
+
+they were doing.
+
+This really held up for a long time thinking about
+
+threatening behaviour, and it persisted into the, you know, the
+
+Middle Ages because these two men, Plato and Aristotle, had
+
+so many insights into philosophy about ethics and the nature
+
+of reality, and they were held up as absolute giants.
+
+Disagreeing with them is hard, but as we go down,
+
+we've gone through the first two characters.
+
+When I moved to Galen.
+
+It's not until we get to ancient Rome and the
+
+gladiatorial combats that occurred there that delivered a huge number
+
+of hideously mangled bodies.
+
+The brutality of ancient Rome in early, you know, 150
+
+A.D. was not a nice place, perhaps unless you were
+
+an emperor.
+
+Even that as an emperor likely to be killed by
+
+your brothers.
+
+But this this man, Galen, was a Greek physician who
+
+moved to Rome, who operated there, was looking at these
+
+cases and saying he found all these bodies and found
+
+out the effects of different bits of damage to the
+
+brain was happening and took penne and produced a cheese
+
+like an argument written down of prescriptions.
+
+The doctors that were preserved in scrolls that were handed
+
+down about the nature of physiology.
+
+And he made those of these not if you're in
+
+a medical school you historically be learning about guy with
+
+lots of reasons today I'm teaching you to he argued
+
+back to evocative was right you the a gladiator comes
+
+in with half his head in this thing he will
+
+lose all sorts of functions.
+
+So we argued against Aristotle.
+
+The brain is responsible for sensation of behaviour.
+
+Now.
+
+Galen was doing physiology, looking at black bodies coming in.
+
+He was thinking about what does this do?
+
+What if we go to ancient Persia, becomes a Powhatan
+
+or Ohaneze and is the Latinised name for this scholar?
+
+So the ancient rabbit country was amazing.
+
+A number of advances they made in thinking.
+
+So it's not just this incredible scientist was not just
+
+about saying, Oh, I can see this.
+
+This body, this brain is important for moving.
+
+He started you can see on the right side there
+
+one of his diagrams.
+
+What you see is hard to make out in that.
+
+But the bottom bit of that curly bit is I'll
+
+get a pointer if I can find.
+
+Oh, no, not at this point.
+
+The bottom part here is the nose and here are
+
+the eyeballs and here are the the trucks, the infant
+
+and the nerve fibres that come out of the eyeballs
+
+and go into the back of the brain.
+
+Now, the current thinking back in, you know, we jump
+
+forward quite a bit and it's it's sort of 900
+
+plus A.D. hundreds of years later.
+
+Host Galen the still the thinking was that a bit
+
+like I can touch the world around me I send
+
+out and I touch this this theatre with my this
+
+lecturer with my fingers Our eyes are doing something like
+
+that with the visual world.
+
+I'm kind of prodding the world with my eyes.
+
+They're actively sensing out there and our hands and said,
+
+No, I do not think this is what's going on
+
+because he was obsessed with optics and the mathematics of
+
+optics.
+
+So you could see the eye was exactly like some
+
+of the incredible optics.
+
+And he wrote, These strategic treaties is arguing that our
+
+brain is absorbing the light from the world.
+
+Like the light coming into my eyes, I can see
+
+because I'm processing the light into the back of the
+
+brain.
+
+He didn't even think it was in the eyes.
+
+Incredible advances from our hands.
+
+And about that is a fantastic YouTube video to watch
+
+about his historical discoveries.
+
+We'll jump forward now, maybe another 500 years until there's
+
+a next big advance in terms of brain behaviour.
+
+Reach up to Renaissance Italy.
+
+This is the time of the Medici and a brutal
+
+life again.
+
+This is a frequently picking this up in the coming
+
+to Italy, but medieval there is a renaissance occurring which
+
+is incredible science, incredible odds.
+
+And in this one man, Andreas Vesalius we have both.
+
+We have incredible scientists.
+
+He was a polymath.
+
+It had lots of different things, highly liked, very charismatic
+
+to it rhymes.
+
+Crucially, we're now in 1500s.
+
+He was able to print what he was doing.
+
+He's able to take, as we can see in this
+
+diagram here, this is one really beautiful drawings, although very
+
+disgusting.
+
+This isn't a human man's head because he's nose with
+
+a skin removed, the skull removed in the brain, much
+
+less nice than the first image of a brain.
+
+But he had labelled it all.
+
+He provided the first book published back in 1500s.
+
+The Doumani Corporis Fabrica structure, The fabric of the human
+
+body, covered everything in real detail so that any anatomist
+
+in the world, anyone teaching medical school could go through.
+
+And now this time we have the brain really in
+
+detail.
+
+Consider what bits might we have in the brain.
+
+He also Andreas Vesalius started this process of thinking about
+
+the maybe the soul, our mind.
+
+This idea kind of interferes with our actions through the
+
+fluid that's in your brain is a milky, pretty disgusting
+
+substance in your head.
+
+I'll talk to you about it next Friday.
+
+When we come back, the lecture to these ventricles, these
+
+holes inside your head look absolutely swollen.
+
+If you have hydrocephalus, it's a very unfortunate condition by
+
+the brain.
+
+If you see someone hydrocephalus, the skull expands the ventricle.
+
+But he thought this was particularly the way in which
+
+our our mind interacts with our body and is a
+
+very charismatic character.
+
+This idea was really picked up in detail about this
+
+very famous philosopher, René Descartes.
+
+So if you had two lectures in philosophy, you would
+
+have heard a lot of our stuff in Plato.
+
+You then hear a lot about René Descartes is famous
+
+for arguing, I think for Rico or ergo, some just
+
+famous statements that What can we really know about reality?
+
+If I'm thinking it must be there.
+
+Today's lecture What's important about René Descartes is that he
+
+argued that there's a big distinction, that there are some
+
+things that I can't If I put my hand in
+
+a fire, I got no choice.
+
+I have to take it out.
+
+I could try and hold my hand in there, but
+
+naturally I'll take it out.
+
+And we share that with all other animals.
+
+What he had, what he.
+
+We have reflexes, things that help us survive without thinking.
+
+But there are other times when I might want to
+
+get up and slap someone.
+
+And I have decided I'm going to do I'm going
+
+to make this decision.
+
+I'm going to use my arm.
+
+I'm not going to take it.
+
+I'm going to take and slap someone.
+
+And he drew diagrams highlighting.
+
+We can see one here about the bottom that you
+
+put your foot in the fire.
+
+You'll need to take it out quickly.
+
+But the other drawing at the top is about the
+
+idea.
+
+He started to think about sensation through to action, that
+
+I might see something in the world.
+
+It passes into my brain and then I can think
+
+and then move my hand to change the world.
+
+Before René Descartes, that wasn't really a distinction.
+
+It was drawn this idea about the process, the science
+
+of what might be going on.
+
+And that's what we'll be obsessing over in the lectures
+
+going forward into a whole range of why is it
+
+exciting topics about emotions, movement, seeing, acting, smelling and memory.
+
+All these things are going on inside our head.
+
+But René Descartes really was the first to argue that,
+
+you know, he discovered all sorts of ideas in mathematics.
+
+The fact we have graphs, you know, algebra, a vast
+
+range of things.
+
+But he was really critical.
+
+He argues that the soul, this mysterious thing that we
+
+can't quite tangibly understand is separate from my body.
+
+The thinking behind me is separate.
+
+Going back to the long historical is not the way
+
+science is.
+
+Good.
+
+Now think.
+
+But you will be getting a lecture from an expert
+
+on consciousness in this course.
+
+We'll take you into some of these ideas where we
+
+are now in 2022.
+
+And if you jump forward into the 100 years after
+
+René Descartes got interested in reflexes and how he might
+
+act and the mechanics of moving, we have this again,
+
+a really charismatic character.
+
+Once again, Italian themes from 1700s.
+
+This is Luigi.
+
+Galvani is primarily a physicist, is messing around with all
+
+sorts of things in physics, but he also got obsessed
+
+with physiology and other things.
+
+A lot of these people back then didn't have to
+
+spend three years in a psychology degree to get to
+
+grips with what was going on there.
+
+He was able to learn a lot and discover things.
+
+What he built was a vast room like this.
+
+I five from here to the wall over there, vast
+
+room filled with copper plates and Wolff are huge, big
+
+thing and copper plates and wool all stacked up because
+
+he discovered, you know, if you accidentally move on a
+
+carpet, if you're wearing the wrong shoes, you can get
+
+this nasty electrical charge this well, let's make loads of
+
+that.
+
+Let's put a lot of this kind of nasty electrical
+
+shock together, put it what we can see here, put
+
+it together is this huge, big building connects all those
+
+copper plates up in and out and to a wire.
+
+I can take a little while now and I can
+
+tap it onto another wire and make a little flush
+
+of electricity.
+
+And what he discovered when he did that was he
+
+was testing out what he could do with this.
+
+And he got, you know, some frogs legs might have
+
+been part of a meal back then, but he was
+
+stimulating the frogs in different bits and finds, you know,
+
+he stimulated blood vessels.
+
+Nothing very boring.
+
+But if you stimulate the top of his legs on
+
+the white bit, the nerve fibres bundle the frogs legs
+
+on their own, will show the exact pattern of movement
+
+the frog would make, the whole frog would make trying
+
+to swim through the water.
+
+He'd reanimated the frog, brought its lower power back to
+
+life using electricity.
+
+And as a young female student who observed this, Wow.
+
+Because he would tour around with this electrical model showing
+
+people in different places.
+
+This young female student called Mary Shelley.
+
+This is amazing.
+
+I went off and wrote a rapid study, the story
+
+of Dr. Frankenstein, his monster drawing from those disgusting little
+
+frogs legs because you just extrapolated from the frog, say,
+
+well, if you could do this with an entire human
+
+body, disgusting.
+
+Why is this important for you?
+
+Today's is the first step forward to discovering that your
+
+brain works through electricity.
+
+The connections between these nerve cells, the brain and nerve
+
+fibres, pulse channel, electrical charge moves down those neurones, allowing
+
+things to happen, like allowing you to see, to hear
+
+all your sensation, allowing you to move.
+
+This comes from Kobani.
+
+A few years later, we move into Germany.
+
+We're going to move into Germany and France and go
+
+back and forward a bit.
+
+Yohannes Peter Muller is a German physiologist.
+
+He started to get obsessed with looking at different fish,
+
+different amphibians and discovering, Oh, they do these in a
+
+building on galvanise ideas.
+
+You could see how the nerve fibres are organised.
+
+And he started to systematise how we might organise in
+
+a more organised way.
+
+Our understanding of these brain structures went far beyond Vesalius,
+
+his books from 1500s.
+
+So now in the 1800s, around that time there's another
+
+man and he he would tool around as well.
+
+A little less charismatic, but still a great performer, Franz
+
+Francisco.
+
+And he had discovered he'd been interested in this idea
+
+that he met people who had different faculties.
+
+Some are really smart, some are really dumb, some he
+
+really quick.
+
+Some people were good at picking up language at different
+
+skills and noticed that their heads might be different shape.
+
+There was a lot of variation in Skull and he
+
+thought that maybe the way the brain maybe there's one
+
+way to to determine how the brain was related by
+
+measuring the skull from the outside, the bones in the
+
+way our brains are.
+
+So some of the big back of the head.
+
+So we were measuring lots of people's head in total
+
+detail of the bumps and what they were good at
+
+the first kind of assessments of IQ and, you know,
+
+memory function and language trying to measure these things as
+
+real move forward to science, but really wrong.
+
+But because nobody really believes that the skill at language
+
+isn't the best, just under AI or the obsequiousness, it's
+
+somewhere at the back of your head.
+
+Or empathy must be in this tiny bit.
+
+But we just know that it was just wrong.
+
+And he came to that through, you know, incorrectly correlating
+
+one set of variables, bumps and another performance in a
+
+very unsatisfactory way.
+
+This whole idea is term phrenology and it's still cropped
+
+up in the modern culture.
+
+Is Homer Simpson, with his brain obsessed with doughnuts and
+
+beer and sleep.
+
+You know, this is a pervasive pervaded to know this
+
+is another man's.
+
+We now go from Germany and France, goobers galore.
+
+A big fall is a big deal.
+
+You'll still find them.
+
+You go to Camden Market.
+
+Phrenology heads.
+
+You know, it's persisted till now, but this rather grumpy
+
+man, Jean-Pierre Florin, hated this idea.
+
+He really did not like goals proposal for the right
+
+reason that it was wrong.
+
+But he decided he would.
+
+He would really try and do experiments on it in
+
+stimulating these frogs is showing electricity.
+
+But what if we went into the brain and start
+
+to find out, do different bits of the brain do
+
+things differently?
+
+As ancient Egyptians had written about it, he didn't know.
+
+In 17 the early 1800s we found when he went
+
+in and started looking at damage to the brain, applying
+
+lesions was that it wasn't really some great kind of
+
+organisation.
+
+His lesions were pretty poorly done, they weren't well delivers.
+
+And he concluded The brain is just this mass.
+
+The upper part of a brain does all these amazing
+
+functions.
+
+It is not organised in a way though, that argues
+
+the language is in somewhere, etc. So he really in
+
+France was a big fight between these positions of organised
+
+versus non organised brains.
+
+So we've moved right down up to the top of
+
+this without coming to the latter part of the modern
+
+year period when things really changed with this man, Paul
+
+Broca, in France, same as Florence, around the same sort
+
+of time.
+
+He's an anatomist, a physician, anthropologist as well, and what
+
+he's famous for is discovering Brook, his area, funnily enough,
+
+named after him.
+
+And this is a picture of one of the disgusting,
+
+preserved brains that Brocket managed to take when he was
+
+doing his anatomy work.
+
+And what we can see in this brain is it's
+
+got a lot of damage.
+
+There was some event, some traumatic event.
+
+It caused damage to this particular area.
+
+And what Rocco realised was that he had a group
+
+of patients who had the same problem.
+
+They all couldn't speak properly.
+
+It could, they could understand language, but they just couldn't
+
+get the right words.
+
+Still very clever.
+
+He do lots of things, but they struggle with speech
+
+and he found all these patients with almost all cases
+
+had damaged.
+
+The right frontal lobes in this particular area might extend
+
+to other places.
+
+But the common area was this area known to termed
+
+Brock Azaria for the production of speech, and he established
+
+that in most humans the left hemisphere is critically important
+
+for language, which is still something that clinicians right now
+
+are somewhere in a hospital in London will be determining
+
+for somebody surgery.
+
+You do not want to do the wrong surgery and
+
+without someone's frontal lobe for language and discovered that they
+
+can't speak and surgically because it could be their right
+
+temporal lobe, one in a hundred is is actually doing
+
+that job.
+
+So it's a very critical thing.
+
+Still, the broker is important in your story because he
+
+is not the first to really say Florence is wrong,
+
+go.
+
+They're all wrong.
+
+But actually there is organisation in the brain.
+
+But we need to really think about the anatomy.
+
+We need to think about specifics.
+
+During this time in Germany, Karl Verner was also looking
+
+at patients and he discovered a bit of wrinkle.
+
+Verner Azaria I mean they named after him, which is
+
+more posterior to rock.
+
+Azaria Responsible for the comprehension of speech, and I put
+
+it in very simple terms, but generally these were the
+
+was the general idea.
+
+You've got language production and language comprehension in the left
+
+hemisphere in two particular areas.
+
+And both these men really led the way into the
+
+world of neuropsychology, of relating psychological function, speech reduction to
+
+speech comprehension, these two different abilities you might have.
+
+So.
+
+Yes, he was an incredible.
+
+These two men are incredible in advancing our understanding of
+
+brain and behaviour, roots change and development of neuropsychology.
+
+And this was going on in in France for for
+
+four.
+
+We go back to Brock having gone in in France
+
+for Paul Brock and in Germany for Calvin.
+
+And just you could walk there in 10 minutes down
+
+the road in Queen Square.
+
+John Healings Jackson is the other major figure in the
+
+understanding of brain and behaviour this time.
+
+So now a little bit for the mid 1800s, sort
+
+of late 1800s.
+
+And John healings Jackson.
+
+Key takeaways.
+
+You provide a whole range of important insights into the
+
+cerebral, the cerebral cortex and study of these brain damaged
+
+patients.
+
+A vast range that I could list, you know, colour,
+
+vision, sensation, spatial orientation, whole range of functions.
+
+And his boss, the sitting in the National Hospital for
+
+Neurology and Neurosurgery, where he worked for his career running
+
+a a ward when he was dedicated to not only
+
+helping patients, but making these discoveries about the brain, how
+
+it's organised.
+
+And so we have him to thank for a lot
+
+of key neuropsychological discoveries, by the way our brains are
+
+organised.
+
+Now one of the most critical cases we're going to
+
+come into a number of in this short lecture, we're
+
+coming to two really famous cases against the celebrities who
+
+made the key discoveries like Rocker and Veronica and John
+
+Hughes Jackson.
+
+But here's a man called Phineas Gauge.
+
+I'm sure many of you in the audience may have
+
+come across Phineas Gauge, but if you haven't, let me
+
+introduce this remarkable story.
+
+We don't really know that the urologist should have more
+
+credit for the person who discovered in his details.
+
+But it seems a move between different doctors and it's
+
+a bit disputed.
+
+The Phineas Gauge.
+
+Here is a picture of his skull and a picture
+
+of figure one in the paper of an iron bar
+
+used for railway sleeper movers.
+
+A Tiffany's gauge was a railroad worker.
+
+He was responsible for moving around, dealing with the the
+
+laying down a railway track.
+
+At that time, they had these huge metal poles that
+
+would allow you to move the big sleepers and move
+
+the big rails.
+
+You're putting a rope.
+
+You needed something really heavy this time.
+
+They're also using explosives.
+
+They're using because they had to cut through the rock.
+
+And for Phineas Gauge, a very unfortunate accident occurred or
+
+was working away.
+
+An explosion occurred on one of these steel rods just
+
+blown right up through his head and lodged inside his
+
+head.
+
+He should have died.
+
+He should have died.
+
+But the fact the reason he didn't was the speed
+
+of the of this rod penetrated his skull so fast,
+
+it sort of it didn't cause the surrounding damage in
+
+the way of a slow moving object.
+
+So remarkably, they were able to remove this pole.
+
+And he went on for a month or so for
+
+some period afterwards alive before he died.
+
+And what was remarkable in the case of Phineas Gauge
+
+was that he retains more or less his knowledge of
+
+who people were.
+
+He could see things all sensation movement, a lot of
+
+these general human properties, you know, things we take for
+
+granted.
+
+He could still do them despite this massive damage he'd
+
+had.
+
+What he lost was his ability to make careful decisions,
+
+to plan for the future, and his personality was really
+
+disrupted.
+
+So he was he would curse is violence.
+
+His entire sense of who he was, the people who
+
+knew him said he's not the same as change.
+
+So from that discovery of Phineas gauge, along with Brauchler
+
+and Guernica, we had this and John Ewing's Jackson, these
+
+discoveries about bits of the brain, it seems the frontal
+
+lobes.
+
+I'll be going through the anatomy on Friday show you
+
+where the frontal lobes are, unsurprisingly in the front of
+
+the brain.
+
+But these frontal lobes are critical for that kind of
+
+personality and thinking.
+
+And and sadly, people went on to run frontal lobotomies
+
+all around the world.
+
+Popping out of these for periods is a very unpleasant
+
+period in history that we may come back to later
+
+in the course.
+
+Paul Burgess in the last lecture will talk about the
+
+history of frontal lobotomies.
+
+So have Phineas Gauge railway worker and let's just listen
+
+to what I've said there.
+
+So he survived his personality disorders.
+
+So what I've been talking to now is Rocco, Veronica,
+
+John who these Jackson cases often escape each one of
+
+these people in cases giving us real insight into the
+
+organisation and function there has persisted.
+
+And to this day we still people look for this
+
+area.
+
+People still think this is true.
+
+What distinctly different Phineas gauge.
+
+Unlike the previous hundred years before, there was a bit
+
+of a mass, but it's around this time in the
+
+1800s that we have this shift towards more careful experimental
+
+science.
+
+So Jean-Pierre Florins, I'll go back and see him again.
+
+This is Jean-Pierre Florence that instigated in France, this idea.
+
+We need to experiment to understand the brain.
+
+We can't just observe in the period following these 33
+
+men and this particular case, they're all about observing.
+
+But at this late 1800s, we had these three men
+
+that then revolutionised our understanding of brain function because they
+
+went back to the idea Galvani had produced and Mary
+
+Shelley had popularised in Frankenstein.
+
+What friction hits segue on the right.
+
+Everyone had big beards back then on the right in
+
+Germany.
+
+We were running a physiology laboratory but able to show
+
+it, start showing that they had much more improved.
+
+They didn't need a huge house to create batteries anymore.
+
+You could get small systems for electrically shocking and working
+
+with electricity.
+
+This is 1800s.
+
+So they were able to show that you could stimulate
+
+bits of the brain and cause movement to occur on
+
+the left here.
+
+David Farrier was a physician, is a Scottish physician who
+
+worked with John Healings.
+
+Jackson's became known as a student who.
+
+Again, 10 minutes away, you walked to where David Faraday
+
+would walk around doing things in the ward, helping patients.
+
+But he got a grant to start doing this experimental
+
+work by stimulating, and he was extremely systematic in that.
+
+And he he produced the first publication publication map of
+
+where what happens when you stimulate where in the brain.
+
+So if I stimulate above here in lots of different
+
+in various different animals, I'll get certain reactions, certain movements
+
+will occur.
+
+And they were really interested in this, and not just
+
+to make the fundamental discoveries we're talking about here.
+
+They wanted to understand epilepsy, and they could see that
+
+if you stimulate electricity in places you've got, movements are
+
+very much like an epileptic fits.
+
+So they're able to argue that epilepsy is this overreaction
+
+to much electrical charge through the brain from these early
+
+experiments.
+
+But it is a very sad tale because they were
+
+not using antiseptic techniques.
+
+These came in.
+
+So the experiments were really traumatic and indeed really drove
+
+in the United Kingdom, the Anti Vivisection Society.
+
+And to this day in the UK, we have some
+
+of the most stringent laws around the protection of animals
+
+do anywhere that animals.
+
+And there's lots of animal work going on at UCL.
+
+It's so carefully regulated and looked at with great care
+
+to make sure that every every effort is made to
+
+minimise any pain to any animals.
+
+But back then, unfortunately things were not so good.
+
+So reading these articles is somewhat is is not pleasant.
+
+Unfortunately, this is the history of historically.
+
+These two men, they move out of they move from
+
+the study of stimulating brains and damaging brains and so
+
+on to what happens if you look down a microscope.
+
+This is going on simultaneously.
+
+In the late 18th, we know in the early 1900s
+
+how on the right and Emilio Golgi, two men who
+
+had developed staining techniques.
+
+You can see how this picture I showed you earlier
+
+on the right and comedian Goldie's picture on the left.
+
+These are the drawings of anatomy.
+
+A key things that they had discovered that they could
+
+use, particular staining techniques that when you stay in a
+
+bit of brain wash it.
+
+I you can see it under microscope.
+
+Now Golgi and his name is all over cells.
+
+Views on any cell biology, any or any biology really,
+
+or probably where the Golgi apparatus inside a cell.
+
+This is this, you know, larger than life Italian.
+
+He put his name on it and he he discovered
+
+an enormous amount of ourselves by very carefully looking at
+
+microscopes.
+
+But what he thought when he looked at the brain
+
+was it was all the kind of big fibrous mass
+
+like a sponge.
+
+You know, sponges are one big kind of fibrous mass.
+
+And how awful this was wrong, how it looked in
+
+lots of sections.
+
+And he could see quite clearly from his notes that
+
+there appeared to be individual nerve cells that were not
+
+connected up and they were growing.
+
+And how argued this hypothesis that a brain is composed
+
+of neurones is something we take for granted.
+
+But it's only 200 years.
+
+All these amazing scientists before that were not aware of
+
+the existence of neurones.
+
+It's quite amazing to think of.
+
+They both received the Nobel Prize for this and they
+
+went up on the stage to collect it.
+
+It was all agreed in this period that pretty much
+
+all scientists agree with the Nobel that the position of
+
+neurones.
+
+But apparently Golgi did not like this idea and his
+
+entire Nobel speech to the community carried on arguing against
+
+the hypothesis which really pissed off.
+
+How does he come to collect the prize for the
+
+same thing?
+
+And they never really spoke to each other.
+
+He had a real falling out over this idea, but
+
+they made incredible advances and move forward this idea and
+
+we looking a lot in this course of neurones.
+
+So these are the guys behind the insights around this
+
+time just a bit earlier.
+
+In fact, we have Hermann von Helmholtz.
+
+We're looking at neurones and we're starting to you have
+
+rokkr looking at brains, but we have this incredible switch
+
+to empiricism.
+
+So if you do a psychology degree or neuroscience degree,
+
+you're taught to take a problem, you reduce it down,
+
+you systematically study it, you've hairy properties of the world
+
+and you statistically test them.
+
+And we have a lot of that in science.
+
+There is a vision, perception of space and so on.
+
+Where we're being examined by Helmholtz back then, the world
+
+was not so big.
+
+So these people neutral.
+
+Helmholtz was David Faraday had worked with Helmholtz.
+
+It was dialogue with John Giddings.
+
+Jackson How was aware of how they were all in
+
+cahoots in some ways, but disagreeing in agreement.
+
+So it was a very productive time in terms of
+
+changes.
+
+Now we come to the 1900s.
+
+We have colleagues shown there are neurones, but in Oxford
+
+we have Charles Scott Sherrington and his work were moving
+
+into the 1900.
+
+This is the 20th century.
+
+Science is now changing big time.
+
+The methods you can employ, the precision of instruments, what
+
+you can do.
+
+Psychology and neuroscience have become topics that are investigated more.
+
+And Charles Scott Sherrington In history, neuroscience is really important
+
+for rolling out the first fundamental explanation of how brains
+
+operate.
+
+Jake Deka had written about reflexes and movement, but just
+
+sketched it.
+
+You saw the diagrams.
+
+Sherrington had detailed diagrams and explanations.
+
+He worked out that there was something wrong.
+
+He went to how far stick the work around this
+
+time, how information must flow through the nerve system, how
+
+these with the stimulation of the frogs legs discovered there
+
+was a gap in the timing.
+
+Something was missing.
+
+These cells should foster.
+
+And he speculated that there must be some gap between
+
+the cells, which he called the sign ups that were
+
+some slowing and that stayed very controversial for 50 years
+
+or so.
+
+Fighting over the existence of sign ups did or did
+
+not operate throughout tricity or chemistry or books.
+
+Charles Scott Sharon's and was really the foundational figure in
+
+terms of laying out the general principles of the nervous
+
+system.
+
+We have to thank for that.
+
+We're going to wrap up now the last two people
+
+for the end of the lecture, and here we go
+
+again.
+
+I think charisma carries through a lot of these.
+
+We have not an Italian charismatic, but a Canadian.
+
+We've got a Canadian neuroscientist while the Penfield, while the
+
+penfield was drawing all that knowledge of fairy friction hits.
+
+It's shown and very mapped out where you should stimulate
+
+in animals to get certain behaviours.
+
+What Penfield argued was that let's use that in our
+
+surgery in Montreal, Montreal Institute back in this period of
+
+the 19, maybe 1930, through to the through to even
+
+now, incredible institute for insights into psychology and neuroscience, they
+
+started to do much more careful work to have a
+
+more experimental brain surgery where they would remove whole sets
+
+of bits of the brain to cure things like epilepsy
+
+or intractable pain, all sorts of things.
+
+What you want you want to do neurosurgery.
+
+What I said earlier with Broca's case, you do not
+
+want to disrupt language and someone can't speak.
+
+It's an utter devastation.
+
+If they can do lots, if they lose other things,
+
+not ever.
+
+You know, if I can't find my way, I can
+
+still get Google Maps or someone to tell.
+
+I can't speak to you.
+
+It's a disaster.
+
+So Penfield was very carefully using electrical stimulation in his
+
+surgeries to then make big discoveries about the brain.
+
+He would go in and stimulate and he discovered there's
+
+an entire map in the human brain of the of
+
+our body where sensations occurred.
+
+So what Penfield would do is have someone in surgery
+
+for the first time awake and careful surgical techniques, open
+
+up their skull, go into their brain while they're able
+
+to speak.
+
+There's no pain receptors in your brain.
+
+They're all on the outside.
+
+If you can anaesthetise all that, get it all set,
+
+you can go in and stimulate.
+
+And they still do this?
+
+No, not quite the way he did, but then much
+
+more carefully that he's able to stimulate and see what
+
+people could tell him.
+
+Things when you stimulate here.
+
+Oh, my hand starts itching, I stimulate there.
+
+Their knee will start to tingle.
+
+You can map all this out and discover that it
+
+was a very organised map of our human body or
+
+surfaces inside our brain running along this area of the
+
+Samantha sensory cortex.
+
+I'll talk about that on Friday in more detail.
+
+There was also a map of if you stimulate in
+
+other places, they might start moving their hand, twitching, a
+
+finger, moving their mouth, their lips.
+
+And you can see one of his drawings there of
+
+the these bits of the body.
+
+And it wasn't just organised 1 to 1 go to
+
+the tongue and the lips take up a huge number
+
+of cells in your brain.
+
+This will be true of all of you in the
+
+audience, your brain.
+
+Well, lots of brain cells.
+
+In fact, somebody once commented The number of brain cells
+
+in your as a human to move your finger is
+
+more than the whole brain cells in a mouse is
+
+so complicated human organising can move.
+
+We have a lot of support cells we have a
+
+lot of a lot of cells in the human brain.
+
+So there is some huge amounts of of cells in
+
+there organising our, our sensation in action, the last personal
+
+ones.
+
+And today's lecture as we come to the end is
+
+a woman.
+
+So she had a lot of bearded men so far,
+
+these people who had the power to do what they
+
+could do.
+
+The Montreal Neurological Institute in the 1940s, 30, 40 years
+
+going forward into the fifties is a change in women
+
+are alive in medicine in fact show Charles Scott showing
+
+some is one of the earliest people to really fight
+
+to allow women into medicine they were not allowed to
+
+study.
+
+You know, when these historical unpleasantries UCLA was actually pretty
+
+good at this changing things.
+
+But here we have Brenda milner, who's 104 years old
+
+at the moment, still alive, still has an office somewhere.
+
+Her office is covered with every possible accolade you could
+
+have in science.
+
+And below her is a normal brain.
+
+On the right, on the left is the brain of
+
+a patient called.
+
+Henry Lawson, who died about ten years ago, was throughout
+
+her career known as Patient H.M..
+
+So Phineas Gauge is famous because that's what was going
+
+through his head.
+
+Hey, Jim was famous because a young maverick neurosurgeon removed
+
+his temporal lobe bilaterally.
+
+You can see in the diagram here, he removed all
+
+that brain tissue there and there, there, that huge amount
+
+of brain tissue all scrutinised very carefully.
+
+He survived perfectly healthy, lived for decades after the surgery,
+
+and the surgery worked for what he was trying to
+
+do.
+
+It stopped.
+
+H.M. had epilepsy, really severe epilepsy.
+
+It stopped.
+
+It was great, but it unfortunately did leave H.M utterly
+
+amnesic.
+
+After the surgery.
+
+He never learned a single thing about anyone he met.
+
+He couldn't remember any new details.
+
+He couldn't find his way around the hospital.
+
+He could remember what had happened to him long before,
+
+but any new memories were unable to be laid down.
+
+That bit of the capacity or other intellectual function, his
+
+knowing language, IQ planning, he could do all the things
+
+for this case couldn't.
+
+His personality stayed the same.
+
+But his memory had disappeared.
+
+And Brenda milner really was the pioneer who brought forward
+
+that and many other discoveries systematically about brain function.
+
+So we'll come back to Brenda milner when it comes
+
+on to our our next hour lectures on memory and
+
+learning systems.
+
+So today, we've gone through a whole sequence of celebrities
+
+of the brain all the way through our ancient past,
+
+Socrates.
+
+So, Brenda milner, on Friday, I'll start to dive into
+
+the neuroanatomy that underlies what we now know about the
+
+brain.
+
+To see you next Friday and enjoy the course.
+

raw_transcripts/lecture_10.txt

@@ -0,0 +1,2081 @@
+Is.
+
+This gone?
+
+Can you hear me.
+
+Out the back?
+
+Yes.
+
+Speak up.
+
+Raise the volume.
+
+And.
+
+I'll just speak louder.
+
+I can't see the volume switch on this.
+
+Is it actually coming through the thing?
+
+Kind of.
+
+Or I'll just try and speak Labs.
+
+Or is it?
+
+I'm not here to help you understand how the brain
+
+helps you love someone like this.
+
+We're here to try and understand a bit about how
+
+we might try and study emotions in the brain.
+
+And to do that, we need to define emotions in
+
+a way that make them scientifically tractable.
+
+And this slide tries to help you do that.
+
+I want to consider emotions that are consistent and discrete
+
+responses to an event of significance.
+
+We need something that's consistent.
+
+We need them to be discrete if we're trying to
+
+understand how they represent in the brain.
+
+I will argue that emotions are important because they help
+
+direct an appropriate course of action.
+
+The most obvious thing in this case is threat.
+
+If you're under threat, you want to fight.
+
+You want to flee.
+
+You need to elevate your blood pressure so that your
+
+body is more prepared.
+
+You need to change your galvanic skin resistance.
+
+You actually need to redirect the blood supply to your
+
+body.
+
+You need to do a bunch of things that are
+
+associated with sympathetic arousal.
+
+It makes sense.
+
+Then, if you start to feel an emotion of fear
+
+that that is associated with a physiological response.
+
+But emotions are also important because they help organise other
+
+aspects of cognition, not just make your body ready for
+
+a particular course of action.
+
+They help you maybe remember things that help you pay
+
+attention to particular aspects of your surroundings.
+
+In humans, we know that emotions are associated with feelings
+
+that might feel sad.
+
+It's a bit hard to ask an animal what feelings
+
+they have.
+
+So we need to, when we study and want to
+
+understand the neuroscience of emotions, we need to examine those
+
+emotions or those aspects of emotions which are reportable, not
+
+those which are subjective and unavailable to scientific analysis.
+
+And I should just mention here that you find in
+
+the literature the word affect and emotion or affective neuroscience
+
+used interchangeably, and it's a little bit discombobulating for the
+
+first few times to read that.
+
+But you just need to think of ethics and emotion
+
+as effectively meaning the same thing.
+
+So there are many ways of describing emotions.
+
+I like this and it is a very influential model
+
+of how emotions can be represented.
+
+This model was developed by asking several hundred, maybe even
+
+thousands of participants in the early 1980s to describe the
+
+relationships between different named emotions, which we'll see in a
+
+second.
+
+And effectively, the mathematical fallout of that experiment was that
+
+most emotions or most emotional states that people recognise could
+
+be described as lying along a space in a space
+
+that's formed by two axes, the two dimensional space.
+
+And those two axes are one of arousal.
+
+So you can vary between being aroused and being sleepy
+
+and one of balance that is between pleasure or positive
+
+affect and misery or negative affect.
+
+So these two axes, it turns out, as sufficient to
+
+describe or at least to place most of the emotional
+
+states that we encounter.
+
+So if we put the various words that were used
+
+in this analysis onto this space, they all kind of
+
+make sense.
+
+So, for example, when you have positive valence and high
+
+arousal, emotions that are associated with those two things, for
+
+example, excited or astonished or delighted and depending on the
+
+relative balance of violence and arousal, you lie at different
+
+points in this.
+
+Similarly, if you have positive violence but low arousal, then
+
+you might have things like serene content at ease, things
+
+that are associated with low arousal but still positive.
+
+So they lie down here, low valence, sorry, low arousal
+
+and negative valence, on the other hand, means things like
+
+sad, gloomy, depressed, those kinds of words.
+
+And finally, high arousal and negative valence means things like
+
+annoyed, afraid, fear.
+
+So it makes sense, the space makes sense, and it's
+
+become a very influential and powerful model for trying to
+
+explain the relationships between different emotions.
+
+And we'll be getting back to that in a in
+
+a few slides time.
+
+What I would like to provide you, though, with the
+
+caveat is that it is still a matter of substantial
+
+debate about whether emotions in the brain represented along these
+
+two axes.
+
+In other words, maybe you have one brain system that
+
+focuses on arousal, another one that focuses on violence.
+
+And together these two brain systems, for example, may represent
+
+all the possible emotions or whether you have dedicated brain
+
+systems for particular emotional states.
+
+So those are the two contradictory hypotheses.
+
+The evidence is still not in about which one describes
+
+brain function better.
+
+But this is a convenient way to think about the
+
+different emotions and the relationship between them.
+
+The study of emotions is had in cognition, and psychology
+
+has had a long and checkered history.
+
+Often called the folk perspective of emotions is the following.
+
+There's a stimulus out there in the world.
+
+We perceive it that then gives that perception and gives
+
+rise to some form of emotional response.
+
+And that emotional response in turn drives physiological actions like
+
+increased blood pressure.
+
+It's not to be pejorative to say this is a
+
+folk explanation, but this is the typical one that we
+
+might if we introspect.
+
+Think about what happens.
+
+This folk, so-called folk was challenged in the late 19th
+
+century.
+
+And indeed, a very popular theory from William James and
+
+Carl Long, which I'll describe in a second, but which
+
+is nicely described in this paragraph, not all of which
+
+are read out.
+
+I just want to highlight a particular sentence.
+
+If I begin to tremble because I am threatened with
+
+a loaded pistol.
+
+That first person is to carry me.
+
+Does terror arise?
+
+And is that what causes my trembling confrontation of the
+
+heart and confusion of thought?
+
+Or are these bodily phenomenon produced directly by the terrifying
+
+cause so that the emotion consists exclusively of the functional
+
+disturbances in my body?
+
+This is a long describing alternative way of looking at
+
+how we start to experience the emotional event.
+
+And in this kind of model, then the stimulus, for
+
+example, a loaded pistol is perceived by axons of the
+
+cerebral cortex.
+
+That perception, in turn drives a physiological response, trembling, increased
+
+blood pressure.
+
+And the emotion that you experience is effectively you reading
+
+out that visceral response with your brain.
+
+I trembled, therefore, I am afraid.
+
+A very popular and and still a model with some
+
+some evidence we process it's the planted in the early
+
+20th century by Canon Bard who suggested that instead of
+
+this model which seemed to be inconsistent with some of
+
+the measurements they were making instead the stimulus, this motor
+
+pistol may still be perceived by the action of the
+
+cerebral cortex, but then its perception of its action in
+
+the cerebral cortex drove two distinct pathways.
+
+In one pathway we get the emotional response and in
+
+the other pathway we get the physiological response.
+
+So this is kind of a parallel description, that descriptor
+
+of emotions and the associated physiological responses arising in parallel
+
+circuits.
+
+And there's some evidence for and against this hypothesis as
+
+described here.
+
+Finding this insufficient to describe some of the experiments of
+
+the kind that you would only probably do in the
+
+1970s sector.
+
+And seeing I came up with a slightly different way
+
+of describing this process that is that that stimulus to
+
+load a pistol again leads to perception again in the
+
+cerebral cortex.
+
+But this then drives a physiological response and there is
+
+a contextual modulation of that and those things are read
+
+out to provide the motion.
+
+So for example, in the famous experiment conducted here, participants
+
+were given an injection of adrenaline, which increases blood pressure.
+
+And then were asked to describe their emotional state.
+
+And some partisans describe it as being excited and aroused.
+
+And others did not.
+
+And it turned out that the particular label, the emotional
+
+state that the people gave, depended on the context in
+
+which they were provided.
+
+That arousing steam was that increase in blood pressure.
+
+So the blood pressure itself was actually generating.
+
+You did seem to be reading that out as a
+
+kind of emotional state, but the label that you attached
+
+to it was that dependent on the context that you
+
+found yourself in.
+
+So this is where we found ourselves in the late
+
+1970s and 1980s.
+
+Not much has changed too much because we haven't had
+
+a huge amount of evidence to decide among these different
+
+alternatives.
+
+It turns out it's quite difficult to study the analysis
+
+of emotions in the brain.
+
+And indeed, almost all the work that we have or
+
+the understanding that we have come from the study of
+
+a very particular brain area, the amygdala.
+
+And we'll be spending a lot of this lecture on
+
+that area to give you a bit of context for
+
+understanding the brain of the amygdala.
+
+I need to introduce you to the limbic system hypothesis.
+
+Has anyone come across the limbic system before?
+
+I presume you have.
+
+Who has not?
+
+Is a few of you who has as a few
+
+more of you, would someone care to describe to me
+
+what you understand the limbic system to be?
+
+The description on here without reading that out.
+
+Back when you when you were talking about the Olympics
+
+this summer, when you encountered it, what did you imagine
+
+it to be?
+
+Yes.
+
+You know.
+
+So the general idea is the limbic system is this
+
+kind of state of something that drives your emotional states.
+
+The kind of larger idea is that the limbic system
+
+that's common, by the way, and if you do study
+
+clinical psychology, you find a lot of clinical psychology still
+
+uses this, what shall we say, simplistic description of the
+
+brain to understand some of the descriptions that I want
+
+to make.
+
+The kind of larger idea is that the limbic system
+
+seemed to evolve long ago.
+
+It's part of the history of our evolution and that
+
+during evolution we have supplanted or added to this limbic
+
+system things like the cerebral cortex and the expansion of
+
+the cerebral cortex in humans.
+
+The idea being that this ancient reptilian brain, which has
+
+continued to be there even as we have evolved and
+
+added in all these other systems.
+
+So the kind of first idea that you have sometimes
+
+the limbic system is this is this ancient pathway or
+
+part of the brain that evolved in reptiles and lower
+
+animals is preserved, still is unconscious, or we have no
+
+access or awareness of its activity, but it drives our
+
+emotions and cognitions.
+
+That, I think, is the kind of idea of the
+
+limbic system that we usually have.
+
+I think know, by the way, that the limbic system,
+
+which is a circuit which includes the hypothalamus, anterior thalamus,
+
+the finger gyrus and we'll get on to that in
+
+the next slide, has over the years had things attached
+
+to it.
+
+So for example, the amygdala, the septum, the orbitofrontal cortex
+
+and portions of the basal ganglia, turns out, as we
+
+see in the next slide.
+
+That first time that basically the limbic system now encompasses
+
+much of the brain and I think its explanatory power
+
+is therefore substantially reduced.
+
+There's other reasons to think that this explanatory power is
+
+not very strong, and that is that actually the idea
+
+that we have evolved on top of this limbic system
+
+is not really a correct reading of evolution.
+
+So this is a graphical description.
+
+By the way, I encourage you to read this article
+
+because it has perhaps the best I've ever seen.
+
+Your brain is not an onion with a tiny reptile
+
+inside.
+
+The classic view of the limbic system.
+
+It's kind of described amber here.
+
+The idea is that evolution is the fishes evolve into
+
+rodents, evolve into humans, and that fishes, which have this
+
+pronounced limbic system, which is still substantially preserved in mass
+
+and then only slightly elaborate and then slightly inverted, sorry,
+
+and then further elaborated in humans that this limbic system
+
+we've inherited from this ancestor.
+
+That's not how evolution works.
+
+We are not so linearly related.
+
+We are not the end product of the chain of
+
+evolution whose goal is to create stupid human beings.
+
+Instead, evolution is a series of parallel processes, and indeed
+
+we diverge from the evolutionary lineage that links us with
+
+fishes.
+
+Before my did.
+
+And indeed, if you look at the brains of each
+
+of these three different species, species, humans and mice, you
+
+actually find shared components there in all the systems more
+
+pronounced or less pronounced in different species, but still same
+
+components.
+
+So the idea that this limbic system is something that
+
+was the kind of entirety of the cognitive system of
+
+teachers and sits there in that sort of unconscious awareness
+
+in ourselves is not really an accurate description of evolution
+
+nor of the brain structure of these animals or ourselves.
+
+So for that reason, I would argue that the idea
+
+of thinking the limbic system has only limited value.
+
+Nevertheless, this is the limbic system and in particular the
+
+circuit here, which you can read about in your letter.
+
+But the idea here is that there's a circuit, as
+
+I said before, the single cortex, the hippocampus, the hypothalamus
+
+and the anterior thalamus missing the four words or working
+
+together in a circuit to produce some emotional state.
+
+This was the state of play in the 1970s, 1980s.
+
+It's now been largely supplanted mainly by studying particular brain
+
+areas such as the amygdala.
+
+And and we'll go through that in the next set
+
+of the lecture.
+
+Before I get on to that, I just want to
+
+make a digression into understanding emotions through emotional phases, because
+
+most of us communicate our emotions through our facial expressions,
+
+and most of us understand the emotions of others by
+
+looking at this facial expressions.
+
+This seems to be the major route through which we
+
+communicate emotions, and also animals can also recognise and communicate
+
+emotions through similar facial expressions.
+
+Turns out that you can actually train computer programs to
+
+recognise categorise very accurately the emotions that people might be
+
+experiencing by simply reading the visual image of their face.
+
+This was now a few years ago.
+
+This particular one technology is substantially improved, but effectively the
+
+kinds of neural networks that bound artificial intelligence that are
+
+bound in our world now are quite capable of using
+
+images of you through your video camera and your computer
+
+or your phone to read, or at least try and
+
+classify your emotional state.
+
+And they do this, unfortunately, very accurately, not always accurately,
+
+but pretty accurately.
+
+That is, there is a set of facial configurations that
+
+we all seem to share when we experience certain emotions.
+
+We've actually known that for a long time.
+
+It's these lovely photos doing the work of Titian in
+
+the mid 19th century who discovered one of the very
+
+first uses of electricity in experimental science discovered that you
+
+can actually create facial expressions on individuals simply by stimulating
+
+particular groups of muscles on the face.
+
+So these in this picture here, this is Dustin.
+
+Again, we don't really do experiments like this anymore, unfortunately.
+
+Maybe.
+
+But these are little electrical stimulating devices being attached to
+
+the muscles.
+
+I told you many lectures ago, the muscles of the
+
+other electrically excitable cell in the body of the nerve
+
+cells.
+
+And it turns out that by passing current into muscles,
+
+we cause them to contract.
+
+And if we cause these contractions in particular muscle groups
+
+in the face, we can provide these things that look
+
+like almost realistic expressions, fear, smiles, etc..
+
+The point I want you to take from this is
+
+that the organisation of the facial muscles seems to be
+
+such that it simplifies and allows expression of emotion through
+
+expressions.
+
+We seem to have developed our face muscles for that
+
+purpose.
+
+Sometime later, Ekman and colleagues discovered that there was actually
+
+a proposal and then provided evidence for the hypothesis that
+
+there are actually universal emotional faces that we can all
+
+recognise, and that we may all just claim that largely
+
+the these emotional faces, the six faces.
+
+So the universally accepted is universal and another couple that
+
+are more controversial.
+
+If you look at these posed actor that faces anger,
+
+fear, disgust, surprise, happiness, sadness.
+
+You should or maybe not, but you should probably recognise
+
+the same expressions and the emotions in those expressions in
+
+work that my wife just published actually yesterday in the
+
+Proceedings of the National Academy of Sciences.
+
+She challenges this distinction.
+
+Turns out that actually these posed acted out expressions are
+
+not very good ways of testing, emotional recognition, and that
+
+if we allow each other to evolve the expressions in
+
+images, devolve the expressions that we think relate to anger
+
+or fear or sadness.
+
+It turns out we can evolve very divergent expressions.
+
+There is many commonalities, but there's a lot of differences
+
+such that two individual people may recognise the one face,
+
+for example, this one here as two different emotions fear
+
+or surprise might be.
+
+However, the reason that Ackman's work became so popular and
+
+influential is that these studies conducted in groups of people
+
+who had had limited cultural contact with other parts of
+
+the world.
+
+In this case, the tribesmen of Papua New Guinea, a
+
+small island just north of the Queensland in Australia, very
+
+densely vegetated, a lot of hills and valleys.
+
+A number of tribes within them who had had very,
+
+very limited contact with any part of the Western world,
+
+even in the 1970s.
+
+And this famous study sought to see whether or not
+
+the facial expressions they produce were similar to those that
+
+we in the West might produce for similar kinds of
+
+emotional states.
+
+And the conclusion was that they were indeed suggesting that
+
+it's not just about cultural conformity or spread of between
+
+different cultures.
+
+That leads us to a commonality in our facial expressions
+
+and emotions, but actually that these are something innate, all
+
+inbuilt in humans.
+
+If we try to put these universal of emotions on
+
+that axis of arousal and violence that we described earlier,
+
+we find that actually, somewhat surprisingly, almost all of them
+
+are associated with higher arousal.
+
+I'm not exactly sure why this is.
+
+I have a feeling that these emotions that I'm feeling,
+
+the emotions that are associated with high arousal that are
+
+most important for us to communicate and for us to
+
+respond to.
+
+It also turns out that the way that we make
+
+these expressions depends on somewhat different brain systems, or at
+
+least a couple of different brain systems.
+
+That's, well, well-established in looking at people with small brain
+
+lesions in appropriate parts of the brain.
+
+And you can see here the two types of emotional
+
+paralysis that you can see in people with these small
+
+lesions, one brain called facial motor paralysis, that's one on
+
+the left here.
+
+The other emotional motor paralysis and emotional motor paralysis.
+
+People have very much difficulty forming the actual expression associated
+
+with an emotion.
+
+In face of murder paralysis.
+
+Since dead people have difficulty in forming emotions if they
+
+are asked to generate that emotion without the appropriate stimulus.
+
+Whereas if they had provided an appropriate stimulus, they can
+
+actually produce a smile.
+
+And the inference from this work is that there's two
+
+strains of facial emotion, a volitional system and law of
+
+Matic system.
+
+And the automatic system is one that includes the hypothalamus,
+
+the amygdala in the frontal cortex, i.e. the limbic system
+
+or its components.
+
+So I want to introduce that because this is the
+
+normal way that we trying to out someone else's emotional
+
+state is to look at the facial expressions or to
+
+communicate.
+
+The emotional state is through that.
+
+And we're going to spend a little bit of time
+
+in the next part of the lecture going through some
+
+of the mechanisms that might be important in trying to
+
+bring these two things together the recognition of textual emotions
+
+and the production of emotion through responses.
+
+So we mentioned the amygdala before.
+
+It's part of the enlarged to kind of larger limbic
+
+system, not the original one.
+
+It was actually discovered in the late 1930s, early 1940s
+
+by Coover and Bucy, who did some experiments on monkeys
+
+in which they removed large fractions of the temporal lobes.
+
+And they discovered very complex behavioural changes in these animals,
+
+including noses, sexuality, inappropriate eating and the lack of fluency
+
+in the constellation of these symptoms is often called Clifford
+
+syndrome.
+
+Now these were very large lesions appropriate to the surgical
+
+techniques at the time.
+
+It took several decades before more improved surgical techniques could
+
+remove smaller parts of the brain.
+
+And asked the same kind of questions.
+
+And indeed, it was Larry Weiss Prince, who's a very
+
+famous and important neurosurgeon, who discovered that by removing a
+
+little bit of the brain called the amygdala, amygdala means
+
+almond.
+
+So it's an almond shaped part of the brain.
+
+But by removing this component, you could reproduce the emotional
+
+symptoms that these animals had experienced.
+
+So this part of the brain, the amygdala from then
+
+on became a very much of the focus for trying
+
+to understand how emotions are represented in the brain.
+
+The other paradigm I want to introduce you to is
+
+that that's been popularised by Joe LeDoux.
+
+Joe to do is at New York University.
+
+He developed and continues to use this paradigm called conditioned
+
+fear.
+
+Now.
+
+I saw Joe.
+
+I invited Joe to give a lecture once, and at
+
+the end of the lecture, I'm about to describe to
+
+you the condition of the part.
+
+On the end of the lecture, someone asked, Have you
+
+ever thought of doing another type of experiment rather than
+
+this conditioned fear?
+
+And his answer was briefly, no.
+
+He said no.
+
+And I get asked that question all the time.
+
+The reason I like this paradigm and why I continue
+
+to use it is that I can predict now the
+
+experience of every animal.
+
+I don't need to do the actual behavioural experiment any
+
+more.
+
+This is such a reproducible behavioural experience experiment that it's
+
+no longer necessary to conduct experiments on animals to actually
+
+look at the behaviour itself.
+
+You can just assume that that is what would have
+
+happened and conduct other measurements that would look at the
+
+neuroscience involved in that.
+
+But conditioned fear in paradigms in love cells which are
+
+incredibly powerful, are very simple.
+
+The basic idea is to put an animal, a rat
+
+usually, or a mouse in a little box, and that
+
+box will have a little grid on the floor and
+
+a little speaker on the wall.
+
+And through the grid, you can pass the small amount
+
+of current that's aversive to the animal, although not actually
+
+painful.
+
+And if you put current through that grid, the animal
+
+will generally freeze.
+
+It's an aversive stimulus, a potentially threatening stimulus.
+
+Now, if you play the sound in of itself before
+
+you without pairing it with that electric stroke, the animal
+
+generally maybe the first time and he was like, what
+
+the hell is going on there?
+
+But very rapidly habituate and then ignores the sound because
+
+it's a neutral, unthreatening stimulus.
+
+However, if you pair or associate that sound with the
+
+electric shock over several trials, the animals then replay the
+
+sound by itself.
+
+The animal is now displays just the reactions that it
+
+would have otherwise displayed to the electric shock.
+
+In other words, it freezes.
+
+So this is a condition.
+
+It's a classic paradigm.
+
+It's been used to elucidate the role of the media.
+
+It's not necessary to do this only in mice or
+
+rats.
+
+You can also do this in humans.
+
+I love this video.
+
+I'm dying to know.
+
+That we have.
+
+Period of classical conditioning I'm trying to get.
+
+This will be the same thing.
+
+And then I've got experience with this.
+
+We learn the relationship.
+
+Between a sounds and it's got more of a super.
+
+Duper so that we can take for are going to
+
+look like that.
+
+Mastery works so you don't need to use rats.
+
+You can use humans.
+
+Let down some ethics people.
+
+Okay.
+
+So this.
+
+Yes, it's a very good question.
+
+And actually fear is the wrong this is what's what.
+
+The conversation goes around every about ten or 15 years.
+
+We just keep on going around the circles.
+
+The question is, is there an emotional response or is
+
+the animal responding to the potential threat?
+
+Okay, so distinguishing between those two hypotheses is almost impossible.
+
+So there's a subjective ness to fear as a concept
+
+that we can't explore in a rat.
+
+So this goes around and around.
+
+Is is fear simply described as a response to a
+
+threat or is it something in addition to that?
+
+And unfortunately, there's been no resolution of that particular discussion.
+
+You do know that the animal is exhibiting all the
+
+signs of having had of of experiencing a potential threat.
+
+Now, whether that is associated with fear in and of
+
+itself is another question.
+
+So it is a good question and unresolved still.
+
+And it goes around this discussion goes around in the
+
+in the field every ten or 15 years because it
+
+threatens the threat of external stimuli.
+
+So the internal response.
+
+So the amygdala is central to to, as Joe has
+
+worked so extensively, is essential to understanding this responses they
+
+may do is actually have quite a complicated nucleus.
+
+It's consists of at least 13 subdivisions.
+
+We tend to ignore all of them except for two
+
+or three.
+
+The two or three that we're usually interested in, the
+
+lateral nucleus, the basal nucleus and the central nucleus.
+
+Usually, indeed, we actually ignore the base of the nucleus
+
+and just think of the lateral, the central nucleus.
+
+The lateral nucleus is where all this sensory input comes
+
+into the amygdala from the cerebral cortex and from other
+
+parts of the brain.
+
+And central nucleus is the output of the one that
+
+goes in control.
+
+The physiological responses.
+
+There are other outputs from amygdala, from the other parts
+
+of it, which instead of controlling physiological responses, actually project
+
+back to, for example, the cerebral cortex.
+
+And we'll go through that briefly at the end in
+
+humans, the images found around here.
+
+In rats.
+
+It's a slightly different location.
+
+So this schematic turns the outcome of two or three
+
+decades of work from Joe and others, which tells how
+
+you might generate this condition.
+
+Fear response.
+
+We think of the condition stimulus as a sound stimulus.
+
+It's conditioned because it's otherwise neutral, and then it gets
+
+conditioned and then there's an unconditioned stimulus or us, which
+
+is the future.
+
+It's unconditioned.
+
+In other words, the response to that stimulus is an
+
+innate response is an instinctive response you don't have to
+
+associate to get that response.
+
+If you play the conditioned stimulus and the unconditioned stimulus
+
+together, sound and food shock, the signals from these two
+
+things are coming through the auditory pathway and through the
+
+similar sensory pathways.
+
+And these signals converge at the level of the lateral
+
+nucleus in the amygdala.
+
+So you have sound inputs coming through, somatic sensory inputs
+
+coming through together.
+
+These can now work together to find mechanisms of synaptic
+
+plasticity to now convert that or allow that sound stimulus
+
+to cause the same physiological response to the unconditioned stimulus
+
+would have otherwise.
+
+And then that output is then provided by the central
+
+nutrients.
+
+Now, you'll note here that there's actually several potential sources
+
+of input to the amygdala, including the cerebral cortex, but
+
+also subcortical areas such as Solomon's.
+
+And it turns out that that's quite important for understanding
+
+some of the reactions that we animals have to people
+
+or other threatening stimuli.
+
+So, for example, one of the early studies from Joe
+
+showed that auditory cortex was not required for responding in
+
+this condition fear, paranoia.
+
+So if you remember before, when we were talking about
+
+versus theories of emotional response, the idea was that you
+
+perceive the stimulus with your cerebral cortex, and then that
+
+generates that cascades through into other events.
+
+What does work started is that at least in rodents
+
+and as we'll see in a minute or so in
+
+humans.
+
+You don't need the cerebral cortex to respond to these
+
+threatening events, suggesting that some of these threatening events could
+
+be communicated to the amygdala via pathways that have no
+
+access to perception or cognition themselves that are below the
+
+level of awareness.
+
+The particular experiments here were to lesion the bit to
+
+the auditory cortex of the retinas, the way the auditory
+
+cortex is in the rat.
+
+And then to put them in this condition fear paradigm
+
+and to measure several variables, including the freezing response, but
+
+also things like blood pressure increases and so forth, and
+
+become long story short.
+
+Effectively, all the components of the threat, response or fear
+
+response in rats were preserved in those animals that had
+
+auditory cortex and didn't have auditory cortex.
+
+In other words, cortex was not required for the animals
+
+to exhibit this condition.
+
+Fear that suggests that subcortical pathways are sufficient.
+
+And indeed, the dominant hypothesis from Joe and others now
+
+is that there are two votes for sensory input to
+
+the amygdala.
+
+One that goes through the thalamus and one that goes
+
+through the cerebral cortex.
+
+So for example, in human brain, the visual thalamus is
+
+here, this blue blob.
+
+The visual cortex is here.
+
+The back of the brain and the amygdala.
+
+It's here down the temporal lobe.
+
+There are some either direct or indirect inputs from the
+
+thalamus to the media, as well as inputs from the
+
+visual cortex, but indirect and direct.
+
+And the idea here is the central idea here is
+
+that for some kinds of stimuli that you need, a
+
+rapid response to those stimuli might be included in this
+
+pathway that simply requires the farmers.
+
+So, for example, snakes on a path in front of
+
+you, you don't want to hit this guy.
+
+It was like a snake.
+
+Maybe it's a tiger snake round snake.
+
+Instead, you want to get out of the way.
+
+Actually, literally, you should freeze.
+
+Many people try to get out of the way, but
+
+if you get out of the way, they'll come for
+
+you actually should just freeze.
+
+That's one of the life tips you learn in Australia.
+
+So the snake is there.
+
+Maybe the signals for the snake were actually passed through
+
+this thalamic pathway, this rapid pathway, the middle rather than
+
+through the cerebral cortex, requires a perception that you can
+
+react to that snake without actually having perceived it yourself.
+
+It's sometimes called the high road and the low road,
+
+the low road from the thalamus to move to the
+
+highway through the sensory cortex.
+
+And that's basically what I've just told you.
+
+In humans, there is some evidence, as in rodents, there
+
+is some evidence that the pathways are sufficient to activate
+
+the amygdala.
+
+This is a fascinating study of a person with blind
+
+sight.
+
+We discussed neglect, a couple of lecture lectures, go blind
+
+sites of different phenomena.
+
+If you lose part of your central cortex, you become
+
+blind spot that you're not unaware of something like this.
+
+You neglecting something be actually, at least according to people
+
+who have these lesions you experience as an absence, a
+
+blackness.
+
+Basically in the US, in that part of the visual
+
+world, people with lesions, the visual cortex report not being
+
+able to perceive anything in the appropriate part of the
+
+visual world.
+
+So, for example, if your lesion on the left part
+
+of your visual cortex, you won't see anything on the
+
+right path of your visual field.
+
+Nevertheless, people with these lesions can still respond appropriately, sometimes
+
+to visual objects presented in that blind part of the
+
+visual field.
+
+A fascinating phenomena.
+
+For example, they can actually navigate through obstacles in a
+
+corridor or tell or actually respond reliably and see what
+
+orientation opinions operate or mind to assign.
+
+In addition, if you put someone in the scanner and
+
+MRI scanner and conduct measurements whilst this person's images in
+
+this case facial images of facial expressions, you can find
+
+that in this part of the brain where the least
+
+means this is a simple cortex is lesion.
+
+The image was nevertheless activated by in this case, people
+
+faces.
+
+So for some reason or some pathway that bypasses visual
+
+cortex, the primary visual cortex allows people to actually get
+
+see moving to the Middle East.
+
+Similarly, in humans with an intact amygdala, you can do
+
+experiments such as backward masking this as you rapidly present
+
+a stimulus and mask it with noise.
+
+People report not being able to see the stimulus that
+
+was presented briefly present a stimulus.
+
+Turns out if you do that and you construct the
+
+stimulus appropriately, you can find different.
+
+You can find responses in the amygdala in mind that
+
+seem to resemble fearful faces.
+
+This is also evidence that you do not need perception
+
+or cognition to actually activate.
+
+So this is evidence that even in humans, as in
+
+rats, there is some subcortical pathways as well as cortical
+
+pathways.
+
+And indeed, if you look at facial mimicry, when we
+
+see people make expressions, we tend to make those expressions
+
+ourselves.
+
+That's called facial mimicry.
+
+You find that facial mimicry is intact in people with
+
+blind side.
+
+Again, further evidence that you don't need to perceive things
+
+to be able to detect and respond to emotions.
+
+There is some.
+
+Caveats.
+
+This thing you should be aware of.
+
+For example, there are very few people in the world
+
+who have had lesions to the amygdala in the one
+
+or two cases that have been studied does not seem
+
+that this is 100% necessary to respond to emotions.
+
+But bear in mind, as we talk about methods lecture
+
+that people with lesions can find compensatory pathways and things
+
+do change.
+
+So it's not clear whether or not these kinds of
+
+responses are true in intact humans.
+
+I want to spend a couple of minutes just illustrating
+
+to you that these emotional networks, such as the amygdala,
+
+impact not only the physiological output, but also other cognitive
+
+processing in the brain.
+
+It turns out actually, that the amygdala is either directly
+
+or indirectly connected to a huge amount of the brain
+
+striatum prefrontal cortex, medial temporal lobe, cerebellum, pixabay neocortex, etc.
+
+There's plenty of opportunity for the amygdala to guide our
+
+cognition via emotional responses, in instance of time.
+
+Because I would just like to introduce something for a
+
+few minutes at the end of this lecture.
+
+I'll skip over these two little slides, but you can
+
+go back to look at them at your leisure.
+
+I want to focus on this one, which describes an
+
+experiment that could have already really been done once or
+
+twice in our history.
+
+As you all know, on September the 11th, 2001, perhaps
+
+before you were born, the Twin Towers in New York,
+
+the World Trade Centre, were destroyed in a terrorist attack.
+
+This was a very emotional experience for many people.
+
+My wife, for example, was based in New York University
+
+at the time.
+
+She stood on the top of the building and watched
+
+those towers come down.
+
+She still remembers that day very clearly.
+
+The question that was asked in these experiments by researchers
+
+whose prioritisation might be slightly strange was the day after
+
+2001 researchers in Duke University.
+
+Contact of Duke students.
+
+The Duke is not New York itself.
+
+Nevertheless, everyone of us was kind of watching these these
+
+attacks and ask very simple questions.
+
+Do you remember what do you remember about the events
+
+on September 11th?
+
+And what do you remember about other unrelated events?
+
+The idea is that these events on September 11th might
+
+be associated with flashbulb memories, things that are emotionally salient.
+
+And the question is, do these emotionally salient events last
+
+longer than nonstate ones, and do they have different content,
+
+the most salient ones?
+
+The answer to the first question is yes.
+
+They seem to be more vivid for longer than non
+
+emotionally salient events.
+
+So these on this graph on the left here for
+
+224 days after September 11th, these ratings were made, some
+
+people for September 11th or other events.
+
+You can see that the vividness for the subjective experience
+
+of remembering events around September 11th was much greater than
+
+that for other events, suggesting that emotion colours, memory, makes
+
+things vivid, makes things more memorable.
+
+On the other hand, the actual number of details that
+
+we were able those people were able to remember about
+
+the 11th and other events didn't seem to be much
+
+different.
+
+So what's the vividness and therefore importance of that memory
+
+for people was higher.
+
+The actual structure, the clarity of that memory was not
+
+necessarily higher.
+
+This has importance for understanding things like, for example, eyewitness
+
+testimony.
+
+So what I wanted to bring you here is that
+
+clearly emotion does colour memory does it in complex ways.
+
+Does this suggest that those circuits within the amygdala and
+
+similar structures influence aspects of the hippocampus and other formation?
+
+The final slide I want to show you simply reinforces
+
+that by looking at some imaging studies.
+
+But I will just mean the time link to go
+
+through that yourself.
+
+Q Would you like to just come down and help
+
+people understand what we want you to do during your
+
+reading week?
+
+So thanks for that.
+
+I hope we've both understood it.
+
+Something about emotions and the brain.
+
+I can't tell you about life, but we can tell
+
+you about one of those things anyway, right?
+
+Q Do.
+
+You think you're going to find something to that.
+
+Effect?
+
+I don't think.
+
+So, but I'm just going to take us through the
+
+process of feedback for this module.
+
+Before I do that, I just would like to take
+
+on you had this lecture and it could take good
+
+care of your brain and your amygdala otherwise ends up
+
+in lots of dangerous situations.
+
+Has anyone seen Die Another Day?
+
+Great James Bond film from the mid-nineties.
+
+Robert Carlyle.
+
+Okay, can watch that.
+
+Yeah.
+
+So the best thing most I think if we see
+
+one of these patients who has no MC to their
+
+fitness emerges loving, playing dangerous snakes and tarantulas and whatever,
+
+there's there's this lack of inhibition and we'll be picking
+
+up that topic in lectures following this.
+
+And the memory system is sound is just getting onto
+
+memory at the end there.
+
+And we'll be looking at methods where they've been able
+
+to implant false memories into rats brains, where they can
+
+turn on the memory, the flash of light, using that
+
+fear conditioning approach and make rats afraid of places that
+
+are completely normal, but they've just inserted false memories.
+
+So we'll come back to that as the great play
+
+into that memory circuits.
+
+So this is the Moodle page for the module.
+
+Just highlighting that we think is yeah.
+
+The different modes.
+
+You can do it.
+
+It's fantastic.
+
+Exactly.
+
+Because a lot of hidden material behind the lectures.
+
+Okay, so there's a keep in touch and we've been
+
+able to look.
+
+At these.
+
+Questions here and we put announcements there and we've got
+
+questions.
+
+People have put in great questions and we'll try to
+
+respond to those through the announcements page.
+
+This is for general questions.
+
+If something comes to you and you want to ask
+
+a general question about the course, feel free to throw
+
+a question into that for each the each of the
+
+weeks from, let's say further onwards is a a at
+
+the end of this fits with this class times is
+
+reading and there.
+
+Are.
+
+Questions about lectures to feel free against remind everyone if
+
+you have a question that pops up after reading maybe
+
+in the middle of reading week or reading material and
+
+you think, Oh, looking back at lectures for next week
+
+for don't post the question in to that.
+
+I will respond to that.
+
+We'll see these.
+
+But really today is the highlight right at the end
+
+is a now exceptional have you would say and we'd
+
+like to get your feedback through the key to have
+
+this continuous module dialogue you still loves acronyms C and
+
+D approach to the.
+
+Module and.
+
+There is now a link to a mental page where
+
+you can go, I want to go.
+
+Now.
+
+Yeah.
+
+It needs to work.
+
+So it's currently sitting in there.
+
+It's still running, but it needs to be updated.
+
+So after this lecture we'll get that functioning.
+
+If you can go in and answer the questions.
+
+Have you understood things?
+
+How do you say what are the things for this
+
+course?
+
+Is that within this large room there are people from
+
+psychology, so you might have different perspectives to people inside
+
+psychology.
+
+It may be useful to get your reflections on this
+
+module compared to other modules you're setting, but it will
+
+be all of the questions.
+
+And that means that you can go in and access
+
+from that link.
+
+In a couple of weeks we'll have another mentor as
+
+you going forwards, more CMC approach, more, more feedback from
+
+you and at the end, surprise, surprise, another mentee page
+
+for feedback.
+
+If you're in any module and I'm sure you're used
+
+to filling out these mentees, but we'd love to hear
+
+from you.
+
+We've had great we've had some useful suggestions on the
+
+page and we'll keep collecting that.
+
+Thank you for all your attendance and enjoying the module.
+
+We'll see you next week.
+
+So there is a lot of great work to do,
+
+but a lot.
+
+Great.
+
+It's a really good question.
+
+It's pretty pretty.
+
+Hard to talk about what's.
+
+Going to.
+
+Happen next week.
+
+Right.
+
+That's because.
+
+It doesn't make.
+
+Sense to.
+
+Keep people from actually able to pick up the phone
+
+call for a living.
+
+Record the next.
+
+It's hard to record the next question.
+
+I found it on the floor of someone to drop
+
+it so we can hand it.
+
+To the psychology man office or.
+
+The main.
+
+Office.
+
+That's the most likely outcome.
+
+Of that discussion.
+
+Yeah, I could just make an announcement.
+
+I mean.
+
+Although if anybody's lost a phone, we found a mobile
+
+phone.
+
+Here, We'll put it in the reception's.
+
+If anybody is walking out and somebody is running back.
+
+That phone will be in the reception for the building.
+
+I mean.
+
+Maybe not so lucky for people who.
+
+Would.
+
+Like.
+
+To see.
+
+Different things.
+
+I do.
+
+Think.
+
+That it's tricky because it's the only way for people
+
+to think that.
+
+That's pretty cool.
+
+I think.
+
+That's absolutely.
+
+Great.
+
+School teaching is not acceptable.
+
+I think things like that.
+
+Very nice to talk to you for a few hours
+
+because sometimes it's a part of the whole.
+
+I want to get some stuff because I don't care
+
+about 15 minutes per 100,000 people.
+
+Because.
+
+People trying to get me to actually try to keep
+
+something that's interesting because I'm focusing.
+
+On you to.
+
+Come to.
+
+You.
+
+Normally you have to start.
+
+To.
+
+Some of.
+
+These private firms to pick these people.
+
+You can.
+
+Make more people want.
+
+To let go.
+
+Why not?
+
+Well, that's.
+
+How.
+
+It lots of things.
+
+You can.
+
+Do about that perspective.
+
+Because unfortunately, it's impossible to get people to look at.
+
+What's going on here.
+
+Yeah, we get really we.
+
+Get feedback to people about the course of events, just
+
+everything updates and you can put that in as a
+
+feedback you'd like.
+
+Stephen That's what I'd like to say.
+
+A lot of.
+
+Students don't want to understand that either, but apparently the
+
+feedback from.
+
+Feedback.
+
+That might.
+
+Be difficult.
+
+For the general nominee is that people get a quick
+
+look at time frames when this happens, but that's a.
+
+Time that it's.
+
+One that might be that may be the case, but
+
+that it's actually you can see back into the things
+
+that we can use that to say, Hey, you look
+
+like you want me to do videos, basically, but.
+
+You don't have.
+
+To do it.
+
+Some of it might take these guys.
+
+Yeah, except this is six years of research.
+
+That's some of.
+
+The material, but not what you want to do to
+
+make.
+
+This work.
+
+Yeah, it's not.
+
+Material.
+
+Why didn't I get a first.
+
+Bite of this?
+
+And I didn't say that.
+
+That's the problem.
+
+It's kind of really happened since, Mr. President.
+
+So I said, Well, I originally said that any on
+
+the day would have been.
+
+The school.
+
+But she's not accepting.
+
+What's been happening in Iraq.
+
+And the way you.
+
+Might.
+
+Have noticed.
+
+The really useful question.
+
+It's good to get feedback about how you doing things
+
+differently, doing something right.
+
+Yeah.
+
+Yeah, I know.
+
+I'm just I'm just hoping that by pinpointing very quickly
+
+that these kind of theories, we do.
+
+Have a lot of people out there who might be
+
+eager.
+
+To meet with individuals, something to discuss how to give
+
+some solutions.
+
+Access We really hate that.
+
+It's the men's lives work, stuff like that.
+
+Yeah, I just.
+
+That because we're not going to make it.
+
+But, you know, I think that there is not much
+
+concern about this because the problem.

raw_transcripts/lecture_11.txt

@@ -0,0 +1,1997 @@
+It's not an easy world out there.
+
+Looks nice there on the campus today, but it's a
+
+difficult world to survive in.
+
+And we have evolution from it.
+
+So what is going on in mammals, your brain right
+
+now and other mammals and other species?
+
+What we going to focus on will focus on the
+
+core part of today's lecture.
+
+There's textbook reading.
+
+If you go to the reading material from Carlson and
+
+Briquettes for Book on Behaviour, there's some other cool references
+
+to read through.
+
+Not too many, just a few examples to read through
+
+after this.
+
+But the cool thing I want you to take away,
+
+there are two systems in your body for dealing with
+
+stress.
+
+The stress is when your body is under pressure and
+
+you have to maintain homeostasis.
+
+You have to maintain your body, your integrity.
+
+Get on with things.
+
+Doing that is not easy to make us make that
+
+happen.
+
+We have two systems in our body, in mammals, a
+
+sympathetic adreno system called Sun for sure, and the hypothalamic
+
+pituitary adrenal cortical system, the HP system or the HP
+
+axis is a company.
+
+So first of all, let's look at this sound system,
+
+this sympathetic adrenal medullary system.
+
+So here's an example of a lion attacking this would,
+
+for a human, be a very stressful event if it
+
+happens to you, where you happen to be in a
+
+situation where a live lion is attacking you and those
+
+stressful things.
+
+And this is coined by a psychologist and somebody with
+
+the idea of flight or flight.
+
+And in this case, it's flying away from the lion.
+
+You might fight that lion.
+
+Very bad decision for most humans, or you might fly
+
+away.
+
+But either way, you need to respond.
+
+You're kind of sitting relaxed, right, and making notes here.
+
+And your body's set to do that.
+
+But it's not going to be well set to run
+
+away or fight a lion.
+
+It needs to change.
+
+You need more oxygen, more blood flow, a lot of
+
+things in your body ready to make you do that.
+
+Same for rabbits and for any animal trying to escape
+
+What happens in the first.
+
+The second lecture I gave a neuroanatomy.
+
+I put up this slide that says, Here's these two
+
+systems from a autonomic nervous system.
+
+I said, I'll come back to it around today, this
+
+lecture after reading week.
+
+So what we have here on the left is a
+
+sympathetic adrenal system that is critical for your response to
+
+threat like a lion.
+
+So what happens is that in your spinal cord or
+
+a number of you can see on the left hand
+
+side a sequence of neurones that are ready to be
+
+activated to project out to a whole lot of bits
+
+of your body, different organs, right the way out from
+
+your eye down to your bottom, right at the bottom
+
+of your body.
+
+So these all these things in these parallel red fibres
+
+coming out and rise, obviously they're marked and right here
+
+they're not really right in your body, but they go
+
+and do things like increase your heart rate, the heart
+
+rate goes up.
+
+You've got more oxygen in your blood to run faster
+
+away from that line.
+
+It's one of the critical things your your stomach is
+
+going to switch into No longer digesting food.
+
+Your bladder may get rid of any urine.
+
+If you're carrying a lot of weight, you know, you
+
+might pay out a fright and run.
+
+There's a lot of things you can see that are
+
+going on that are regulating your body to make your
+
+pupils dilate, ready to to to react.
+
+And again, sorry, the lighting system I can't control as
+
+high as read these off, but hopefully you can see
+
+that the core idea is on the left is the
+
+system Upregulates Now now, if you kept having this going
+
+on, your heart rates going higher and higher and your
+
+your body's getting ready for threat, you would die.
+
+You overstimulating your body beyond the amount of food you
+
+can take in.
+
+It's not going to digest anything.
+
+It's just going to go into the stress state of
+
+a reaction to a line.
+
+Now, on the right hand side of that diagram, we
+
+have the parasympathetic system which runs on a molecule called
+
+a seat coordinates.
+
+These two systems have their own specific molecules, adrenalin and
+
+noradrenaline as written on the bottom.
+
+There will come into that and there is a seat.
+
+Alkaline is the other molecule on the right.
+
+Now on the right hand side we have the system
+
+allows you to calm down, come down from the heightened
+
+state of threat, analyse your digestion to pick up, lowers
+
+your heart rate, gets your body to digest things as
+
+part of the rest and digest system.
+
+So we've got this circuitry there and you can see
+
+that on the left side, you've got the sympathetic system
+
+coming out of the spinal cord and on the right,
+
+right on the bottom of the spinal cord.
+
+There are some key parts of the sympathetic system, but
+
+a lot of these pathways come out right at the
+
+top of the brain, right at the top of this
+
+of the spinal cord section to regulate the heart.
+
+And some of these are nerves from the cranial nerves
+
+covered light to the heart to regulate the heart, heart
+
+at the top there.
+
+So this is what I'm talking about.
+
+You can see my mind, maybe not up here.
+
+These pathways to the eye and the heart and the
+
+lungs and so on.
+
+Okay.
+
+And there's a little icon to highlight.
+
+This is where we're going to spend a bit of
+
+today's lecture looking at this particular organ in your body
+
+you'd never really think about, here is a kidney.
+
+So you need to, you know, organise your fluid or
+
+the fluids in your body.
+
+If you're a medic, you'll be learning a lot about
+
+the kidney and you're doing brain and behaviour.
+
+So we're not very interested in the kidney today.
+
+What we are interested in is the adrenal glands.
+
+Your body has all sorts of glands hidden behind it
+
+and one of them is critical for running away from
+
+that line is your adrenal gland.
+
+And this, this adreno, the sympathetic adrenal medullary system is
+
+the medullary part refers to the medulla, the middle part
+
+of this adrenal gland.
+
+And this is where adrenaline is when you you may,
+
+as some of you ever come across EpiPens or this
+
+worry about people eating peanuts and dying from it is
+
+because they, you know, they take an EpiPen with them
+
+filled with adrenaline because it will react.
+
+It will allow their body to increase their heart rate.
+
+The lungs will expand rapidly, bypass this circuit.
+
+But if your body's acting normally, it's not part this
+
+little structure here above your kidneys, the adrenal glands, and
+
+does this beautiful job of secreting adrenaline around your body.
+
+Written here is the nephron because that's what the US
+
+system United States, they usually get epinephrine.
+
+They like their own words for different things at times.
+
+Okay on the left.
+
+So that's all that.
+
+That's all the bits of the body drawn.
+
+If you look at this, these two major divisions within
+
+the autonomic nervous system on the left, we have that
+
+sympathetic system for regulating a fight or take flight system
+
+which causes all these different things that including some unhelpful
+
+things like nausea.
+
+If you attack by line, you may feel a bit
+
+sick, but it allows your eyes to expand and get
+
+live raises.
+
+Your heart rate raises your blood pressure.
+
+Everything's ready for running or attacking.
+
+On the right hand side, this parasympathetic system allows you
+
+to eat things, steadies your hands.
+
+Just, you know it.
+
+It's all sorts of different parts of this.
+
+You can see here, lowering heart rate and blood pressure
+
+is also known the rest and digest state.
+
+So this is two key systems for this.
+
+Some this is the sympathetic or the sympathetic adrenal system.
+
+Let's take a real world example to contextualise this.
+
+Just something that came on Twitter.
+
+This is this particular person.
+
+I haven't put their their name and details up here,
+
+but they provided this on Twitter some time ago, several
+
+years ago.
+
+This just describing using a Fitbit.
+
+So monitoring the heart rate and reading text messages.
+
+And that day that girlfriend broke up with them at
+
+exactly noon in their timeline.
+
+And you can see here this person's resting heart rate
+
+just tracking along New noon occurs and up goes the
+
+heart rate and it's sustained.
+
+Go right.
+
+And so midnight after they got this message of a
+
+girlfriend of broken up with them, it's just one real
+
+world example of what happens to your heart rate under
+
+stress.
+
+This is clearly this person describing a very stressful, horrible
+
+experience and breaking up and seeing it live and seeing
+
+that the heart rate has gone up and it hasn't
+
+he hasn't gone back to rest and digest.
+
+Yeah, even at midnight.
+
+This is a carrying on the process.
+
+So we've covered that same system.
+
+We're now going to turn to this HD access system.
+
+The other one, the two systems, because you just saw
+
+in this example, the upregulated heart rate set to react.
+
+Now a line is an immediate threat.
+
+Breaking up with your partner, like maybe you've be with
+
+your girlfriend for two years and you break up.
+
+It's really severe.
+
+And as your brain is going to think about all
+
+the implications of Break-Up and what this means for me,
+
+what are my what am I going to do with
+
+my social life?
+
+Lots of things go on.
+
+That heart rate is going to be raised, raised for
+
+some time, this extra stresses.
+
+But it doesn't just have a rapid response, it has
+
+it organised.
+
+Longer term response allows you to adapt to challenging situations.
+
+So what we've shown here is the human brain.
+
+Here's the nose of the challenge we discussed and we're
+
+looking at the corpus callosum, for example, not coloured in
+
+just so you can identify them are number of little
+
+nuclei here in the middle of the brain.
+
+Now in a rat or of old or something, these
+
+are really big because they're really important words for humans
+
+have a huge amount of cortex.
+
+We've added all round that these, these key subcortical structures.
+
+And again in my, my second lecture in your anatomy
+
+talks about cortex cortical structures and sub cortex.
+
+Today we're looking at to keep it of that.
+
+There's a whole load of this here.
+
+There's a familiar body will come in a couple of
+
+weeks time to someone who had a snooker cue smashed
+
+into their face skewering and damaging their military bodies.
+
+And I explain what happened to that patient.
+
+But it bypassed that type of thalamus, went under here,
+
+and it didn't have the problems I'm going to talk
+
+about today.
+
+So they didn't have any stress responses.
+
+So here it's hard to build different nuclei in the
+
+real brain.
+
+They're not coloured.
+
+This is just coloured to highlight them.
+
+And these are the hypothalamic nuclei hypothalamic.
+
+The word hypo just means lower.
+
+So here's the thalamus above you that does all the
+
+processing you need for connecting the cortex together.
+
+But underneath is the hypothalamus and has these different nuclei.
+
+All the top underneath them is another gland, the pituitary
+
+gland.
+
+So this is a bit this is very strange.
+
+Your brain is structured inside your skull, encased in the
+
+skull to protect your brain.
+
+Very important organ in your body sticking just out of
+
+the skull.
+
+And this little stalk is the pituitary gland, and it's
+
+a little gland that goes into your blood system.
+
+And it allows cells to send chemicals straight out of
+
+your brain into your blood circulation outside your skull.
+
+So it's it just sits there inside.
+
+You can see it encased in bone here, but the
+
+blood circulates through it.
+
+So let's dig into this in a bit more schematic,
+
+sort of what are they doing?
+
+So here is the hypothalamic pituitary adrenal axis and stress
+
+system.
+
+So here's the brain we just saw in the last
+
+slide is zoom in.
+
+This little tiny nuclei in here.
+
+We're just going to call these the hypothalamus now.
+
+And the key thing they do here is to release
+
+time into pituitary gland.
+
+There are cells there that produce a chemical called cortical
+
+growth in releasing hormone.
+
+So these cells are releasing a hormone, not a neurotransmitter,
+
+but a hormone into the anterior pituitary gland.
+
+In the anterior anterior pituitary gland, there are a number
+
+of cells that release their the adrenal cortical trophic hormone.
+
+So you've got CRH and 88 C THC.
+
+These two different hormones, the cascade of hormones.
+
+And those hormones go on to land on your adrenal
+
+gland just above your kidney.
+
+So this is like on here is I so seems
+
+a bit like a lot of, a lot of different
+
+steps.
+
+Why not just do one step?
+
+But we'll see.
+
+We'll see why that might be the the adrenal cortex
+
+a bit right on the edge.
+
+So we had that reaction.
+
+That same system is the bit in the middle of
+
+it, but on the edges, the edge of it, the
+
+sort of the outer layer, the adrenal cortex is where
+
+a number of hormones are released.
+
+And if there are, there are glucocorticoids, mineralocorticoid and sex,
+
+steroids, there's a whole lot of that gland is producing
+
+a lot of hormones for your body.
+
+You don't want to damage that gland.
+
+That's very important to you.
+
+The key one, you may have heard all this you
+
+haven't heard anything about stress is corticosteroids is a particular
+
+hormone that goes and then regulates here.
+
+This is called different organs like your heart, your lungs,
+
+your digestive system, all being updated by this hormone.
+
+So these are circulating.
+
+So three steps.
+
+These these kind of ACLs like cortisol as corticosteroid erodes
+
+the cortisol.
+
+So the reason what is always a chemical that you
+
+can use like a salivary test, so you can look
+
+at policemen and say, oh, did they go out and
+
+have to do some particularly difficult experience?
+
+Recently you might take a Swoboda saliva and find you.
+
+Half of them have read high cortisol rates.
+
+It's used very classically in stress studies.
+
+Now this cortical cortisol is it circulates around your body,
+
+has all these effects to regulate your body for better
+
+or.
+
+This distress, but it also goes back into the pituitary
+
+gland that goes back into the hypothalamus.
+
+And you can see these going down or plus positive
+
+driving up signals.
+
+Red pluses have got some blue minus signals here.
+
+These this circulating cortisol goes to actually reduce the responses
+
+in these two.
+
+This is the brain.
+
+This circulates back.
+
+So it's like it's a system that as you produce
+
+more of it acts.
+
+But as you get too much of it, it dampens
+
+it down, but it does more than just short circuit.
+
+So what we've looked at in this previous slide, if
+
+I go back, we've looked at this cascade from the
+
+hypothalamus time.
+
+There are a few more brain areas involved because your
+
+brain is not just your hypothalamus has all these other
+
+amazing that state.
+
+So here's the human brain we're going to you've had
+
+a lecture from Sam Sullivan on the amygdala.
+
+You're going to hear a lot about memory.
+
+And at the campus of the campus will talk about
+
+today in relation to stress is the pituitary gland that
+
+is the hypothalamus.
+
+So here we're going to slice through a kernel section,
+
+through the brain.
+
+Here's a kernel section looking right in the middle of
+
+the brain, and here's the cortex in the side.
+
+Right in the middle is a particular nucleus called the
+
+power.
+
+The let's look at this very carefully, the power of
+
+an ocular nucleus of the hypothalamus, a tiny little bit
+
+of a massive in a rodent, the tiny in your
+
+brain, because you've got a lot of extra bits to
+
+do.
+
+It's the key that is the brain that releases this
+
+molecule that then cascades because the pituitary release, this act,
+
+and then you get this adrenal cortical and cortical means
+
+that they go and feed back into the system that
+
+exist.
+
+But cortisol also acts on the hippocampus and on the
+
+hypothalamus itself.
+
+There's also this higher level process in the hippocampus.
+
+So inhibits these three structures.
+
+Very nice.
+
+Just highlighting this is a negative response is also it's
+
+turning off the activity of these cells in these various
+
+regions in the hippocampus.
+
+So what happens, though?
+
+Okay, so that's your stress response.
+
+And if you go through some stress, period and it
+
+lasts like that break up, we saw in that person
+
+an elevated heart rate, eventually the cortisol to bring that
+
+down.
+
+But if you keep going through ongoing stress on and
+
+on, so say you're put into a war zone and
+
+you're in extended war zone.
+
+The Vietnam War went on and on and on and
+
+people did not know when they were coming home from
+
+that war.
+
+They were drafted into it.
+
+So that is an example of a long term for
+
+stress.
+
+Six exposure experience.
+
+What's been what's been studied is that the people who
+
+experience that prolonged stress will end up with a shrunken
+
+hippocampus.
+
+So this is a coronial, sectional coronial section through the
+
+brain.
+
+Here's the hippocampus showing healthy hippocampus here and a smaller
+
+hippocampal.
+
+It's quite hard to see, but you wouldn't want your
+
+hippocampus to be shrunken like in this diagram.
+
+It's not a good effect.
+
+So ends up with this bad effect on the brain.
+
+But if we dive in and look at in more
+
+detail, so we're looking at beyond just humans and brain
+
+imaging, but we can't get that close.
+
+What we can do is study things like primates where
+
+we can look at a situation where some primates are
+
+housed in a slightly stressful situation and end up with
+
+ulcers in their stomach.
+
+These are the ones that they know they were stressed.
+
+They can look at their physiology to check things like
+
+that.
+
+He's not a very pleasant experiment to read about, but
+
+it has highlighted exactly what happens at a cellular level
+
+in primates brains like ours.
+
+And you can see that a control panel here who's
+
+not stressed as nicely organised cells in the campus, and
+
+it's all nicely disrupted in the hippocampus of a stressed
+
+animal.
+
+So that's a problem.
+
+This is not something you want to have.
+
+Your brain reacts to too much stress.
+
+Prolonged difficulties can cause problems in your brain.
+
+Now, this is quite a detailed slide.
+
+This is going back to scanning humans.
+
+We're looking at animals in the last one, but this
+
+is an example of the hippocampus and Gulf War related
+
+post-traumatic stress disorder.
+
+Patients at the end of this course, near the end,
+
+the second to last lecture going go back to post-traumatic
+
+stress disorder, the fascinating condition where treatments have advanced a
+
+lot in the last decade in terms of treatment.
+
+Back when this study was done in 2005, they weren't
+
+so advanced.
+
+What is this showing is that people who experience PTSD
+
+had smaller hippocampi, this they had of it.
+
+People who not healthy controls or even people who has
+
+who had been sent into the war zone are not
+
+experienced this disorder.
+
+So that these PTSD is kind of like flashbacks.
+
+They're afraid generally they panic very easily.
+
+They can't sleep at night.
+
+They get these Night-Time dreams.
+
+And in those cases, you get this reduction in the
+
+hippocampus, and I'll come back to that.
+
+That's an example in humans.
+
+Another experiment was done was to actually administer cortisol.
+
+And so to see if this.
+
+So what we're looking at here is the hippocampus being
+
+disrupted the size this for experiment done some time ago
+
+in 1996 and some time back but it's published in
+
+the journal Science because quite a breakthrough experiment in terms
+
+of understanding what may be going on is that that
+
+stress is a knock on effect.
+
+It shows that over prolonged stress, this cortisol, this is
+
+here the cortical response in on the right hand side.
+
+So a very low response to stress or a high
+
+response to to the cortisol is leads to less memory.
+
+So almost leading down into amnesia and not quite the
+
+person is really stressed, suffered, prolonged stress, you can you
+
+can look flying placebo or so what they did was
+
+they injected either just saline and just the salt water
+
+or this this same saline mixed with the cortisol was
+
+increasing people's response in physiologically inducing stress by injecting the
+
+hormone directly.
+
+And if you if you've had this prolonged stress, your
+
+response is very poor.
+
+A big response to that is people's memory is disrupted.
+
+And we'll come on to the link between the hippocampus
+
+and memory and a follow on nature.
+
+So one way that's been studied and I'll delve into
+
+memory in more detail is instead of taking warzone veterans
+
+and that's hard to study under control, what they'll do
+
+is take mice or rats and put them in.
+
+This is a rat here in a home cage and
+
+introduce a cat.
+
+I picked a ginger cat in this diagram, but it
+
+could be any time cat and the cat is placed
+
+in the environ for 75 minutes.
+
+And that's a very stressful experience for for a rodent
+
+because they are very evolved to smell like there are
+
+smell receptors in the tax cuts as is a threat.
+
+And so it will stress them out.
+
+They'll just high they won't be harmed.
+
+They're just introduced to this potential threat for a period.
+
+And what they can see is that the the what
+
+we're looking at here is this this is a measure
+
+of how close the come back to this top side
+
+of the bottom.
+
+One is, is the easiest one to understand.
+
+So this is this is.
+
+This is a hoax and nothing's happened to the rat.
+
+This is a rat who has been placed in the
+
+specific cage, but nothing happens.
+
+Very boring.
+
+And this is the plot for a cat that has
+
+been sorry.
+
+That rat has been exposed to the cat.
+
+And this is a task where rats have to scurry
+
+through a maze to find bits of food at the
+
+end of different alleyways.
+
+And if they remember very well, though, avoid going back
+
+down alleyways.
+
+The food is not very good at memory.
+
+They'll keep going back down the same alleyway and it's
+
+forgotten they've eaten the food there.
+
+And this is that normal rat.
+
+Fantastic.
+
+Rats are very good at this.
+
+But the rat has just been exposed to the cat.
+
+Keeps to getting ready to go.
+
+That stress, putting it just 75 minutes with the cat
+
+has induced this the stress response in that in that
+
+rat and it's having a harder time remembering where the
+
+food is in a maze and different school the radio
+
+maze as these little alleyways radiating out from the centre
+
+of it.
+
+So this middle one will come back to is a
+
+measure of synaptic plasticity.
+
+Like you two, you learned about neurones in the sign
+
+ups in the way they can form and communicate with
+
+each other.
+
+In brief, in synaptic plasticity they sign up to this
+
+can change and you can measure using different methods, increases
+
+or decreases in the way in which sign in sign
+
+ups.
+
+This can cause cells to communicate with one another to
+
+send action potentials.
+
+And what's shown here is that if you take this
+
+approach that the rats that had no interaction with the
+
+so very nice, typical robust responses to this procedure of
+
+stimulating its brain to check the synaptic plasticity, this was
+
+being written about in this in this here this this
+
+change to stimulating his brain.
+
+If it's been put in the chamber, we either have
+
+that same response very good plasticity.
+
+But if it's had the cat, there is always nothing.
+
+There's no almost no synaptic plasticity.
+
+This rat is still in a highly stressed state and
+
+is unable to really acquire that new information.
+
+It's not able to update.
+
+So if you combine these two things together, it suggests
+
+that we need we need to this over prolonged stress
+
+can disrupt memory and it disrupts the natural plasticity in
+
+the hippocampus.
+
+So we we can link this these two things together,
+
+these lost memories due to stress.
+
+So here in this diagram, this comes from a review
+
+by Kim and Diamond.
+
+They are talking about low level stress, up to high
+
+levels of stress.
+
+And you can have activation of new neurochemical systems.
+
+This is our assignment for you, which HPI access systems.
+
+And I have some effect on learning a memory.
+
+But as that stress goes higher, it damages the synaptic
+
+plasticity, it causes changes in the structure of the cells,
+
+and eventually here necrosis and cell death and disruptions and
+
+growing of cells in your brain.
+
+And we'll see the hippocampus grows, new cells, all of
+
+that gets highly disrupted.
+
+So you have this sort of how much stress you
+
+got causes brain cells to die and you have the
+
+campus and so on.
+
+So all of these have an impact on learning and
+
+memory in the short term or the long term.
+
+So stress is good for being able to respond to
+
+threat critical.
+
+You need it.
+
+You know, you need to get a focus on an
+
+exam.
+
+And that stress response needs you to be alert and
+
+not sit and just back and digest, but too much
+
+of it, and you'll end up causing problems.
+
+So how do we how do we know about more
+
+of these problems and the social impact?
+
+We're going to dive now into what happens in the
+
+impacts of early life so that the Fitbit example I
+
+gave from that person earlier, he broke up with his
+
+girlfriend at noon, got a text message, heart rate went
+
+up all day, and so the night is really bad.
+
+But that's a one shot late in life.
+
+What happens to stress?
+
+This example looking at Harlow.
+
+It was the key.
+
+Scientists looking at a social bonding will come on to
+
+that on Friday was exploring what happens if you give
+
+adversity early in life.
+
+There's a sort of sense in which we're all born
+
+equal.
+
+We can get on with it.
+
+It's fine.
+
+Well, he was able to do was to study macaque
+
+monkeys.
+
+And look what happened.
+
+This is a photograph is this is back in the
+
+1950s.
+
+This is Harry Harlow.
+
+And he explored the idea that maybe innately our bodies
+
+built to seek out warmth and protection, not just food.
+
+And he did a critical experiment.
+
+We would raise these these small baby monkeys, these really,
+
+really sad to read experiments.
+
+And of course, they haven't been carried out since those
+
+days.
+
+So people don't do these experiments now.
+
+You've established a scientific discovery around early life stress, and
+
+now we can do lots more with it.
+
+Back in the fifties, he was able to highlight the
+
+value of early life intervention for avoiding detrimental impacts.
+
+So these monkeys were given the option of food.
+
+They could they could hang on to a wife or
+
+a mother and an artificial mother for these monkeys that
+
+would give them food, or one that just gave them
+
+no food, nothing at all.
+
+But it was just soft and furry.
+
+And what they found was that the little monkeys, baby
+
+monkeys would go and get the food when they needed
+
+it, but cling on to the fur of the artificial
+
+mother.
+
+And we show that these cloth mothers would be in-built
+
+into their DNA, driven from a very early stage of
+
+their birth to focus on not to seek out that
+
+wolves.
+
+And so that's really important for the development.
+
+He then went on to, sadly, show that they're not
+
+even given this.
+
+These poor little monkeys, unfortunately, end up being what he
+
+described as depressed.
+
+But really, they show very little interaction with other other
+
+other eyes, all monkeys, and they're disturbed through the whole
+
+life.
+
+So you can take away those early supports very early
+
+on and then get them later and it's too late.
+
+They never quite adapt to the social hierarchy and later
+
+lives.
+
+So something's happening early in the early phases.
+
+Development when the primate is born through to growing up
+
+to becoming an adult.
+
+It has profound impacts on social interactions and stress coping.
+
+They won't couch that well with stress.
+
+So this is just a highlight of his that the
+
+care that a mother brings to the children, the offspring
+
+regulates those glucose, those those that the steam that cortisol
+
+is this glucocorticoid.
+
+So this lecture goes on.
+
+There's a number of clues here.
+
+Glucocorticoids as part of the HPI axis.
+
+The core one is corticosteroid is so is cortisol.
+
+Corticosteroid rots, the cortisol is released and it binds to
+
+receptors, has all these effects, raises your heart, does all
+
+the things we need to do, but you can regulate
+
+as paper key paper from this team so that the
+
+maternal care that's given during development affects this is in
+
+rats of a rat.
+
+In rats, they can monitor mother rats.
+
+If you give a lot of care and attention to
+
+their pups, it would change the physiology of their bodies,
+
+increase the capacity for these receptors and the response to
+
+stress.
+
+So the access response is improved in these mothers.
+
+They can show all these is more detail than you
+
+need to know about in this abstract.
+
+Don't worry about the these various details here.
+
+But the main point is all these things that allow
+
+the body that are gone through the HP axis, the
+
+hypothalamus, pituitary adrenal cortex, how to regulate with the cortisol
+
+is upregulated by maternal care.
+
+And this is an example of how you can look
+
+at you can measure this.
+
+So we're looking at rat pups for more nurturing mothers
+
+compared to ones that have low nurturing mothers.
+
+So we're going to track what we're going to do
+
+to two graphs now.
+
+So this is.
+
+Before the intervention this period.
+
+And this is after.
+
+This is the period after.
+
+So how what happens to the body when you apply
+
+these?
+
+The.
+
+The stress hormones.
+
+So what we're looking at is looking and grooming algae.
+
+More how much licking and grooming is applied versus the
+
+grooming and off back nursing.
+
+So grooming and nursing is not positive particularly.
+
+So it's it's you're looking at this licking and grooming
+
+the mother rats do for their pups.
+
+So humans you cuddle and maybe kiss and take care
+
+of and nurture your child and stroke them and sing.
+
+Nursery rhymes is what humans do.
+
+Pups for rats.
+
+They do.
+
+They groom them for and they lick them to make
+
+sure they're good.
+
+Good mothers do that, love.
+
+So here we have a group of rats, the high
+
+treatment and low treatment.
+
+And what we can see is the response, the way
+
+the plasma this this molecule is released by the pituitary
+
+gland.
+
+It targets the the the cortex of the of the
+
+the.
+
+Of the adrenal gland.
+
+This particular hormone is a better, higher response.
+
+So is a.
+
+Is is much higher high response in those those rats
+
+that didn't get the maternal care.
+
+So they're not bringing it back down as fast.
+
+And you can also look at the the cortisol Rask
+
+is up and it stays high throughout that period for
+
+these not very well treated rats.
+
+So these are the the black dots are the pups,
+
+the ones that grew up with that care going to
+
+Harlow's monkeys.
+
+Harlow's monkeys were maltreated.
+
+They didn't do well.
+
+You've got these rats that are not well treated by
+
+the mothers.
+
+And these graphs serve to show like on a on
+
+a evolving basis, the stress response differs between well treated
+
+ups and not treated pups.
+
+They look identical.
+
+And this experiment is taking these two groups of little
+
+pups.
+
+They look fine.
+
+But one thing well treated, the ones not being well
+
+treated.
+
+And this shows evidence that the early life experiences that
+
+care and the parents bring has an effect.
+
+The way we respond to stress.
+
+Sadly, you can go on to look at this in
+
+humans.
+
+So this is the axis of women after sexual and
+
+physical abuse and childhood.
+
+And these women have a higher response.
+
+Their cortisol levels are altered years and years later after
+
+childhood abuse.
+
+So this is quite sad.
+
+It will go on into the images of how sexually
+
+impacts of this.
+
+So you can see you can see these links between
+
+the previous rats experiment.
+
+We can most of this in the lab and we
+
+can measure this six fold change in these women who
+
+suffered abuse.
+
+So what's going on is that we've looked at these
+
+sort of general responses in humans and rats.
+
+So let's dig a little bit deeper.
+
+So what you can see in this diagram here is
+
+a one double helix of DNA.
+
+So, you know, many of you have a biology background,
+
+those that don't.
+
+DNA is the main molecule in our body.
+
+It leads us to storage and assembly.
+
+Information allows you to replicate, and we can pass on
+
+our DNA.
+
+It's the main way in which your children, your offspring,
+
+will pass on the facets of your eye colour, particular
+
+traits.
+
+You have all those things that's in most textbooks.
+
+Most people in society have heard of DNA.
+
+It's quite a common thing, particularly things like Jurassic Park
+
+have highlighted that example.
+
+What I'm showing you here is we can pass on
+
+our DNA to our children, but also the proteins that
+
+line the DNA inside your cells.
+
+Every single cell has a dense copy of your DNA,
+
+and it has these proteins called histones.
+
+It's just the proteins that induce the DNA folding.
+
+These are like little bulls that keep your DNA nicely
+
+tucked up in the cell.
+
+And histones can actually change.
+
+They can change the proteins so you can change those.
+
+And in fact, the particular thing that causes them changes
+
+methylation, a particular really simple chemical reaction.
+
+You can mitigate these histones or demethylation and just a
+
+very simple chemical change in these histones, these DNA winding
+
+molecules.
+
+And the key impressive thing is those changes, if you
+
+change your histones in the cell, can be passed on
+
+because when you cell separates and passes on, it will
+
+pass on not only the DNA, but these histones with
+
+it.
+
+So that's been found away without modifying an animal's DNA.
+
+What you can do is modify the histones, and that
+
+can potentially be passed on generations.
+
+So here's an example of a mother.
+
+We talked about this licking, grooming.
+
+Here's this mother who does high licking and grooming, and
+
+here's a cute little two pups that she's going to
+
+lick and groom.
+
+She's a very attentive mother.
+
+What happens is that her pups we've just heard earlier
+
+have this increased response.
+
+So they particularly show another molecule pick up on that
+
+is serotonin.
+
+So here's written out 5 to 7 receptors.
+
+That's the particular specific scientific name for the receptor for
+
+this molecule, serotonin.
+
+So we've talked about cortisol so far.
+
+We know what happens to serotonin.
+
+And this little pup, it's got this increased serotonin response
+
+that's activated, but also this methylation suppresses activity.
+
+So if they get d methylated, which is near a
+
+particular genes, there's more details in you need to have
+
+a particular gene and r3c1.
+
+And that changes the way the histones around that little
+
+mouse's DNA is operated.
+
+And the effect of that, which is known as epigenetics
+
+is epigenetic effect is a regulation of the licking, licking,
+
+grooming all in this particular gene, that particular gene, this
+
+modified by the mother's licking and grooming.
+
+And this is just the way that geneticists will describe
+
+this, both pathways, the direct effect and this this this
+
+effect on the histones cause a change in this little
+
+mouse that it's got a change in it and inside
+
+of it, cells and its own receptors, his own receptors,
+
+and got up to be able to respond effectively.
+
+And it's dealing.
+
+Is not been changed.
+
+The DNA is changed, stayed the same.
+
+But the way in which these things are configured has
+
+changed and it's now better able to cope with stress.
+
+This lucky little top goes off the stress coping and
+
+the idea is that that can then turn on and
+
+pass down generations.
+
+So there's no DNA changes, no reordering of the actual
+
+genetic structure, but these epigenetic effects I passed on.
+
+So here's just an abstract written out from a key
+
+study.
+
+By this this epigenetic regulation of this glucocorticoid receptor and
+
+human raises.
+
+So you can see examples of this.
+
+That gene I just talked about earlier that one with
+
+the pups is been able to look at it and
+
+people who had suicide victims who are abused or not
+
+have used it.
+
+Charlotte, it's a really sad study.
+
+They can look at the brain pathology post-mortem and see
+
+changes in the regulation of these structures.
+
+Very difficult scientific work to acquire these brains and it's
+
+worth a put a highlight that this work is controversial.
+
+So there's still ongoing debate.
+
+The key thing is here is the extent to which
+
+that epigenetic thing really does go over.
+
+Many generations seem very strong in some animals, but it's
+
+still motivated in and in in mammals.
+
+So a lot of scientists will agree with what I've
+
+just described, that there's an epigenetic passed on through the
+
+histone regulation and others may take the view that the
+
+evidence still needs to be really confirmed in more detail.
+
+So finally, just looking at the early life stress, we
+
+can also see impacts not just on the response of
+
+the sister for in the previous slides have shown changes
+
+in the brain.
+
+Right.
+
+We looked at how these changes in the design, not
+
+the DNA changes in the histones.
+
+What we're looking at in these last slides is really
+
+the fact of of this.
+
+The again, we're going back to rats who were next
+
+to it, who had their nesting material taken away.
+
+So we talked about if I go back to that
+
+last example of that mother, really attentive mother looking after
+
+her pups, great passes on these great skills that you
+
+wouldn't agree with, like a pass it down.
+
+The world's great, right?
+
+But that's not the real world, is it?
+
+So you could have a nice little nice and they
+
+all go well and suddenly something comes in an invader
+
+and all the nest.
+
+And now there's no nesting material for these animals.
+
+It's a bit like an earthquake occurring for humans.
+
+Your house is destroyed.
+
+You have to go live in a tent for a
+
+while.
+
+These are really negative impacts.
+
+What this study in rats looked at was the impact
+
+of having nesting material removed so it's no longer warm.
+
+And so the rats and growing up, they're unable to
+
+be looked after in the same way.
+
+And that means to fragmented nursing and grooming.
+
+The grooming is not happening as effectively What's shown here
+
+is the cortisol equivalent in rats.
+
+Corticosteroids and army is much higher.
+
+There's a much higher stress response.
+
+And these these animals that experienced that nest removal, so
+
+they're not able to respond more to later life stress.
+
+So this isn't the effect of the nest material being
+
+taken away.
+
+It's when they're nine days later, they've left the home,
+
+these little pups walking around and you give a stress
+
+response and you get this much higher stress response, just
+
+like we saw earlier with the childhood abuse says women
+
+who've been suffered childhood abuse.
+
+Much higher response, of course, is a sixfold higher, really
+
+high.
+
+Here you can see this very little response.
+
+These control mice or rats that grew up with the
+
+rats grew up in a nice, messy environment.
+
+The ones that didn't like the nest material have an
+
+adverse impact later in life.
+
+What's shown here is a spatial memory test that's better
+
+shown, I think, with the diagram.
+
+You take a little rice and you put it in
+
+a nice warm pool of water, like a bath, a
+
+large bathtub, a circular one.
+
+And the not the rat learns to swim around is
+
+looking for a way out of the water.
+
+It's nice and warm, is filled with milk powder so
+
+it can't see anything.
+
+But hidden under the water is a platform.
+
+If the rat finds it, it can get out, It
+
+can give it a treat.
+
+And it's taken out of out of out of this
+
+water maze.
+
+And it's called a morris water maze after Richard Morris,
+
+who developed this task.
+
+Very simple one, but it's used to thousands of houses
+
+and studies.
+
+So here the rat can't see that little maze.
+
+The platform.
+
+And what we're showing over here is a top down
+
+view into a maze with the video cameras tracked.
+
+One of these are rats all over the place.
+
+You can see it's swimming past what they've done.
+
+They're a bit, a bit cheeky and taken away that
+
+platform.
+
+So the mouse is going, Oh, great, I'll go to
+
+the platform.
+
+And this is it heading off to that platform, but
+
+it's not there and elsewhere.
+
+And that's when and you can see it's like circling.
+
+Where is that hidden platform in a sort of.
+
+Estimate what the rats thinking.
+
+What happens if you get that early life stress?
+
+So those rats were raised in their bedding.
+
+All they have was just an estimate table taken away
+
+long back early on.
+
+Take those rats much later.
+
+Give them the same test.
+
+That's horrible.
+
+Screaming all around, unable to remember where that platform is.
+
+So you can see the difference between the ones that
+
+had the control.
+
+Rats were quite efficient at going in the right space,
+
+but the stressed rats were pretty much likely to search
+
+anyway.
+
+They had almost no memory of where the platform was.
+
+So these kind of experiments really have been driven clinical
+
+teams to think, Wow, we really need to intervene.
+
+So that's why we have a very large and we
+
+should have more work on social workers trying to help
+
+make sure small children are really well cared for and
+
+don't suffer these kind of adversities.
+
+Same goes for animals.
+
+There are lots of charities to help make sure we
+
+don't have this kind of negative impact because it's unfortunately
+
+quite, quite impactful.
+
+So this is the last slide.
+
+So summary you've heard about there are particular maternal care,
+
+so you could pass on information from caring mothers and
+
+interactions with peers, and that regulates this access.
+
+We've heard about effects, this epigenome, the histones.
+
+That's what these white things are.
+
+Regulate that.
+
+This is where advisor press and hair will come back
+
+on Friday to learn more about vs the presence of
+
+adrenaline and serotonin molecule that changes the way our brain
+
+operates.
+
+That's what this icon is here that regulates how aggressive
+
+animals in the car, how emotion reactive and how that
+
+cognition and memory operates.
+
+And you get this operative, the social functioning.
+
+So rats, humans, monkeys, whatever mammal you're looking at, will
+
+have to interact socially.
+
+And that's where the stress has one of its most
+
+powerful negative impacts.
+
+You have pathological effects.
+
+If this pathway is badly dealt with, you also have
+
+memory impacts be heard.
+
+But if it's well cared for, you have adaptive, good,
+
+social functioning and on.
+
+So this is the overall summary.
+
+At the end, I recommend you read some of the
+
+last pages of the pages in particular from Costa Rica,
+
+and you can find enough is the cortex book.
+
+You log into these the library, you'll find that and
+
+then to just nice reviews and look at this axis
+
+and explain it in a helpful way.
+
+I'll give you some example essay questions here of how
+
+we might have informed surveillance.
+
+And if you can do those readings, you'll be able
+
+to nail these questions very well.
+
+You can discuss how stress affects the hypothalamic pituitary axis,
+
+how the genes, the environment interact and regulating stress and
+
+questions you might get asked is what does it stand
+
+for?
+
+What does it stand for?
+
+Where is the hypothalamus?
+
+Hypothalamus in a given brain section.
+
+And you saw our point that it too is right
+
+next.
+
+It's just under the corpus callosum.
+
+So if you study all these slides and you look
+
+through and read the material, read the reading are provided,
+
+she'll do very well in exam.
+
+So I will see.
+
+You say you had some negative stories about stress and
+
+bonding and problems.
+
+Friday's lecture over in ICU will be about love and
+
+social bonding, so that will be a more positive experience.
+
+See you next Friday.
+
+Thank you very much.

raw_transcripts/lecture_12.txt

@@ -0,0 +1,2141 @@
+Good morning.
+
+So welcome back.
+
+Friday.
+
+Monday.
+
+We heard about stress.
+
+Today we're going to talk about social bonding.
+
+Before we kick off, I just want to remind everyone
+
+about while you're doing this module, do keep checking your
+
+anatomy.
+
+So this is a page in the anatomy and your
+
+guide.
+
+So here's the web guide from lecture two.
+
+There's a whole load of brain sections to memorise.
+
+And here is where one of them goes by halfway
+
+through, about halfway through this module.
+
+Now a bit more.
+
+So you keep playing with this.
+
+Can you tell some easy ones in this?
+
+Where's the cerebellum?
+
+Where's the corpus callosum?
+
+Where's the military bodies?
+
+That's much harder, right?
+
+So here's where it says Yeah.
+
+What number?
+
+Three bodies.
+
+So if you thought that was the military bodies, well
+
+done.
+
+But this is the way.
+
+Just keep testing yourself.
+
+Where's the midbrain?
+
+Where's the pons?
+
+Where is the body?
+
+Keep looking through this material.
+
+As you go through this course, I'm going to provide
+
+some new anatomy today.
+
+That isn't the place to do with the hypothalamus picking
+
+up on last week.
+
+That story on Monday's lecture.
+
+Okay.
+
+So let's go to our slides.
+
+So Monday's talk on stressed is quite negative most of
+
+the time.
+
+Stress is a part of our life.
+
+You going to have to sit in exam for this
+
+module.
+
+That's inherently stressful.
+
+But another key way in which our way in which
+
+we deal with stress is part of that is our
+
+friendship groups, our parents, our sisters and brothers.
+
+All potentially killing all these people around us really help
+
+as humans mitigate stress and other primates and some of
+
+the species.
+
+Here's an example of two types of what we might
+
+call social bonding.
+
+A parent with a child or two people who have
+
+couple together romantically in the textbooks.
+
+And the research on this topic of how do these
+
+bonds form between these two groups.
+
+This is known as affiliation, and we'll dive into that
+
+in this lecture.
+
+So there are many ways in which bonds form between
+
+people of different species.
+
+On the left at the top, down the top left
+
+is humans holding hands.
+
+In many cultures around the world, that's a way of
+
+single signifying bonding.
+
+Swans have an amazing kind of approach with their heads.
+
+And I think the cutest one of all really is
+
+the two old world monkeys who twine their tails together.
+
+So these are the monkeys bond for life as partners.
+
+And when they do that, they sit together with their
+
+tails bound up.
+
+You can go and see them in London Zoo.
+
+They have, or at least the last time where the
+
+London Zoo in the tropical house, they have two world
+
+monkeys.
+
+So these are these are some of the things we
+
+see, but we don't there are groups studying humans or
+
+a group studying monkeys, small number of groups.
+
+But a lot of the time research has been done
+
+on these animals is not rats, but actually voles.
+
+Those turn out to be a fascinating story in terms
+
+of our understanding of social bonding.
+
+And for humans, what social bonding bonding is linked to
+
+is love, the love we have for our parents, our
+
+family, our friends, our partner, etc., and our children.
+
+We don't know if these animals experience love, but they
+
+have very similar biochemical effects in their brains to us.
+
+And because we can study those in more detail, we
+
+can understand that.
+
+So I talk about social bonding in this lecture, but
+
+the technical term is affiliation that encompasses the bonds between
+
+individuals, partners who come together to produce children and the
+
+parent parents that bond.
+
+And look at the general process of that bonding in
+
+the beginning part of this lecture and turn to the
+
+parental bonds at the end.
+
+So this I mentioned this this coupling up the social
+
+bonding promotes adoption to the world.
+
+You can cope better when you've got friends, to put
+
+it another way, and stress, the social isolation which doesn't
+
+occur is linked to a whole range of psychiatric disorders.
+
+So it's an important endeavour in our society to improve
+
+social bonding, really.
+
+So here's the more of a longer and a bit.
+
+One of the key things you need to learn in
+
+this lecture is the word called specific to the ability
+
+to recognise a specific.
+
+So this is another species of the same of another
+
+individual of your same species.
+
+So as humans walking around, you can detect humans.
+
+So you as the human, the most dangerous thing out
+
+there for humans and most of their animals.
+
+So you really do need to detect humans, but also
+
+the most useful animal you probably interact with animals, I
+
+imagine the vast majority of you.
+
+So you need to be able to do that.
+
+You don't really need to be able to recognise as
+
+a human, but which humanism?
+
+Who is it I'm recognising and then do I need
+
+to remember to maintain a relationship with this person?
+
+So this all comes under this bonding process of not
+
+only do tend to find that is that is the
+
+human.
+
+I do know that human and I do need to
+
+invest time with that humans.
+
+So the there are a number of tasks that have
+
+been used.
+
+That's all fine in theory, but how do we test
+
+that?
+
+One is to look at approach.
+
+So here are two dogs.
+
+Dogs love to approach each other.
+
+Are people that dog owners know this.
+
+They love to get in and sniff each other's bottoms.
+
+They do more than that.
+
+They really get in there and get in there with
+
+them with the urine and material to understand.
+
+They do more than we do as humans.
+
+They also need to learn to recognise and said who.
+
+And there's a lot of work which cheap, cheap but
+
+very, very similar to us humans.
+
+But they have to identify the individual sheep they're interacting
+
+with.
+
+And again, that investment with sheep, how does the sheep
+
+know its mother and how does the mother know which
+
+individual lamb is its lamb to take care of?
+
+And there's been research on that.
+
+Now, how a lot of those animals do that is
+
+through smell of action.
+
+So in red highlighted that humans are a bit unusual
+
+in other primates, that our visual system is so good
+
+we can see people far off and we can hear
+
+thing.
+
+We can use that visual information to guide our social
+
+interactions.
+
+Not all other animals share that ability, and what they
+
+do is use of actions that ferments.
+
+You may be aware from popular culture are floating in
+
+the air.
+
+These are these are gas tight released chemicals that have
+
+some role in humans, but most are important for other
+
+species in terms of their their interrelationships.
+
+But beyond you know, beyond that, we have a particular
+
+organ in the brains of most vertebrates.
+
+So we have here reptiles and mammals that's shown by
+
+rats and a snake, and they have what's known as
+
+a bomb or a nasal organ.
+
+It detects in the air these, these pheromones I can
+
+relay them to.
+
+A particular bit of the brain illustrates that in both
+
+species called the accessory olfactory bulbs.
+
+So if you're smelling like a beautiful perfume, you'll likely
+
+be using your main olfactory system to detect that process
+
+that, Oh, this is lovely and it passes through your
+
+factory system.
+
+Separate to that main pathway is the access, the real
+
+factory bulbs, and they're helpful for detecting those social cues
+
+in these.
+
+So they pass that information that's shown here to the
+
+thalamus, that campus and the amygdala to various other bits
+
+of the brain that we'll come see.
+
+So this will really keep it to the brain to
+
+do that.
+
+Social detection, Who is this?
+
+And that's what we're looking for, the vulnerable nasal organism,
+
+very much in action in that picture.
+
+The two dogs, humans don't seem to have a formal
+
+gaze.
+
+Morgana starts to develop in the womb when you're a
+
+tiny baby and then gets regressed, it becomes removed.
+
+You don't end up coming out of the womb with
+
+the vulnerable base puts a set of eyes focussed on
+
+it.
+
+So the how do we test that?
+
+Once we've got that detection, how do we how do
+
+we explore that So it rodents and that's voles and
+
+rats and mice.
+
+And one approach is to take the top the two
+
+to the top one is to take that rat, expose
+
+it to another rat to play with.
+
+The two rats will play with each other a bit.
+
+I spent time in a board and run away into
+
+it during sniffing and grooming.
+
+If you put them back together a little bit later,
+
+don't just ignore each other again.
+
+They remember, Oh, it's this right?
+
+But if they're given a new rat again, explore and
+
+extending, you know, sniff each other and greet each other,
+
+and all those things that rats do when they interact.
+
+So you can measure that systematically how much times these
+
+two animals interact with each other and use that as
+
+a measure of social recognition.
+
+So if you were to damage the ability to do
+
+social recognition, a rat can't do that.
+
+We just treat all rats as if they knew they
+
+won't trust, will not know who it's mated with, who
+
+is it's daughters or sons or in terms of rat
+
+pups.
+
+It would just it wouldn't have that ability.
+
+So that's one way to measure it more.
+
+Find ways to use a social discrimination procedure that's been
+
+used extensively in bowls.
+
+So put the test participant in the neutral middle chamber
+
+with door flaps that can run through doorways into other
+
+chambers.
+
+What they'll do is have one.
+
+Another animal on one of these is tethered, is a
+
+little tether around its legs.
+
+They can't escape that chamber.
+
+Just briefly, for the purposes of a short experiment and
+
+another chamber with another one with a little tether.
+
+That's what shown here holding.
+
+It's like they can't get into the middle chamber, an
+
+experiment test whether the devil in the middle will spend
+
+more time with the partner than it's mated with recently
+
+might be.
+
+Or it might be.
+
+It could test lots of things, but typically it might
+
+be a partner that the vole has mated with or
+
+obviously spent a lot of time with to invest the
+
+time with or completely unknown vole that it doesn't know,
+
+or it could just hang out in the middle.
+
+But what this this fascinating work, there's a review we
+
+recommend you read in the reading material and so in
+
+young which really explored all of this work was there
+
+are two two different distinct species that probably more but
+
+two distinct species of vole, a montane voles, a prairie
+
+voles.
+
+There they look almost identical, but they have different genetic
+
+backgrounds and different environments.
+
+Now what you can see is this time spent in
+
+each of the chambers and we've colour coded these.
+
+So the green period is the partner one, the neutral
+
+one is the sort of purple one and the beige
+
+one is the stranger.
+
+So what you can see for Montane Voles is they
+
+don't.
+
+Let this go in the middle is just mated with
+
+this other one, but it would rather spend time on
+
+its own.
+
+It's just going to spend time sitting here grooming, maybe
+
+eating and doing what it wants to do, but it
+
+doesn't really distinguish between the two other goals.
+
+That's not true of prairie voles.
+
+They're less likely than anywhere to be in the neutral
+
+chamber, and they're very late to spend time with a
+
+stranger.
+
+What they spend most that time is with the partner
+
+they've made up with each other.
+
+That's helpful.
+
+So this shows these two different species that look very
+
+similar, have very different social behaviours.
+
+And as you can see in the wild, these, these
+
+variables will mate and the bond and they'll spend time
+
+together and they'll snuggle up.
+
+If I go right back to this early picture.
+
+That's two prairie voles together with their offspring.
+
+And they really co-invest and raise those offspring together.
+
+So that's one way.
+
+So what's different with these these voles?
+
+What's different between montane and prairie voles?
+
+And this review goes into this in a lot of
+
+detail.
+
+And so for this lecture and we've got 40 minutes,
+
+I'm just going to highlight a key takeaway message, and
+
+that is when you look at the brains of Montane
+
+voles and prairie voles is a particular molecule or two
+
+particular molecules that appear to be different.
+
+Oxytocin, the vasopressin, come on to explain those in the
+
+next slide.
+
+So these two molecules are much more abundant.
+
+They have many more receptors in key areas of the
+
+brain for motivation in prairie voles than they do in
+
+montane voles.
+
+So what's going on?
+
+So they discovered this.
+
+What's going on?
+
+Why these molecules?
+
+Well, the next experimental thing is for scientists to do
+
+is let's manipulate that.
+
+What if we were to inject these voles with oxytocin?
+
+What happens if we boost it artificially?
+
+Or what if we knock it out by giving a
+
+drug that stops them working?
+
+A lot of that painstaking work over decades of research,
+
+lots of graphs, statistics, publications, somebody just put it together
+
+in a cartoon slide to explain a lot of billions
+
+of US dollars being spent.
+
+What you're looking at the top is two voles.
+
+And what brought to this picture to me, but they're
+
+mainly work is work is on voles.
+
+And what they'll do is what this thing at the
+
+top is.
+
+Normally this slide would be even clearer, is that typically
+
+the two would be the thing with love with each
+
+other for the diagram.
+
+But the top one, the male profile has been injected
+
+with very suppresses and he hasn't before mating.
+
+So the two the two goals here typically ignore each
+
+other.
+
+In this first instance, they don't know each other that
+
+strangers.
+
+If we go back to that previous slide, this is
+
+this state here.
+
+The stranger doesn't care, the verbal.
+
+But what they've done in this experiment is inject visa
+
+pressing into the male.
+
+Now he keeps trying to snuggle up to the female,
+
+but what does she do?
+
+She runs off.
+
+She doesn't know.
+
+She's not interested in it.
+
+And so that's what this diagram, this this illustration is
+
+sort of looking away.
+
+What is this male sorry to do here?
+
+What if they inject oxytocin into the female?
+
+You get the same effect the other way round.
+
+Now the female is trying to couple up with the
+
+male, but the male is confused and running off.
+
+Normally, if they mated together, they would both show higher
+
+vasopressin oxytocin levels, but they're not.
+
+So this showing that you can boost this bonding process
+
+just by injecting one chemical that turns out to be
+
+very depressing for male voles and oxytocin for female voles.
+
+They're different.
+
+They work slightly different in these two species and humans.
+
+It's a more mixed picture.
+
+It isn't that simple for other animals, but for voles,
+
+it turns out to be these two, this to just
+
+this way.
+
+Right?
+
+So the problem here is that's the period before.
+
+This is about confusing the animals, artificially boosting bonding when
+
+it hasn't happened down at the bottom is saying they
+
+have mated.
+
+Now, these two, those should have enough eyes for each
+
+other and be snuggled up.
+
+And that's indeed what the female is doing after mating
+
+here.
+
+But they've injected an antagonist, a blocker agent pervasive present
+
+in the male and that he's not wanting to couple
+
+up and bond.
+
+So they've turned off his natural inclination to snuggle up
+
+with the female and invest time with her just by
+
+injecting one chemical change this entire behaviour and then they
+
+find they can do the exact same thing with the
+
+female just using oxytocin antagonist.
+
+They've blocked oxytocin after meeting in the female and now
+
+she's sort of in this illustration telling him he's a
+
+loser and he should get lost in this illustration to
+
+highlight what the scientists are inferring because is much more
+
+biological than then.
+
+To this, what's going on?
+
+Let's turn to the anatomy now.
+
+Let's turn to the human brain.
+
+The brain is sitting at this lecture theatre in front
+
+of me.
+
+And so here's a here's a sagittal section through the
+
+human brain.
+
+You can see the pons and the midbrain and so
+
+on.
+
+And if we zoom in on this bit underneath the
+
+corpus callosum, we have the thalamus in the middle here.
+
+Here we have a region of the brain underneath the
+
+thalamus called the hypothalamus, and we learned about it in
+
+lecture last Monday going on stress.
+
+We talked about the anterior pituitary previously as the output
+
+of the stress hormones, a hormone that goes in activates
+
+the adrenal cortical to growth hormone from the anterior.
+
+Now we're going to look at the posterior pituitary.
+
+The anterior is involved in stress.
+
+The posterior is involved in that building process.
+
+So what the scientists discovered, looking at the voles and
+
+then exploring in humans, is that there's a particular nucleus,
+
+the power of ventricular nucleus.
+
+It's very similar in your brain as a mammal to
+
+evolved, very similar.
+
+It just sits next to a bit ventricles.
+
+That's the reason that gets his name.
+
+There's also a super optic nucleus just above the optic
+
+plasma.
+
+That's where it gets its name from.
+
+So these two nuclei have nothing to do with ventricles
+
+or optic fibre optic pathways.
+
+It's just the name comes from where they're located in
+
+the brain, but they're tiny nuclei.
+
+They have more than five cells.
+
+This illustrations obviously schematic, but these are these are the
+
+bodies with cells that act with dendrites and they have
+
+axons, a good tone and an interface onto the blood
+
+cell, the blood, the circulation system, the capillaries.
+
+And they release, as is shown here, oxytocin, invasive breast
+
+and into the bloodstream from the Stewart the posterior pituitary
+
+gland.
+
+So typically this is what's known as neuroendocrine communication.
+
+So here we have our classic sounds of them and
+
+talked about in lecture three about sign ups, this and
+
+the transmitter systems.
+
+You also have endocrine responses in your body where you
+
+have hormones that operate here, like puberty is driven by
+
+our hormones.
+
+Here.
+
+What we're talking about is this other third pathway where
+
+you've got neurones that are connecting into the blood and
+
+releasing.
+
+This is known as neuroendocrine function.
+
+And that's how this this process is occurring.
+
+Now, this slide takes us on the journey from voles
+
+in a lab and injecting them to humans rather than
+
+injecting humans.
+
+They will take a nasal infusion of oxytocin into people's
+
+nose and get it through circulating up into the brain.
+
+And then what they found is that there's a whole
+
+range of different experiments.
+
+But one is that to show that oxytocin changes the
+
+way in which we treat faces, it's been a bit
+
+controversial.
+
+There's, you know, trying to get these expressed.
+
+Replicate can vary because not everyone reacts.
+
+Some people are really good at facial detection and others
+
+not so good.
+
+And these individual differences can be a challenge.
+
+But overall, the evidence weights the oxytocin and upregulate your
+
+ability for social processing.
+
+So detecting people, treating a neutral face is a slightly
+
+more positive game.
+
+Experiments where you have to trust other people to solve
+
+problems apparently are sort of elevated by oxytocin.
+
+But here's an experiment shown here by DOMS without biological
+
+psychiatry where they injected a placebo, so nothing going into
+
+the body or oxytocin or not injected these infusion again.
+
+And you can see, going back to Solomon's lectures, the
+
+amygdala responses to angry faces in the placebo condition is
+
+really high.
+
+There's an emotional response basically to these against the neutral
+
+faces.
+
+But what you see is that this is dampened so
+
+you get less reactivity, too fearful or angry, but in
+
+fact happy faces.
+
+So the whole thing sort of reactivity in the amygdala
+
+is lowered.
+
+That means that you're more likely to approach people, you're
+
+more likely to engage in activities of behaviours.
+
+That bonding process is what's argued by these authors.
+
+And there's a review in 2009 in Frontiers in neuro
+
+and chronology.
+
+So just to take that from a lab experiment, injecting
+
+people in the lab looking at brain scans is a
+
+real world example like I gave in the Fitbit on
+
+Monday.
+
+This is a couple of Nick Fleming and Linda Gaddis,
+
+who had their blood molecules, had their blood circulation taken.
+
+Here's Linda.
+
+Having her blood extracted on her wedding day, consented to
+
+a centrifuge and examined out her wedding alongside her husband,
+
+their parents, for their close friends and various people.
+
+And this is a wedding I actually attended.
+
+So is that what you're going to write it up
+
+for?
+
+The Daily Mail?
+
+So this became known as the cuddle, the cuddle chemical
+
+oxytocin in the study.
+
+And what is this?
+
+This just highlights the kind of thing that would occur.
+
+And this is to give a real life example.
+
+A month later, after the wedding, Linda got an email
+
+from Zach, the research scientist.
+
+And to her delight, the predictions were correct over oxytocin.
+
+Her husband Nick, and her experienced rise in the the
+
+love hormone with the cuddle chemical or oxytocin during the
+
+ceremony and the mother of the bride, the father and
+
+the relatives, they all boosted.
+
+But the friends were more mixed to experience the rise.
+
+But five didn't.
+
+Perhaps they were not feeling the love.
+
+So that's the way the Daily Mail has covered this
+
+kind of research.
+
+And you should be sceptical.
+
+Be careful about overinterpreting.
+
+This is the love molecule.
+
+It's a molecule that is raised and you can see
+
+that that actually does fit the predictions that these these
+
+molecules will rise in a small sample in a very
+
+particular scenario.
+
+But it's a very well studied phenomenon.
+
+The rise in oxytocin relates to social bonding, but it
+
+does more than that.
+
+So there's a really nice article called Oxytocin, the Great
+
+Facilitator of Life.
+
+And we're looking at this period here, social recognition, and
+
+we've been talking about social bonding and mate choice and
+
+feeling of trust and recognising social partners and children involved
+
+in play, but it's also involved in a whole lot
+
+of things that enable, as you can see here, through
+
+sexual behaviour, dampening aggression, potentially unintended childbirth, raising children, tiny
+
+babies through lactation and improper parenting is the mother right
+
+through.
+
+So they've argued this this whole cycle of life or
+
+maintenance as a species is somewhat dependent on oxytocin functioning.
+
+But it's not the only one like oxytocin works with
+
+others.
+
+There's things like serotonin and adrenaline.
+
+To all these molecules you need.
+
+Oxytocin appears to play this great, facilitative process that improves
+
+and enhances all these things.
+
+So that's the first part of the lecture I'm now
+
+going to focus.
+
+I've been talking about the bonding process here.
+
+I'm not going to look at this bit parenting, what
+
+happens in maternal and paternal behaviours.
+
+There's a really great review.
+
+It's quite sure maybe four pages by Dulac and colleagues
+
+in science from 2014 on the Moodle page is also
+
+a short 15 minute video.
+
+The Catherine du Lac is one of the best researchers
+
+in the world on this.
+
+Just talks through the camera about parenting process and what
+
+she's uncovered in her work and various prestigious institutes and
+
+what they've been able to do.
+
+It is absolutely remarkable when we dive into this work.
+
+So what they've shown in this work is that parenting
+
+occurs in a surprisingly large variety of vertebrates and invertebrates
+
+insects, arachnids, molluscs, fish recipients, reptiles, birds and of course,
+
+mammals.
+
+We've been talking about I've been talking about mammals all
+
+the way through here.
+
+But you have beetles that carry around their young.
+
+You have frogs that occur after they're young, you have
+
+birds and of course birds.
+
+And the most classic thing is birds.
+
+They have to look after their nests with their eggs
+
+in it.
+
+They have to pay it.
+
+Young, bring them food when they hatch.
+
+And so so there's a lot of analysis of parenting.
+
+The most common form of parenting is its female unit,
+
+parental.
+
+That means that the female is giving birth to the
+
+young and takes the majority of the role in raising
+
+that young.
+
+The male may lost.
+
+She's responsible and that accounts for that.
+
+And that's, as noted here, to carry the offspring.
+
+She has them.
+
+But there are many species that show this by parental
+
+care.
+
+Birds are amazing.
+
+When 90% of birds are shown in examples here, both
+
+parents are involved in raising the young.
+
+And that's partly to do with the one of them
+
+sitting on the eggs and looking after them.
+
+But the challenge of bringing food in for their offspring
+
+means the birds are particularly, you know, we'll spend a
+
+lot of co-investment.
+
+But that's also true of snakes and reptiles in some
+
+cases.
+
+Then they share this.
+
+But there are also some species of bird important to
+
+be aware of where there's a male unique parents.
+
+Also stickleback fish or a good example.
+
+And seahorses are not shown here, but they show particular
+
+male that the female will lay the eggs, but the
+
+male will then take over the role of raising those
+
+young to the point at which they're they grow up
+
+and become independent.
+
+So it's quite fascinating.
+
+So what's what's the takes on this new lots of
+
+different species here.
+
+But one of the conclusions of studying them in Europe
+
+biologically is that there appear to be across beetles to
+
+the to the stickleback fish through the reptiles and amphibians
+
+here, all the way through birds and mammals at the
+
+top are highly conserved, antagonistic circuits.
+
+What I mean by antagonistic these things don't work together.
+
+They are on or off.
+
+You can't be doing this and that.
+
+They are antagonistic in controlling either the activity of social
+
+bonding, parental behaviour, or aggressive behaviour towards offspring.
+
+And adult animals can display parental care or aggression according
+
+to their physiological state.
+
+Are they ready to do that?
+
+And what is the environment?
+
+So it's a combination of that.
+
+So these are these are statements.
+
+These are course conclusions that come from that review, and
+
+we'll dive into those in a moment.
+
+But it's worth being aware, we live in quite a
+
+civilised vertical society that if you step out of the
+
+door, you're not going to see a huge amount of
+
+aggression, I hope, today.
+
+But I have to go back more than 200 years
+
+and you would see a lot of aggression in humans
+
+and there is a lot of aggression in other parts
+
+of the world.
+
+Very sadly, there are wars going on.
+
+We are quite violent species.
+
+But that's also true of a lot of other mammals
+
+and other species.
+
+There's a lot of fighting for survival out there, and
+
+that requires that fighting and obtaining the the nutrients and
+
+the food and water you need requires aggression.
+
+You have to fight for things, for survival that Lucian
+
+has built into the brain of these mammals and other
+
+other vertebrates.
+
+Aggressive behaviour to survive.
+
+But whether they're aggressive or caring depends on the situation.
+
+So this is a graph from that paper that'll take
+
+a little while to unpack.
+
+So what we can see here and explain the y
+
+axis, first of all, this y axis, and this comes
+
+from a this review.
+
+As I said, here's some quick actions.
+
+If you look at the Y axis is what percentage
+
+of a group of male laboratory mice, these are males
+
+who are virgin as and they're not they're not mated
+
+previously.
+
+And they're previously this is this is a graph after
+
+those male cf1 strain mice have first and they're like
+
+mated.
+
+So they have mated.
+
+They're not going to have offspring.
+
+And what it shows you in the initial period before
+
+or just after that is the natural behaviour.
+
+This is what most male male mice will do, and
+
+this is quite similar to a lot of other rodent
+
+species and other mammals.
+
+Lions, for example, BE The classic example is that most
+
+of the time, given the opportunity, if that mice finds
+
+another unprotected pup in other mice, it will attack it,
+
+it'll destroy it.
+
+It's, it's trying to unless it's a pup, it won't,
+
+it will treat it with attack.
+
+It might ignore it in many cases.
+
+Occasionally it might retrieve that pup.
+
+There might be social circumstances under which it gets activated
+
+to help retrieve that problem.
+
+But you can see just in the spirit this fluctuates
+
+from here.
+
+80% of all the male mice to looking at Habitat,
+
+the men being given this experiment just a few days
+
+after mating.
+
+But then there's a radical shift in these male mice.
+
+His brain.
+
+Something is switching off that aggressive circuit, and it dropped
+
+to 10% of them are attacking and 80% of them
+
+are switching to retrieving pups.
+
+That can't be their own pups because they've just mated.
+
+But it will be other pups they find scattered in
+
+the environment.
+
+And that slowly declines and is a shift after about
+
+60 days.
+
+And the idea is that they're.
+
+Is a rapid a period where they need to avoid
+
+attacking to support the female.
+
+But after that period isn't that they will typically be
+
+left that scenario and they'll be back to their standard
+
+state and switching.
+
+So what we get out of this experiment, is it
+
+really true?
+
+Is it real physiological change induced by that process of
+
+mating?
+
+And so we can see a similar pattern to what's
+
+going on here in wild female mice.
+
+But that doesn't happen in laboratory female mice, intriguingly, that
+
+sort of they've been bred to be a bit more
+
+docile and nicer to pups.
+
+That's what ends up being used in lab experiments.
+
+They're not as aggressive.
+
+So what causes that?
+
+So this is a great grass in Davidson, could be
+
+in the wild watching this and describing it and say,
+
+Wow, look at this.
+
+Amazing behaviour is a remarkable behaviour we can see in
+
+the animal kingdom.
+
+But you're not in nature show.
+
+You're in a neurobiology lecture.
+
+Why?
+
+Why do we get this?
+
+Well, what these scientists have done their research is this
+
+their time dependent?
+
+So in that process, synaptic changes to the sign ups
+
+as there have a changing in those male mice brains
+
+and rest transcriptional.
+
+So that's within the DNA you're having different readout of
+
+the genes is a change in gene expression and triggered
+
+by that mating process.
+
+So that mating process causes the release of different chemical
+
+cues that change that.
+
+And some of them are released by females during pregnancy,
+
+can drive that radical behaviour shift from killing to parenting.
+
+What they found is if you disrupt the verbal maze
+
+Logan in wild male virgin males, it will reduce that
+
+process.
+
+If I go back to that graph here, you took
+
+a mouse, take a group of mice and you disrupt
+
+their vulnerable needs.
+
+Logan They normally would attack, but the ones we don't
+
+have the capacity to detect those cues drop down.
+
+They start behaving as if they mated.
+
+They're no longer detecting the signals that cause them to
+
+attack.
+
+So that formalised logic is not just useful for going,
+
+oh, detecting your friends or your children, but detecting strangers
+
+for the mice.
+
+Why they attacking these pups?
+
+Is it trying to preserve their own particular gene pool
+
+of their own genes?
+
+If they can make the mouse, the male mice can
+
+maybe all the other female mice and it can have
+
+its offspring grow up.
+
+The best thing it can do is kill off the
+
+other competitors children.
+
+And again, there are lots of other mammals that do
+
+this.
+
+Lions or the famous example, it will kill a new
+
+line and just the bride takes it will kill the
+
+the cubs from the other lions.
+
+That happens to be in that pride.
+
+But you also see these going to patterns and berry
+
+burying beetles.
+
+So not just vertebrates and lots of birds.
+
+The changes in the female are more varied.
+
+So you have the well known features to do with
+
+oestrogen.
+
+Progesterone and prolactin are all three hormones that circulate through
+
+the body in females during pregnancy that change that maternal
+
+behaviour in males.
+
+There's also testosterone very familiar culturally with the idea of
+
+testosterone is linked to aggression.
+
+It regulates a lot of that is very high in
+
+the males and it can be reduced in fathers to
+
+produce less aggressive behaviour.
+
+But of course this varies.
+
+I always remember all these things vary between people.
+
+That graph shows you this.
+
+There are some, you know, some animals, some of these
+
+males after after mating, they're still attacking and killing and
+
+there are some before they mated that are not doing
+
+that.
+
+So just be aware.
+
+There's a lot of variation out there too.
+
+Now, I've written on this slide down memory you do
+
+not need for the exam to memorise the layout and
+
+the interconnections of all these nuclei.
+
+That's not what this is about.
+
+This is a this is a figure four from that
+
+really great review.
+
+What you need to take away for this second module
+
+is that there are two of these circuits.
+
+One circuit is involved in parental care and one circuit.
+
+This involves an aggression, so particularly violence towards other strangers
+
+and pups.
+
+And the important point here is that these two circuits
+
+are linked.
+
+You can see the accessory olfactory bulb.
+
+That's the pathway you heard in the slide three where
+
+I talked about the vulnerable days and going to this
+
+area.
+
+And it projects into the aggressive aggression circuit.
+
+And if you damage that that circuit, it won't get
+
+turned on as much.
+
+They're not going to show as much aggression.
+
+The here we have another circuit involved in parental care
+
+that can get switched on.
+
+And instead they have they have these two interacting circuits.
+
+So they will, if one is on the axons from
+
+these brain areas, will terminate.
+
+And a lot of these other is to shut them
+
+down.
+
+They'll be negative impact and vice versa because you can't
+
+be both aggressive parenting at the same time.
+
+That's just because you just can't do the two different
+
+behaviours.
+
+So you notice to you there are a lot of
+
+other brain areas we come across.
+
+We've got here various areas in the amygdala that are
+
+important for Christmas, think parental care and we've got the
+
+prefrontal.
+
+Text.
+
+It's receiving and sending information back in.
+
+And you have again to remind you have a lecture
+
+at the end of the course and what the prefrontal
+
+cortex is doing by Professor Paul Burgess.
+
+So we come back to that.
+
+You can hold on to this for the moment that
+
+the prefrontal cortex, it shows a modulatory control in a
+
+lot of behaviour.
+
+One of them is the the exertion of parental control.
+
+So these two circuits exist and they they're antagonistic.
+
+What do we know about them?
+
+Is that the aversive circuit?
+
+First of all, that that red one is dominant.
+
+It's the one in charge most of the time in
+
+female virgin rats and male virgin rats.
+
+We talked about in lab female rats, mice and rats.
+
+The same sort of idea here that can can be
+
+quite docile.
+
+But generally that aggressive circuit is long.
+
+It will it will lead them to survive more.
+
+The aggression will save them as a as a rodent
+
+post-partum.
+
+So after mating and the desensitisation that occurs with in
+
+females, there's this hormonal neuro modulatory experience dependent factors that
+
+activate that, that other affiliated circuit that also acts to
+
+silence that that that the circuit, the one that does
+
+the aggression and avoidance.
+
+So just to highlight here it does this this is
+
+the avoidance and aggression.
+
+I've mainly talked about fighting, doing things, but this circuit
+
+is also important for just ignoring, running right, just not
+
+caring all these behaviours that again, are part of survival
+
+for for mice and rats.
+
+As part of us walks the toasting we talked about.
+
+That is really key in the initiation of that material
+
+behaviour.
+
+So we talked about if you inject these goals with
+
+oxidation, they won't thorns, but they also won't treat their
+
+children.
+
+They won't do the licking and grooming that we heard
+
+about under the stress lecture.
+
+So it really is important for oxytocin to be to
+
+be to be engaged for that.
+
+There's an area we're going to talk about next week
+
+in the detail of the ventral segmental area.
+
+We spend a lot of time talking about that and
+
+the molecules don't the mean and that's involved.
+
+It's a state just at this point, this brain areas
+
+involved in initiating this process and maintaining the behavioural maternal
+
+behaviour.
+
+So oxytocin is not shown here, but bonds on the
+
+receptors in the ventral segmental area and the ventral segmental
+
+areas you hear next week is the brain area that
+
+motivates and drives animals to do things again and again.
+
+So in this case, the drive here is that the
+
+animal is the, the, the females to really spend time
+
+investing with a the pups and be the partners.
+
+So that brain area is key for drives initiating and
+
+maintaining that behaviour.
+
+We'll come on to how it does that for all
+
+sorts of things.
+
+So people, the things we get involved in are habits,
+
+bad habits, Ferals that driven by this all depends on
+
+the situation.
+
+But beyond that there's also adrenaline and serotonin.
+
+Serotonin.
+
+These circuits are involved in maternal behaviours.
+
+Just to highlight in this picture here you have these
+
+various brain structures showing up here and these are the
+
+areas, the rough and the locus to release these two
+
+brain areas that release that involved in in regulating our
+
+attention, our arousal and our focus.
+
+These here appear to be part of that circuit that's
+
+involved in paternal care.
+
+And so these are also involved in that in that
+
+process.
+
+So just to end on, I'll talk through one experiment
+
+that just gives a really good two experiments.
+
+This one and the next one is a wrap up
+
+today's lecture.
+
+This is a figure from a news and Views article.
+
+So Rodriguez are writing up, trying to explain this experiment.
+
+But another group had done so.
+
+What they did in this experiment to understand the maternal
+
+paternal process for male and female is what's happening in
+
+their brains.
+
+And in this case they're looking at the medial pre
+
+optic area of the hypothalamus.
+
+So earlier on in this lecture, I showed you the
+
+hypothalamus and I explained this like a number of different
+
+nuclei within there.
+
+One of these is called the medial pre optic area.
+
+It's got nothing to do with optics.
+
+It just happens to be next to the optic nerve.
+
+So the medial pre optic area and after the animals
+
+have mated, you tend to get activation of neurones in
+
+this brain area.
+
+They're not as active before, but they become activated after
+
+mating this small bit of brain area.
+
+And that's what's indicated here by the red neurones.
+
+These are neurones that are sending out the highly active,
+
+the sending out transmission, That transmission of those neurones of
+
+the medial pre optic area they're arguing is driving that
+
+parental behaviour.
+
+And the reason they're finding these are critical is that
+
+they can go in and they can deplete those neurones
+
+just in that one tiny area.
+
+You barely see it in the brain.
+
+They've gone in and selectively damage those neurones by clever
+
+chemical techniques.
+
+But after that process you get no parental behaviour from
+
+the female or the male remaining looking at female mice
+
+and experienced male mice and experienced female mice.
+
+Like I mentioned, it's the virgin males where you don't
+
+get this pattern right.
+
+These all show this, this.
+
+If you damage this, you don't get this parental type
+
+behaviours.
+
+So that's the grooming, the retrieving pups and taking care
+
+of them.
+
+Okay, that's, that's one experiment to show it's important.
+
+That's one way of doing it.
+
+But ask these these four groups, virgin females, experienced males
+
+who mated and experienced females and mated experience here is
+
+little about mating on the right hand side.
+
+Now, this is for me.
+
+This is why this paper was published in science.
+
+That first experiments.
+
+Okay.
+
+It damaged the brain.
+
+They can't do it.
+
+That's fine.
+
+Very long.
+
+Here is the kicker.
+
+Experiment around.
+
+From a scientific perspective, it was virgin male mice.
+
+First of all, you can see they're not active.
+
+These cells that are active in these all three other
+
+categories of mice in the virgin males, they've not mated.
+
+They're just like young, aggressive male mice who have not
+
+made it yet.
+
+And what do they show?
+
+Aggression.
+
+They attack.
+
+They tap upset.
+
+They get rid of them.
+
+Here's what they did.
+
+They went in and artificially using optogenetics, find those cells
+
+that could be activated, activating and activate those cells by
+
+shining the laser light onto the genetically tagged cells.
+
+So what you can see is before and after that
+
+light is this this is a couple of milliseconds.
+
+You've got a normal functioning male.
+
+You shine a light.
+
+2 milliseconds later, a whole of the cells are turned
+
+on.
+
+What does it do?
+
+So rather than running across the cage and attacking and
+
+possibly trying to bite and destroy pop, it runs over,
+
+it picks it up, puts it back in the nest.
+
+So by just turning on a light, affecting a small
+
+number of cells, more than the number of neurones in
+
+this illustration here, but still you're talking about tiny cell
+
+nucleus in a small part of the brain.
+
+You switched one animal from showing this aggressive behaviour to
+
+a whole different approach.
+
+And it's really worth what's quite amazing about this is
+
+it's not like you've improved motor function or its ability
+
+to perceive light in some way.
+
+You've changed the radical feature of its entire behaviour in
+
+a millisecond.
+
+You've with this experiment, they've turned to mice that would
+
+attack and kill.
+
+It's one artificially thinks it's mated effectively.
+
+It's not thinking about this, but you've artificially activated a
+
+parental circuit in an animal that's never undergone any change.
+
+So this shows the power of the kind of optogenetics
+
+approach of exploring behaviour.
+
+So you got to ask, why did you use the
+
+light?
+
+How do you see through this activity?
+
+Yes.
+
+So optogenetics, as you heard in your lecture on the
+
+methods lecture, remember that the methods, the techniques you learned
+
+about what you could do is genetically tagged those cells
+
+in these particular rats.
+
+I think it is for mice in mice more likely
+
+get mice.
+
+They've gone and bred these animals with specific proteins that
+
+are sensitive to the wavelengths of light.
+
+When those wavelengths of light are show shot, shine down
+
+on those cells through a cut in the top of
+
+the brain of the rat, the mouse, they can artificially
+
+turn them on and they can do it within a
+
+couple of milliseconds.
+
+And so you can have a rat, a mouse running
+
+across the cage to attack and switch the behaviour in
+
+an instant from attack to being attacking an aggressive and
+
+killing to being attacked in milliseconds through one circuit interruption.
+
+So what does that what makes that amazing is that
+
+it's quite a complex behaviour you're looking at.
+
+Now this is a experiment where they were looking at
+
+another particular nucleus.
+
+The this particular part, the AVP haven't read that, but
+
+it's in this paper.
+
+So this is a hypothalamic nucleus which differs between Virgin.
+
+So a difference between males and females in virgins.
+
+But what they showed is that this particular is not
+
+just the nucleus involved with the particular subcategories of neurones
+
+that can start to get to that.
+
+You can regulate in the parents, the females.
+
+So males after mating don't show a change here, but
+
+the female mice can show a change in the number
+
+of active neurones in this particular nucleus after mating.
+
+So not only do you get these patterns of expression,
+
+but you can get them in particular male or female
+
+situations as well.
+
+But it's worth going to watch these movies to see
+
+the patterns of behaviour.
+
+So in this link, if you don't follow it through,
+
+you will see the use of optogenetics where you get
+
+mice, which is not really fighting with each other, and
+
+then they'll turn on these these neurones artificially and they
+
+can do it in males as well.
+
+So they can turn on the mouse.
+
+Yes.
+
+This is almost certain case.
+
+Oh, yes.
+
+But this is all about.
+
+So if they might be right, they might not get
+
+children from mice.
+
+It's extremely likely their breeding capacity is way higher.
+
+That's one of the reasons they've ended up being laboratory
+
+animals that are really higher breeding.
+
+They require fast turnover.
+
+They can have children very quickly, but very likely they
+
+would, but it's not dependent.
+
+So these activation patterns are not dependent on the sex
+
+success.
+
+Well, I think you would need to activate pregnancy, though,
+
+so if they don't end up being pregnant.
+
+But I think the idea of the meeting alone will
+
+activate patterns of change in the male, because they can't
+
+detect that necessarily.
+
+But to pick up on that point, when the female
+
+does become pregnant, her pheromones secretions, what she's secreting, will
+
+change.
+
+And that provides a cue because humans, we don't really
+
+dissect these things but might do dogs do.
+
+They can detect other animals can smell these things.
+
+We can't in the same way those they go and
+
+watch these movies because you can see them turning off
+
+again with the optogenetics and the midpoints to attack, making
+
+an animal docile and parent and pick up a tree
+
+pups.
+
+It's it's really one of the most dramatic pieces of
+
+evidence I've seen.
+
+And again, one of the reasons it's published in the
+
+most prestigious journal in the world in Nature.
+
+So to wrap up today, there's a nice section in
+
+the physiology of behaviour that calls in or brisket on
+
+social bonding.
+
+That review is really clear and really nice to read
+
+into and Young.
+
+I talked about the voles again, extremely easy to read
+
+article and then there's some other reading.
+
+If you're really interested you could look into This is
+
+not essential, but we can go into that and we'll
+
+see you next week.
+
+The consciousness and motivation, why we do the things we
+
+do.

raw_transcripts/lecture_13.txt

@@ -0,0 +1,2029 @@
+Okay.
+
+So my name is Steve Fleming, and I'm going to
+
+be giving you a lecture on consciousness today.
+
+I am.
+
+So what's the focus of this lecture is is the
+
+problem of perceptual awareness.
+
+So imagine your standing on whatever bridge this would be
+
+in London.
+
+Mostly bridges, maybe.
+
+And you're looking at the sunset.
+
+Then you will also be most likely to be aware
+
+of that sunset and be able to communicate its properties
+
+to other people, to your friends and so on.
+
+But at the same time, there's a lot of other
+
+perceptual inputs that you may well be unaware of, such
+
+as the feeling of the clothes on your skin or
+
+changes in your posture.
+
+And a cool question in consciousness science is what are
+
+the computations in the brain that differentiate between conscious and
+
+unconscious information and what are the mechanisms, what the neural
+
+mechanisms that supports that difference.
+
+Now, when you hear the word consciousness, people often start
+
+thinking about mysterious phenomena.
+
+So in the media you might hear about panpsychism or
+
+plants, consciousness and so on.
+
+So we're not going to be encroaching on this territory
+
+today.
+
+So there are some somewhat out there consciousness that are
+
+doing the rounds and we can't rule them out 100%.
+
+But the approach I'm going to tell you about today
+
+is taking an approach very much squarely within cognitive psychology
+
+and neuroscience.
+
+And the questions that we can tackle with experiments in
+
+the lab are these ones.
+
+So what differentiates Conscious from unconscious processing as a neural
+
+level?
+
+What is it in the brain that makes a difference
+
+for conscious processing?
+
+What's the difference that makes the difference?
+
+So in today's lecture, there's quite a lot to get
+
+through.
+
+There's a bit of material towards the end of the
+
+lecture, which is some unpublished work from my lab that
+
+is optional.
+
+It won't be examined, for instance, is not published, but
+
+if we get there, then I can talk about it,
+
+but I might skip over that if we are short
+
+of time.
+
+So we're going to cover these topics.
+
+Conscious the difference between conscious level and conscious concepts, and
+
+talk briefly about some methods for manipulation in consciousness in
+
+the lab.
+
+Talk briefly about what's been found, found out about the
+
+neural collective consciousness, and then I'll talk about some theoretical
+
+issues, such as the importance of controlling for performance.
+
+And then at the end, we'll look at some ethical
+
+issues that arise.
+
+Well, it's now become possible to detect the presence or
+
+absence of consciousness in non responsive individuals.
+
+So what do we mean by the difference between consent
+
+and level of consciousness?
+
+So the idea here is that we differentiate in the
+
+level of consciousness from, say, sleep to wake you go
+
+you become unconscious when you are in a dreamless sleep,
+
+you then maybe become conscious of your dreams, and then
+
+when you wake up in the morning, you're fully conscious
+
+of the outside world.
+
+So that's different, a difference in the level of consciousness.
+
+But the idea is that even when conscious level is
+
+constant, so even when you are awake and engaged in
+
+your surroundings, then the content of your consciousness might fluctuate
+
+over time.
+
+So you might be conscious of my voice right now,
+
+but in a few minutes, if you zone out for
+
+a few seconds, think about something else.
+
+You might not be conscious of my voice in in,
+
+in, in that in that moment of time.
+
+So the question that we're going to focus on in
+
+the main question we have to focus on today is
+
+what contributes to conscious experience over and above simple information
+
+processing.
+
+The information is getting processed to some level.
+
+We know that from experiments, so I'll talk about next.
+
+But sometimes it's conscious and sometimes it's not.
+
+What makes what underpins that difference.
+
+So a lot of the work that's been done to
+
+study consciousness in the lab has been a variant on
+
+a paradigm called visual masking, which some of you may
+
+have heard about, say masking is quite simple.
+
+The idea is that you present a stimulus on a
+
+screen and then a very short time later you present
+
+a mask.
+
+And the the time interval between the stimulus and the
+
+mask is known as the entire stimulus interval is I.
+
+And sometimes you'll see that written in papers.
+
+Is the stimulus onset a synchrony or the way those
+
+two terms are interchangeable?
+
+And that's in say, Sorry, I should have told you
+
+to be ready for this.
+
+So if you have a look at the screen now,
+
+I'm going to flash up an example of a mask.
+
+So some hashtags followed by the stimulus, followed by the
+
+happens again.
+
+And you should be able to see this one.
+
+Let's just back up.
+
+So we're ready.
+
+Here we go.
+
+Everyone see what the word was.
+
+Okay.
+
+So that was a relatively long as.
+
+So the word is visible.
+
+This is now a shorter AISI.
+
+And it isn't even sure to ISI.
+
+He put your hand up if you saw the.
+
+Okay.
+
+So about 50%.
+
+So that's that's.
+
+So, I mean, PowerPoint is not the best technology for
+
+presenting these kind of stimuli, but as easy as the
+
+mask and the stimulus interval decreases, it becomes harder and
+
+harder to see.
+
+The word that last one was orange for those of
+
+you who saw it.
+
+So the masking effectiveness has been studied in a number
+
+of studies.
+
+It depends on the timing, as we've seen.
+
+It also depends on the stimulus intensity.
+
+So if I keep the icy effects and drop the
+
+contrast of the how black or grey that stabilises, then
+
+I can increase the masking efficacy and also stimulus content.
+
+So interestingly, things like your own name or emotion always
+
+will jump out even the same level of masking.
+
+And there are also individual differences, as we saw.
+
+So some people saw it, some people didn't.
+
+This is obviously not a control.
+
+It's like a business experiment.
+
+But when we do controls like this on this, we
+
+see individual differences in masking threshold.
+
+Now, this would be less interesting if this just meant
+
+that you didn't see the work.
+
+It wasn't even processed on your retina, for instance.
+
+That would be less interesting because that just means the
+
+stimulus hasn't got into the system.
+
+But we know from a number of studies in cognitive
+
+psychology that mass stimuli can affect behaviour even when people
+
+say they didn't see it.
+
+So often this is done using what's known as an
+
+indirect test of and the processing of the words.
+
+So you might go through an initial phase of an
+
+experiment where you get flash words or different stimuli that
+
+were masked.
+
+And on some trials of that experiment, you might say,
+
+I didn't see it.
+
+I don't know what the word was.
+
+But then in a second, indirect test, for instance, this
+
+is an example from ten up in the eighties.
+
+If you then ask people to say whether somebody is
+
+a word or a non word, you'll be faster.
+
+If the word is semantically related to the last word
+
+that you claimed not to see.
+
+So in this case, banana is semantically related to orange
+
+and you're faster to say that you banana is a
+
+word.
+
+So that indicates some depth of processing.
+
+It's not just that it's failed to get into the
+
+system on the retina.
+
+It's got into the system.
+
+But people still claim that on the Web.
+
+Now, more recently, people have used brain imaging to show
+
+that it's at least into the visual system.
+
+And even they're processed into, say, areas dealing with language.
+
+So this is an experiment from Garrett Research Group in
+
+Queen Square.
+
+And what they did here was use masking to make
+
+the orientation of these lines invisible.
+
+And they used a slightly more sophisticated masking procedure so
+
+they could, rather than just flush it once, they could
+
+flush it continuously.
+
+And people would still claim not to see the orientation
+
+of the grating.
+
+Right.
+
+So that what they're actually being flashed is a left
+
+tilted or a right tilted grating.
+
+But they just see a mask, applied mask.
+
+And what you see on the right, that it's a
+
+machine learning classifier that's trained to try and decode the
+
+true orientation of the invisible grating from activation of different
+
+brain areas.
+
+And as you can see, they can decode above channels
+
+and the visual cortex.
+
+So that suggests that the grating is being processed in
+
+early visual cortex, even though the subjects themselves say they
+
+didn't see it.
+
+So that's some evidence, both behavioural and hopeful.
+
+The processing of stimuli without awareness.
+
+Then what happens when you become aware of it?
+
+This is the other side of the coin.
+
+And so when you do this, you can show that
+
+when you see a masked word.
+
+Then you get elevated activation in a widespread network in
+
+the frontal cortex, whereas when the word is invisible, then
+
+the activation is much more restricted to early visual areas.
+
+I can't find a pointer, but not read is maybe
+
+I can come up.
+
+Yeah, I think.
+
+Yes.
+
+Good.
+
+So this.
+
+This.
+
+This red blob on the right hand side here is
+
+the activation you would get in individual cortex X to
+
+straight cortex when word is invisible compared to baselines, suggesting,
+
+again, like any experiment, some processing of my stimuli in
+
+early visual areas.
+
+But when you become aware of it, when you see
+
+it, you see it and you get much more widespread
+
+activation in your friends across the network.
+
+These are experiments.
+
+These are both experiments from Standard Hands Group reviewed in
+
+this paper newsroom.
+
+Again, you get a similar pattern when it's in the
+
+auditorium with a mask.
+
+Or interestingly, in white noise.
+
+Sometimes you say you see it, you heard it, sometimes
+
+you didn't.
+
+When you didn't.
+
+When you say you didn't hear, hear it, you get
+
+some activation in auditory cortex suggesting some data processing.
+
+But when you say you heard it and you get
+
+much more widespread activation in front of prosecutors.
+
+We'll come back to what this means in a second.
+
+Just for completeness, another popular technique for manipulating an awareness
+
+of the stimulus is binocular rivalry.
+
+So often this is done using red green goggles.
+
+So you present an overlapping stimulus.
+
+So the house is in red here, the face is
+
+in green.
+
+If you put red green goggles on, the images compete
+
+for dominance between the two eyes.
+
+Sometimes you see the faces, sometimes you see the house.
+
+But the stimulus that's on the screen is identical in
+
+both cases.
+
+And so this is useful because then you can create
+
+this kind of phenomenon where there's an unchanging stimulus, but
+
+your perception is changing.
+
+And when the stimulus is unconscious, we can also track
+
+it.
+
+We can then track its influence on information processing.
+
+So just to give you one example of work in
+
+this.
+
+So here is a study from Dell PCS Group.
+
+What they did here was used by knock the rivalry
+
+to mask the movement of some moving dots.
+
+So this is the this is the stimulus that people
+
+actually see in the other eye.
+
+What they don't see is some coherently moving dots.
+
+And then after this initial period of binocular rivalry, they
+
+have to make a decision about some consciously moving dots.
+
+And what they find is that if the unconscious information
+
+is helpful and people will be better at that decision
+
+when it's coherent in red than when it's just random
+
+and in green.
+
+But interestingly, this so this unconscious information boost your performance.
+
+So again, it shows the process, but it doesn't change
+
+people's confidence in that decision.
+
+So to them, subjectively, subjectively, it feels as though it's
+
+just the same in both the helpful and the unhelpful
+
+cases.
+
+But in the helpful cases, even though the information is
+
+unconscious, it's actually making your decision better.
+
+So we can then ask and we've already seen some
+
+of this information already.
+
+What are the what are the new correlates of consciousness?
+
+So we know that we can input information into the
+
+system that is sometimes unconscious.
+
+So then we want to know what's the difference between
+
+when you're conscious of a stimulus and when you're not.
+
+And so the neural correlates of consciousness have been defined
+
+in the early 2000s as the minimal set of neural
+
+events that are sufficient for a specific conscious experience.
+
+So the idea here is to keep the stimulus inputs
+
+similar, but contrast conditions between when you say you were
+
+white or something and when you were unaware of something.
+
+Okay, so we've already seen this slide.
+
+So this is the idea.
+
+When you're aware of something, there is a global ignition
+
+through the brain, through the frontal and the price of
+
+cortex.
+
+And when you're not aware of that stimulus, you don't
+
+get that global ignition.
+
+So just to give you an detailed example of this,
+
+this is actually from a study using EEG and combined
+
+with Meg.
+
+And so here they were able to look at the
+
+fine grained temporal dynamics of what happens, what the fate
+
+of a stimulus when you show it on the screen,
+
+either when someone says they saw it or when they
+
+didn't see it.
+
+Yeah.
+
+Yeah.
+
+See, that's what you.
+
+Right.
+
+Sorry.
+
+That's actually prefrontal cortex.
+
+But you should.
+
+There is also activation in the parts of what occurs
+
+in the prefrontal cortex and the Bronco area where they
+
+are.
+
+That's right.
+
+That's right.
+
+Yeah.
+
+And so, again, they used this masking procedure with a
+
+variable delay, stimulus onset synchrony.
+
+And what they could then do is plot these activity
+
+time courses as a function of this asset way.
+
+Right.
+
+So people gradually became more and more aware of the
+
+stimulus as the way increased.
+
+And what they found was that in early in early
+
+visual cortex, see this this box here, there was a
+
+pretty linear increase with SLA.
+
+So it's like the stimulus is getting a bit stronger,
+
+a bit stronger, a bit stronger in the early visual
+
+areas.
+
+But when you look at the prefrontal cortex signature later
+
+in the trial, it's more all or nothing.
+
+It's almost as if like on some trials, the whole
+
+system is nice and you're conscious of it.
+
+On other trials, it doesn't.
+
+So this is this idea of a bifurcation response.
+
+So it's like a nonlinear system where occasionally the stimulus
+
+will trigger this ignition and make it into violence, and
+
+other times it won't.
+
+So there's been various models proposed with what might be
+
+going on here.
+
+So one of the most popular ones from the bars
+
+and stand the hands grip.
+
+Has been the global workspace theory of consciousness and the
+
+idea that consciousness occurs once information is may be sequestered
+
+in perceptual areas, gains access to a global neuronal workspace.
+
+And that's proposed to be supported by these fronts of
+
+prior to networks.
+
+And so that would explain why you get ignition, because
+
+when the information is weak or subliminal, it just kind
+
+of reverberates around the visual cortex.
+
+Then as it crosses the threshold for admission into consciousness,
+
+you get recruitment of these fronts across all regions as
+
+well.
+
+An alternative view is the recurrent processing VAT that was
+
+put forward by Ptolemy in the 2000.
+
+Is that.
+
+What happens is that when you get some visual input.
+
+If it's very weak, then you'll just get feed, food
+
+processing and you won't get any conscious person.
+
+But if it's a bit stronger and long lasting, then
+
+you'll get both people and feedback activation along the cortex.
+
+And that supports consciousness.
+
+And what Lamaze this additional ignition into the parts network
+
+is secondary.
+
+It's not causal or conscious experience, but it might be
+
+involved in things like reporting that you've seen something.
+
+So this is quite a deep divide between what are
+
+called local theories of consciousness, which propose the activation in
+
+recurrent loops within the perceptual system are sufficient for consciousness,
+
+experience and global theories which propose you need to get
+
+the information out into a global workspace for consciousness to
+
+arise.
+
+How.
+
+And so so this this activation here would be just
+
+for reporting your experience for assistance, but not for actually
+
+being conscious of that experience.
+
+Then you might be, for instance, you might be conscious
+
+of something and then immediately forget it and be unable
+
+to report it.
+
+And the recovery process.
+
+If you say that your your conscious is in the
+
+moment that is supported by recurrent processing, even though you're
+
+unable to report on it.
+
+Now, personally, I find this new quite difficult to get
+
+my head around because it would suggest that there could
+
+be cases where the subject themselves says, I definitely wasn't
+
+conscious of this thing.
+
+But the neuroscience, as we say now, and I can
+
+see your reverberating loops in your visual cortex, you must
+
+have been conscious of it.
+
+So I think this actually goes against the folk psychological
+
+notion of consciousness is something we're able to communicate to
+
+others.
+
+But I think it's still worth taking seriously.
+
+Okay.
+
+So the final theory I just want to cover is
+
+higher order theory.
+
+This is got similarities with the global workspace theory.
+
+And the idea is that there are first order representations
+
+in perceptual systems, and these first order representations themselves are
+
+not sufficient for conscious experience.
+
+They might drive behaviour, they might allow you to respond
+
+above chance on a task, but they're not sufficient for
+
+conscious experience.
+
+And instead the idea is that consciousness of that content
+
+needs to have some higher order representation that allows the
+
+system to become aware of that first order state.
+
+So this entails that the first order representation in the
+
+perceptual system should be monitored or matter represented by the
+
+higher order representation.
+
+And so that's another prominent view.
+
+And again, with, you know, ongoing debate about which which
+
+view is correct.
+
+And new experiments are coming out all the time to
+
+try and distinguish between them.
+
+And one important issue that we need to do here
+
+affects all these different theories is the problem of performance
+
+compounds.
+
+So when we look at the neural coral, it's a
+
+conscious one.
+
+When we look at the these emission signatures, are we
+
+really just isolating consciousness or are we isolating the neural
+
+correlates of the improved performance or information processing that often
+
+accompanies consciousness?
+
+Because we know that when we're aware, some people are
+
+often able to use that for various functions like Oops.
+
+Like language, working memory, communicating it and so on.
+
+And the reason that is really important to control for
+
+performance is also got its roots in philosophy and in
+
+the theory of consciousness.
+
+So the idea is that consciousness or sentience is not
+
+the same as being sensitive to something.
+
+I say we can think of plenty of systems that
+
+are sensitive to the outside world without being conscious.
+
+Your camera appliance, maybe a thermometer, those all those are
+
+all sensitive to the outside world, but we don't usually
+
+think of them as being conscious of what they are
+
+sensitive to.
+
+And because under some theories like higher order theory, these
+
+first order representations are held to drive tough performance as
+
+well as contribute to consciousness.
+
+The problem is that if we have some experiment that
+
+boosts consciousness in some way, like changing the soul in
+
+a masking experiment, if we change both consciousness and performance
+
+in tandem, then we don't know whether the neural or
+
+behavioural change we see is due to the changes in
+
+performance or the changes in consciousness.
+
+And as I said, this is particularly crucial for testing
+
+the predictions of higher order theories, because if performance is
+
+not controlled, then we might unfairly stack the deck in
+
+favour of these first order theories that might see correlates
+
+of consciousness in only, only perceptual areas.
+
+And if you're interested, this has been really nicely unpacked
+
+in a book.
+
+It's very accessible by heart for love.
+
+So one reason to believe that we can do this
+
+and control for performance and still study consciousness is the
+
+phenomenon of Blind Side that was discovered by Larry Weiss
+
+Krantz, who was a eminent psychologist at Oxford.
+
+And what he did was study patients with damage to
+
+the early visual cortex.
+
+And so these patients would often have time is just
+
+to one hemisphere caused by an injury.
+
+And that led to their clinical visual field tests looking
+
+something like this.
+
+They'd be perfectly well aware of things on one side
+
+of space, but they be essentially blind in the other
+
+side of space.
+
+So when they came into the doctors, when they went
+
+to the apologists, they would be classed as having a
+
+brain lesion causing blindness in one half of space.
+
+But what's really interesting here is that when you study
+
+them in more depth, patients with Blind Eye are actually
+
+able to guess while above chance.
+
+What is being presented in that Blind Army field.
+
+Now, I won't show this just for the sake of
+
+time.
+
+If you're interested, you could watch a YouTube video of
+
+a black patient doing exactly this.
+
+The light lights are flashed in the blind field, and
+
+when he's forced to guess where they were, he's often
+
+close to 100% accurate, even though he himself will say,
+
+I didn't see anything.
+
+Right.
+
+So that's a case of performance being high, but always
+
+being zero.
+
+And in experiments you can then adjust the stimuli in
+
+both the normal and the blind hemi field.
+
+So that performance is matched between the two hemi fields.
+
+But now he's only aware of the stimuli in the
+
+normal hemi field, not aware of the blind happy field
+
+that creates an really nice, well-controlled case where performance is
+
+matched in the two hemi fields.
+
+There's no compounded performance now you're just he's able to
+
+process the information just as well in both cases.
+
+And yet awareness is only present for the stimulation one
+
+field and not the other.
+
+And when we then look at brain activation in relation
+
+to this difference, you still see the controlling performance elevated
+
+activation in the front supports.
+
+In that way when you're presenting stimuli in the normal
+
+impairs the blind.
+
+HAVERFIELD.
+
+It's also possible to do these kind of experiments in
+
+otherwise healthy observers.
+
+So this was a study of blind side in normal
+
+subjects, in healthy subjects without a brain lesion.
+
+And this was done using a masking procedure.
+
+So participants were first asked to decide whether a diamond
+
+or a square was presented on the screen.
+
+And this was difficult because it was masked.
+
+It was flashed very briefly.
+
+And they then had to indicate whether they saw the
+
+target or whether they simply guessed the answer.
+
+And what was found in this experiment was that it
+
+was possible to find two conditions.
+
+Across the whole range of ways where performance was modest.
+
+So that's the the red line here.
+
+Performance at these two areas is matched.
+
+But this is the way people say they saw it
+
+less often than this as a way.
+
+So you can see that down here performance is nicely
+
+matched conditions.
+
+Information processing is just as good.
+
+But people are less aware of the stimulus that this
+
+has away in this X-ray.
+
+And when that contrast is then done between these two
+
+ways within the fMRI scanner, you get localised activation in
+
+the lateral prefrontal cortex in relation to increase in conscious
+
+awareness.
+
+And just a final example of this.
+
+This is from, again, a study of patients with brain
+
+lesions, but now with lesions to the prefrontal cortex.
+
+So patients with prefrontal damage were asked to provide a
+
+false choice of which of to stimuli were presented on
+
+the screen and to rate the visibility of their stimuli.
+
+So how aware they were.
+
+And what's interesting is that compared to controls.
+
+The subjective visibility of those stimuli was reduced in the
+
+patients.
+
+And that's even the case when performance is match between
+
+the controls and on the patients.
+
+Right.
+
+So this is now plotting the the the difference in
+
+visibility for trials on which the patients got correct patients
+
+and controls got correct.
+
+On the upper lines here on trials in which they
+
+got incorrect here.
+
+So even when you split out the trials, according to
+
+ones that there were right and wrong, you still see
+
+that subjective visibility is lower in the patients in grey
+
+compared to the controls in black.
+
+And what's interesting is that if you then correlate the
+
+extent to which visibility was reduced in the patients with
+
+the location of their brain lesion, you can get a
+
+map like this.
+
+So this is known as lesion lesions into mapping.
+
+This is a map of the lesions that were most
+
+correlated with the drop in consciousness threshold.
+
+And here you get a evidence for a contribution of
+
+damage to the prefrontal cortex, to the anterior prefrontal cortex,
+
+to the threshold for conscious awareness.
+
+There's one other compound that we need to think carefully
+
+about here, and that's not just performance, but I mentioned
+
+a while ago that you can find cases where people
+
+are performing better in one case rather than the other
+
+due to unconscious information, but their confidence level is not
+
+different.
+
+Now, the problem is that in a typical Moscow experiment,
+
+when people say that they saw a stimulus, then they're
+
+often more confident on those trials than when they say
+
+they didn't see a stimulus.
+
+And you can see that here.
+
+This is actually some data from our lab when subjects
+
+say they saw a massive stimulus.
+
+And they're more confident on the y axis compared to
+
+when they said that they didn't see a massive it.
+
+So the problem is that all these existing findings in
+
+the literature on the front surprise activation being related to
+
+conscious awareness might be consistent with these brain areas, coding
+
+for the visibility or your awareness of the stimulus.
+
+But it could also be consistent with these brain regions
+
+being involved in representing confidence in your decisions.
+
+So to look at this.
+
+This was work done by my pastry student, Martha mazur,
+
+and post-doc Nadine Easter.
+
+And what we did is apply a machine learning decoding
+
+procedure across the whole brain to try and deep code
+
+people's allowance of the stimulus where they said they saw
+
+it or not, and also what the identity of that
+
+stimulus was.
+
+So we can decode the identity of the stimulus, whether
+
+it was tilted to the left or the right in
+
+early visual areas.
+
+And we can then decode their awareness in front of
+
+proximal cortex.
+
+So that's consistent with the picture of global ignition when
+
+people say they saw it.
+
+You get more activation, more decoding of awareness in response
+
+across the network.
+
+But when we then control for confidence in this analysis,
+
+when we artificially match the distributions of confidence on yes
+
+and no trials when they said they were aware of
+
+it or not, and a lot of this activation actually
+
+disappeared.
+
+So after DOWNSAMPLING to ensure confidence was matched on these
+
+trials, there was no longer any visibility, decoding, any awareness,
+
+decoding in large swathes of the pre-frontal cortex.
+
+Now, it was possible to still decode awareness from some
+
+subregions of of all time, such as the posterior medial
+
+frontal cortex.
+
+So I think this is a very recent study, and
+
+we just presented this a conference over the summer and
+
+published it a few weeks ago.
+
+And so I think we're still figuring out how to
+
+interpret this.
+
+So there's I think there's two implications of this work.
+
+So the first is that this is a big issue.
+
+This is a big deal that these are two distinct
+
+phenomena.
+
+On the one hand, we have confidence formation, monitoring, metacognition,
+
+thinking about whether you got an answer right or wrong.
+
+And this has been confounding all the studies of awareness
+
+in the literature.
+
+And so we could need to control for that to
+
+isolate a pure awareness signal.
+
+And this has been this view has been supported by
+
+people like Standard Hand who think that monitoring self awareness
+
+of whether you get things right or wrong should be
+
+considered as distinct to global broadcast.
+
+The alternative view is one that I favour is that
+
+there are shared computational substrates for both monitoring and wireless.
+
+Essentially what we mean by that is the ability to
+
+be aware of how things are being processed and that
+
+includes being confident in a response that you get.
+
+The very feasibility confidence can be defined in terms of
+
+being confident in a first order representation.
+
+So that means there might actually be shared mechanisms that
+
+underpin both confidence and awareness, and therefore it's unsurprising that
+
+much of the classical correlates of consciousness disappear when we
+
+control for confidence, because that's what we should expect under
+
+that view.
+
+So this is an ongoing debate and it's not been
+
+resolved.
+
+Yes.
+
+And so what I've described is that we now have
+
+a number of empirical signatures of consciousness.
+
+We also have a number of theories.
+
+And I just want to tell you one thing about
+
+what's happening at the moment and in, I guess, conscious
+
+to science as a ongoing project.
+
+So one thing that people are a bit worried about
+
+is that.
+
+These theories are somewhat siloed.
+
+They're being tested by different labs that don't often talk
+
+to each other.
+
+And there was actually a really interesting study from Italy,
+
+Iran and the moderates group in Israel that they collected
+
+all these different papers on consciousness in the literature together.
+
+And then what they did is they mined the text
+
+of those papers and asked which theory is being tested
+
+in those papers.
+
+And slightly concerningly in papers that said that they were
+
+testing recurrent processing theory.
+
+They would often report evidence for activation in the visual
+
+cortex in support of consciousness, whereas in papers that said
+
+they were testing global workspace theory, they would often report
+
+activations in the front sprouts of network consciousness.
+
+This is a bit of a concern, right?
+
+Because it can't be that they're both right.
+
+So there seems to be quite a bit of bias
+
+between some labs focussed on one area, some labs focussed
+
+on another theory.
+
+And I think that there are now ongoing, really interesting
+
+ongoing initiatives such as adversarial collaborations that have tried to
+
+stop this happening and try and get labs who are
+
+favouring different theories to actually work together and test competing
+
+predictions.
+
+I also think there might be a deeper problem here
+
+in consciousness science, and that is the fact that actually
+
+the theories of consciousness are not really thinking about what
+
+the functions of consciousness are.
+
+So in this recent article I suggested that there is
+
+a consciousness, a solutions in need of problems.
+
+People are putting forward theories of how consciousness might work
+
+in the brain, but they're not necessary thinking about why
+
+consciousness exists in the first place, and that is at
+
+odds with other fields of psychology, right?
+
+So if you have a theory of memory, for instance,
+
+then you want to know what that memory is being
+
+useful.
+
+How is it helping the organism survive?
+
+And instead, in conscious decisions, we often rely, I think,
+
+a bit too much on intuition about the kind of
+
+experience we're trying to explain.
+
+Just as I introduced in a stop, I started the
+
+lecture by saying, Imagine you are on a bridge in
+
+London and looking at something sunset.
+
+That's very intuitive, but it's not really constrained functionally.
+
+And this lack of functional constraints is a problem because
+
+the test of a good theory in psychology or neuroscience
+
+is whether it can explain how a system performs a
+
+particular function, how a theory of vision explains how we
+
+categorise objects, or how a theory of memory explains how
+
+we remember and forget.
+
+All right.
+
+So I think we can take a lot from the
+
+next levels of analysis from David Marr.
+
+So this is the idea that if you're trying to
+
+explain, for instance, how a bird flies, you first need
+
+to know something about why it's trying to flap its
+
+wings.
+
+What is the goal of flights is to take off
+
+and leave the ground.
+
+And that then constrains your search for the algorithm that
+
+does that job.
+
+Maybe you're going to take off and leave the ground
+
+with jet engines and fixed wings.
+
+Or maybe you're going to take off and leave the
+
+ground with flapping your wings.
+
+And then you can think about how that might be
+
+implemented at the physical level.
+
+And people have suggested that in neuroscience and psychology, it's
+
+useful to think about all these levels of analysis.
+
+So both the levels of implementation, such as how it
+
+works at the level of brain areas in seconds and
+
+algorithms, so computation, but also and this thing, this is
+
+the level that often gets missed out.
+
+What's the goal of the hour?
+
+Why is it there in the first place?
+
+And one thing I think is useful to constrain theories
+
+of consciousness is the notion that consciousness, at the very
+
+least, seems to be for sharing information.
+
+And this has been put forward by Chris Pratt, who
+
+used to be.
+
+He's emeritus professor at UCL.
+
+And he writes, The conscious experience is the one outcome
+
+of the brain's information processing that can be shared with
+
+others.
+
+I think it's very hard to disagree.
+
+This is essentially the definition of what we mean by
+
+conscious experience.
+
+When I'm a stimulus and you don't see it and
+
+you can't tell me what it was, that's the definition
+
+of it.
+
+There may be lots of things that are influencing our
+
+behaviour unconsciously.
+
+I can't tell you what they are.
+
+If I could, I would be conscious of them.
+
+The consciousness is at the very least for sharing.
+
+And what's interesting is that this kind of idea is
+
+floated around the literature, but being somewhat obscure for many
+
+years now.
+
+So this is a book chapter written by the famous
+
+neuroscientist Horace Barlow.
+
+And and it's not as widely known as Chris's work
+
+because it appeared in this book chapter in 1997.
+
+But he writes here, I think, things that are very
+
+similar.
+
+So what makes the pursuit of communal goals possible as
+
+humans is our ability to communicate with each other, which
+
+is surely the direct and obvious result of being conscious.
+
+Because if we weren't conscious of what we're thinking about
+
+and feeling, we couldn't share that with others.
+
+On the current hypothesis conscious experience gives one communicating one's
+
+own experience to others.
+
+That is its purpose and survival value.
+
+So what we're what we've been working on recently is
+
+trying to drill down into the algorithms that might support
+
+sharing of conscious information.
+
+So first of all, it's useful to think about what
+
+is being shared.
+
+And at the least, I think we can think of
+
+both content.
+
+So I might share with you the fact that I'm
+
+feeling a bit tired or hungry, or I can see
+
+a bird over there or, you know, that nice content
+
+of words.
+
+I also might share with you the vividness of that
+
+experience.
+
+I might say to you, I just can't continue this
+
+lecture because my headache is so strong.
+
+That's a very strong experience dominating my conscious experience.
+
+And these things are interchangeable, right?
+
+So I might be vividly aware of having a headache
+
+or dully aware of it.
+
+Partially.
+
+Well.
+
+And this in philosophy is known as the idea of
+
+mental strength.
+
+It goes all the way back to David HUME.
+
+Recently, this paper from George Moralez, who has suggested that
+
+the idea that mental strength is a phenomenal magnitude is
+
+the strength of vividness, of an experience.
+
+And it said by all conscious experience and explains that
+
+degree of intensity.
+
+And indeed, it seems that this is capturing something deep
+
+about what it means to be aware of different types
+
+of mental content.
+
+Because when you put people in an experiment where they
+
+actually have to share information to succeed, they naturally fall
+
+back on this sharing of mental strength.
+
+So this is an experiment from Barbara Graham's group where
+
+they asked people to sit and look at two different
+
+computer screens.
+
+They have a different visual task to do.
+
+The task is not so important at the moment.
+
+But the important thing is that they would then allow
+
+us just chat to each other and come up with
+
+a joint decision about what they saw on the screen
+
+and the kind of words they used.
+
+This was done in Denmark, but the translations there are
+
+things like, you know, I, I, I see see this
+
+very well, but these I didn't see anything will go
+
+with yours because I saw nothing.
+
+I took a guess, a wild guess so that communicating
+
+degrees of experience, strengths of experience.
+
+And by doing so, they can then achieve a better
+
+performance together than the best individual could alone.
+
+Okay.
+
+I just want to give you a flavour of this
+
+model.
+
+This is the part that I said was, uh.
+
+That could be, could be sketches.
+
+This is very much ongoing work, and it's not the
+
+kind of thing you would necessarily be expected to talk
+
+about in an exam, for instance.
+
+But the idea that we're working with in our lab
+
+is that we can start building in a this this
+
+notion of awareness of mental strength into a generative model
+
+of perceptual content that we can simulate in the computer,
+
+and then we can devise hypotheses that test this awareness
+
+related computation against its implementation in the brain.
+
+So the idea behind generative models, this is very broad,
+
+and you might have heard this idea in vision science
+
+is the idea that what the brain is doing is
+
+essentially building a generative model of the incoming sensory data.
+
+So it's trying to infer the best guess of what
+
+it's seeing based on the incoming prediction errors and the
+
+sending predictions.
+
+So this is known as predictive coding theory, predictive processing,
+
+and more generally it's known as the theory of generative
+
+models.
+
+But what's interesting about this architecture is that awareness of
+
+the degree of phenomenal magnitude or awareness of content is
+
+not in that a lot of this stuff is suggested
+
+to be proceeding completely unconsciously.
+
+That's why we're not aware of how that percept of
+
+an animal is being formed, how what's called an unconscious
+
+inference.
+
+We just unconsciously infer that an apple is there in
+
+front of us.
+
+And so we might need to start thinking about how
+
+we can extend out these models to include additional higher
+
+order levels that monitor the extent to which the system
+
+thinks there is content in its first order generative model.
+
+So this is a higher order theory of consciousness.
+
+And the idea here is that awareness states are abstractions
+
+about the presence or absence of perceptual content, and that
+
+might support communication of mental strength.
+
+And I will now just skip over the experiment because
+
+I wanted to go to the part on on the
+
+ethics.
+
+But you have the slides and if anyone has any
+
+particular questions about this and feel free to to come
+
+and talk to me afterwards.
+
+As I said, this is very much ongoing work that's
+
+not published yet.
+
+And so what we're trying to do with this work
+
+is reverse the arrow here.
+
+So we have functional constraints on what awareness is for
+
+and that we hope we're very much at the start
+
+of this project will start to enable us to, rather
+
+than just remain siloed, testing different favourite theories that are
+
+built often on intuition, to actually develop a working model
+
+of the minimal types of computation that might allow the
+
+communication of mental strength, the communication of degrees of experience,
+
+and then test that against behaviour and brain activity.
+
+Okay.
+
+So just to derive some interim conclusions.
+
+So we've looked at how techniques such as visual masking
+
+and binocular rivalry allow the precise manipulation of awareness to
+
+simple stimuli.
+
+Conversion evidence for unconscious processing of stimuli is provided by
+
+people performing above chance on indirect measures of information processing,
+
+such as priming or forced choice responding.
+
+The Neural correlates Consciousness research program identifies awareness with front
+
+surprise selectivity and recurrent processing.
+
+But note that it's important whenever you are reading this
+
+literature to assess whether there whether the research is a
+
+much different potential composition of performance and confidence when assessing
+
+the basis of awareness.
+
+And finally, I am excited by the idea of adopting
+
+a more functional perspective, just like we do in other
+
+fields of psychology.
+
+So what is consciousness for might and allow us to
+
+build a conversation among the consciousness related processing.
+
+Okay.
+
+So mainly we've talked about this difference in conscious content.
+
+We talked briefly about difference in conscious level at the
+
+start.
+
+But now I just want to turn to the problems
+
+that arise when we're able to start detecting conscious level
+
+independence of what clinicians call vigilance.
+
+So people who are in a vegetative state or some
+
+forms of advanced dementia that are non-responsive might actually be
+
+vigilant in the sense that they're awake, their eyes are
+
+open.
+
+But they may have very little.
+
+In a consciousness.
+
+At least that's what a lot of ICU doctors think
+
+about people who are in a vegetative state.
+
+And.
+
+What's fascinating and somewhat disturbing is that there are cases
+
+where, while clinically is usually described as condition, is wakefulness.
+
+Without awareness, a subset of patients may show no reliable
+
+behavioural signs and yet be able to communicate known as
+
+a minimally conscious state.
+
+And this is famously described by Jean-Dominique OB, who is
+
+a former editor.
+
+Elle and then became locked in in a minimally conscious
+
+state and went on to write this beautiful book, The
+
+Diving Bell and the Butterfly, just by fluttering his eyelid
+
+to indicate what words he wanted on the page.
+
+A whole book that.
+
+And the problem is that recovery from this vegetative state
+
+after around one year is very rare and often involves
+
+severe disability.
+
+So it raises ethical issues because you might read in
+
+the media sometimes about decisions, controversial decisions to be made
+
+by the legal and medical professions, about whether it's right
+
+to remove life support from someone who's in a vegetative
+
+state.
+
+That's actually how this is not living anymore.
+
+Now, obviously, this changes a lot.
+
+If science can come along and say, actually, maybe there
+
+is some in a conscious experience there and maybe it's
+
+a meaningful one.
+
+And a real advance came in this area from work
+
+done by Adrian Owens Love, who's now in Canada.
+
+And he showed that in some vegetative state patients, when
+
+you put them into a functional MRI scanner and you
+
+ask them to imagine either walking around the house or
+
+playing tennis, then the activations you got in, say, the
+
+motor cortex and the networks such as the prior to
+
+cortex involved in spatial navigation were very similar to those
+
+you got in controls.
+
+Being asked to imagine walking around the house, all things
+
+tennis.
+
+So that was taken as some evidence that the patients,
+
+even though they're behaviourally unresponsive, may well be conscious to
+
+the same degree as the controls.
+
+Similarly, it's been possible to use non-invasive transcranial magnetic stimulation
+
+to ping the brain and then look at how distributed
+
+responses reverberate around the brain using EEG.
+
+I won't go into all the details of this, but
+
+essentially what you can do is then take these recordings,
+
+compress it down and ask how complex is the activation
+
+that is elicited?
+
+This is known as the Participation complexity index PCI.
+
+And when you plot this perturbation to index on the
+
+y axis here as a sorted according to the different
+
+patient groups, then healthy subjects are up here.
+
+So you see complex brain responses and patients who are
+
+confirmed vegetative state down here.
+
+But what's interesting is these behaviourally unresponsive MCI patients sometimes
+
+drift over into the healthy range and even some vegetative
+
+state patients might start to be providing some evidence of
+
+consciousness.
+
+So I just want to end with a single case
+
+study.
+
+So this was reported in this paper made you know,
+
+in reviewing a lot of this literature in 2013.
+
+So this was a 26 year old male who'd had
+
+a motor vehicle accident, was admitted to hospital in a
+
+coma.
+
+And over the next 12 years remaining consistent behaviour defined
+
+vegetative state.
+
+And in February 2012, he used I wouldn't use this
+
+tiny house method to answer multiple externally verifiable questions so
+
+you could ask the subject to imagine playing tennis.
+
+Yes.
+
+Or imagine play walking around your house for no.
+
+And then he was able to answer using that non-invasive
+
+brain imaging method his own what his name was, the
+
+name of his support worker and so on.
+
+These are things that.
+
+You know, only he could have known and were able
+
+to be verified by the medics.
+
+And then what becomes very difficult is the same technique
+
+could then be used to ask non verifiable questions that
+
+might be important for quality of care, which is what
+
+he wants to watch on TV and whether he is
+
+in pain.
+
+So there's clear ethical implications here.
+
+I won't read all these out, but just to highlight
+
+what sorry, just to highlight a couple of things.
+
+So first of all, we might have an intuition that
+
+that must be a terrible quality of life being locked
+
+in.
+
+All you could do is imagine and create brain activity
+
+patterns that you can't do anything.
+
+You're sitting there just completely stationary.
+
+But our intuitions about this might actually be wrong.
+
+When you measure quality of life in patients who in
+
+locked in syndrome patients, the majority say they're happy with
+
+their quality of life even though they're locked in and
+
+this is covered in the baby book.
+
+And so the advantage of then single patient communication is
+
+that a subset of those patients might not be happy,
+
+but there might be very simple things that we can
+
+do to change and be able to communicate with them.
+
+Noninvasively is potentially very important.
+
+Okay.
+
+So just to conclude, so I've said a few of
+
+these, and the last point here is that neuro imaging
+
+may facilitate communication with behaviourally non-responsive patients and allow classification
+
+of peaceful levels of awareness, but this raises deep ethical
+
+issues.
+
+Thanks very much.

raw_transcripts/lecture_15.txt

@@ -0,0 +1,2715 @@
+Okay.
+
+Good morning, everybody.
+
+I think we're on the mic.
+
+Yeah.
+
+Welcome back.
+
+Unfortunately, last week we had a strike.
+
+Action affected you.
+
+Today, there's no strike.
+
+So please be quiet for the start of the lecture.
+
+So today, this week, returning from last week, all motivation
+
+and consciousness to memory.
+
+We're today going to focus on human memory, a particular
+
+condition that illuminates a lot of our memory.
+
+And on Friday, we'll pick up on animal research.
+
+This holiday on tonight.
+
+What do we know about what the cells are doing?
+
+So in this lecture, you should know about different types
+
+of amnesia.
+
+This is the topic of today, the brain regions involved.
+
+Examples of the neuropsychological tests which would be important if
+
+any of you are interested in going on into clinical
+
+psychology and the functions lost or retained in amnesia and
+
+controversies.
+
+So what is happening here?
+
+Amnesia is defined as a profound loss of memory in
+
+the in the in the presence of relatively preserved cognitive
+
+abilities.
+
+That's a bit of a mouthful.
+
+So what it implies is not some of these just
+
+lost memory.
+
+So we're interested in people who have lost memory and
+
+profoundly not forgot where the book is or where they
+
+park their car or something like that.
+
+Someone who just can't remember any experience of having.
+
+And also they can do other things that have normal
+
+function.
+
+So if you say somewhere else, Alzheimer's and amnesic patients,
+
+the answer is no.
+
+And we'll see you in a moment.
+
+So why is it interesting?
+
+As you'll see in and as you've seen from lots
+
+of lectures in this course, when the system breaks down,
+
+this case amnesia goes that we can learn a lot
+
+about how the system normally functions.
+
+How does healthy memory work when we do have our
+
+memory?
+
+And if you take an example from culture about memory
+
+is a quote from Michael Crichton, who wrote Jurassic Park,
+
+and this is his book, Sphere At the end of
+
+the entire narrative of the book around memories, as though
+
+the characters in the sense the character thought, all we
+
+consist of is memories.
+
+That's who you are in the audience and the way
+
+our personalities are constructed from memories.
+
+Our lives are organised around memories.
+
+You came here today because you had a lecture.
+
+Our culture is built upon memories.
+
+The foundation of shared memories is what we call history
+
+and science.
+
+So this is kind of an attempt to capture the
+
+profound nature of having memory and how devastating we didn't
+
+need it to survive.
+
+What to eat?
+
+Where are you supposed to be?
+
+What you're what to avoid?
+
+All these things that allow us to survive.
+
+What I'm going to talk about today is despite having
+
+a lack of memory amnesia, patients will say, you can
+
+do an amazing range of things.
+
+So here's a YouTube link to something.
+
+I'll show you an example.
+
+It starts with the man with amnesia playing a piano
+
+and remarkably well.
+
+Hopefully the audio work for this.
+
+One man is consigned to live entirely within the.
+
+Present with terrible consequences.
+
+Clive Waring has the worst case of amnesia.
+
+He lost his memory.
+
+And now his wife, Deborah, is the only person he
+
+recognises.
+
+Oh, ho ho, ho, ho!
+
+It really only has less than 30 seconds memory, and
+
+sometimes it's as little as perhaps 7 seconds.
+
+It's as little as a sentence.
+
+I'm going to see your sister down at dances.
+
+Got married recently in New Zealand and said they're having
+
+a party from her.
+
+The Ladies Club title.
+
+A married man will see to know how much he
+
+knows how many guests he didn't put down.
+
+I need to know why I'm going.
+
+She's having a party at her house tomorrow.
+
+She will say no.
+
+I know it is to do with her daughter.
+
+Do you mind have daughters having a party?
+
+Yes.
+
+No.
+
+She's just got married.
+
+She just got married.
+
+And did what country?
+
+She just got married in New Zealand.
+
+Oh.
+
+Yeah.
+
+The sentence he is in.
+
+He will probably have forgotten the sentence before you ask
+
+him a question, and he'll give you an answer.
+
+But while he's giving me the answer.
+
+He's already forgotten the question.
+
+But so bad it is and is worth watching to
+
+the end of it.
+
+I'm not going to court that because it highlights just
+
+that case of Clive wearing just tie for normally tense
+
+and these you can be trying to trying to imagine
+
+how crippling that would be if as I'm talking to
+
+you now, you forgotten why I started the sentence.
+
+What was I talking about?
+
+This is the classic description from Dani's ex, like Clive
+
+Waring, is that it's like waking from a tree.
+
+You know, you woken up in the morning, you're a
+
+bit dazed, and you've been having a really intense dream
+
+about something and it just fades.
+
+And someone says, What were you thinking about in your
+
+dream?
+
+It is really intense for you, but it just evaporates
+
+and you can't remember that.
+
+And they say, certainly Clive says this in the video.
+
+That's like it all the time for him.
+
+And he's really angry because he knows he should know
+
+things, but he can't.
+
+And he says the doctors have been useless, unable to
+
+help.
+
+He's just absolutely straight.
+
+So it's quite it's a quite a side effect of
+
+amnesia.
+
+But let's not forget what he did at the beginning.
+
+He's got no memory.
+
+But how did he remember to play the piano with
+
+absolute expert precision?
+
+So he does have some memory.
+
+And what is the memory he has now as we're
+
+starting this lecture is that's the interesting bit about Clive
+
+and his wife, Deborah.
+
+And also she dies every time he meets his wife,
+
+Deborah, that you saw when he opened the door, He
+
+jumps up and kisses her and cuddles her every single
+
+time.
+
+So she goes to make a cup of tea and
+
+comes back.
+
+He's felt like he's not seen her for years.
+
+And so it's extremely difficult for his wife as well
+
+as her.
+
+So just to highlight the challenges.
+
+So Clive, in that narrative has what's known as organic
+
+amnesia.
+
+There's a there's a he has brain damage that has
+
+caused his amnesia.
+
+There are fascinating.
+
+The psychogenic amnesia is caused by causes where patients suffer
+
+mental health problems and cannot remember things.
+
+We're not going to touch on that today, but they
+
+are they are fascinating and much more complicated.
+
+And I'm talking about the transient amnesia is so epileptic
+
+amnesia is, for example, a schema accompanies.
+
+Is that cause a complete loss that people wake up
+
+from this condition unable to remember what they're doing in
+
+the hospital, where they are, why they're there, what's going
+
+on?
+
+They're amnesic like lies.
+
+But within a couple of days or weeks, it returns
+
+to normal, comes back.
+
+They don't have persistent amnesia.
+
+Clive has this organic, persistent.
+
+He's never remembered anything since his brain damage.
+
+And the other thing Clive has is this non degenerative
+
+form.
+
+He isn't changing.
+
+He's just got the same memory problems day in, day
+
+out.
+
+Degenerative amnesia has come under Alzheimer's disease and other conditions
+
+that keep getting worse.
+
+And sometimes you have this new terrible specific you can
+
+have brain surgery and end up losing memory for words
+
+then on other things or in the case of Clive.
+
+And what we'll be talking about today is the classic
+
+Amnesic syndrome.
+
+Where is all material?
+
+There's another audio, verbal, written, any information coming to him
+
+that he's trying to recall?
+
+It's it's lost.
+
+So let's dive now from the what is amnesia to
+
+what was causing that.
+
+This is a brain in behaviour.
+
+So it's about the behaviour that's going to the brain.
+
+Well, the first place to start with that is the
+
+most commonly damaged brain area for amnesia is the structure
+
+of the hippocampus.
+
+Now he focuses a picture through a schematic of the
+
+human brain and one of the images from the tutorial
+
+you get on anatomy.
+
+And we talked about the hippocampus in regards to the
+
+impact of stressors and how that stress disrupts memory.
+
+And today we're going to talk about it a bit
+
+about the hippocampus beyond stress in terms of other factors
+
+that can damage it.
+
+And on Friday, we'll come back to the two things
+
+that sort of tests that can be used in animals
+
+we thought about in more detail.
+
+But here's the hippocampus gets his name because it looks
+
+a little bit like a seahorse.
+
+You can see that stylised in the brain of a
+
+human post-mortem brain.
+
+Here it is curled up in the medium term for
+
+lobe.
+
+So where is the hippocampus is in the temporal lobe
+
+and it's in the medial powers.
+
+If we take a coronial section is the temporal lobe,
+
+and here is this folded up structure of the hippocampus.
+
+Here, let me slice through a horizontal or a horizontal
+
+section.
+
+We can see the hippocampus is tucked away here.
+
+There's one hippocampus in each hemisphere, and it's huge in
+
+most mammals in the sense.
+
+Takes up a lot of the brain.
+
+And interestingly, it looks very, very similar.
+
+Here's your hippocampus.
+
+Here's what you have to have.
+
+This would look like a version of your brain.
+
+So the cadaver is level surgically.
+
+You don't want to happen, of course.
+
+But if you had to do that with a bat
+
+or a sheep or a giraffe, it would look almost
+
+identical to yours.
+
+So the evolution is tinkered with these things, but hasn't
+
+really changed the hippocampus.
+
+It's doing something utterly important for giraffes, bats and humans
+
+and whales.
+
+All of them have a very similar looking hippocampus.
+
+There's this stuff around in the neocortex that has radically
+
+changed in humans and other species.
+
+Now, this massive wiring diagram, which is very simplistic because
+
+it's from 1991, contains what they call the element of
+
+an and first described is a sort of general structure
+
+of the visual system.
+
+So you covered sensory systems earlier in the course.
+
+Here's your retina where light arrives on the the different
+
+P and cells in your retina and passes through different
+
+processing sections.
+
+And right on top of that is seeing the hippocampus.
+
+This is getting visual input from your eyes.
+
+So what you're seeing now is getting into your hippocampus.
+
+But as we're thinking out, there's a lot of processing
+
+that's occurring across the entire brain before it reaches your
+
+eye.
+
+So there's a lot of.
+
+So the hippocampus is getting information about highly, highly processed
+
+information.
+
+So it's doing something quite important.
+
+Of course, we'll focus that today.
+
+One of the key things the hippocampus is doing is
+
+memory.
+
+Let's dive into the anatomy a bit more.
+
+Here's that picture I showed you earlier of a cadaver.
+
+Here's the section where they stated The brain is really
+
+microtransaction.
+
+They say that these are the black dots, individual cells
+
+for a human, a healthy human.
+
+And what you've got in the middle here is the
+
+hippocampus.
+
+We've got the cortex, the neocortex on the outside.
+
+And what this very simplistic story is showing us is
+
+that there are all these areas in the neocortex that
+
+associate information together.
+
+So going back to this story here, use the retina.
+
+Here is the early processing of the brain provision.
+
+And then there are all these associative areas here.
+
+And that's what we're looking at here.
+
+Lots of information that feeds into two key areas the
+
+power of the campus, our campus cortex and the prefrontal
+
+cortex.
+
+And I showed here in this slide, we've got the
+
+prefrontal cortex here.
+
+And that sends information to an area called the entering
+
+cortex.
+
+This bit here and then it's around the cortex, as
+
+you'll get a lecture from Solomon is one of the
+
+earliest areas affected in Alzheimer's disease.
+
+There's a lot of interest in what this brain areas
+
+doing, the various more elaborate bits in anatomy but effectively
+
+the main pathway information from your eye and other senses
+
+are reaching the hippocampus.
+
+It's through the interactive cortex.
+
+And they terminate their cells into these areas in here.
+
+And we'll come on to that in more detail on
+
+Friday, the anatomy that's going on inside here.
+
+But suffice to say, today we're looking at this area,
+
+the hippocampus in here.
+
+Here's a diagram from a textbook trying to outline the
+
+hippocampus and how it's linked to other areas for amnesia.
+
+This blue area is the hippocampus.
+
+And what we're highlighting is the meat, the temporal lobe,
+
+and an immediate temporal lobe.
+
+That's the corpus callosum that we now had in a
+
+number of markers.
+
+What we're looking at here is a circuit.
+
+So the hippocampus is receiving that information of the Toronto
+
+cortex.
+
+The arrows are showing us that it's passing up a
+
+white matter pathway equal to phonics, which occurs under the
+
+white matter of the corpus callosum, and that terminates in
+
+the anterior thalamus on these military bodies.
+
+So when you learn your anatomy, that's kind of a
+
+clear pathway through.
+
+And there are also structures that come through this.
+
+You can see the point axis terminating and what's known
+
+as the septal nuclei in the basal forebrain.
+
+So these are subcortical structures.
+
+It's kind of shown within the cortical area, but there
+
+are nuclei here and these then pass on to the
+
+cingulate cortex.
+
+And there's a generic or directly split neocortex behind the
+
+corpus callosum, the spleen of the corpus callosum rupturing meaning
+
+behind and spleen, you being this spleen him here of
+
+the corpus callosum.
+
+So these are all key areas.
+
+And the reason I'm highlighting the area this way, if
+
+you damage each of these areas individually or globally, you
+
+will end up with someone like Clive.
+
+And Clive has very, very just like extensive damage.
+
+So amnesic patients aren't always as bad as Clive as
+
+Deborah.
+
+His wife's or the intro sequence says he has one
+
+of the worst cases of amnesia.
+
+But I certainly met patients who were similarly affected.
+
+And so these are the key brain areas.
+
+Let's walk through these and get to know them a
+
+bit more.
+
+They also come under the term paper circuit, which is
+
+originally the scientists papers had described the circuit for kind
+
+of motivation, emotion and memory that included these areas.
+
+And there are two key areas, key types of amnesia
+
+in the literature.
+
+There's what's known as hippocampal amnesia, which is areas disrupted
+
+by the hippocampus and the phonics.
+
+But there's also course some easier, which is we'll see
+
+is linked with thiamine deficiency.
+
+There's more affected by the the bodies of the anterior
+
+thalamus here.
+
+So we'll mostly focus on hippocampal amnesia today.
+
+But there are cases where they suffered a particular damage
+
+that leads to to these particular areas.
+
+Now, of course, the cough was the clinician that spotted
+
+a number of cases and they all came in with
+
+severe alcohol poisoning, really drinking an enormous amount.
+
+They should have died, but they didn't.
+
+But they ended up with really, really like low wearing
+
+severe amnesia.
+
+They didn't have hippocampal damage, but they did have in
+
+thier anterior thalamic, miliary body damage.
+
+And we know that these areas important from these kind
+
+of clinical case studies that this seems to operate as
+
+a circuit which isn't necessary, if you like to remember
+
+what I'm saying to you.
+
+Now if you remember what I'm saying a couple of
+
+sentences ago, you can hear inside your head your anterior
+
+thalamus, and you remove the bodies and the hippocampus.
+
+So what causes amnesia?
+
+Sometimes physical damage, head trauma or surgery?
+
+Viral diseases are one of the common reasons you can
+
+end up.
+
+Encephalitis is one of the most common causes.
+
+Other common causes are loss of blood flow, a schema
+
+or anoxia.
+
+When someone is, as you know, being carbon monoxide poisoning
+
+is a classic example.
+
+And finally, we talked about Corsica syndrome, which is a
+
+low thymus, a thiamine is a key molecule.
+
+A key molecule.
+
+What he needs to process and do a number of
+
+things for your body.
+
+One of those is keep the brain is processing areas
+
+in the brain.
+
+Now, earlier in the course, in the end of my
+
+slides for the first lecture, I talked about this patient,
+
+H.M. Really classic important case.
+
+Brenda milner is the scientist still alive in her late
+
+hundreds and early hundreds is well over 100.
+
+And she studied patient H.M. where he had his bilateral
+
+temporal medial temporal lobes removed the areas we talked about
+
+in that circuit.
+
+Here's the diagram of his brain.
+
+I mean, this is a classic case of amnesia, dense,
+
+just like life.
+
+But he didn't have amnesia before surgery and after surgery,
+
+he did align the scientists to see that if you
+
+intervene with that area, you would result in that dense
+
+amnesia.
+
+Now, we can go from a very severe that's a
+
+huge amount of brain tissue to remove from somebody's brain.
+
+They do not do that anymore.
+
+They're very much, much more selective in surgery.
+
+You don't have to have that level of damage.
+
+Here's patient P.J..
+
+Now, this is a study reported by Van and Ableton,
+
+and here's an MRI.
+
+This is from 2004.
+
+See, MRI scans clinical and it's a bit fuzzy.
+
+But what the arrows point to is an area of
+
+darkness in the sky.
+
+And what that means is water in his brain.
+
+And you can see here what looks like a nice
+
+organised brain has two kind of holes here.
+
+Unfortunately for patient B.J, they got into a fight in
+
+a bar and had a snooker cue forced through their
+
+face in a fight and it skewered the patients and
+
+misery bodies.
+
+They survived a bit like Phineas Gauge, the person on
+
+a on Bach countryside.
+
+But that patient and the period they lived after the
+
+say after having this new cookie removed and the damage
+
+alleviated has severe amnesia despite it disrupting just one small
+
+areas of brain injury bodies.
+
+If you go back to another reason that can cause
+
+amnesia is encephalitis, we can see a case study by
+
+this very famous researcher in amnesia, Larry Squire.
+
+This is Patient EPI.
+
+He's been reported in lots of studies.
+
+And this is an MRI scan of his brain.
+
+It should all look.
+
+This is a scan where the grey grey matter in
+
+the blade brain is dark.
+
+And these areas of white show where there's a lot
+
+of fluid, but the tissue is not normally presents.
+
+And effectively, this patient had a really bad case of
+
+encephalitis affecting the damage to the brain very much like
+
+patient.
+
+H.M. As if they'd had surgery to remove their hippocampus
+
+and patient.
+
+EPI is extremely dense.
+
+The amnesic.
+
+Again, flipping back, you don't always have to have this
+
+extensive massive damage.
+
+Patient y are who will come on the later in
+
+this in the slides.
+
+Here's a healthy MRI scan.
+
+This is the hippocampus on a coronial section curled up
+
+nicely in the medial temporal lobe.
+
+And here it is flattened in this patient who unfortunately
+
+suffered severe carbon monoxide poisoning, just survived.
+
+It had to be revived after being revived, had quite
+
+severe amnesia really affecting their life.
+
+Finally, we can get onto Ischaemia where this is not
+
+anoxia is not like a loss of oxygen environment, but
+
+something in the body that caused a loss of blood
+
+supply.
+
+This can be a stroke, for example, very targeted stroke.
+
+And here's the healthy brain we looked at earlier, and
+
+here is the disruptors.
+
+You can see the nicely laid out cells in our
+
+in the hippocampus.
+
+This nice line of cells.
+
+We'll talk about those cells next week, sorry, this week
+
+on Friday.
+
+And here you can see this area here, nicely organised
+
+in the patient healthy brain and utterly disrupted inside this
+
+patient who had quite severe amnesia, but relatively normal brain
+
+otherwise.
+
+So amnesia can sometimes result from acts massive damage or
+
+very small amounts of damage.
+
+That's the brain.
+
+Let's turn it back to studying what happens to that
+
+brain damage.
+
+So let's look at those patients in different studies.
+
+First thing we'll look at is what can they do
+
+in amnesia?
+
+And then we'll move on to what can they not
+
+do.
+
+Think a bit more about what this tells us about
+
+long term memory and we'll pick up some controversies where
+
+there's been disagreement.
+
+So starting with spared functions.
+
+Oh, I talked to.
+
+So let's just take Clive notes, take the way he
+
+talks about to his wife.
+
+In that interview.
+
+We would say that Clive's general cognitive abilities in that
+
+interview were pretty good.
+
+His IQ seemed quite normal.
+
+It wasn't.
+
+We didn't see him do an IQ test, but I
+
+can tell you his IQ was very high.
+
+His language was entirely normal.
+
+You could hear Clive talking away, perfect prosody, very good.
+
+He was attending to what his.
+
+His wife said he could see Deborah coming in the
+
+door.
+
+He acted appropriately.
+
+We get into executive functions and the last lecture on
+
+this course, that is the ability to organise your behaviour
+
+to achieve goals.
+
+And he was perfectly fine.
+
+So you can say all that.
+
+To say, Look, we watched Clive just now.
+
+He looked entirely normal.
+
+But as a neuropsychologist, which is what we into the
+
+realm of amnesia, we want to study that.
+
+We organise psychological tasks that are quantifiable and have psychometric
+
+properties so we can we can have numbers that come
+
+out of them, we can analyse and make predictions.
+
+There's a standardised test called the Waste Weschler Adult intelligence
+
+scale, which can tell you how someone's IQ is and
+
+what their attention is like.
+
+And Clive will have been assessed and defined to be
+
+very high on this particular test.
+
+And there are other tests like the Wisconsin cause sorting
+
+task will come on to a test for executive functions
+
+and we will come back to that at the end.
+
+Again, Paul Burgess, we'll talk about this later.
+
+And then there are other things that you might show
+
+people, pictures of camels or a tiger, for example, and
+
+say, what is this animal?
+
+And if they've got a normal functioning knowledge, they will
+
+tell you what that camel is or the tiger or.
+
+And you can make that harder and harder with complicated
+
+objects that most people wouldn't know.
+
+Now, all of that makes sense.
+
+We heard Clive do all that.
+
+But what about short term memory?
+
+So we come on in these lectures, the distinction between
+
+long term memory and short term memory.
+
+Now, if Clive was able to have that conversation with
+
+Deborah and respond, she said to him, guess, guess what
+
+your daughter's up to.
+
+He had to hold that information in mind and say,
+
+I had no idea that was an appropriate answer for
+
+Clive to say.
+
+I have no idea if he blurted out elephants.
+
+That would have been absolutely make no sense.
+
+Right.
+
+He had to have heard what his wife Deborah, said
+
+and then respond.
+
+Well, he couldn't do was remember what she said in
+
+the sentence before that his daughter was getting married in
+
+another country.
+
+And so we can see that functionally in Clive.
+
+But scientists have found ways to study that you need
+
+numbers to be able to say Clive is getting worse
+
+or he's stable or or and so on.
+
+And part of the reason we need these kind of
+
+tests is we might want to know whether we want
+
+to do neurosurgery or take an intervention.
+
+You can't do that without these tests.
+
+And so one of these tasks will be span.
+
+Another is the course he blocks on.
+
+And let's take a look at the.
+
+The judge.
+
+The judges found first really simple tests developed going back
+
+to Donald Hebb and others of getting people a sequence
+
+of numbers.
+
+So what they'll do is sit with Clive and say,
+
+okay, Clive, focus on me now.
+
+I'm going to give you some numbers and tell me
+
+what you heard.
+
+And you can say Clive one four.
+
+And Clive probably say one four.
+
+Great.
+
+So he can remember the numbers one four.
+
+But if he said to Clive, okay, I'll give you
+
+one, I'll read out the list here that is used
+
+for all the clinical work.
+
+143928675.
+
+Very likely Clive might say seven five, but he wouldn't
+
+remember the numbers earlier in that sequence.
+
+He's unable to remember what the start of the sequence
+
+was.
+
+And you can do.
+
+If you have those questions.
+
+I like your point.
+
+So he seems to remember what the questions were.
+
+He said, no idea, or so you might likely remember
+
+what the question was.
+
+But you're right.
+
+After a certain number of if you gave him nine
+
+numbers is very likely to say, sorry, what is this
+
+about?
+
+And you know, he don't remember it even knows.
+
+But if you say, can you tell me the number
+
+is one to repeat back 1 to 1 two, because
+
+we heard in there.
+
+So we have very, very small digits than is what's
+
+number.
+
+So you can have a digits of one or maybe
+
+zero.
+
+If they can't hold that, that's extremely, extremely rare.
+
+Maybe someone have a digit span if they're a genius
+
+memory, sort of, you know, maybe they can remember up
+
+to 20 numbers or so, probably more if they're very,
+
+very clever.
+
+But you can do this forwards and backwards as well.
+
+So and if you're doing experiments, you might repeat numbers
+
+where people tend to get better.
+
+So hidden in a sequence of numbers, you might go
+
+through the first sequence and the next and there can
+
+be some hidden repeats, but that's not what we're getting
+
+on since the main thing is that this is one
+
+way of assessing memory amnesia.
+
+Another one is to not use numbers but just visual
+
+information.
+
+So someone has problems of language and they can't remember
+
+words or what you're saying.
+
+You can still use this visual task, which is that
+
+the patient sits opposite you across the table.
+
+If you are the clinician, you see these numbers on
+
+the blocks that the patient opposite can't see the numbers.
+
+And what the clinician will do is tap out a
+
+sequence with their fingers over the blocks and the patient
+
+has the top back the same sequence, either in the
+
+same order or in reverse order.
+
+And again, if they've got a good memory, they'll tap
+
+the right sequence through.
+
+But if it's forgotten, they'll struggle to remember what the
+
+sequence was.
+
+So this is, of course, in long span.
+
+Now, another way of looking at memory going beyond the
+
+short term test is to get into what's known as
+
+procedural or implicit memory.
+
+And there's many different types of this.
+
+So one of the key ways of studying what's known
+
+as procedural memory, we'll get on in a moment to
+
+taxonomy.
+
+The memory is to how people one of the earliest
+
+studies that came up with a way of looking at
+
+this was to say, Well, maybe there are other types
+
+of memory that Clive, that I can't remember what Deborah's
+
+asked, and he can remember how to play a piano,
+
+how And in fact, people found people like Clive could
+
+learn new tasks, procedures for doing things, but be unaware
+
+of it.
+
+So here's one classic example.
+
+In this in this psychometric task, people are shown a
+
+star on a piece of paper, but they can only
+
+see it through a mirror.
+
+So there's a piece of cardboard looking and they can't
+
+see the piece of paper directly.
+
+They can only see it through a mirror and they're
+
+given a pen and just write really simple.
+
+Can you just draw on the inner bit of the
+
+star lists that you're going to draw exactly along the
+
+stars edge and draw around it?
+
+Now, if you just looking directly at a star, you
+
+should be able, if you're most of you in the
+
+room, to be able to do that perfectly, I'd imagine
+
+all of you would do it perfectly.
+
+But if you're looking through a mirror, every move that
+
+you make is reversed.
+
+It's really hard.
+
+You've got to reverse your movements.
+
+So it's very hard.
+
+And so the average person when they're doing this makes
+
+30 errors that go outside the line 30 times, trying
+
+to make their way round the star.
+
+And if you say, Right, okay, great, you do that,
+
+and I do it again.
+
+And another session, they'll get down to say, 12 errors.
+
+You know, they'll get down and eventually you keep giving
+
+them this task by the end of the whole day.
+
+So lots of trials, they'll get down to making maybe
+
+five errors.
+
+So they've got better and better messages over the day.
+
+You get them back, the next day they'll make more
+
+errors as they've gotten a bit very quickly, they'll get
+
+back down to this and then on the third day
+
+of coming back doing this task, they're not flawless, but
+
+they're making very few errors.
+
+So.
+
+Right.
+
+And they know how to do this task and they've
+
+learned how to do mirror drawing with this particular set
+
+up.
+
+So this type of procedural memory.
+
+Now, what's amazing about this is that that score sequence
+
+you're looking at, there is not a healthy person and
+
+someone with amnesia.
+
+And the interesting thing is that they would learn how
+
+to do this pretty much just as fast as a
+
+healthy person.
+
+But on day three, they're surprised.
+
+The reason this surprise is they've never seen this before.
+
+There's no memory of sitting down.
+
+They don't know how to do.
+
+They've never seen the experience and not met the researchers
+
+to them as an uneasy, but yet they know how
+
+to do the skill suddenly got this ability.
+
+So it shows this dissociation between things you can be
+
+conscious and aware of and abilities and memories you're not
+
+conscious that you had.
+
+Another way to do this is as perceptual priming.
+
+This is devised by Elizabeth Warren's.
+
+And so this starts out as an easy version showing
+
+a white and a more difficult version shown on the
+
+left.
+
+So in this particular task, if we focus on the
+
+right hand side, the person is presented with a blank
+
+piece of paper and said, okay, we're going to turn
+
+over this to show you the next picture on the
+
+page.
+
+And I turn over the presentation with the sequence of
+
+dots or this sequence of scrambled dots and it's okay.
+
+Yes.
+
+Guess what these dots are.
+
+There are some there are some thing you can name.
+
+What are they?
+
+And if you've never done this before, you'd have no
+
+idea.
+
+If you had to guess, you might say I could
+
+be anything.
+
+Could be the house, could be anything.
+
+I don't know.
+
+But then they flip the page over to the next
+
+image and they say, What do you think this is?
+
+I know it's not a house.
+
+Something else Maybe you don't know exactly.
+
+You cannot guess what that might be.
+
+Okay, look it over again.
+
+Now it's getting a little clearer what this might be.
+
+And on the last page, you flip over and.
+
+Okay, okay.
+
+If the person's got normal memory, normal functions that he
+
+hasn't caused us an elephant.
+
+I can name the elephant.
+
+Okay.
+
+So they get they can name the elephant on the
+
+last page.
+
+What the clinician will do is repeat this again and
+
+say, okay, here's.
+
+And they'll do that with a whole load of animals.
+
+So you're not just getting one elephant, you're getting you're
+
+getting a seagull or a canoe or whatever.
+
+It's just those little dots.
+
+And so the person might see this and say, Is
+
+it the canoe?
+
+No, they're wrong.
+
+And I go forward and I say, Is it the
+
+elephant?
+
+Yes, it's the elephant.
+
+They've learned that that sequence of dots.
+
+And if you do this again and again, this time
+
+they see this this sequence in dogs.
+
+They can say elephants.
+
+Now, they don't necessarily know.
+
+Sometimes they might know, but they might not necessarily know
+
+why This feels like it's the elephant, particularly this one
+
+here, because it's really difficult to guess.
+
+But the key point of this work is that amnesic
+
+patients likewise can still do this.
+
+He can still guess well above chance that that sequence
+
+of dots is an elephant.
+
+And he's surprised again.
+
+No idea how he knows, but his brain has learned
+
+to associate those dots with elephants.
+
+And what's been shown is that that involves areas of
+
+neocortex and other areas of the brain that are not
+
+the hippocampus.
+
+Hippocampus can help because you can remember things, but this
+
+type of rapid naming of dots can be done by
+
+other brain areas.
+
+So you can do this in amnesic.
+
+Another classic is before we move on to the other
+
+things that are lost.
+
+Example of preserved.
+
+Yeah.
+
+If you're you to.
+
+He only played one time.
+
+He could only play what he'd learned there.
+
+It's very difficult to learn new sheet music, as far
+
+as I know.
+
+I don't.
+
+I don't.
+
+There's a whole Wikipedia page all about Clive, and he
+
+may well tell us whether he has learned, but my
+
+memory is that it's this type of learning can be
+
+done.
+
+And a good point is, if you came back to
+
+Clive in a month's time and said, Right, can you
+
+name this elephant?
+
+He's already forgotten that.
+
+But have also had many normal, healthy people.
+
+Like if I came back to you in a year's
+
+time and said, Right, what was that?
+
+With these dots, you might remember if I was only
+
+an elephant I showed you.
+
+But if I showed you a whole ton of animals
+
+and things, you wouldn't remember it.
+
+This is something in the immediate area of learning.
+
+But yeah, it's a good question.
+
+As I say, I don't know the exact answer, but
+
+it's very likely he couldn't learn.
+
+And again, the challenge is finding styles, specifically tasks.
+
+You can go metrics and numbers out.
+
+So here is a task developed by Barbara Knowlton and
+
+others published in Science some time back and has been
+
+reused in lots of studies, and they tested it on
+
+both patients with Parkinson's, Huntington's or amnesic cases, the brains
+
+of different patients.
+
+And what they found was that what they did in
+
+this ask is take a sequence of cards that only
+
+show one of these at a time and a whole
+
+sequence of these cards for these cards.
+
+But they keep flipping through them and saying, okay, when
+
+you see a card, let's take the latest item.
+
+And you say, okay, what with each of these cards
+
+is going to give you, you going to have to
+
+guess whether it's going to be sunny or rainy today
+
+based on the card.
+
+And then they guess you might say, well, I've no
+
+idea, but I'm going to get some.
+
+And they're told, yes, you're right, that son.
+
+And he's the son.
+
+Perfect.
+
+Okay.
+
+Next card, son.
+
+Right.
+
+They said, Well, you guessed right.
+
+And I've been told, no, you're wrong, that that was
+
+done.
+
+And they go and they see the cards and they
+
+have to learn what the association is between a card
+
+and an outcome.
+
+And of course, this goes back to our reinforcement learning
+
+lecture last week where I talked about the idea.
+
+If you watched the movie of the idea that you'd
+
+need that motivational circuit, the dopamine to learn this association.
+
+And so what's really important here is that it's not
+
+100% probable.
+
+So if you given this card 80% of the time,
+
+it will lead to say something and 20% it will
+
+be right.
+
+So you can't by using one shot experience memorise, you've
+
+got to learn over lots of trials.
+
+What each card is associated with.
+
+All of them will give you some rain.
+
+But these two, for example, might give you some more
+
+of the time.
+
+And these.
+
+Right more of the time and was exciting and why.
+
+This is published in one of the world's leading science
+
+journal Science was that amnesic patients could have learned that
+
+rule over 50 trials.
+
+They could they could learn what this is they don't
+
+get as an doctor.
+
+Guess some well done Huntington's and Parkinson's patients.
+
+Damage destroys them.
+
+And about the last week, they struggle to learn that
+
+rule their VCA, that whole circuit to do it opening
+
+is disrupted the VCA and that circuit is not disrupted
+
+and classic amnesia.
+
+And so what was fascinating was that they got this
+
+dissociation between amnesia able to learn, and Parkinson sometimes is
+
+not able to learn.
+
+But when you test them an hour later, have you
+
+seen these stimuli?
+
+Which of these eight cards and there's four of these
+
+and four other ones did you look at Parkinson's patients
+
+and Huntington's?
+
+Yeah, it's obvious it was.
+
+I spent ages looking at these cards as these four.
+
+They know what they saw.
+
+They can recognise the stimuli, but Clive Waring and other
+
+amnesia patients would have no idea that they seen these
+
+cards.
+
+So you have this association with learning a rule and
+
+being able to remember the stimuli.
+
+What did you see before you recognise it?
+
+So this this is this is this implicit with this
+
+learning of the rule is described as habit learning.
+
+Like your brain is constantly learning habits all the time,
+
+sitting down, setting up laptops where you turn to when
+
+you leave this.
+
+You been in lectures here lots of times.
+
+You're not thinking very hard about where the doors are.
+
+You have a habit ingrained in your brain.
+
+That's what's the amazing things that are stated in these
+
+amnesic patients.
+
+But what is lost?
+
+Okay, so we're going to measure that.
+
+What appears to be lost is cut encapsulated by this,
+
+what's known as episodic memory.
+
+Memory for events and episodes which were personally experienced.
+
+The things that happened to you.
+
+So, Clive, to go back to that video I showed,
+
+Deborah asks him and says, I'm going to tell you.
+
+Let me tell you, divorce is getting married.
+
+She's getting married.
+
+Australia.
+
+She's getting married soon.
+
+I'm trying to remember exactly what he said.
+
+I'm sure I didn't get it right, but that is
+
+the gist of it.
+
+He's then tested on.
+
+Well, do you remember what's happening tomorrow?
+
+He has no idea.
+
+So he's failed to remember.
+
+And she asked him several questions.
+
+He can't remember any of them.
+
+This all comes under episodic memory, personally presented events, information
+
+that was given to him or episodes made or experience
+
+that he experienced himself.
+
+Episodic memory.
+
+Now, there's two types of amnesia when we delve down
+
+into this.
+
+What we've just looked at was anterograde amnesia.
+
+So Clive Waring had a lesion in his brain, and
+
+this is his life after that lesion.
+
+His inability to remember whatever his wife is telling him
+
+is known as an interim great amnesia.
+
+He can't remember that his daughter's getting married and told,
+
+but he might remember that he has a daughter.
+
+He wasn't surprised as my daughter's getting married.
+
+I have a daughter.
+
+Do I really have a daughter?
+
+He didn't say that.
+
+Except that he knew he had a daughter.
+
+There's no loss of memory he could have.
+
+There's all sorts of things that Clive knows about happened
+
+in the past.
+
+But there's a period typically in amnesia just close to
+
+the lesion where he had his damage.
+
+But perhaps, for example, let's say his daughter, this is
+
+this is a fictitious narrative.
+
+It's something that happened to his daughter.
+
+This quite significant just before his lesion, his brain damage
+
+is quite likely.
+
+He would not remember that.
+
+And whenever his wife brought it up, he'd be surprised.
+
+And what's important here is that his brain was perfectly
+
+healthy when he learned that information, but it had not
+
+been stored in some way that made it.
+
+Safe or protected.
+
+Where is the memory that he has a daughter from
+
+some time back in his life when he was an
+
+adult has been protected.
+
+He has retained that despite their amnesia.
+
+So you have some retrograde and there's constant anterograde amnesia
+
+in the classic amnesia syndrome.
+
+So how do we test the I'm sorry, great amnesia?
+
+Let's focus on how we test that on the classic
+
+test.
+
+To do that, to look at episodic memory in a
+
+laboratory or at a clinic is to give people this
+
+task where you're shown a abstract picture like this, isn't
+
+it?
+
+Is the real stress complex figure based on the clinicians
+
+that develops it and they give it, the person is
+
+given another piece of paper.
+
+And so can you draw this out as carefully as
+
+you can, do this really carefully?
+
+Drew exactly what you see on this paper, nothing else.
+
+And then after 50 minutes, they're given a blank piece
+
+of paper.
+
+And so, okay, I showed you a piece, a drawing.
+
+Please, can you redraw that?
+
+And again, Clive would have no idea that he has
+
+a drawing or something, but sometimes the amnesic have some
+
+sense they had too.
+
+Earlier on, I showed you patient brain with really small
+
+selective damage.
+
+Here's on the far right of this nine he's is
+
+a control participant who's drawn out the shape.
+
+Each of these are patients with a brain with really
+
+severe damage.
+
+They've all drawn that shape perfectly relatively perfectly.
+
+And the control participants and a fantastic job, they've drawn
+
+it themselves.
+
+So they they've got a better memory than if you
+
+just seen the picture.
+
+You can see they've gotten the lines across.
+
+Yes, they're not perfect.
+
+But each of these participants here, they've remember these are
+
+amnesic patients.
+
+And remember something arises.
+
+And that in itself is kind of fascinating.
+
+That is something, remember, for retained, but a vast amount
+
+is lost.
+
+So there seems to be some preserved information about this
+
+going into that's very likely.
+
+Is that implicit memory for something about the context of
+
+that.
+
+But it's a great question as to why we still
+
+don't fundamentally understand all the things that occur in amnesia,
+
+and that would be an example of it.
+
+Semantic memories.
+
+You got that memory for Clive.
+
+What was he told in that short chat with his
+
+wife?
+
+Another memory type that's really key is the ability to
+
+remember facts information independently from the initial experience.
+
+So an example of that is knowing what is this
+
+for English speakers and people in the room?
+
+You're hearing this lecture in English.
+
+So you should know that this this diagram here is
+
+a tiger.
+
+That's the knowledge you gained over many experiences.
+
+Now, it's unlikely that you remember the first time you
+
+learn Tiger.
+
+You may do, but many people have grown up in
+
+the first languages.
+
+English Well, I had no idea when I learned I
+
+was very young.
+
+John Another example one was the capital of Peru is
+
+a fact.
+
+I also have no memory of when I first learned
+
+that Lima is the capital of Peru.
+
+So there's much later in life, there's still, for me,
+
+a semantic memory.
+
+I have no idea when I learned that site.
+
+These are just classic examples.
+
+Clive Waring in that interview knew what a daughter was.
+
+He was straight in questions.
+
+A lot of the things he has, a lot of
+
+facts he knows about the world and these are retained.
+
+And Larry Squire, who I put his picture up next,
+
+the patient NPR there.
+
+In fact, Larry Squire, there's a short 50 minute movie.
+
+And this section you can watch where he talks through
+
+declarative memory and taxonomies of memory and history of amnesia.
+
+It is quite helpful if you want some more information.
+
+But here, what was developed by Larry Squire and many
+
+others, Neal Cohen is an example.
+
+The key person here was that long term memory can
+
+be split between explicit memory he describes as declarative memory,
+
+an implicit memory or non declarative memory.
+
+So explicit memories are things like Clive Clive wearing saying,
+
+you know, I do, I do know this or I
+
+don't know that my daughter's getting married tomorrow.
+
+Yes, you can.
+
+You can say yes or no to that.
+
+But how did he play the piano?
+
+It's not a yes, no question.
+
+He used to move his fingers in a particular way.
+
+He could tell you what is happening, but he just
+
+knows how to do it.
+
+It's like riding a bicycle.
+
+You don't really think about it.
+
+You just kind of do it.
+
+And that's what's described here is non declarative skills and
+
+habits and emotional responses to things like priming that can
+
+occur, knowing that that was an elephant given the dots.
+
+So how did you know that?
+
+I just know might be the answer.
+
+And within declarative memory, we're drawing a distinction between episodic
+
+memory events and times, the things that happened, and semantic
+
+memories of facts and figures and things.
+
+And the controversy will now look at.
+
+So that's that's the kind of where we got to
+
+in general agreement these things will exist and that there
+
+are this side of the pathways, damage and amnesia.
+
+Going to end the lecture and the last 8 minutes
+
+or so on controversies.
+
+And one of them has been the brain areas involved
+
+in supporting recognition, memories, semantic memory.
+
+So here, if we look down here, the events of
+
+episodic memory.
+
+You can split if your scientist in two things, you
+
+can recollect, go back in time and remember and say,
+
+Yeah, I was in this lecture theatre in the past.
+
+It was on a monday.
+
+I remember that.
+
+Or you can say you were familiar.
+
+So what classically might be meeting somebody and knowing what
+
+their name is and who they are versus meeting somebody?
+
+You think I know you, but I don't know what
+
+your name is or who you want to know how
+
+I know you, but I just know who you are.
+
+And that's the similarity.
+
+Now, some of the work is shown, and I just
+
+highlighted that example, a feeling of knowing that's what this
+
+slide is running over.
+
+An example here is recognising someone you seen before, not
+
+knowing the name of who they are.
+
+Now, that's fine, I can tell you that.
+
+But if I want to do a test badly, one
+
+of the key forefathers of like a lot of working
+
+memory and neuropsychological assessments developed the task of the two
+
+and people test.
+
+We have to remember people in names or visual shapes
+
+of an either figure or you have to do a
+
+recognition task.
+
+You are given a spotlight, a whole sequence of names
+
+like Jill, Ashley or Doors to memorise really boring doors.
+
+Unless you are tested on that always, you can recognise
+
+those names.
+
+The reason you estimate this side really hard is that
+
+you want us to equate record recall with recognition.
+
+And we're much better recognition because the information's in front
+
+of us.
+
+I was shown here are a number of patients, so
+
+with this test, the rules and people is standardised.
+
+The score of ten is normal and plus or minus
+
+two captures.
+
+And those people I was shown in prior work.
+
+Is that patient?
+
+We are on another case.
+
+This patient John, we're amazingly good if we are really
+
+good are recognising which of these doors you give that
+
+door and they pick it out.
+
+You can even see the colours change the bit.
+
+They recognise this door from having seen 12 doors with
+
+that particular door really good at it and patient John
+
+Similar, but they cannot remember the name.
+
+So the fact this guy's call, Tom Webster utterly forgotten,
+
+absolutely devastated on the on recall side are the patients
+
+suddenly have terrible on both scores.
+
+So what what it shows is generally amnesia damages both
+
+the ability to recognise things like names and pictures and
+
+recall things.
+
+But sometimes the damage can be selective and preserve, says
+
+some other areas of the brain must be doing this
+
+recognition memory.
+
+And that's been somewhat controversial.
+
+Controversial?
+
+The argument is the hippocampus is not essential.
+
+This brain area for tasks using familiarity.
+
+What about semantic memory?
+
+So if I'm going around the world like Clive and
+
+trying to Deborah sitting there, trying to teach Clive about,
+
+say, what a tsunami is.
+
+So it's anomalies are not really discussed in the literature,
+
+in the culture before a certain point.
+
+Big tsunamis came in and killed lots of people and
+
+culture.
+
+So this Endeavour might be trying to explain to Clive
+
+all about tsunamis.
+
+And he's going have a really hard time remembering what
+
+a tsunami is.
+
+And eventually, with all the research shows, he will never
+
+learn new facts.
+
+Clive is so densely amnesic, he can't learn new science
+
+information.
+
+So H.M.
+
+He talked about his famous patient.
+
+He could not remember new word definitions being done.
+
+And the other patient I talked to about both episodic
+
+and semantic information, they can't learn new things.
+
+However, there was a startling discovery in 1997.
+
+Away from, in fact, pretty much in the offices where
+
+the lecture Friday is Fridays lectures at the Institute of
+
+Child Health.
+
+Finally, Volker Kardon is a client, is the lead clinician
+
+for the clinical neuropsychology team for the paediatric pathway in
+
+the ICU in Great Ormond Street.
+
+And her team led the discovery in 1997 of a
+
+group, a number of patients who couldn't remember anything like
+
+Clive come in, no memory, couldn't get a cup of
+
+tea.
+
+They forget who you are.
+
+Yeah, I had amazing knowledge about the world.
+
+And one of those patients I mentioned a second ago
+
+was John, this patient, John.
+
+John went on to pass a GCSE in history.
+
+You got a He didn't get an A-grade, but he
+
+remembered lots of facts.
+
+Somehow this patient, John, had learned over repeated, repeated repetition
+
+facts about the world.
+
+What this tells us is that the neocortex, John, John
+
+and all these patients has severe hippocampal damage.
+
+My patient, while John's hippocampus was shrunken, the key thing,
+
+the word his early onset, all of them had damaged
+
+in childhood, really early in life.
+
+So these are their their neocortex, the survival supplies for
+
+this gradual learning, or there's something about their hippocampus when
+
+damaged early in life, still able to pull off this
+
+trick.
+
+You still don't know the exact mechanism.
+
+It's very hard to study in humans, these things.
+
+So this has been controversial and caused a lot of
+
+disagreement.
+
+But the current no doubt there's no dispute.
+
+These children have grown up with eyes and memory and
+
+can't remember what happened to them over their lives in
+
+terms of experiences they don't know facts about.
+
+They know they got a brother, for example, but they
+
+don't.
+
+You said, Don't you remember your 14th birthday when Joe
+
+came and it was a disaster?
+
+No.
+
+No memory.
+
+Most people remember the disastrous birthday they might have had.
+
+They won't have that ability.
+
+Finally, I'm going to touch on the last moments of
+
+this lecture on consolidation.
+
+So here's patient H.M. Here's the dense.
+
+I'm Terry Great amnesia.
+
+He had utterly after the surgery he lost all capacity
+
+to learn new things.
+
+But they asked him questions before the surgery and just
+
+before it.
+
+Very few details.
+
+But you go back into his childhood and he could
+
+remember.
+
+So he lost.
+
+He lost the memory of an uncle who died very
+
+sadly.
+
+And his childhood memories are fantastic.
+
+What was argued around from that information was that it
+
+seems like the hippocampus in that circuit we've been looking
+
+at is damaged in amnesia, is critical for inquiry into
+
+memories.
+
+But then over time that becomes consolidated.
+
+Consolidated is strengthened.
+
+Those memories become strengthened and stored in a much more
+
+robust way, and then they become independent of the hippocampus.
+
+So let's take another patient.
+
+So that was H.M. But here's a patient p Z
+
+who had a diary.
+
+He kept a meticulous diary.
+
+So you can go back and work out how much
+
+of his diary did he remember and what matters.
+
+And Sir Mark showed in a paper study was that
+
+it was like up and up linearly.
+
+I just went up backwards over time.
+
+And there are a range of ways to probe this
+
+with a diary or with photographs of famous people.
+
+If you're an American, these are famous celebrities.
+
+You might recognise one or two if you're lucky, and
+
+there are standardised ways of interviewing people as highlights.
+
+So most of these suffer from some retrograde amnesia, but
+
+it's variable pace, I think is a case of patient
+
+RB Where we went a few years back, another case
+
+l.D.
+
+This famous face, no memories their entire life back to
+
+childhood.
+
+It's hard to study few standardised tests if you're not
+
+motivated, it's very hard to study and all the stimuli
+
+are very hard to match how salient they are.
+
+And it's hard to know whether those memories are going
+
+back up and synthesised or episodic.
+
+So that's one of the other debates.
+
+And what scientists think is going on is that when
+
+you first acquire memory, your neocortex or go back to
+
+that slide on the hippocampus, the neocortex, signs of.
+
+Mason is at the campus and creates links and binds
+
+together information between areas in the neocortex, which, of course
+
+talk to each other, connect connections between the cells.
+
+But over time, these connections between these great areas become
+
+strengthened and able to operate, and the connections with the
+
+hippocampus become downregulated not necessary for the retrieval of the
+
+memory.
+
+And that's that is the standard model of consolidation.
+
+Very simple model that if you remember things initially, like
+
+H.M. learns that he's got a uncle, he's who's died
+
+very sad.
+
+He uses hippocampus to bind it, but he then has
+
+his hippocampus removed.
+
+It doesn't have a chance to strengthen or the fact
+
+there was a fire in his and his in his
+
+an environment of his young really early along back in
+
+his childhood.
+
+It does get strengthened and he can remember it because
+
+his neocortex has got that memory strengthened and consolidated.
+
+Now that was argued against in 1997 by two scientists,
+
+Maurice Moscowitz.
+
+And then they tell you argue that actually the details
+
+and never really there.
+
+If you go back to these kind of the pollen
+
+and the fire is not detail in nature and cannot
+
+tell you when you could when he was alive about
+
+the details of it that in fact, as we get
+
+as things go on, they argue the visual details get
+
+strengthened with the hippocampus and MCO, the medial temple who
+
+are strengthened.
+
+That view was updated in 2011 in this journal article
+
+by Whittaker Moskovitz to argue that there's a transformation that
+
+occurs in the brain for detail.
+
+And here's just one case example from Pelosi and colleagues
+
+who are on the case who absolutely could not recall
+
+things from their life, the detail they could recognise, not
+
+the things that happen to them.
+
+So we can see this distinction between vivid, rich detail
+
+of recall and massive dishonesty and retrograde amnesia.
+
+But there's no gradient, and it's this episodic loss that's
+
+occurring.
+
+So I'm just going to end on a few last
+
+points.
+
+Let's take an example of this kind of consolidation.
+
+This is an amnesic taxi driver.
+
+I was fortunate to study with Eliot and McGuire at
+
+UCL.
+
+He was hippocampus, was disrupted bilaterally, very severe damage damages,
+
+hippocampus like Clive wearing.
+
+I stepped out to get him a cup of tea
+
+and came back.
+
+He reintroduced himself to me and said Hello, but we've
+
+been talking for some time.
+
+I gave him I gave him the compass with an
+
+arrow on it.
+
+He couldn't see the compass.
+
+It was hidden so I could measure his direction pointing.
+
+I just I could just point to various places around
+
+London.
+
+We're standing in the middle of Queen's Square.
+
+Where is London Bridge?
+
+I'd be very surprised if you do see it.
+
+The audience could point from here to London Bridge.
+
+I can't do it if you take a London taxi
+
+driver.
+
+He spent 40 years.
+
+He knows exactly about London Bridge.
+
+He knows where Peter Street is.
+
+He knows where all the streets in London, they have
+
+to memorise it to be London taxi drivers.
+
+And this is the chart.
+
+A little little white dots of all the taxi drivers
+
+with healthy brains we measured on in the black dots
+
+this amnesic and he doesn't know how he knows this,
+
+but he knows these directions.
+
+We then were able to put him into a virtual
+
+reality simulation of London back in 2006 and have him
+
+drive round a virtual simulation of London.
+
+And here's a route driven across the virtual simulation by
+
+a group of ten healthy cat taxi drivers.
+
+And in black.
+
+Here's his route.
+
+So it was terrible.
+
+He was really bad at actually navigating.
+
+So we had this knowledge of things, but his ability
+
+to actually find his way in London in a virtual
+
+simulation was terrible.
+
+And what we found was that if he had to
+
+go on minor roads, he couldn't remember.
+
+But the major A-roads he could had been consolidated.
+
+So he had this.
+
+Some of his knowledge that we repeated have been strengthened.
+
+Finally, Demis Hassabis, who was in Newcastle before he's founded
+
+the company DeepMind, ran some studies asking patients to imagine
+
+things like, Can you imagine lying on a sandy beach?
+
+If you ask most people's room, they'll give you a
+
+long, long description, all sorts of things happening.
+
+But if you ask Clive Waring or patients, he was
+
+tested.
+
+They gives you a bit of a vague answer.
+
+They report various things, but it's a bit vague.
+
+And in particular they're missing all of the references to
+
+where things are, things the normal, healthy person.
+
+Things are behind them and they're left there.
+
+But this is all missing.
+
+And what damage some of the elements.
+
+They can't actually imagine the scene.
+
+You can imagine objects like a football.
+
+They have problems processing, constructing the world.
+
+So what this means is that where we are in
+
+2022, the hippocampus is necessary for amnesic to remember things,
+
+but it goes into imagination as well.
+
+Clive Waring would not be able to imagine his daughter's
+
+wedding.
+
+This is what this work shows.
+
+So here's the overview of what we talked about today
+
+for time.
+
+I won't read it out and can't read this and
+
+there's a great review in 2008.

raw_transcripts/lecture_17.txt

@@ -0,0 +1,2205 @@
+Okay, let's let's get started.
+
+Everyone.
+
+Can everyone hear me?
+
+I'm not used to speaking in such a big lecture
+
+theatre.
+
+Okay.
+
+I'm Dan Bender.
+
+I'm the associate professor of Behavioural Neuroscience.
+
+My lab studies sleep, among other things.
+
+And that's what I'm going to talk about today.
+
+I do have to leave at a little bit before
+
+11 for sure.
+
+So if there are any lingering questions, I'll have my
+
+email address over here and you can email me.
+
+But my P.A. soon is operating and I can't miss
+
+her presentation.
+
+So we'll we'll jump right in.
+
+So before I talk about sleep, okay, which is a
+
+very interesting topic, I want to take something.
+
+Go back a little more basic and ask the question,
+
+why do animals have a brain?
+
+Right.
+
+That's that's probably one of the most basic things in
+
+neuroscience.
+
+Why do we have a brain?
+
+And we look through that animal kingdom.
+
+We can see that you have sort of the most
+
+primitive species, such as sponges.
+
+Okay.
+
+And these actually don't have any neurones at all.
+
+Okay.
+
+So the first animals did not have neurones.
+
+It happened some point in evolution.
+
+Okay.
+
+And you see that neurones appear around the time that
+
+jellyfish and similar creatures developed in evolution.
+
+And then if we get to more complex animals, it's
+
+no longer just neurones, but we have ganglia and brain.
+
+Okay.
+
+So it's clusters of neurones working together to do something
+
+that individual neurones can't.
+
+Now, this is where it gets interesting that if we
+
+look at our closest one of our closest invertebrate invertebrate
+
+relatives, the starfish.
+
+So the starfish is closer than roundworms and molluscs and
+
+insects.
+
+It's closer to us than all those other animals.
+
+Starfish actually lost the ganglia.
+
+They lost the brain.
+
+They just have neurones that are connected together in a
+
+ring.
+
+Okay.
+
+Same with sea urchins.
+
+Next time you have uni for sushi, you're thinking you're
+
+eating one of your closest relatives in the invertebrate kingdom.
+
+Now, where it gets very interesting is sea squirts.
+
+The sea squirts actually have a brain in the larval
+
+stage, but then they lose it when they're an adult.
+
+And if we look at sea squirts, it gives us
+
+an answer to the question, Why do we have a
+
+brain?
+
+Okay.
+
+So if we look at a larval sea squirt, it
+
+looks a bit like a tadpole.
+
+It has two little eyes spots.
+
+It has a tail.
+
+It's not a spine, it's not a vertebrate, but it
+
+has a new record, which is, you know, very close
+
+to what vertebrates would have.
+
+And it has a digestive system.
+
+And its main goal and its early life is to
+
+find a nice rock, because once it finds a nice
+
+rock, it's going to attach that rock for the rest
+
+of its life.
+
+And that rock is where it gets all its food
+
+and acts as a filter filtering the water.
+
+So if you place a bad rock, it kind of
+
+sucks, right?
+
+That's the rest of his life.
+
+It's there.
+
+So the thing that's so interesting is that when you're
+
+attached to a rock, why would you need to see
+
+it if a predator was coming?
+
+You can't escape from it.
+
+You're stuck to the rock.
+
+So vision is useless.
+
+Motion is useless, right?
+
+You're just stuck to the rock.
+
+So you're just floating in the water.
+
+So what does a sea squirt do?
+
+It eats its nervous system.
+
+Okay.
+
+It doesn't need it anymore.
+
+It's useful energy.
+
+It digests it.
+
+Okay.
+
+So here's the thing.
+
+If you don't need to move, you don't need to
+
+see.
+
+You don't need a brain.
+
+Okay.
+
+So why do animals have a brain?
+
+Animals need a brain to convert sensation to action.
+
+A jellyfish does that and moves around the water looking
+
+for food.
+
+A sponge doesn't.
+
+It just filters the water.
+
+Doesn't need a brain.
+
+Okay.
+
+Now, this is where it leads to sleep.
+
+Every animal thus far that we know of, if.
+
+If an animal moves, it sleeps.
+
+Okay?
+
+Sleep is a really primitive aspect of the brain.
+
+How do we measure sleep?
+
+Right.
+
+You can't measure it in a jellyfish.
+
+It seems know when you wake it up, it snores.
+
+You have no way of measuring it, you would think.
+
+But it turns out that the most primitive forms of
+
+sleep there is a lack of motion for a prolonged
+
+period of time.
+
+Much like us, there is an elevated threshold to react
+
+to sensory stimulus.
+
+Right.
+
+So if I mention your name now, you're.
+
+You know, you'll look around, right?
+
+You'll hear me.
+
+If you were sleeping in class, you might not unless
+
+I was loud enough.
+
+Right.
+
+Don't worry.
+
+I won't test that out.
+
+The third thing, and this is a bit harder to
+
+test, but you can test in a lot of animals.
+
+There is a rebound after sleep deprivation.
+
+Right.
+
+Which.
+
+Which makes sense.
+
+If I.
+
+If I keep you for three days without sleeping, you're
+
+probably going to fall asleep really, really fast and sleep
+
+for a longer period of time to compensate.
+
+Okay.
+
+So those there is of course, sleep is a lot
+
+more complex.
+
+When you talk about mammals.
+
+But the most basic definition of sleep are these three
+
+things.
+
+So now you can ask the question when you move
+
+up the food chain in evolution, how to sleep in
+
+the animal kingdom.
+
+So let's start with the jellyfish.
+
+This is the upside-down jellyfish.
+
+I believe this was a was an undergraduate project from
+
+a bunch of students, and it got published in Current
+
+biology.
+
+That's the story I heard.
+
+So they had a bunch of jellyfish in an A
+
+tank and they tracked the activity of the jellyfish.
+
+And they found that in the daytime it was moving
+
+a lot.
+
+And the Night-Time it wasn't moving so much.
+
+Now, that does not mean that the animal is sleeping
+
+on its own.
+
+Right.
+
+During this class, some of you might not be moving
+
+a lot.
+
+It doesn't mean that you're sleeping.
+
+Right.
+
+So how can you tell the difference?
+
+So what they did is they perturb the animal so
+
+it couldn't rest.
+
+Okay.
+
+There would be a gust of water coming up.
+
+And every time the animal was sort of, you know,
+
+resting, it would have to move again.
+
+And what they found is that when they perturbed one
+
+night asleep, there was a recovery where there was less
+
+activity than you would expect prior to the perturbation.
+
+Okay.
+
+And even when the animal slept over here, we would
+
+consider sleeping.
+
+There was even less activity.
+
+So it was almost like a like you could say
+
+a deeper sleep.
+
+Now, this is maybe not the same as being able
+
+to record EEG and EMG.
+
+You know, all the signals from the brain of humans
+
+and monitoring their sleep.
+
+But this is the jellyfish, right?
+
+And we're already seeing some basic aspects of sleep here.
+
+Okay.
+
+Remember, they don't have a brain.
+
+They just have neurones.
+
+That's key.
+
+Now, if we go up the food chain to the
+
+fruit fly, which is obviously a lot more complicated than
+
+the jellyfish and its nervous system, we see that the
+
+fruit fly rests more at Night-Time.
+
+You know, lack of movement than in the daytime, which
+
+is already good because usually sleep doesn't have to be
+
+12 hours a night and you're awake 12 hours during
+
+the day.
+
+There are lots of different ways sleep can manifest.
+
+But you do see that there is a preferred time
+
+for the animal to rest.
+
+And what they can test here is also the arousal
+
+threshold that if you, you know, lightly do an air
+
+popper, do something that would preserve the animal.
+
+You have to put more force to get the animal
+
+to wake up.
+
+Okay.
+
+So an animal to move.
+
+So this is one of the key things for sleep.
+
+It's not simply the animals not moving, but it's paying
+
+attention.
+
+And you have to somehow break through.
+
+It's it's an intention to to get through the animal.
+
+Okay.
+
+Now, once we're in the fruit fly.
+
+There is one other thing that's quite cool that you
+
+can start doing that this would be very difficult to
+
+do with the jellyfish, but you can put electrodes in
+
+the brain.
+
+You can tell the animal in a ball so it
+
+walks around and you can actually record neural activity and
+
+combine this with the movement of the animal.
+
+So now you have a way to to not just
+
+look at sleep behaviourally, but look electrophysiological of what's going
+
+on, to see if there are characteristics of neural signals
+
+that that tell you, oh, the animal is sleeping because
+
+you see this animals awake because you see this.
+
+Okay.
+
+Now we're going to go to a larger animal now,
+
+the lizard and the lizard here.
+
+You know, it's it's a vertebrate, first of all.
+
+Right.
+
+It's a lot closer to us.
+
+They definitely sleep.
+
+Okay.
+
+And in the lizard, you start seeing it.
+
+Sleep is not just a homogeneous pattern in the brain.
+
+There's actually two stages.
+
+Now, we don't know if it's exactly like the two
+
+stages of sleep in humans, but it does seem to
+
+be one stage where you have synchronous activity in one
+
+stage where it's less synchronous.
+
+And these seem to oscillate back and forth.
+
+So it's quite different from what you see in other
+
+mammals.
+
+But you already start seeing neural signatures of two different
+
+types of sleep.
+
+And reptiles.
+
+Okay.
+
+Now when you get to birds and mammals, now you
+
+have a more defined sleep pattern.
+
+And this is typically called slow wave sleep and REM
+
+sleep, Slow wave sleep.
+
+You can also call non-REM sleep.
+
+But essentially, when you go to sleep, you fall into
+
+deep sleep.
+
+And you have a lot of this in your early
+
+sleep.
+
+And then you have a little bit of REM sleep.
+
+And then each cycle of sleep, which is about 90
+
+minutes, you have a little bit more REM and a
+
+little bit less slow wave.
+
+Okay.
+
+And by the end of the night, it's mostly REM
+
+sleep.
+
+Okay.
+
+Show of hands.
+
+Do you typically dream in your slow wave sleep or
+
+REM sleep?
+
+Raise your hand if it's slow.
+
+Wave sleep.
+
+Raise your hand in his REM sleep.
+
+Good.
+
+So REM sleep is where you typically dream, but you
+
+can dream also and slowly sleep.
+
+You typically remember your dreams from REM sleep more.
+
+Okay.
+
+So when you're in slow wave sleep and you put
+
+up electrodes so you can record neural activity, you can
+
+see that there's slow oscillations which relate to cortical cortical
+
+communication.
+
+There's spindles which are high oscillation signals that relate to
+
+the thalamus talking to cortex.
+
+And there are also sharp wave ripples, which are extremely
+
+high frequency oscillations in the hippocampus that help it talk
+
+to cortex.
+
+In REM sleep, you see completely different brain activity.
+
+You see theta activity in the hippocampus and you see
+
+tiger waves as well.
+
+Okay.
+
+So if you just were watching the signals coming from
+
+the brain, you could tell if someone is sleeping and
+
+whether it's REM sleep or non REM sleep.
+
+Okay.
+
+And the key thing to remember is REM sleep activity
+
+is very similar to awake activity that is not synchronised
+
+and sort of like all the neurones.
+
+Imagine if the orchestra and there all every instrument is
+
+just practising on its own.
+
+They don't seem coordinated.
+
+Slow wave sleep.
+
+The whole orchestra is going boom, boom, boom together.
+
+And that's what the slow waves are.
+
+Okay, so you have these two different types of sleep.
+
+Now we can look at the animal kingdom to see
+
+how does this type of sleep?
+
+Very right.
+
+Do all animals sleep like us or is there a
+
+lot of variability?
+
+And what you find is that at least with REM
+
+sleep, it is really, really different across the animal kingdom.
+
+So the platypus is the king of REM sleep.
+
+They have 8 hours a night.
+
+We only have two.
+
+Okay.
+
+The dolphin is unfortunately the animal with one of the
+
+least amount of REM sleep.
+
+They have minutes every night.
+
+Okay.
+
+So we know REM sleep is really important.
+
+The same time.
+
+That dolphin is a lot smarter than the platypus.
+
+So it's not really clear why all this extra sleep
+
+a platypus is getting what it gains from us.
+
+Now, if you look at overall sleep times across the
+
+animal kingdom, one thing you notice is that two animals
+
+that are genetically very similar can have very different amounts
+
+of sleep.
+
+So a nice example is the owl monkey below over
+
+here compared to the human right.
+
+We're both primates.
+
+We actually both have the same amount of REM sleep
+
+per night, about 2 hours.
+
+But the owl monkey sleeps 17 hours.
+
+We sleep well.
+
+We're supposed to sleep 8 hours.
+
+It's probably a lot less.
+
+In general, you're staying up late at night, you know,
+
+with your Twitter accounts and bingeing Netflix, like.
+
+Like all of us.
+
+So it's not just genes, right?
+
+There's something else going on.
+
+And it's very likely to be ethology, which means there
+
+are specific constraints on animals, behaviour and habitat.
+
+So, for instance, if you could sleep all day, right,
+
+because you didn't have to worry about food and resources
+
+and other things.
+
+Yeah, maybe.
+
+Maybe over many, many millions of years, you would start
+
+sleeping more, right?
+
+Another thing that's quite buried in the animal kingdom is
+
+unit hemisphere of sleep.
+
+So we sleep with both hemispheres.
+
+At least most of us do.
+
+The dolphins are famous for sleeping with one hemisphere than
+
+the other hemisphere.
+
+And you can see this as they will sort of
+
+circle around when they're sleeping with one side and then
+
+they circle the other direction when they're sleeping with the
+
+other part of their brain.
+
+And they have to do this because.
+
+They need to breathe consciously, so they have to keep
+
+part of their brain on.
+
+Otherwise, they die.
+
+Okay.
+
+So it turns out that it's not just dolphins that
+
+are cool, that there are lots of species that are
+
+capable of this, including birds, water, animals, reptiles.
+
+It's almost that we are the oddballs of the year.
+
+And if you think about it, it's it's quite smart
+
+that you always keep part of your brain on is
+
+if a predator comes or you need to be able
+
+to do something, you would react faster, right?
+
+Or your brain is a bit groggy, but the other
+
+part is awake.
+
+And I mean, I've even heard stories of lizards that
+
+will sleep, you know, with both eyes closed.
+
+But if they sense that there is a predator in
+
+the room, one eye opens and they switch to, you
+
+know, have a third sleep.
+
+So there's probably some flexibility, but a lot of mammals
+
+sleep in or birds will sleep in nests and they
+
+have sort of very safe habitats.
+
+And over time, maybe you have a unit of hemispheric
+
+sleep is not necessary anymore.
+
+And it's not as efficient as sleeping with both hemispheres.
+
+Right.
+
+It takes the dolphin twice as long to sleep because
+
+it have to do one side at a time.
+
+Okay.
+
+It's not just non-REM sleep that is due to hemisphere.
+
+REM sleep requires both hemispheres as far as we can
+
+tell.
+
+So dolphins have a hard time during REM sleep.
+
+Right.
+
+It's like they do.
+
+They have their little dream and then they have to
+
+breathe.
+
+Right.
+
+So that's that's tough.
+
+They're doing this at, you know, seconds or a minute
+
+at a time.
+
+They can hold their breath longer than us.
+
+Fortunately, when we get to the first seal, it's interesting
+
+because the first seal has a behaviour that's more like
+
+terrestrial mammals, but it also lives in the water.
+
+And it turns out that when it's in the water,
+
+you can't do very much REM sleep.
+
+And it also has to sleep with one hemisphere at
+
+a time.
+
+But as soon as it comes to land, then it
+
+says, okay, great.
+
+I don't need to consciously breathe, you know, underwater.
+
+I can have my REM sleep and I can sleep
+
+with both hemispheres and it switches.
+
+So it shows you two really important things.
+
+First, this is the this is much more efficient to
+
+sleep with both hemispheres and to have REM sleep.
+
+At the same time is not essential, right?
+
+It's hard to wrap your head around.
+
+How does an animal get away with not having REM
+
+sleep yet?
+
+As soon as it has an opportunity, it will do
+
+loads of it.
+
+Right.
+
+So it must have a function.
+
+We just don't know what it is.
+
+Okay.
+
+So to sum up so far, all animals with a
+
+brain need to sleep.
+
+As far as we know.
+
+If you discover an animal that doesn't need to sleep,
+
+nature paper, great sleep structure and requirements vary greatly across
+
+different species with different ethology, the habitat, the behaviour, all
+
+of that seems to influence how the animals sleep.
+
+So there is flexibility in what a species can do.
+
+It's not like I'm human.
+
+I have to sleep 8 hours.
+
+But it might take a long time for me to
+
+adapt to then sleep more or sleep less.
+
+So the big question is why is sleep important?
+
+So you have to look at sleep and say this
+
+is the worst possible idea evolution could have come up
+
+with.
+
+Right.
+
+What is your function as a species?
+
+It is to make more of you.
+
+To make more.
+
+Right.
+
+So mating.
+
+You need to get food for energy so you can
+
+do that.
+
+Okay.
+
+So foraging, hunting.
+
+And then there are other animals that are looking for
+
+food, too.
+
+And if they hunt you, you're not going to mate.
+
+Right.
+
+So you need to avoid predation and sleep is one
+
+third of your life and you can't do these essential
+
+things.
+
+So why would why would the brain evolve to take
+
+give you a disadvantage in these things?
+
+You must be getting something in return.
+
+But it's we still don't really understand what we are
+
+getting in return.
+
+And just to emphasise how important sleep is, right.
+
+You would probably say, well, you need food and water
+
+more.
+
+Right.
+
+Well, the world record for no water is 18 days.
+
+Okay.
+
+No food.
+
+74 days.
+
+How long can someone go without sleep, you think?
+
+11 days.
+
+Hey, Randy Gardner.
+
+Hey.
+
+Now it's even possible that part of his brain was
+
+sleeping.
+
+There are some reports of local sleep, but I think
+
+he had problems after this experiment that he performed on
+
+on himself.
+
+And you probably have tested yourself on going one day
+
+without sleep, maybe two.
+
+It's quite difficult.
+
+You don't function well.
+
+But I can tell you, as someone who has young
+
+kids, I went through a lot of sleep deprivation.
+
+You are not the same person.
+
+Okay.
+
+I'm still recovering.
+
+And they have done this as well on on rodents.
+
+And, you know, you put the animal basically on a
+
+on a dish that's rotating.
+
+So the animals not just have to move quickly, but
+
+it it's not continuously awake and where it goes into
+
+the water.
+
+And within 11 to 30 days or so, all the
+
+rats died on this experiment.
+
+Now, one very important thing one can found is that
+
+lack of sleep leads to stress.
+
+And stress has a huge effect on your mental mental
+
+health and well-being.
+
+Okay.
+
+So it's hard to know whether the ability to remove
+
+stress when that's gone, we are in trouble.
+
+And that's why we're having these problems.
+
+Or is it sleep itself?
+
+Okay.
+
+And it's also a vicious circle, as many of you
+
+probably realise that when you're stressed, you can't fall asleep.
+
+When you can't fall asleep.
+
+It will lead to more stress.
+
+Okay.
+
+So sleep is as important as mating, hunting, foraging for
+
+food, avoiding predation.
+
+But we don't know why.
+
+So some ideas.
+
+All of you have been sick at one point.
+
+What?
+
+What do you do?
+
+You go to your bed.
+
+You rest.
+
+You sleep.
+
+You sleep often more.
+
+So there are some benefits to your immune system and
+
+wound healing.
+
+Now, why that is special.
+
+To sleep and not just resting in bed.
+
+There seems to be your immune system does seem to
+
+be synchronised to your sleep cycle and there is probably
+
+a lot more there.
+
+But why that's the case.
+
+Why do you have to be unconscious for your immune
+
+system to kick in and act differently?
+
+We don't know.
+
+Second thing is energy conservation and protection.
+
+So many animals are adapted for hunting or foraging at
+
+night or during the day, but not both.
+
+Okay.
+
+So a good example is, you know, like the nocturnal
+
+primates that you find with these huge eyes.
+
+Right.
+
+Those are great.
+
+In Night-Time, they see much better than we do.
+
+But if you turn the light on, they're like, Oh,
+
+right.
+
+They would not be able to hunt.
+
+And in fact, they would be a danger of predation.
+
+So the best thing they can do is just hide
+
+right here during the day, hunt at night.
+
+But that still doesn't answer the question.
+
+Why do they have to be asleep?
+
+Why can't they just, you know, hang out in their
+
+their cubby-hole and just wait for the right time?
+
+The next idea is homeostasis.
+
+So when you're learning, hopefully today you're learning or your
+
+neurones are building new synapses, the synapses are getting stronger.
+
+But if you do that again and again and again,
+
+there might be some negative effects of scaling up your
+
+synapses too much.
+
+So during sleep, it's thought that there is a homeostatic
+
+mechanism that rebalances things, that things don't go too high
+
+or too low.
+
+And while still maintaining the changes that occurred during learning.
+
+Okay.
+
+Fourth is what's called the washing machine hypothesis that when
+
+you sleep, your brain is able to get rid of
+
+all the crap that's built up.
+
+Okay.
+
+So what do I mean by that?
+
+Well, if you look at amyloid beta, right, related to
+
+dementia, humans have a higher risk.
+
+Okay.
+
+If your sleep efficiency goes down.
+
+So if you're not sleeping well, you have more build-up
+
+of these toxins, which then can lead to dementia.
+
+Okay.
+
+And another example, you can look at how another thing
+
+related to Alzheimer's and there is a build-up of tell
+
+if someone is sleep deprived.
+
+So every time you're going out and partying all night,
+
+you're like, I don't need to sleep.
+
+I'm young, you're building up towel your brain, okay?
+
+You have a big capacity, you know, for how much
+
+you can have.
+
+But at some point you want to sleep and clear
+
+this stuff out so it doesn't build up over time.
+
+And it's not surprising that as you get older, sleep
+
+quality does decline.
+
+And these are associated with a lot of these sorts
+
+of problems.
+
+Okay.
+
+Now, if we look at the brain, this is with
+
+MRI, you can see that there are ways of activity
+
+happening during sleep.
+
+And when the activity goes up, okay, this happens slowly
+
+up and down when it goes Sorry, when it goes
+
+down.
+
+There is a CSF exchange which you see in blue.
+
+So activities in red, when the activity goes down, the
+
+CSF in the brain gets flushed out.
+
+And with this CSF, we think there are a lot
+
+of toxins that have built up and then it's sort
+
+of replenishes.
+
+So that's a bit like a washing machine, right?
+
+It's sort of flushing the brain out.
+
+And then you have new CSF filling up the region
+
+and this way you're getting rid of stuff.
+
+Okay.
+
+If you don't sleep, maybe this can still happen, but
+
+it seems that it's not as efficient.
+
+And there's something about sleep that is ideal for this
+
+to happen.
+
+Okay.
+
+So I talked to you about four hypotheses.
+
+The fifth one I'll focus on for the rest of
+
+the lecture, because that's what my lab does.
+
+And I know more about that than the other four.
+
+So the fifth hypothesis where there is a lot of
+
+evidence is that sleep is important for memory.
+
+And this idea that your recent memories need to get
+
+backed up to long term storage.
+
+And this has to happen during sleep.
+
+So there are lots of experiments you can find out
+
+in the literature where there is some sort of task.
+
+I mean, there are really dozens and dozens of these
+
+sorts of studies.
+
+On the y axis, you see that there's an improvement
+
+in the task.
+
+And if you've taken a nap after you do the
+
+task, you'll do better than if you didn't take a
+
+nap.
+
+Okay, so sleeping is beneficial At the same time, if
+
+you sleep deprived someone, you'll see that their memory retention
+
+is is not as good.
+
+So sleeping is good and not sleeping.
+
+When you're supposed to sleep, you do worse than you
+
+should.
+
+Okay.
+
+Now, as I said before, not sleeping leads to stress.
+
+And there are you know, there are other factors you
+
+have to examine.
+
+But even when you do these things, sleep seems to
+
+be better beneficial for your memory.
+
+So I told you that sleep is divided into REM
+
+sleep and non REM sleep and mammals and birds.
+
+So what is what do you think is more important
+
+for memory?
+
+Is it the REM sleep or the non REM sleep?
+
+Ram.
+
+Raise your hand if it's Ram.
+
+Raise your hand if it's non-REM.
+
+Okay.
+
+A couple brave souls.
+
+Good.
+
+So here's a task.
+
+I'll answer the question in a second.
+
+Here's a task where someone has to remember the location
+
+of different different dots on the screen.
+
+And while they're doing the task, they smell this odour
+
+in the background.
+
+Okay.
+
+I believe it's not a very good odour, but it's
+
+for the purpose of getting their attention and making that
+
+association.
+
+And then when they go to sleep, they can present
+
+that odour while they're sleeping.
+
+And the idea is because the olfactory bulb has direct
+
+connections to the campus, that smell is going to activate
+
+neurones and remind the brain, the hippocampus over here, which
+
+is active during sleep, reminding the hippocampus that, oh, this
+
+is what you were doing.
+
+Think about this memory and perhaps bias your your your
+
+memory processing towards the task rather than all the other
+
+things you did during the day.
+
+So it turns out if you do this during REM
+
+and waking, there is no effect at all on your
+
+memory.
+
+But if you do during slow sleep, if you present
+
+the odour, the performance improves after the sleep session compared
+
+to if there is no odour at all.
+
+Okay.
+
+So this doesn't mean that REM sleep is not important
+
+for memory.
+
+But it seems that slow wave sleep is where this
+
+might this process probably starts.
+
+Okay.
+
+The other thing is this works If you just have
+
+a nap.
+
+And a nap is almost entirely slow wave sleep.
+
+We're non-REM sleep.
+
+Okay.
+
+So you can do these control experiments that even without
+
+any REM sleep, you are benefiting from having having non-REM
+
+sleep.
+
+Okay.
+
+So what do you think is happening during this process?
+
+What?
+
+Why does this work?
+
+So.
+
+The brain is very complicated in lots of different areas.
+
+We're going to focus on the neocortex, which is, you
+
+know, the outside region, all your cortical areas for seeing
+
+and hearing and touch and the hippocampus, which is in
+
+your medial medial temporal lobe.
+
+Okay.
+
+Which is in blue over here.
+
+So it's thought that during non-REM sleep or sorry, prior
+
+to non-REM sleep, when you're awake, cortical activity is happening,
+
+which is representing your whole world.
+
+Right?
+
+It's very much like if I stimulate part of part
+
+of my visual cortex, I'll see a flash of light,
+
+right?
+
+It's not.
+
+What is actually happening out there, is what my brain
+
+is doing that gives me perception.
+
+So all these signals in my brain that are giving
+
+me my conscious experience are being transmitted to the hippocampus.
+
+And the hippocampus is recording this.
+
+Okay.
+
+And when you go to sleep during non-REM sleep, the
+
+hippocampus plays back all these memories.
+
+The cortex, of course, is not as active.
+
+It shouldn't be active at all from the outside world
+
+because your eyes are shut and you're unconscious, but your
+
+brain is actually still very active and your hippocampus talks
+
+to you in your cortex and said, Hey, this is
+
+what you do during the day.
+
+Let's talk about it.
+
+Okay.
+
+And the analogy is that it's very much like your
+
+computer.
+
+You download content during the day when your computer is
+
+on, you're working on it, and then you put your
+
+computer in sleep mode and everything gets backed up to
+
+the cloud.
+
+Okay.
+
+And you have these two modes.
+
+When the computer is active and you're doing stuff, it's
+
+going in one direction.
+
+When your computer is in sleep mode, it can still
+
+be active and can still do stuff when you don't
+
+need the computer.
+
+And it uses that opportunity to back up the data
+
+if it did it while you're working at least, well,
+
+maybe now computers are much faster.
+
+But back in my day, it would slow things down,
+
+right?
+
+So it's better to have these two modes.
+
+So what is the evidence that this is happening?
+
+All of you know H.M.
+
+I don't need to go through the story.
+
+But he had his hippocampus removed to try to stop
+
+the seizures.
+
+And when I said the campus was removed, he suffered
+
+from anterior grade and temporally graded retrograde amnesia for episodic
+
+and semantic memory, which meant he couldn't form new memories,
+
+and his old memories were partially affected.
+
+The further back in time those memories were initially encoded,
+
+the better his memory was, Which means the new experiences
+
+require the hippocampus and hippocampal damage does not erase old
+
+memories.
+
+So if a computer example we just had.
+
+If I take my computer.
+
+Right.
+
+And I don't know, it just blows the fuse.
+
+Doesn't work anymore.
+
+Okay.
+
+Everything.
+
+I backed up to the cloud I still have access
+
+to that's still there.
+
+I can't store new memories.
+
+I can't download content.
+
+I don't have a computer anymore, but I still have
+
+access to the old memories.
+
+And that's what we think the hippocampus is, is for.
+
+Taking new memories and storing it somewhere else.
+
+So the hippocampus is gone.
+
+You just can't do it again.
+
+You can't store new memories.
+
+Okay.
+
+Now, that's in humans.
+
+What happens when we look at rats, right?
+
+We can study neural signals in the brain.
+
+These are experiments I do in my lab.
+
+This video is not from my lab, but we record.
+
+We put electrodes.
+
+Many, many electrodes to record 5000 neurones at the same
+
+time.
+
+And when neurones, when you're listening to neurones, they act
+
+very much like instruments in an orchestra.
+
+They're all doing their thing.
+
+And when they produce the melody together, it's very easy
+
+to recognise they form patterns.
+
+And the question is what are those patterns there they're
+
+forming?
+
+What do those patterns mean?
+
+So.
+
+Okay, so you can hear the sound.
+
+Isn't the sounds of the spikes when you're recording.
+
+What you're seeing is a colour code over here of
+
+the different spikes.
+
+Okay.
+
+And what you find is that when the animals and
+
+when a particular neurone is is responding, it likes a
+
+particular region of the track, the animals running.
+
+So I know I talked about the hippocampus as being
+
+important for memory, and this will come full circle to
+
+that.
+
+But when you're recording in the Rat, it seems like
+
+these neurones act like a GPS.
+
+And so the neurones like one location, another neurone will
+
+like a different location.
+
+And as the animal is running, you have neurone A
+
+and B and C and D firing.
+
+Okay.
+
+And I'll give you a little cartoon over here.
+
+Here's animal running.
+
+And you see the first cell fire, then the the
+
+second, the third, the fourth.
+
+And if you were listening to the brain and you
+
+saw blue, green, red, orange, you say, are the animals
+
+running along this track?
+
+Hey, I know what the animal is doing.
+
+But then the animal goes to sleep and you see
+
+the same neurones fire in the same sequence.
+
+This is a phenomena called replay.
+
+It happens much faster, but it's in the same sequence.
+
+And because this sequence is very unique to both the
+
+track and animal's behaviour and can decode this and say,
+
+we know the animal is thinking about the track and
+
+its sleep.
+
+I don't know if this is a dream.
+
+You can't ask the animal what it's what's the conscious
+
+experience.
+
+Right.
+
+But we can see these patterns are very unique.
+
+They don't happen by chance very easily.
+
+And this seems to reflect what has happened.
+
+So just so you can hear how that sounds.
+
+And remember, that replay event is 5 to 20 times
+
+faster.
+
+So it sounds like all the neurones are fired at
+
+once.
+
+We'll look at the video again.
+
+You're going to see a neurone fire on the bottom,
+
+in the middle, on the left side, on the track.
+
+And when it gets to the corner all the way
+
+on the left, one is rounding.
+
+That's where the replay event will occur.
+
+And I'll I'll tell you when that happens.
+
+So.
+
+So it's running the blue cell fires.
+
+And another the science cell.
+
+Another blue cell.
+
+And here, that was a replay event.
+
+Okay.
+
+And if you saw the cell activity that we play,
+
+there are actually cells active in front of the animal
+
+where it's planning to go.
+
+Okay.
+
+Now.
+
+So the animal is not asleep here.
+
+Okay.
+
+This happens when the animal's awake as well, when it's
+
+sort of tuned out and not running.
+
+You see these replay events, but when the animal goes
+
+to sleep and you're listening to the brain, you hear,
+
+Shh, shh, shh.
+
+And these are all replay events.
+
+Okay.
+
+Yes.
+
+Dear me while I was.
+
+Is the replay as fast.
+
+Yeah.
+
+So when it's asleep and when it's awake.
+
+There are probably differences in the replay, but we don't
+
+really understand those differences.
+
+But the speed is similar.
+
+During REM sleep.
+
+There's one study finding replay.
+
+Okay.
+
+And it's the same speed as the actual experience.
+
+So maybe this is closer to what you have as
+
+a as a as a dream.
+
+The other thing is that during slow wave, sleep is
+
+very fragmented.
+
+So it's like part of the track boom animal replays.
+
+And then one second later, another part of the track,
+
+boom, there's replay.
+
+Okay.
+
+So it's not this.
+
+Imagine a dream is you have this whole storyline that
+
+doesn't seem to be happening here.
+
+Maybe REM sleep does.
+
+Okay.
+
+So you have a behavioural episode.
+
+Animals running along, you know, looking for food on the
+
+track.
+
+This is all getting encoded in your cortex.
+
+It's getting sent to the hippocampus to store.
+
+And then when the animal is not paying attention, you
+
+know, sort of zoning out or sleeping.
+
+We call these offline periods and there's a process of
+
+memory consolidation where the hippocampus backs up this information, the
+
+cortex.
+
+And one reason for this is that the hippocampus learns
+
+things quickly.
+
+Okay.
+
+And it has to decide what are the most important
+
+things to store.
+
+You can't store everything you experience in your brain.
+
+The hippocampus has to make that choice.
+
+So one thing we study in the lab is a
+
+phenomena of memory triage.
+
+Just.
+
+Just like a Annie, right?
+
+You can't help everyone.
+
+You have to rank.
+
+What are the most important cases to see first?
+
+So what are the most important memories?
+
+And during sleep, those get replayed.
+
+So what happens if we disrupt replay so we can
+
+do this by putting electrodes in the brain near the
+
+anterior comissioner?
+
+So the connection between the hippocampi and when we see
+
+this high oscillation, which is called a sharp wave ripple
+
+where replay events occur, we'd give a little pulse and
+
+disrupts neural activity for 100 or 200 milliseconds in the
+
+brain.
+
+And if we time it right, we prevent replay events
+
+from occurring.
+
+Okay.
+
+So we can train the animal on a memory task
+
+involving different arms that are baited.
+
+And when we disrupt replay, we find that the rate
+
+of learning is slower in those animals.
+
+They're still able to learn, but the rate is slower.
+
+And you have to keep in mind that you're blocking
+
+replay just for an hour after the task, and then
+
+the animal can sleep in its own cage after that
+
+normally.
+
+So you're able to disrupt some, but it's not the
+
+perfect experiment where you've blocked all replay that will ever
+
+occur, you know, during the sleep session.
+
+But this is already a hint that replay is important
+
+for learning a memory.
+
+So an experiment that I did a while back rather
+
+than disruption, where you always wonder, maybe I have screwed
+
+something up in the brain by shocking.
+
+Can we do something that is positive?
+
+And so where we improve behaviour or we can bias
+
+activity towards certain memories.
+
+So I train rats on a task where they had
+
+to run to one side if they heard a high
+
+frequency sound, like high notes on the piano, and they
+
+ran to the other side or they heard lower frequency
+
+sounds okay.
+
+So they can do the task and it takes a
+
+while.
+
+Humans are a bit faster.
+
+Rats can learn this in a week to two weeks,
+
+but they learn.
+
+Hey, I hear the sound around this.
+
+I hear that sound runs the other side and they
+
+go to sleep.
+
+And what you would expect if you're recording brain activity
+
+is you would see replay of running to the right
+
+and replay of running to the left right.
+
+These are relevant memories for the animal to learn.
+
+It was getting a reward.
+
+It has to figure out the task.
+
+So you're going to see these replay events.
+
+Now, the question is, if I play sounds associated with
+
+the task, the sound telling the animal to the left,
+
+the sound telling the animal to go right.
+
+Does that affect the replay?
+
+Right.
+
+Just with the like, the old factory cue I showed
+
+you before that influenced the memory.
+
+So potentially, since the brain is still able to hear
+
+sounds, maybe not in exactly the same way you still
+
+hear sound when you're sleeping.
+
+Maybe I can sort of tease the hippocampus to replay
+
+what I wanted to replay.
+
+And that's what I found, that you can you can
+
+have a measure called the mean rate bias, which is
+
+basically you have more activity for these neurones.
+
+If the neurone likes running to the right.
+
+Are those neurones more active for sound?
+
+Are compared to sound.
+
+The sound telling it to go right.
+
+So the blue bar is higher, which means the neurones
+
+are more than neurones unlike to run right respond in
+
+animal runs.
+
+Right are more active when you play sound.
+
+Ah and the neurones that like going left are less
+
+active when you play sound are.
+
+So there seems to be a preference for what replays
+
+when you play a sound.
+
+And what's interesting is that this bias over here persists.
+
+So you might think I play a sound.
+
+I get a replay of just like that.
+
+That's not what happens.
+
+Okay.
+
+You play the sound and you create a state in
+
+the brain for almost 10 seconds where if a replay
+
+event occurs, it is more likely to be in the
+
+direction that is associated with that sound.
+
+Okay.
+
+So you're not causing more replay events.
+
+You were just biasing what will happen when a replay
+
+event occurs?
+
+But as soon as you play another sound, the fact
+
+goes away.
+
+So it seems to be very, very intolerant to say
+
+lots of different things you're doing.
+
+Supplying a sound cue caused a greater reactivation of play
+
+cells associated with that sound for more than 10 seconds,
+
+which was the max tested.
+
+So the summary so far is if you train the
+
+animal to run left for.
+
+A high pitched sound and run rate for a low
+
+pitched sound.
+
+Playing the high pitched sound will cause replays that left
+
+at a low pitch Sound will cause replay to the
+
+right.
+
+If you do this in humans, humans, you don't have
+
+to train them to run right or run less for
+
+just two sounds.
+
+You can do things that are more complicated so you
+
+can have 50 objects.
+
+Each object is the subject has to remember the location
+
+the object should be.
+
+So they're touching on the screen.
+
+Oh, I see the cattle.
+
+I need to press this part of the screen.
+
+And each object is also paired with a sound.
+
+Okay, so you have 50 pictures, sound pairings that the
+
+subject has to remember and during a nap.
+
+So that's only slow wave sleep.
+
+They present half the sounds to the subjects while they're
+
+sleeping.
+
+Okay, So the sounds they present are called the cued
+
+stimuli and the unseen stimuli are they still have a
+
+sound, right?
+
+But those sounds were not played.
+
+Then they test the subjects with acute versus on cued.
+
+Okay.
+
+Importantly, they do not present the sound in the test.
+
+It's only the visual objects and the person has to
+
+remember the location.
+
+And when they do this they see there is less
+
+errors in the cued sound.
+
+So there is learning, there is an improvement in the
+
+cued versus on cued.
+
+So presenting a sound during sleep from the right literature
+
+suggest that we can actually bias what is replaying in
+
+the brain.
+
+And then on top of that, in humans, if you
+
+have presumably more replay of one memory, you have a
+
+better memory than if you're replaying it less.
+
+Okay.
+
+So.
+
+What's the take home message when you study?
+
+Maybe you should have some sounds in the background.
+
+I don't know how robust this is for normal sleep
+
+conditions outside the lab, but if you have test specific
+
+sounds, not music per se, but test specific sounds so
+
+like you have a word you have to remember for,
+
+you know, anatomy.
+
+And then you say, okay, every time I'm thinking about
+
+this word, I'm going to hear the sound that if
+
+you present that sound when you're sleeping, you'll probably remember
+
+the word pairing better.
+
+And so if yes, if you present those sounds while
+
+you're sleeping, you should have a better test performance than
+
+if you just sleep on it on your own.
+
+Now, even more important, if you don't sleep, your performance
+
+will definitely be worse.
+
+Okay.
+
+If there is one take home message, you need to
+
+sleep.
+
+And.
+
+This.
+
+This leads us to evidence that more replay leads to
+
+better memories.
+
+This phenomenon of replay, and that's something that we study
+
+in the lab now of how do you manipulate the
+
+amount of replay in a rats or mouse?
+
+And how does this change the performance of the animal?
+
+Okay.
+
+So thanks for your attention.
+
+I have time for a few questions, but.

raw_transcripts/lecture_18.txt

@@ -0,0 +1,2267 @@
+Earlier in the week.
+
+And now we'll move on to there's two lectures today
+
+on mental disorders.
+
+Next week, neurological disorders.
+
+And then we'll wrap up with the prefrontal cortex.
+
+Just a reminder, two things.
+
+Keep up looking at the neuroanatomy.
+
+It's quite intensive learning about your anatomy.
+
+So keep doing that training as you go through the
+
+degree module.
+
+And also, please do fill in the have your Say
+
+documents where you can return feedback on the course.
+
+We've had all sorts of interesting issues with the the
+
+videos and lecture cast that we're getting.
+
+They're getting That's good advice, good feedback from my side.
+
+So I'll make a start.
+
+In today's lecture on mental disorders, I'm going to cover
+
+a number of topics.
+
+I'll just change the lights to a little darker, particularly
+
+helpful.
+
+And that's because, you know, maybe a bit better.
+
+Okay, so I'm going to cover the following things.
+
+There's a huge range of disorders to do with the
+
+mind.
+
+These are inner regarding these are these are conditions that
+
+are not got a clear individual neurological cause this lecture.
+
+So next week you hear about neurological disorders where you
+
+can see disruptions, clear disruptions in the brain, circuits giving
+
+rise to it.
+
+There are disruptions in the brain and the disorder results
+
+I could talk about today.
+
+But they're not focal.
+
+They don't part of a particular circuit.
+
+So there are vast range of disorders that come under
+
+mental disorders.
+
+We're going to focus on two in today's lecture.
+
+Post-Traumatic stress disorder and schizophrenia.
+
+That is because there's a lot of research on these
+
+topics in the talk in the domain of brain behaviour.
+
+So if you want to look at how strange behaviour
+
+operates and you're interested in what can go wrong with
+
+the brain, these two studies, we're going to look at
+
+the behaviour and the cognitive phenomenon associated with these conditions.
+
+We'll talk about current thinking in the field around these
+
+disorders, about the neural basis.
+
+And we'll start with post-traumatic stress disorder.
+
+Now, if we were sitting in this lecture theatre in
+
+the blizzard bullets whizzing around and there's a gunfight going
+
+on, you would quite rightly be stressed and you could
+
+be extremely stressed because your life is in threat and
+
+you should rightly be stressed.
+
+It would be good if your body has got a
+
+high level of adrenaline.
+
+If you go back to the electrons stress, you have
+
+that continued response, your heart rate.
+
+So you're able to escape the gunfight.
+
+That is a stress response.
+
+The key word in the disorder here is the stress
+
+disorder.
+
+A disorder related to that is the post traumatic nature
+
+of it.
+
+So if you've got a high heart rate, you're worried
+
+about bullets whizzing around, but you're actually just sitting a
+
+calm lake, having a cup of coffee, relaxing and your
+
+heart rates up, your worry, you are extremely stressed by
+
+that.
+
+Is this post-traumatic stress disorder an example of that process?
+
+So according to the main manual on disorders, DSM five,
+
+they they describe post-traumatic stress disorder as caused by a
+
+situation which of which is which a person witnesses experiences
+
+is confronted by threat, actual or perceived that could do
+
+serious injury or cause death to the person or threat
+
+to the physical integrity of the self or other.
+
+So basically, your thoughts that you're going to die or
+
+someone very close to you was going to die, but
+
+you could you could see or you're going to die,
+
+or you might see your child is going to die
+
+or your parents could somebody extremely close to you would
+
+come under this category.
+
+So it then provokes the response described as an intense
+
+fear, helplessness and horror is what the technical type that
+
+describes post-traumatic stress disorder as.
+
+This is very serious.
+
+It can't just be you had a bad day.
+
+It was pretty bad.
+
+And it has to be something really intense.
+
+The symptoms of the current post-traumatic stress disorder, the recurrent
+
+dreams, recollections of the event or events is often a
+
+sequence of events that can cause these things, but it
+
+can be a single event and the feelings that accompany
+
+the trauma or traumatic event.
+
+And in particular there are flashbacks that occur and these
+
+for this to come under the disorder, these have to
+
+cause intense psychological distress.
+
+So if you experience like so you go to a
+
+party, you say some really stupid things and you keep
+
+going back to that and you can get these.
+
+What happens to me?
+
+I recall some stupid thing I said, I'm not I'm
+
+not planning to recall it.
+
+It just flashes into my head and it is distressing,
+
+but it's not intense and it isn't recurring.
+
+And I'm not like stuck in the moment, can't escape
+
+and thinking about my horrible party.
+
+It's it's I can escape that for people who have
+
+post-traumatic stress disorder, they're sucked up into a world inside
+
+their head of these intense psychological distressing feelings And these
+
+flashbacks And these dreams, recollections of flashbacks can lead to
+
+the person trying to avoid thinking.
+
+Or talking about re-engaging with these events.
+
+And this was not the results of diminished interest in
+
+social activities.
+
+And I don't want to go out typically as much.
+
+They feel detached from other people as they suppress their
+
+emotions because they're trying not to break down.
+
+And this leads to this feeling that the world is
+
+bleak and empty, unfortunately.
+
+So really a brilliant bad disorder to have.
+
+Now, the symptoms that go with this include this difficulty
+
+falling asleep, irritability, outbursts, anger, difficulty keeping, concentration on things
+
+and heightened reactions to things in the world.
+
+So the classic example, one of the things we'll see
+
+in some of the studies is, is war.
+
+So you might say not to be a soldier.
+
+You're sent off to fight in a war.
+
+You're constantly surrounded by gunfire.
+
+The friends get shot.
+
+You get shot.
+
+It's your life is in danger.
+
+And your friends have been killed.
+
+After that, you then associate these soldiers, some of them
+
+a small number of associate the sound short bang noises
+
+with threat to their lives.
+
+And so it could just be a cost of putting
+
+up someone, putting a cup down too heavy on a
+
+table.
+
+These can just set off this stress response in these
+
+individuals that have post-traumatic stress disorder, PTSD, as this description
+
+indicates, it really does need to have to had mental
+
+health functioning so that they're not keeping themselves in good,
+
+well, mental states, but they also have poor physical state.
+
+If you're not sleeping very well, then if you've experienced
+
+that prolonged lack of sleep through stress or whatever else
+
+can cause that noisy neighbours, you end up feeling rundown,
+
+your immune system lowers.
+
+These are all things that happen.
+
+But one of the factors we start to go into
+
+this beyond the symptoms is that men on average are
+
+exposed to more stressful events.
+
+There's more at least currently these things are changing.
+
+There are more men in the military movement.
+
+It's now up to police officers, fire workers, etc..
+
+And so they tend to be exposed.
+
+But for some reason, women tend to generate end up
+
+generating more cases of PTSD than men.
+
+They may and it's difficult to say there's a paper
+
+on this, but it may be the way women on
+
+average.
+
+This is a really important thing about gender differences, about
+
+the way perceptions of threat occur.
+
+And there are things that one of the one of
+
+the common things that can cause PTSD is childbirth, which,
+
+of course, is a female specific thing.
+
+So the gender of women who are going to have
+
+babies is very stressful events and it can cause lots
+
+of threat to your life and the baby you're trying
+
+to give birth to.
+
+So the evidence from the research suggests using twin studies.
+
+If they look at twins and non twins, they can
+
+see that if one child in a twin identical twins
+
+experiences PTSD, two events is very likely, the other one
+
+will.
+
+Also, it's not very late is a higher likelihood.
+
+The other twin also reacts with PTSD to traumatic events.
+
+So they've shown that there are some genetic susceptibilities towards
+
+PTSD.
+
+This is not surprising, and I think you should take
+
+this as true of almost every behaviour you express that
+
+there's likely to be some genetic loading that leads to
+
+it.
+
+And you know, the your body is built by genetics,
+
+but the environment influences the last couple of aspects of
+
+you.
+
+And PTSD is one of those things, you know, they
+
+influence not just the likelihood that someone will develop PTSD,
+
+but their exposure.
+
+So this comes under there will be just certain genetic
+
+factors that make some people take more risks than others.
+
+I haven't chosen to go into the military.
+
+It's a bit too risky for me and it's not
+
+something I want to do.
+
+But for other people, the idea of being in a
+
+war zone is an attractive life possibility.
+
+And that puts them at greater risk.
+
+There is definitely there's a number of criteria.
+
+People have worked over lots of research over the years
+
+about what can cause PTSD.
+
+So getting a traumatic event earlier in life, for example,
+
+suffering, being early in life is more likely to lead
+
+to PTSD than suffering abuse later in life.
+
+Exposure to repeated events like that, that's going to lead
+
+to more likelihood of PTSD.
+
+And we'll come to a dramatic example of that.
+
+Suddenly having a depressive father has been found to be
+
+a risk factor.
+
+Is it clear from that one of those bits of
+
+data where depressive mothers don't have such an impact, depressive
+
+fathers do?
+
+That could well be that the data that's available increases
+
+in education allow you to be less likely to have
+
+PTSD, if you will, low level of education.
+
+So doing a degree and doing a degree still is
+
+somewhat protective of reducing your PTSD risk.
+
+It seems to have social support.
+
+This goes back to lecture on stress.
+
+You remember the mothers who were licking their pups and
+
+taking care of them better and having a social access
+
+to other animals.
+
+We see this in humans as well, and surprisingly, the
+
+people who don't have to get social support are more
+
+likely to develop these topics.
+
+It also, unsurprisingly, does not help if you have generalised
+
+anxiety disorder, panic disorder or depressive disorders.
+
+These are other mental health conditions that put you at
+
+greater risk if you experience a traumatic event.
+
+So few studies have identified specific genes that are possible
+
+risk factors.
+
+Unsurprisingly, these things go back to the lecture on stress
+
+and reinforcement.
+
+You can see that the serotonin receptors and the dopamine
+
+receptors a really key important features for that association.
+
+So if you for example, one classic example of a
+
+study on PTSD was a ship went down or boats
+
+in the River Thames, a number of people died in
+
+the incident.
+
+Several people survived that.
+
+They felt they had post-traumatic stress disorder.
+
+Watching people drown in front of them now that that
+
+exposure to that, the person has to band together, that
+
+experience of seeing that person's hands slip out of their
+
+ears and drown in the water.
+
+Now, their dopamine system and the serotonin system are an
+
+important regulation of the processes in which they can bind
+
+that information to their memory.
+
+So what the research has shown is that genetic genetic
+
+dispositions come from those circuits.
+
+And as you noted, it's not just if you have
+
+the right genes, you'll get PTSD.
+
+It's utterly the environment that will influence that.
+
+Now, this is a dramatic example from 2010.
+
+So 12 years ago, some impressive researchers, Calasso and colleagues
+
+studied survivors of the Rwandan genocide.
+
+This was a really awful genocide where one group, one,
+
+one and one particular cultural grouping of people in Rwanda
+
+massacred another group of individuals in the exclusion of Hutus.
+
+Unfortunately, what that team were able to do is look
+
+at the survivors who survived these events.
+
+And what made it actually dramatic was that they were
+
+hacking people to death with machetes so that people were
+
+seeing loved ones killed, but also by their neighbours.
+
+So all of these things made it extra traumatic.
+
+And this graph they developed from the data.
+
+So this is of Carlson and Birkin's book, which you
+
+can as one of the core textbooks here.
+
+So what you have on the y axis is the
+
+frequency of PTSD.
+
+And on the x axis is the number of traumatic
+
+events people experience.
+
+So we'll have a group of people down here who
+
+experience no traumatic events, and they had no PTSD, no
+
+surprise whatsoever.
+
+And then you can have people who experience maybe one
+
+event but have no PTSD.
+
+But then you have a group of experience, three events.
+
+And for people, it's been three events.
+
+They found there's a kind of 35% who have PTSD
+
+and higher than none.
+
+The increase in the number of traumatic events they experienced
+
+this could be seeing their family members hacked to death
+
+or seeing people burned or were shot all sorts of
+
+ways in which horrific events occurred in that incident.
+
+As you go up to over 20 events, there wasn't
+
+a single person after 20 events who didn't have PTSD
+
+from observing these.
+
+So what this graph is showing us is that the
+
+more events, the one experience is, the higher probability you
+
+will develop PTSD.
+
+There's pretty clear evidence.
+
+It can be one shot.
+
+It doesn't show in this graph.
+
+But like I said, if you were to lose your
+
+partner or your parent and they slip out of your
+
+hands in a boat disaster, you would feel this intense
+
+guilt and that that could be a factor driving over.
+
+But on average, this graph tells us that story.
+
+Now, this is this is a redrawing of a diagram
+
+you saw in the stress lecture.
+
+You remember that we talked about this pathway, the D
+
+axis and the hippocampus is critical for stress.
+
+So what people have done, and I mentioned in that
+
+stress fracture, we're coming back to that, the work that
+
+was done to look at using MRI, genetic resonance imaging.
+
+And you heard the lectures earlier in the course and
+
+how this worked.
+
+And they were able to look at combat related so
+
+back into the war, post-traumatic stress disorder.
+
+So veterans who had been at war come back, have
+
+their brains measured.
+
+Those veterans who had PTSD compared to veterans who didn't
+
+tended to have a smaller hippocampus.
+
+And they described that as hippocampal damage to something smaller
+
+in their head.
+
+The campus.
+
+And in fact, one study found that that was reduced
+
+by 20%.
+
+And critically, the evidence they provided wasn't just that, oh,
+
+they have a smaller hippocampus, but more exposure to combat
+
+as a veterans.
+
+So the more that person had experienced combat in Iraq
+
+war in this case, I think it was or maybe
+
+it was either the Vietnam War with Iraq war.
+
+It's an American study.
+
+The more the smaller their hippocampus would end up.
+
+And that goes back to the stress lecture.
+
+We talked about work with primates where we could look
+
+at studying macaque monkeys or rats.
+
+How you do stress experimentally, it can damage the hippocampus.
+
+So we see that occurring in post-traumatic stress disorder.
+
+And another study listed here that police officers also went
+
+on to or did not go on to have PTSD.
+
+So, again, this is all building a picture that PTSD
+
+will tend to lead to a smaller effect.
+
+Campus in 2002 was a very interesting study published in
+
+Nature Neuroscience by Gilbert Stephens studies, who argue that at
+
+least part of the reduction may pre-date the exposure to
+
+the stress.
+
+And I mentioned before that certain genetic factors will predispose
+
+you to go into risky situations more than others, and
+
+that will lead you to potentially end up with PTSD
+
+more than others.
+
+What they found remarkably was that the smaller hippocampus may
+
+be a previous predisposing factor for the acquisition.
+
+So what they did, and this is just an incredible
+
+study they've managed to track down.
+
+I don't know how they did this because it's very
+
+difficult for two pairs of identical twins once they got
+
+it.
+
+Twins were only one of the two went to the
+
+Vietnam War and the other one did not.
+
+They were able to scan those and almost half of
+
+the men just let you take a group of 40
+
+people.
+
+Half of these men went on to get PTSD and
+
+half didn't get full.
+
+You have three groups that people who didn't or the
+
+people who didn't get PTSD, people who went and people
+
+to people who went and got PTSD, people who didn't
+
+get PTSD, and the twins who stayed at home.
+
+So the people who had been exposed to the trauma
+
+developed PTSD.
+
+Unsurprisingly, as more have the combine than the people who
+
+did not develop PTSD in that twin group matching the
+
+past studies.
+
+But and indeed, the smaller the hippocampus, the more severe
+
+the PTSD providing that link.
+
+But the really surprising thing was that the brothers, the
+
+Monozygotic twins, didn't go and also had a smaller hippocampus,
+
+which is really weird is this By at a distance,
+
+the hippocampus have been shrunk by news that that brother
+
+had gone through war.
+
+That is not what what the scientists argued.
+
+Rather, they argued that maybe having a smaller hippocampus gives
+
+you less capability to deal with the stressful situation.
+
+It's not harming you as well, and you are more
+
+likely to go on.
+
+This is all about likelihoods, not about this is not
+
+a deterministic.
+
+If you have a small hippocampus, you will get this.
+
+Not at all.
+
+It's more like a predisposition.
+
+So what you have from this story is really the
+
+case that the hippocampus in your brain that you process
+
+in your life of development for you through your genetics
+
+and your exposure.
+
+Growing up grows in a certain size.
+
+It will it will not cause you to be at
+
+risk of PTSD.
+
+If you do suffer PTSD, it will have a knock
+
+on effect and actually also reduce the size.
+
+So there's multiple factors at play there.
+
+So that's the key story.
+
+Comments in literature.
+
+But let's turn to another key brain area in Sam
+
+Solomon's lecture on emotions.
+
+You've heard all about the amygdala and it being critical
+
+for fear.
+
+And what I've described at the beginning of this is
+
+somebody sitting by a lake and feeling about bullets whizzing
+
+around and they're having a really threatened fear.
+
+They're in fear, but there's nothing actually happening.
+
+So the several studies have found that the amygdala well,
+
+is is is is showing these when these when they
+
+look at people lying in a scanner and they look
+
+at how they're reacting to stimuli, food reacting to to
+
+the to the for their symptoms, they can see increased
+
+activity and the link to that.
+
+They've also looked into the prefrontal cortex, as you'll hear
+
+next week is a is a brain area critical for
+
+regulating our behaviour.
+
+We heard early in the course of the lecture one
+
+of us and this gauge who couldn't regulate his behaviour
+
+after Paul was blowing through the front of his head.
+
+So there's a, there's a clear long history going back
+
+to early 1900 on the role of the PTSD in
+
+regulating this.
+
+Clearly sitting at a lake and worrying about bullets flying
+
+around, whether or not there is a failure to regulate
+
+your your emotion.
+
+And so what's argued by colleagues Ralston and Phelps in
+
+the key paper is that the people who've developed PTSD
+
+are lacking that that that controls in their prefrontal cortex
+
+to their amygdala.
+
+They're unable to dampen down the responses in the amygdala.
+
+It's a bit like if you experienced some stressful event
+
+and you could keep ruminating over it and keep thinking
+
+about it and your heart rate will keep going up.
+
+Or you can sit and rationally think, that wasn't that
+
+bad.
+
+It's okay, I'm still here.
+
+Things are going to be alright.
+
+You talk to your friends and you're not worrying about
+
+it.
+
+Why are you worrying about this?
+
+And you have that whole dialogue that is your prefrontal
+
+cortex at work working to lower your your stress response
+
+to make it look So that's wrong.
+
+And me giving a narrative about you talking to your
+
+friends.
+
+What we're showing now is data from a key imaging
+
+study by this team and colleagues, which is that this
+
+helps that.
+
+So this helps as a key researcher in this area
+
+and in the US.
+
+So what they did was take this is a graph,
+
+here's the on the y axis going up and down
+
+is the amount of estimate reactivation.
+
+So if you have a high response, it means this
+
+area is highly active.
+
+Here at point eight or zero, there's no activity.
+
+And compared to baseline, I'm going can look at the
+
+data from just two areas and I'm going to show
+
+you the whole break.
+
+We're just going to average the activity in either the
+
+amygdala or we're going to average activity in the medial
+
+prefrontal cortex.
+
+These two areas have been talking about and what they
+
+did in this study was just to show people with
+
+PTSD or not PTSD lying in this scanner, these two
+
+groups faces happy faces or fearful faces.
+
+And what they found was that the amygdala in people
+
+with PTSD shows a much higher reactivity.
+
+It's more reactive to faces in general, but the favourable
+
+faces are driving more activity in these people, whereas in
+
+fact the fearful faces drive less frontal activity compared to
+
+control participants.
+
+Just is sort of crossover.
+
+This is real data, so it's not as neat as
+
+you would want from an absolute textbook story here.
+
+It's like why is there no response in controls and
+
+why do they switch?
+
+There's not a good explanation for these exact patterns.
+
+The key conclusion, the expansion in colleagues and then has
+
+been following through the field is that with PTSD there's
+
+an increased response of reactivity in the amygdala driving reactions
+
+and less less exerting control from the free prefrontal cortex
+
+in PTSD to dampen that.
+
+So why?
+
+What's going on?
+
+That's okay.
+
+That's that's two brain areas.
+
+Things that in very simple, if you go back to
+
+2001, AI central theory was put forward by Chris Bruin
+
+at UCLA that has really dominated this article and the
+
+one following it had 4000 citations.
+
+It's a really, really influential idea to bring that forward.
+
+So Chris Bruin is the I was thinking about why
+
+is that?
+
+What is going on when people have flashbacks or not
+
+flashbacks?
+
+And he argued back in 2001 that a lot of
+
+what we do but I just described earlier talking to
+
+a friend of mine, a stressful experience is that you
+
+might go back into it and think about that memory.
+
+It'll be some cue.
+
+It could be a picture from the party, or often
+
+he describes it as verbal.
+
+You might talk about it, talk about something and the
+
+cue of the party, the embarrassing party then drives recall
+
+going, Oh yeah, I remember the party.
+
+You were there.
+
+It was really embarrassing.
+
+That's happened.
+
+What he describes at the bottom here is that sensory
+
+input going into your brain is this cue party.
+
+Last week's party course is a complete recall.
+
+See, it happens.
+
+All of the memory is verbal access, memory systems, standard
+
+operating system in your brain.
+
+And you don't really get there because you remember the
+
+party.
+
+It's all contextualised.
+
+You know who was there.
+
+You can recall it.
+
+There's also at the same time, the sensory access memory.
+
+You get the sensory information about who was standing where,
+
+what the colour of the party was, and was it
+
+what was going on in the party visually in your
+
+mind's eye.
+
+But that's what he argued was the typical kind of
+
+you don't really you can inhibit the fear system in
+
+that sense.
+
+Why argue that the flashbacks occur when you can't?
+
+The participants get a sensory input and this pathways weakens.
+
+They're not able to recall the the memories through a
+
+verbal description is not sufficiently and there's a strengthening of
+
+the pathway through the sensory access memory.
+
+And so, for example, people who have road traffic accidents
+
+is another classic PTSD that nearly died.
+
+They had an awful crash.
+
+They had maybe all their limbs are broken.
+
+They're in hospital for months that whenever they smell petrol,
+
+it causes a flashback to that horrific crash.
+
+And in that scenario, this flashback is the smell of
+
+petrol driving this memory and activating the fear system.
+
+And that was a theory put forward in in 2001.
+
+It was then updated is when he collaborated with new
+
+versions that use the two other colleagues in again, a
+
+very influential psychological review article where they essentially invited a
+
+lot more boxes to the is one of the first
+
+things to say anything that more boxes they've now added
+
+a lot of brain areas to to sketch out what
+
+exactly is this mean in terms of the brain and
+
+the replaced the idea of the sound system, the verbal
+
+and non-verbal systems with the idea that some memories you
+
+have contextual memory.
+
+So the context is a broad word, but if I
+
+say to me the past and you say, Yes, I
+
+know that was a policy, or you might say for
+
+the party, yeah, you was there was in my friend's
+
+house and we had drinks and there was the, there
+
+was a big noise and everyone had to leave.
+
+And that's contextual memory.
+
+You remember the house, you remember who was there.
+
+It's not, you know, these are all the details that
+
+can be drawn up from the contextual representations and sensory
+
+representations.
+
+It's what was the colour in the party, what was
+
+the drink, what was the if you had a juice?
+
+What was the colour of the juice you were drinking
+
+at the party?
+
+What was the smell in the party line?
+
+All these sensory experiences would be processed by your brain.
+
+So what the idea, if we start at the top
+
+here, is that in normal recall remembering that party, you
+
+have this top down.
+
+If you start in the right, that prefrontal cortex is
+
+processing the verbal information or the pictures or whatever it
+
+is, it reaches your prefrontal cortex to allocate the decision
+
+that you're going to go in and recall this party.
+
+And you then you can see there are three arrows
+
+coming out.
+
+You start to derive a whole range of brain areas
+
+critically, including the hippocampus.
+
+So if you don't have that hippocampus module in there,
+
+it's been caused by surgical removal bank slices for whatever
+
+would come up under the amnesia lecture recovery, you won't
+
+be able to complete the circuit and retrieve the memory.
+
+It will be incomplete.
+
+But there's a range of areas you don't need to
+
+worry about the full detail in this, in this circuit.
+
+But the core idea is that you can at the
+
+end of that, you get this visual imagery, you can
+
+you can see in your mind's eye or you can
+
+describe that some people don't pick on imagery.
+
+They can describe what was happening at the party.
+
+But there's also a pathway down here that's, you know,
+
+that can be activated.
+
+This to do with the sensory features of the past
+
+involving the amygdala.
+
+Was it a positive party?
+
+How did it feel?
+
+The intercepted parts of the interception?
+
+It's about your body's feeling in you, feeling hot, you
+
+feeling irritable.
+
+All sorts of aspects of this would be under the
+
+insula.
+
+Okay, that's normal.
+
+Let's imagine.
+
+This was this was a gunfight.
+
+Breaks out at the party and it is your life
+
+was in threat.
+
+You survive the people that shot and die.
+
+Now, when you later hear a noise like a car
+
+backfiring, what they've argued is that this kind of situation
+
+or cue a loud noise, doesn't go through the prefrontal
+
+cortex.
+
+It goes straight through early sensory cortex, through your auditory
+
+cortex, in the case of noise.
+
+But it could be through your visual cortex for a
+
+picture that could stimulate you to remember the party.
+
+And you get this rapid.
+
+All these red areas are activated directly without any control,
+
+and you do not remember the details in the same
+
+way you flooded by images and sounds.
+
+So this this description comes from the idea that when
+
+people remember that gunfight in the party, they can't walk
+
+their way through it in the way you would describe
+
+because you've been to that just flooded by sounds, pictures,
+
+images in a quite fragmented way.
+
+And this model tries to explain why that occurs.
+
+So in summary, there are symptoms that occur occurring in
+
+dreams that could move on into the next topic the
+
+recurrent dreams, recollections of traumatic events, feelings of of hopelessness
+
+and so on.
+
+Intense psychological distress occur.
+
+There are genetic environmental factors that lead to people acquiring
+
+PTSD.
+
+Hippocampal size may be a risk factor being smaller or
+
+being bad, and a dominant view is that traumatic events
+
+that they don't tend to get contextually bound together when
+
+they're encoded or learned and become associated with that kind
+
+of sensory reactivation pattern.
+
+So so one of the features out of this treatment
+
+is trying to allow people to go back and find
+
+re-exposed to to reconsider in a more contextual way.
+
+The events, normal retrieval occurs through this top down process
+
+of directing your attention to a memory.
+
+Flashbacks occur by a bottom up, sensory driven process.
+
+So this is some of the key takeaway messages in
+
+what we're covering on PTSD.
+
+I'm now going to move to the second part, second
+
+part of this lecture on schizophrenia.
+
+So this is a serious mental health disorder affects 1%.
+
+The cost to society is enormous.
+
+This exceeds all counsellors.
+
+Descriptions of the symptoms go back to ancient times, really
+
+long time back to ancient Greeks and there's a movie
+
+that I recommend you watch about a patient called Gerald.
+
+Gerald in the movie is interviewed.
+
+He's constantly twisting his hair.
+
+He describes when when asked, How are you?
+
+How are you doing?
+
+He talks about sperms and eggs and nuclear fusion and
+
+then said, Just how does that make you feel?
+
+And he says, Well, the painting on the wall has
+
+a headache.
+
+It's really covers all the different features of schizophrenia.
+
+But so do go and watch this movie.
+
+We don't have time not to actually watch it.
+
+But what Gerald highlights in one individual case and it's
+
+important to recognise that's unusual.
+
+Normally patients with schizophrenia have a number of symptoms, but
+
+not all of them that the symptoms are categorised into
+
+positive ones, negative ones and cognitive ones going back to
+
+2004.
+
+So it's a very serious mental disorder.
+
+There are thought disorders, delusions, hallucinations, bizarre behaviours that in
+
+the movies world is constantly.
+
+Twisting his hair all the way through the movie.
+
+It's not a normal behaviour.
+
+It's a feature that occurs in schizophrenia.
+
+So positive symptoms are not good things.
+
+It's a bit of a misleading term.
+
+Positive symptoms are symptoms the patients express to make themselves
+
+known the evidence, the presence.
+
+So people don't normally have these.
+
+So these include delusions, hallucinations and thought disorders.
+
+So we look at thought disorders.
+
+This is basically that Gerald, when asked in the movie,
+
+how are you feeling?
+
+And he says, well, that picture has a headache.
+
+That is not a rational response to the question.
+
+Or if you go to listen to the movie of
+
+Gerald, everything he says contains perfect syntax and grammar.
+
+There.
+
+There's no words he's made up.
+
+It's all real words put together.
+
+It sounds like it's incredible, but it's disorganised.
+
+It isn't.
+
+It isn't coordinated.
+
+The ideas jump from one topic to another.
+
+They go off on a complete tangent.
+
+So it's very difficult for the patient to cope with
+
+life if that's how the brain operates, that they're disorganised
+
+and it's very difficult for people to care for them
+
+and look after.
+
+If they have this severe schizophrenia and they think rational
+
+things about it, they can talk about what is the
+
+point?
+
+Why does the picture of will have a headache?
+
+And they really have a hard time organising their thoughts
+
+and logically sorting out what's plausible that could have happened
+
+and not plausible and absurd.
+
+And they jump from one topic to another.
+
+Sometimes they use meaningless words.
+
+They can move off.
+
+But as you hear Gerald, it's they slip these in
+
+here or there.
+
+And sometimes the conversation and just choose the next word
+
+because it rhymes rather than it being the most appropriate
+
+one.
+
+That's the disordered thought.
+
+The delusions are fascinating and schizophrenia.
+
+So these are things that are contrary to facts.
+
+So my wife previously is a clinical psychologist and worked
+
+with schizophrenic patients in hospital.
+
+And one day she was talking to a man saying
+
+he's later that afternoon going to travel to Bath from
+
+London.
+
+And it's very late in the day.
+
+And he's he's locked in for his safety there.
+
+And she said, how are you going to get to
+
+bars?
+
+And he looked at her as if she was completely
+
+crazy and said, why, of course.
+
+They started beating his hands up and down.
+
+And she slipped.
+
+This is quite a common occurrence that this belief is
+
+not only that they are deluded, but they think he
+
+believes he can fly and used to say, how are
+
+you going to fly and change the conversation and move
+
+on.
+
+But this is one key example.
+
+I remember an experience I had talking to someone.
+
+So there are different types of delusions that delusion that
+
+patient had was a delusion of grandeur.
+
+He believed he could fly or had a special magical
+
+power.
+
+There are delusions of persecution, and these are these are
+
+the thing that makes schizophrenia quite dark and a very
+
+unpleasant disorder to have.
+
+So the real classic problem in schizophrenia is belief that
+
+they're being plotted against or somebody or a group of
+
+people are conspiring against them.
+
+So if you're in the UK, it's very likely they
+
+start to believe that it's all either of them.
+
+If you were in the US, they will be the
+
+FBI.
+
+If you go back to the ancient Greeks as written
+
+in text, it'll be whoever the bogeyman or whoever, the
+
+secret people that are in charge of of society, you
+
+know, the guards in the tower, whoever it is.
+
+Delusions of grandeur are like this belief.
+
+They can fly to the channel to remarkable things or
+
+have special godlike powers is a classic example that no
+
+one else has.
+
+But they have these powers.
+
+One of the other unpleasant features is schizophrenia, delusions of
+
+control.
+
+They believe that they are being controlled by others, forced
+
+to do the bidding of someone else and often believe
+
+that there's an implant in their head.
+
+Something's got inside them that's causing them to do it.
+
+If you go and watch the movie of Gerald's, you
+
+see, he feels like voices in his head are telling
+
+him to hurt people, making him do unpleasant things.
+
+And they said, Do you want to do these things?
+
+And he says, No, I don't want to hurt people.
+
+But the voices commanding me to do it.
+
+And it's hard.
+
+So that takes me on to the third symptom is
+
+just hallucinations.
+
+These are often auditory.
+
+They can be visual.
+
+They might see things that aren't there, but often the
+
+auditory.
+
+And very often they involve voices of somebody talking to
+
+them inside their head.
+
+So if you've ever seen the film A Beautiful Mind,
+
+it explores that whole idea of Russell Crowe as the
+
+actor in a film of a voice of a person
+
+who is really present to the actor.
+
+That situation in the film.
+
+And it's highly disruptive because the person can tell them
+
+to do things that aren't out there.
+
+That's all positive, but not particularly nice symptoms.
+
+Negative symptoms occur that are taking away things from the
+
+person.
+
+So these include and include things like what an emotional
+
+response he'll see.
+
+If you watch Gerald, he's just looks really dumb.
+
+He's very he looks tired.
+
+It doesn't look very happy.
+
+He doesn't look very well.
+
+So, you know, people don't speak as much of schizophrenia.
+
+They don't initiate things.
+
+They persist on things they shouldn't.
+
+And they show this effort to anhedonia, but they can't
+
+really take much pleasure from things like a really great,
+
+great food or a lovely meal.
+
+They just can't they don't tend to be as excited
+
+by it.
+
+And that partly leads to the other symptoms lead to
+
+social withdrawal, which is not a good thing for them,
+
+for their well-being.
+
+There are negative effects as well.
+
+So this causes this lack of affect to reduce motivation
+
+in the negative symptoms.
+
+Cognitive symptoms are also things that are lost, so they're
+
+also negative in that sense, but they're specifically not to
+
+do with the emotional well-being.
+
+They're to do with things like IQ.
+
+So sustaining attention, learning of memory, abstract thinking and problem
+
+solving that all get disrupted.
+
+We'll see in a moment the key areas of the
+
+brain for learning and memory and problem solving of the
+
+hippocampus, the medial temporal lobe in the frontal cortex, which
+
+are disrupted in schizophrenia.
+
+So these symptoms don't just appear overnight.
+
+It's not like you suddenly wake up like, you know,
+
+through neurosurgery and suddenly you lose these things.
+
+They come in over 3 to 5 years.
+
+Negative symptoms occur first, then the positive, then the cognitive,
+
+and then the positive ones become florid at the end.
+
+Pharmacological evidence.
+
+So we're going to.
+
+Journey.
+
+Now, there's been a long story in the literature going
+
+back decades about the idea that dopamine might be the
+
+key molecule that is disrupted in schizophrenia.
+
+The dopamine hypothesis, which is no longer thought to be
+
+true, as we'll see, but is still the still very
+
+good evidence that dopamine is involved in schizophrenia, but that
+
+it's the sole pathway is not.
+
+This came around from the mid not the 1950s.
+
+This particular man took a drug that was being used,
+
+the surgical shot and applied it to other disorders of
+
+mood and found schizophrenia.
+
+This compound proved chlorpromazine actually was quite effective at helping
+
+treat some of the symptoms in schizophrenia.
+
+And he's tried it on a range of different disorders
+
+and it became a first line treatment for schizophrenia fighting,
+
+particularly this psychotic, which is these hallucinations and delusions.
+
+So is not very effective at certain aspects of features
+
+of it.
+
+But it did.
+
+Dramatic benefits for schizophrenia changes.
+
+Their attitudes, hallucinations and delusions are diminished somewhat with this
+
+drug.
+
+But it has lots of corrosive side effects.
+
+And therefore, a number of medications have been developed since
+
+that time.
+
+All of them had a similar compound feature in common.
+
+They block the antagonise.
+
+They just they antagonise these dopamine receptors than normally the
+
+ones involved in that reinforcement process.
+
+Now, another group of drugs that have the opposite effect,
+
+they agonise, they increase the response of these these these
+
+responses.
+
+And these are things like amphetamine, cocaine.
+
+And you remember my lecture on reinforcement learning and the
+
+rate of these increase dopamine responses.
+
+So in that case, these drugs can you know, if
+
+you take a schizophrenic, if you give them cocaine, they
+
+will have higher schizophrenic experiences, worse than worse than their
+
+their experience.
+
+Drug taking is a real problem in schizophrenia.
+
+So really impressive.
+
+Again, this is like one of these heroic studies.
+
+And you think that this group, by the rule managed
+
+to to put by intravenous injection a group of schizophrenic
+
+patients and control participants in and out in a scanner
+
+and monitor the amount of dopamine released in the striatum
+
+using positron emission tomography.
+
+And they found that in Fetterman caused more dopamine release
+
+in the striatum of schizophrenic patients compared to criminal subjects.
+
+So what we're seeing in this graph here is the
+
+amount of dopamine release.
+
+And you can see here this is controls being given.
+
+Amphetamine is just like the rats in the lecture previously
+
+on Striatum.
+
+They're increasing their dopamine on most of them.
+
+But schizophrenics don't have a higher response.
+
+And the key thing you're taking from this graph is
+
+that, okay, so they have a higher response.
+
+But impressively, the greater the response of this person up
+
+here has a really high response.
+
+And there on this graph over here, the more they
+
+have this response, the mean, the more the positive symptoms
+
+are expressed during the scan, the more the hearing voices
+
+having having hallucinations.
+
+So an impressive link.
+
+But of course, the small samples are very hard work
+
+to do.
+
+Okay.
+
+Another possibility that's been explored is that the dope receptors
+
+are changed in schizophrenic patients.
+
+So this is not that they're releasing more of me,
+
+but their receptors are are are changed.
+
+And that's because the drugs work by blocking those receptors.
+
+So the researchers and performed an analysis of post-mortem brains.
+
+They got hold of schizophrenics, brains and looked at them.
+
+They also use positron emission tomography to look at this
+
+late radioactive ligands.
+
+And they can make radioactive dopamine and explore responses to
+
+the amount of dopamine released.
+
+And in reviews, they concluded, this story doesn't stack up
+
+so well.
+
+There's only a modest increase in the different receptors in
+
+schizophrenics.
+
+And it seems unlikely that this is the primary cause
+
+of the disorder.
+
+It's the other structures occur in the brain that are
+
+just moving so we can get get through the lecture.
+
+So they're in when they do neuropsychological testing and brain
+
+imaging studies, they can see that there are these changes
+
+in the problems of moving and memory.
+
+And unsurprisingly, this could be linked to the frontal lobes
+
+in the hippocampus.
+
+That's that's stating what we know from the amnesia lectures
+
+and a reduction in the brain volume is occurs in
+
+these schizophrenic patients because these highlighted brain areas but much
+
+more in Alzheimer's.
+
+Next week you'll hear some Solomon talk about Alzheimer's where
+
+there are some dramatic loss.
+
+So in an Alzheimer's patient, when they reach an end
+
+stage, their brain is shrunk to the size of an
+
+orange.
+
+It's not.
+
+It's still there, but it's absolutely diminished.
+
+Schizophrenia.
+
+These are damaging similar areas, but much, much smaller extent.
+
+Now it's uncertain as this highlights this key point whether
+
+those volumetric changes in these areas occur because of the
+
+disease and the symptoms or the always there.
+
+Were they existing before the development of the disease or
+
+indeed the drugs is another feature of this.
+
+And there have been associations between the deficits and the
+
+brain volume.
+
+So if you have a smaller frontal cortex in schizophrenia,
+
+you have less good abstract problem solving.
+
+If you have a shrunken hippocampus, you have more problems
+
+with learning and memory.
+
+This fits with the other lectures you've had on learning
+
+and memory in this course, because those neural circuits are
+
+altered.
+
+And it's also been suggested that it's not just brain
+
+areas drinking.
+
+The whole circuits are disrupted.
+
+The schizophrenia should be considered as a collection of neurodevelopmental
+
+disorders.
+
+It's worth unpacking that one sentence is very easy to
+
+get up and just read through the slide and go,
+
+okay, so schizophrenia is altered neural circuits and it's a
+
+collection of neurologic neurodevelopmental disorders.
+
+So first of all, the last word on there is
+
+disorder is not disorder.
+
+So what it's highlighting is that schizophrenia is the collection.
+
+It's a syndrome.
+
+It's got there are many ways in which someone could
+
+express similar overlapping conditions.
+
+It is not like, for example, Parkinson's disease, which you
+
+have next week, although there are different types of Parkinson's,
+
+the subtle differences, there is a general pattern in Parkinson's
+
+disease.
+
+You'll see schizophrenia.
+
+You can have some positive, some negative, a range of
+
+symptoms.
+
+And what is believed there are different pathways by which
+
+you can end up with descriptions.
+
+So the argument now is that all of those involve
+
+neurodevelopment.
+
+You don't get schizophrenia having a very healthy, happy life
+
+and suddenly in your forties you get schizophrenia.
+
+It just doesn't happen.
+
+There's something that occurs early in life and in many
+
+cases in the womb and birth.
+
+So there's some things happening in the brain and development
+
+that leads to schizophrenia.
+
+So we'll come back to that and a key slide
+
+in a moment.
+
+Now there's debate over whether the treatment with antipsychotics can
+
+itself cause the reduction in brain volumes.
+
+So if you're on chlorpromazine, it's a drug that disrupts
+
+your brain, stops the functioning of hallucinations and other things,
+
+but it really lowers your you know, it may it
+
+may be that it's one of the features.
+
+It's very hard to know because ethically testing these things
+
+is very hard.
+
+And as I mentioned at the beginning, that dopamine hypothesis,
+
+the old, for example, mean function in schizophrenia underlies the
+
+condition is not thought to be far too simplistic.
+
+And that is partly because the newer drugs, the antipsychotic
+
+drugs that are given, they no longer prescribing chlorpromazine because
+
+of its side effects.
+
+But atypical antipsychotic medications can be very effective and those
+
+don't work by.
+
+So for me, those work by affecting serotonin and the
+
+other key molecule in the brain has but also has
+
+a slight dopamine blocking effect.
+
+Right.
+
+So it's not as simple as is worth highlighting.
+
+When you give a drug that affects their tone, it
+
+will have a knock on effect on the circuits of
+
+your brain to also affect dopamine circuits.
+
+These aren't totally independent brain circuits.
+
+What was interesting in the last decade or so has
+
+moved on to is looking at glutamate and glutamate.
+
+As you remember Solomon's lecture on how neurones operate.
+
+Glutamate is the main excitatory transmitter used most sign up
+
+to this in your brain and it is thought that
+
+alterations in glutamate, particularly the NMDA glutamate receptor, may be
+
+one of the features that's gone wrong in schizophrenia.
+
+So this NMDA, this is a molecule named for the
+
+name is a particular receptor and it has a particular
+
+role in binding and learning and memory and associating things
+
+together.
+
+And it's disruption is thought that may underlie the rise
+
+in schizophrenia.
+
+Everything I'm saying now is quite well covered in the
+
+textbook chapters that are highlighted in the last slide.
+
+So just, just take you away.
+
+So on that note, there's abnormally low levels of this
+
+glutamate receptors in the post-mortem brains.
+
+So remember earlier I highlighted that when they went to
+
+look at the brains of schizophrenics, the post mortem, they
+
+were confident the scientists that were going to find way
+
+less receptors for dopamine also had receptors in dopamine.
+
+And then they were shocked when they didn't find that.
+
+But they did find was actually these abnormal levels of
+
+these receptors, these glutamate NMDA receptors in the brains of
+
+these patients.
+
+So the belief now is there's something disrupted in those
+
+circuits, and that's we'll see is not just the receptors,
+
+but the.
+
+The neurones themselves.
+
+There's there's too many neurones in some places.
+
+They don't have enough myelin.
+
+And again, remember back to Step Solomon's lecture neurones the
+
+myelin sheath that allows the neurones to communicate well that
+
+is disrupted.
+
+So new drugs like this, like could even ketamine have
+
+been around for some time.
+
+Ketamine can mimic these symptoms in schizophrenia.
+
+So I remember particularly as a scientist of the UCL
+
+who's not Cambridge for a long time, he's a medical
+
+doctor, so he could give himself ketamine.
+
+I'm bringing in this presentation where he's on a very
+
+high dose of ketamine and he just looks drifted off
+
+into another world and he sees an aeroplane going by
+
+and he's just focusing on the aeroplane the entire time.
+
+And in this description he describes the fact that the
+
+aeroplane just took over his entire world and it felt
+
+like it was an hour watching this aeroplane travel through
+
+the sky and it completely absorbed him.
+
+And he looks, he has the kind of pattern around
+
+his behaviour, somewhat like someone with severe schizophrenia.
+
+So what this is from my experience I've seen, is
+
+that drugs like ketamine that act on these glutamate receptors,
+
+they block glutamate these particular NMDA functions and can mimic
+
+some of the features, not all of them, that clinician
+
+and that scientists didn't end up having delusions of grandeur.
+
+He didn't think he was going to win the Nobel
+
+Prize after on the ketamine.
+
+So that reduced glutamate function is linked to poor performance
+
+on these tests, the frontal lobe and hippocampal function.
+
+So early onset, if you have a small hippocampus, a
+
+reduced volume in your frontal cortex, you'll be worse at
+
+problem solving and memory and so on.
+
+But they cannot link it more detail to the glutamate
+
+function.
+
+So it's just our research pinning down more closely to
+
+it's not just the size of the brain, it's the
+
+glutamate function in schizophrenics that is giving rise to the
+
+problems.
+
+But an important factor, again, like I've highlighted, serotonin and
+
+dopamine interact.
+
+Glutamate and dopamine interacts.
+
+The glutamate changes.
+
+The glutamate levels.
+
+They affect dopamine function.
+
+And of course, there are dopa glutamate receptors landing on
+
+the ventral segmental area which projects that intense the dopamine.
+
+So what's happening is suggests that the glutamate pathways are
+
+playing important affect mediating and possibly causing the conditions that
+
+are occurring in schizophrenia and having a knock on effect
+
+on that dopamine pathway.
+
+There is disruption deepening, but it's not the primary cause.
+
+And and as this states, the positive symptoms, the delusions
+
+of grandeur, delusions of persecution and the delusion and the
+
+hallucinations are not so well kept on by glutamate.
+
+The last slide the put up is a really large
+
+one, and this is a really key review that's really
+
+critical in the field of schizophrenia is a review by
+
+Insel in 2010 provides a neurodevelopmental model of what they
+
+think of, and lots of evidence is happening in schizophrenia.
+
+So on the y axis here, we have changes and
+
+things going up from zero to a top.
+
+So and so here we have fertilisation of an egg.
+
+And so here we have in the womb things are
+
+happening in terms of brain sign ups and brain cells
+
+occurring and inhibitory.
+
+Synopsis Here we have the age of five after someone
+
+is born expanded out.
+
+So what each of these pathways is showing the top
+
+of the changes in the grey matter during normal development.
+
+What is highlighted down here is that someone who experiences
+
+schizophrenia well before the symptoms that in 18 to 24
+
+is already thought of having these reduced into neurone activity,
+
+excessive removal of their brain cells in the prefrontal cortex.
+
+So it's these, these excitatory signatures of being removed in
+
+both excitatory and into neurone inhibitory sign absence.
+
+And as I mentioned, this deficient myelination of these cells.
+
+So they charting this not now.
+
+So the key takeaways, schizophrenia is a neurodevelopmental condition that
+
+starts very early in life.
+
+We can now track some of the brain changes that
+
+are occurring in it.
+
+So I just stated that the evidence, the current is
+
+that is the frontal cortex and the tempo loop, including
+
+the hippocampus, and there is disruption of dopamine function, but
+
+also that glutamate dysfunction, dysfunction in the disorder, these are
+
+the suggested readings is a great chapter, the textbook chapter.
+
+There's a nice review by this, this one on flashbacks.
+
+This is a really short and fantastic review in nature.
+
+And if you want to read more about how your
+
+genetics, your environment and the stress you experience, give rise
+
+to death mean, this is a really great review by
+
+one of the world leaders down south of the river,
+
+Robyn, my friends Robyn Murray.
+
+You very much missed the last lecture of this course.
+
+Good luck with the exams.
+
+Thank you.
+
+Very.

raw_transcripts/lecture_19.txt

@@ -0,0 +1,2389 @@
+Just.
+
+This is Christopher in gold XO d2.
+
+It is eight degrees in my theatre at the moment.
+
+I'm not sure if you can do anything about that,
+
+but I do think that certainly if we work the
+
+incredible work rate in the.
+
+Thank you for joining me.
+
+It's a I grew up in a very home country,
+
+Australia, and I don't think I saw snow until I
+
+was in my mid-twenties.
+
+So for me, it's still awe inspiring to walk through
+
+a white snow field.
+
+So I hope you enjoyed your journey.
+
+And today I am in my place.
+
+But yeah, I'm here.
+
+This is behaviourism.
+
+Yeah, I.
+
+My brain is frozen.
+
+I just.
+
+I hope that's not on, but it's not going to
+
+help us in the next hour, I'm afraid.
+
+So thank you for joining me today.
+
+It's really nice to see you all again.
+
+I'm going to be talking about neurological disorders.
+
+It's a little bit I mean, I have mixed feelings
+
+about giving this lecture.
+
+I always feel a little bit depressed.
+
+But this year I tried to be a to alleviate
+
+my depression a little bit by introducing a couple of
+
+slides illustrating some very recent advances in treating these disorders,
+
+which give me hope at least that we're entering a
+
+period where we might be able to take these on
+
+and generate cures, or at least treatments for people.
+
+Sorry, my brain has actually frozen, so I'll try and
+
+get through this if I put my jacket on.
+
+Well, the problem is if I put my jacket on,
+
+it rustles the volume.
+
+But I see.
+
+Why a neurological disorder is so problematic.
+
+I think what you've learned so far in the course
+
+should give you a bit of a cue to answering
+
+this.
+
+I think the major thing, the first major things, that
+
+nerve cells are not self-renewing, but you're basically born with
+
+the same number of nerve cells you end up with.
+
+And you just lose them.
+
+There's a few that are born maybe in the hippocampus
+
+and the old factory lobe, but most of the neurones
+
+that you have on you now are ones that you
+
+were born with.
+
+And that means that if one of them dies, you're
+
+not going to get replaced.
+
+The second thing is that neurones are excitable cells.
+
+As we've talked a lot.
+
+I like action potentials.
+
+I do a lot of work to try and generate
+
+these action potentials and I can actually be overexcited or
+
+it's a bit of a loose term, but I can
+
+this generating this activity can lead to disorder within the
+
+cells.
+
+So those cells, if they get overexcited, can actually trigger
+
+apoptosis.
+
+That is cell death.
+
+Generating all this activity requires a lot of energy.
+
+It requires a very specific way of getting and be
+
+very, I think, by the way, in the brain of
+
+getting the energy to the right part of the brain.
+
+If we disorder that blood supply, energy supply as we
+
+go through time.
+
+Those neurones also form what we will call what we
+
+have called recurrent circuit.
+
+That is circuits where the axons from one cell connect
+
+to the dendrite to another cell and vice versa and
+
+so forth.
+
+These are very exquisite connections that are both partly genetically
+
+predetermined, but a lot of which is set up by
+
+experience early in life and in later life.
+
+Recapitulating those networks generated in those networks again, or putting
+
+a neurone in that network and asking it to replace
+
+the function of a new one that's already there.
+
+That's effectively impossible.
+
+You would have to recapitulate the experience that those neurones
+
+have had to be able to regenerate that network.
+
+So these for all these reasons, it's very difficult when
+
+the brain starts to be disordered, so start to die.
+
+Treating those disorders is really, really hard.
+
+So in this lecture, I just want to take you
+
+through a couple of different disorders that we know something
+
+about.
+
+And I've chosen these very carefully because there's many disorders
+
+that we do not know much about at all.
+
+In talking about these, I will be talking about disorders
+
+are called intrinsic rather than extrinsic.
+
+Extrinsic ones are ones like, for example, tumours being developing
+
+in the brain.
+
+By the way, since nerve cells and not the actual
+
+part of the tumour because they don't replicate in the
+
+same ways.
+
+Extreme disorders also include traumatic brain injury.
+
+For example, if you have a car accident or if
+
+you get concussed many times as a footballer.
+
+And those kinds of disorders are not a consideration here
+
+because they're really just a result, not just the result
+
+of things that the brain can't do much about.
+
+So we want to talk a little bit about intrinsic
+
+one, things that arise because of the particular structure of
+
+the brain, because of the way the brain works.
+
+I won't be talking about developmental brain abnormalities in this
+
+particular lecture.
+
+What I will be talking about is degenerative disorders, looking
+
+at Alzheimer's disease in particular, and also epileptic seizures.
+
+I'd like to start by talking about seizures.
+
+Seizures?
+
+Does anyone know much about seizures at all?
+
+You come across them.
+
+You may have seen someone having a seizure at some
+
+point in time.
+
+This is quite distressing experience.
+
+I find it's a this is a cause that we'll
+
+find out in.
+
+The second is caused by overly synchronous brain activity, by
+
+synchronous means that the neurones, the nerve cells are all
+
+firing at the same time.
+
+We'll see what the effect of that is in a
+
+second.
+
+About 3% of all people suffer from epilepsy at some
+
+time in life, most commonly in childhood or older age.
+
+I think it's not unexpected because that's the time at
+
+which the brain is changing most and therefore the balance
+
+that is required to prevent seizures, it's most likely to
+
+be disordered.
+
+At least 30% of athletic facilities have some known genetic
+
+basis, whereas about 25% have what we call acquired antecedents
+
+that, for example, rheumatic brain injuries.
+
+So professor of epilepsy, a friend of mine, has suffered
+
+from epilepsy since he had a bike accident 20 years
+
+ago, and he's under treatment for it.
+
+But it's still something that affects his life.
+
+You know that that doesn't add up 100%.
+
+And the other 50% of their bounce that the causes
+
+are known either because there was inadequate record taking at
+
+the time or because they have a complex, multifactorial basis.
+
+We know a lot about seizures since the development of
+
+electroencephalogram, ability to measure the activity of the brain from
+
+the scalp.
+
+On the left hand side to see what would look
+
+like a normal EEG.
+
+And is the traces in the brain due to the
+
+electronic wiggle a little bit that they're not overly wiggly
+
+and they're not overly synchronised between different electrodes.
+
+Two types of seizures as shown on the right here.
+
+The generalised seizure here, which would be part of a
+
+grand mal seizure.
+
+It means that the activity in the brain is synchronised,
+
+basically causing time brain.
+
+And you can see that here because the big wiggles
+
+on the on the electron system, grandma all happen at
+
+the same time.
+
+That means that neurones in each part of the brain
+
+that is generating these EEG signals are firing together at
+
+the same time in big discharge bursts of discharge synchronising
+
+their activity.
+
+Of more interest from a psychological perspective really is the
+
+partial seizures, which is shown in the middle here.
+
+And that is where some parts of the brain start
+
+to synchronise and other bits seem to be untarnished.
+
+We'll be going into that in a second.
+
+We've touched a little bit on brain rhythms over the
+
+course of these lectures.
+
+Rhythms are effectively a natural part of any biological system.
+
+Can anyone tell me one rhythm you can think of?
+
+Circadian rhythm.
+
+That's a daily rhythm in trained by light, but actually
+
+set by pacemaker cells or cells within this whole area
+
+of the brain.
+
+Probably the super charismatic nucleus whose activity varies with over
+
+about a 25 hour cycle.
+
+I think if you take if you if you take
+
+someone and put them in or if you take an
+
+animal and put them in the constant dark, you'll see
+
+they still have a circadian rhythm, but it's not quite
+
+locked to the 24 hour clock.
+
+That's that locking comes from exposure to light, which resets
+
+that pacemaker.
+
+Is there any other rhythms that you can think of?
+
+What am I doing right now?
+
+Well, that's a good one as well.
+
+But that's not a that's actually set by within within
+
+the heart pacemaker activity in the heart.
+
+What am I doing?
+
+What are most of us all doing?
+
+We're all breathing, right?
+
+The breathing is also a rhythm that's set by the
+
+pacemaker cells and a loop part of the brainstem.
+
+I do fact reports, and if I remember rightly, these
+
+activity pulsates, of course, can be modulated.
+
+They can be fast and be slow.
+
+Hold your breath.
+
+It normally would act to inflate the diaphragm.
+
+These kinds of brain rhythms are those are those are
+
+the properties really of individual cells, or at least there's
+
+cycles or rhythms within those individual cells.
+
+The kind of rhythms that get disordered in seizures, though,
+
+are not really properties of individual cells, but properties of
+
+networks of cells.
+
+So what happens is that when you have excitatory cells
+
+talking to each other and then feeding back to each
+
+other, and if you have inhibitory cells helping set that.
+
+These cells.
+
+When you fire an action, potentially send it to another
+
+one and that fires an action potential and sends it
+
+back to you.
+
+That creates a loop and that creates a natural rhythm
+
+from that circuit.
+
+And so depending on the structure of the circuit, you
+
+get different archetypal rhythms emerging.
+
+So this slide here shows you three of the classic
+
+rhythms, the alpha rhythm, the spindle rhythm and the ripple.
+
+They found, or at least are most prominent in particular
+
+brain regions, and they are the result of particular pathways
+
+for communication between brain regions.
+
+So, for example, the rhythm, which is most prominent actually
+
+in the visual cortex at the back of the brain,
+
+is primarily a cortical rhythm.
+
+It's about 12 hertz.
+
+The really prominent rhythm.
+
+It's much stronger when your eyes are closed, when your
+
+eyes are open.
+
+A spindle rhythm is about the interaction between the thalamus
+
+and the cortex.
+
+So neurones in the thalamus send signals to the cortex
+
+to send signals back to the thalamus.
+
+And this loop itself, which is responsible for a large
+
+part of slow wave sleep, also generates what's called spindle
+
+rhythms.
+
+And then these ripple rhythms are the communication between cells
+
+within the hippocampus, which generate a very sharp, very fast
+
+rhythm.
+
+You can see the timescale here is 100 milliseconds as
+
+opposed to one second here.
+
+So this slide also shows this seems to show that
+
+these rhythms are not just a product of something found
+
+in humans.
+
+They're actually found in almost all species that have been
+
+studied.
+
+In fact, all species that have been studied.
+
+You can identify these rhythms if you look in the
+
+right place and search hard enough.
+
+So in humans, in non-human primates, in dogs, cats, bats,
+
+rabbits, rodents.
+
+In other words, you can find these are rhythms.
+
+And it is quite striking that if you look at
+
+the frequency, that is the number of cycles per second
+
+that these rhythms take place over.
+
+As I said, Alpha was about 12 hertz or 12
+
+times per second.
+
+So 12 of these little squiggles per second and the
+
+ripple is about 250 hertz.
+
+If you look across a large range of species, you
+
+find that the rhythms in each of those species are
+
+about the same frequency, even though their brains can vary
+
+in orders of magnitude of number of neurones and all
+
+of the magnitude and numbers of signs.
+
+And that suggests to us that these rhythms are important
+
+for brain function.
+
+What they do is not so clear.
+
+So there's many hypotheses out there, for example, in camera
+
+rhythms, very fast rhythms, about 30 or 50 hertz are
+
+important for consciousness and for propagation of signals between cortical
+
+areas.
+
+Yet there is very little hard evidence that they are
+
+necessary for that those activities.
+
+So, yes.
+
+You can't.
+
+I think it's just been not studied there.
+
+I'm not sure if it's not present.
+
+I'd be willing to know.
+
+I haven't studied all of those animals.
+
+It's you do have to report them in particular ways
+
+and in particular circumstances.
+
+For example, slow way rhythms or any form during sleep.
+
+And so you have to be recording from an animal
+
+during sleep.
+
+So I'm not quite sure if they're missing on this
+
+one a bit older.
+
+So if they're missing because they're absent or missing just
+
+because I haven't studied, it's a good question.
+
+So these rhythms of what is disordered and what a
+
+what prominent about seizure disorders.
+
+This slide just simply classifies the general types of seizures.
+
+We're not going to be talking about the grand mal
+
+seizures, these massive changes to the brain function.
+
+However, what I would like to go through a little
+
+bit is partial seizures, because they tell they're explicit explicable
+
+going from the structure of the brain.
+
+Possible seizures can be either simple or complex.
+
+Complex partial seizures results in a second often involved impairment
+
+or loss of consciousness, or a simple partial seizures.
+
+A person who suffering a seizure suffers no loss of
+
+consciousness during the.
+
+This slide, which is a little bit busy here, but
+
+you can look at in more detail when you feel
+
+like it.
+
+On the top left is a description of some of
+
+the features of a complex partial seizure.
+
+On the bottom right, a simple partial seizure.
+
+Partial seizure complex Partial seizures often start in the temporal
+
+lobe or in the frontal cortex.
+
+And maybe that's why they're actually associated often with a
+
+loss of consciousness, or at least an impairment of consciousness.
+
+The squiggles over here show that the frontal and temple
+
+ones are undergoing large amplified rhythms, whereas the simple ones
+
+are not so prominent.
+
+In this process.
+
+He's a simple, partial Caesar here, however, usually involving the
+
+sensory with the motor cortices.
+
+You can see here that over a typical and a
+
+little bit the motor cortex, some big spikes, but not
+
+so much in the frontal and temporal lobes.
+
+So simple procedures often involve motor disturbances, for example, tremor
+
+that emerge because your motor cortex is being disordered and
+
+cortex is oscillating in a rhythmic fashion.
+
+So your muscles will be oscillating in a rhythmic fashion.
+
+And simple procedures are quite interesting because we can because
+
+someone is conscious and because they're not too problematic, we
+
+can actually track their progression through the cortical structures.
+
+So, for example, I really like this description, and I
+
+should know, by the way, that John Huling Jackson, who
+
+you go introduce you to back in the first lecture
+
+I think was based in Queens where when he made
+
+these discoveries was the one who proposed that the progression
+
+of simple partial seizures reflected the structure of the brain
+
+organisation.
+
+It's a nice description of what might be a typical
+
+seizure.
+
+Is on his right foot, began to shake.
+
+Now a lower leg was shaking than a proper leg
+
+as well.
+
+With horrified fascination, she felt her body begin to shake
+
+and reason with her leg.
+
+Is shaking slowed and then finally stopped.
+
+This is a real case.
+
+A CT scan showed a small white circled spot between
+
+the frontal lobes above the corpus place and a small
+
+tumour.
+
+This woman had a simple procedure that actually progressed to
+
+a complex seizure.
+
+Sometime later.
+
+So this little tumour that emerged in the brain was
+
+up here between the two lobes at the very top
+
+of the motor cortex.
+
+If you remember back to the monthlies that we looked
+
+at when we talked about sensorimotor cortices, the progression of
+
+disease or progression of the disturbances make sense from the
+
+structure that most of us.
+
+A foot is represented at the top of the brain,
+
+near the open close, and the tongue, the face and
+
+head emphasised.
+
+So is the progression of that seizure of that epileptic
+
+form activity move across the cortical surface?
+
+So the shaking in different parts of the body reflected
+
+that among the organisation.
+
+This makes sense for everyone.
+
+This simple partial CS is effectively a travelling wave starting
+
+from a particular point and moving across the surface of
+
+the cortex.
+
+Gradually recruiting different parts of the body that represent or
+
+control the muscles in particular parts of the body.
+
+Some, as I mentioned before, some seizures seem to be
+
+familial, inherited.
+
+I've learned quite a lot about them by studying rare
+
+cases of one of the psychotic twins and looking at
+
+the seizures that they sometimes have.
+
+This is one famous example.
+
+This is a pair of Monozygotic twins, Constance and Catherine,
+
+who have absence epilepsy in this case.
+
+What I want you to take away from this is
+
+electroencephalogram recordings taken from Constance and Catherine, I think at
+
+different times.
+
+Or you should notice the structure of the epileptic form
+
+discharges that are happening on these EEG channels are remarkably
+
+similar across the two twins.
+
+So over here, these these structures, these regions are very
+
+similar over here and so forth.
+
+So the structure of the seizures that they're having seems
+
+to be very similar, seem to have the genetic basis
+
+should be identifiable and seem to control the seizures that
+
+they're having.
+
+Indeed, if we actually look across a large number of
+
+cohort studies and trends, we find a large piecewise concordance
+
+between those two things.
+
+In generalised epilepsies, about 80% of the variance is explained
+
+and even in focal epilepsies, about 40% of the variance
+
+is explained.
+
+This case was concordance goes down substantially if you look
+
+at guys iconic twins rather than monozygotic twins.
+
+So there's something particular about some of the genes in
+
+these individuals that is disrupted.
+
+And remember, back to the first couple of lectures we
+
+had when we talked about the presence of ion channels
+
+in the membranes of nerve cells, it should make sense.
+
+A lot of these disorders are the disorder of specific
+
+kinds of ion channels that are important in regulating neuronal
+
+excitability, particularly sodium channels and potassium channels.
+
+These channels get disordered and therefore the normal structure of
+
+new activity is disrupted and the cells or the circuits
+
+that they are part of become susceptible to the possibility
+
+of being pushed into regimes where they become epileptic form.
+
+Remember, this letter form activity is not just an individual,
+
+so rhythmically discharging its spiking activity across a network of
+
+nerve cells, hundreds of thousands of cells, it suddenly becomes
+
+entrained makes this reverberant circuit of activity.
+
+So normally the activity of really cold, only the activity
+
+of the brain is sufficient to suppress the epileptic form
+
+discharge.
+
+But in people with these channel up with these, as
+
+they called that activity, is that the normal ways of
+
+controlling these these activity, stopping neurones from getting hyper excitable
+
+is disrupted and these people are therefore susceptible to seizures.
+
+She'll also say that you can actually many people are
+
+also sensitive to what's called photosensitive epilepsy.
+
+You're probably all aware of those trigger warnings that come
+
+up often between newspaper.
+
+News reports on the TV saying there will be flash
+
+photography in the upcoming segment.
+
+And the reason those trigger warnings are there is because
+
+if you have sensitive epilepsy, you can be susceptible.
+
+You can be induced to have a seizure response seizure
+
+anyway by the presence of that flickering light from the
+
+flash photography.
+
+It's not exactly clear how or why this this works,
+
+why the light entering the eye in trains, rhythms in
+
+the brain, therefore causes his epileptic seizures.
+
+But about 3% of people suffering from epileptic seizures have
+
+this sort of sensitive epilepsy, generally triggered by lights of
+
+flicker and about 15 to 25 frames per second.
+
+Close to the aphorism that we mentioned over visual cortex,
+
+and maybe that's got something to do with it.
+
+We just don't know.
+
+And can be triggered by ceiling fan, strobe strobe lights,
+
+etc. for anything that makes this rhythmic on 15 to
+
+20 times per second.
+
+Visual image.
+
+The following statement I leave you because I don't actually
+
+really understand.
+
+I wrote it down because I remember this happening.
+
+But who hears what's spoken on?
+
+Are too ashamed to admit?
+
+Or are you just too old to have done that?
+
+Apparently.
+
+Apparently, I've never worked for one in my life.
+
+The 38 episode broadcast on 64th December 1997, includes a
+
+scene where Ash, Ashes and his friends need to go
+
+inside the pokey for whatever that is through any device.
+
+I remember when it happened, I remember it being a
+
+big news story across the world, presumably because a lot
+
+of people watching Pokemon on that stage, I suppose very
+
+few of you actually born then.
+
+But what happened in this thing was the repetitive red,
+
+the blue flicker about five times per second, which ash
+
+was presumably seen and which was transmitted through the TV
+
+screens and induced about 600 to 700 people to have
+
+to go to hospital for photosensitive epilepsy in Japan at
+
+the time.
+
+So this is the reason that we have these trigger
+
+warnings when we see flash photography and the people making
+
+TV and movies now much more aware of the possibility
+
+for sensitive epilepsy.
+
+I want to show you some recent progress actually from
+
+Queen Square.
+
+Again, just as John Houston's Jackson, some from whatever, years
+
+ago.
+
+This is work from a group of people at a
+
+very large epilepsy research group at the Queen Square Institute
+
+of Neurology.
+
+I think this is a really interesting and important innovation.
+
+I'll take you through.
+
+It came out earlier this year.
+
+It also speaks a little bit to some of the
+
+noise that you've picked up over the last few weeks.
+
+The underlying thought from these researchers was the following.
+
+Epileptic activity is this increase in discharge above the normal
+
+rate in nerve cells?
+
+It follows that that increase in discharge triggers some processes,
+
+interestingly, that we might be able to tap into.
+
+In particular, this thing called IED or immediate.
+
+Early gene is something we've known for about 25 years
+
+now that when neurones become more active than normal, that
+
+triggers this expression of this thing called IED.
+
+We don't know exactly what it's doing, but we know
+
+it gets expressed.
+
+And these researchers have the idea.
+
+All right, We know that this stuff only gets expressed
+
+in these regimes of very heightened activity.
+
+So if we can introduce a construct into the cells
+
+that are sensitive to the expression of those immediate early
+
+genes, we might be able to turn down the activity
+
+in the cells that have been over activated.
+
+And so they introduced what's called a form of potassium
+
+channel that actually decreases neuronal excitability and whose expression expression
+
+of this protein was linked to the expression of this
+
+immediate early gene.
+
+So when an epileptic discharge starts, the hypothesis is that
+
+when they discharge start, that increases neural activity, which in
+
+turn drives the production of this immediate early gene.
+
+That immediate early gene production in turn drives the production
+
+of this novel protein that they've been able to introduce
+
+into the cells by means of a virus is otherwise
+
+not destructive to the cells.
+
+And then that that expression of that protein in turn
+
+will drive down the activity and stop the seizure.
+
+That was a hypothesis they wanted to explore.
+
+And the work that I published earlier this year suggests
+
+that this is true and might be a mechanism for
+
+actually treating fungal epilepsies, at least in some patients.
+
+To do this, they induced in a mouse model to
+
+test this hypothesis because epilepsy is a product of brain
+
+networks and not easily reproduced and induced, although they did
+
+do work in vivo before doing this in vivo working
+
+mouse they induced.
+
+There's a standard model of generating epilepsy in mice.
+
+In mice don't suffer too much from this.
+
+They do get seizures, but this doesn't seem to cause
+
+much pain or distress.
+
+After after these seizures were induced, they then measured the
+
+electrical activity by an electrical program electrode placed on the
+
+brain.
+
+And they injected these viruses into the parts of the
+
+brain where the seizures were occurring.
+
+So if they inject this far in the brain, they
+
+can then compare the reduction of seizures in the mice
+
+that have been treated with the control virus or this
+
+virus that produces this particular protein.
+
+And sure enough, they find it was in the control
+
+virus conditions.
+
+Mice continued to have seizures as each of these little
+
+batches shows over the course of several weeks at a
+
+time of a seizure.
+
+They're recording continuously, by the way, from the animals.
+
+They find that in these animals treated with the active
+
+form of the virus, that those ones are stopping the
+
+seizures.
+
+So this opens up the possibility that we might be
+
+able to inject into people who are having intractable epileptic
+
+seizures, at least focal seizures.
+
+We start from particular part of the brain.
+
+We can inject into that part of the brain some
+
+virus that expresses a protein like this, but then in
+
+turn allows that part of the brain to effectively control
+
+production of epileptic discharges.
+
+I showed.
+
+In other words, that I'm not showing here, they showed
+
+that the presence of this virus in doesn't interfere with
+
+normal behaviour, but only really with epileptic seizures.
+
+They're really important and encouraging evidence because people with intractable
+
+epilepsy at the moment, the sole way of trying to
+
+address the seizures is to try and excise from the
+
+brain a little bit of brain tissue to generate the
+
+seizure.
+
+So instead of taking out that piece of brain tissue,
+
+the hope is that we can use a virus that's
+
+otherwise safe but allows the neurones to suppress the epileptic
+
+discharge.
+
+A really important advance from my colleagues over Queensway.
+
+So remember with a simple partial seizures which spread from
+
+a part of the brain down to another, therefore causing
+
+trembling and different things that focal because they start at
+
+a particular point and then they spread like a travelling
+
+wave across the brain, as opposed to generalised epilepsy, which
+
+is a large.
+
+Synchronisation of brain activity across the entire brain.
+
+So this focus on start at particular point and spread.
+
+And because I started at the point you can actually
+
+introduce a virus at that particular point I should have
+
+said that those focal partial seizures, they start from a
+
+reproducible place in the person's brain.
+
+It's not like they start from different places on different
+
+seasons.
+
+They start from the same place each time and spread
+
+across the brain from that same place.
+
+So because the you can then introduce this virus and
+
+try to.
+
+See this as an end or partial.
+
+Or is are there like an off?
+
+I don't think there are.
+
+I think they have to be focal otherwise that generalised.
+
+I don't know whether or not the size of that
+
+focus could be quite variable.
+
+I have a friend who studies epilepsy epileptic patients in
+
+Australia.
+
+He actually a lot of people, as you may know,
+
+a lot of people that have epilepsy have aura associated
+
+with a preceding the epileptic discharge.
+
+And often this aura has structure a bit like the
+
+migraine has associated with migraine has structure and can actually
+
+because of that, people know when they're about to have
+
+or at least some time before they're about to have
+
+an electrical seizure.
+
+And my friend has been studying those people by putting
+
+them in a brain scanner during the seizure, actually.
+
+These are at least four seizures, partial seizures, which don't
+
+have massive consequences for the individuals.
+
+And you can see the progression of this activity in
+
+the brain during during scanning.
+
+Okay, So that's I just want to take through the
+
+seizures that clear result really of probably of mainly of
+
+channel opposites all these disorders of ion channels that regulate
+
+the normal excitability of neurones.
+
+The hope is that we can try and treat these
+
+by effectively resurrecting that normal control of those ion channels.
+
+Seizures are fairly rare and we're going to make a
+
+lot of progress in trying to deal with them.
+
+Other disorders were made much less progress, and one of
+
+the most prominent is Alzheimer's disease, a form of dementia
+
+which is increasingly prevalent.
+
+So there's actually many different types of dementias.
+
+My grandmother had Alzheimer's disease.
+
+Many people's grandparents, I suspect, or even parents will be
+
+suffering from Alzheimer's disease or related dementia.
+
+Alzheimer's disease is by far the largest, most common occurrence.
+
+How?
+
+How well it can be distinguished from other types of
+
+dementia is still a matter of debate.
+
+These dementias have common causes.
+
+It's still quite.
+
+Another common form of dementia is vascular dementia.
+
+That's where three years old strokes, which then allow a
+
+little bit of blood in parts of the brain, turn
+
+triggers the brain to start self-destruction basically in that area.
+
+You can get dementia from having many of these multiple
+
+little strokes, which then have an impact on brain function.
+
+There's also much less common forms of dementia which have
+
+been important, like the one those iconic twins with seizure
+
+disorders.
+
+Those common those rare forms of dementia have been very
+
+important to understanding the potential mechanisms of dementia, because we
+
+can look at some of the genetic contributions of those.
+
+This includes frontotemporal dementia, Pick's disease course for Jakob Disease,
+
+Huntington's disease, Parkinson's dementia and Lewy body disease.
+
+Many of these diseases have other effects as well.
+
+Dementia is a part of the condition, not necessarily the
+
+entire condition.
+
+I got this line from This is the last World
+
+Report from the World from the Outside Disease Foundation.
+
+This just goes to show you the kind of prevalence
+
+of Alzheimer's disease now and predicted prevalence in the future.
+
+About one person around the world becomes diagnosed with dementia
+
+every 3 seconds.
+
+In 2015, there are already 50 million people in the
+
+world who suffering from dementia is projected to be triple
+
+that in 2050.
+
+It's a huge we spend a large amount of resources
+
+that we produce treating people with dementia.
+
+And it's a worldwide phenomenon in particular as life expectancy
+
+increases in the global south.
+
+Dementia is becoming more and more prevalent there as well
+
+and has to date being primarily a ritual disease because
+
+life expectancy is longer in those parts of the world
+
+and Alzheimer's disease or other dimensions.
+
+And we strike older people.
+
+I think the current ratio is something like 20% of
+
+people over the age of 18 will have Alzheimer's disease
+
+or dementia before they die.
+
+The number is much less for people over 65.
+
+So as as life expectancy increases, as more and more
+
+people live over the age of 80, respect dementia, profound
+
+increase around the world.
+
+It's hard for those of us who don't have dementia
+
+to gain some insight into what it feels like, what
+
+it is like to suffer from dementia.
+
+I find this William Autumn Olin's.
+
+Ought to be at least one attempted insight into that.
+
+He was diagnosed with the Alzheimer's disease in 1995.
+
+He actually lived a bit longer than most people who
+
+suffer from Alzheimer's disease.
+
+And he was able as an artist to try and
+
+describe some of the.
+
+Changes in his cognition as he developed Alzheimer's disease, or
+
+at least in the first few years.
+
+This is the first portrait he made when he was
+
+diagnosed, actually a man untethered, someone lost in the world.
+
+As dementia progressed, as his disorder progressed, his his art
+
+takes on particular forms.
+
+You can see that he's a very accomplished artist, very
+
+capable of generating self-portraits.
+
+Back in 1996, in this case, when he's only a
+
+year or so after the diagnosis.
+
+What I hope you notice is that the structure of
+
+these images changes substantially over the next five years.
+
+There's a lot of death, lots of structure.
+
+There's a changing affect.
+
+There's capacity to see and to feel is changing fairly
+
+quickly over these several years.
+
+And really having a disorder of both his representation of
+
+the world, but also his internal representation of himself.
+
+Alzheimer's disease is named after Alois Alzheimer, who was an
+
+Austrian neuropathologist at the turn of the last century.
+
+He made his discoveries by studying data.
+
+Peter Peter, who was one of the unfortunate people who
+
+suffered early onset Alzheimer's disease.
+
+She was only about 50 when she was taken to
+
+his unit by her husband, who was a railway worker,
+
+needed to, couldn't take care of her anymore, and needed
+
+someone else to take care of her and outside to
+
+work with her while she was alive and asked her
+
+questions and so forth.
+
+And then when she died in, I think, 1986 and
+
+performed histopathology on her brain afterwards to see what had
+
+happened to her brain.
+
+And that might be part of the disorder that he
+
+recognised or witnessed in her cognition.
+
+The first thing she said basically when she met him
+
+was that he had lost her so that his wasn't
+
+able to remember who she was, why she was there,
+
+etc..
+
+You remember something?
+
+What is your name?
+
+Augusta.
+
+What's her last name?
+
+Augusta.
+
+Struggling to try and find the elements of her memory
+
+that she could bring to bear to the questions asked.
+
+But she wasn't capable, really, even when he saw her
+
+when she was 50.
+
+Of doing much in life anymore.
+
+And Alzheimer's disease is a very rapid progressive disease.
+
+On average is about eight years.
+
+This is increasing now as our treatments have improved, but
+
+on average about eight years from diagnosis to death.
+
+That's a very rapid.
+
+And for those who suffer a debilitating and disorienting disorder.
+
+One.
+
+One way of thinking about Alzheimer's disease is that it's
+
+a be like development in reverse.
+
+So, for example, if you think about how we develop
+
+over our normal life.
+
+And I think we can hold up ahead off the
+
+one, two, three months.
+
+We can speak a word after year.
+
+We can write sentences.
+
+After about 18 months, we can control and our defaecation
+
+and urine.
+
+After a couple of years, we can shower unaided.
+
+After four or five years, we can handle simple finances.
+
+After about ten years of age and hold it over
+
+for about 12.
+
+And if you look at the progression of the Alzheimer's
+
+disorders like this in reverse, you first lose your capacity
+
+to hold a job with the capacity to handle your
+
+finances, to dress yourself, to actually out of words, and
+
+finally to actually do most of the functions that we
+
+take for granted.
+
+So this is an idea that Alzheimer's disease is a
+
+bit like Retford genesis or development in reverse.
+
+So you probably have seen pictures like this before.
+
+This is a gross pathology of an Alzheimer's disease patient.
+
+On the left is a healthy brain.
+
+On the right is someone with advanced Alzheimer's.
+
+You can see the substantial thinning of the grey matter
+
+in the cortex as a large enlargement of the ventricles,
+
+in this case of very severe hippocampal damage, losing much
+
+of the hippocampus and therefore very much of our capacity
+
+for memory.
+
+On a microscopic level.
+
+This is what Alzheimer found 120 years ago as two
+
+major features that still remain prominent in our understanding of
+
+Alzheimer's disease.
+
+The first is that there are these things called senile
+
+plaques, which are these things about anywhere between about 1/10
+
+and one half of a millimetre in size.
+
+Sometimes you can see them on unaided with the naked
+
+eye.
+
+And these are little disruptions of the brain structure, which
+
+are filled with a protein called amyloid beta.
+
+And on the right here is the other aspect of
+
+pathology that seems to be very prominent people with Alzheimer's
+
+disease.
+
+That's what's called neurofibrillary tangles.
+
+These are basically disordered conglomerations of a protein called Tao
+
+Utown, which has a large number of roles in regulating,
+
+especially transport of substances to the cell.
+
+And there's a lot they organise into long filaments and
+
+somehow they start that filaments start breaking down and start
+
+breaking into what we call tangles.
+
+So these Tao and Amyloid are the two major proteins
+
+associated with Alzheimer's disease.
+
+Yeah.
+
+Does it look like it?
+
+Absolutely.
+
+Yeah.
+
+It's one of the more fundamental proteins in ourselves.
+
+So now the question was, is Tao normally present or
+
+is it just present in in Alzheimer's disease brains?
+
+It is normally present.
+
+It's because of a particular.
+
+Way of how it interacts with other molecules of Tao.
+
+If this gets disordered, it starts to out of the
+
+solution and form these tangles.
+
+And so in Alzheimer's disease is proteins get slightly disordered.
+
+They get called hyper phosphorylated.
+
+Once they are hyper phosphorylated, they can come out of
+
+the solution form these tangles or neurofibrillary tangles within the
+
+cell.
+
+This slide here shows the kind of progression of these
+
+two different proteins, amyloid and TAL, as a function of
+
+time in the progression of Alzheimer's disease.
+
+It's hypothesised, it's not yet clear that there's not a
+
+huge amount of evidence for it.
+
+The amyloid first is causal.
+
+But certainly the case that amyloid emerges early on in
+
+dementia, followed by TAL and then after that followed by
+
+neurodegeneration loss of cells and sinuses, and after that followed
+
+by cognitive decline.
+
+The cognitive decline is probably paralleling the loss of self
+
+and finances, in fact, may even be emerging earlier.
+
+But the overt signs of cognitive decline happened late on
+
+in the season.
+
+The consequence of that means is that by the time
+
+you know that someone is suffering from dementia, from a
+
+cognitive perspective, it's already too late.
+
+Basically, our brain is very capable of making up things
+
+for ourselves and hiding the fact that it's losing its
+
+function.
+
+And by the time we find that someone is demented,
+
+that his pathological calmness, not to mention already too far
+
+gone to do much about it.
+
+We actually know surprisingly little about how amyloid and tal
+
+affect brain function.
+
+One of the reasons for this is it's actually been
+
+surprisingly difficult to generate animal models of Alzheimer's disease.
+
+It's not completely clear why this is.
+
+We can certainly generate animal models where we introduce mutated
+
+forms of amyloid or mutated forms of cow that have
+
+been mutations for which have been deduced from people who
+
+suffer from Alzheimer's disease.
+
+And we can see that those things can lead to
+
+the formation of plants and the formation of these neurofibrillary
+
+tangles.
+
+Often they do not lead to neurodegeneration and they only
+
+have mild effects on the cognitive performance of these animals.
+
+So why it is that it seems to be more
+
+the case in humans and so hard to generate these
+
+animal models of it is unclear.
+
+But the consequence of that is that we actually know
+
+precious little about the functional aspects of neurodegeneration.
+
+However, we do know a little bit.
+
+Whereas in the control condition here, these neurones are healthy
+
+of normal neuronal activity.
+
+This, by the way, is from a view from a
+
+Bush who is in the Dementia Research Institute.
+
+He's based.
+
+100 metres away in the old building.
+
+No critical building site.
+
+Mark is a very prominent researcher in this field.
+
+We've also joined in the last little while.
+
+Be sorry when this app.
+
+This is a particular precursor to more don't worry too
+
+much about this is basically in animals who have this
+
+overproduction of amyloid beta and stand on these plaques.
+
+We often find hyperactivity increased activity in the brain.
+
+Later on when that android over production is joined by
+
+talent misfolding, we find a reduction in activity.
+
+It seems to be the case that this stage of
+
+the amyloid production stage.
+
+We can still rescue some of these phenotypes in mice,
+
+whereas once the towers joined the amyloid and started leading
+
+to hyperactivity, this phenotype seems to be incapable of being
+
+rescued.
+
+But it's still very early days to.
+
+So what do you mean by that?
+
+Is that you can rescue brain function.
+
+Yeah.
+
+Okay.
+
+Sorry.
+
+All right.
+
+Just use the word phenotype.
+
+And unfortunately, you can rescue brain function.
+
+That is, if you stop the production of amyloid, you
+
+can get cells back into the normal healthy state and
+
+stop degeneration.
+
+If you if you leave it later than that, you
+
+get to a stage where you can't seem to stop
+
+this process.
+
+In humans.
+
+We know quite a lot about the progression of Alzheimer's
+
+disease and the and the pathology that's associated with it.
+
+And in the large number of people that we see
+
+in the clinic, Alzheimer's disease is started in the temporal
+
+lobe, in the internal cortex or in the hip around
+
+the hippocampal formation.
+
+So starts this accumulation of talent and amyloid plaque starts
+
+down here and then starts to spread across the rest
+
+of the brain.
+
+It's a fairly slow process.
+
+Why is the temple open?
+
+I'm sorry.
+
+I just want to be see with my face and.
+
+Do have a of.
+
+Yeah, I think I believe the slide from this presentation,
+
+but I think is there in your notes which is
+
+an example where.
+
+PET imaging, positron emission tomography imaging, which can be used
+
+later to visualise the location of radio labelled proteins or
+
+substances we can introduce using PET.
+
+We can detect where this disordered amyloid or disordered pal
+
+is and we can therefore look at the location of
+
+those things in people.
+
+So.
+
+I think your next question would be why can we
+
+therefore say, is this person starting to suffer from dementia
+
+or something like that even before the cognitive symptoms emerge?
+
+That we haven't progressed to that stage yet.
+
+So we know that doing in people who are suffering
+
+from Alzheimer's, dementia, that you can see this structure and
+
+location of these disordered proteins.
+
+But these proteins are present in normal brains as well.
+
+And so in the early stages we can track it
+
+and we can kind of post-hoc reconstruct that this has
+
+happened.
+
+But in terms of being a specific predictor of what
+
+will happen in someone's brain.
+
+We're still not at that stage, if that makes sense.
+
+So we can see the presence of these proteins and
+
+the possibility that someone might be more likely to suffer
+
+from degeneration of dementia.
+
+We can't say on an individual specific basis that you
+
+will suffer from degeneration of dementia.
+
+It's not at that kind of specificity at the moment,
+
+but we can track those proteins at least with p
+
+t, which is very invasive.
+
+It's not something you can scale out to 150 million
+
+people in the world, but it that way.
+
+There is some hope, by the way, that and I
+
+haven't put it here, but we are starting at the
+
+moment.
+
+Other techniques.
+
+So, for example, the electroencephalogram, which, as I showed you,
+
+is very important at picking up seizures.
+
+Turns out there's very characteristic changes in that transfer ground
+
+at some stages of Alzheimer's disease as well.
+
+We'd like to think that maybe if we knew more
+
+about the structure of the circuits involved, also what's happening
+
+to the circuits involved?
+
+Early stages, we might be able to find signatures of
+
+that disorder even earlier on in patients and therefore be
+
+able, since EEG is a very cheap, easy thing to
+
+introduce, might be able to say have that in the
+
+clinic somewhere and just somewhat construe brief EEG study or
+
+something like that, four years age and see whether or
+
+not they're easy activities, predicting that they might be at
+
+risk of these diseases, whether we'll ever move to like
+
+proper predictive, I'm not sure.
+
+But it might be able to pick up some people
+
+from these methods.
+
+If you look at the stages of Alzheimer's disease and
+
+what you know of brain function, Hugo and I and
+
+others have told you over the last few weeks that
+
+the different stages of Alzheimer's disease make sense.
+
+If it starting in the temporal cortex, then the first
+
+stage is going to be hippocampal formation and final cortex.
+
+We know that these areas are important in spatial navigation,
+
+sexual orientation, and it's no surprise, therefore, to discover that
+
+one of the first things to go in Alzheimer's disease
+
+is your capacity to navigate around the world as the
+
+disorder moves up through the brain.
+
+This is just a schematic of that.
+
+For example, in the prior two cortex that you start
+
+to lose your visuospatial kind of organisation as we discuss
+
+the consequence of neglect.
+
+And as it moves more to say, the frontal cortex
+
+and you start to lose your abstract reasoning capacity.
+
+So the structure of the brain, a bit like those
+
+focal seizures, it is travelling wave on a much faster
+
+timescale, moving out across the brain.
+
+So this kind of travelling wave disorder from the temporal
+
+cortex to the rest of the brain has predictable cognitive
+
+consequences.
+
+I won't go through the news this time, but this
+
+is the kind of exam that you might do in
+
+the clinic to try and assess whether someone has dementia.
+
+I encourage you to do it and particularly to try
+
+and do it.
+
+The Where is it?
+
+Serial seventh task count back in seven for 100.
+
+I sometimes think I have to mention when I do
+
+this, I won't go through it now.
+
+What I want.
+
+And I also want to go through a couple of
+
+these hypotheses just in time.
+
+For a long time, we thought that some disruption to
+
+the cognitive system was important in the pathogenesis of dementia.
+
+It doesn't.
+
+Well, it might well be important for treating that.
+
+It doesn't seem to have much effect.
+
+Studies are being made trying to treat the cognitive system
+
+to see whether that has an impact on the occurrence
+
+of dementia.
+
+Very little progress has been made.
+
+By studying rare familial cases of dementia, that is, people
+
+who get early onset dementia.
+
+These tend to be much more genetic link and sporadic
+
+cases that occur later on in life.
+
+And there are some clear genes that are involved, most
+
+of which are related.
+
+Most of the known genes are related to some part
+
+of the amyloid pathway.
+
+And John Hardy, who is at the Institute of Neurology,
+
+is the one who's promoted the idea that amyloid is
+
+important in the pathogenesis of Alzheimer's disease.
+
+This is a slide, I think, from one of his
+
+reviews, but this is his basic hypothesis that there's some
+
+kind of change in how the brain metabolises and like
+
+beta, which in turn leads to all the other steps
+
+that cause degeneration and also the sort of power that
+
+we know happens later on.
+
+I won't go through these in any particular detail.
+
+The point is that this changes in the amyloid beta
+
+metabolism cause the the kinds of inflammation and injury to
+
+nerve cells that we see later on in the disorder
+
+and end up with dementia with plaque and have pathology.
+
+Now, consequence of this hypothesis is that if you were
+
+able to treat the amyloid beta early on, you might
+
+be able to stop the rest of the cascade and
+
+prevent or at least slow down degeneration.
+
+And many of you may be aware of this study
+
+from two weeks ago that came out among eight month
+
+study in collaboration with pharmaceutical companies looking at antibody against
+
+and why beta of people, family beta and immunising people
+
+with that antibody and seeing whether or not it might
+
+protect against Alzheimer's disease.
+
+And this is a figure from that paper which is
+
+cited down here and yet has a doesn't yet have
+
+an issue number.
+
+You can see that in placebo, there's no change in
+
+employee burden.
+
+There's when you immunise with this antibody, you get a
+
+substantial reduction in amyloid burden in the brain.
+
+The top one here.
+
+This shows the the dementia score.
+
+A person might take them to a clinic, but no
+
+one here says one of the performance measures for cognition.
+
+The yellow shows what's happening in patients who are being
+
+treated with this antibody, and the blue shows a placebo.
+
+And the fact that yellow line is above the blue
+
+line means an improvement in performance in those people who
+
+have taken the antibody over placebo.
+
+So this is, I think, something like a 20% improvement
+
+in cognition over this 18 month time period, which if
+
+you're excited, is a great improvement.
+
+If you're not excited, not much.
+
+It all depends which side you see on the fence
+
+there.
+
+I think even the hottest proponents here would say this
+
+is just the first step.
+
+Being able to try and treat Alzheimer's disease.
+
+It's certainly a long way to go.
+
+And it shows it is potentially, theoretically possible to try
+
+and stop Alzheimer's disease by blocking or interfering with this
+
+amyloid beta process early on.
+
+I'm aware that we need to shut up now.
+
+I just want to in the last couple of slides,
+
+just point out to you, we still don't know why
+
+some people suffer from dementia and others don't.
+
+What is it?
+
+Is there a is it just solely divide by genetics?
+
+Is it some kind of combination of genetics and environmental
+
+factors?
+
+What is actually the trigger for the start of degeneration
+
+in those people who have identical genes?
+
+There are several hypotheses about.
+
+I've listened to them in in this.
+
+At the end of this presentation you can go and
+
+read about them and the references there as well.
+
+The fundamental point at the end is that we don't
+
+know why some people are suffering from dementia and why
+
+others are not.
+
+It does seem, though, the most obvious thing to do
+
+for all of you and for me is that exercise,
+
+for whatever reason, seems to slow down dementia or prevent
+
+it.
+
+So I can only encourage you to walk more, run
+
+a bit, and exercise and have will also be here
+
+in about 50 years time.
+
+All right.
+
+Thanks for listening.
+
+Have a good week.
+
+Hope you get the.
+
+Still nine degrees.
+
+As a coach I'm wondering about.
+
+It's a good question.
+
+Should.
+
+That's a very good question.
+
+I don't know what's happening, but what I do is
+
+when I get back to October, I think, you know,
+
+I'm.
+
+I think in the limit you should be able to
+
+be done over at the zoo.
+
+But yeah.
+
+That's a good question because my.
+
+Sorry.
+
+What's that?
+
+You know what I'm saying?
+
+Yeah.
+
+You've got to let it go.
+
+Tell me nothing.
+
+Ever happened to you.
+
+Three.
+
+Yeah.
+
+Yeah.
+
+This is a component from the premise of migraine and.
+
+So from whatever, I think migraine itself is a spreading
+
+depression.
+
+So it's kind of the opposite in terms.
+
+Of so.
+
+The reduction in activity.
+
+I think it's.
+
+Kind of spreading the or the seasonality is pretty significant.
+
+So they're having different effects, but they're both spreading.
+
+They seem to have some link.
+
+And they're both chronic disorders of the normal people.
+
+So I don't know why they should be doing that.
+
+I think I just I know I, me, I oh,
+
+I'm like always like that sort of interesting that you
+
+look at the brain go away and it's like how
+
+like ultimately or mean like sort of like blind spots
+
+and then like, paralysis in the right hand spreading of
+
+the right side.
+
+Yeah.
+
+Yeah.
+
+Yeah.
+
+So and it's I mean, it is interesting.
+
+I know it's not to be treated as a patient
+
+over these things, but it is actually fundamentally interesting for.
+
+I remember seeing a.
+
+Presentation.
+
+A lot of people with migraine or or there's always
+
+structured and ways the leading edge of people often has
+
+these kind of it's clear answers.
+
+Which is the hope was that actually one should be
+
+able to correlate.
+
+Kinds of special circumstances getting on with the part of
+
+the visual cortex that was disrupted at the time.
+
+So it was I believe the early visual cortex had
+
+been disrupted.
+
+Can you see things like.
+
+Edges and stuff like that?
+
+Whereas.
+
+Like a bit of prudence.
+
+Maybe you'd see something, for example.
+
+I think that they hope to do that by.
+
+Because it's such a subjective experience.
+
+You have to be trying to ask people to map
+
+out what you see or represent.
+
+Mm hmm.
+
+Mm hmm.
+
+I don't know what is going to happen to.
+
+Not very strongly, but there was a couple.
+
+All right.
+
+Just a quick question to you.
+
+So do you get.
+
+Partial processes.
+
+Or do you mean that the neurones hiring, that's what's
+
+being asked you, don't you just just that because all
+
+of a sudden.
+
+Yeah, it's a really interesting point.
+
+You can kind of think of like this is one
+
+way of thinking.
+
+The brain is looking with a certain here.
+
+And then that.
+
+And so you get a little disruption here.
+
+The net effect of an isolated incident.
+
+Yes.
+
+And you were talking to each.
+
+Other over and over.
+
+I saw you.
+
+If you get disrupted this little circuit.
+
+I said.
+
+And then just to read this letter by something else.
+
+And that's how and how we keep.
+
+Says the student who was just here.
+
+Not it's not clear when that is on.
+
+At this stage, it doesn't seem like.
+
+It seems like.
+
+To start.
+
+Either that or the disruption of.
+
+To get something to.
+
+And.
+
+And if maybe it triggers.
+
+So that's one possibility.
+
+But this is too.
+
+Important for him to tell what causing.
+
+But I mean, I do think that.
+
+It's very hard and it have to bear in mind
+
+that these are within your own self.
+
+So.

raw_transcripts/lecture_2.txt

@@ -0,0 +1,2219 @@
+Can you hear me?
+
+Okay.
+
+Hello?
+
+Hello?
+
+Can you hear me?
+
+Seems to be.
+
+Hello.
+
+Good morning.
+
+I'll start off from here.
+
+I'm going to wear this mikes that we've been recording.
+
+Lachica.
+
+That seems to have worked.
+
+Anything wrong with those who got backup lectures?
+
+Any point and worry, we'll always have something to post
+
+to Moodle.
+
+If you can't make one of the lectures, there will
+
+be clashes that will be strikethrough, these sorts of things.
+
+So last week, Monday, not a week ago, we talked
+
+about historical perspectives, the brain and behaviour.
+
+Today we're going to look more intensively at neuroanatomy.
+
+So this is a this is a much more intense
+
+lecture than the previous one.
+
+The sense of the material is is more factual.
+
+It's more like if you're a medical student, you can
+
+get this every day.
+
+But the core idea here at this lecture I'm going
+
+to run over these slides is to introduce you to
+
+some of the key anatomical parts of the brain that
+
+will keep cropping up.
+
+In the lectures we talk through.
+
+There'll be slides which are full of information because that's
+
+what the information is, that I won't I work my
+
+way through them.
+
+I'll just highlight this worth being aware of these things
+
+as opposed to being really detailed in knowledge.
+
+Alongside these lectures on the moodle page, you the middle.
+
+There's a guide to neurone estimate word document you should
+
+download that guides and access the resource within.
+
+It explains what it is.
+
+I'll just see if that word control should take us
+
+to the next website.
+
+So it's like this word document would take you to
+
+a website where you can train yourself on on learning
+
+the images from the from this topic, and it's inside.
+
+So go back to the end to remind you.
+
+But this is the key way to learn about your
+
+anatomy.
+
+I'm going to talk to you about things, but it's
+
+not the kind of material you can kind of go,
+
+Oh yeah, I know this.
+
+It's a bit more like you'll need to test, retest
+
+yourself with that material.
+
+If you've got a great ability to visualise by spatially,
+
+imagine things in your head, you'll do well in this.
+
+But if you don't, it's tricky.
+
+A lot of this is looking at images of cuts
+
+through the brain.
+
+Let's get into my lecture.
+
+Let me start by highlighting what we're going to learn.
+
+Basic understanding.
+
+It's not a detail is their basic understanding of brain
+
+anatomy.
+
+We can look at the basic divisions within the nervous
+
+system, which we talked about in last Monday's lecture about
+
+the red car and the nerves that go on and
+
+so on.
+
+We're going to talk about how you divide those up.
+
+And at the end of it, after you've done the
+
+material, you should be able to identify some of the
+
+basic different structures of the brain by looking at images.
+
+So if someone at the end of this lecture says,
+
+Oh, where's the going, calories, you have some idea and
+
+going, Oh, it's kind of there.
+
+I don't want to know everything there is to know
+
+about the group as colleges.
+
+Just one example of lots of brain areas, but that's
+
+the idea.
+
+Let me start with three myths related to your anatomy.
+
+One is that the adult brain doesn't grow any cells
+
+that you're born with your brain cells, and they just
+
+all die.
+
+And that was the view held by scientists.
+
+But it's not true or certain bits of your brain
+
+to do with smell of memory for some reason that
+
+do carry on growing throughout your whole life, a process
+
+known as neurogenesis.
+
+One this as well as you use 10% of our
+
+brain.
+
+You characterised recently by a best known film you where
+
+the character unlocks the 90% of the brain they were
+
+using.
+
+And this is just nonsense.
+
+We're constantly using all of our brain while I'm standing
+
+here.
+
+Neurones are doing different things that I needed to do.
+
+Sure, you can train up to be a fantastic athlete
+
+and use more of your brain for that.
+
+But it's not.
+
+Not what people have argued in the past that we
+
+really aren't using the brain very much.
+
+It's not true.
+
+There's also the thing I was in a meeting with
+
+somebody yesterday said, Oh, yes, you know, this thing or
+
+that brain people who are really analytical and quite cold
+
+and then you get these wonderful creative right brain types
+
+who really write dominant and kind of big thinkers.
+
+And this is kind of this is nonsense.
+
+It's inaccurate with Paul Brooker.
+
+And that because we thought that language appears to be
+
+dominance in the left hemisphere and there is some evidence
+
+for kind of more analytical prose, this thing in the
+
+left in the last hemisphere and more visuospatial things in
+
+the right dots.
+
+There's no such creative types.
+
+Analytical types based on brain hemispheres.
+
+Studies is not everything when it comes to brains.
+
+Sitting here with giant brains, you can look at a
+
+spot or a mouse.
+
+They've got a small brain.
+
+Think we.
+
+You certainly have very big brains compared to our bodies.
+
+But if you compare our brain to a sperm whale,
+
+ours is much smaller as the sperm whales brain cut
+
+through giant and arguably it's not a lot cleverer than
+
+we are.
+
+It could do some amazing things.
+
+Sperm whales can sink to the bottom of the ocean
+
+and capture squid and pitch blood.
+
+But it hasn't been to the moon.
+
+Just one example of what humans can do.
+
+So size isn't everything.
+
+Okay, I said at the beginning of the lecture, learning
+
+objective is to understand the divisions within the nervous system.
+
+And this is.
+
+That's right.
+
+So here's it's in a very, very kind of simplistic
+
+diagram of a human body in that you can see
+
+this in the central nervous system, but it is protected
+
+from the immune system, the immune system beyond and other
+
+aspects.
+
+And then there's the peripheral nervous system.
+
+So the central nervous system, also known as the CNS,
+
+if someone says, Oh yeah, we're studying, the CNS contains
+
+the brain which we will spend all the current lectures
+
+coming on and also the spinal cord.
+
+If it was a neurology that you learn a lot
+
+about spinal cords.
+
+But because we're interested in cognition and psychology, we're not
+
+very interested in the spinal cord.
+
+Least I'm not.
+
+The penis is the bit beyond which is the contains
+
+a number of divisions.
+
+The peripheral nervous system contains the somatic nervous system.
+
+So that's going to you in your face.
+
+You will be using your somatic nervous system to feel
+
+that slap on your face.
+
+All those tense moves on your own, the skin of
+
+your body are being used to sense that everything in
+
+your body, these sensations are passing down.
+
+You can see those pink nerve fibres running all over
+
+the body to detect what's not there.
+
+More interesting to me, at least as a psychologist, is
+
+that autonomic nervous system, this is the bit of the
+
+body that's involved in dealing with threat and stress and
+
+other aspects of behaviour.
+
+We'll have a whole lecture by me coming up on
+
+stress and how the autonomic nervous system operates.
+
+It contains a sympathetic system and a part sympathetic system.
+
+I will come back to those when we get to
+
+our stress lecture.
+
+Finally, there's an internal system which is in our guts.
+
+It helps to digest things and does things related to
+
+food processing, which again is a psychologist running a brand
+
+of behaviour.
+
+I'm not so interested in gut maturity.
+
+Some of you might be fascinated by it.
+
+That's not this course.
+
+Next few slides, it's three or four slides rule about
+
+orienting you.
+
+So if you think about the planet Earth and where
+
+we are now in London, we're quite close to the
+
+Greenwich Meridian line, so there's always meridians running over the
+
+surface of the earth.
+
+Through are latitude and longitude and the prime meridian, this
+
+gets all of these runs through Greenwich.
+
+You can walk around probably 40 minutes or something.
+
+You need the same sort of organisation to understand where
+
+things are in the brain.
+
+And anatomists have come up with the idea of labelling
+
+things in two or three different ways.
+
+One is to describe rostral bits in the brain towards
+
+the front, caudal bits towards the back and things that
+
+are towards the top is dorsal and ventral towards the
+
+bottom.
+
+So here's a rat's brain and here's a human brain
+
+showing you, whereas rostral caudal, it gets a little confusing
+
+with humans because our brains, as we we evolved, we
+
+start standing up and our heads bent forward.
+
+As you can see, the line axis of our eyes,
+
+our relative to our spine is unusual amongst other species,
+
+experienced in mammals, many other mammals.
+
+But you know, there are kangaroos and other animals.
+
+This is also true.
+
+So this is one way of doing it.
+
+Another way is to describe things that are superior towards
+
+the top and inferior towards the bottom of the brain.
+
+And we can also think about things that are towards
+
+the front of your head about the anterior parts of
+
+the brain that's towards above your eyes and the posterior
+
+parts of your brain towards the back.
+
+So if we think about posterior, except we'll get into
+
+that.
+
+So this is a very simple way of allocating that's
+
+different.
+
+We also need to think about when we get into
+
+the middle of the brain versus going out in the
+
+middle of the brain.
+
+As we go towards the middle, we call that going
+
+medial as we go out, we call that lateral just
+
+because of terms from Latin to use.
+
+Then once we get in, we're going to be showing
+
+you some slices through the brain, some disgusting slices.
+
+There's another disgusting image of the brain with its blood
+
+vessels removed.
+
+And if we're going to cut a slice through the
+
+brain, you want to know what is that slice?
+
+What are you looking at?
+
+And there are a number of ways of describing that.
+
+One of the most common ways of labelling that are
+
+to describe one is the horizontal plane.
+
+So if you think about the earth, the surface of
+
+the earth, we're all standing on it.
+
+Gravity's attracting us down.
+
+If you cut a plane up from that, it's horizontal
+
+to the surface of the earth, and that's what this
+
+plane is.
+
+If we cut through flights in the back of the
+
+head forward, that's a horizontal cut.
+
+If we cut butt into my eyes straight at me,
+
+that's.
+
+The sagittal plane.
+
+You can see that there.
+
+And if we cut like a cross down past your
+
+ears from the top downwards, that's the coronial plane.
+
+These are just anatomical terms you come across in these
+
+lectures.
+
+So if we cut through these things.
+
+Here's a diagram.
+
+I said, One drain to all three cuts.
+
+You get images like this.
+
+So you should be able to decide, is this a
+
+is this a coronil slice or sagittal slice or a
+
+horizontal slice?
+
+And so you can kind of see how these are
+
+mapped.
+
+There's another word which is also described.
+
+Coronil is also described as the transverse plane, not transverse
+
+to the main axis of the of the brain.
+
+And that, again, is slightly confusing because again, along the
+
+axis, if I go back, you see that that's the
+
+that's the axis of the brain running from the front
+
+down to your bottom.
+
+And therefore if you cut along that transverse, it becomes
+
+a kind of bends round from the through the middle,
+
+down through the spine in a different orientation.
+
+So that's what the spinal cord looks like if you
+
+cut transverse sections.
+
+Right.
+
+But really the key things to take away this is,
+
+this is this transversal coronal section, the sagittal section and
+
+a horizontal section.
+
+So here's an example where there's a human body and
+
+you cut through sagittal, coronal and axial, and we end
+
+up with these three images.
+
+So if you've been watching carefully and thinking about this
+
+in your head, you should be able to guess what.
+
+So if you have a little moment to think about
+
+it, can you guess which of these images is which,
+
+which is coronal, which is horizontal or axial is the
+
+other word for this.
+
+Just at that in there, which is the actual horizontal,
+
+which is the sagittal one, which is the corona.
+
+And if you're if you're good at this, you should
+
+have got these answers.
+
+So this is also horizontal.
+
+The axial is the same as horizontal in this case.
+
+So there we go.
+
+That's just a way of thinking about orientations.
+
+You can see the same in cats, frogs, fish, and
+
+so on.
+
+This just gives you another diagram to think about how
+
+we're orienting ourselves because we'll start to talk about the
+
+medial hypothalamus in the lateral hypothalamus.
+
+After this slide, I have an idea.
+
+Okay, We've got orientation.
+
+We know where we're going in the brain.
+
+Here's what's known as a mid sagittal, disgusting section.
+
+Again, this is even more disgusting for the blood vessels.
+
+That's the cut through the brain right here.
+
+And this is known as a lateral view looking at
+
+the left hemisphere and that area there.
+
+Now, one of the first things you need to know
+
+is if this fundamental fact of neuroanatomy, you should note,
+
+is that there are four lobes in the human brain.
+
+The very basic piece of knowledge that you should all
+
+know.
+
+Many of you may well have known this coming into
+
+this lecture, but just to orient you is the frontal
+
+lobe, temporal lobe, parietal lobe and occipital lobe.
+
+And of course, as you can see, they're not actually
+
+coloured like that.
+
+It's just a diagram to illustrate them.
+
+Now, here's a structural system.
+
+We've got our brain and spinal cord and our central
+
+nervous system, and they are all encased by bone.
+
+Right?
+
+My head, I knock it now.
+
+It's got nice bone protecting me from damaging my brain.
+
+You couldn't have boxing if you didn't have brains, the
+
+skull protectors.
+
+We would have died that long ago with the eyes.
+
+But a spinal cord is also vertebrate, right?
+
+So protected by the vertebra as well.
+
+The peripheral nervous system is not protected by that.
+
+It contains cranial nerves, spinal nerves, peripheral ganglia.
+
+And this is also these are encased in the vertical
+
+column as well as these.
+
+So these are these are other bits that we'll dive
+
+into.
+
+But it's just important to know these are we won't
+
+be talking much about these will get onto the cranial
+
+nerves in a bit.
+
+And if you would, doctors training for medicine have lots
+
+of lectures on the great nerves in detail, but we're
+
+not.
+
+Large part of the peripheral nervous.
+
+System.
+
+That's the good point.
+
+So it's the it's these the the sort of the
+
+the spinal cord has peripheral ganglia which encased by bone
+
+in a virtual column.
+
+We'll see a picture of that in a moment.
+
+It's a good question.
+
+Cranial nerves kind of come out.
+
+So Queenslanders, as I'm speaking now, I'm moving my tongue
+
+will be using a for combat.
+
+Good question.
+
+That's not as clear as it could be.
+
+Thanks for that.
+
+So do do prompt if there's something super unclear.
+
+Very quickly answer that.
+
+Now we're going to start seeing lines like this is
+
+a bit of a detailed lecture and some I will
+
+skip over for speed because they're more of the need
+
+to know.
+
+But there are two ways of dividing up into the
+
+sections we're interested in.
+
+Like I mentioned to give, you've got six sections through
+
+the central nervous system, fluid just looking at the spine
+
+in the brain.
+
+So there are four sections to the spinal cord, the
+
+sacral bent down at your bottom, the lumbar section, which
+
+is most of the back thoracic at the top and
+
+right at the top of the spinal cord is the
+
+cervical section.
+
+And again, we won't be dealing with this much in
+
+our lecture, but there are interesting autonomic nervous system aspects
+
+that you will come back to this.
+
+And mostly we're not very interested.
+
+Above these we get into the more you sort of
+
+going up evolutionary from an evolutionary perspective here.
+
+These are the simplest bits of your body that, as
+
+we said, if you cut off the brain in a
+
+frog as you go in, that you can still make
+
+it do those fantastic reflex movements from these parts of
+
+the spinal cord.
+
+Above that, we come to the medulla.
+
+So we're going to have a whole lot of the
+
+medulla, the pons and the midbrain all form what's known
+
+as the brainstem, both in this section, Pons and the
+
+midbrain will form part of this brainstem area above them.
+
+We now get into higher order bits of the brain
+
+that are doing the things that we're interested in.
+
+This course, mainly these include the dying stuff along and
+
+the cerebral hemispheres, the cerebral hemispheres, the really clever bits
+
+that make us human really did bits that expanded massively
+
+in humans compared to, say, a mouse.
+
+And you can see they're are all folded over to
+
+cram in there.
+
+But if we we're going to focus on those in
+
+a bit, here's all these extra bits of things we'll
+
+come back to.
+
+But the distinction I'm trying to draw out with this
+
+slide is this distinction between a brain stem, the dying
+
+step along the cerebral hemispheres and below it the spinal
+
+cord.
+
+The dying step along here is composed of two regions,
+
+the thalamus, a big central kind of organising structure in
+
+the middle of your brain and the hypothalamus.
+
+And we'll spend two lectures thinking about the hypothalamus because
+
+it does fascinating things to do with paternal or maternal
+
+behaviour.
+
+Regulating your stress response, the thalamus, those magical things to
+
+sleep.
+
+You'll come back to that sleep lecture.
+
+But down here we don't spend much time on the
+
+fascinating nuclei within these brainstem areas to do.
+
+Arousal.
+
+So if a lion suddenly got into the room deep
+
+down, glad you had all these nuclei to wake you
+
+up and get you going to escape out of here
+
+from the lion, the medulla again we wouldn't spend much
+
+time on contains bits of your brain to do with
+
+temperature regulation breathing.
+
+So if you get a tiny stroke in your medulla,
+
+that could be you dead because you stop breathing or
+
+you just overheat.
+
+You can't turn off your raising of temperature.
+
+So it's a really crucial bit of the brain common
+
+to all mammals and reptiles and something.
+
+Okay, another way of thinking about this is to divide
+
+up between the hind brain, brain and the forebrain with
+
+just to understand the division of the nervous system.
+
+So if someone says, Oh, we're going to look at
+
+forebrain, they mean the cerebral cortex of the dinosaur got
+
+the thalamus again in the midbrain is a particular bit
+
+of the brain here that sits between these hind brain
+
+areas.
+
+And the main forebrain contains some key pathways that will
+
+come onto intellectual sensation.
+
+And again, down here of the structures at the back
+
+of the brain is called the cerebellum.
+
+It means that she the little brain, and it contains
+
+half of all the neurones that you have in your
+
+head.
+
+And it's critical for timing.
+
+Everything you're doing.
+
+That pretty much involves timing, making sure you don't fall
+
+over, hold a pen, speak lots and lots of things.
+
+We're still, as neuroscientists, really trying to figure out how
+
+much of the cerebellum is where we will be focusing
+
+in these lectures, much on development.
+
+It's a vast topic.
+
+This institute you're sitting and having this lecture is an
+
+institute of child health, but it's fascinated over these issues
+
+around child development inside the womb before babies born.
+
+This is its brain just before it pops that it
+
+starts off this journey from a very simple looking brain
+
+structure to a mouse to a chicken, and by the
+
+end of a baby, developing in the mother's womb is
+
+very different to any other animal on our planet.
+
+You can see it's massively expanded.
+
+The talons have long, which is another term for the
+
+the cerebral hemispheres in development.
+
+We have a dying step along with a mesons balloon
+
+and a mess and stuff.
+
+These are just distinctions during development.
+
+Again, I'm just highlighting this as an important slide for
+
+if you come on to thinking about brain development and
+
+growth of the brain in the womb, these are the
+
+kind of terms.
+
+But again, just taking you through that is to say
+
+we won't be returning to these topics much, but to
+
+make you aware, there's a fantastic world out there.
+
+The research on babies brains in the womb.
+
+Okay, here's an adult brain and it's disgusting for cadaverous
+
+state.
+
+One of the key things to learn about when you
+
+think about a brain like this is that there are
+
+all these bumps and there are grooves that little gaps
+
+in here, and these bumps that stick up are known
+
+as gyri and the gaps in a soul kind.
+
+So when anatomists label bits of the brain and say,
+
+Oh, we're going to put an electrode in and stimulate
+
+that, we often refer to it as a gyrus if
+
+it's a bit sticking out or if they have to
+
+get that electrode right deep into the brain, they'll be
+
+going into the sulcus.
+
+So there is some big cell guy.
+
+So there's some really big ones too.
+
+Here.
+
+The temporal lobe is the frontal lobe and the temporal
+
+lobe, the bit that separates the temporal lobe from the
+
+frontal lobe is known as the sylvian picture for some
+
+reason.
+
+Look.
+
+Okay, carry on.
+
+Okay.
+
+So that that's that is the maybe the general brain.
+
+We're going to dive in and highlight some gyri.
+
+Now, this is where these lectures start.
+
+I was a student studying theories and go, Oh, gosh,
+
+you showed us the lot of brain pictures.
+
+Now I got to take it.
+
+But as I said, this is a lecture where I'm
+
+just introducing the terms.
+
+If you go and study them at the level we're
+
+highlighting here, it should it should all locked into place
+
+this thought in the right hemisphere.
+
+Over here.
+
+We'll start here.
+
+Let's go.
+
+Here is probably the frontal lobe and there's all these
+
+little clever bits here, the orbital triangular in a particular
+
+part of the frontal lobe through part of a gyrus.
+
+That is the Brockers area that we talked about, where
+
+you get a bullet through that and you will lose
+
+the ability in 90% of people to be able to
+
+speak.
+
+So if we look at the right hemisphere, one of
+
+the key organisations goes back to wild open field and
+
+favours various work.
+
+But we have the central sulcus.
+
+But there are all these okay in the brain, but
+
+this is the most important, it's the central.
+
+So because it divides the frontal lobe through the parietal
+
+lobe, the central sulcus, and you can see it more
+
+clearly in the left hemisphere, but here it is in
+
+the right hemisphere and really unimaginatively very descriptively.
+
+The gyri in front of it is known as the
+
+pre central sulcus pre is ahead of it and the
+
+one behind the post central sulcus sort of potential gyrus
+
+these two gyri.
+
+So if you split the electrode onto the pre central
+
+gyrus, there's the hand area that makes them want flick
+
+their hand around and.
+
+You just move the electrodes backwards to the coast, then
+
+to charge.
+
+Don't start to feel an itch on their hands.
+
+Yep.
+
+So central focus is that.
+
+You know, there's still been fissures tucked under.
+
+What we're doing now is looking down a top of
+
+the head.
+
+So, Silvia Fisher, if I go back, is this fit
+
+to separate the temporal lobe from the frontal lobe?
+
+What we're going to do is now slip up and
+
+look down.
+
+It's a great question.
+
+Thank you for asking that.
+
+We're not looking at the top of someone's head.
+
+The eyeballs would be under here.
+
+So very useful questions to have.
+
+So you got a frontal lobe here.
+
+We've got this typical the not label, but just part
+
+of this diagram is to highlight.
+
+There are a number of names gyri like the angular
+
+gyrus, the super marginal gyrus, a superior parietal lobe gets
+
+a special name and there's an into parietal sulcus.
+
+Now, this is me introducing it to you.
+
+You have a whole lecture that focuses on what the
+
+integrated sulcus is doing later in the course.
+
+But there are all these gyri that come up in
+
+lectures, But that's really where the organisation highlights and links
+
+back to the previous lecture about the fundamentals of learning
+
+about how the brain is organised for sensory systems and
+
+motor systems.
+
+Okay, so we were looking from the top down previously.
+
+There's the frontal lobe is the parietal lobe is where
+
+the eyeballs would be and this is the highlight that
+
+there are the division here is pretty clear as a
+
+motor and a sensory system, but the actual division between
+
+the parietal occipital and temporal lobes is very much an
+
+argument made on a number of different criteria that businesses
+
+don't agree with each other.
+
+So histology is looking at the cells, the architecture, the
+
+structure of the cells, the chemicals in the cells, the
+
+how, the different bits, the brain are connected and what
+
+they are doing.
+
+Phineas Gauge agreed in lecture one lost his personality due
+
+to frontal lobe damage that doesn't occur elsewhere.
+
+So we have all these ways of dividing up these
+
+lives, but they don't all agree.
+
+I just described that issue just to give you another
+
+way, a nice way of looking down previously, we've both
+
+been from the side and we've got these areas that
+
+I just described offhand.
+
+So it's just thing if you put an electrode into
+
+the brain, increase ventral sulcus, sorry, gyrus is the central
+
+sulcus is the central gyrus, It will make the hand
+
+move, move the electrode back, you'll feel the stimulation, tickling,
+
+sensation, pointing fingers, face, lips, etc..
+
+These are known as the primaries, the map of sensory
+
+cortex.
+
+When you feel it in primary motor cortex, where it
+
+allows us to move at the back of the brain,
+
+we have the primary visual cortex, which going back to
+
+our hands and in the dark ages of 1008, argued,
+
+is where vision is process to.
+
+It's 10,000, 3000 years later, wouldn't that when I'm looking
+
+at that in detail.
+
+We also have a primary auditory cortex in our temporal
+
+lobe.
+
+So these are the areas where the information reaches the
+
+higher order bits of your brain.
+
+These are the primary bits.
+
+And if I showed an example of a mouse, a
+
+lot of its brain is taken up with those topics
+
+of feeling, acting and hearing and seeing and the other
+
+bits of today we're kind of putting these things together.
+
+If you look at your brain, this is a diagram
+
+of what your brain is doing as a lot of
+
+brain area.
+
+They're doing other things.
+
+And that's a lot of the topic of this course
+
+as we come forward.
+
+We do more than just sense the world and move
+
+in it.
+
+We construct our internal understanding of it.
+
+We have language to dive out into the middle of
+
+the brain.
+
+So this is a mid-size view into the brain.
+
+You can see the nose, the tongue clipped someone's teeth
+
+here.
+
+But what we can see, there's a lot of labelled
+
+sections here.
+
+You can see the cerebellum and bits labelled the.
+
+What are highlighting in this slide?
+
+All right, a few things.
+
+One is the corpus callosum to come back to another
+
+diagram with that in the moment, which is the major
+
+a pathway superhighway that connects your two hemispheres together.
+
+There are two hemispheres in our brain and they're connected
+
+by this superhighway for what's highlighted in blue.
+
+You can see this disgusting cut through the skull and
+
+the sap and the skin, but there's a little blue
+
+section here running all the way round, and that is
+
+a meninges part of your brain that saves you from
+
+being hit on the head from catastrophic brain injury.
+
+It's like a packing around your brain to protect you.
+
+And they.
+
+We'll come into the detail within those.
+
+And there are also ventricles.
+
+So ventricles we talked about with Vesalius and Descartes, they
+
+thought that's where the soul came to our brain in
+
+this deep in this anatomical diagram, we can see there's
+
+a fourth ventricle here so invincible and there's no ventricle
+
+One and two, there are two giant lateral ventricles.
+
+I'll show you where they are in a moment.
+
+So I'm going to go on and look at the
+
+brain, what's going on in the spinal cord if we
+
+cut through this and what that looks like and then
+
+going back to these meninges.
+
+So here is our spinal cord.
+
+If I go back and imagine it's cut through the
+
+human head, sliced out in the middle, like gone in
+
+someone between their eyes and cut with a knife, this
+
+person's dead, we assume.
+
+But now we're going to take a knife and just
+
+cut through this.
+
+Just take this bit out and cut horizontally through it.
+
+What do we see?
+
+This is what we see.
+
+So this is towards someone's chest and this is towards
+
+their back.
+
+This is the bone, is that vertebrae?
+
+And inside it is the spinal cord.
+
+And in there, the neurones that allow a signal to
+
+go out.
+
+To the to make you act like I want to
+
+move my fingers.
+
+I'm going to need to use one of those spinal
+
+neurones in my spinal cord to do this, to make
+
+my fingers move, but it still slaps my hands, tells
+
+me to stop clicking.
+
+That's annoying.
+
+I'll need to sense that on my fingers.
+
+And again, that will come back down a neurone into
+
+the spot and back up the spinal cord is a
+
+relay.
+
+The neurones sending things out to act as sensory information
+
+to come back and surrounding it.
+
+It's sort of like spider's web of material.
+
+It's form the these meninges.
+
+They're easy to see on the spinal cord.
+
+You can see this yellow stuff, this fat, disgusting stuff
+
+that people like to see in certain cases.
+
+But the the the this this material here is known
+
+as the arachnoid structure.
+
+There's a durable lack of the juror matter and a
+
+protective matter.
+
+So we'll look at these in the next slide.
+
+These are the meninges.
+
+So here is a sort of Halloween esque picture of
+
+the brain and the skull looking into someone's head.
+
+And we can see that it's the brain is all
+
+the brain cells.
+
+There are blood vessels and there's this arachnoid by spider
+
+like layer with a juror and a plasma and arrange
+
+the matter protects the brain and the juror matter creates
+
+a tough substance on the top.
+
+So these are the meninges introducing you to things.
+
+I'm not putting this slide up saying, right.
+
+Can you memorise what number 29 is in this picture?
+
+We will not be testing you like that in this
+
+course.
+
+What I'm doing this slide is to show one of
+
+the main ways of dividing up the brain into more
+
+detail, but still use to this day since the 1940s
+
+is work done with the German anatomist Carl Brockman.
+
+He divided up be looked at microscope images had lots
+
+of different bits of the human brain and just divided
+
+them up into about 42 regions, maybe 50 or so
+
+just under that that number.
+
+And there are key like the primaries, the multisensory cortex
+
+is number one.
+
+And number two is that there are various bits of
+
+that system.
+
+This is this is one way of dividing up the
+
+brain labelled areas based on the cell types.
+
+For example, the cells in areas for huge, the biggest
+
+cells you have and these are the motor neurones that
+
+come out if you to dissect the brain of a
+
+giraffe to Giant because the giraffe needs to send a
+
+signal from its brain to its toe and it needs
+
+a big cell to do that.
+
+So this is called Brockman's division of the nervous system.
+
+You come back to this his later lectures.
+
+So just to highlight how else can we divide up
+
+the brain, another way is to look at the brain
+
+and there are bits of the brain that are dark
+
+and grey and there are the bits that are white
+
+made of many of fat.
+
+And so the way the cortex will talk is this
+
+the bits we've been looking at, these bumps, it's all
+
+kind gyri.
+
+There are also subcortical structures.
+
+We come to the moment and these are also grey,
+
+these are all the grey.
+
+That's the brain grape, it's the where the neurones sit
+
+and you'll hear all about neurones next week on Monday.
+
+But what bits, the connections, the pathways.
+
+So much of your brain is taken up by the
+
+white matter, which are the pathways between the neurones where
+
+they send information.
+
+And this inside is the corpus collective.
+
+The superhighway will come to look at some more images
+
+of us in a moment.
+
+So we have a distinction between the areas with nuclei
+
+and there is ganglia that just happens to be terms
+
+anatomists use for clusters of groups of cells.
+
+These are two other ways of staining the brain.
+
+So you can see you can pick out the white
+
+matter, which is confusing here because the white matter staying
+
+dark, a dark colour and another classic lab use all
+
+round, you will be using a missile stain to get
+
+the grey matter in.
+
+You can see colour, so there are different ways of
+
+staining the brain and looking at white matter and grey
+
+matter.
+
+The next two slides were getting towards the end of
+
+the kind of drugs big pictures in the brain.
+
+There are two kind of core systems to pick out
+
+your brain.
+
+There's the limbic system and again, just I'm introducing them
+
+now to come back to the limbic system.
+
+When we go into emotions and memory inside the limbic
+
+system, you can see some eyes here.
+
+We have an area known as the hippocampus, the bit
+
+that was removed in patient H.M. and to dense amnesia.
+
+There's also an area known as that which sits.
+
+He actually has one hippocampus in each hemisphere, the left
+
+and right hippocampus.
+
+There's the thalamus in the middle, and there's a brain
+
+structure called the amygdala, which looks a bit like an
+
+island.
+
+And that's what the rat environment is, amygdala.
+
+So the link to the nucleus contains cells that are
+
+critical for emotional processing and fear.
+
+There are patients out there that are just completely lost.
+
+They damaged by laxity, their amygdala, and they will quite
+
+happily pick up giant snakes to a pet, a tiger.
+
+There's literally no fear in these patients.
+
+This is absolutely critical for threat setting throughout the processing.
+
+There other bits that are coming to the hypothalamus and
+
+our lectures on stress and social bonding.
+
+And again, just really briefly, I'm not expecting you to
+
+take away this and walk through it in more details
+
+in here.
+
+Another bit of the brain, another circuit we have the
+
+limbic system is another circuit in the brain called the
+
+basal ganglia.
+
+Again, if you a neurologist training medical school, you'd get
+
+a lot of detail about the system.
+
+For you.
+
+It's really worth being aware that the basal ganglia contain
+
+the caudate nucleus actually stamen and the globus paladins, and
+
+they're arranged in this way, shown here, the nucleus, the
+
+glow of asparagus and the potatoes and vitamins here, Globus
+
+Palace.
+
+And we have some other the sub nuclei.
+
+We'll come back to these as we go through our
+
+lectures.
+
+When you get into movement, these are the brain areas
+
+and in particular brain structure down here, the substantia nigra
+
+will come on to that and that's the keep it
+
+in the brain that goes wrong in Parkinson's disease.
+
+Now we have a later lecture all about neurological diseases
+
+and this goes to come back to these repeatedly.
+
+Plot three that's just talking about what we look what
+
+we're looking at here.
+
+Here's the human brain from the outside.
+
+Is it from the back?
+
+And we're going to dissect this little bit shown here
+
+in the shaded area.
+
+So here is the thalamus.
+
+This is all as if you've removed the three hemispheres.
+
+We peeked inside the back of the brain and we
+
+can see the cerebellum.
+
+If we cut through here, through the midbrain, what we
+
+see inside it are a number of areas.
+
+So these do look a little bit colour.
+
+They're really overly accentuated here, but this substantia nigra means
+
+black substance and it is black.
+
+There's a red nucleus which is a bit red, and
+
+then there's a reticular formations is a little bit pale
+
+blue ever so slightly.
+
+And this is the area of the Perry aqueduct all
+
+grey.
+
+Now the other part is another bit, the superior molecular.
+
+We'll talk about that later in vision.
+
+I will talk about these when we get into the
+
+stress fractures and neurological diseases.
+
+But this is just to show you the main key
+
+structures.
+
+If you were to cut through the midbrain, just introducing
+
+the various characters to play out as actors in our
+
+story, to come to these lectures.
+
+So ignore the giant arrow across this image and focus
+
+on this arrow.
+
+This is the corpus callosum, which is the highlight in
+
+the middle of the brain.
+
+This superhighway used all the brain, the grey matter grooves
+
+of the gyri, and they're all connected to one hemisphere,
+
+to the other through the corpus callosum.
+
+And it means hard, durable substance.
+
+If you cut through correctly, we saw this before.
+
+Here's the superhighway.
+
+So there are cells down here that will send a
+
+message all the way to the cell over here through
+
+your corpus callosum.
+
+Okay.
+
+So white matter.
+
+We're just looking at pathways in the brain.
+
+Just to orient you.
+
+There are things called trapped, which mean it goes from
+
+one bit to another.
+
+Two verticals area.
+
+To Brock area has a truck.
+
+It connects these two brain areas together.
+
+There are things called for Siculus for Nicholas Peduncle, a
+
+break in the collections of nerve fibres that go to
+
+different places.
+
+Like a like a, like a sort of connecting highway.
+
+The M25 takes cars to various places around it and
+
+then the way little bits go to the sky.
+
+In this case, these are sending fibres going up and
+
+down.
+
+They're just different types of white matter sitting in your
+
+brain.
+
+I mentioned previously the ventricles, these fluid filled spaces.
+
+The Descartes thought was how your soul gave rise to
+
+your whole conscious experience.
+
+You have a lecture on consciousness.
+
+This here in the course and deep learning will not
+
+be, I think, talking much about the ventricles.
+
+But you could.
+
+You can ask him.
+
+I talked about the fact there's a there's a fourth
+
+ventricle right at the bottom.
+
+There's a third ventricle, and then there's these lateral ventricles.
+
+Let me highlight these here.
+
+So these gaping holes here and here are the two
+
+lateral ventricles.
+
+And this is the core reflex that's this disgusting stuff
+
+inside your head.
+
+If you open up the brain that allows the this
+
+fluid inside of this milky white fluid to maintain its
+
+consistency and it bathes the brain, particularly powerful fluid that
+
+is necessary for the optimal functioning of the neurones in
+
+the cells that exist in your brain, unlike the rest
+
+of your body.
+
+But these are just to show with the length the
+
+ventricles are.
+
+What happens if you block these ventricles?
+
+No doubt there have been many discussions in this building
+
+of Institute of Child Health about this is that the
+
+fluid builds up and up and they need to surgically
+
+go in and put in a shunt.
+
+The children that would really stretch skull huge heads.
+
+Unfortunately, due to a condition known as hydrocephalus.
+
+And so it's a really devastating condition.
+
+But the cells are all there to someone's got this
+
+huge damage, but the cells are still sitting there so
+
+they can end up living fully functional, impressive lives.
+
+They just suffer a few challenges of memory and executive
+
+and things to do with the frontal cortex.
+
+But it's amazing this can still work, but if it's
+
+not treated, it can lead to death, of course.
+
+Now, this is a very intense slide, and I'm putting
+
+it up here just to say there are 12 cranial
+
+nerves.
+
+You'd have a whole lecture on the cranial nerves if
+
+you were a neurologist trying to be or if you
+
+were medical students.
+
+You do not need to know this material in detail
+
+other than the fact there are 12 of these to
+
+go to the heart.
+
+They deal with the eyes.
+
+Visit this the nerve fibres for the the optic nerve.
+
+We'll come back to that to pick up on some
+
+of these cranial nerves in other lectures to do with
+
+sentence in the world.
+
+But they're really about the fact that I had for
+
+moving my hands, The stuff I was talking about before
+
+of my clicking my fingers goes to my spinal cords.
+
+If I want to wiggle my tongue, it's above the
+
+spinal cord.
+
+I need a cranial nerve to wiggle my tongue.
+
+And you can see there are tongue based cranial nerves
+
+there.
+
+They'll come out of the bottom bit of the brain.
+
+So these are the cranial nerves.
+
+So yeah, they.
+
+They cover a range of different, different functions to do
+
+with the head.
+
+Now, this is a slide that will come back.
+
+I'm introducing it now and we'll go back to it
+
+again when we get onto stress, because this is the
+
+autonomic nervous system.
+
+We've been focusing in all the previous slides on this
+
+bit of the topic of the brain where all thoughts
+
+and memories and emotions and they're all gathered from from
+
+this that our paternal or maternal behaviour, it's all there,
+
+but our spinal cord has these incredible neurones embedded within
+
+it, the not just the sensory and motor function, but
+
+actually protecting us from the world out there.
+
+So as we go through the world, as you've all
+
+experienced by the point you've arrived here, there are stressful
+
+things that they're even in our nicely protective world now.
+
+I was a health service and we organised society and
+
+we still have threats, get the stress of exams, for
+
+example.
+
+These are the bits of the brain that help you
+
+get activated or allow you to calm down in that
+
+sense.
+
+So there's a range of different neurones up and down
+
+the spine to go to.
+
+Let me pick out one of the key ones here
+
+is your heart.
+
+So if a lion suddenly rushed into the lecture theatre,
+
+you're not wanting to sit down, relax and read a
+
+book who like to be the one person doing that
+
+in the lion?
+
+You kids right?
+
+Hungry, alone.
+
+Your brain needs to get you ready to get the
+
+hell out of here, out of an expert.
+
+And it does that by regulating your heartbeat.
+
+So if your heart's running higher, you can pump more
+
+blood, you can run faster, you can get to running
+
+thoughts, you need more glucose for your muscles to get
+
+you where you need to be.
+
+And so the the the the system, the sympathetic nervous
+
+system also acts to stimulate the release of glucose from
+
+your liver to get that going.
+
+If it does everything it said, it dilates your pupils
+
+to get more light, stops you sweating inhibits you salivating.
+
+It does all these things that get your body ready
+
+to escape that lion or that threat.
+
+But imagine you just kept going and going.
+
+Your heart rate goes higher and higher.
+
+You don't ever salivate again.
+
+You're just pumping out glucose around your body.
+
+You die, you live overdriven your body to excess.
+
+So once you're away from the line and you're safe,
+
+you want to bring that all back down.
+
+And there's a sort of it's a connected system.
+
+You can see that while all this driving stuff's in
+
+the spine.
+
+All right.
+
+The top here are these various descending nerve fibres or
+
+at the bottom here, some that deal with that process
+
+of dampening things, lowering your heart rate, halting the amount
+
+of glucose coming home, stimulating things to do with eating
+
+and digesting because you need to take time.
+
+Digesting isn't instant.
+
+Your body needs time and care to digest and take
+
+things and to relax, you need to sleep as well.
+
+For example, if this is all if your heart beats
+
+going through the roof, it's very hard to sleep.
+
+So again, all these things are allowing you to keep,
+
+maintain a calm environment that allows you to do a
+
+range of of the things that we need to biologically.
+
+You know, you can see down here with things like
+
+if you get really stressed out, people pee and they
+
+lose the urine, but you don't want to do that
+
+when you're relaxing.
+
+So these are kind of some strange aspects of our
+
+nervous system.
+
+We share this autonomic nervous system at all of the
+
+mammals and reptiles.
+
+Another sapiens vertebrate is basically any animal from millions of
+
+years back that developed a spinal cord has these autonomic
+
+sympathetic for rising up a parasympathetic for dragging down.
+
+So these are was an open our system will come
+
+back to what these are doing when they link to
+
+the brain later in the course for stress.
+
+The last bit of today's lecture.
+
+Yes, sir.
+
+I'm speechless.
+
+So that information comes first.
+
+The response.
+
+Is not.
+
+Information.
+
+Yes.
+
+How did you.
+
+Great question.
+
+So how does the spinal cord know this aligner?
+
+Right.
+
+So you have to have your eyes and your ears
+
+and maybe smell all these sensory bits of information that
+
+gather information about the world, feed two parts of the
+
+poor bits of the brain, then descend.
+
+And you want to do that as fast as you
+
+can so that are very fast route to get from
+
+your visual system.
+
+The threat of, say, a giant snake or lion is
+
+just to draw.
+
+That is one example down to your spinal cord to
+
+do.
+
+Another key thing to highlight here is this is called
+
+the autonomic nervous system.
+
+It's very hard for you.
+
+You can start to think about stressful things, right?
+
+And it'll start to raise your heart rate.
+
+You'll get stressed by thinking about things, but you have
+
+to actively do that, wait for it to respond.
+
+You can't control directly.
+
+You can't just go, I want to raise my.
+
+Heart rate by so many beats go.
+
+It doesn't work like that.
+
+It's not a voluntary process.
+
+It's autonomic.
+
+It's automatic.
+
+You can't stop but feel stressed, do certain things.
+
+So, my friends, getting off on this.
+
+Right.
+
+To end today's lecture, I want to highlight there are
+
+four different neurochemical circuits in your brain that again, this
+
+is not a one off.
+
+We keep going back to these circuits.
+
+So I'm introducing them here as actors in our story
+
+about threatening behaviour.
+
+One of these is the the noradrenaline system.
+
+You'll hear about this next week again.
+
+And there's a particular nuclei in your brainstem called the
+
+locus surrealists and it sends out fibres.
+
+Here are the neurones.
+
+They sit here and they send fibres, axons all the
+
+way through the whole brain.
+
+And this is part of our central activation systems that
+
+get converts that line when you want to upregulate the
+
+to activate the brain to take on an act, you
+
+need a system.
+
+Widespread power.
+
+Enhance my vision.
+
+I want to listen better.
+
+I want to be able to focus.
+
+You need you need a brain wide broadcasting system.
+
+And that's what the noradrenaline system does.
+
+Adrenaline, you may be aware of this is that this
+
+is something you might treat some of it.
+
+Anaphylaxis is something you might want to take an active
+
+hand and inject adrenaline directly.
+
+And this this drug is very similar, very, very similar.
+
+The molecule to noradrenaline in the brain, adrenaline is doing
+
+that in your body and noradrenaline is the activation molecule
+
+in your brain.
+
+Last bit talk the dopaminergic system which which is a
+
+much more restricted section of the brain, this molecule dopamine,
+
+we'll come onto that later also described as the desired
+
+molecule and we'll get to that.
+
+Finally, we have our choline molecules, both in sleep and
+
+memory.
+
+That comes from two particular nuclei and a bizarre nucleus,
+
+right?
+
+Peduncle, pontine nucleus.
+
+We'll come back to these again.
+
+Finally, we have serotonin, a molecule that gets involved in
+
+the treatment of depression and mood disorders, and that comes
+
+from a number of the RAF finding them again very
+
+widespread.
+
+So this is an example of a kind of question
+
+you might get at the end of the course.
+
+Which ventricle are we looking at here?
+
+Is it the for the third or the lateral ventricles?
+
+The way to learn that material is taking that resource.
+
+I said that word document.
+
+I'm playing with that and looking up because this image
+
+is taken directly from that web tutorial.
+
+So I've linked.
+
+So if you go and explore that, you will learn
+
+your your anatomy very well.
+
+That's the resource here.
+
+Do use my guide because it's more information you need.
+
+I'll see you next post for you next week for
+
+more on neurones and their structure.
+
+Thank you.
+
+Thank.

raw_transcripts/lecture_3.txt

@@ -0,0 +1,2363 @@
+And someone up the back just told me.
+
+It's very hard to tell what the volume is here
+
+at the back.
+
+And you hear me fairly well.
+
+Okay.
+
+Thank you.
+
+And just make sure since I once started a lecture
+
+and got 10 minutes through it until someone told me
+
+they were in the maths department, weren't quite sure what
+
+neuroscience to do with that degree.
+
+We are here for brain and behaviour.
+
+Is that correct?
+
+Good start.
+
+Okay.
+
+Oh, I get a little bit slowly over the next
+
+couple of minutes.
+
+Just make sure if there's any other people who are
+
+coming in can come in.
+
+My name is Sam Coleman or Professor Sam Kaufman.
+
+I don't think I've met you yet.
+
+You may have seen me in the video.
+
+I'm not sure.
+
+I'm the head of Department of Experimental Psychology.
+
+I base is a better way along with you go.
+
+I'm the person you'll be seeing most in this course.
+
+That may or not may not be a good thing.
+
+I feel nervous today because this is the first letter
+
+I have given for about three years, so I apologise
+
+if I'm a little bit stumbling.
+
+I'll get back into the swing of it over the
+
+next few weeks, I hope.
+
+Please come in.
+
+So the aim of these two lectures today and on
+
+Friday is to give each of you make sure you're
+
+all up to about the same place and understanding a
+
+little bit about the cellular function of nerve cells and
+
+how their activity helps us to see the here, etc..
+
+Can I just as a matter of starting point, can
+
+I ask who has done some form of biology before
+
+on neuroscience?
+
+Fantastic.
+
+Who has actually specifically done some form of neuroscience before?
+
+A few of you.
+
+So for some of you, this might be a little
+
+bit of old rope.
+
+For the next couple of lectures.
+
+I hope you'll be able to think about some things
+
+that you might not have thought about.
+
+For many of you, this might be the first introduction
+
+to neuroscience that you've had over these last couple of
+
+weeks, and I hope that you'll be able to get
+
+up to speed to where we want you to be,
+
+where we hope you'll be pretty quickly.
+
+Well, that is a really annoying door squeak, isn't it?
+
+Or just let people come in.
+
+She.
+
+I have a feeling this door is going to squeak
+
+for a while, so I'm going to have to kind
+
+of get started and try and talk over the squeak.
+
+I studied molecular biology when I was an undergraduate.
+
+Sometimes I go back and think things have changed a
+
+lot since I started.
+
+That was 25, 30 years ago.
+
+I practised as a neurophysiologist for most of my life.
+
+Sometimes it's a little bit hard for me to step
+
+back and understand what I do know and don't know
+
+what I should know and should not know.
+
+For these reasons, I'm very happy for you to interrupt
+
+and tell me you don't understand what I'm talking about,
+
+right?
+
+Sometimes it's difficult to pitch something that you know intimately
+
+to the right level.
+
+Okay, So please do interrupt.
+
+I hope that what I'm trying to do is trying
+
+in this lectures to try and keep some of the
+
+flavour of what we learn to do over the pandemic
+
+years.
+
+And and I'm going to try and be a bit
+
+more interactive towards the end of this lecture.
+
+Hopefully we'll get through in time and get through to
+
+it.
+
+I want to get I want to make sure you're
+
+all up to speed about the basic concepts.
+
+There's a lot of additional reading you could do to
+
+understand more detail.
+
+There are some fundamental things I think we need to
+
+understand about nerve cells, about brains, to understand how it
+
+is that our cognition is structured, to understand how it
+
+is that we think about things, to understand how it
+
+is that I see you when you see me.
+
+And that's the purpose of these two lectures.
+
+You might have seen this before.
+
+When I started out, as I said, training as a
+
+molecular biologist.
+
+My second year, I finally found a neurone and after
+
+about a year and a half of studying crab cycles
+
+and everything else, which I tell you, I'm not that
+
+interesting.
+
+This structure was something that really fascinated me.
+
+And this is a neurologist as a basic function of
+
+your brain, a very basic functional unit of your brain.
+
+And neurone has several defining characteristics.
+
+What I want to draw your attention to in this
+
+slide are the dendrites, these profusion of little tree like
+
+structures that come off the cell body or soma, the
+
+thermal self, which is where the DNA in the nucleus
+
+is, for example.
+
+And then the axon, which extends from the SOMA, a
+
+very specialised process and heads out towards the terminal boot.
+
+And this neurone has a bipolar kind of structure.
+
+It has inputs at the dendrites and outputs of the
+
+axon or nerve endings and the functions, the activity of
+
+these neurones, the computations that they perform which underlie all
+
+of what we do.
+
+So I'd like to start off with the central question
+
+Why do we actually have brains?
+
+When I try to ask myself this question, I come
+
+up with many different answers.
+
+And this is one I've said all along over the
+
+last few years as limit brains around the body, this
+
+collection of organs, muscles, etc., to respond to its environment
+
+and to allow plastic control of the body so something
+
+we can adapt to changes in the environment or changes
+
+in the body itself.
+
+If you think about the simplest possible nerve cell circuit
+
+that we have in our bodies, for example, the reflex
+
+circuit that allows us to withdraw our hand rapidly from
+
+a hand that is a very simple circuit.
+
+There are two sign ups as to connections between neurones
+
+involved.
+
+There is a sensory neurones that goes from the periphery
+
+or from this case, the hand goes up the spinal
+
+cord.
+
+Little things and you're on there and then there's a
+
+motor neurone that goes from the spinal cord back to
+
+the muscles that control that hand in this case.
+
+That is the simplest possible neural circuit that we have
+
+in our body.
+
+It allows us to react very quickly to something that
+
+happened in the environment.
+
+In this case, touching something hot that might cause damage
+
+to our skin or other parts of our body.
+
+It is functioning very simple and really helpful.
+
+If we wanted then elaborated by, for example, reaching out
+
+and touching something.
+
+And for me, that's what the brain does.
+
+It's a centralised way to try and control these circuits
+
+and others like them that allow us to adaptively react
+
+to our environment and to plan and to do things
+
+that we couldn't simply do with a simple two neurone
+
+circuit.
+
+The neurones in the brain allow centralised and plastic control
+
+of the body, and a simple task in these two
+
+lectures is to try and understand how it is that
+
+those neurones allow that form of control to illustrate the
+
+complexity of the issue.
+
+This is a slide.
+
+This raises some of the brains in relative scales of
+
+the species that might be studied in neuroscience, including the
+
+bottom right there, the human brain, about one and a
+
+half kilos of stuff, about 86 billion nerve cells at
+
+the top left there have highlighted a couple of other
+
+animals that are often studied mouse and rat, both rodents.
+
+A mouse, for example, has a brain about half a
+
+gram in weight, and about 71 million cells do quite
+
+a lot, but a far cry from 86 billion.
+
+And then there are other animals like marmosets and macaques,
+
+both of whom are non-human primates, and have been important
+
+models in understanding human brain function.
+
+Now, our brain is substantially bigger than those of these
+
+studied species, mainly study species, but we shouldn't get too
+
+cocky if we look at the size of the brain
+
+of an African elephant, for example, it's much bigger than
+
+ours.
+
+Now I leave it up to you to decide whether
+
+an elephant is smarter than us or not, but I
+
+simply mean that size itself doesn't really matter.
+
+The complexity and function of these brains is all enough
+
+to allow the species to adapt and survive in their
+
+environments.
+
+Now emphasise that there are 8 billion nerve cells in
+
+the brain.
+
+Neurones.
+
+But that's about equal numbers of other types of cells.
+
+These are loosely cuentas glia.
+
+And I just want to explain to you why we're
+
+not going to be talk about and talking about glia
+
+for almost the entire rest of the course.
+
+They are about half the cells in the brain, and
+
+yet we're not going to be talking about them.
+
+Why is that?
+
+So this photo or this series of photos on the
+
+right here that some guy took several years ago now
+
+obtained by a technique called photon microscopy.
+
+We'll be talking about that a little bit next week
+
+in the methods section.
+
+What I've done here is find some cells in the
+
+brain with a substance that makes them appear black in
+
+the slide.
+
+And those cells are astrocytes, a form of glia, one
+
+of these non nerve cells in the brain.
+
+These images are a series of images taken a very
+
+narrow depth about two micrometres or 2000s of a millimetre
+
+apart.
+
+Down through the brain of actually, in this case, a
+
+living rat.
+
+And you can see these different black things here.
+
+Hopefully you can see my area up there.
+
+These black things here are these astrocytes and they have
+
+these lovely processes that connect neurones.
+
+Many of these white holes, the neurones and the blood
+
+vessels, some of these larger one of the blood vessels
+
+in the brain unstained in this preparation.
+
+And can see these lovely processes connecting all these neurones
+
+and blood vessels together.
+
+So those cells are there.
+
+These are just one form of the known neuronal cells,
+
+but we don't really study them.
+
+Now there are three basic types of cells we'll come
+
+across.
+
+One is the neurones, as I said, will get to
+
+them.
+
+Most of this course, these are what we call excitable
+
+cells.
+
+And hopefully by the end of this lecture you'll understand
+
+what I mean by excitable cells.
+
+Two other very common parts of cells in the brain
+
+of the microglia, which are effectively the immune system of
+
+the brain, very important.
+
+For example, there are many diseases which seem to be
+
+basically a malfunction of the immune system of the brain
+
+of microglia.
+
+And then there's these other cells, astrocytes and other known
+
+example cells, for example, which connect these things together, which
+
+seem to provide the kind of super structure in which
+
+these nerve cells can survive and thrive.
+
+They also do other important things like maintaining what we
+
+call homeostasis.
+
+That is the amount of energy that you need for
+
+neurones to survive or the kinds of chemicals that they
+
+need to survive in the brain.
+
+The neurones are excitable and they can send signals over
+
+long distances.
+
+There is no cells capable of integrating and propagating signals
+
+very, very rapidly.
+
+An action potential which we spent a large amount of
+
+this lecture going takes about one millisecond or one thousandths
+
+of a second to occur.
+
+Those action potentials can travel sometimes up two metres down
+
+the axons neurone sends.
+
+These neurones have distinct zones as illustrated before for input
+
+the dendrites and output the axon terminals.
+
+That directional flow of input output allows them to do
+
+computations to take some summation of the inputs, compute and
+
+send a single output.
+
+Neurones also therefore formed these what were called hierarchal networks.
+
+Computations done at one stage of neural processing are then
+
+sent by the axons in the form of action potentials
+
+to the next stage of neurone processing.
+
+And we build up these successive representations, much like we
+
+do in computer models of the brain where we try
+
+to build.
+
+If you're familiar with kinds of nets that Google uses
+
+to do image recognition, for example, these are successive hierarchical
+
+representations of the image, and they're based actually on brain
+
+function, our understanding of the visual system in particular.
+
+On the other hand, astrocytes are not excitable cells, so
+
+they tend to have slow signals, their signals not formed
+
+in the order of one millisecond, but rather on the
+
+order of 3 to 5 seconds, slowly fluctuate much slower
+
+than we think.
+
+The normal perception of cognitive events or perception, you are
+
+able to type much faster than that.
+
+Astrocytes also connect to each other via various things called
+
+gap junctions.
+
+It's a little holes in the membrane between the way
+
+the membranes with true cells meet.
+
+Allows electrical current to flow through these membranes.
+
+So those astrocytes that you saw in those beautiful pictures
+
+from the rat cortex are actually one large network.
+
+We call this a synthetic network.
+
+And those that network, the activity, that network very slowly
+
+over time and space, again, incommensurate with what we think
+
+cognitive events are like, which are precise, rapid and very
+
+particular events.
+
+So for these reasons, we do not think the glia
+
+are important for the particular structure of cognition that you
+
+have.
+
+They are almost certainly very important for maintaining the neural
+
+signals.
+
+Failure in astrocytes and other forms of glia can lead
+
+to neural malfunction and disordered activity of neurones.
+
+But we don't think that the activity of those cells
+
+that are important for the kind of cognitive events that
+
+we experience.
+
+Instead, we think those are the job of the nerve
+
+cells, those 86 billion nerve cells in your brain, not
+
+the 86 billion other cells.
+
+I, as I've said, carry on.
+
+Euroclear clears word for glue.
+
+You can tell what the unanimous thought of them when
+
+they made up that name.
+
+I thought provide physical support that actually struck to the
+
+brain to remove debris and vacuum cleaners, basically provide immune
+
+function, work out when things go wrong.
+
+They also provide things called myelin while sheath, which we'll
+
+get to in the second, which help nerve cells communicate
+
+to each other.
+
+No particular cell types are called Oligodendrocytes.
+
+And they relative in the peripheral system out there and
+
+the arms are called formed cells also make myelin.
+
+Now, I've mentioned that astrocytes help maintain homeostasis, and I've
+
+shown you in those pictures that the blood vessels and
+
+the neurones are connected by these networks of astrocytes.
+
+And actually those astrocytes are doing two basic functions, at
+
+least one or two, but two that we need to
+
+think about.
+
+One is they actually help communicate energy levels or energy
+
+from the blood vessels, from the blood supply to those
+
+neurones, help those neurones work.
+
+And the second thing they do is actually signal to
+
+the local blood supply whether they need more energy or
+
+not.
+
+So if the local area of neurones is being very
+
+active, the energy supply like a fabulous.
+
+I think it's gone up.
+
+It didn't.
+
+See if you somewhat.
+
+Is this one working?
+
+So these astrocytes help communicate to the blood vessels that
+
+they need more energy.
+
+And when that happens, those blood vessels expand, they dilate,
+
+the blood flow to that area increases, and the energy
+
+to that local area increases supply.
+
+As important for understanding, for example, the bold signal with
+
+the blood oxygen level dependent signal that you see in
+
+the AFM range.
+
+That is a change effectively in the blood flow to
+
+particular parts of the brain that is organised by those
+
+astrocytes in response to local neuronal activity.
+
+And you can show this by, for example, using this
+
+technique, like I said, called to photon microscopy to stimulate
+
+the little processes of those astrocytes surrounding blood vessels.
+
+When you do that, you see the blood vessels increase
+
+in diameter, allowing more blood, more nutrients to get to
+
+local area.
+
+So they help these astrocytes help brains maintain local energy
+
+homeostasis.
+
+The oligodendrocytes that I mentioned.
+
+These helped make the myelin sheets, these little fatty liberty
+
+things that surround the axons.
+
+And we'll get to the importance of that in a
+
+second.
+
+You can see them here.
+
+These myelin sheath, they are interrupted.
+
+They're not the entire acts neurone toppled by little slices
+
+of exposed membrane organised around here.
+
+And you can see that these oligodendrocytes make these little
+
+seeds.
+
+One oligodendrocyte may be making seeds for many different axons.
+
+Similarly, in this one person in the periphery.
+
+Important is low seats are very important, as we'll see
+
+in the second disorders of the root of many of
+
+the disruptive brain diseases that we know.
+
+For example, multiple sclerosis is a demyelination disease, removing the
+
+myelin from the axons.
+
+Why would that be important?
+
+We'll try to find that out in a couple of
+
+slides time.
+
+So I'm taking you through them the basic function of
+
+several of those non neuronal cells.
+
+Just to illustrate to you that they are important.
+
+There's a reason that 6 billion in the brain.
+
+I hope the photo to why we're not going to
+
+study them, why we think that the neurones which can
+
+provide these very rapid hierarchically organised signals are the ones
+
+that are important for the structure of thoughts, perception, cognition.
+
+And that is the last, I would say, almost certainly
+
+of glial cells in the next ten weeks.
+
+So I illustrated you before I sent it to you,
+
+by the way.
+
+Now, I'm going to interrupt these things into a little
+
+section that will become clearer if we go on.
+
+This might be a bit of time for us to
+
+understand whether or not it went to some issues with
+
+talked about so far.
+
+Are there any questions you'd like to resolved in the
+
+meantime off the back of your own?
+
+Sorry.
+
+You have to speak up a little bit is.
+
+Really happens here.
+
+Sorry.
+
+Let me just come up closer.
+
+And is.
+
+It's a very good question.
+
+I'm not going to go into it because there's actually
+
+several things wrong with that slide.
+
+And it does make me want to just make clear
+
+there are some small white lies I'm going to tell
+
+you over the next lecture.
+
+Bear with me.
+
+Including that one.
+
+Okay.
+
+Bear with me.
+
+It's to help us all understand the basic issue of
+
+energy supply, for example, not the particular aspects of the
+
+cycles that they go through.
+
+So I understand the question.
+
+I just don't want to try and make it too
+
+complicated at the moment.
+
+There are a couple of white lines here.
+
+I hope that neither of them make it problem.
+
+Why are they metabolising lactate, not glucose that was there?
+
+I think that was the question.
+
+There's an answer to that, but I think it's beyond
+
+what we need one after this typical lecture.
+
+Okay, I'll just move on to the next week, which
+
+is the neurones are excitable cells.
+
+So why is it important to understand new signal transmission?
+
+Maybe this is like, Well, duh, but I just want
+
+to try and convince you that it's actually an important
+
+thing.
+
+I've stated already that the function of the brain and
+
+the nervous system in general is to receive, transmit and
+
+process signals.
+
+This is what it does.
+
+So to understand how the brain works, we need to
+
+understand how it transmits processes.
+
+Those signals is no point otherwise.
+
+And if further, if we understood how the brain does
+
+this, this would allow us to do things like understand
+
+how little anaesthetics work.
+
+Who here has had a local anaesthetic before?
+
+Anyone.
+
+They wanna know what a local anaesthetic is.
+
+Little you might rap on something.
+
+Injections you've got.
+
+I have to get these things called basal cell carcinoma
+
+for my face every so often.
+
+I grew up in Australia.
+
+It's terrible.
+
+I get so many injections of local anaesthetic in my
+
+face.
+
+Hate me.
+
+Has anyone else had anaesthetic injections?
+
+What are they?
+
+What do they help?
+
+You do not feel pain or anything or anything.
+
+Is that where he said that or anything?
+
+Not feel anything?
+
+Exactly.
+
+Actually, it's a really strange sensation.
+
+And it's like a an absence of anything.
+
+Not actually a presence or some or lack of in
+
+something.
+
+And hopefully we'll understand why they work in a second.
+
+They hope this knowledge would also help us understand how
+
+anti-depressants work, how drugs affect the brain, how diseases like
+
+multiple sclerosis and Alzheimer's disease damage the brain, and why
+
+they cause the symptoms they do, as well as these
+
+aspects of cognition.
+
+I want to make clear to you that I think
+
+that understanding how nerve cells processing was actually at the
+
+core of all of brain and behaviour, all of psychology,
+
+for example, because without that understanding it's very difficult to
+
+know what it is we are trying to explain.
+
+So this is going to be a bit of another
+
+white lie, but just bear with me about this again,
+
+helps us understand, I hope, the kind of signals we'll
+
+be talking about.
+
+So in the old days, by the old days, I
+
+mean probably starting the beginning of last century.
+
+This is how most of neurophysiology, the physiology of nerve
+
+cells was conducted.
+
+A large squid would be captured.
+
+It's giant Exxon, which is huge, much larger than any
+
+of your icons, is excised and put into a bath
+
+of saltwater seawater.
+
+A couple of fine glass electrodes are pooled on some
+
+machine which can pull them.
+
+These electrodes have small tips filled again with another salty
+
+solution.
+
+And we generally take two of those electrodes or at
+
+least one of those bathymetry and something else like a
+
+piece of wire.
+
+We put the wire in the salt bath and put
+
+the electrode into the axon and you can record the
+
+difference in electrical potential between these two things.
+
+And that's what's recorded on something like a little camera.
+
+So this photometry is recording the difference between the inside
+
+and the outside of the cell.
+
+In this case, the axon of that cell.
+
+That whole time, too, was very much like a light
+
+lotus when you attach it to the both ends of
+
+the battery.
+
+Potential difference of process to enter the battery causes current
+
+flow and the like per well.
+
+So we're going to do something similar to that with
+
+electrical device.
+
+This is the only bit of chemistry you need to
+
+know.
+
+From my perspective.
+
+I don't.
+
+Who here knows what an island is?
+
+We all remember back to those dark organic chemistry days,
+
+but some little bit like ions, atoms and molecules that
+
+have lost or gained one or more electrons.
+
+So an iron is positively charged.
+
+What we call the cation is one that's lost an
+
+electron, for example, a sodium atom.
+
+And a sodium has this one little poor electron wandering
+
+around on this outer shell.
+
+If it loses that electron, it becomes positively charged with
+
+electrons themselves and negatively charged it lose.
+
+The electron becomes positively charged, and we denote this item
+
+now as having an A plus plus relative charge.
+
+Similarly, if a atom gained electron would become negatively charged
+
+if the sample chloride gains electron becomes negatively charged.
+
+We do know that with a little minus sign.
+
+The substances we call salts, combinations of these positively and
+
+negatively charged molecules ions.
+
+So, for example, table salt, the stuff that we eat
+
+is a combination of sodium chloride.
+
+When you put into water, those two ions can dissipate
+
+and move around freely.
+
+Coming in sodium, potassium chloride minus.
+
+And the body is basically 80% water.
+
+So you can imagine the pool of ions floating around
+
+in there, including the brain.
+
+Okay.
+
+The next bit of that is, I think, over chemistry.
+
+We're going to have to know.
+
+The next bit is just to try and get you
+
+through some terminology that we're going to use as well.
+
+Way to think about cells.
+
+I sometimes find that we talk about self and then
+
+don't really think about what they are.
+
+So this is a sale, or at least if I
+
+had a blackboard, I would put it that this is
+
+a cell.
+
+What's distinctive about this thing?
+
+Anyone with a.
+
+Tell me.
+
+Or the.
+
+Wants to think about that.
+
+It's a regular.
+
+Thing.
+
+Regular.
+
+They will ignore that for the moment.
+
+What else is there?
+
+It's not so long.
+
+It's got a cell wall or a membrane.
+
+Exactly.
+
+It's got an inside and outside.
+
+It's basically a bag of stuff.
+
+Right.
+
+That membrane or cell wall, whatever you want to call
+
+it, which is a bunch of fats.
+
+Sometimes phospholipid is a little formula bag in which you
+
+stick stuff.
+
+And those phospholipids are really tightly bound and don't allow
+
+things to move across the membrane fairly impermeable to a
+
+lot of the things you think are important.
+
+So this bag means there's an intra or within cell
+
+and extra or outside cell space, three different spaces for
+
+two different things.
+
+And inside the cell is what we're kind of concerned
+
+about.
+
+Although to understand what's happening inside the cell, we have
+
+kind of also understand what's happening outside the shell.
+
+It's that's itself just a bag of spice.
+
+A bag of stuff includes the nucleus, includes, you know,
+
+the DNA and gene stuff and proteins and things like
+
+that.
+
+But in the end, it's a bag, this bag formed
+
+by cell membrane.
+
+The next thing is the science.
+
+A little bit of chemistry are not all in the
+
+same place.
+
+So, for example, throw mines which are described mainly outside
+
+the neurones in the extracellular space.
+
+Potassium, which is tonight confusingly with this K is mainly
+
+inside the cell.
+
+And calcium, which has two parts because it's lost to
+
+electrons, is also mainly outside the cell.
+
+Or the negative ions or anions.
+
+There's two different types we're concerned with generally.
+
+One is chloride, which is kind of an extra electron
+
+that's mainly outside the cell, and the other are proteins
+
+themselves.
+
+That's stuff that makes up our cellular machinery also usually
+
+in charge, and that's mainly inside the cell to do
+
+with the cell.
+
+So if we look at the cells or a few
+
+cells here, we would see that there are some anions
+
+and potassium ions within the cell.
+
+And then there's a bunch of calcium chloride and sodium
+
+floating around outside of.
+
+And so these different locations, special locations that these islands
+
+are really important because basically there's a gradient between the
+
+inside on the outside of the cells for the concentration
+
+of those ions.
+
+More potassium inside, more sodium outside.
+
+Those gradients of concentration set up.
+
+What are cold set up are the basis of the
+
+electrical potentials that we see in nerve cells.
+
+Now, if we go back to how we measure the
+
+activity of nerve cells of the electorate inside and outside
+
+of the cell.
+
+We find that actually, generally speaking, in fact, almost always
+
+these nerve cells are what we call negatively charged.
+
+They have a resting membrane potential that is in the
+
+absence of anything else of about -70 millivolts.
+
+Minus 70,000th of a vote.
+
+They don't seem like much, but it's a lot.
+
+It's enough.
+
+That negative potential.
+
+The difference between the insight into so and so the
+
+space is the basis for all of new single use
+
+signalling.
+
+And this the statement here is this show is polarised
+
+and it doesn't have the same inside and outside.
+
+So if the potential difference gets smaller, i.e. goes towards
+
+zero, so it gets to 60, we say the will
+
+be polarised, less polarisation.
+
+If it gets more polarised, it gets further way from
+
+zero, like the -80 with a hyper polarised, more polarisation.
+
+So this resting membrane potential, which I've argued, which I
+
+will argue is the basis of all our brain function,
+
+is actually the largest single sink of energy in the
+
+body.
+
+Most of the energy that your brain uses in your
+
+brain uses most the energy in your body towards keeping
+
+this resting resting memory potential at about -70 millivolts.
+
+So again, if we put the electrode from outside into
+
+the axon that we were seeing before, you see the
+
+potential go from 0 to 60 miles, 70 millivolts.
+
+The difference between the inside and the outside of the
+
+cell.
+
+As I explained, to try to explain, I encourage you
+
+to read about this.
+
+Way too many books on this many articles.
+
+You can have a thank you in much clearer way
+
+than I'm trying to do it now.
+
+This potential the rest of member States was a result
+
+of the difference in the ionic concentrations.
+
+So for example, sodium is more common outside the sodium
+
+inside itself.
+
+Potassium is more common inside the cells phone outside the
+
+cell.
+
+And the fact that that membrane so membrane, the fact
+
+that this is a cell is largely permeable to a
+
+lot of these ions.
+
+By impermeable I mean that those ions cannot easily cross.
+
+If I could easily cross half the sodium, we're going
+
+to be the inside of the outside the cell.
+
+And if there was no difference between the inside the
+
+outside.
+
+So the concentration of those ions, there would be no
+
+membrane potential.
+
+So the fact that this membrane, this bag is largely
+
+impermeable to ions is what allows the cell to set
+
+up this potential difference between the inside and outside the
+
+resting membrane potential.
+
+And then what you need is little things in those
+
+membranes, little holes, little pores that you can open and
+
+close to allow ions to flex across.
+
+Once you've made this bag, you then have to put
+
+new pinpricks in it and have it be controllable or
+
+something.
+
+And once you got those three things, the ability to
+
+control the flux lines across the membrane and this difference
+
+between the similar concentration and extracellular content of those items,
+
+you can make a cell.
+
+And they can help us so communicate.
+
+There is a little pump movie which has a on
+
+on the middle side, which I like to look at,
+
+which has an interesting take on this.
+
+I encourage you to look out when I say this.
+
+I mean what I was about for it.
+
+So I've already said the potential requires energy and is
+
+actually responsible most of the brain's energy consumption.
+
+And the reason for that is that there is this
+
+one particular set of proteins sitting in the cell membrane
+
+called the sodium potassium pump.
+
+So I described that there's a difference in interstellar concentration
+
+of ions that doesn't just arrive by chance.
+
+These loop pumps sitting in the membrane, exchanging, constantly changing.
+
+330 miles took them out, bringing through potassium mines, putting
+
+in.
+
+Thereby setting up these concentration gradients across the cell membrane.
+
+This little thing.
+
+This little thing uses adenosine triphosphate, which is the body's
+
+major source of energy.
+
+And it's consistently reactive.
+
+It's always growing.
+
+And that's why the rest of my body was sitting
+
+at 1780 volts.
+
+If it fails, you die.
+
+Having this resting membrane potential allows you to then form
+
+action potential.
+
+This slide looks a little bit complicated.
+
+Very straightforward.
+
+So let's go through if you haven't seen this before,
+
+but it is really straightforward.
+
+We've discussed there's a resting membrane potential about -70 millivolts.
+
+And I've discussed that.
+
+That's not very.
+
+Imagine that there is a little input within you on
+
+the cause of that resting membrane potential to deviate a
+
+little bit.
+
+Go towards zero depolarise.
+
+This little.
+
+Sometimes I just love it.
+
+Yeah, because sometimes it is a critical point that mine
+
+is 6365 millivolts.
+
+At which.
+
+What are called voltage gating.
+
+Gated sodium channels are opened.
+
+Now that voltage gated means a particular voltage potential difference.
+
+At which these channels are open.
+
+Otherwise, they closed the when they closed the bags to
+
+the bag with the bag suddenly permeable to throw mines.
+
+Over 30 mines have been sitting outside for sale.
+
+You open this lock.
+
+Suddenly they can go into the cell.
+
+You have a bunch of positively charged demands and flexing
+
+to sell very rapidly.
+
+There are thousands of these channels in the membrane.
+
+Millions of.
+
+All these 30 mines really rapidly rush into the cell,
+
+overwhelming everything else, all that positive charge that comes with
+
+them depolarise it even further.
+
+So you can see here, which is route threshold, a
+
+threshold is open these channels that allows the sodium to
+
+come in and suddenly the cell's potential difference changes dramatically.
+
+It goes back to there and often overshoots because if
+
+too many of these 30 mines come in.
+
+At some point in time, those towns can close again.
+
+Oh, that's not.
+
+Then stuff allows the to return back to resting potential,
+
+in particular the influx of potassium ions.
+
+Also the active action of that 30% pump.
+
+So you have this low threshold offer which is exceeded.
+
+You have this massive in your arms and then a
+
+relaxation back to the basic steady state.
+
+And that is an actual potential.
+
+That's all it is.
+
+Basically, it's transient in Russia, 30 miles.
+
+It's just been get switched on.
+
+Very simple.
+
+But incredibly important because this is what we mean by
+
+this has been excitable.
+
+So if you can and you can make them.
+
+Produce listings.
+
+Does anyone know what the other major example?
+
+Selling bodies.
+
+My muscle cells.
+
+Yeah, muscle cells.
+
+So muscle cells contract because of a very similar flux
+
+of ions based on calcium in this case.
+
+So that movement of muscles, which I've never had, actually
+
+the filaments all work together, driven by this transient change
+
+in the calcium and potential calcium fox.
+
+The brain cells are very much like that, except faster
+
+and different ions.
+
+And different connections.
+
+Clearly they don't move.
+
+I mean, there's a lot of differences between.
+
+By the way, those voltage sodium channels will be blocked
+
+by something called tetrodotoxin or ctcs, often abbreviated because no
+
+one can actually save it for the toxin.
+
+I have to practice for 5 minutes before coming.
+
+You say Dax's neurotoxins about 1000 times more potent than
+
+cyanide.
+
+It blocks those voltage settings.
+
+Of course, if you block this into account for maximum
+
+potential, if you can't perform actual controls, you can't move
+
+your muscles, including your diaphragm.
+
+You can't breathe.
+
+You know.
+
+So that's why Fuku or Pufferfish has been prepared so
+
+carefully, because actually those fish are large source of so.
+
+If you prepare them incorrectly, you'll consume a little bit
+
+of that.
+
+And that's enough to stop your breathing and make it
+
+on.
+
+Blocking the voltage gate to certain terminals is also how
+
+local anaesthetics were very similar.
+
+They stop.
+
+Therefore the sensations from that part of your body.
+
+We have an injection in your arm, for example.
+
+You feel strange absence of sensation as from there, because
+
+the sensory neurones which rely on these certain channels are
+
+not sending the signals anymore.
+
+Now, this what?
+
+Angular?
+
+Slightly different.
+
+So painkillers generally, a lot of painkillers are based on
+
+morphine analogues.
+
+And morphine analogues.
+
+Opioid receptors for morphine, as we've discussed, actually makes it
+
+terrific targets opioid receptors that opioid receptors are really important
+
+to controlling breathing, but they're not actually important in the
+
+regulation of.
+
+As a generation.
+
+Yeah.
+
+Yeah.
+
+What?
+
+Isn't it?
+
+Yeah, well, technology is much more powerful than any local
+
+anaesthetic.
+
+Use The local anaesthetic has been designed to kind of
+
+only work in that slight place.
+
+Referred to a toxin.
+
+Generally speaking, it's consumed and therefore systemically, rather than just
+
+being consumed.
+
+At some point it's very apparent.
+
+Yes, you shouldn't treat like McCain or other local anaesthetics,
+
+like they're being perfectly designed to actually overcome these issues.
+
+They just work in a kind of similar way.
+
+Local versus.
+
+Yeah.
+
+What?
+
+They get cleared out and diluted effectively by the system.
+
+Any other questions?
+
+The.
+
+Just take time.
+
+Okay.
+
+I was going to do this interactive thing, which I
+
+think I've got to wait till next lecture because this
+
+is reminding me how long lectures actually take action potentials
+
+move along that move to the sciences and that little
+
+action potential.
+
+They've been describing all that process, initialisation that takes place
+
+in a place called the Action Hillock.
+
+This is the bit where the action beach itself, on
+
+a blue and a V-shaped thing will be incredibly special
+
+specialised be the membrane.
+
+Recent work by some colleagues in the Netherlands have shown
+
+that the density of the sodium channels is only 37
+
+channels in the axon hill.
+
+It is ten 100 fold greater than anywhere else in
+
+the neurone.
+
+They really important for generating the action potential.
+
+But once the action generated, why is it?
+
+How does it work?
+
+You've got this accent, which is maybe a metre long.
+
+You've got this little bit of membrane potential happening, this
+
+little bit of membrane just where the accent meets the
+
+sun.
+
+For neurones, a signal that explains how to leave the
+
+Soma and get to the end of the axon.
+
+And it does that by a very simple process, which
+
+is basically regeneration.
+
+So if you get an affinity for forming this little
+
+bit of the membrane here.
+
+In the neighbouring little bit of membrane has a little
+
+bit of a deflection.
+
+Depolarisation.
+
+And then that starts the cycle of the action potential
+
+again.
+
+That neighbouring bit of membrane that happens here and and
+
+happens here, it's turning off.
+
+It happens here.
+
+It happens to propagates down the axon.
+
+If you think about it carefully, can imagine it can
+
+happen both ways.
+
+That is actually the case, actually potentially can go from
+
+not only into the action, but also the dendrite.
+
+It's a very deconstructive that's on the table.
+
+That means that that's the way we think the signal
+
+progresses.
+
+Little regenerating action potential.
+
+Somehow manages to depolarise this little bit of membrane and
+
+move along that membrane.
+
+What an amazing thing that we evolved.
+
+Now, if you just left it to his own device
+
+to travel down that piece of membrane, probably through about
+
+a metre a second, some general speed for a potential
+
+move down a bit of an.
+
+And insulated membrane.
+
+That's a bit slow.
+
+One second.
+
+You know something?
+
+Hit me.
+
+Like.
+
+So a lot of the major axons in the body
+
+and some of the direct forms in the brain are
+
+in chief.
+
+Myelin with myelin is basically just like wrapping insulating tape
+
+around the acronym.
+
+Stop the actual potential for really from generating at that
+
+point and instead allows maximum potential from this position to
+
+jump across the next note of review.
+
+And so instead of just slowly moving along, it takes
+
+massive, long strides down the axon.
+
+It can speed up transmission tenfold, at least.
+
+Yeah.
+
+Is it likely that people like the signal won't reach
+
+from one?
+
+Like some of the others.
+
+So that's the danger, right?
+
+The mine was too long.
+
+So the question was, isn't there a danger that the
+
+little depolarisation here doesn't reach the next note?
+
+I think of what you are.
+
+And so clearly that's a danger.
+
+So that bit of myelin can't be too long.
+
+Yeah, there has to be critical distance between the two
+
+nodes above which we just to the actual would not
+
+propagate.
+
+At the moment.
+
+She's really important in speeding up production in Europe.
+
+Okay.
+
+I'm going to have to move along.
+
+So we'll just keep by the way, at the end,
+
+later.
+
+I think we're meant to leave this door and I
+
+will wait out there if you have additional questions for
+
+me so that people can come in once we're doing
+
+now.
+
+This is how I think an action potentially works.
+
+Music, all the dinosaurs.
+
+I think anyone ever tried to do this at home.
+
+Right.
+
+Good old school.
+
+Yes.
+
+Okay.
+
+Now, why am I using this analogy?
+
+I made the point before because it was quite impressive
+
+one.
+
+I like to think of that can pretend to be
+
+an asleep and then it gets to some point and
+
+triggers the ball ball moving towards the pocket.
+
+Right.
+
+By the way, this keeps going.
+
+I think this entire video is actually.
+
+What's that.
+
+Is the ball you're.
+
+Tracking?
+
+Yeah.
+
+We'll get there in a second.
+
+So the ball.
+
+The ball, Yes.
+
+Is a basically neurotransmitter.
+
+The pocket is supposed to be cleft.
+
+Let's see if we can understand those statements.
+
+Pretty impressive.
+
+I mean, I'm glad they caught on video.
+
+You can imagine.
+
+So we'll get to that right now.
+
+So bear that in mind.
+
+That's how I think of neurones.
+
+Okay.
+
+So each of these acts on this axon is a
+
+single axon, but it sprouts.
+
+Multiple contacts with the same and about thousand on average,
+
+I think.
+
+Multiple contacts, multiple output points.
+
+So what's happening in each of those Apple points?
+
+That's the question.
+
+So this is a couple of schematics which try to
+
+illustrate to you what it looks like.
+
+Each of these outputs in this case is what we
+
+would call an access somatic finance assignment between the Exxon
+
+and the Soma.
+
+You can also have accident reading between acts on the
+
+dendrite.
+
+This is actually somatic signups.
+
+So if you look on the left, you have this
+
+line at the end of the tunnel, good on the
+
+axon coming to the cell.
+
+We look in there.
+
+This is what it looks like, the green thing here.
+
+That's the sign at the end of the axon.
+
+And over here, that's the post traffic sign personality.
+
+So after the sign ups.
+
+The sign up is actually this whole thing together, the
+
+presynaptic, postsynaptic.
+
+And in between this thing we call the synaptic cleft.
+
+About 20 nanometres in size.
+
+Really?
+
+Really.
+
+Molecules can actually diffuse across that little cleft.
+
+And quite rapidly less than a millisecond.
+
+So if an accent comes down.
+
+That's right.
+
+I can take what comes down this axon.
+
+It enters this sinus presynaptic space.
+
+When it does that, it actually causes the influx of
+
+calcium ions.
+
+Don't worry too much about that.
+
+The presence of calcium.
+
+Causes these little bags, which we're going to call critical.
+
+Wilbanks Within bags or bags?
+
+Within bags, through bags to move towards a membrane presynaptic
+
+membrane.
+
+So this bag contains a little bunch of neurotransmitters, a
+
+particular chemical.
+
+That bag growth was a membrane binds with the membrane.
+
+Cause a little gap in the membrane to open up
+
+the bags of neurotransmitter.
+
+So the neurotransmitter then crosses into the sign of a
+
+cleft.
+
+What is in the Senate declared didn't go anywhere.
+
+But a lot of it goes to the other side
+
+of the cliff and on the other side of the
+
+Senate to propose an epic membrane of things we call
+
+neurotransmitter receptors.
+
+The proteins within the person.
+
+I pick my brain, which are designed to receive these
+
+neurotransmitter signals.
+
+Yeah, I do.
+
+So not supposed to be able to do drugs.
+
+Good question.
+
+I don't know the answer to that.
+
+Look it up.
+
+I mean, this is not a passive process.
+
+There's an active process here.
+
+I'm not exactly sure how to go about coming from
+
+it.
+
+It's a good question.
+
+If we look at the electron microscope picture, this is
+
+a real Darnold schematic.
+
+On the left is a high as a relatively high
+
+power.
+
+This sort of a sign ups in this case is
+
+connected and really connects to the dendrite and the axon.
+
+You can see all these little bags.
+
+These this is what we call a postsynaptic density.
+
+That's a that's the way you can recognise these sign
+
+with an electron microscope.
+
+And there's these bags that kind of near this.
+
+And we looked at this and even more detail we'd
+
+see here these bags, some of which are binding with
+
+the membrane, allowing the neurotransmitters to enter synaptic cleft.
+
+What happens when a neurotransmitter enters unhappy cleft?
+
+On the other side, you have these neurotransmitter receptors.
+
+Each of these are designed to be sensitive to one
+
+or very small number of molecules.
+
+When that molecule wanders across the crest of bonds, this
+
+protein that spans the postsynaptic membrane.
+
+That protein undergoes what we call inflammation, trying to change
+
+the shape.
+
+When it changes shape, it creates a pour in the
+
+membrane, when it creates that pore in the membrane.
+
+IONS In fact, through the membrane.
+
+So, for example, glutamate, which we call an exaggerated neurotransmitter,
+
+a lot of its receptors which bind glutamate, open up,
+
+allow sodium lines to flex across the membrane for 30
+
+lines, are positively charged.
+
+That polarises the person.
+
+I think so.
+
+Gabba.
+
+Gabba Gabba Gabba is an inhibitory neurotransmitter because its receptors,
+
+generally speaking, open up a loophole that allows corridor lines
+
+to cross the membrane of Florida ions and negatively charged
+
+that are hyper polarised so they inhibit activity.
+
+Deconstruction of these receptors might be sensitive to a particular
+
+type of neurotransmitter and allow particular type of ion to
+
+cross the membrane.
+
+These are called iron or tropic receptors because they directly
+
+flex the lines of the membrane in the neurotransmitter.
+
+There are another class of neurotransmitter receptors which we will
+
+encounter in the next lecture called metabolic Tropic.
+
+They rely on post processes inside the postsynaptic cell that
+
+in turn called the flux lines.
+
+I don't really open pore in the membrane.
+
+I just want to spend 2 minutes playing them.
+
+Why?
+
+These are important.
+
+If you imagine glutamate and GABA, imagine a neurone here
+
+which has three sign ups, two green, one red green
+
+sign ups as we're going to call glutamatergic sinuses.
+
+That is glutamate is released to the presynaptic space causes
+
+the membrane synaptic membrane.
+
+The other sign ups is a inhibitory neurone.
+
+It's a sign.
+
+It uses GABA release from release from prison up in
+
+space.
+
+Causes a cleft or the postsynaptic membrane.
+
+So this neurone has two glutamatergic finances and one refinance.
+
+As I said before, government allows positive ions into the
+
+next year.
+
+So they polarises.
+
+The person I think you're on is that it allows
+
+negative ions.
+
+I almost imagine the sequence of events over several milliseconds
+
+here.
+
+Whereby one of those finances is active, government finances is
+
+active and therefore allows a small excited person, active potential
+
+dps p small depolarisation away from the rest and the
+
+potential towards the threshold for activation of certain channels.
+
+Now that may not be sufficient to reach that threshold,
+
+but if you have the two sign ups as active,
+
+then you might increase that threshold allowing that neurone to
+
+generate an action potential.
+
+On the other hand, for example, inhibitory signups, since everyone
+
+here would continue on to operate away from the resting
+
+potential, or if you activate that inhibitory sign at the
+
+same time as to group protected classes, effectively cancel out
+
+one of those two glutamatergic sign ups, therefore stopping the
+
+neurone from firing.
+
+So these little neurotransmitter receptors in these different sinuses allow
+
+this neurone to compute.
+
+If it crosses the threshold, the signal crossed threshold for
+
+an action potentially only crosses the threshold if the neurones
+
+input in have enough inputs.
+
+And that exactly input outweighs the inhibitory input.
+
+There is a simple algebraic computations.
+
+He says what in your and does?
+
+It sums to hundreds and thousands of inputs that it
+
+gets to ten drives to produce a single number of
+
+the axon hillock which says Am I above or below
+
+the threshold for generating maximum potential?
+
+And then sends that signal number one or zero down
+
+to the axon terminals.
+
+That is the fundamental computation of frame systems is what
+
+allows us to see allows us to think of what
+
+allows us to hear, for example.
+
+And that is the fundamental point I want you to
+
+take away from this lecture.
+
+All little chemical transmitters, etc. allow these neurones to perform
+
+simple functions to some eight inputs.
+
+But those when you cross those functions, make them hierarchical,
+
+as we'll discover in the later lectures.
+
+You can now build into that.
+
+Interesting.
+
+But it all relies on this very simple process.
+
+One last question.
+
+What decides what your interests?
+
+That's a great question and we'll get back to that
+
+in the next lecture, actually.
+
+So the question is, which neurotransmitter has been expressed by
+
+the presynaptic, Kiran, that makes it exciting or inhibitory?
+
+And the answer to that is very complicated and has
+
+to do with evolution and genetics and everything else.
+
+But it will get back to the major point that
+
+one expects.
+
+All right.
+
+Thanks, everyone.
+
+If you can leave by this time.
+
+You.
+
+I now feel less nervous.
+
+It's a great warming up at the believe through here.
+
+I'll wait out there if you have any questions as
+
+well.
+
+Thanks.
+
+Yeah.
+
+I just want to be very aware of the network.
+
+Right outside of the other.
+
+Networks.
+
+Thanks.
+
+So.
+
+Yeah.
+
+I'll be out there and checking out.
+
+What is.
+
+If we had questions, if we just wait outside for
+
+the people to come in and we'll be out there
+
+and giving.
+
+All right.
+
+Those questions.
+
+Do we just wait out?
+
+Oh.
+
+Humphrey with the math right now, I.
+
+We see it in the summer.
+
+But yes, I've.
+
+Yes.
+
+It'd be great to chat with you guys.
+
+I think they're going to try to.
+
+I forgot how long it takes.
+
+I have this whole exercise.
+
+If you can actually help me out.
+
+I didn't like.
+
+Yeah.
+
+You can just follow me outside, then.
+
+That's fine.
+
+No, I'm sorry.
+
+Let me just check to make sure.
+
+Think.
+
+Okay.

raw_transcripts/lecture_4.txt

@@ -0,0 +1,2743 @@
+A quick.
+
+Poll.
+
+I have three clocks here.
+
+It has very different times.
+
+My my phone says 10 a.m..
+
+The U.S. system says 10 to 10.
+
+The other one says ten.
+
+What time do you have a ten?
+
+Okay, if I.
+
+A bit.
+
+I really need those of you at the back to
+
+tell me if I lapse into a little bit of.
+
+An.
+
+Indecipherable must I load.
+
+Myself up with a bunch of.
+
+Anti cough medicine stuff?
+
+Since I last saw you on Monday?
+
+I've had a bit of a cold, and when I
+
+get congested I tend to speak a bit more quietly.
+
+So please do tell me if you can't hear me
+
+right.
+
+And that was all a bit of a lead in
+
+to this lecture's title.
+
+It says Neurotransmitters, but which I like to think of
+
+as why do drugs work in other parts and discipline.
+
+This might be called psychopharmacology, which is the idea that
+
+specific neurochemicals.
+
+Specific chemicals have.
+
+Specific effects on.
+
+Brain systems.
+
+And we want to try and understand some of that
+
+today.
+
+As I said, if I.
+
+If I'm not audible at the back.
+
+Please let me know.
+
+I'll just try and speak louder.
+
+I just can't get much feedback myself.
+
+At the moment.
+
+So I want to frame this lecture around cocaine.
+
+Cocaine was first arrived, at least in Western societies about
+
+150 years ago, being used for many years in the
+
+South Andes, for example, as a stimulant for workers in
+
+the high out alpine regions.
+
+When brought to Europe, the.
+
+Drug was first used as a.
+
+Local anaesthetic.
+
+We won't be going into its local anaesthetic properties at
+
+all and was initially in the hopefully as a hopeful
+
+treatment for morphine addiction soon, however attracted widespread recreational use.
+
+But if you look.
+
+At the old advertisements, you say lovely, you know, it's
+
+a sociological lesson lesson in the in the the value
+
+of different substances.
+
+This is an advertisement for.
+
+The.
+
+Cocaine basically as a local anaesthetic for your teeth.
+
+Again, toothache drops really.
+
+You know there's a lot of tooth problems back in
+
+the day then, you know, things got a bit darker
+
+study in scarlet you know, cocaine addiction, cocaine, the thrill
+
+that kills this is now mid century.
+
+And we're really heavily into the period of time where
+
+drugs were really frowned upon.
+
+And then more recently, of course, if you follow Netflix,
+
+ET cetera.
+
+There's a whole profusion of things about drug trade.
+
+But the question I want.
+
+To address here is why does cocaine have its psychoactive?
+
+Not It's like my anaesthetic for the psychoactive effects.
+
+Oh, that's a a device.
+
+I didn't.
+
+Know what that.
+
+Was.
+
+I wonder if it works.
+
+For me.
+
+Now.
+
+There's evidence.
+
+I'm here.
+
+Okay.
+
+I was wondering what that sound was.
+
+It was very disturbing.
+
+Okay, so the question is, why does cocaine change behaviour?
+
+And I'm going to give you a very simple neurochemical
+
+answer in a second.
+
+And then the aim of this lecture is effectively to
+
+break down the sentence.
+
+And the sentence is that cocaine has its effects because
+
+it blocks the re uptake of the neurotransmitter dopamine after
+
+its release.
+
+And it's finance, not just any old sign ups, but
+
+a sign ups.
+
+And by the end of this lecture, I what.
+
+I hope to help you understand is what we think
+
+is what neurotransmitters are.
+
+And anyway.
+
+Why does it have a specific effect?
+
+I still find it striking that so many of these
+
+drugs, these psychoactive drugs, LSD and etc..
+
+Have such specific cognitive effects.
+
+When you just smoke them, inhale them, eat them, whatever.
+
+They get into your bloodstream, they somehow get to your
+
+brain.
+
+How is it these chemicals can have such a specific
+
+cognitive effect when the brain is so exquisitely wired to
+
+help us do things?
+
+This dissonance between.
+
+The global kind.
+
+Of potential effect of cocaine and its specific actual effects
+
+is what I hope to try and get through to
+
+you today as.
+
+Well.
+
+It's really it's an annoyance.
+
+And so, as you all know, you can ingest some
+
+drug in many different ways.
+
+This graph just simply serves to illustrate that the concentration
+
+in the blood.
+
+Depends on the route of administration, as does the time
+
+course.
+
+I don't want to take too much away from this.
+
+The point being that there is.
+
+Quite a.
+
+Significant change in the blood concentration that lasts for a
+
+while.
+
+Then at some point in time that concentration falls below
+
+this threshold level.
+
+For.
+
+Effect.
+
+So before and after ingestion to have an effect when
+
+when the concentration exceeds a particular level.
+
+The other.
+
+It's going to be a few definitional slides in this
+
+lecture because really setting you up for the rest of
+
+the lectures, we need to.
+
+Make sure that you are all on.
+
+Board with the kinds of phrases that we might.
+
+Use.
+
+Many drugs, too much drugs, something what we call a
+
+dose response curve.
+
+That is what we call sigmoid function typically looks like
+
+this.
+
+On the x axis is the drug dose of.
+
+The drug going from low to high.
+
+On the Y axis is the effect of that drug,
+
+whether it be on behaviour or on a specific neurochemical
+
+systems.
+
+And you can see that again, as you increase the
+
+dose of a drug, you might expect to see an
+
+increase in the effect of that drug, which then saturates
+
+afterwards.
+
+Increasing the amount of drug in the system doesn't have
+
+any further effect.
+
+And the reason for that, that saturation is.
+
+Because at some.
+
+Point in time this drug is basically.
+
+Occupying all the.
+
+Potential sites it might have in.
+
+The brain.
+
+Again, this is the idea of a threshold that below
+
+this particular concentration you won't be able to experience or
+
+at least be able to detect the effect of those
+
+substances.
+
+The other thing you should.
+
+Be aware.
+
+Of is that drugs can have multiple effects on different
+
+systems in the body and in the brain.
+
+So, for example, many of you may be aware.
+
+That the drug.
+
+Morphine, which is an agonist of opioid receptors in the
+
+brain.
+
+It's both important for pain relief.
+
+It's why it was developed or it was used.
+
+But at higher doses, it can lead to arrest of
+
+breathing and death.
+
+And the reason for this is that if you look
+
+at the dose response curves for the drug in the
+
+two different behavioural effects, that is the pain relief on
+
+the left and the yellow.
+
+Any effect on breathing on the right?
+
+In the blue you see the different regimes, different concentrations
+
+of the drug are appropriate.
+
+In the two cases.
+
+So there is a margin of safety where you might
+
+be able to have an energy equal pain relief effect,
+
+but you won't have any impact on breathing.
+
+Now, the actual reason.
+
+The major reason for this in this particular case is
+
+illustrative of all drugs.
+
+Is that the type of receptor for morphine that's present
+
+in the brain?
+
+Again, we'll get there in a second.
+
+But the type of the receptor that the present in
+
+the pain system is a slightly.
+
+Different type of receptors and that is present in the
+
+breathing.
+
+System.
+
+And the.
+
+Two receptors have slightly different sensitivities.
+
+To morphine.
+
+And so therefore.
+
+As you increase the dose of morphine, you get more
+
+effect on one of the systems before we get an
+
+effect on the other system.
+
+So the idea that you can have these different effects
+
+at different concentrations relates.
+
+To the fact that different.
+
+Receptors for this.
+
+Agonist have to be found in the brain systems.
+
+Okay.
+
+So the major as I said, the major question I
+
+want to ask in this lecture is why do these
+
+drugs work at all?
+
+I want to put to you a thesis that the
+
+drugs that we are interested in usually act.
+
+At the sign ups between neurones.
+
+I want to suggest that they usually have their.
+
+Effect by changing the strength or duration.
+
+Of activity.
+
+Of particular neurotransmitter systems.
+
+In those same lapses.
+
+And I want to suggest that it's possible for.
+
+Drugs to.
+
+Ingest, to have a systemic.
+
+Administration ingested.
+
+Injected.
+
+Digested, etc..
+
+Have a specific effect because they activate specific pathways of
+
+neurones.
+
+Through the brain.
+
+And we'll go.
+
+Through a few of those pathways at the end of
+
+this lecture.
+
+That is, each of these pathways has a particular neurochemical
+
+signature.
+
+And to try and illustrate that, I want to.
+
+Help you understand how neuroscience has changed since I started
+
+as an undergraduate student.
+
+And now this is a photo, I think.
+
+It was about ten years old, this.
+
+Photo now.
+
+But at the time it was revolutionary.
+
+For me.
+
+This photo is a black.
+
+And white version.
+
+It is a is an image of a slice taken
+
+through the hippocampus of a mouse in the hippocampus.
+
+It's a beautiful structure.
+
+And it has this really dense layer of cells.
+
+Called the principal cell layer.
+
+And you can see at high magnification these cell lines
+
+here.
+
+So each of these little pyramidal shape things is one
+
+of the nerve cells in the perimeter, in the principal
+
+cell.
+
+And all these little processes up here that dendrites do
+
+coming off.
+
+Now, when you first when.
+
+When histology synonymous with first looking at the hippocampus.
+
+First, these cells looked.
+
+Identical to them.
+
+However, recent.
+
+Technologies, for example, by being able to genetically manipulate a.
+
+Mouse.
+
+Have allowed researchers to insert little proteins into cells, the
+
+expression of which.
+
+Depends on the particular types of neurochemicals that those cells
+
+produce and those.
+
+Proteins in turn for when you stimulate them with light.
+
+And so what.
+
+You can what seem to be a relatively homogenous mass
+
+of cells in the hippocampus, for.
+
+Example.
+
+Is now much, much more clearly.
+
+Now a really diversity of cells.
+
+Each of which has a different neurochemical signature.
+
+And I want to outline this to you, particularly because
+
+even in my lifetime there's been a massive change in
+
+what we understand about the specificity of pathways in the
+
+brain because of these kinds of techniques.
+
+So a lot of what I am going to tell.
+
+You is probably going to be out of date in
+
+ten or 15 years as we.
+
+Learn more and more about.
+
+The specificity of those systems.
+
+Okay.
+
+So in the next section, we're going to talk about
+
+how we define neurotransmitters and your modulators.
+
+We've discussed two major neurotransmitters.
+
+In the last.
+
+Lecture, those GABA.
+
+And glutamate.
+
+And I alluded to the fact that there are many
+
+other neurotransmitters, just to remind you of assign naps and
+
+what neurotransmitters do.
+
+This is a sign ups the presynaptic space here in
+
+green, the post and haptic membrane here.
+
+Someone pointed out in the last lecture this line is
+
+point in the wrong place.
+
+It should actually be pointing to the presynaptic membrane here.
+
+These are little bags of vesicles of neurotransmitters that have
+
+docked at the presynaptic membrane and release the.
+
+Contents into space.
+
+For these neurotransmitters.
+
+Can cross that little space to sign acting cleft and
+
+have an action on receptors at the person action membrane.
+
+So that's the sign ups activated when an action potentially
+
+invades that sign.
+
+So there's been a lot of discussion for many years
+
+now.
+
+About what neurotransmitters are and which substance we might like
+
+to call neurotransmitters.
+
+It seems like a pretty easy question to ask, but
+
+actually.
+
+It's tremendously difficult.
+
+And the reason for this is that there are many
+
+chemicals that are released in the brain.
+
+And whose release depends on the activity of neurones.
+
+But not all of those chemicals.
+
+Actually act as something that transmits.
+
+Information from one neurone to another.
+
+They're not really.
+
+Neurotransmitters.
+
+Neurotransmitters.
+
+The idea.
+
+In the name is helping.
+
+Transmit signals.
+
+From one to another.
+
+A lot of his.
+
+Chemicals might be released as.
+
+By-products of just simply.
+
+Stopping active or clean up.
+
+Processes and stuff like that.
+
+So we have to define what a neurotransmitter is.
+
+And there's a fairly generally agreed definition now that I
+
+think 40 years old, which is it's stated here, neurotransmitters
+
+are those molecules that are made and stored.
+
+By the presynaptic.
+
+That's the.
+
+Neurone who sign up to these.
+
+Is a putting this cosmetic membrane, the prisoner.
+
+So that neurone has to make and store that substance
+
+that's kind of important to that neurone.
+
+So it's making and.
+
+Storing.
+
+That substance is released.
+
+At the presynaptic terminal.
+
+When that terminal is activated, that doesn't make any sense.
+
+If you have a substance that's being just released.
+
+All the time because it's not going to be able
+
+to transmit any information, its release level won't depend.
+
+On the activity.
+
+Of the neurones.
+
+This neurotransmitter has.
+
+To be its release has to be dependent on the
+
+activity of the presynaptic.
+
+And finally, it seems a bit of a.
+
+Of course, but that substance has to have an effect.
+
+On the postsynaptic.
+
+Near as I said before, there are many chemicals in
+
+the brain that are.
+
+Released at the when neurone is active.
+
+But not all have effects on person.
+
+I think neurones and therefore not all transmit information.
+
+To those neurones.
+
+Similarly, we can define a neurotransmitter receptor as molecules that
+
+are activated by them.
+
+So there's many proteins.
+
+In the cell membrane.
+
+All of those are activated by a neurotransmitter.
+
+So they need to be activated by a.
+
+Neurotransmitter.
+
+And they need to be able to change.
+
+The flow of ions, either directly or indirectly.
+
+Into.
+
+The person active.
+
+So as we discussed in the last lecture, sodium chloride
+
+ions are the primary mechanisms that.
+
+Finds use in this.
+
+Process.
+
+I want to note here that each neurotransmitter may have
+
+several receptors.
+
+As we discussed before, the morphine.
+
+Morphine has multiple opioid receptors.
+
+And each.
+
+Neurotransmitter may.
+
+Have several receptors which express some different neurones.
+
+Sometimes even in the same neurone, unfortunately.
+
+And may be different.
+
+Be sensitive to the neurotransmitter again by analogy to the
+
+morphine thing.
+
+Breathing is affected at one concentration of the neurotransmitter, whereas
+
+pain is effectively another concentration.
+
+Because the receptors for morphine are different in those two
+
+cases.
+
+I've said before, but I'm just going to reiterate because
+
+we do tend to focus on the other neurotransmitters, but
+
+the major neurotransmitters in the brain are glutamate.
+
+And it's some people who think that every.
+
+Neurone in the brain is sensitive to the expression of.
+
+Glutamate, and that is it has.
+
+Sinuses, closing spaces that express receptors for glutamate and GABA.
+
+It's not the case that all neurones in the brain
+
+express or make glutamate.
+
+Think about.
+
+It.
+
+If you look at the cerebral cortex, for example, we
+
+find that about 80% of the neurones in the cerebral
+
+cortex express or make the neurotransmitter glutamate, and they send
+
+back neurotransmitters to the neural.
+
+Whereas 15 to 20%.
+
+Of those Neurones Express and gather and send that one
+
+the person.
+
+If you have a think about that, that seems a
+
+little bit strange.
+
+It's such an imbalance between the amount of neurones.
+
+That produce excitatory neurotransmitters, any amount of neurones that produce
+
+inhibitory neurotransmitters.
+
+Because wouldn't that mean that the brain.
+
+Is hyperactive time?
+
+It's not actually the case.
+
+Indeed, the average.
+
+Number of spikes to.
+
+The neurone, the cerebral.
+
+Cortex.
+
+Every step of.
+
+Action, potential neurone, several cortex produces every second is about
+
+one.
+
+That means, you know.
+
+Several billions.
+
+I think, that were being produced in your brain every
+
+second, but only about one of those per year.
+
+And the.
+
+Reason for that is that the.
+
+Actual.
+
+Inhibitory surface to surface in cerebral cortex acts as the
+
+principal surface.
+
+In addition to these two major classes of neurotransmitters, there
+
+are many other.
+
+Putative and identified neurotransmitters.
+
+And indeed.
+
+This list would change next year because again.
+
+Every year it seems that we identify.
+
+Another chemical as a putative single neurotransmitter in the brain.
+
+The major ones that we would talk about today acetylcholine.
+
+Dopamine, serotonin and noradrenaline.
+
+But you should also know that there.
+
+Are a bunch of other ones.
+
+Including what are called neuropeptides loop proteins, effectively the active
+
+neurotransmitters.
+
+Also nitrous oxide purines endocannabinoid.
+
+Which is the target of THC.
+
+So there's a lot of other ones is thought.
+
+There for a reason.
+
+There's at least 20 or 30.
+
+Substances or neurotransmitter at the stage and as I say,
+
+more being.
+
+Discovered each year.
+
+And then I would define for you what neurotransmitter uptake
+
+means.
+
+So one thing we talked about in the last lecture
+
+is that these neurotransmitters.
+
+Get released into the.
+
+Sinuses.
+
+And the synaptic cleft.
+
+And if you think about it, if they just hang
+
+around there, they just continually.
+
+Activate the person at the exit.
+
+They're bound to the person that's receptors.
+
+Causing ions.
+
+To flow into the postsynaptic neurone, and that pretty well
+
+renders those sinuses useless.
+
+So they can't change the.
+
+Information that the signalling becomes stopping.
+
+Stop and stop and stop.
+
+It is always active.
+
+So we have to get around that some way.
+
+We have to clear that out.
+
+Of the fine, finance those neurotransmitters.
+
+Resetting the.
+
+Science so that can continue to signal more than new
+
+information.
+
+And that's what these re uptake, so-called re uptake mechanisms
+
+are.
+
+There's many of them I don't even know these in
+
+complete detail.
+
+But you won't be able to see much of the
+
+things on this slide.
+
+But if you look at the presynaptic neurones releases the
+
+neurotransmitters into synaptic, they cross the postsynaptic neurone.
+
+And you remember that around these sign ups is.
+
+As we discussed in the last.
+
+Slide, also these glial cells and.
+
+Other forms of non neuronal cells.
+
+It turns out.
+
+These re uptake mechanisms.
+
+Can be found at.
+
+Of those three signs.
+
+The glia actually have very important vacuums.
+
+For this to suck up a lot of the neurotransmitters
+
+and listening to the assignments resetting that so that.
+
+Some of the neurotransmitter gets for some reason.
+
+Unknown to us absorbed into the postsynaptic and some of.
+
+The neurotransmitters get reabsorbed.
+
+And that makes more sense.
+
+But then you can repackage that neurotransmitter.
+
+If you want.
+
+Into another.
+
+Basically, we use that neurotransmitter.
+
+So these people, transporters which take neurotransmitter across the cell
+
+membrane into one of these three cells and out of
+
+this line ups is basically the re uptake mechanism.
+
+This these kind of rehab mechanisms exist for most, if
+
+not all, of the neurotransmitters.
+
+And we'll be.
+
+Discussing the specific one for me, which is important for
+
+the effects of cocaine towards the end of the lecture.
+
+There's a few other terms I need to help you
+
+understand.
+
+It's one that you see a lot in the literature
+
+is these two words agonist and antagonist.
+
+And unfortunately.
+
+These words get.
+
+Used in.
+
+Very different ways by different.
+
+Literatures.
+
+So just trying to accommodate them into some sort of.
+
+Synthesis here for.
+
+You to help you understand.
+
+And agonists can be thought of as a drug that
+
+increases the effect of a neurotransmitter.
+
+Whereas the antagonist is a drug that decreases The New
+
+York Times.
+
+Generally speaking, an agonist that increases the.
+
+Effect of the neurotransmitter.
+
+Does so by increasing production.
+
+Or storage of the your.
+
+If you're making more of it, that's a pretty significant.
+
+You've got more.
+
+To give.
+
+You sign ups.
+
+Or it could increase the release of neurotransmitter.
+
+You've already got enough there, and now you're sending more
+
+fans of this food to the.
+
+Membrane to release.
+
+Into the finals.
+
+Or you could stop.
+
+The New York Times would have been clear so you
+
+could alter those reuptake.
+
+Transporter mechanisms.
+
+Or you could actually.
+
+Bind.
+
+Directly to the.
+
+Postsynaptic.
+
+Receptors as if you.
+
+Were a neurotransmitter and activate those postsynaptic receptors.
+
+So there's multiple ways.
+
+Of increasing the effect of neurotransmitter in the brain's.
+
+And you can do basically the.
+
+Opposite for an antagonistic.
+
+Effect.
+
+The next slide, I think.
+
+Yes.
+
+Do not write these things down.
+
+You can look at them at your leisure.
+
+What this does is try to show you is an
+
+example.
+
+Different drugs and how they might have an effect on
+
+different parts of the neurotransmission process.
+
+I will go through a few just to illustrate it.
+
+For example, L-dopa, which you may know has been targeted
+
+for.
+
+Parkinson's and so forth.
+
+Acts as a precursor but does not mean and we
+
+get the drug.
+
+Meaning the second.
+
+There are other drugs, for example.
+
+Botulinum toxin or Botox.
+
+Inhibits the release of neurotransmitters, in.
+
+This case, acetylcholine.
+
+Into the spine.
+
+Therefore paralysed.
+
+Can anyone tell me why Botox paralyses muscles?
+
+So yeah, so we're not going to talk about it
+
+at all.
+
+But one of the most important snacks is in the.
+
+In the it was.
+
+One of the most important sinuses in the in the
+
+whole body.
+
+Is the.
+
+Neuromuscular junction, the junction between neurones and the muscles that
+
+they have an effect on.
+
+The neurotransmitter at that neuromuscular junction is acetylcholine.
+
+So if you block.
+
+The release of acetylcholine into that sign.
+
+That.
+
+You effectively.
+
+Paralyse those muscles because they're no longer getting stimulated, you
+
+want to paralyse muscles.
+
+And a difference is that with changes.
+
+Other drugs, for example.
+
+Can block the.
+
+Synthesis of enzymes as an.
+
+Antagonist or block.
+
+Presynaptic receptors as an antagonist.
+
+For example, cure are a very potent paralytic blocks.
+
+Again, acetylcholine release affects your muscle production and because of
+
+that paralyses.
+
+Unlike Botox, it has.
+
+A much more of contract.
+
+It's much more powerful and therefore the rest of breathing
+
+death.
+
+You can also have have.
+
+Much weaker effects by adding atropine because anyone been to
+
+an eye doctor has something to stop the eyes.
+
+Pupils dilate.
+
+Yes.
+
+First of all, across the story, I mean, I realise
+
+this practice is dying out.
+
+So the reason for that.
+
+Is that acetylcholine.
+
+Is the major neurotransmitter.
+
+Of the parasympathetic nervous system.
+
+And if you remember the difference between sympathetic.
+
+And sympathetic, nervous and sympathetic nervous system of flight arousal,
+
+increased.
+
+Pupil dilation, when.
+
+You get more sympathetic activity and vice versa than.
+
+Parasympathetic.
+
+If you block the parasympathetic system, you effectively increase the
+
+weight of the sympathetic system.
+
+So you get people dilation.
+
+So these different chemicals are acting in different ways.
+
+As I say, I don't want you to write down
+
+all these things that just there's a way for you
+
+to understand how different drugs have different effects on the
+
+whole process of neurotransmission.
+
+And I thought that might be a little bit vague
+
+and complicated.
+
+You get worse.
+
+Unfortunately, neuro modulator, as anyone heard this term before.
+
+Maybe I shouldn't say, You know, it's important.
+
+And your modulator is a is a messenger release when
+
+you're on, that often affects groups of neurones.
+
+So unlike a classic neurotransmitter, these substances.
+
+Have effects often on a large.
+
+Number of.
+
+Neurones.
+
+They often have slow affects.
+
+They seem to modulate the activity of neurones.
+
+Without really providing this fine grained information of the New
+
+York Times.
+
+Confusingly, unfortunately, some.
+
+Neuro modulators also act as neurotransmitters.
+
+So you're going to have to.
+
+Deal with that in your head as you go through.
+
+This course.
+
+One way to think of.
+
+One way I like to think of neuro modulator is
+
+that basically, has anyone ever done sound mixing frequency with
+
+anyone.
+
+Even on your.
+
+Computer, to do the.
+
+Ones.
+
+Who have.
+
+But mixing gets to got like.
+
+Three channels of dials that can push up and down.
+
+Right?
+
+Like in Mozart sneakers.
+
+So you've got like 32 channels or something like that,
+
+65 to 60.
+
+You can change the game, the loudness of each of
+
+those channels.
+
+We're not changing.
+
+The content of the music that's being played that's taking
+
+place.
+
+So you can modulate.
+
+What the sound sounds like without actually driving the content.
+
+I think of newer models, that kind of thing.
+
+Yeah.
+
+Amplifying and.
+
+Amplifying some sounds with some neural.
+
+Activity.
+
+We're not actually changing.
+
+The structure of that directivity.
+
+So think of these new.
+
+Modulators as.
+
+Like a big mixing desk for the brain.
+
+And clearly, you know, if you do.
+
+Something like shutdown.
+
+31 out of 32 channels, I mean.
+
+Leaving one.
+
+Active, you're going to really.
+
+Have a major spectrum and also have very subtle effects.
+
+You can tweak attention.
+
+You can help with learning just by changing the game
+
+on some of these things.
+
+I was going to go through the slight backseat.
+
+I might leave.
+
+But the only thing I wanted to point out from
+
+the slide is that your modulators can increase the activity
+
+of slowing and decrease the.
+
+Activity of sinuses.
+
+But I think I'll.
+
+Leave this one for the moment.
+
+If we want to, we can discuss it afterwards.
+
+I will spend most of this lecture.
+
+In talking about.
+
+Specific.
+
+Neurotransmitter systems.
+
+I've told.
+
+You already that glutamate.
+
+And GABA are the two.
+
+Major.
+
+Neurotransmitters in the brain.
+
+We're going to ignore them for the rest of this
+
+lecture.
+
+Because these other.
+
+Systems are thought to have particular key role in cognition.
+
+And I sometimes wonder why it.
+
+Is that these transmitters are given such ubiquitous.
+
+Such importance in neuroscience.
+
+When actually the.
+
+Bulk of work in the brain is done by glutamate
+
+and these things are we will execute.
+
+I think it's because it's so ubiquitous.
+
+Kaplan glutamate that they don't have specific effects that are
+
+being pointed really to.
+
+If you have something that has a system wide effect
+
+like glutamate.
+
+Fiddling with the effects.
+
+Of those particular neurotransmitters isn't.
+
+Going to have a huge specific sort of very specific
+
+effect on cognition.
+
+To have a specific effect on cognition.
+
+You need the substance to be expressed by a limited.
+
+Number of neurones with a particular set of connections.
+
+And that's the case for the following.
+
+Systems that we're going to go through some detail.
+
+So I'm going to go through all.
+
+Four of these.
+
+Don't try to copy this down.
+
+We're going to be bigger in slightly next lines.
+
+All four of these systems are going to be described
+
+within the context of the road brain for the simpler.
+
+And that's why we have lost the knowledge.
+
+Each of these schematics here shows a slice as if
+
+down the centre of the brain like this way.
+
+And what this shows you is kind of like the
+
+overall structure of the rat brain.
+
+In each case, at the back of the brain is
+
+the cerebellum.
+
+If you ever see the cerebellum slide, you go back
+
+to the brain at the front of the brain in
+
+the rat.
+
+Anyway, So effectively the top of the brain is up
+
+here, sometimes called the dorsal surface, dorsal fins.
+
+And the bottom.
+
+Here, ventral surface.
+
+It's important that this is given to you here, by
+
+the way.
+
+Back towards the spinal cord or whatever.
+
+The opposite of courteney's.
+
+Ventral and.
+
+Dorsal.
+
+So back to the brain front of the brain of
+
+the brain.
+
+Part of the brain.
+
+Each of these little purple things I'm going to show
+
+you in each of these.
+
+Slides.
+
+Is the location of the.
+
+Sort of the cell bodies of the neurones we're going
+
+to be talking about.
+
+There's not just one you on there in these cases.
+
+Eyes, but this is the.
+
+Location.
+
+Of those bodies.
+
+These are the black lines.
+
+Indicates in a very schematic way.
+
+The projections of the.
+
+Axons, the bodies from that area for the rest of
+
+the time.
+
+So let's have a look at the first one.
+
+The first system that we concentrate on is noradrenaline or
+
+the north entrance system.
+
+And if you're reading American textbooks.
+
+It's the north atmosphere, not norepinephrine, something like that.
+
+So noradrenaline is the same thing as norepinephrine.
+
+So this is a very special system.
+
+All the cell.
+
+Bodies for the neurones that.
+
+Produce this neurotransmitter are found in a little area called
+
+the locus, really found their brain junctions with migraine in
+
+the brainstem.
+
+In Iraq, there are about 300.
+
+Nerve cells in that.
+
+So what is in that region?
+
+Sorry, 3000 in that region.
+
+In a human, there are about.
+
+10,000.
+
+If you compare that, for example, in the human 86
+
+billion.
+
+Neurones in the brain.
+
+This is only 10,000.
+
+A drop in the ocean.
+
+If you had an impact, a stroke in your cortex
+
+and lost only 10,000.
+
+However, if you lost.
+
+These neurones, you would notice.
+
+And the reason for that is that these neurones project
+
+almost everywhere in the brain.
+
+They send.
+
+Axons to almost every pore in the brain.
+
+And therefore they release.
+
+The neurotransmitter noradrenaline to almost every location in the brain.
+
+The excellence of these individual neurones are very large.
+
+They cover many millions of cells.
+
+Over several decades.
+
+We now understand that they have multiple roles, but they
+
+can be kind of class in the following term.
+
+That is the idea that they promote.
+
+Vigilance for arousal.
+
+So, for example.
+
+If you say I also want to know, by the
+
+way, that noradrenaline is the major.
+
+Neurotransmitter of the sympathetic nervous system, which is why it's
+
+involved in blood pressure and stuff like that.
+
+And you should also know distances involved in sexual behaviour
+
+and appetite, as you see in later lectures, as well
+
+as decisions which were.
+
+Also seem like lectures.
+
+And one of the more interesting things that features of.
+
+The small group of neurones in this little area of
+
+the brain.
+
+Is its activity.
+
+It seems like.
+
+We can attract this.
+
+Activity with.
+
+These little set of neurones by measuring your pupil diameter.
+
+Not directly.
+
+It's not that.
+
+These.
+
+Neurones directly protect the people, but their effects on the
+
+brain surface and.
+
+Manifest.
+
+In the signs of the people.
+
+So, for example, in this work.
+
+From Darius Jones and his colleagues in Monkey, what's shown
+
+here is the average number of action potentials produced by
+
+a new.
+
+White animal reporting from the three of us.
+
+That's in the bottom curve.
+
+And on the top.
+
+Is the.
+
+Pupil diameter, with.
+
+Dilation being.
+
+Larger and.
+
+District of being smaller.
+
+This is a very long time.
+
+This is about an hour of recording or even an
+
+hour and.
+
+A half of.
+
+Recording.
+
+You can see that over time, the number of spikes.
+
+Produced by the cell and other cells.
+
+Near it varies.
+
+So sometimes it's about two, sometimes it's about one spike
+
+perspective.
+
+It's a factor of two.
+
+From the variance in the activity of these.
+
+Cells.
+
+When you can see that the number of executions being
+
+produced by the cells varies with the pupil diameter, such
+
+that when you have large pupils, that's indicative of these.
+
+Those haven't quite high rates.
+
+And that correlation of causation and correlations is now used
+
+quite.
+
+Frequently to try and assess.
+
+The state of the system in humans, because we can
+
+measure pupil diameter fairly.
+
+Straightforwardly with the.
+
+Top electrode and really it's in humans.
+
+So we can track the activities population of neurones simply
+
+by looking at your pupil diameter.
+
+Many things affect the people.
+
+Don't have very controlled experiments.
+
+Be able to.
+
+Rule them.
+
+Out.
+
+But in the right conditions you can.
+
+Try to affect.
+
+This vigilance.
+
+Or arousal system.
+
+Indeed, perhaps particularly for this lecture.
+
+You may know that you're exposed in relationship, which is
+
+the idea that performance is based on the intermediate.
+
+Level of arousal.
+
+When you have low arousal, good.
+
+We have very high.
+
+Arousal, very distractible.
+
+Good.
+
+When you somewhere in between those two extremes.
+
+That's when you perform it best.
+
+And actually, strikingly, the activity, the neurones.
+
+In this little area seem.
+
+To vary in a.
+
+Way that might be expected by some underlying this relationship.
+
+So, for example, when you're measuring from the stimulus and
+
+you're measuring the activity of neurones in each of these
+
+bars, the approximate activities of.
+
+Neurones that fires fire, the more active.
+
+The heat and the arrow in this case is, by
+
+the way, the onset of a particular.
+
+Task.
+
+You can see that when the animal is inattentive.
+
+Or not, alert monkeys when they're doing experiments, Wolf, has
+
+been.
+
+Several minutes.
+
+If not longer.
+
+You sign and they don't really want to participate in
+
+this experiment and just kind of go to sleep.
+
+Or when they go to sleep, they become inattentive.
+
+And you can see the activity in the local cities
+
+is reduced in these conditions, whereas when the animal is
+
+highly distractible.
+
+Seems to be wanting to do the task wasn't able
+
+to accomplish it might be to terminate the trial too
+
+early, etc..
+
+You can see also that the activity.
+
+In local surrealists has increased during these conditions in a
+
+chronic way.
+
+And then some.
+
+Nice intermediate position.
+
+The arm was engaged, is actually able to do the
+
+task is performing well.
+
+In this case you have low activity in the really
+
+in general, the little little epochs of high activity seemingly
+
+signalling the.
+
+Fact that the animal is actually attending to particular aspects
+
+of the path has been undertaken.
+
+So these neurones really seem to track quite well the
+
+vigilance that an animal is producing, be a.
+
+Task, engage aspects of.
+
+Their activities.
+
+Behaviour.
+
+Get to the point where it's over the cuts, defence
+
+cuts.
+
+Why do you think they should be much more distinct.
+
+Kind of reforms?
+
+Is that what you mean?
+
+And why Is it because you have a record that
+
+you have to use against other?
+
+What do.
+
+You mean?
+
+Why, for example, is this black over here and this
+
+black is here?
+
+Is that is this what you mean by overlap?
+
+Sorry, I'm not quite sure what you mean.
+
+By the overlap.
+
+In on the x axis.
+
+The thing that.
+
+Is pointing that out, I didn't actually describe what this
+
+chart which is.
+
+Important.
+
+These are what we would call histograms.
+
+Or.
+
+Event time.
+
+Histograms of periosteum stimulus time variances.
+
+If you will see this word eighth grade line.
+
+Who go through more in a couple of weeks time.
+
+Each little box.
+
+Now indicates the average.
+
+Number of spikes produced by neurone or the total number
+
+of spikes because you find you're in a particular time
+
+period.
+
+In this case, what was showing before is on that
+
+axis of these black things.
+
+It's time.
+
+But the access component here is just some schematic idea
+
+of what activity is.
+
+So there are actually very different axes and they're not
+
+meant to be taken seriously as a kind of relative
+
+to each other.
+
+So each of the stages.
+
+Is the same time scale.
+
+And they have.
+
+No relationship to the other actually on the ground.
+
+I think.
+
+We.
+
+Will go through stages ad.
+
+Nauseum in about two.
+
+Weeks because the next system is the cholinergic.
+
+System and the set of colony.
+
+Is the major.
+
+Neurotransmitter of the parasympathetic nervous system, which also neurotransmitters.
+
+The neuromuscular junction.
+
+And it's also produced in several places in the central
+
+brain in particular.
+
+But until now that no one knows how to say
+
+that.
+
+But also here, the medial septum in the coordinate nucleus
+
+and importantly, the nucleus.
+
+Now, these different groups of neurones, which have different projections
+
+to the rest of the brain, also seem to have
+
+different.
+
+Functions in combination.
+
+So example.
+
+Those cholinergic neurones that are down, in.
+
+Fact.
+
+They seem to connect to separate.
+
+Seem to have an influence.
+
+The influences animals waking.
+
+Up from sleep and going back to sleep and other
+
+forms of arousal.
+
+By contrast, the neurones that are in the medial.
+
+Septum known to be very.
+
+Important prospects for navigation.
+
+And a large prediction of a campus influence activity.
+
+The present projection primarily and in those in numerous besides
+
+seem to project to the cerebral cortex.
+
+You can therefore influence learning intention.
+
+The cerebral cortex is a strong hypothesis that calling is
+
+one of the major neurotransmitters of helping us tend to
+
+different parts of our brain and therefore the outside world.
+
+The next one is serotonin, which many of you were
+
+familiar with, at least in name.
+
+And this neurochemical is produced by neurones whose bodies.
+
+Line these beautiful little nuclei in the brainstem called the
+
+regulating events.
+
+And there's three or four that actually separate the 3.3
+
+of them at least, which produce the substance serotonin.
+
+And again, these axons, these neurones project in many different.
+
+Parts of the brain.
+
+I'll show you in a second, was stunned to.
+
+Learn that they're not all the same description.
+
+But for a long time it's been assumed that they
+
+were doing pretty well.
+
+The same.
+
+Function.
+
+What that function is, is not really.
+
+There is some models out there, but I don't think
+
+anyone would agree on them yet.
+
+I would note that LSD is an agonist of serotonin
+
+receptors.
+
+And if those of you who.
+
+Are interested in.
+
+The idea of using.
+
+Small amounts of energy in therapy, for example, might be
+
+important to.
+
+Know that at UCL.
+
+As well as Imperial, there are ongoing programs looking at
+
+the use of small.
+
+Amounts of those to help people.
+
+Overcome depression of the major illnesses.
+
+MDMA is also very active in the serotonin system, has
+
+an effect on sinuses by multiple mechanisms.
+
+It was originally used as an appetite inhibitor.
+
+But it also targets the hypothalamus.
+
+And is a tool in marriage therapy.
+
+As you well know.
+
+I suspect selective serotonin.
+
+Reuptake inhibitors.
+
+Or SSRI, is a.
+
+Major.
+
+And potent human.
+
+So as we've discussed before, we now should not have
+
+to decide for that selective serotonin reuptake inhibitor, selective serotonin.
+
+System, serotonin, that's neurotransmitter.
+
+It changes the way that neurotransmitters in.
+
+Particular.
+
+Inhibit so that you're going to therefore increase the level
+
+of suppression in the sense that it's believed in.
+
+So SSRI is basically work to increase the amount of
+
+serotonin in some finances.
+
+Which synopses are.
+
+Important.
+
+For the antidepressant effect?
+
+It's not known.
+
+If there.
+
+Is a substantial debate about how and why these substances
+
+are having their effect in those people who are receptive
+
+to it as an antidepressant.
+
+There's an interesting study which is going to suggest that
+
+serotonin may have very.
+
+Similar cognitive effects across multiple species.
+
+This is a.
+
+Lovely study in octopus.
+
+I like it because it's very clear.
+
+You'll see here there's an octopus, a lovely pitcher in
+
+a tank, and there's two doors, the hand octopus hands
+
+from his central tank, one to an inanimate object, the
+
+other one to him, playmate.
+
+So the question is, does the.
+
+Octopus choose to spend more time with an object or
+
+playmate?
+
+And then does that change when you add in the
+
+eye to the tank and you can almost almost the
+
+focus on this one here we see that the social
+
+activity of the.
+
+Octopus.
+
+Goes up substantially after introducing MDMA to the tank.
+
+All the other relationships seem to be non-significant.
+
+So, for example, it does seem to spend a little
+
+less time with the object.
+
+It doesn't seem to spend any more time in the
+
+centre.
+
+It does seem to spend.
+
+More time that might.
+
+Be increasing.
+
+The social.
+
+Activity of these.
+
+Octopuses in a similar kind of way to how it
+
+does in humans.
+
+Yes.
+
+Oh, sorry.
+
+It's very hard to say what you should just say.
+
+Just say something if I got.
+
+Into the.
+
+Spotlight.
+
+Yeah.
+
+Well, so good to have this episode of Facebook or
+
+something like that.
+
+Yes, actually, if you just come.
+
+Back to it in the next slide.
+
+I think that a lot.
+
+Of that uncertainty around the.
+
+Specificity of these drugs.
+
+So why does it seem to have precisely the same
+
+kind of effect, have different kinds of things?
+
+Apart from the fact that the different individuals are very
+
+different.
+
+Anyway, getting set aside for a moment, I think a
+
+lot.
+
+Of that comes down to the fact that these systems.
+
+Are much less homogenous than we thought they were.
+
+Very kind of of that.
+
+You know, we used to think these were all basically
+
+the same thing, but now it's very clear or becoming
+
+very clear.
+
+They do quite different things.
+
+So, for.
+
+Example, this study from a couple of years ago shows
+
+that some of those neurones project the frontal cortex and
+
+others projects the amygdala.
+
+Now, those of you who don't.
+
+Know about the amygdala will find out ad nauseam again
+
+this course.
+
+Later that there is very important fear generating behaviours.
+
+Frontal cortex, on.
+
+The other hand, reporting in.
+
+Hallucinations and executive.
+
+Control.
+
+And three different groups of neurones and it.
+
+Is in at least in rodents.
+
+Seem to project to these two.
+
+Different regions because I think a lot of the reason
+
+that these substances can have to protect is because there'll
+
+be different sensitivities.
+
+And maybe.
+
+Of those climaxes of circuits that are involved in particular
+
+substances.
+
+So depending on which.
+
+Form the kind of tapping into more about, you have
+
+a different kind of stuff.
+
+But it.
+
+Could well be I can't.
+
+Remember, I come in with this study whether they explore
+
+the difference, sometimes.
+
+I think they did those of you.
+
+Know this, but they called 5ht receptors and there's multiple
+
+subclasses.
+
+Not common there, but it's highly likely that it's different
+
+expression patterns.
+
+But it's a good question.
+
+Yes, but it's just stories here that certain lunatics of
+
+projects to the frontal cortex is activated by rewarding exhibited
+
+by punishment, whereas that which is projects, the amygdala is
+
+activated by space.
+
+Just to point out really something to think about too
+
+much, but just to point out that what we thought
+
+of as kind of model systems are now being pulled
+
+apart and.
+
+Described as pretty separate systems.
+
+Or maybe the same neurotransmitters.
+
+So I want to spend the last 5 minutes just
+
+talking about don't mean because that's how we started off
+
+trying.
+
+To understand why cocaine has its.
+
+Specific effect and dopamine has two major sources, one in
+
+the substantia nigra and one in the mental area.
+
+Sitting.
+
+These two areas sit next to each other just here
+
+in the midbrain.
+
+Now, substantia nigra has a large projection to the.
+
+Pelvis and striatum.
+
+It's very important to work on control.
+
+For that reason.
+
+Degeneration to the substantia nigra.
+
+Neurones is.
+
+The basis of.
+
+Parkinson's and Parkinson's.
+
+If you.
+
+Haven't come across.
+
+It is a debilitating disease whose early stages.
+
+Are indicated by substantial tremors and tremors.
+
+Basically.
+
+The absence of control of your muscle.
+
+Movements.
+
+This happens because of the type of nurturing signal that
+
+normally comes to suggest migrants, not in the present.
+
+I want to show you one video.
+
+It's going to be video, but uses deep brain stimulation,
+
+which is the idea that we can put an electrode
+
+into the brain to.
+
+Simulate.
+
+The now absent.
+
+Signals to try and recover those neurones and signals.
+
+And it's an amazing video.
+
+Here it is placed in the brain and then comes
+
+level with the top of the nose and the ear.
+
+And it is connected to a battery in my chest
+
+and in my head, the skin of my chest here.
+
+And this is controlled.
+
+I can control the amount of the voltage coming in.
+
+I can control the length of time that the pulses
+
+and I can identify the number of times per second
+
+as it goes in my chair myself now.
+
+So I'm not having to issue.
+
+Personal hygiene.
+
+It took my concentration.
+
+It's up to.
+
+90% of my term.
+
+I'm trying to control it.
+
+I'm thinking about Parkinson's all the time.
+
+I'm not terribly I'm not concentrating on my conversation with
+
+him at all.
+
+Okay.
+
+It's seen as quite.
+
+I've seen that many times.
+
+I support it deeply affecting.
+
+So what's happening there.
+
+Is that the deep brain stimulation implant is effectively replicating
+
+what the.
+
+Nerves would.
+
+Normally be.
+
+Providing.
+
+And that controls the.
+
+Tremor or helps some control the tremor.
+
+I've got a slide in there about deep brain stimulation.
+
+We want to think we go through this again next
+
+lecture.
+
+The other major system that users don't meet is the.
+
+So-called reward system that stems from the vengeful, sentimental area.
+
+Of several places.
+
+But the main circuit that's been studied is that from
+
+the bedroom has been married to the.
+
+Nucleus accumbens.
+
+And thought that this circuit is one of the ones
+
+primarily responsible for experience.
+
+Of reward.
+
+And potentially pleasure.
+
+So why do we continue to do something?
+
+Well, why do we do something again, just because we've
+
+got something.
+
+Positive out of this time?
+
+It was a rewarding experience.
+
+The teaching.
+
+Signal that would tell us how we would.
+
+Like to repeat that.
+
+Behaviour.
+
+That's the reward.
+
+Signal.
+
+It turns out that these neurones in the middle area,
+
+the projects, the nucleus accumbens, so every indication of being
+
+part of a circuit that helps us learn from positive,
+
+rewarding events.
+
+So if I've told you that cocaine changes behaviour because
+
+it blocks the uptake of neurotransmitter opening, and that has
+
+a specific effect potentially because.
+
+It's a very specific.
+
+Circle in the brain that.
+
+This expresses this certain perception.
+
+I haven't yet told you what.
+
+Cocaine does it blocks the uptake of don't mean in
+
+back into the presynaptic areas from the sign ups that
+
+re uptake that transporter that normally active.
+
+During out of the sign.
+
+Out into the presynaptic space is blocked by cocaine cocaine.
+
+Increasing the level certainly in the sign ups.
+
+And in particular.
+
+We think the finance.
+
+Between the beta and the nucleus.
+
+Accumbens.
+
+And that.
+
+By having an action on that side, it.
+
+Increases the reward or pleasure.
+
+Signals.
+
+In the brain.
+
+That's the reason.
+
+That cocaine.
+
+Could have an impact.
+
+On.
+
+Parkinson's disease.
+
+I'm pretty sure I may be wrong is that the
+
+two receptors, the.
+
+Receptors slightly different.
+
+I'd have to look.
+
+I don't know the answer to that.
+
+Again, a bit like the serotonin question.
+
+I think the.
+
+Question is whether or not.
+
+There's different circuit sets of different receptors and different chemicals.
+
+Being both the trigger for.
+
+This is the topic from the video, the nucleus accumbens.
+
+I put it here to indicate that actually many of
+
+the substances.
+
+That we think are psychoactive drugs, opioids.
+
+Caffeine, nicotine, cocaine seem to have an action on this.
+
+So this could be a common sentence for the mode
+
+of action for a lot of these addictive substances.
+
+They activate or activate.
+
+Circuit that normally leads to the sensation of.
+
+Reward, sensation of pleasure.
+
+And that's one of the reasons they're likely to be
+
+addictive.
+
+It's not the only reason.
+
+Clearly, one of the reasons they're likely to be so
+
+hope.
+
+Of being able to break down that sentence and that
+
+you've understood a little bit more about why some drugs
+
+work.
+
+That includes a kind of like foundational series of lectures.
+
+I suppose next week we'll be talking a little bit
+
+about research methods that we can use to study brain
+
+activity.
+
+And then we'll be looking at this brain.
+
+So thank you and have a good day.
+
+All right, let's just keep talking.
+
+Six months after the holidays.
+
+Yeah, that's good.
+
+But I don't think we know enough about the differences
+
+between different organisms in the same place that.
+
+We don't know the.
+
+Answer to that.
+
+Question.
+
+Because that would be my question.
+
+Which is really some people don't think it's a good
+
+question.
+
+I have no contact with someone else.
+
+That's why it seems like complexity.
+
+What what kind of thing?
+
+Yeah, exactly.
+
+So why.
+
+I'm.
+
+Calling.
+
+Because.
+
+It's.
+
+Not can.
+
+Look.
+
+At.
+
+Requirements.
+
+That makes sense.
+
+How do you go about doing stuff like this?
+
+Because I mean.
+
+Otherwise, except.
+
+As required by applicable because we want to participate.
+
+The central focus on the subject in the weeks before
+
+Google, which might be possible this.
+
+Week, is something.
+
+That we support.
+
+But I think it's difficult for people to try to
+
+keep up to date with all the of.
+
+Okay.

raw_transcripts/lecture_5.txt

@@ -0,0 +1,2215 @@
+So that's best thing.
+
+Dr. Richard Francis.
+
+That's the they to take the word.
+
+What is.
+
+Hello.
+
+Welcome back.
+
+If you are.
+
+My name's Sam Solomon.
+
+It's my pleasure also to introduce to you today Professor
+
+Elliott Carton.
+
+He'll be taking a lot of this lecture.
+
+So in the last two weeks, we've discussed the different
+
+components of brains and brain function.
+
+The purpose of this week in general is to help
+
+you understand a little bit better to survey the variety
+
+of techniques that are available now to study brains and
+
+behaviour.
+
+To set us up properly for the subsequent weeks, which
+
+were on specific terms.
+
+So the purpose of today is not to go into
+
+in-depth any particular technique.
+
+We just like to help you understand the panoply of
+
+techniques that are available with the strengths and the limitations
+
+of some of those techniques are and why one might
+
+choose to employ them in particular circumstances to understand the
+
+relationship between brains and behaviour.
+
+This is now quite an old slide, or at least
+
+most of it is.
+
+I adapted it slightly on the x axis is the
+
+timescale of which one might like to make a measurement
+
+ranging from milliseconds through hours, days and even lifetimes.
+
+On the y axis.
+
+It's a spatial scale of which one might like to
+
+make that measurement from the scale of a single snaps
+
+of a single nerve.
+
+So through two o columns of those whole brain areas
+
+and perhaps even the whole brain, each of the little
+
+things in the box are different types of techniques, most
+
+of which will encounter some time today.
+
+These include things that are, for example, called patch clamp
+
+electrophysiology.
+
+This is old school electrophysiology, incredibly powerful technique.
+
+You put in a glass electrode, so its tip is
+
+only 1000 or maybe 5000 millimetre wide.
+
+You put that glass tip up against the membrane of
+
+a single nerve cell in a slice usually, but sometimes
+
+in a whole animal.
+
+You suck that little membrane onto the end of the
+
+pipette and then you break the seal from the glass
+
+into the inside of the cell, what's called a giga
+
+arm seal.
+
+And that allows you to measure precisely the internal electrical
+
+life of that.
+
+So that's basically the smaller scale measurement techniques tend to
+
+get through on the top.
+
+Right, as we'll be discussing soon, is a kind of
+
+knowledge you can gain from studying humans or animals with
+
+lesions, maybe to large parts of the brain or to
+
+even small parts of the brain, often formed by strokes
+
+or other kinds of accidents.
+
+And in between.
+
+These are a range of different techniques that we'll be
+
+encountering today, including electrophysiology, calcium imaging, optical imaging that Magneto
+
+and Safflower Graham or the electroencephalogram MEG or EEG, but
+
+also techniques that are not necessarily aimed at revealing the
+
+functional activity of the brain, but the kind of connections
+
+between different brain areas.
+
+If we were to have this lecture back when the
+
+slide was first made.
+
+I think the slide was first made back in 1994
+
+because there had been some profusion of techniques, including MRI,
+
+into the field.
+
+These techniques have now even grown more stronger and more
+
+varied in their ability to answer these kinds of questions.
+
+Hopefully we'll give you a flavour of that today, so
+
+I'll hand off now to the radio to take you
+
+through the first component, which is largely to do with
+
+how we try and measure brain function in human beings.
+
+Hello, everybody.
+
+Can you hear me?
+
+Yeah.
+
+Hi.
+
+It's really nice to be here.
+
+I'm Andrea.
+
+I'm one.
+
+This is a professor of experimental psychology, and I mostly
+
+do research on human cells quite nicely to telling you
+
+about some of the techniques that we use.
+
+And we wanted to start a little bit with.
+
+Well, the first thing that was available for us to
+
+study the human brain.
+
+Right?
+
+And that was sort of lesions in patients.
+
+And that's something that's very much like we call neuropsychology,
+
+although neuropsychology implies all those things as well.
+
+And you're going to be seeing this a lot through
+
+your modules.
+
+And so I'm not going to go into a lot
+
+of detail about it, but it is fair to say
+
+that sort of the groundbreaking studies of Paul Broca were
+
+the ones that sort of get this field going in
+
+many ways.
+
+So Rocco had a patient that had some language production
+
+issues, and when that patient, that patient died and then
+
+they examined the brain, they saw that they had a
+
+lesion in the left hemisphere, in the frontal charges, in
+
+the frontal cortex.
+
+And they could also see that that happened again with
+
+a couple of patients.
+
+So that was the first real sort of link between
+
+a function behaviour and sort of something localised to a
+
+certain part of the brain.
+
+And that was really groundbreaking for for neuroscience and for
+
+psychology.
+
+And it is the technique that we still use up
+
+to today.
+
+We're going to we're going to talk a lot about
+
+hair and burn care during the language recognition lectures.
+
+And we also are going to talk about a fascia
+
+and how we still use neuropsychology to study the brain
+
+in humans.
+
+So as I said, it's just really good in terms
+
+of getting this still going and making sort of relationships
+
+between structure and function in the brain.
+
+And what we can do now is also say, okay,
+
+well, we have these Asian to have this lesion.
+
+Let's try to see how they perform different tasks.
+
+And again, you begin to see this a lot.
+
+A classic example, the studies of our friend Amelia with
+
+patients, H.M. and.
+
+So yeah, really groundbreaking as well.
+
+That went to a lot of studies.
+
+We learned a lot about memory from those and that
+
+this technique obviously, you know, has advantages which are like
+
+and how we can link brain, um, behaviour and potentially
+
+identify regions that are necessary and lesions that never sort
+
+of sort of constrained to certain regions of the brain
+
+if you want.
+
+We don't really know what's damage.
+
+The damage will be different between patients.
+
+So it's a little bit, it's a kind of like
+
+what people call sometimes a nature experiment.
+
+Well, someone had a listen.
+
+Let's try to understand what happened.
+
+And I think in terms of disadvantages was that it
+
+was that the lesions are not selective and that also,
+
+obviously, the brain has this this capacity of plasticity of
+
+of change in potentially structure and function to compensate for
+
+what's happening environments is what happened in its own physiology.
+
+And so there are a lot of cases that actually
+
+the brain compensates over time.
+
+So we see this a lot in patients and you
+
+will say the cases of aphasia were potentially at the
+
+beginning after lesion.
+
+A patient has like several sort of potential issues with
+
+producing or understanding language.
+
+Let's say that as time passes, many of them recover.
+
+So not all of them.
+
+And that's like a real interesting or like a big
+
+area of research trying to understand why a patient will
+
+not recover.
+
+Many of them do.
+
+And that has to do with how the brain can
+
+compensate for that damage.
+
+However, there are lots of things that you can't really
+
+do.
+
+You can't really study dynamics between brain regions because you
+
+know that lesion is already damaged.
+
+So, you know, that's the only thing that you know.
+
+And and I think I think for me, the biggest
+
+one is that, well, deletion is not selective.
+
+So you wouldn't know what exactly is damage or to
+
+what extent.
+
+And therefore, it's very difficult to make sort of inferences
+
+between the structure and the function.
+
+We can do it by studying sort of large groups
+
+of patients.
+
+But for example, there is currently study in Queens at
+
+UCL where they're trying to look at that Netflix of
+
+yeah, so people would have patients are going to be
+
+all the brain lesions and therefore sort of language production
+
+and perception problems and they're trying to look at what
+
+predicts recovery and they really need to recruit thousands of
+
+patients to be able to do this properly.
+
+So it is, it is quite hard.
+
+Okay.
+
+So I'm going to talk now about some other techniques
+
+that we can use to actually measure brain function and
+
+structure in healthy individuals and in a non-invasive way.
+
+And the first one I'd like to talk to you
+
+about is magnetic resonance imaging.
+
+And I'm just going to show you a video that
+
+explains this very well from one of the developers of
+
+this technique.
+
+If you take, let's say, a human being and put
+
+him in one of these big, very homogeneous magnetic field
+
+magnets, then there's a tendency of that magnetic field to
+
+line up the magnetic moments of the nuclei, the spin
+
+of the nuclei and the hydrogen in your body, which
+
+is in your muscle and in your blood.
+
+Now, put on a radio frequency pulse, say 60 megahertz
+
+or something like that.
+
+Then you can make this magnetisation of your hydrogen nuclei.
+
+You can turn it 90 degrees away from the direction
+
+of the magnetic field.
+
+Your magnetic moment will process.
+
+If you have coils around, pick up coils, they it
+
+will induce a signal.
+
+If I want to see where the signal is coming
+
+from in your body, I put on another magnetic field
+
+on top of the very homogeneous one that's called a
+
+magnetic field gradient.
+
+By that I mean it makes a feel stronger in
+
+one place and weaker in another place.
+
+What you do in order to actually get the image
+
+that you want, the fan resolution that you need, that
+
+you put on magnetic field gradients of different strengths, a
+
+series of pulses.
+
+That's why if you get an MRI machine, you're here.
+
+Bom, bom, bom.
+
+It's all these pulses that we're putting out with different
+
+strengths of magnetic field, perhaps even different directions, because we
+
+want to get a three dimensional picture of you.
+
+You record all of these data and when you finish,
+
+you can now use what's called Fourier transform.
+
+It's a mathematical technique.
+
+You can work back to how strong the signal was
+
+in each of these voxels.
+
+And so this is how the image is developed.
+
+Okay.
+
+So that was a very quick intro to.
+
+Right.
+
+So am I in the wrong one?
+
+Okay, so MRI stands for magnetic resonance imaging, and we
+
+usually use this really big magnets, scanners to to sort
+
+of scan people to conduct this technique.
+
+And functional MRI refers to the kind of specific scanning
+
+that is used for measuring, you know, something that relates
+
+to brain function.
+
+And I what I'm going to expand as I'm going
+
+to explain both of them.
+
+And so how I.
+
+It's just plain.
+
+Old.
+
+Okay.
+
+Thank you for your input on my music selection.
+
+And so in Ryan ephemera and material I'm going to
+
+talk about a little bit later, it really changed the
+
+game in terms of what we could do to study
+
+the human brain.
+
+And in the last 25 years that these techniques have
+
+been around, we have gained a lot of understanding of
+
+how many functions that we can only study in detail
+
+in humans, such as potential language or some complex decision
+
+making or, you know, metacognition and so on, how they
+
+work and how how, how the brain represents or like
+
+produces its functions.
+
+And so how does an MRI what I mean to
+
+me, it's absolutely amazing that we can look into the
+
+people's brain and actually look into their function without even
+
+putting anything inside.
+
+We can just take pictures of their brains by measuring
+
+how hydrogen atoms move, which is why I was trying
+
+to say here.
+
+So this is what happens.
+
+You put the subject a the participant in a big
+
+magnets.
+
+The magnets and had a really, really strong magnetic field.
+
+And to do that you need liquid helium and you
+
+need to keep that constant all the time.
+
+So the energy cost of doing this is quite high.
+
+And that's why MRI is actually a really expensive technique.
+
+And when you put a person in this big magnetic
+
+field, as it was thought by all the sort of
+
+elite hydrogen atoms were aligned in the same direction.
+
+Right.
+
+That's why you don't use trying to put them all
+
+in the same direction.
+
+So then when you sort of disturb them and when
+
+a radio wave.
+
+Right, they will sort of rotate.
+
+When you turn that off, they're going to go back.
+
+And when they go back, they're going to miss the
+
+signal that you can think about sort of like a
+
+kind of singing in a certain frequency.
+
+You can see these electrons.
+
+And so these hydrogen atoms are thinking in a special
+
+frequency when they're going back to the alignment.
+
+Right.
+
+And that's why we're measuring now how how then can
+
+we measure different parts of space if they're all aligned
+
+in the same way?
+
+That's where you introduce these gradients.
+
+So the gradient is just changing the magnetic field slightly.
+
+So in a way, you can think about these hydrogen
+
+atoms sort of kind of moving and what this thing
+
+that's going to be sent is going to be at
+
+a different frequency.
+
+You can think about it as thinking in a different
+
+frequency.
+
+So for example, if I wanted to know, you know,
+
+how this lecture theatre was populated, but I couldn't see
+
+it, I was in a different room.
+
+I could just put microphones all around with different with
+
+different frequencies and then just have a recording here.
+
+Right.
+
+So the guys at the very top are going to
+
+have really low frequencies, and that's going to be a
+
+great note here to very high frequencies.
+
+So I'm going to go in the other room and
+
+she's going to be recording the signals from all those
+
+microphones when you're talking or whatever.
+
+And by looking at the frequencies of those recordings, I'm
+
+going to be able to exactly say who was sitting
+
+where.
+
+Because that's the link between frequency and space.
+
+And that's why MRI dogs and that's why I like
+
+to see pictures of your brain, which is amazing.
+
+So if there's like a really strong signal at a
+
+specific frequency, I know where it's coming from.
+
+That part of of their image is going to look
+
+quite bright.
+
+And if it's a really low frequency, then it's going
+
+to look like that.
+
+And that's how we construct and it's really nice brain
+
+pictures.
+
+And so, yeah, pictures like this, for example.
+
+Right.
+
+So you can see and this is just a transformation
+
+of light, really strong powers.
+
+These things are like y by looking wide or depending
+
+on what y your technique is, depending on the contrast.
+
+And this the opposite for things that, you know, they
+
+don't have that much signal.
+
+Now this is just to get a structural image.
+
+This just gives you a picture of the brain, right,
+
+That doesn't link at all to brain function.
+
+So what is it that allowed us to use functional
+
+MRI to look at brain function?
+
+And it is the fact that when a certain part
+
+of the brain is active, there will be an increase
+
+in blood flow to that part of the brain.
+
+When there is an increase in blood flow, there's going
+
+to be more haemoglobin, haemoglobin coming into that and that
+
+has iron.
+
+And it's in a sense the iron is ferromagnetic so
+
+interferes with that magnetic field.
+
+So by measuring how much interference there is with the
+
+magnetic field, we can measure brain function.
+
+But as you can see, the images and I'm sure
+
+you hear one is the structural image to the kind
+
+of images that we use for studying the structure of
+
+the brain.
+
+And this is a functional image.
+
+It's just very low resolution because we actually want to
+
+see.
+
+How it changes with time.
+
+So acquiring one of these images it takes for the
+
+whole brain, it takes at least 5 minutes, whereas acquiring
+
+this one could take 2 to 3 seconds depending on
+
+what you're doing.
+
+So we kind of compromising some of the spatial definition
+
+to have like a better temporal resolution.
+
+But we're still measuring blood flow, and blood flow is
+
+quite slow.
+
+That's why ephemeral is not a good technique for measuring
+
+brain function.
+
+So and you think it's no good technique for measuring
+
+sort of Air Force temporal events is not it doesn't
+
+have a great temporal resolution.
+
+That being said, last week there was this really exciting
+
+paper published where they had an MRI technique and so
+
+milliseconds resolution now like very fast.
+
+And it was done in animal models and it was
+
+thought like in a single slice.
+
+So it's not the whole brain, it's just the very
+
+first step towards this technique.
+
+But I think, you know, everybody in the field is
+
+really exciting because it really looks like in a few
+
+years, like maybe ten, 20, who knows?
+
+We are going to have a technique that allows like
+
+a really great temporal resolution potentially to study the human
+
+brain as well.
+
+And so when you get these images where you do
+
+in the functional case and ephemera is that you take
+
+many, many, many of them and then you compare them
+
+across conditions.
+
+So, for example, let's say here I will record like
+
+lots of images do one of my goodness conditions of
+
+my experiment, which could be it could be a memory
+
+experiment, right?
+
+So it could be like memorise these items.
+
+And then I have a control condition where I just
+
+tell people to, you know, look at them, don't memorise
+
+them.
+
+And then you can look at how like activity changes
+
+across the whole brain.
+
+Or like in here you can like look specifically into
+
+a certain region, right?
+
+So this region here is a few voxels, a voxel
+
+instead of the minimal units and ephemera you can look
+
+at as a three dimensional pixel.
+
+And then we can average, for example, the activity through
+
+that.
+
+So if you look at this, the intensity in these
+
+conditions is going to be different.
+
+But this is something that you can't really tell, you
+
+know, just by looking at.
+
+And the difference is very, very small.
+
+It's usually around, you know, between 1% to like 4%
+
+or 10%.
+
+Best case.
+
+And and yeah, it's it's really small, but it is
+
+very consistent.
+
+So you can measure that and you can measure how
+
+it changes.
+
+And that's what we're doing here.
+
+We have like these three measurements here, for example, from
+
+that region in red, and then we compare them to
+
+the measurements during the second condition and averages and see
+
+this a difference in the amount of like bull's signal
+
+in that area.
+
+And by doing that across the whole grain, we can
+
+come up with these statistical maps where we're showing where
+
+in the brain there are significant differences between conditions.
+
+Okay.
+
+And so as I said, FEMA has brought lots of
+
+advantages.
+
+I think one of the really nice things is that
+
+we can study the dynamics of the whole brain.
+
+And, you know, that doesn't only apply to humans, but
+
+it's also been used in animal models for this specific
+
+purpose as well.
+
+And after certain spends, we can understand how different parts
+
+of the brain interact and how they form functional networks.
+
+So we can like sort of do more complex analysis
+
+of network dynamics and see how reaches interact under different
+
+situations.
+
+And you could do things that we couldn't do for
+
+like with patients because, you know, patients essentially have some
+
+sort of behavioural deficits.
+
+So like there's things that they wouldn't be able to
+
+do that we could do now because they're healthy participants.
+
+And I'm very nicely we can think we can study
+
+human brains, right?
+
+We can study things that are so specific to humans
+
+that would be difficult to study in all that and
+
+which models.
+
+So, for example, I study deafness and how the brain
+
+of deaf individuals changes.
+
+And you know, when the congenitally deaf and continues with
+
+deafness in many cases results in a delay in language
+
+acquisition, which then has a lot of impact on cognitive
+
+functions as well.
+
+So it's not that animals are not great for answering
+
+those types of questions, so great for studying the effects
+
+of sensory deprivation or lack of sensory experience, in this
+
+case, a hearing and in the development of the brain
+
+in plasticity.
+
+And so it not so much to study what are
+
+the impacts on cognitive processes.
+
+And I think the best example of how we gain
+
+from ephemera is we can do things like communicating with
+
+patients in a coma.
+
+And I really recommend you to look at these videos
+
+from Agent Owen and his group where they are using
+
+ephemera and what we know about from right.
+
+They have been able to communicate with and with patients
+
+that before we didn't have any insight into their entire
+
+health status.
+
+And so that has been a really amazing ground breaking
+
+discovery.
+
+So I'm not going to go into detail here right
+
+now of time.
+
+And there are tons of limitations, though.
+
+And again, I think know, we have some understanding of
+
+what the f MRI signal is.
+
+So is this mix of like presynaptic activity and like
+
+sort of cells firing as well.
+
+And like, we don't know which ones it's coming from.
+
+So you never really know what type of activity you
+
+measure.
+
+And you've just seen a difference in overall blood flow
+
+in one region to the other.
+
+So that is quite limiting.
+
+And and again, the spatial resolution is great, you know,
+
+like in comparison with other things.
+
+But still, like we're looking at a bunch of cells
+
+like and it's going to be quite hard to tell
+
+what individual cells or small networks of self are actually
+
+doing.
+
+And and again, it's like this really big magnets.
+
+So people have to stay, you know, sort of still
+
+they can move around and that just gives limitations as
+
+well.
+
+I think, as some said, there's been a lot of
+
+advances in these techniques and now we have MRI for
+
+humans where we can measure layer specific activity.
+
+So different layers of the and, you know, the cerebral
+
+cortex.
+
+But still, you know, that's still a lot of cells
+
+and not specific.
+
+Now, before we pass into other techniques, I wanted to
+
+talk a little bit about this technique called functional, and
+
+yet infrared spectroscopy, which works a little bit like ephemera
+
+in sense that it measures changes in blood oxygenation.
+
+So you have different sources of light that are attached
+
+to the skull, and then you have others that you
+
+use for detecting them.
+
+And again, if there's a change in blood flow because
+
+of haemoglobin, that will that will affect how the light
+
+is reflected.
+
+So you can measure changes as well.
+
+Now, the spatial resolution of this technique is way worse
+
+than if it were high, right?
+
+Because you just only have a few seconds.
+
+So why am I talking about it?
+
+What would be the advantage of having this technique?
+
+Why do you think?
+
+Any ideas?
+
+Yeah.
+
+Yeah.
+
+So exciting.
+
+So one of the advantages that you don't need is
+
+a big piece of equipment and is way more mobile.
+
+Yeah.
+
+People.
+
+But you were always trying to.
+
+Are you?
+
+So hospital?
+
+Yeah, exactly.
+
+They don't have to be like in a specific lab
+
+as well, although many cases are.
+
+That is exactly that is one of the advantages.
+
+So you're sacrificing some spatial resolution to actually be able
+
+to do things like, you know, study people moving around
+
+or like study children that are not going to be
+
+staying very still in an MRI scanner.
+
+And I think these are the kind of decisions that
+
+we as scientists need to make, as we want to
+
+learn about something, we're going to discover something about specific
+
+behaviour, about the brain.
+
+What's what is the best approach for doing this, given
+
+the options that I have?
+
+So in cases where you want to study brain function
+
+in children, for example, or for example here where you
+
+want to sort of like study people interacting and moving
+
+around the environment, then obviously it's is going to be
+
+a better technique that if I'm right.
+
+Um, okay, so there are other techniques that are kind
+
+of the opposite of around some that they have great
+
+temporal resolution but not so good spatial resolution.
+
+And those are magnetic photography and electroencephalography and energy and
+
+energy.
+
+So EEG have been around for a, for ages and
+
+that was kind of the main technique that was used
+
+to study the human brain in sort of healthy individuals
+
+before any CnF MRI arrive other than just behavioural studies,
+
+of course.
+
+And so how do they what that means?
+
+Just yeah, Okay.
+
+So if you have a group of neurones, let's say
+
+a line like it will be the case in the
+
+cortex, they will have like went in different conditions but
+
+actually they will have these currents moving in one direction.
+
+Right.
+
+And that is what generates EEG signal.
+
+That's like the actual electrical activity.
+
+And at the same time there will be a magnetic
+
+field form surround that current that has gone in one
+
+direction.
+
+And that's why you can detect with energy.
+
+And I think where you can see the main difference
+
+in this really retro slide that I call it, because
+
+it just happens quite clearly is that if you have
+
+this current here, like in the case of ETI, it
+
+doesn't go like and in sort of predictable way into
+
+the skull because there is like, you know, sort of
+
+bones and other tissues and liquid and so on, it
+
+kind of deteriorates in a way that is quite difficult
+
+to understand where it's coming from.
+
+So you can still measure it here, but it's hard
+
+to say where it's coming from.
+
+And that's why EEG has a pretty bad spatial resolution
+
+for energy.
+
+This is much better because it is somehow more predictable
+
+but still difficult to understand where exactly in the brain
+
+this these signals are generated from.
+
+And there's been a lot of work in trying to
+
+do that.
+
+And there have been some advantages based like kind of
+
+I mean, when you talk to people that try to
+
+understand this and try to sort of generate models of
+
+where signals are coming from an EEG, and they basically
+
+say this is an impossible problem to solve.
+
+Like, you know, we can have like a really good
+
+like closed solution as possible, but there's always going to
+
+be a few different options.
+
+So you're going to have to make decisions in terms
+
+of how that now vanishes.
+
+There's that that because I mentioned electrical activity, basically, you
+
+know, this is direct recording of electrical activity, of neurones
+
+firing or the magnetic field is generated and the temporal
+
+resolution is excellent.
+
+So again, you might want to try to understand what
+
+experiments you want to do and whether, you know, this
+
+technique is the best.
+
+One of these techniques is by a technique that MRI,
+
+for example.
+
+And so I think I just want to show you
+
+again, you can see there's a real difference in set
+
+up here as well.
+
+So energy, again, has like this really big machine, huge
+
+magnetic field.
+
+There has to be sort of maintain you could helium.
+
+So again, quite expensive, but it now has to stay
+
+really, really still whereas EEG is quite portable.
+
+You know you can have a cap it's way cheaper
+
+as well.
+
+So trust me, you took my meds, you were like
+
+the v0y is the best thing that I could do.
+
+And then you have limitations of what your budget is
+
+as well.
+
+So, you know, that comes into it as well.
+
+And so sometimes you might want to use one or
+
+the other.
+
+And I kind of did this sort of comparison here
+
+to show you what are some of those things that
+
+you will have to take into account.
+
+So they both have excellent temporary solution, but similarly, they
+
+both have problematic spatial resolution, although as I say, energy
+
+is way better, right?
+
+However, it is way more expensive and participants have to
+
+stay very, very still.
+
+I would say that applies to each year to some
+
+extent as well, but potentially less and the sense.
+
+US.
+
+I'm in this big machine and that sort of how
+
+the people haven't thought.
+
+So you can't really move around.
+
+So you need this special lab as well.
+
+Whereas EEG is way more but more mobile and that
+
+spatial resolution is was.
+
+And I think it's also is good to take into
+
+account that the signals come from different places as well.
+
+So I'm not going to go into that.
+
+But there are differences in where they're generated as well.
+
+And and I think what is really nice as well
+
+is that right now here at UCL in Queen Square,
+
+in collaboration with all the labs in the UK, there
+
+are developments to do with some portable e.g. such as
+
+have like a few sensors that potentially measure brain activity
+
+in a specific part of the brain so that people
+
+can be more mobile and potentially have this much better
+
+temporal resolution, so much better spatial resolution with this really
+
+good temporal resolution as well.
+
+And so I think this is the main so summary
+
+of things that you can use for measuring brain activity
+
+in humans.
+
+I would really recommend you to watch all of these
+
+videos, professors from our department talk more about these techniques.
+
+And I think more once there's this is not an
+
+extensive coverage of all the techniques that you can use
+
+to study brain behaviour is more just to give you
+
+a flavour of why the possibilities are and what are
+
+some of the considerations that you have to take into
+
+account when choosing one of those techniques?
+
+So I'm going to pass to some now.
+
+So it's going to be nice.
+
+So the structure of this session is a little bit
+
+maybe obscure for you.
+
+Just to make clear why Bailey is talking about some
+
+things that I'm talking about.
+
+Other things is a video works on humans, particularly if
+
+humans.
+
+But I was always it's not quite always exclusively.
+
+I grew up as a scientist working on primates, non-human
+
+primates.
+
+Both macaque monkeys and marmoset monkeys.
+
+And I then moved when I moved to UCLA.
+
+One of the reasons I moved here is that you
+
+is basically the world centre of focus.
+
+But for trying to understand the massive small world they
+
+introduced in the last week.
+
+Writing about half of France €70 million.
+
+So the question I would like to pursue is what
+
+I want you to think about.
+
+Why would I choose to study animals?
+
+And if I'm studying animals, including mine, which seems to
+
+be so different from.
+
+Why that I'm in the experimental psychology department.
+
+Not only can I keep ahead of the problem.
+
+So I'd like to then explain to you why I
+
+find this such a beautiful experimental technique.
+
+It's really exploded over the last ten years or so.
+
+I'm going to introduce you to some of those techniques
+
+that are really appropriate for the last ten years, and
+
+we will be going into those in more detail.
+
+We've actually.
+
+But basically the reason we use animals or the reason
+
+we turned out in some kind to understand why we
+
+make based from them.
+
+By that I mean that we can and.
+
+Make small holes in their brain and introduce devices that
+
+we can then use to measure cellular function in those
+
+apple.
+
+We can never be able to cover.
+
+Study.
+
+Study.
+
+So.
+
+But why do my people wear what I love about
+
+Merhi?
+
+Even in the best case scenario, one includes something like
+
+$100,000.
+
+But we can look at the active.
+
+You need to be in the range and find out
+
+how that could be.
+
+That single macro might relate to cognitive functions.
+
+If the animals, the kinds of things that do have
+
+probably going to be very.
+
+For example, we're in the very early parts of the
+
+program.
+
+People that critics are similarly enamoured with.
+
+That makes me wonder.
+
+I mean.
+
+And I think we can learn a lot about how
+
+we see or hear, or at least the signals that
+
+come from that is or is at the centre of
+
+the brain.
+
+It's less clear how much we can learn about cognitive
+
+structure thought, for example, by studying animals.
+
+So it is when meant when we're measuring in invasively
+
+would not be very limited circumstances that if we have
+
+time we'll get back to at the end of this
+
+lecture able to make these recordings from humans and he's
+
+already introduced electroencephalogram or EEG.
+
+That's a scalp based measurement, something that's non-invasive.
+
+All the other things here, invasive measures, we might measure
+
+the electrocardiogram, this liquid surface dura between the scalp and
+
+the brain measuring almost directly neurones line underneath the electrodes.
+
+Or we could use a little invasive, like a little
+
+piece of silicon.
+
+Let it be inserted into the brain first.
+
+Slowly.
+
+And located a particular point in the brain.
+
+These have different spatial scales of measurement.
+
+Electrocardiogram from each of the electrodes from the surface of
+
+the brain, intermediate between B, g, and something else.
+
+So maybe it measures that mm accumulated the brain issue.
+
+The local feel and the electric car they find at
+
+the end of one of the electrons moving about the
+
+activity of about maybe half of their brain tissue.
+
+And then if your electrodes, these little wires on fit
+
+have been made well enough, you can actually start to
+
+see the.
+
+Speaking to people there for 2022 that you that in
+
+the next slide we call those things spikes.
+
+So this might be the signal that you would you
+
+would acquire from one of the white actor to.
+
+And the top.
+
+This is 3 to 3 traces of the same trace.
+
+On the top is what we would estimate as the
+
+local fuel potential.
+
+That's the sum that at the end of the start
+
+to activity between the records and the ground, my whole
+
+area.
+
+And you can see that normally it's a local film
+
+that was varying fairly slowly as the red line traces
+
+out some of the slow fluctuations.
+
+It's traced maybe a second or 3 seconds long.
+
+And you can see that it is dominated by these
+
+two things that are going.
+
+But it would be very gratifying to deal with these
+
+fluctuations if we then are able to look at those
+
+little rapid events and those are indicated by the red
+
+dots here.
+
+We will see that they are the extracellular signal of
+
+the action that we discussed in the last lecture.
+
+How next?
+
+Looks like from outside the city mirror.
+
+There's not quite.
+
+Now because his electrode is still quite large and there's
+
+many cells around the end of those action potentials will
+
+come from one another.
+
+It doesn't really look.
+
+Really?
+
+Okay.
+
+This better here.
+
+Okay, I'll do that.
+
+Thank you.
+
+So the point to hear the difference down here, sir.
+
+Thank you for that.
+
+Each of each of those made.
+
+It is like five or ten nerve cells around the
+
+tip of the electrode.
+
+Each of them are producing action potentials occasionally.
+
+Often you cannot distinguish between the shapes of the action
+
+potentials.
+
+Just find your own one on your own.
+
+Two on your own.
+
+Three on your own.
+
+For.
+
+So we can combine these action potentials and say, well,
+
+they're coming from single nerve cells.
+
+It's just a few of them.
+
+Five or ten of those may be in the local
+
+area.
+
+And therefore, we would call this activity the multi-unit activity.
+
+So there's multiple units.
+
+And by the way, you will come across this word
+
+unit quite frequently in this course.
+
+That just means a nerve cell in the brain recorded
+
+in this way.
+
+But sometimes if the electorate really is really nice and
+
+it's really close to the so some of her neurones
+
+in the brain tissue, you see a reproducible waveform.
+
+Looks the same every time you identify in the recording
+
+and that we would call single unit activity the activity
+
+of a single nerve cell, the same nerve cell on
+
+each turn, so able to record with this piece of
+
+wire or multiple pieces of wire.
+
+The activity of these nerve cells in the whole living
+
+brain, in animals that are awake, behaving, even moving around
+
+all environments.
+
+So we can.
+
+I think that this technique, which has been around now
+
+for several decades, try to recall the activity of nerve
+
+cells in the brain.
+
+Oops.
+
+This video shows you a video from the laboratory of
+
+Torsten Wiesel and David Hubel trained maybe 50 years ago.
+
+They won the Nobel Prize for these recordings.
+
+These videos are hard to find, so I'd like to
+
+show it here.
+
+You're going to hear you can actually play those phrases
+
+I showed you through an audio speaker and you can
+
+actually listen to the action potentials that are being fired
+
+by neurone.
+
+In this case, they're recording from the visual cortex of
+
+a cat.
+
+And they're able to work out what this neurone is
+
+saying by presenting different visual stimuli.
+
+And you'll be able to see that during the course
+
+of this video.
+
+Well, you can hear the.
+
+As I continue to continue to find.
+
+What they're doing is they're going to the frontier now
+
+where it's going to have to be a little crazy
+
+for these things to be generated.
+
+Reporter But this is a receptive field.
+
+Getting into that.
+
+And this particular unit is selected for the director most
+
+of the time and.
+
+Academic Congressional.
+
+Important political orientation of the.
+
+So that video just shows you you can use this
+
+technique to see that these nerve cells in the visual
+
+cortex are selective with the orientation, the motion direction of
+
+of a visual stimulus.
+
+And that's why they won the Nobel Prize.
+
+By using this technique, you would not have been able
+
+to determine that if you looked at the MRI signal,
+
+which is something over hundreds of thousands of nerve cells.
+
+You have to look at individual nerve cells to be
+
+able to work that out.
+
+Oops.
+
+So the ultimate goal of all this new activity is
+
+to control behaviour.
+
+And I said that there were some limited circumstances in
+
+which we could make these measurements in humans, including people,
+
+for example, who are suffering from epilepsy, where we need
+
+to measure from the brain to work out whereabouts the
+
+surgical intervention could take place.
+
+It also includes from people who in this case are
+
+suffering from paraplegia, automatically paralysis.
+
+Where the hope is that we recording the activity of
+
+ourselves.
+
+Cells will be able to help them regain function of
+
+a robotic limb.
+
+You have to effectively take what their brain, which is
+
+still intact, is sending the signals that are sending and
+
+use that to control something that we can then help
+
+them move around the world.
+
+In this particular case, these devices, which are often called
+
+utile rays, which we have used in animals, I've never
+
+used them in humans.
+
+They were developed from being used in humans, have been
+
+implanted in little part of the brain for the motor
+
+cortex, which is important in generating movements.
+
+And we'll get that in about two weeks time.
+
+I just wanted to show you this video briefly because
+
+it's incredibly evocative, like the Parkinson's video we watched the
+
+other week and say to you, when we know how
+
+we can interpret the signals and nerve cells, how powerful
+
+that can be.
+
+In this paper to people with Tetra and as two
+
+people who were unable to move their arms or legs
+
+in any functional, useful way, were able to control a
+
+prosthetic or a robotic arm simply by thinking about the
+
+movement of their own paralysed hand.
+
+And they did that using the investigational BrainGate neural interface
+
+system.
+
+So they thought about using their own arm and hand
+
+as though they were reaching out themselves with their own
+
+limb.
+
+And the robotic arm moved much the way their own
+
+arm would have moved.
+
+One of the longstanding questions not only in neuroscience but
+
+in neuro rehabilitation, is whether the cells in the motor
+
+cortex and other parts of the brain, whether they continue
+
+to function the same way years after that original injury.
+
+It is possible for people to use their thoughts to
+
+control devices, either a computer or a robotic arm.
+
+The way that happens is that we implant a tiny
+
+sensor just about the size of a baby aspirin just
+
+into the surface of the brain, and that sensor pick
+
+up the electrical impulses from a bunch of neurones.
+
+And each of those neurones are like radio broadcast towers
+
+putting out impulses.
+
+And when they get to the outside, the computer translated
+
+converts the pattern of pulses into something that is a
+
+command.
+
+One of our participants was able to do something that
+
+when all of a sort for the first time gave
+
+us all pause.
+
+She reached out with the robotic arm.
+
+She thought about the use of her own hand.
+
+She picked up that thermos of coffee, brought it close
+
+to her, tilted it towards herself, and sipped coffee from
+
+a straw.
+
+That was the first time in nearly 15 years that
+
+she had picked up anything and been able to drink
+
+from it solely of her own volition.
+
+There was a moment of true joy, true happiness.
+
+I mean, it was beyond the fact that it was
+
+an accomplishment.
+
+I think an important advance in the entire field.
+
+So I want to say that because actually that work
+
+has, as we'll go into it next week, based on
+
+the foundation of recording from these individual nerve cells or
+
+small groups of them, in this case, maybe 50 or
+
+100 nerve cells from the motor cortex.
+
+And because we know what those individual nerve cells are
+
+doing, and because we can record them simultaneously with these
+
+kinds of devices, we can infer what the signal is
+
+that she was trying to send her now arms at.
+
+And now she's now disconnected from because she has paraplegia.
+
+And because we were able to look at those individual
+
+nerve cells, we can interpret that signal in ways that
+
+is able to involve a prosthetic limb.
+
+Now, when we when that device came out into the
+
+market about 15 years ago, it seemed like a game
+
+changer move from one electrode to 100 electrodes.
+
+Well, recently and this is work from Nick Steinmetz and
+
+colleagues from just across the road here.
+
+We've developed new devices that can actually record from thousands
+
+of neurones.
+
+At the same time.
+
+These are sometimes called neuro pixel devices.
+
+We use these routinely.
+
+Most people, many people use they'll now use these routinely.
+
+We can record from multiple brain areas.
+
+Sometimes the individual nerve cells, in each case a groups
+
+of them within each of these brain areas.
+
+And I don't want you to try and understand what's
+
+on this line in terms of signals and measuring.
+
+But the point is that we can start to interpret
+
+how individual nerve cells across the brain are working together
+
+to make cognitive decisions in these small animals lives which
+
+share some of our brain capacity.
+
+The other technique that you'll be exposed to over the
+
+next few weeks is called calcium imaging.
+
+I won't again, I won't take you through this in
+
+any great detail.
+
+It relies on the fact that every time an action
+
+potentially is produced, I've talked to you about how sodium
+
+ions come flexing into the cell.
+
+There's also a little thing called calcium line to become
+
+flexing in the cell.
+
+And by designing particular molecules to sense the presence of
+
+those calcium lines and make line signals dependent on how
+
+many calcium lines are present, we can actually engage with
+
+light the internal activity of so many cells at once.
+
+We make injections or use animals of being transgenic engineered
+
+to express these little proteins in many cells in the
+
+cortex.
+
+And we can use funky little microscopes or very large
+
+ones, actually very expensive ones, to try and image the
+
+activity of those cells in the brain without, in this
+
+case, electrodes rather, using light to record the activity of
+
+these nerve cells.
+
+And this particular technique has a visual advantage with electrical
+
+recordings.
+
+We can't work out which cell we were recording from.
+
+We know it was a single cell, but we don't
+
+know which side it was.
+
+But with calcium imaging, with imaging the brain, we actually
+
+know which cell produced the activity.
+
+We can take the brain down the animal after the
+
+experiment, having killed the animal and then remove the brain.
+
+And then we can process the brain tissue in particular
+
+ways that allows us to look at the anatomical structure
+
+of that brain circuit so we can take this functional
+
+activity is activity recorded in, say, a hundred neurones in
+
+a particular part of the brain and relate it to
+
+the structural connections between those neurones and between those neurones
+
+and the rest of the brain is not to bring
+
+together.
+
+Finally, how does individual nerve cells work together in a
+
+circuit to provide cognitive function?
+
+So that's why I'm interested in studying animals, because I
+
+think that it's only by looking at the real structure,
+
+the size structure of new activity in these circuits that
+
+we'll understand the structure of cognition.
+
+Now, I think they might disagree and say that animals
+
+don't have interesting enough cognitive functions to allow us to
+
+make much inference about humans.
+
+But I hope that there will be some intersection between
+
+those two things where we can actually find some cognitive
+
+function in animals that we find interesting as humans, and
+
+where we can understand the neural circuits that actually allow
+
+that cognitive function.
+
+So that's the span of the different techniques that we
+
+might come across in this course.
+
+The next election will be about how we can apply
+
+some of these to, for example, rehabilitation.
+
+And then after that, from next week onward, movies are
+
+about specific systems, specific pathways for the brain.
+
+We better wrap it up there as as was last
+
+week, and you lead by this talk as well so
+
+we can.
+
+Thanks, everyone.
+
+During.
+
+Hi.
+
+Hi.
+
+Yeah.
+
+Yeah, I know.
+
+I worked that out this morning.
+
+You think?
+
+Yes, I'll do that.
+
+Thanks for reminding me.
+
+Like mom and.
+
+Dad.
+
+Oh, fantastic.
+
+Love to see that.
+
+Yes.
+
+Good.
+
+All right, well, I'll send those things to you today.
+
+Anything else?
+
+Not at the moment, I think.
+
+Thanks.
+
+I know at the amount of money.
+
+Tucker Carlson get.
+
+At the end of last week, they spoke briefly and
+
+say how he's doing.
+
+Yeah, I just want to know that we know from.
+
+I can't blame the people.
+
+Who are involved in the rescue issue.
+
+In 1945.
+
+Clinical Psychology.
+
+I think having different people on the floor.
+
+If you if you get.
+
+I don't get the story.
+
+I didn't.
+
+I didn't.
+
+Pretty promptly.
+
+It's getting better.
+
+I found last week because I'm given a lecture and
+
+I live next to my two or three years.
+
+Pacing was completely wrong.
+
+Yeah, I know that.
+
+She goes.
+
+Is getting inadequate lecture fees?
+
+Yes.
+
+Down here.
+
+Yeah.
+
+I knew about luck.
+
+Because the natural instinct is to end up that way.
+
+Yeah.
+
+Last week Hobson did it, and it's a week away
+
+from doing it.
+
+That's right.
+
+There's no reason show will be the best.
+
+But.
+
+Oh, come into right now.
+
+He's like, friend.
+
+We think.
+
+That there.
+
+41.
+
+Former.
+
+Better.
+
+It's been more than a game.
+
+She.
+
+Can.
+
+But.
+
+You.
+
+Life.
+
+Yeah.
+
+So that was the thing that I think everybody.
+
+That.
+
+Great.
+
+And you?
+
+I want to point out.
+
+Thank.
+
+I didn't.
+
+So.
+
+So.
+
+Okay.

raw_transcripts/lecture_6.txt

@@ -0,0 +1,1919 @@
+Hi, everyone.
+
+Do you hear me?
+
+Do you hear me?
+
+Okay.
+
+Hi, everyone.
+
+If you can take your seats and settle down, I
+
+can.
+
+Make some concessions.
+
+Okay.
+
+So today we're going to talk about technologies to treat
+
+neuro disorders.
+
+And this is kind of a follow up of this
+
+week's series of lectures, which is about kind of methods
+
+and techniques that are used for neuroscience in general brain
+
+and behaviour.
+
+So just a bit about myself.
+
+I actually started off as an engineer, which is probably
+
+why they picked me to take this lecture so I
+
+can talk a bit more details about that stuff, but
+
+you won't be examined on that anyway, so.
+
+Okay, so how can we use technology to treat neuro
+
+disorders?
+
+There's basically three main ways in which we can try
+
+and get at this kind of three broad categories.
+
+One is to use it to read from neurones.
+
+So this is something where you can use prosthetic devices
+
+that are controlled by interpreting neural activity or something like
+
+that.
+
+The second is to actually write to neurones.
+
+This is something where we try and look at something
+
+that's happening in the external world and try and write
+
+into right to the subject's brain directly.
+
+And the third is to actually just use it to
+
+control abnormal activity.
+
+So this is something where we have something like a
+
+pacemaker to control abnormal brain activity.
+
+So I'll cover these three during this lecture, mainly focusing
+
+on the first two.
+
+So in terms of the first one, you might have.
+
+So if you're trying to read from neurones, there's three
+
+kind of stages to it in general.
+
+The first thing is we need to be able to
+
+observe neural activity.
+
+So what's happening in the brain?
+
+You want to try and read that first, interpret this
+
+activity, to try to understand, well, what's happened, what's the
+
+kind of process that the individual or the subject is
+
+trying to do?
+
+And finally, then control or manipulate an external device.
+
+So in general, the last bit, which is about controlling
+
+and manipulating external devices, is more of an engineering problem.
+
+So we're not going to get into that.
+
+The main focus is going to be on observing neural
+
+activity, which is something where you need a recording device
+
+and this is kind of using neuroscience to try and
+
+develop these ones.
+
+And then we need to understand this by using some
+
+kind of computational approaches and in combination with an understanding
+
+of what the brain is doing.
+
+Okay.
+
+So what type of activity can actually be used?
+
+I mean, when I talk about observing neural activity.
+
+So this is something you might have covered, Sam Solomon
+
+would have covered in the previous lecture.
+
+The first thing is something like recording spiking activity, which
+
+is the firing of action potentials across a population of
+
+neurones.
+
+This could be either by implanting electrodes into the brain
+
+or reading from peripheral nerves in around the body.
+
+Another technique that could be used is ephemeral, kind of.
+
+Briefly touch upon that.
+
+And finally, something that's broader at a larger scale is
+
+using things like brain oscillations or EEG.
+
+So electro echo or electro cortical grabs, which is something
+
+that Sam would have covered, but it's something where we've
+
+kind of got either an external device or something like
+
+a.
+
+Cat.
+
+That's recording oscillations still.
+
+How do we then use it to how do we
+
+interpret the activity and control a device?
+
+So a third of it, the broadest device, which is
+
+the EEG, it's a non-invasive technique.
+
+So what we record is neural oscillations.
+
+These are brainwaves or from large regions of the brain.
+
+So as you can see this, it's just a.
+
+Cat which.
+
+Is looking at different.
+
+There's multiple electrons placed across the across the head.
+
+And you just basically looking at the electrical activity around
+
+that, around each of those points and using that, you
+
+can slightly localise what's happening in the brain.
+
+So what we can actually interpret is quite coarse because
+
+it's kind of recording from large regions of the brain.
+
+It's not something we can get very specific information about,
+
+but kind of contrasting activities between different regions is something
+
+like left versus right side of the head or the
+
+front in the back.
+
+And so given that it's very coarse measurement, what we
+
+can actually do is get very coarse control over things.
+
+So you can get something like you can get yes,
+
+nuances or something where you can move forward or move
+
+backwards and so on.
+
+So that is going to show an example of this
+
+in action.
+
+So this lecture is going to have a lot of
+
+videos because I think the best way to actually see
+
+what's happening, it's quite dramatic.
+
+But something.
+
+Like 50 different.
+
+Countries in the Middle East.
+
+Okay.
+
+So as you can see, this subject is able to
+
+control the wheelchair based on this new act, based on
+
+this age group that is thinking about something or based
+
+on what he's thinking or what is in this case,
+
+he was moving his head down as well.
+
+Based on what he's doing, he's able to control the
+
+wheelchair.
+
+But know that, you know, this is quite something complex
+
+happening in terms of like going up the stairs and
+
+so on.
+
+Is this probably not being controlled by the by the
+
+device?
+
+Because, as I said, it's quite coarse measurement.
+
+So what he's able to do is something like move
+
+up and down.
+
+They're just moving the wheelchair up and down or maybe
+
+move the wheelchair forwards and backwards.
+
+So there's like some amount of control that he can
+
+have, but that's about it.
+
+There's another this is it's a link to a video
+
+which is probably going to show as an idea.
+
+I know it's for you to watch later.
+
+It's I just put the link up there, but it's
+
+got quite a detailed explanation.
+
+If you're interested of how a group of students from
+
+a school come together to actually build a wheelchair that's
+
+based on EEG.
+
+So it's a group of like I think ten students
+
+and they split the problem up into the various aspects.
+
+So one team is doing kind of the EEG aspect
+
+in the data collection.
+
+One team is each there's like multiple teams doing these
+
+things.
+
+And finally they're able to control a wheelchair based on
+
+just the EEG.
+
+Okay.
+
+So one other thing is, like, this is quite a
+
+cost measurement.
+
+So in some cases what you have is what you
+
+can do is rather than use, try and interpret what
+
+exactly the brain is saying.
+
+So, you know, if you're trying to, you know, grab
+
+something and and do something, it might be quite hard
+
+to interpret that fine scaled action using this such a
+
+coarse measurement.
+
+So what you can do is do some.
+
+Hacks.
+
+And this is an example of that.
+
+To demonstrate how this technology works.
+
+Well, you get some studying nonverbal communication you can do.
+
+A lot of people are learning.
+
+What.
+
+It's like to get a lot of different types of
+
+responses, like the specific one picked up by the victim
+
+or.
+
+And nobody reported.
+
+Well, I that.
+
+Frequency of no.
+
+Except for, you know, the computer interpret the signal to
+
+give the correction some response.
+
+So the reason I picked this video is something where
+
+what they've used is kind of a hack of trying
+
+to control this, trying to get some answers.
+
+So they put this flashing light one a 12 hertz,
+
+one and 13 hertz.
+
+And it's just when you look at a flashing light,
+
+you're visual cortex usually lights up, tries to go between
+
+certain frequencies.
+
+It follows what's happening with the lights.
+
+If it's if it's oscillating, if the light is oscillating,
+
+the visual cortex is going to oscillate in in sync
+
+with that.
+
+And so they're able to just detect what the oscillation
+
+frequency is, and they're using that as kind of a
+
+hack to try and look at like, does a subject
+
+want to go left or right?
+
+So it's kind of a binary answer or.
+
+It's a binary answer and they're able, but it's quite
+
+effective at trying to get this subject who is immobile
+
+to.
+
+You can read their brain in a sentence, as I
+
+said multiple times.
+
+Now the limitation is it's a very close spatial resolution.
+
+It's the amount of information you can get is quite
+
+limited.
+
+So we can now move to another non-invasive technique, which
+
+is MRI.
+
+And you might have heard about this before.
+
+It's something that records blood oxygen levels in the brain.
+
+And we can interpret this based on the activation levels
+
+from different regions of the brain.
+
+And this is kind of going from the very coarse
+
+resolution of a few of multiple millimetres in the EEG
+
+to something more at a millimetre scale or this quite
+
+low temperature resolution.
+
+So you need like hundreds of milliseconds to actually interpret
+
+the activity.
+
+So it's a really cool demonstration that was there a
+
+few years ago.
+
+It has actually gotten a lot better in the recent
+
+years, but here's an example of it.
+
+So let me just explain what this is showing.
+
+So this is the movie that is presented to the
+
+A subject.
+
+This is a variation of that which is just they're
+
+just looking at what are the edges in that image
+
+And this is what is decoded.
+
+So you look at the brain activity in the scanner
+
+and based on the activity of the brain, they actually
+
+just trying to try and decode or guess which movie
+
+was presented based on the brain activity.
+
+So this is.
+
+So.
+
+Yeah.
+
+What's happening there.
+
+But in.
+
+General.
+
+We have to do things.
+
+Okay.
+
+Anyway, in general, what you would see is that as
+
+in this example here, you don't quite get a perfect
+
+match of what the subject is seeing, but you see
+
+some approximation of it.
+
+So it's it's it's decent, but it's it's, it's just
+
+an approximation.
+
+Again, here edges are slightly better in the movie.
+
+If you see the movie, it's usually.
+
+Okay, maybe with back elements.
+
+If you see the movie, you can see that it
+
+doesn't quite always get it right.
+
+There's there's a lot of variations in general.
+
+So one of the major limitations of ephemera is the
+
+fact that it's a huge device.
+
+So this is like it takes usually it takes a
+
+whole room and another room to have like a cooling
+
+system and so on.
+
+So it's something that's not really practical to use as
+
+a day to day device to kind of help treat
+
+or to use as a neural interface.
+
+I really hope the following videos work, but so another
+
+option is to record from periphery nerves.
+
+So this is where it's cool.
+
+So far we've been talking about recording from the central
+
+nervous system, so just the brain as such.
+
+But there's a lot of nerves in the in the
+
+body and sometimes maybe it's more effective or easier to
+
+actually get to the periphery.
+
+There's a few advantages, advantages to this.
+
+The first thing is you don't need to get to
+
+the skull where, you know, implanting anything or interpreting activity
+
+through the skull is actually quite a big challenge.
+
+So you can get across that by recording in the
+
+periphery.
+
+And this is I really hope it works an example.
+
+Okay.
+
+This is an example.
+
+So this particular subject has two kinds of prostheses.
+
+The prosthesis is either controlled by a electrode that is
+
+placed on the surface of his arm and shoulder, or
+
+there's a there's a second option, which is that they
+
+actually implant the electrode into the arm and the aid
+
+record from within the neurone as such.
+
+So the idea this demonstration is basically showing how by
+
+implanting the electrodes into the body, you're able to get
+
+better control because there's a little bit more information.
+
+So as you try to record from outside, the information
+
+is a bit more noisy in terms of as a
+
+recording technique.
+
+So this is an example of him trying to control
+
+holding an egg.
+
+You can see that with the external electrodes he is
+
+able to control it, but he's not able to control
+
+every aspect of it.
+
+And that's something where you can imagine the number of
+
+things that are needed.
+
+So in general, I was talking to you about like.
+
+Yes, nuances in the.
+
+We can just watch this again.
+
+So the surface electrodes.
+
+He's not able to really control it.
+
+Hopefully.
+
+Implanted electrodes and you can see that it's a lot
+
+better.
+
+The fact that he's able to do either just control
+
+the arm is actually quite amazing compared to what we
+
+used to have, where you just have like a phantom
+
+thing which is just attached to the body and you
+
+kind of passively control it.
+
+So in this case, this device is actually integrated into
+
+the kind of the periphery nervous system where the subject
+
+is able to control kind of the action of light,
+
+how much is moving, grabbing something and moving it in
+
+different directions.
+
+So going back a little bit to what I was
+
+saying before with the EEG, it's kind of, yes, the
+
+onesies or maybe for four ounces.
+
+Here again, you've got your recording from various neurones and
+
+you're trying to get a few different quick answers.
+
+In the case of the prosthetic arm, it's how much
+
+you want to press.
+
+How how do you want to grab something?
+
+So if it was just like grab and release, that's
+
+probably something you can get from a surface electrodes.
+
+The more information you have, the more accuracy you can
+
+get at various things.
+
+So that's the general idea of the difference between the
+
+surface electrode and the implanted electrode.
+
+And this kind of holds across various devices.
+
+So the more information you have, the more accuracy you
+
+can have in controlling various things.
+
+So this is just an example of a periphery system.
+
+And here we're recording the neural activity of individual or
+
+sorry, that was the periphery neurones.
+
+And I guess one of the limitations here is that.
+
+But in this particular case, it was pretty clear that
+
+the prosthetic arm was something that just the subject needed.
+
+But if you want to try and control, let's say,
+
+like a wheelchair or something, maybe you don't have access
+
+to these with these nerves.
+
+A lot of these the videos I'm going to show
+
+you next are in paraplegic subjects who really can't actually
+
+control any of their nerves, make them.
+
+So in that case, you need to then go up
+
+and record from the brain directly.
+
+And in this case, what you're able to record is
+
+actually a neural activity from an individual or a collection
+
+of neurones that are in the brain.
+
+And given that you're actually recording from within the brain,
+
+you can now record from a large number of neurones
+
+and you can record spiking activity at a higher temporal
+
+and spatial resolution.
+
+So I just show an example of things that showed
+
+some of this in general.
+
+So this is a braingate system which has been deployed
+
+in human subjects.
+
+This is an example of what the electrode looks like.
+
+So there's like a ten by ten grid of electrodes.
+
+It's about this big you can see in a human
+
+now, and this one is implanted usually within the brains
+
+around the motor cortex or this embedded sensory cortex of
+
+some subjects.
+
+So just to show you.
+
+This is why we call it.
+
+I think I'm showing you a bit of this video
+
+before I like to show this as an example, where
+
+this patient who's.
+
+Out.
+
+Here is abled is controlling an arm using one of
+
+these systems.
+
+And this is an example of her trying to drink
+
+coffee, have a sip of coffee from this.
+
+From above.
+
+By controlling the robotic.
+
+Arm.
+
+Then when you watch the video, you can make note
+
+of the fact that it's around 140 at a time.
+
+Samba was at 140 with in the video.
+
+You can have a look at this later.
+
+But it's something where it's quite moving because it's the
+
+first time she was able to actually actually control something
+
+by herself and then have a sip of of coffee
+
+from there.
+
+One of the things to note and this is like,
+
+as I mentioned, this is a huge engineering feat to
+
+get like an arm, a robotic arm to do something
+
+like this.
+
+So a lot of these technologies are also based on
+
+some very cool engineering that goes into the backflip.
+
+I'm not going to show, if I can, a newer
+
+version of this.
+
+Oh.
+
+Okay.
+
+So in this case, this subject again, it's got this
+
+BrainGate device and very able to browse the Internet.
+
+And usually what that is, is like you've got the
+
+cursor here bottom, it's the other video.
+
+So what this subject is able to do is actually
+
+control the cursor on the monitor.
+
+Then again, by controlling the cursor on the monitor, they're
+
+able to type in an email.
+
+Okay, So this is kind of where this is at.
+
+They're doing a lot of human tests.
+
+But as you can see, it's ethically it's basically something
+
+that you would use for paraplegic patients where they're unable
+
+to use.
+
+There's very few other options for them to actually try
+
+and interact with the world.
+
+So I'm finally going to show you something that's beginning
+
+Looking to the future.
+
+This is a demonstration by model group.
+
+Sorry, let me shut my female.
+
+Yeah.
+
+This is a demonstration from Elon Musk's team that are.
+
+So just to give you an idea of what they've
+
+come up with is as he does, he started a
+
+new company that is trying to revolutionise neuroscience.
+
+But anyways it's debateable.
+
+But one thing that they've definitely been quite successful at
+
+is developing some of these devices.
+
+So what you actually see here is a robotic device
+
+that's used to implant electrodes into the brain.
+
+And the reason for that is they've come up with
+
+this new electrode design, which is quite like what you
+
+saw before in this slide was this kind of device.
+
+Now, this is this, as you can see, the rigid
+
+structure that is placed on the surface of the brain.
+
+Neuralink instead has come up with a new version of
+
+it, of a new design where you've got independently movable
+
+electrodes.
+
+This is something that we usually use in the lab,
+
+but more but not as many simultaneous people.
+
+So they actually put in like about a thousand electrodes
+
+in to try and target individually different brain regions.
+
+And that then goes into this device, which is which
+
+is really tiny.
+
+And that's actually one of the innovations of the company.
+
+It's quite impressive.
+
+It's it's about the size of a coin, maybe like
+
+a pound coin or something like that.
+
+And so it's also quite thin and can it is
+
+within the thickness of the skull.
+
+So for a human skull and in this case they
+
+demonstrated on pigs.
+
+And so it's also within the thickness of a pig's
+
+skull so they can just implant it.
+
+So it's flush with the the surface of the of
+
+the skull.
+
+And another innovation that they came up with is when
+
+you look at the BrainGate videos, you see that there's
+
+this big cord coming out, there's this big device attached
+
+to the head, and then there's a big wire coming
+
+out instead.
+
+The other innovation that the companies come up with is
+
+that they've made everything kind of via Bluetooth.
+
+So it's wireless and so it's just on the skull.
+
+You can actually have.
+
+A go back or.
+
+You can have like the skin cover up that area
+
+once, once everything is done and then everything's going over
+
+wirelessly.
+
+So this is a demonstration of this is.
+
+Actually, this animal actually has.
+
+This animal actually has an electrode implanted in it.
+
+You just don't see any any sign of it.
+
+It's it's moving around really healthy.
+
+And so now this is where they're going to move
+
+it into an area where it can actually get to
+
+wireless signals.
+
+Okay.
+
+So the recording from like thousands of neurones, then each
+
+of these each of these rows here represents the action,
+
+an action potential firing from an individual neurone.
+
+You can see they're able to actually like while the
+
+pig is moving around, you can see looks is.
+
+Happening in real quick signals.
+
+So literally neurones that are out over here and put
+
+them on a virus which is affected here.
+
+Okay.
+
+So I was just going to show you another towards
+
+the end of this video, they're looking at like how
+
+they can interpret the activity.
+
+It's a while that hopefully loads up.
+
+So it's a bit of a weird system.
+
+So one of the things that Neuralink was it's quite
+
+controversial among neuroscientists because they kind of said it is
+
+this big advance.
+
+But in terms of to the neuroscience end of things,
+
+there's actually like a lot of what they've been talking
+
+about is something that we've known, for example, the BrainGate
+
+system, it's been there for over ten years now and
+
+it's something where you can actually decode activity in control
+
+devices.
+
+Okay.
+
+So this is an example.
+
+Of a digital activity.
+
+An example of a pig running on a walking and
+
+a treadmill.
+
+And by recording from the motor areas of the brain,
+
+they're able to actually decode the positions.
+
+I've been reading they're going to look like on that
+
+record.
+
+And we think that the photographs and records submitted.
+
+Okay.
+
+So just this that's just trying to predict various points
+
+on the limbs of the limb of the animal.
+
+And you can see that basically the actual limb position
+
+versus the predicted limb position, it's quite accurately decoded.
+
+So the mission statement of the company is kind of
+
+weird.
+
+They want to have everyone have access to these things,
+
+but that's kind of scary to me to enhance your
+
+brain.
+
+It's scary because you need to put something in the
+
+brain and make a big hole in your skull.
+
+So now they've kind of toned it down.
+
+They're talking about, Oh, we're going to use it for
+
+paraplegic patients.
+
+So they're getting human they're they're kind of getting to
+
+FDA.
+
+I think they've got FDA approval to test in paraplegic
+
+subjects who similar to the BrainGate device.
+
+And so I think that it's pretty cool for that.
+
+I just don't know how they're going to.
+
+Make.
+
+Money off of it like they want to.
+
+But it's a pretty cool tech and lot of innovations
+
+on the engineering end of it in terms of being
+
+able to record neural activity.
+
+Hopefully they bring it back, they send it back to
+
+science.
+
+Right now, everything's closed.
+
+We don't have access to any of these technologies.
+
+Okay.
+
+So the limitations, as you can expect, it's highly invasive.
+
+So again, you need to put these electrodes into the
+
+brain so it's not something that you can do that
+
+easily.
+
+And like I said in the beginning of the Neuralink
+
+thing, you've got this huge robot that they've actually designed
+
+and that's part of their part of their innovation that
+
+they needed to develop this robot to be able to
+
+implant these electrodes.
+
+Okay.
+
+So I've just reviewed a few different ways in which
+
+you can read neural activity.
+
+I'm going to skip ahead now to the second part
+
+of the talk, which is about writing to neurones.
+
+And this is something about transmitting information that a subject
+
+cannot access.
+
+And for this, we kind of.
+
+Rather than go this way, we have to go the
+
+opposite way.
+
+Who would observe or monitor the external events, interpret this
+
+information, and then edit neural activity to send it back
+
+to the brain.
+
+So how can we edit or manipulate activities?
+
+It is generally, there's a few different ways you can
+
+either electrically stimulate neurones.
+
+This is the most common method and this is something
+
+I've been talking about mostly.
+
+And then there's also a possibility of using magnetic stimulation.
+
+It's much more cause they're not that well understood.
+
+It's a very commonly used.
+
+And then more recently, there's something like optical stimulation, where
+
+you use some genetic approaches to make neurones fire when
+
+you shine light at them.
+
+Chemical stimulation is possible, but it's very hard to have
+
+precision in terms of controlling that.
+
+So I'm going to jump straight into cochlear implants, which
+
+is probably the most impressive and most commonly used brain
+
+machine interface.
+
+So this is the issue is that there's loss of
+
+hearing due to some issues in the early stages of
+
+auditory processing and by early stages that's around this region
+
+here before the auditory nerve, there's there's issues that are
+
+happening before the auditory nerve.
+
+So one of the advantages and one of the reasons
+
+why this has been such a success story is because
+
+of the structure of the ear and the auditory nerve,
+
+and that's specifically the cochlear of the.
+
+Of.
+
+The cochlear system.
+
+So this is an example.
+
+This is kind of an illustration of what the cochlear
+
+is, is is this this bit here it's the coined
+
+surface.
+
+And at different parts of the cochlear, the auditory nerves
+
+kind of go along different parts of the cochlear.
+
+And just based on sound frequencies, the way sound travels
+
+through the surface, it attenuates different frequencies at different points.
+
+So it's a beautiful design of evolution and it's the
+
+way it takes advantage.
+
+So you've got the highest frequencies at the outermost point
+
+of this.
+
+So this is around 20 kilohertz and you go down
+
+up until like a 200 hertz region that's at the
+
+apex.
+
+So this is kind of the the structure of the
+
+human cochlear.
+
+I illustrated here where you've got like the different medium
+
+frequency coming into the middle and then the lowest frequency
+
+waves reaching all the way to the apex so that
+
+the auditory nerves kind of in a way, different regions
+
+of this.
+
+And so in a sense, what this the advantage of
+
+this is this has brought all of auditory processing, which
+
+is quite a complicated process into a single one dimensional
+
+axis here.
+
+So this is one long.
+
+So if you stretch out this coil, it's basically one
+
+thing, one long stretch of tissue.
+
+And the advantage now is that if you estimate a
+
+different point of this tissue, they're able to generate different
+
+perceptions of different sounds.
+
+And that's what is taken advantage by the cochlear devices.
+
+They have a device that goes all along this.
+
+Coil and.
+
+It can stimulate different portions of this.
+
+So this is what a cochlear system would look like.
+
+So on the external side of things, you've got a
+
+recording device that this is something that's recording sounds from
+
+the outside and it's kind of doing some amount of
+
+processing of those sounds and then transmitting this to a
+
+transmitter that's on the surface of the of the skull.
+
+And then internally you've got a receiving device that's there
+
+just just on the inside of that.
+
+And then you've got another kind of stimulator or kind
+
+of a processor there and then goes into this coil
+
+device that going all along the cochlear.
+
+And you can see there's these different bits here.
+
+These are like the electrode sites and this is the
+
+electrodes that are able to kind of the cross currents
+
+to stimulate different portions of the of the cochlea.
+
+And by stimulating different parts of the cochlea, they stimulate
+
+different sound levels and different sounds.
+
+And so by having like a nice simple linear transformation
+
+and then because it's an electric signal, it's quite fast.
+
+So you can have, you know, as I'm speaking, all
+
+the different frequencies of sound that I'm conveying, are able
+
+to, you can actually process that and get it to
+
+all the different points at a very fast times.
+
+So that's the kind of advantage.
+
+And I'm just going to show you this video here,
+
+which you can watch later.
+
+It's the nice description of a doctor describing how a
+
+cochlear works.
+
+But what I find really moving is this is this
+
+is a documentary.
+
+I would highly recommend watching all of it.
+
+At some point, I'm just going to.
+
+The complete 100% sound science.
+
+What can happen?
+
+I hear what I'm saying and how it sounds because
+
+I know it sounds different.
+
+But this I find that my voice is back to
+
+normal.
+
+Hi.
+
+Makes me 70% or so.
+
+So I usually show a longer plate of the clip.
+
+I just realise it's too late.
+
+But if you noticed that her voice was changing, she
+
+took out the implant.
+
+And actually, if you saw it from earlier, it progressively
+
+gets worse and worse as she's speaking.
+
+And you can also see her getting not very confident
+
+and as she says, insecure.
+
+And then as soon as she puts it on, the
+
+voice changes completely.
+
+And that's just the fact that she gets this feedback.
+
+Rather than putting our accessibility first.
+
+We want to get people who.
+
+Actually.
+
+Complete 100%.
+
+I'll go back a little bit because.
+
+I think so.
+
+What kind of stuff?
+
+I take it off, so I keep it off for
+
+the more exciting stuff, seems to become more convoluted and
+
+becomes more difficult to think about what they ought to
+
+be something.
+
+You know what I'm saying?
+
+Because I don't think it's a matter of speaking to
+
+the cow when I pick my husband so I can
+
+hear people.
+
+So I'm not even being a complete 100%.
+
+So what's possible?
+
+So I'm a little insecure about what I'm saying because
+
+I know it sounds different.
+
+But the 70 seconds and trying to keep things back
+
+to normal, I think means.
+
+I think that one might have been clearer as you
+
+saw the progression as well as how the design changed.
+
+So you can see it's actually a really for me,
+
+this is probably the biggest success stories of a neural
+
+interface that you.
+
+So you need to have something.
+
+The deftness where it works is something where the auditory
+
+nerve is intact and then like further on, it's able
+
+to it's able to process.
+
+And most of the hearing disabilities come from kind of
+
+early hearing, early stage hearing loss.
+
+So it is quite.
+
+That's why it's so commonly used, because it's kind of
+
+an early stage thing.
+
+So moving on from hearing actually, the next one would
+
+be, well, can we actually then take this into the
+
+eye, which is the other sense.
+
+Organ or.
+
+Something?
+
+So.
+
+So this would be something where if you have loss
+
+of vision at the level of the eyes.
+
+So again, like there's quite a few issues that do
+
+happen at the eye.
+
+I think vision has a broader range of issues happening
+
+in general.
+
+So as I mentioned, the the auditory system had this
+
+nice coiled structure that actually just boiled down to like
+
+a single thing.
+
+So when it comes to the eye, it becomes you've
+
+just added another dimension.
+
+Now things are in 2D, you've got like a 2D
+
+scene that you have.
+
+You could argue that that's there in the auditory system
+
+as well, but at least the amount of information you
+
+can get across with this one dimensional structure is sufficient
+
+for a subject to get a good perception of things.
+
+But with vision, it tends to be a lot harder
+
+because you've got you've got a lot more detail in
+
+structure and we're kind of used to seeing this amount
+
+of detail.
+
+So it becomes harder to and again, you've moved from
+
+a one dimensional structure.
+
+Now you've gone to a flat surface, which is the
+
+retina here, and you've got like a two dimensional structure.
+
+So the general idea of how an implant like this
+
+would work is that you have a camera that's, you
+
+know, subject with bathroom glasses, with a camera attached on
+
+them.
+
+They've got some kind of processing that's happening on an
+
+external unit that then gets transmitted into the device that's
+
+within the eye, and then that goes onto a kind
+
+of a chip that's then this retinal implant that's then
+
+stimulating either electrically or optically.
+
+It's the surface of the retina.
+
+Now, one of the issues with this is that actually
+
+there's a lot of different receptors in the eye.
+
+So it's not just about, you know, on off in
+
+one retina region, you have colours, you have edges, you
+
+have lots of different things.
+
+So what you would get is kind of flashes of
+
+light at different parts of the of your visual field.
+
+So it's not quite detail information that you would, that
+
+we would usually do so wouldn't be able to see
+
+faces or recognise faces but kind of a flash of
+
+image.
+
+So in general I think the target of this is
+
+to help subjects get some amount of information which would
+
+help them with their day to day lives through something
+
+like if you're a child across the road and there's
+
+a car coming, you could flashlight light towards which part
+
+where the car is coming or something like that.
+
+But it's not something where you would be able to
+
+get a subject.
+
+You read a book or something as detailed as that.
+
+So it it is a much more challenging area, are
+
+trying to get a device into the eye.
+
+There's been a lot of attempts at it, but it's
+
+been quite challenging at the same time.
+
+There's also been some issues of the levity of the
+
+implant and how effective they can be and the health
+
+of the surrounding tissue, because it's quite a different tissue
+
+in the eyes.
+
+One other thing.
+
+Yeah, I'll move.
+
+On to another way of writing to nuance.
+
+I'm not going to go into the details of this,
+
+but it's something that would be useful for you all
+
+to be aware of.
+
+So this is something called optogenetic manipulation of the nerve
+
+cell activity.
+
+And this is where.
+
+So I think last week you've got you had a
+
+lecture on neurotransmitters and how things are going between the
+
+membrane of a neurone.
+
+So this is an example of this, the internal area
+
+of the brain of a neurone and the outside.
+
+And there's various proteins that are expressed on the membrane
+
+of a neurone.
+
+So what this was an innovation that was there a
+
+few years ago where they implanted, where they expressed a
+
+protein that's the ion transmitter.
+
+That was when you shine a light on it.
+
+This is actually a Dobson, which is something like what's
+
+in the eye when you shine a light on it.
+
+It then opens this channel and lets various ions through.
+
+And using this technique you're able to get a neurone
+
+to get excited or to get inhibited.
+
+So this is an example where this is kind of
+
+an illustration.
+
+You've got these blue, they're shining a blue light at
+
+different points in time, and every time there's a blue
+
+light you get, you get an action potential.
+
+And then if you use the other kind of hyper
+
+polarising protein you can get, like when you apply a
+
+different kind of the colour of light, you can even
+
+get suppression.
+
+Of.
+
+Firing in neurones.
+
+So this is a general strategy where you can use
+
+the light to activate neurones either in the brain.
+
+And actually this is something that is.
+
+Being tried out even in the eye.
+
+So trying to rather than putting in electrical activity, which
+
+is kind of which damages the tissue as well.
+
+They're trying to put in a a chip that then
+
+just transmits a light pattern onto it.
+
+I'm so not going.
+
+To go into that, but I'm just going to move
+
+on to the next part, which is about controlling abnormal
+
+activity in the brain.
+
+And this is where.
+
+So in general, when you have a normal activity, the
+
+most common method is to try and use prescription drugs
+
+to control abnormal activity or anything except like something invasive.
+
+So these methods that I'm going to talk about are
+
+usually only considered with all the other methods being targeted.
+
+No, we're going to show this slide, which is not
+
+being used, but hopefully not being used anymore.
+
+But, you know, something like in the 1930s where I
+
+used electroconvulsive therapy, the reason I put this up is
+
+this is kind of something maybe that is popular.
+
+You might have seen movies doing this or heard about
+
+something like this where they put a large current between
+
+the between across the brain, which is just causing it
+
+is the large electrical stimulus that is affecting the electrical
+
+activity in the brain.
+
+And that then causes changes in the in the neural
+
+structure.
+
+And that was used.
+
+It induces a seizure.
+
+And the idea was that it would then help relieve
+
+symptoms of mental illness.
+
+So it's highly controversial and there's like severe side effects.
+
+So, you know, it's been covered in popular media quite,
+
+quite a lot.
+
+So I'm sure you can find more information about that.
+
+But it's something that is a historically used technique, but
+
+it's not no longer used.
+
+But I thought it's useful to just talk about things
+
+that are not being used as well.
+
+So it's something that's actually much more effective is and
+
+currently used a lot.
+
+It's deep brain stimulation.
+
+So this is something where you've got electrodes that are
+
+implanted into the brains of an example of you've got
+
+a bilateral implant into two parts.
+
+And it's the common targets include the dynamic nucleus, which
+
+is around there within the brain of the Globus paladins.
+
+That's also another structure.
+
+Both are within the stratum of the brain.
+
+So this is so these are implanted.
+
+You can see these there's like three little points there.
+
+Those are the electrode sites.
+
+And this is then goes into something like a pacemaker
+
+that's placed somewhere in the body, which then can be
+
+recharged and so on.
+
+And that's delivering pulses periodically.
+
+I'm just going to show you a video.
+
+Of how.
+
+This can be quite effective.
+
+I hope this works.
+
+So this is a subject with deep brain stimulation on
+
+and off.
+
+So you can see that.
+
+Yeah.
+
+They just can do some.
+
+Tasks or.
+
+They have this huge tremor that they.
+
+So you can see it's really effective at alleviating some
+
+of the symptoms.
+
+This is a this is a subject with Parkinson's disease.
+
+Another huge success story.
+
+To be honest, I don't think we actually we do
+
+know a little bit about how it works, but some
+
+of it is a bit of a mystery.
+
+It just works.
+
+So that's kind of there's quite a lot of research
+
+going into how how it's being used and how they
+
+can improve the design of it right now.
+
+So yeah, so one of the other things about debate
+
+simulation before I end the lecture is that it is
+
+I think coincidentally it has been doing some research going
+
+into how it might be useful in chronic pain or.
+
+In.
+
+Depression and so on.
+
+So there's some trials happening in trying to use it
+
+in other mental health or other issues, but I think
+
+these are just kind of coincidental where somebody with an
+
+implant might show an elevation of other symptoms.
+
+And so they're exploring these possibilities.
+
+It wouldn't be implanted in a subject unless it's the
+
+last it's kind of like the last choice because it's
+
+quite an invasive technique.
+
+So some advantages of using these simulation techniques is that
+
+while the methods are used as a last resort, there
+
+are some unique advantages.
+
+So they can be spatially very specific regions of the
+
+brain.
+
+So this is pretty clear.
+
+With deep brain stimulation, you get to a specific area
+
+rather than stimulating the whole area by drugs kind of
+
+systemic.
+
+So it goes across the whole grain.
+
+So there's an exception to this where you can maybe
+
+present an L-dopa drug, which is something for Parkinson's, which
+
+goes just to open the magic cells, or there's some
+
+new techniques where you've got some designer drugs, where you
+
+can use some genetics to target specific cell types.
+
+But this is something that's kind of being geared up
+
+for the future.
+
+And the other advantage to this, other than being spatially
+
+specific, is that it can be temporarily specific.
+
+So you could just turn on the stimulation for some
+
+periods of time and run them for short periods.
+
+I haven't really covered this, but there are some trials
+
+in using magnetic transcranial magnetic stimulation, which is the magnet
+
+kind of stimulating and externally.
+
+And there's some attempt to at that using that for
+
+depression and other disorders.
+
+Okay.
+
+So that's that's it for the lecture today thank you
+
+very much.
+
+Invited to take a look at this.
+
+Okay.
+
+Let me just you know I'm for the course.
+
+I guess I'm wondering if it's kind of like it's
+
+a very different kind of question.
+
+And I think it's very.
+
+I didn't recognise.
+
+This.
+
+Right.
+
+My first.
+
+Question was, yeah, you know, they looked like that they
+
+would use classification so they would use.
+
+But I don't think so.
+
+I don't.
+
+Think that's.
+
+It.
+
+But I think a lot.
+
+Of it because that's kind of where.
+
+The question.
+
+I've read about it.
+
+Yeah.
+
+I was wondering.
+
+If you think.
+
+Different stuff and stuff.
+
+Yeah.
+
+Yeah.
+
+Yeah, I think so.
+
+Either it's just people.
+
+People look at the number that people because are looking
+
+for something better not to excavate.
+
+You know.
+
+Some people from different parts of the country or.
+
+But increasingly critical of the United States is going to
+
+get to the point where it looks like you're going
+
+to have to talk to people from different parts.

raw_transcripts/lecture_7.txt

@@ -0,0 +1,2213 @@
+Okay.
+
+Is this working?
+
+Is this working.
+
+On the back?
+
+Okay.
+
+The task in this week's lectures is try and help
+
+you understand a little bit about what comes into the
+
+brain and what goes down.
+
+We're going to spend a lot of time in discussing
+
+what goes on between those two stages, but the access
+
+to the outside world and how we affect our muscles
+
+are the two primary functions of the brain.
+
+Yohannes Mueller was one of the parents of sensory science,
+
+along with Helmholtz in the late 19th century, and it's
+
+hard to put it better than this.
+
+So I'll just read this out from his book in
+
+1935, where he detailed a lot of specific nerve energies.
+
+What Miller said was that the same cause, such as
+
+electricity, can simultaneously affect all sensory organs, since they are
+
+all sensitive to it, and yet every sensory nerve reacts
+
+to it differently.
+
+One never passes as light, another hears it a sound,
+
+another smells it, another tastes.
+
+The electricity, another one feels it as pain and shock.
+
+One nerve perceives a luminous feature through mechanical irritation.
+
+Another one hears it as buzzing.
+
+Another one senses it as pain.
+
+Sensation is not the conduction of a quality or state
+
+of external body to consciousness or the conduction of quality
+
+or state of our nerves to consciousness.
+
+Excited by an external cause.
+
+So in this lovely, flowery 19th century prose that we
+
+don't use, unfortunately now what we were trying to say
+
+is that we do not have access to the outside
+
+world.
+
+What we have access to in terms of our perceptions,
+
+our cognition is the activity of the sensory nerve fibres
+
+that sense the outside world and provide the signals to
+
+the rest of the brain.
+
+It seems rather commonplace now, but at the time it
+
+was quite a revolutionary idea.
+
+It has analogies in more modern sensory science, and when
+
+we would talk about things called labelled lines, where we
+
+think that individual nerve cells contribute to a particular quality
+
+or sensation, for example, one nerve cell might signal the
+
+readiness of something in the world, another one might signal
+
+the greenness of something.
+
+Another one might signal the fact that that object appeared
+
+in a particular part of your visual field or on
+
+a particular part of your skin.
+
+Those are the labels that are attached to the activity
+
+of those nerve cells.
+
+One of the major challenges of neuroscience is to understand
+
+how the activity of nerve cells is translated into perceptual
+
+and cognitive states.
+
+And we are not there yet.
+
+But what we do know a lot about is how
+
+it is that those nerve cells can provide the signals
+
+that we need to access information about the outside world.
+
+I can spend several lectures talking to you about the
+
+structure of sensory nerve cells and cells, but I'm not.
+
+And I'm going to try and instead try and communicate
+
+to you three general principles, which I think for me
+
+at least, are the basis for understanding sensation.
+
+The first is that sensory receptors and we will understand
+
+a bit more about sensory receptors in the moment and
+
+not evenly distributed.
+
+Different parts of the body have different densities of sensory
+
+receptors, and for that reason, we use different parts of
+
+our bodies for different things.
+
+For example, we touch stuff with our fingers.
+
+We have a high density of contraceptives.
+
+We look at things in particular ways.
+
+We trying to bring their gaze, our gaze on objects
+
+so that the objects are projected onto the centre of
+
+our visual field.
+
+There are more photoreceptors in the centre of our visual
+
+field, so these different densities of receptors have large implications
+
+for how the brain is structured.
+
+And I'll take you through that.
+
+The second principle is that sensory signals are sent to
+
+the cortex along parallel pathways.
+
+This doesn't have to be the case.
+
+We can imagine a sensory receptor trying to encode everything
+
+it can about the outside world and sending all those
+
+signals to the rest of the brain.
+
+Instead, it seems that some receptors encode something the readiness
+
+or the grain issues and others and other things the
+
+blueish ness or the green regions of the brain of
+
+the outside world.
+
+These signals are therefore sent along parallel pathways to the
+
+rest of the brain.
+
+And this parallelism is the idea that different parts of
+
+the outside world are represented within the same modality by
+
+different nerve cells is key to understanding how the signals
+
+get the cortex.
+
+And may also be key to understanding how the cortex
+
+is organised.
+
+And the third thing I really want to get through
+
+in this lecture is that cortex creates the cerebral cortex
+
+creates topographic maps of the sensory periphery.
+
+I hope you understand the sentence in detail by the
+
+time we get through this next 15 minutes.
+
+The idea is that the cortical represents representations that we
+
+have that we use to see, to feel, to hear.
+
+They are constructed representations of the outside world such that
+
+the map of the body or the visual field is
+
+projected onto the cerebral cortex.
+
+And these topographic maps are key to understanding how at
+
+least early parts of the cerebral cortex, the initial stages
+
+of perception are organised.
+
+So these are the three things I really want to
+
+try and get through to you in the next 50
+
+minutes.
+
+As I said, I could spend five or six lectures
+
+on sensory receptors themselves.
+
+I'm not going to spend one slide.
+
+This is because the basic structure of sensory receptors is
+
+pretty similar, and there's only one thing you really need
+
+to know about it.
+
+That is that those sensory receptors take some form of
+
+what we want to say.
+
+Interruption of the sensory surface and convert that into a
+
+nerve nerve signal, a spiking action potential.
+
+For example, photons of light come through in the eye
+
+and hit the back of the retina where they sign
+
+photoreceptors.
+
+And those photoreceptors in turn, transduced that light into an
+
+electrochemical energy, which they then pass on to the rest
+
+of the brain touch receptors and specialised nerve endings which
+
+are sensitive to the displacement of the membrane.
+
+So when there's a pressure on to the skin that
+
+membrane displaces.
+
+And that in turn is converted into electrochemical energy and
+
+sent to the rest of the brain ordering auditory receptors.
+
+Hence those in the ear specialised receptors which in which
+
+those things sense the vibration of the membrane, the tympanic
+
+membrane, and they then transform that vibration into magical electrochemical
+
+energy that is sent to the rest of the brain.
+
+So these sensory nerve endings are all just simply basically
+
+transmuting that external stimulus into something that is an action
+
+potential.
+
+Effectively.
+
+I've learned a lot in that sentence, but it's what
+
+you need to think about.
+
+There's a couple of definitions I just want to get
+
+us through as well.
+
+The first is that essentially receptors signals the presence, that
+
+is the actual detects the presence of an object and
+
+signals at a location on the body.
+
+So if we can imagine a stimulus saying, let's just
+
+think the easiest to think of touching your skin, if
+
+you touch it very lightly, you can't feel it.
+
+Or you can because if someone else touches in very
+
+lightly, you would feel that is only when you make
+
+a strong enough indentation of the skin that you can
+
+feel pressure.
+
+And so as we discussed in a couple of lectures
+
+ago, now, those have thresholds.
+
+They need a minimum intensity of a stimulus to generate
+
+an action potential.
+
+And so you can imagine gradually increasing the amount of
+
+pressure that someone applies to your skin.
+
+And at some point, you will notice that.
+
+And that's because as the stimulus intensity increases, so there
+
+are small changes in the resting membrane potential of these
+
+nerve cells.
+
+And at some point in time, that small change is
+
+sufficient to drive the occurrence of an action potential.
+
+As we talked about in the third or fourth lecture.
+
+So there's a threshold, there's a minimum intensity which are
+
+below which you're not sensitive.
+
+INVISION Minimum intensity is several photons.
+
+In a perfectly black environment.
+
+We turn all life off here.
+
+We did what we call dark adaptation that is sat
+
+in the dark for half an hour.
+
+And your world photoreceptors incredibly sensitive.
+
+They can actually detect the presence of a few photons
+
+is really useful if you're running around the savanna late
+
+at night trying to avoid lions.
+
+And so they can be very sensitive, these receptors, but
+
+they still need a minimum level before they can sense
+
+something and signal something that would be, say, the threshold.
+
+The next point is that as you increase the intensity,
+
+the stimulus, at some point in time, you generate a
+
+number of action potentials.
+
+So at this point in time below here, below the
+
+stimulus intensity, this neurone may not be signalling the presence
+
+of the stimulus above that it does signal the presence
+
+of the stimulus and indeed the action potentials that the
+
+neurone produces increase with the intensity of the stimulus.
+
+So the number of action potentials is neurone produces signal
+
+something about the intensity of the stimulus in the outside
+
+world.
+
+This function is often called a sigmoid because it looks
+
+a bit like an S, and you'll be encountering it
+
+several times over the next few weeks.
+
+The second related concept is that all sensory neurones have
+
+receptive fields.
+
+While sometimes we try and work this out, but it's
+
+really, really simple.
+
+The idea is that sensory stimuli, even if it's an
+
+effective stimulus, let's just say it's a finger press on
+
+your arm.
+
+Each individual nerve cell is sensitive to a particular location
+
+on the arm that that finger is put.
+
+And if the finger is put somewhere else and the
+
+rest of the body at nerve cell is not going
+
+to sense it.
+
+So it has a receptive field.
+
+It has an area of the skin within which this
+
+object, your finger, needs to be placed for the pressure
+
+to elicit a response from that nerve so that its
+
+receptive field will go through that in the second.
+
+The same concept can be thought of in terms of
+
+vision.
+
+In that case, nerve cells in a visual pathway may
+
+only respond if a light stimulus is placed in a
+
+certain part of the visual field, say up here and
+
+to the right.
+
+It won't respond if in space over here or down
+
+here or up here is the location in the visual
+
+field or exactly equivalently the location on the retina where
+
+that image is projected, where those receptive fields are.
+
+So that's a receptive field location on your body, whether
+
+on your body sensory surface, whether it is in the
+
+eye, the cochlea, wherever, whereabouts.
+
+So it takes information from.
+
+It only takes you from a limited part of the
+
+visual world, from limb, part of the body, etc..
+
+And you can think of this.
+
+We often think of these receptive fields as having a
+
+non-uniform sensitivity across that, and we'll get into that in
+
+a second.
+
+But the idea here is that basically at the periphery
+
+of the recipe field, the nerve cell is not very
+
+sensitive.
+
+You have to make very strong indentations for the nerve
+
+cell to respond, whereas in the centre of the receptive
+
+field, it's very sensitive in response to slightly weaker indentations.
+
+We can measure that by, for example, placing a stimulus
+
+at different points relative to the receptive field.
+
+And if we do that and measure the number of
+
+spikes that are produced by a neurone, we would see
+
+something like this profile, like a Gaussian, usually a normal
+
+distribution whereby the same stimulus is capable of finding many
+
+spikes when space in the centre of the receptive field,
+
+but only a few in space on the periphery.
+
+Now, the observant of you there will think, well, hang
+
+on a sec.
+
+If if there is any field means that the number
+
+of spikes in your produces for the same stimulus depends
+
+on the location with respect to this centre of the
+
+receptive field.
+
+And the number of spikes produced depends on the intensive
+
+stimulus.
+
+Isn't there a confound there?
+
+Isn't there something?
+
+Couldn't I trade off the intensity of stimulus for the
+
+spatial position and get the same number of action cancels
+
+from this nerve?
+
+So.
+
+And if you were thinking that that's precisely correct, that's
+
+one of the major compounds in sensory pathways, trying to
+
+extract the important things from what is often multiple different
+
+types of causes that could give rise to the same
+
+number of action potentials.
+
+And hopefully we'll be able to get through that a
+
+little bit later in this lecture.
+
+So I said that receptive fields at his low clients,
+
+discreet places in your skin or in your eyes or
+
+wherever with something is responsive to this is most nicely
+
+exhibited in the snout essentially system because the body the
+
+skin provides his surface, which he can explicitly think about
+
+or simply feels.
+
+And there's actually been some recordings from humans here where
+
+you put a small electrode into one of the nerves
+
+in the arm and you can, in five circumstances, pick
+
+up the activity of sensory nerve cells and those nerves.
+
+And you can map out the respective fields of both
+
+sensory nerve cells.
+
+And it turns out that they look a little bit
+
+like this, honey, to form circles on the hand here.
+
+And you see that they have different sizes such that
+
+they're a bit larger.
+
+If you're on the palm of the hand and it's
+
+quite a bit smaller from the fingertip.
+
+And you can think of that here.
+
+For example, having many small receptive fields on the thumb
+
+of the finger and large ones on the palm of
+
+the arm.
+
+Fewer of them.
+
+So it turns out this is, as I said, as
+
+a general principle, since we systems that distribution of receptors
+
+on the body or in the eye is not the
+
+same across the whole body.
+
+Some parts of the body have much higher density of
+
+receptors and some have much lower density.
+
+However, the whole surface is what we call tile or
+
+antisense receptors.
+
+That is, every part of the skin or every part
+
+of the eye has at least one sense for detecting
+
+stuff in there.
+
+So the combination of these two things, the timing and
+
+the sizes, has profound consequences on our sensory abilities.
+
+You can actually do this yourself, or rather you can
+
+do this with a partner.
+
+If you get a paper clip and expose the two
+
+ends, you can do what's called a two point discrimination.
+
+The idea there is that if you move the ends
+
+of the pits further and closer together, you can change
+
+the distance on the other parts of the skin that
+
+you're going to stimulate when you press that paperclip onto
+
+the skin.
+
+Now, if those two points are close enough together and
+
+you put it on, say your arm here, you detect,
+
+you experience the sensation of just having a single pinprick
+
+on your on your arm.
+
+If, on the other hand, you stuck that on the
+
+finger, you will detect or experience two different distinct pinpricks
+
+in your fingertip.
+
+So what's the reason for that?
+
+Why is it that the same stimulus feels like one
+
+thing?
+
+One's on your arm or on your palm for two
+
+things.
+
+One is on your fingertips.
+
+So the reason for that can be is logical from
+
+the structure of these receptive fields on your fingertips or
+
+on your thumb.
+
+The receptive fields are very small, so that seems distance
+
+apart of those two pinpricks will activate two distinct sensory
+
+receptors and evacuating two distinct sensory receptors, you will sense
+
+two distinct objects that are touching your skin.
+
+On the other hand, if those same interests are made
+
+on your arm, you're activating only a single sensory receptor.
+
+And if you activate only a single sensory receptor, you'll
+
+feel only one object on your skin.
+
+So the size of these receptors means that you can
+
+distinguish between two objects or one object being present.
+
+I'm not going to talk much about the subcortical pathways
+
+for presentation.
+
+The key point here in the Spanish sensory system, and
+
+as we'll discover in a second in the visual system,
+
+is that these signals are taken from the skin, in
+
+this case through the spinal cord, taken up through the
+
+thalamus, everything goes through the thalamus of cerebral cortex, and
+
+they project upon what is called the primary somatic sensory
+
+cortex.
+
+It's not a sensory to touch primary because that's the
+
+major source of input from the thalamus.
+
+So the primary cortices are those part of the cerebral
+
+cortex, the input from the thalamic relay cells for each
+
+different modality.
+
+And they form this, they project in this case onto
+
+the present.
+
+So we'll see in a second in the cerebral cortex.
+
+By the way, a lot of what we know about
+
+this is actually from work, from Walter Penfield and his
+
+colleagues in McGill.
+
+Back in the 1940s and fifties, where as they were
+
+preparing patients for surgery for epilepsy, actually made in different
+
+parts of the cerebral cortex.
+
+And that's what the patients felt.
+
+These experiments are no longer very often conducted, but they
+
+were incredibly illuminating at the time.
+
+They were able to map out in humans the structure
+
+of this amount of sensory cortex, for example, by asking
+
+people what they felt when you stimulated different parts of
+
+the cortex.
+
+So this is the central stool because these are going
+
+to be the potential supertankers get some fees.
+
+This is a central focus as part of the major
+
+Suvi in the brain and before pre and post after
+
+the simple superset is post mains behind towards the back
+
+of the brain premiums in front was a frontal brain
+
+and if you looked along this potential suitcase, you find
+
+a structure which is incredibly beautiful.
+
+What happens there is that if you stimulate different parts
+
+of this personal sulcus, some person will report that they
+
+feel sensations at different parts of their body.
+
+So, for example, if you down on the lateral side
+
+and you stimulate it, you might find that some reports
+
+that they felt a sensation on their face.
+
+Whereas if you're up on the top medial side, that
+
+report, instead of sensation on that front or on the
+
+foot or leg.
+
+So depending on whereabouts alone, this person was suicidal whereabouts
+
+and cerebral sucres are you are encoding.
+
+You are representing activity on different parts of your skin.
+
+I think this gives rise to the concept, which is
+
+the homunculus in terms of the touch among us means
+
+little man.
+
+And if you look at the representation of the body
+
+on this first episode, the touch representation, you find that
+
+this continuous representation of different parts of the body and
+
+different parts of the body that are closer together are
+
+generally speaking, represented closer together on the cortex.
+
+So if example, the foot is represented a similar location
+
+to the leg or the trunk, whereas if face the
+
+lips and the nose are represented close to each other
+
+and in between these of that hand in the arm.
+
+So you get this map of the body that's formed
+
+on this matter sensory cortex.
+
+It's the different types of touch that you can get
+
+in different parts of your body as represented on the
+
+similar sensory cortex.
+
+And you find that actually some parts of the body
+
+seem to be overrepresented.
+
+For example, the face is a large part of the
+
+sensory cortex, whereas the foot is quite a small part,
+
+even though its size is relatively speaking, even not in
+
+many cases in the face or the trunk, for example,
+
+occupies almost a minuscule part of the cerebral cortex.
+
+And the reason for that is fairly obvious if you
+
+think of just one simple principle.
+
+Every sensory receptor has about the same amount of cerebral
+
+cortex devoted to it.
+
+It follows then that we have more sensor receptors, for
+
+example, on your finger, on your thumb, on your face,
+
+you'll have more cerebral cortex devoted to that part of
+
+the body.
+
+And when you have less sensory receptors, it shrunk your
+
+arm, your leg, you have less part of the body
+
+devoted to that is what we would call cortical magnification.
+
+The idea that the cerebral cortex is like a magnifying
+
+glass onto your body.
+
+That magnifying glass, how much it magnifies depend on the
+
+density of the sensory receptors at that part of your
+
+body.
+
+This is what the locomotive looks like if you're trying
+
+to represent it as an intact human being.
+
+This cortical magnification has some implications.
+
+It means that your ability, as I said, to detect
+
+small changes in the position of objects or the presence
+
+of two objects instead of one depends on the density
+
+of sensory receptors and therefore the amount of cerebral cortex
+
+that's actually devoted to that part of the skin.
+
+This graph here shows you compares is perceptual, the psychophysical
+
+acuity that you have the different parts of your body
+
+and that low numbers in mean high acuity.
+
+That means you're very sensitive to small distances and large
+
+numbers being low acuity.
+
+That means you in much larger distances between objects to
+
+determine tunes at one there and can see that the
+
+areas of the body with the largest or the lowest
+
+acuity at a lower arm of the arm, shoulder, belly,
+
+back breast, thigh, half all those areas where you know
+
+yourself that when you touch those things, you're very less
+
+tense, very much less sensitive to the structure of the
+
+things that are touching that part of the body.
+
+Whereas for example, the fingers and the upper lip, the
+
+cheek, the nose have much higher acuity and much more
+
+sensitive to different the structure of the things that are
+
+touching the body.
+
+So this density of receptors determines the amount of cerebral
+
+cortex that is actually devoted to that part of the
+
+sensory apparatus.
+
+And that amount of cortex is devoted to that.
+
+Sensory in turn dictates how sensitive or how how much
+
+acuity you have, the sensory stimuli that impinge in that
+
+part of the body.
+
+I just briefly wanted to show you the structure, the
+
+visual pathways, very similar.
+
+I'm not going to go through all these lines.
+
+I just want to illustrate to you from a paper
+
+that we produced many years ago now, that in the
+
+eye there are retinal nerve cells which include photoreceptors that
+
+signal they're actually communicated by a little network of cells
+
+in the retina, which you learn about later stages via
+
+ganglion cells, whose axons make up the optic nerve.
+
+Those ganglion cells in turn go to this little structure
+
+in the thalamus the lateral clinic is, and from there
+
+their signals projected the primary visual cortex or V1.
+
+So very similar in structure to this, not a sensory
+
+pathway, except that one went through the spinal cord to
+
+get the thalamus and then the cortex or this one
+
+from the eye or straight through the optic nerve, through
+
+the thalamus and the visual cortex.
+
+There are different pathways from the eye to the thalamus,
+
+and that's to visual cortex.
+
+We often call these the P of the M or
+
+the PARTICELLE, and the Minnesota pathways is quite a bit
+
+in the reading that I suggested you do that discusses
+
+how the signals of these nerve cells differ.
+
+I just want to introduce you to the idea that
+
+they actually have different structure and different types of signals.
+
+Now, I said on the cement essentially surface, you can
+
+tell quite easily that the finger, for example, is what
+
+you used to touch on things, and you can feel
+
+the fine gradations in the texture, for example, the surface.
+
+Similarly, if you look in the eye, if you take
+
+a photo through the eye and this is what a
+
+photo through the eye looks like, you see an object.
+
+This is the bit where the optic nerve starts with
+
+the axons of the ganglion cells come out of the
+
+eye and go into the optic nerve.
+
+It's also the place where the blood vessels come into
+
+the eye from the optic nerve.
+
+This is the picture of the eye through a fan
+
+scope and in the middle of the eye.
+
+See, the structure is called the phobia.
+
+It's an incredible structure.
+
+And this structure, you've got no blood vessels.
+
+This is Photoshopped as a smaller than anywhere else in
+
+the body.
+
+And then the other apparatus in the retina has been
+
+pushed away.
+
+So the photos have to have direct access to the
+
+light that comes through the lens and hits the retina.
+
+And in this location, in this part of the eye,
+
+the small part of the eye is about three or
+
+four millimetres in size.
+
+You have this incredibly dense population of nerve cells called
+
+cone photoreceptors, and that's represented by this paper down here.
+
+You can see the density of these cones peaks in
+
+that area.
+
+And that means that there's because there's so many different,
+
+so many more photoreceptors in this particular part of the
+
+eye that you can distinguish between an object that's slightly
+
+displaced.
+
+So when I wanted to see the structure of the
+
+visual world, what I need to do is I need
+
+to move my eyes around so that part of the
+
+world that I'm interested in falls on the phobia.
+
+Because then I can distinguish the difference between what might
+
+be, for example, a happy face, a sad face, a
+
+bald face.
+
+So if I want to see that fine special detail,
+
+someone at the back of the room who's sitting there
+
+looking at me, that is about one quarter of my
+
+thumb.
+
+And is it slightly less than one degree of ice?
+
+If I want to be able to distinguish the difference
+
+between someone's eyes or their face to recognise their face,
+
+I have to bring my phobia onto that object.
+
+I have to move my eyes so that that part
+
+of the visual falls onto my phobia where I have
+
+this really dense array of photoreceptors.
+
+I won't talk about them at all.
+
+But the gods, the ones which are important for night
+
+vision actually more dense just outside of the phobia.
+
+And so it turns out if you're ever out there
+
+in the dark night looking at the stars, if you
+
+want to see a star, you don't look directly at
+
+it, you slightly side of it.
+
+And that's because of what photoreceptors are actually absent from
+
+the photograph from the centre of your gaze.
+
+And instead you need to bring that light onto the
+
+side of your phobia with regard to actually most dense.
+
+It turns out that this structure, this density photo receptors
+
+in the in the phobia, which is so much greater
+
+in the phobia than elsewhere in the eye, is paralleled
+
+by changes in the structure of the subsequent nerve cells
+
+in the eye.
+
+And the consequence is that we can't see fine spatial
+
+detail in the periphery of our vision.
+
+This again is the idea of cortical magnification.
+
+We can see fine spatial detail when we're looking directly
+
+at something, but not when away from that centre of
+
+our guys.
+
+Our cortex has magnified that small part of the visual
+
+field, which is occupied by the phobia.
+
+I think that's about the size of your thumb.
+
+That part of the visual field where all these thousands
+
+of kind photoreceptors are sitting waiting for light to come.
+
+The primary visual cortex is actually totally magnifying that part
+
+of the visual field.
+
+Some estimates would put it to be something like 20
+
+or 30% of primary visual cortex is devoted to this
+
+tiny little part of the visual field, and the rest
+
+of the visual field is consequently represented by many fewer
+
+ganglion cells, cells in the cortex.
+
+So therefore we're much less capable of seeing the finer
+
+spatial detail away from the centre of gaze because the
+
+cortical magnification is so pronounced for us.
+
+For real.
+
+You can see this yourself.
+
+If you have a look at this slight demonstration here.
+
+If you look in the centre of this thing here
+
+on the projector, you should be able to read.
+
+If you look where the arrow is, you should be
+
+able to define or distinguish what each of the different
+
+letters is.
+
+Does everyone agree with that?
+
+Approximately.
+
+If you look at the centre, you can still see
+
+this on the left, the K on the right and
+
+left from bottom on the top.
+
+It's like going to.
+
+I then if, on the other hand, you look at
+
+the air over here, you should not be able to
+
+define many of the letters.
+
+They are present there.
+
+So you may be able to see that the ace
+
+in the S is there and you could see the
+
+K in the R, But many of the things like
+
+T.P. y are actually indecipherable to you.
+
+And the reason for that is that what I've done
+
+in making this diagram here is scale the size of
+
+the letters so that they occupy approximately the same amount
+
+of cerebral cortex when you're looking at the centre of
+
+the diagram.
+
+And because they'll find the same amount of cerebral cortex,
+
+you're equally able to see all those letters.
+
+But when we look at the eye and this is
+
+no longer matched, sometimes that is a much smaller and
+
+occupying enough of the cerebral cortex.
+
+The magnification is wrong.
+
+So this viewpoint.
+
+So you are less able to be able to detect
+
+what these different letters are.
+
+Hmm.
+
+I said that there were parallel pathways that take the
+
+signals from the eye to the visual cortex, and these
+
+are quite pronounced if you look in the thalamus.
+
+You can see in this little structure overlap, which is
+
+a beautiful structure.
+
+I spent most of my life studying it.
+
+So I think it's beautiful.
+
+It's called that unique because it looks a bit like
+
+a me.
+
+If you're younger than me, actually bend your knee, then
+
+you would look a little bit like me.
+
+And in this little genic nucleus, which you can see
+
+by the naked eye is these different layers or parts
+
+of magnet.
+
+So it layers smaller and larger cell bodies.
+
+And it is these layers.
+
+Now we know that these cells would communicate different things
+
+to the cerebral cortex.
+
+These different layers get different inputs from the eye, in
+
+particular these ganglion cells, the cells that form apple to
+
+the eye, to the thalamus.
+
+The particular ones are much smaller.
+
+They're going to pass through the magnet.
+
+So everyone's a much larger.
+
+They're going to be sterilised.
+
+And then these signals of these thalamic neurones then go
+
+to primary visual cortex.
+
+Now, turns out there's very few ways to test this.
+
+But the only in fact, the only way to really
+
+test is supply small lesions, as we discussed last week.
+
+You can place small lesions in the brain, in animals,
+
+in a small controlled lesions, and you can destroy some
+
+of the nerve cells in the palm.
+
+So all the magnet, some of the layers.
+
+And if you try an animal farm to report things
+
+about the outside world and therefore ask whether or not
+
+these nerve cells that come from the right things in
+
+the retina and send them to the cerebral cortex with
+
+these nerve cells saying different things, the cerebral cortex.
+
+And it turns out they do.
+
+So, for example, in this set of beautiful work is
+
+Bill Murray and to conduct in the late 1980s and
+
+90.
+
+Summarised in this review that I cited here, the idea
+
+is that there's a lesion this place in the palm
+
+of the layers of the macaque monkey.
+
+Or in the magnesium layers of the of a different
+
+macaque monkey with monkey before the length made.
+
+This monkey is trained to report simple things about the
+
+outside world.
+
+What the colour they trying to simply report.
+
+What is something they will not.
+
+In a particular location.
+
+Hmm.
+
+If there was something that I went to make one
+
+important.
+
+If there wasn't a to make another report.
+
+These graphs here, the solid lines show the capacity of
+
+the animal to detect something which varies either in the
+
+kind of striping this of the patterns that are present
+
+or in the flicker.
+
+That is the kind of amount of times per second
+
+something flickers, a light flickers.
+
+Africa is defined by the tempo frequency.
+
+That is how many times a second something, because the
+
+spatial frequency here is just how many of these fine
+
+bars you have in one degree of visual angle, the
+
+solid limestone, what the monkey does in the normal case
+
+without a lesion and the different points.
+
+So the monkeys performance when you've after you've made a
+
+lesion, it turns out that if you make a lesion
+
+at the end pathway, you have almost no impact on
+
+the monkey's capacity to detect the spatial form of an
+
+object.
+
+Whereas if you make a leap into the pathway, this
+
+is almost most.
+
+On the other hand, if you make a lesion at
+
+the pathway you detect, you abolish the animal's capacities, the
+
+black lines here to detect very rapidly flickering things.
+
+Whereas if you abolish the pathway, we preserve the capacity
+
+to detect those rapidly flickering things.
+
+And finally, if you lesion the pathway, you kind of
+
+the monkey cannot see coloured objects, whereas if you lesion
+
+the pathway, the monkey can.
+
+So these things, these different perceptual abilities in the presence
+
+and absence of different pathways suggest that the different signals
+
+that come from the eye to the cortex carry qualitatively
+
+different and qualitatively different signals about the outside world that
+
+carried along the parallel pathways to the cerebral cortex where
+
+they are.
+
+Then we combine.
+
+So when we get to Cortex, we've got all these
+
+parallel pathways doing stuff in the sensory periphery, whether in
+
+visual cortex and other sensory cortex, wherever it is.
+
+We have these parallel pathways from a sensory final thalamus,
+
+bringing all this information up to the cortex.
+
+And somehow the cortex has to rearrange these interesting judgements
+
+about the outside world.
+
+For many years.
+
+Before that, the brain was basically you what you're born
+
+with.
+
+You had that there was no plasticity in the brain.
+
+It took several decades of experiments to actually reject that
+
+hypothesis.
+
+I want to show you a couple of those experiments
+
+in the substance lines on this line.
+
+These are some of the very early experiments that were
+
+able to reject the hypothesis that the brain, the cerebral
+
+cortex in particular, was indifferent to experience.
+
+It was the same when you were born as when
+
+you were dying.
+
+These two experiments relied again on work on monkeys because
+
+these monkeys were easy enough to be trained to report
+
+what had happened to to the outside world.
+
+In the first experiment here, I want to say is
+
+the monkey was trained to hold the fingers against a
+
+little rotating disc, and I had to make judgements about
+
+that rotating this, I think the direction of motion, that
+
+rotating disk using the fingers only.
+
+The question was, would the experience, the long term experience
+
+of making this judgement with your fingers change the representation
+
+of the fingers in the cerebral cortex?
+
+And the way that the researchers went about trying to
+
+address that question is that they made electrophysiological recordings from
+
+this ninth century cortex of these monkeys before, during and
+
+after training to do this simple task.
+
+And what they find is summarised in this slide here,
+
+which is a little bit complicated, but the end result
+
+is very straightforward.
+
+So this is recording from this mid-century area of an
+
+al monkey, people that monkey, and they're recording from the
+
+region that is most important in representing the hand associated
+
+before it's a monkey.
+
+Listen, the sensory cortex that's there now monkeys as it
+
+is in humans.
+
+What they did was they made recordings from these part
+
+of the cortex before experience, and they found a particular
+
+representation of the digits, the final four digits, five, which
+
+of the hand in this part of the cortex.
+
+And that's described over here.
+
+So is the fifth, fourth, second or third digit.
+
+And the normal here.
+
+In the normal case, these different digits have approximately equal
+
+parts of the cortex devoted to them.
+
+However, following this experience, following this training, you find a
+
+substantial overrepresentation of the second and the third digit, and
+
+those are the two digit, the two fingers that the
+
+animal is using to make this judgement.
+
+So prolonged exposure to these kind of tasks has changed
+
+how the cerebral cortex is organised.
+
+It has increased the amount of cerebral cortex that's important,
+
+that's used for extending information from those two digits.
+
+The animals used to do the task.
+
+So the brain is plastic.
+
+The organisation, the cerebral cortex is plastic.
+
+It can adapt to the structure of experience and tasks
+
+that we would need to accomplish.
+
+Although a substantial amount of work as shown this many
+
+different systems since, and this was the original work to
+
+show that this plasticity was there.
+
+I really encourage you to read it with a beautiful
+
+set of experiments.
+
+The converse is it can also be studied.
+
+That is what happens when you lose a digit or
+
+lose some part of your sensory periphery.
+
+In this case, if the animal, for example, loses a
+
+third digit.
+
+This case is surgically removed and the seizure.
+
+Again, you can make the recordings before and after that
+
+surgery.
+
+And again, you can measure in this case again from
+
+one case in the parts of the brain that represent
+
+the hand.
+
+And you find, at least in some cases and this
+
+is still controversial, that when the third digit is removed,
+
+a bit of the cerebral cortex that was responsible for
+
+including things that happened on that anger now include things
+
+that happened on the second or the fourth or the
+
+ninth and fingers.
+
+It's like this piece of cerebral cortex wants to do
+
+something, wants to do anything.
+
+And in the absence of any input from the third
+
+digit, it's asking for input from the second and the
+
+fourth digits help the brain represent things that are going
+
+on there.
+
+So the brain is the cerebral cortex is plastic.
+
+It can adapt to changes in the input from the
+
+outside world.
+
+Say this is not uncontroversial.
+
+In some systems, this seems to be less the case,
+
+and some systems seem to be more the case.
+
+It is certainly dependent on what kind of life injury
+
+happened early.
+
+Younger people who suffer injuries have more cortical plasticity.
+
+Older people have less.
+
+One of the things that this leads to is phantom
+
+limb.
+
+And I just want to spend a couple of seconds
+
+showing you a really effective video from one of the
+
+leaders in this field.
+
+Ramachandran.
+
+I find this quite an effective video, so just spend
+
+a couple minutes on.
+
+Twins First patients this Derek Steen.
+
+All right.
+
+One of Ramachandran first patients was Derek Steen.
+
+13 years ago, he was involved in a motorcycle accident,
+
+and I pulled the nerves out of my spinal cord
+
+up in my neck.
+
+They told my parents directly that I would never use
+
+my arm again.
+
+About seven years ago, I was reading through the classifieds
+
+and I saw an ad in there.
+
+Amputees wanted that.
+
+It was a joke like that.
+
+It's just basically connecting the club to the ball.
+
+So I called the number and it was Dr. Ramachandran.
+
+Go relax.
+
+Today, Derek is teaching Ramachandran how to play golf.
+
+But several years ago, Derek made a crucial contribution to
+
+Ramachandran pioneering work in brain science.
+
+Yes, I was amazing.
+
+After my surgery, I sat up in the bed and
+
+still felt the arm there.
+
+Still felt everything there.
+
+And I'm looking down and I'm seeing nothing.
+
+It was pretty bizarre.
+
+The more I thought about it, the more it hurt.
+
+The more it hurt, the more I thought about it.
+
+So it was it was like it was never ending.
+
+I mean, I'd break out in a cold sweat and
+
+turn pale.
+
+Just standing here talking to you because the pain would
+
+hit so bad.
+
+If there is any one thing about our existence that
+
+we take for granted.
+
+It's the fact that we have a body.
+
+Each of us has a body.
+
+And, you know, you give it a name, it has
+
+a bank account and so on and so forth.
+
+But it turns out even your body is something that
+
+you construct in your mind.
+
+And this is what we call your body image.
+
+Now, of course, in my case, it's substantiated by the
+
+fact that I really use a body with bone and
+
+tissue.
+
+But the sense I have, the internal sense I have
+
+of the presence of a body and arms and all
+
+of that is, of course, constructed in my brain and
+
+it's in my mind.
+
+And the most striking evidence for this comes from these
+
+patients who have had an amputation and continue to feel
+
+the presence of the missing.
+
+How?
+
+It was the beginning of an important relationship.
+
+Important for Derek, because not only would he finally understand
+
+his phantom pain, he would also get to the bottom
+
+of a mysterious sensation he felt while shaving.
+
+When I first started shaving after my surgery, I would
+
+feel my absent hand start to hurt and tingle whenever
+
+I shaved this left side of my face.
+
+Meeting Derrick was important for Ramachandran because the explanation he
+
+came up with would rock the world of neuroscience.
+
+Photograph.
+
+That's just my arm.
+
+The first thing Ramachandran did was to invite Derek to
+
+his lab for a simple test that I want to
+
+touch different parts of your body.
+
+And I just want you to tell me what you
+
+feel and where you experience the sensation.
+
+Close your eyes.
+
+I could feel that on my forehead.
+
+Anything anywhere else?
+
+No.
+
+So my nose.
+
+Okay.
+
+My chest.
+
+Your chest.
+
+Okay.
+
+I can feel that on my cheek and I can
+
+feel rubbing on the phantom left hand.
+
+On the phantom left hand in addition to your cheek,
+
+I'm going to run the Q-Tip across your jaw and
+
+see what happens.
+
+I can feel like you did by my cheek and
+
+I can feel a stroking sensation across the phantom hand.
+
+You actually feel that stroking across your phantom hand.
+
+Okay, so that small visual video and you can just
+
+it goes on for a while.
+
+I encourage you to watch it.
+
+That shows the fact that this person has lost their
+
+arm, that some part of their representation of their body
+
+has distorted not just the inside of the brain, but
+
+also perceptually cognitively.
+
+And the likely explanation for this is that one part
+
+of the likely explanation for this is that the representation
+
+of the face is actually quite close to the representation
+
+of the hand.
+
+And as we saw with the monkey who is missing
+
+the third digit, when you lose inputs to certain parts
+
+of the cerebral cortex, that cortex seems to want to
+
+do something anyway, stop to draw input from neighbouring cortical
+
+areas.
+
+So that part of the body which was representing the
+
+arm is now no longer there.
+
+Now he's also drawing input from the face as clearly
+
+more complicated than just simply saying that because this person's
+
+body image is constructed, image is something that is not
+
+simply explained just by the amount of sensory cortex, but
+
+that distortion in the cortical representation is going to contribute
+
+to the fact that this person feels something, even though
+
+there is no longer there is plasticity is important in
+
+helping this, in helping the brain effectively try to reconstruct
+
+or to do what it would like to do, even
+
+in the absence of inputs.
+
+I just want to spend a couple of minutes facing
+
+what will be spending most of the next lecture on
+
+or the next one.
+
+And I'd really like you to do some reading in
+
+the next section, which is this review that I've put
+
+up online from Colby and go back to leaders in
+
+the field reviews to look at old.
+
+Now that is probably the best conceptualisation of the ideas
+
+we'll go through in the next lecture.
+
+We discussed that, that sometimes that is kind of a
+
+frame of reference in which you understand these sensations is
+
+is depends on how you want to think about things.
+
+I just want to explain to you what I mean
+
+by frames of reference for a few slides.
+
+So when we look at the cerebral cortex, we see
+
+this translated into many distinct areas and visual cortex, for
+
+example, as primary visual cortex.
+
+But then there's about three or four, maybe even ten
+
+or 15 different visual areas that sit next to primary
+
+visual cortex, the whole higher order cortical areas or association
+
+cortex.
+
+The same is the case in similar sensory cortex, the
+
+same effects in the auditory cortex.
+
+You have these primary areas, then you have these multiple
+
+other satellite areas.
+
+And the question arises, one that actually puzzled researchers for
+
+many decades now is why do you have so many
+
+cortical areas?
+
+Why don't we just have one area that's responsible for
+
+vision, one area that's responsible for autism?
+
+And the hypothesis that I'd like to explore in the
+
+next lecture is very much like these parallel pathways from
+
+the sensory periphery to cerebral cortex.
+
+These different cortical areas act as parallel representations or parallel
+
+constructions of the outside world.
+
+Each area is doing something, creating a slightly different interpretation
+
+of the outside world.
+
+This then raises the question of how can these different
+
+the things that are arising in these different cortical areas
+
+be brought back together?
+
+How can the different maps of the outside, both the
+
+construction of the outside world, be reconciled?
+
+And the second thing that starts when I ask is
+
+these topographical photographs and statements, these things that are maps
+
+of your body, your maps of your eyes, that's fine
+
+If we want to, you know, represent the precise location
+
+in our body that something happens.
+
+But it's not very useful if we want to move
+
+around the world where I need to know where my
+
+location is with respect to this table.
+
+With respect to the microphone.
+
+With respect to these chairs.
+
+So the question that arises is how these topographic maps
+
+of the sensory body of the body of the eye,
+
+how these transformed into something that could be behaviourally useful,
+
+could actually help us move around the world accomplish tasks.
+
+It was not very useful.
+
+Just simply know that this is a place of my
+
+hand or my arm.
+
+Sorry.
+
+I would like to know where that place is with
+
+respect.
+
+For example, if my arm is moved with respect to
+
+the rest of my body.
+
+So I want to order frame a frame of reference
+
+in which I can understand these different aspects of my
+
+movement throughout the world.
+
+And that's that is the majority past of what we
+
+call the parietal cortex.
+
+And that's what we're going to be spending the next
+
+half, the next lecture on.
+
+And as I said, I'd really like you to read
+
+that coding review because that will help you understand what
+
+it is that the cortex is trying to do, how
+
+it's constructing maps of the outside world that we can
+
+use to move around them.
+
+And so we, we, we investigated that on Friday, and
+
+I look forward to seeing you there.
+
+Thanks.
+
+Yeah.
+
+I was.
+
+Yes.
+
+So it's and particularly in two volumes.
+
+It was.
+
+Particularly a good topic for the show.
+
+But something about.
+
+Are you actually doing.
+
+It where it's kind of.
+
+Surprising for you to feel particular?
+
+I can't quite remember where where we are at with.
+
+I think the general sensation of like, I'm going to
+
+take on you, that's relatively easy enough to understand.
+
+This is the migration and it's kind of been associated
+
+with the reaction.
+
+You know how it is that.
+
+According to what's called a predictive coding framework in the
+
+world.
+
+Where you can predict quite well what the temptation is
+
+that you.
+
+Should get.
+
+Right because you're doing.
+
+Something and you can because you know what you should
+
+be getting ready to.
+
+Predict and therefore surprise what is predictable.
+
+And think there's a framework of understanding brain function, which
+
+Professor SEO has been particularly.
+
+Important from guidance.
+
+Which is that the job of the brain, you basically
+
+find out things that are not.
+
+And so a lot of the architecture, the brains that
+
+Christians are predicting, that includes, you know, perception, suppressing, not
+
+encoding things that, you know.
+
+I mean, for example, I think that.
+
+You can suppress your own sensations, especially during actions.
+
+So that's predictive protein, which is really influential in.
+
+On the questions regarding the object.
+
+Yes.
+
+So yes, in exactly the same way.
+
+It's easier to see the things overlap altogether.
+
+Like, yeah.
+
+That's where you can.
+
+Something.
+
+I think, optimism.
+
+And because here.
+
+And in my.
+
+You.
+
+Yeah.
+
+Yeah.
+
+The overlapping.
+
+For one thing, the idea of hiring people sometimes out.
+
+I'm very.
+
+Part of life, as you can imagine, is just a
+
+single.
+
+You would.
+
+But even in this case.
+
+Consequently.
+
+That often.
+
+That changes.
+
+Central brain function.
+
+Yes.
+
+Like many.
+
+And so even when you figure.
+
+It was final.
+
+Expect to really point and explain everything.
+
+Thank you.
+
+Thank you.
+
+So.
+
+And would the to.
+
+Yeah, I look at that because it's so much easier
+
+to like.
+
+Yeah.
+
+Okay.
+
+Yeah.
+
+You know, like in our.
+
+I mean, the idea is to.
+
+Always have an interactive story, but I don't know the
+
+exact exact.
+
+I like.
+
+I felt.
+
+I don't know.
+
+I mean.
+
+Yes.
+
+Okay.
+
+And I knew it would be like.
+
+Well, this.
+
+So people.
+
+And.
+
+We know.
+
+Know.
+
+I.
+
+You know this.
+
+Yeah.
+
+Yeah.
+
+Oh.
+
+Yeah.
+
+People.
+
+I think.
+
+And.

raw_transcripts/lecture_8.txt

@@ -0,0 +1,2111 @@
+Nothing like working with your kids at 9:00 in the
+
+morning.
+
+Can you hear me up the back there?
+
+Is it being amplified?
+
+Okay.
+
+Thank you.
+
+So in the last lecture, I tried to help you
+
+understand convey to explain to myself that the input to
+
+the brain from the senses is this array of signals
+
+carried by nerve cells that represent something about the outside
+
+world.
+
+But that array of signals coming in through the sensory
+
+nerves is carried, is constructed over a series of parallel
+
+pathways, each of which carries slightly different types of information
+
+about the outside world.
+
+And that when you get to the cortex, these pathways
+
+are then converge and build maps, topographic maps of the
+
+sensory periphery.
+
+That might be a topographic map of the retina, a
+
+topographic map of the skin of the cochlea, etc..
+
+And what I hope that I got for you as
+
+well is that those maps are distorted and distorted by
+
+the density receptors in different parts of the skin or
+
+the eye.
+
+For example, those maps can be plastic, although we don't
+
+know exactly how much and when.
+
+Those maps aren't.
+
+Incredibly useful for the in the world, they're very good
+
+at representing what's happening on the surface of our body.
+
+But if we want to make movements through the world,
+
+then we have to do something else.
+
+We have to transform those maps into something that is
+
+in a coordinated frame, a frame of reference that is
+
+behaviourally useful.
+
+And the structure of this lecture is to try and
+
+take you through some of the folks in the brain.
+
+So some of the mechanisms that seem to be at
+
+least the starting point of constructing those frames of reference.
+
+That.
+
+I want to reinforce in this lecture as well.
+
+That.
+
+Interest in the signals that come through the sensory periphery
+
+of the cortex are carried in parallel.
+
+These reference frames are also constructed in parallel.
+
+We build many different reference frames at the same time
+
+in the brain.
+
+And what we seem to do is to try to
+
+use a particular reference frame when we need to accomplish
+
+a task like picking up the phone.
+
+In that case, I might use a reference frame which
+
+is centred on my hand because that's where the most
+
+important part is.
+
+So I'm going to take you through those reference frames
+
+in the first part of this lecture and then I'm
+
+going to use those to provide a framework to try
+
+and understand potentially what the mechanisms are for a new
+
+or interesting type of nerve nerve circuit in the brain,
+
+which is that from mirror neurones, which many, many of
+
+you may have heard about.
+
+Now, I said to you a couple of lectures, Alexa,
+
+ago that these lectures were designed when we were in
+
+the pandemic and I was pre-recording them, and I'm struggling
+
+to work out the exact pacing, and I discovered that
+
+to my course this week.
+
+I've what I've done is there's a section of the
+
+notes in your slides called Controlling Movements, which I'm going
+
+to omit from today's lecture so that we can discuss
+
+these more interesting aspects of the brain.
+
+I have uploaded a pre-recorded version of that sections about
+
+10 minutes long and it's accessible for me on Moodle.
+
+Simon and I'd like you to have a look at
+
+it when you have a chance.
+
+It won't be necessary for understanding the rest of the
+
+content of this lecture, although there are a couple of
+
+subtleties that may be apparent.
+
+I want to be the performance of the U.S..
+
+Oops.
+
+I just want to start the selection with with a
+
+recording that I obtained some years ago from sources I
+
+can't remember.
+
+There's one particular reason which I want to show you
+
+this recording, and I'll tell you that at the end
+
+of it.
+
+But it also introduces to the idea of spatial neglect.
+
+Has anyone here heard of spatial neglect before?
+
+Anyone?
+
+Put your hand up.
+
+Oh, in that case, you prepare for your mind to
+
+be blown because spatial neglect is one of the most
+
+interesting unsolved mysteries of brain function.
+
+So this video, this first video should help introduce you
+
+to it, and then we'll discuss a little bit about
+
+that and the mechanism why that occurs.
+
+To be to the point of this of this the
+
+first part, you turn to the benefit of the doubt.
+
+Frequently you start to look at all of the actual
+
+numbers.
+
+Positional alignment serve the purpose of this guide to address
+
+those with respect to state of excellence.
+
+Hold accountable for their support for the weakest example of
+
+the various forms of principle over interesting example.
+
+Just the complication of that simplistic classification to perform this
+
+simple graph, for example, statements that not appear for the
+
+first time to read the code, to describe the patient,
+
+etc. to make sense of this cause some features of
+
+the text, but contextually so.
+
+Another way of testing the directive to ask the patient
+
+to open page because he came over to Iraq and
+
+the patient neglected to use the right side of the
+
+page only occasionally some consideration of extended meditation or whether
+
+is something in the collection.
+
+So this is not behaviour so cheerful coffee perception whether
+
+they succeed in school.
+
+But of course this difficult because because of excessive force
+
+mistakes exceed the features which they create are not really
+
+active.
+
+However, you can get something set up and use that
+
+can be completed in subject.
+
+In this case the patient of social with a reserve
+
+of the device.
+
+Stick with the public, look at the same table for
+
+the right side, etc. but for the patient safety and
+
+security of the same patient Refugee Convention.
+
+These findings, together with the description the patient suggests that
+
+medical detectives actually complete the sight of a doctor, at
+
+least a photo with ways for them to gather, to
+
+look at symmetrically to take.
+
+Okay, So I want to share that video, particularly for
+
+the verbal description from the patient who has neglected completing
+
+those letters on the page.
+
+And you can sense from from that description how automatic
+
+recollect or her description of the scene is.
+
+It's not like she's struggling through all that, something we
+
+think that she does perceive through the letters that she
+
+is aware of.
+
+So this neglect is a really strange and powerful thing.
+
+It's very rare.
+
+It seems to entail the distortion of a perceived space,
+
+and it seems to, although not described particularly here, it
+
+can actually occur in more than one of different reference
+
+frames.
+
+Two of them were were illustrated here, those reference frames,
+
+one with the left side of visual space, and the
+
+other was the left side of an object.
+
+I'll get back to the second one in a minute.
+
+And in fact, it's a very complex film.
+
+We don't understand it very well.
+
+A lot of this work and some of these references
+
+in the slides actually come from colleagues at the Institute
+
+of Cognitive Neuroscience, which is about 120 metres that way
+
+in Queens Square particularly.
+
+Don't drive it.
+
+It's now unfortunately dead.
+
+But a lot of the descriptions came from studying patients
+
+with particular types of lesions that we'll get to in
+
+a second.
+
+This is a very automatic absence of awareness of a
+
+part of your visual field or part of an object
+
+or part of something.
+
+It really suggests that when we construct and model our
+
+vision now interpretation of the outside world, we're using different
+
+types of representations to do that.
+
+And depending on whether or not they are all intact,
+
+we have the capacity to access an appropriate one for
+
+the task at hand.
+
+So as was alluded to in that description, neglect is
+
+not simply an absence of awareness, at least not in
+
+some simple way of being blind.
+
+So, for example, these are two particular examples of how
+
+you might test neglect in some patients, and in this
+
+case, a person, a patient with a left hemisphere stroke
+
+was asked across that sort.
+
+I think there should be right hemisphere stroke should actually
+
+cross out the components of a navel figure.
+
+And they both figure as these figures which have a
+
+structure but are actually made up of themselves of little
+
+structures, in this case, letters like A's.
+
+And so the patient in this case crosses them all
+
+the right hand side of the figure.
+
+However, when when asked to describe the figure can actually
+
+say it's a square or a circle.
+
+So there's some strange things going on in this neglect.
+
+And similarly, down here on the on the bottom, this
+
+is a really lovely experiment from John Driver, where they
+
+did something akin to what you see in the in
+
+the video.
+
+Here's what the patient is asked to to draw.
+
+You can see that when asked to draw a right
+
+hand side cap, they can reproduce that fairly well.
+
+However, when I draw a left hand side, a very
+
+poor reproduction of that cat, this is a very interesting
+
+way of asking the question Is it part of the
+
+left visual field or left hemisphere part of my vision,
+
+or is it the left part of an object?
+
+Very simple test.
+
+Ingenious.
+
+To come up with this, ask the patient simply to
+
+draw.
+
+We draw each of these two identical objects and you
+
+can see that in both cases, the left hand side
+
+of the object is emitted, not the left hand part
+
+of the visual field.
+
+So when the object is tilted to the right, it's
+
+still the left hand side of the object that is
+
+emitted.
+
+So neglect is a really strange and worrying for the
+
+patient, but intriguing for the experiment.
+
+A form of brain damage.
+
+And a lot of that research still goes on at
+
+the Institute of Neurology and the Institute of Cognitive Neuroscience
+
+just down the road.
+
+So what does neglect tell us about representation of the
+
+world in our brain?
+
+As I said, neglect entails an inability to perceive the
+
+relationships of things within a particular frame of reference, a
+
+part of the visual field upon the object and other
+
+ones that I haven't gone through here.
+
+Depending on the spread and the focus of the brain,
+
+there is the damage the affected frame of reference can
+
+be.
+
+Egocentric, olive centric, extra or personal.
+
+And I hope that you understand each of those terms
+
+by the end of this lecture.
+
+It suggests that there isn't one single spatial reference frame
+
+in which the world is viewed through which we see
+
+the world.
+
+Instead, there are several, each with their own neural representation,
+
+each of which can be deployed depending on the task
+
+at hand.
+
+And we expect that it should be possible to identify
+
+the different frames of reference in the brain.
+
+And I should note here, by the way, that most
+
+people that show neglect also show other forms of deficits.
+
+And the reason for that, generally speaking, is that the
+
+brain damage that leads to neglect often spreads to other
+
+areas and other functions.
+
+So to understand then what we're gonna be talking about,
+
+I need to describe to you the different types of
+
+frames of reference that we can describe.
+
+And this picture summarises them.
+
+The two classes are really egocentric for Ellis and egocentric.
+
+It's very easy to think about.
+
+It's just with respect to the ego, to the body.
+
+So, for example, with respect my body, this is my
+
+right and this is my left.
+
+If I turn around, that's to my right and that's
+
+to my left hand to my eye.
+
+If I'm looking at you, then that's part of the
+
+visual world in my right, part of the world on
+
+my left foot.
+
+If I look over there, there's two parts of visual
+
+world to my right and my left.
+
+But who was in the left field now is on
+
+the right hand side of my.
+
+That's an egocentric form of representation, something that's with respect
+
+to my body.
+
+It could be my head, my retina.
+
+It could also be other forms that discover in a
+
+second.
+
+The other major class of frames of reference is our
+
+essential world centric spaces.
+
+So, for example, a GPS gives you coordinates in north,
+
+south, east, west.
+
+That's a world centre in space.
+
+It doesn't depend on the direction I'm facing.
+
+Again, if we go right here, this is my right.
+
+That's my left I'm facing.
+
+So it's my right and it's my left.
+
+I'm facing east now, So although east and south have
+
+not I worked with and south have not changed in
+
+the other central continents, by my figures, in accordance has
+
+changed.
+
+So the Alessandra coordinates base that will based or even
+
+sometimes object based reference frames.
+
+These are things that are independent of our and our
+
+own body position and depend only on the structure of
+
+the world outside.
+
+It turns out that that's the most stable representation to
+
+use because that doesn't depend on where I'm moving.
+
+But we do choose when we describe something in the
+
+world to other people, we often choose to use egocentric
+
+reference frames.
+
+So for example, if I was to describe how to
+
+get out of the building, in my case, I got
+
+that turn left, turn left again, turn right and then
+
+go straight ahead.
+
+That's an egocentric description.
+
+I could say that third, south and east and slightly
+
+north and east again.
+
+And that would be another centric description of the same
+
+towns.
+
+I won't describe much about either centric, but I will
+
+just introduce you to the idea that these two things
+
+can be distinguished in development and in perception.
+
+These really elegant experiments show you that kids originally formed
+
+egocentric representations of the world around them and then gradually
+
+formed these worlds and centric presentations.
+
+So in one in one experiment shown on the top
+
+infants, less than one year, I placed in a room
+
+and the there's two doors to the room and they're
+
+sitting around the table with the experimenter, and their mother
+
+appears at one door and then the child is rotated
+
+in the room.
+
+The room doesn't change.
+
+The charges were rotated around the table.
+
+And the question is, where does the child expect the
+
+mother to peer from from the same door that she
+
+was at before or from the door that is on
+
+the right hand side of that child, which is the
+
+egocentric reference point.
+
+And the answer is that at least in young infants,
+
+they will prefer to look and to expect that for
+
+the mother to come from the right hand or that
+
+is the wrong doors.
+
+But the one that is on their right hand side
+
+is to their egocentric preference example.
+
+Now this Dallas centric discapacidad show which World Baseball and
+
+its fans develop very slowly.
+
+And indeed, some people remain pretty poor even when they
+
+get into adulthood, including myself.
+
+So this task is illustrative of that.
+
+In this task, one would ask a child or a
+
+toddler to indicate on the right here what the view
+
+from this horse is of this pattern of events here.
+
+Is it A, B, C, or D, just have a
+
+loophole here.
+
+Who thinks it's A, The view of the horse is
+
+represented.
+
+Okay.
+
+What about B?
+
+A couple of people see.
+
+Few people.
+
+They have a few people.
+
+The answer is B, with the red, blue and yellow.
+
+Proceed from left to right in the view of the
+
+horse would be to see it from the left to
+
+the right.
+
+So that's an that's a reimagining or interpret the world
+
+from another point of view.
+
+And that's interpreting what from another point of view requires
+
+that kind of understanding, because you have to build that
+
+representation in a world based audience based on your own
+
+context.
+
+So these two abilities, egocentric and polycentric reference frames develop
+
+at different rates and the egocentric comes first.
+
+As I said, I'm not going to talk much about
+
+our centric map here because Hugo is actually going to
+
+take you through that quite a bit.
+
+And I feel like this time when we talk about
+
+spatial memory and other aspects of historical function, but the
+
+fundamental basis of these other centric maps, these cognitive maps,
+
+was actually discovered at UCL by John O'Keefe, whose building
+
+is in the anatomy building.
+
+I think somewhere in the top drawer.
+
+He's still there, still researching.
+
+He must be 80 now.
+
+He won the Nobel Prize a few years ago, but
+
+it hasn't stopped him.
+
+And he discovered, as Hugo described to you, that if
+
+you recall from the hippocampus of a mouse or a
+
+rat wandering around a small wooden box, that the cells
+
+in that hippocampus will often fire in a particular location
+
+in that particular part of the puzzle.
+
+And further experiments show that that the position in the
+
+box where they respond to the red dots and the
+
+thing, the black things, the trajectory down through that space,
+
+red dots, when the neurone fires, we can show you
+
+via various manipulations that that representation of space that is
+
+embodied in that Nero's place cells activity is actually half
+
+a century.
+
+I want to spend the next few slides discussing taking
+
+through some of the egocentric reference frame that emerged in
+
+Cortex.
+
+So I've discussed already.
+
+One might be an extended work from reference.
+
+That is, if you move your eyes from this red
+
+dot here.
+
+If you look at this on the red dot, Wall-E
+
+is on the right hand side of your visual field.
+
+If you then transfer your case to the right to
+
+the dot on the right one is now on the
+
+left hand side of the visual field.
+
+That's an eye centred reference frame your eye moves and
+
+therefore consequently the position of the objects in the world
+
+moves with respect to the centre of gaze and with
+
+respect to your retina, even though they haven't changed position
+
+in the world.
+
+Similarly, this hits into reference frames, things which with respect
+
+my head.
+
+One example of that is audition sounds that have arrived
+
+at the head and are encoded with respect to the
+
+direction of the head and the eyes don't move unlike
+
+the eyes.
+
+And so that reference frame is based.
+
+There's other frames of reference, for example, joint frames of
+
+reference again for reaching out and grasping this thing.
+
+I might like to include the world in the context
+
+of the joints that are required to pick up this
+
+and handle this environment to tell me that the 20.
+
+So a good deal of work in monkeys that are
+
+described in humans has shown that these special frames of
+
+reference I'm almost certainly built to start to be built
+
+in the parietal cortex and prior to the cortex, the
+
+visual cortex, back of the brain.
+
+Frontal lobes are here, temporal lobes are down here in
+
+the proper lobes here, and it's parietal cortex, or at
+
+least this bit of the parietal cortex is important in
+
+generating representing the spatial reference frames found in the particular
+
+part of the parietal cortex around the parietal sulcus.
+
+What this image shows here is a summary of many
+
+studies looking at neglect with left sided neglect and the
+
+density, the colour of the blobs on the side of
+
+the brain that represent the probability effectively that damage in
+
+that part of the brain would have been associated with
+
+neglect.
+
+You can see there's very high concentration around this issue
+
+prior to Super Square.
+
+If you have damage, then you get this form of
+
+neglect or some form of neglect.
+
+So if we we Inhumans, we find out it's quite
+
+difficult to look in the exact new machinery in this
+
+part of the brain.
+
+But it is possible in monkeys.
+
+And it turns out that the newer machinery there in
+
+monkeys looks pretty similar to what we might expect from
+
+brain imaging in humans or from these lesions.
+
+And so we can use that information, these recordings, from
+
+a way about having monkeys be trained to do a
+
+task.
+
+Monkeys can usually perform a much more complicated task.
+
+Another animal such as flies or rodents.
+
+And we can use those recordings to try and work
+
+out what's actually going on in these little brain areas,
+
+particularly those around this practice focus area that's received most
+
+attention so far is the lateral improperly lip might be
+
+coming back with in the next class and even more
+
+involved questions about how we decide to make movements.
+
+There is some evidence that this area, this little area
+
+called LIP, is at least partially involved in starting to
+
+generate or start to move as you place an eye
+
+based reference frame, which is the kind of topographic map
+
+you find in primary visual cortex or in early parts
+
+of visual cortex.
+
+If we want to change that reference frame into something
+
+that is not dependent on when we are looking, we
+
+need to start making some changes to the representations that
+
+we encode this graph.
+
+We actually do a little bit about how why we
+
+think that is involved in starting to transform this visual
+
+tropic retina topic representation to something that does not depend
+
+on the direction of gaze.
+
+I mean, explain what these graphs all show first, because
+
+you're going to see a field in the next few
+
+slides on the x axis.
+
+Here is the time, and you can see here it's
+
+about this little black bar is about 200 milliseconds or
+
+one fifth of a second.
+
+There's several different things on the on the y axis
+
+here on the top is the position of the animal.
+
+Now, he's actually hit fixed in this case, which head
+
+is restrained, but he's able to move his eyes around
+
+because that is the vertical movements of the eye and
+
+the horizontal movements of the eye.
+
+The next block shows you, when the stimulus appears, indicates
+
+the times when the stimulus is on these little rows.
+
+Here are what we call a Rasta plot.
+
+And each row is one trial.
+
+One time the animal performed this task.
+
+And each of those dots is the time of occurrence
+
+of a single action potential from a neurone in IP.
+
+Now, you may repeat that trial many times in this
+
+case, say 15 or 20 times, and you get pretty
+
+similar activity across each trial.
+
+And so when you average that activity, you get something
+
+like this black box below which we call a pair
+
+of stimulus time histograms.
+
+And the height of that box basically reflects the magnitude
+
+of the response of the neurone at that point in
+
+time.
+
+The number of spikes the neurone is discharging on each
+
+trial at that point in time.
+
+And so in each of these cases, you can see
+
+that just after the stimulus comes on, the neurones respond
+
+very short latency about 50 or 80 milliseconds, less than
+
+1/10 of a second after the appearance of stimulus.
+
+That's how long it takes the visual information to get
+
+from the retina to this part of the brain.
+
+Now there's three different trials shown here.
+
+These are all recordings from the same nerve cell likely
+
+in the monkey doing this task.
+
+And the monkey's task is simply to find look at
+
+the dot bit like when you're looking at Wall-E.
+
+But we're not trying to look.
+
+But look at the dot in the letters, the thing
+
+that's all the monkeys required to do.
+
+In the other two trials, the monkey is required to
+
+move the eyes from that dot to another dot that
+
+appears.
+
+So you can see here, that's what's indicated by the
+
+arrow.
+
+And you can see that the monkey is successfully doing
+
+that because it's horizontal traits which are the sort of
+
+the right position, horizontal and position changes just after the
+
+stock comes on.
+
+And that comes on at this line here.
+
+And then a stimulus has been displayed to the animal
+
+at a particular location on the TV screen that the
+
+dog is also placed on.
+
+So in this particular case on the left here, this
+
+is what we would expect from a neurone that is
+
+simply representing visual stimuli.
+
+Responding to a visual stimulus, Stan was fixating flecks of
+
+light appears neurone stops responding.
+
+Pretty simple.
+
+In the second case here, this is a bit more
+
+of a funky task in this case.
+
+Just before the animal makes nine movement, the stimulus appears
+
+on the right hand side.
+
+And here you can see what happens is that the
+
+neurone still responds to the stimulus that appears when when
+
+the eye move to that location.
+
+So that that is also consistent perhaps with the with
+
+the new on including the position or appearance of an
+
+object at a particular position with respect to its iris.
+
+However, if you display the stimulus just briefly at its
+
+new location here, the same written location with respect to
+
+the days before the animal makes the second you actually
+
+see that response physically or even though that stimulus was
+
+placed in the part of the visual field, it's not
+
+normally effective for the mirror.
+
+In other words, this new on CTV anticipate.
+
+In fact, the animal is about to make a second
+
+to this new location in middle place, and it seems
+
+to be reaching out to that new location to see
+
+if there's anything there already.
+
+So these neurones are already starting to disassociate the retina
+
+properly.
+
+Framework that is encoding really powerful visual cortex is something
+
+that doesn't depend on the location of the eye.
+
+It's not a complete disassociation to pinpoint.
+
+So that's like P going to see patent in this
+
+VR trial area eventually further down in the brain, away
+
+from the brain.
+
+And these neurones are really interesting.
+
+Again, this is a monkey performing a task.
+
+And again, the task is primarily to maintain fixation on
+
+a particular point on the screen.
+
+In this case we see the monkey and we can
+
+see from the lateral side he's looking at the screen.
+
+And his task here is simply to look at this
+
+central location.
+
+And while he's looking down, a stimulus is presented that
+
+comes either towards the mouth.
+
+From the top to the bottom, from different locations on
+
+the screen or towards the top of the head, again,
+
+from different locations on the screen.
+
+And what you should see here is that this neurone
+
+is very active for the two situations.
+
+On the left hand side here, there's lots of activity,
+
+lots of spikes, and that's when the object is moving
+
+towards the mouth and not when the object is moving
+
+towards the forest.
+
+If we then change the stimulus slightly.
+
+So then what?
+
+She has to look up here.
+
+You can see that the neurone is too responsive when
+
+the animal is when the object is coming towards the
+
+mouth, not towards the first.
+
+So the activity this neurone seems to depend on whether
+
+an object is moving towards the mouth, not on where
+
+the animal's viewpoint is.
+
+It doesn't matter where abouts in the visual field.
+
+It started as long as it was coming towards the
+
+end of the forest.
+
+So this vector into prior CO areas seems to be
+
+standing to construct this representation of objects in the world
+
+that depend on that location.
+
+With respect to the amount of fibre that's important for
+
+feeding.
+
+Exactly.
+
+And not just the math.
+
+If you look at other neurones in other parts of
+
+the head that represented.
+
+And it's also interesting you report the medial enterprise area
+
+rather than the lateral, the medial being close to the
+
+middle of the brain.
+
+We find exactly what we call rich second frames of
+
+reference.
+
+That is, that neurones are responsive when animals make a
+
+movement towards an object with their arms is also neurones
+
+in there that are also responsible to animals.
+
+Make seconds.
+
+This is a fairly complicated slide.
+
+I don't want to take too much away from it,
+
+but the point is here that this new one, some
+
+of these neurones are active when the animal makes a
+
+reaching movement, but not when it makes an eye movement.
+
+It seems to be this and other forms of evidence
+
+seem to suggest that it was using something about the
+
+coordinate space of the joints to actually represent the outside
+
+world.
+
+There's another area called the anterior inter parietal area, and
+
+we're going to discuss that in greater depth in a
+
+moment.
+
+So to summarise what I've said to you there, there
+
+are multiple frames of reference that can be used to
+
+represent the world.
+
+There's good evidence for the existence of multiple frames of
+
+reference in separate circuits in the brain.
+
+Spatial neglect means losing a representation of a specific frame
+
+of reference for at least one or two, and not
+
+all of them.
+
+But for that reason we can all.
+
+Be aware of objects in a particular coordinate frame.
+
+And the other point here is that there's multiple frames
+
+of reference represented in parallel different areas in the brain.
+
+Simply constructing in parallel with different reference frames.
+
+And the consequence of that is that the could have
+
+been executed or generated in parallel.
+
+When we go to form a task, we can select
+
+immediately or quickly which frame of reference we want to
+
+use to actually complete that task.
+
+We don't have to wait to redo the entire computation
+
+again, take the visual image on whatever I want to
+
+do with this.
+
+I want to reach there.
+
+I want to do this instead.
+
+That preference frame is already being built.
+
+We may not use that reference frame.
+
+We may select another reference frame, in which case the
+
+question becomes what happens to the new workflow detection of
+
+that reference frame that we did not use?
+
+And that, I think, is going to be something that
+
+should become clear in the next part of the lecture.
+
+Is there any questions about that particular component?
+
+Okay.
+
+So skip over a section, which is basically how the
+
+motor cortex controls the muscles.
+
+And I could say that there's a there's now a
+
+video on your little page, which is through that, and
+
+it's five people.
+
+What I want to spend.
+
+The next lecture discussion is how we control and even
+
+understand actions.
+
+And I want to take us through some of the
+
+really interesting what has happened in this field in the
+
+last ten or 15 years.
+
+We've talked about the parietal lobe.
+
+We skip over what I call the primary motor cortex,
+
+which is the actual guts of controlling the muscles.
+
+That's in the middle page.
+
+We're not going to talk too much about supplementary motor
+
+areas, but these are areas which help generate the initial
+
+plans for the muscle movements that go to the primary
+
+motor cortex.
+
+But between these areas, the premotor cortex and the prefrontal
+
+cortex seem to take information from the parietal lobe and
+
+then distribute them to the motor areas.
+
+That's a lot of what we understand about this has
+
+been done in the context of a particular term, and
+
+I think we can grasp something.
+
+Rastafarian or a monkey's case brought a little bit of
+
+food.
+
+Turns out that the circuits for this simply quite similar
+
+in monkeys and humans.
+
+The talk shows a schematic of a monkey brain, the
+
+bottom of the human brain, the areas of interest in
+
+the monkey brain of the those around the enterprise, those
+
+focus in particular the anterior area is a little area
+
+called F5 and also F1 in humans.
+
+The same areas exist.
+
+We know that from the anatomy and from the tracing
+
+of connections between pathways.
+
+We don't really know exactly how signals get from one
+
+area to another.
+
+So we're going to use the monkey to try and
+
+understand a bit of that, but also look at some
+
+of the human pathways.
+
+So this here is in the same kind of way.
+
+Actually, the previous slides, a description of several neurones in
+
+anterior into parietal area during grasping, which I find is
+
+absolutely fascinating because there's one particular type of neurone here
+
+in the bottom right, which seems to be important in
+
+taking that sensory information that's coming up from the sensory
+
+periphery through the visual cortex and starting to transform that
+
+into something that's useful for motor movements.
+
+So this slide shows three separate neurones in each row
+
+and for each new on the three different paths.
+
+The different tasks.
+
+The different columns are to perform a manipulation in light
+
+that is to create something more certain.
+
+See it?
+
+The second one is to reach out and grasp that
+
+thing in the dark.
+
+So I can't see there is no visual information.
+
+And the third thing is just to look at the
+
+object and not reach the ground.
+
+So the neurone on the top here shows falling rates
+
+like we might expect from a visual appeal if it's
+
+near or it's active.
+
+When the animals manipulate an object in the light, it's
+
+also active when it sees the object to manipulate it,
+
+but it's not at all active when it makes the
+
+muscle movements, they can't see the object.
+
+On the other hand, this middle row here is a
+
+kind of demand that we might expect to be important
+
+in controlling the movements that we're about to make so
+
+that no one is active.
+
+When we reach out across the line and is active
+
+when we reach out and draw something, the dog can
+
+see it, but it's not at all active.
+
+When we just look at the optics.
+
+So it's active during the past, but when you look
+
+at it, so these visual motor neurones, it's a kind
+
+of classic distinction between sensory input and motor.
+
+And for the third part of neurone there, which we'll
+
+call a visual motor neurone, combines these two features.
+
+These neurones again are active during the regrouping task in
+
+the light.
+
+These neurones are also active when the animals cannot see
+
+the objects and they're also active when they see it,
+
+but don't perform the movement.
+
+So they have both sensory input seen in the visual
+
+only component and motor inputs in the motor and components.
+
+And they seem to combine, they seem to be able
+
+to combine these two forms into one neurone.
+
+And these kinds of neurones, these visual motor neurones can
+
+be found in different parts of the brain.
+
+The most prominent in the kind of cortex, the frontal
+
+cortex.
+
+And they are, we think, a very important interface between
+
+sensory information.
+
+They combine these two things.
+
+As we'll discover in the next lecture, You want to
+
+combine these two things to make the interesting contributions to
+
+defining about what we want to do.
+
+So this is the kind of neurones you find in
+
+the final area.
+
+You actually find is also further up the chain area.
+
+Fine.
+
+We'll get to that in a moment.
+
+These neurones that can be quite selective for the further
+
+features of the task.
+
+So this is recording from one neurone in this case,
+
+and this is a visual motor neurone that is a
+
+neurone that you can see both the visual component and
+
+motor in front of the task.
+
+In this case you can see that just in the
+
+visual component alone that the neurones are responsive.
+
+This is.
+
+This is during the top three.
+
+This is the actual during the top when they can
+
+see and make the movement.
+
+You can see that these neurones are active for particular
+
+configurations of grasp and not others.
+
+If in addition you look at the visual component alone,
+
+that is in the absence of the tons you see,
+
+these neurones are also selected for particular objects.
+
+How many of you have heard of the concept of
+
+affordable?
+
+Performance is a really interesting thing.
+
+When we design objects, the objects that work, the ones
+
+that we want to use for those are for particular
+
+actions.
+
+The chairs are for the ideas to be.
+
+I don't do that with.
+
+That means phone too, for the idea of picking them
+
+up and scrolling through them.
+
+That is the very particular structure.
+
+Those objects seems to promote the execution of particular motor
+
+planner.
+
+Unfortunately.
+
+They forward those.
+
+Actions.
+
+Maybe these neurones are part of that kind of affordances,
+
+because when these neurones which are helping, which have both
+
+sensory input and motor output, are actually representing particular types
+
+of objects, people, okay, So perhaps they help us not
+
+to generate the plants when we see that object.
+
+One of the plants that I might execute if God
+
+wants, but I might not execute one of the plants,
+
+I might get a clue that that would afford that
+
+particular action.
+
+Indeed, if you look at human cortex now rather than
+
+monkey cortex, you look at it from signals rather than
+
+single unit recordings.
+
+You also see a good deal of evidence for the
+
+presence of areas that are effectively related to performance.
+
+These are the responses or MRI responses in human cortex
+
+to observed axons in the top row.
+
+Here is when one observes actions without associated objects, and
+
+the bottom is when objects are present with chewing, grasping
+
+and kicking.
+
+Again, this is a person sitting in a scanner and
+
+not actually performing his actions that is viewing the action.
+
+We think maybe when they're viewing these actions, maybe they're
+
+kind of replaying them in their head as well.
+
+Or maybe they're viewing them also for to start to
+
+build their idea of a particular course of action.
+
+And you see from these slides here, but I want
+
+you to take away mainly is that there's a substantial
+
+amount of activity not only in motor cortex, but also
+
+in provider cortex consistent with what we see in the
+
+monkeys that when they're looking at particular objects, neurones are
+
+active so that those objects may afford particular actions.
+
+Similarly, if you just look at the particular example of
+
+tools, if they present a hammer to someone sitting in
+
+a scanner as opposed to a house or other objects,
+
+they would do not forward actions.
+
+You find that in prior to Cortex as well as
+
+in premotor cortex, this area equivalent to the monkey even
+
+at five feet, gets a standard manner of activity.
+
+Again, these parietal and motor cortical region seem to be
+
+responsive when you're viewing objects that are full potential for
+
+action.
+
+This experiment I find really beautiful.
+
+You've heard about transcranial magnetic stimulation.
+
+That's the idea where you put a magnetic pulse outside
+
+to stimulate a little bit to the cortex.
+
+When you do that, you activate the neurones, the electrical,
+
+the cortex.
+
+You can choose the pulse and intensity that which doesn't
+
+overtly cause an action, but you can measure the activity
+
+of muscles in the relevant part of the body.
+
+For example, in the hand.
+
+And that's what's going on here.
+
+These will pass through the amplitude of the muscle movement
+
+recorded during stimulation of the cortex.
+
+And these measurements are made.
+
+What people are feeling for different objects.
+
+These are right handed subjects.
+
+In one case of viewing a cup with the left
+
+hand of one face, right hand to the other cases.
+
+Left and right.
+
+Broken handles.
+
+And what you should see here is that the bar
+
+is much higher when the cops are right handed.
+
+When their visual object affords particular action.
+
+Grasping with the right hand activity, motor cortex seems to
+
+be potentiated by viewing this object consistent again with the
+
+from right results because cool and consistent again with the
+
+work and try to poaching monkeys.
+
+So this brings me on then the mirror neurones.
+
+How many people have heard of Mira Nair?
+
+One of the few who you might know.
+
+And if you've read the if you read the Sylvia
+
+Hazily speaking, if you read the review that I've included
+
+in your reading, you'll understand a lot more about them.
+
+Their neurones have gained particular notoriety because they may, they
+
+are hypothesised to be a source of understanding the actions
+
+of others and perhaps even the higher cognitive social events
+
+like empathy.
+
+These are circuits to be active when viewing an object
+
+for viewing someone doing something as opposed to actually doing
+
+it yourself as well as when you're doing so.
+
+So these are neurones originally that were discovered.
+
+The reason I've talked to you about this search for
+
+grasping is that these neurones were discovered by Richard Lockie
+
+and colleagues when they were trying to understand these brain
+
+circuits across that recording from monkeys.
+
+And they noticed that and trained the monkeys to reach
+
+out and collect food objects.
+
+I wanted to know what was happening during the different
+
+phases of movement and plenty of movement.
+
+They're reporting from the pool area of the prefrontal cortex
+
+called a client.
+
+And they notice that a certain fraction of neurones consistently
+
+seem to fire, not when the animal, not just when
+
+the animal restarting something, but when the experimenter was actually
+
+moving or reaching out or grabbing that.
+
+And so.
+
+So in the writing of the classroom, one of the
+
+first neurones that they discovered the classical mirror neurones.
+
+So these neurones are active when an animal is reaching
+
+out and grasping an object that's shown here.
+
+They're also active when the experimenter is reaching out and
+
+grasping the object that's shown here.
+
+Some of these new ones, it turns out, with finer
+
+investigations, were active in particular cases when the animal when
+
+the object was available to the animal's reach and when
+
+it was not available within the animals, when it's within
+
+the animal's reach, that's a very personal space that the
+
+space around you when it's not within the reach of
+
+the expert personal space.
+
+The space is beyond that.
+
+You can see here that some neurones seem to respond
+
+when actions are performed outside of personal space and other
+
+neurones respond when it's in the very personal space.
+
+Yeah.
+
+So the idea here is that these neurones are responsive
+
+to when both an animal is making an action and
+
+when the animal is viewing the action.
+
+So that's where the idea of mirror neurones comes up
+
+in mirroring responsive when you're viewing something as if you
+
+were generating that they embody in your brain an interpretation
+
+of the action potentially that took place or the accident
+
+that person is performing.
+
+That might be important.
+
+For example, imitation, learning, fine imitation like children do.
+
+If you perform an action should take it and learn
+
+how to perform that action.
+
+However, monkeys don't really live by invitation, so weather is
+
+certainly a problem with monkeys.
+
+Another question Immigration could also be important for trying to
+
+predict what someone else is going to do.
+
+If I see someone reaching out for an object and
+
+predicting that they're going to be taking an object, I'll
+
+be able to understand the potential intentions of the other
+
+person.
+
+That's the idea of the founding at five.
+
+Why?
+
+I wanted to introduce you to them in the context
+
+of this pathways that you should be clear to by
+
+now that they're not just on an incline.
+
+They're also found an intuitive triangle area.
+
+They also find another part of the brain.
+
+So there seems to be a whole network of neurones
+
+that seem to be providing not just the actions that
+
+we are making, but when we just view those actions
+
+will result in a positive step forward.
+
+These circuits are collectively known as potentially very neurone circuits
+
+and they are thought to be in some context important
+
+for things like embodiment and empathy.
+
+I do want to make clear, though, that there's there's
+
+a lot of controversy.
+
+ACLU review makes clear as well.
+
+There's a lot of controversy about the role of these
+
+neurones in these functions.
+
+I don't think there's any controversy about the presence of
+
+these neurones.
+
+What is of interest and what is of concern is
+
+whether these neurones are actually representing what another person is
+
+doing with these neurones, basically generating internal but complete the
+
+plan of action.
+
+As I said to you before, we provide different spatial
+
+reference findings in parallel in our brains, we choose which
+
+spatial reference frame we're going to use when we execute
+
+a particular action.
+
+The implication of having multiple parallel reference frames, not all
+
+of which are used, is that many.
+
+Action plans are made and never executed and never whenever
+
+aware of.
+
+It's a mirror neurone that for a neurone that is
+
+actually representing the actions of others.
+
+Or is it a neurone that's representing an on executed
+
+plans that we are protecting.
+
+Which.
+
+Afforded.
+
+To us.
+
+And that's the central question that still exists in the
+
+mirror neurone.
+
+Which are these neurones effectively anonymous, or are they there
+
+to help us interpret the actions of others or not?
+
+And these of course are not there to speak of
+
+things they could well be that they, for example, evolved
+
+or arose simply to provide clues and execute plans that
+
+are co-opted to then try and provide an interpretation understanding
+
+of others actions.
+
+So I really suggest that you do read Sylvia's article.
+
+She's a leader in the field.
+
+And at this stage, I will leave you with those
+
+with one dichotomy.
+
+That's the dichotomy that exists in the field with the
+
+laity who discovered these very new ones originally.
+
+His group of sceptics were neurones.
+
+He's his interpretation, as if this mirror mechanism is fundamental
+
+to understanding actions and intentions, then the classical view to
+
+the motor system has only a role in generation and
+
+by implication the central system has any role in sensation,
+
+have to be rejected and replaced by the view that
+
+motor system is also one of the major players in
+
+cognitive functions.
+
+The motor system helps us embody the actions that we
+
+view around us.
+
+The contract.
+
+The contract view is that from Hitchcock and colleagues, he
+
+spoke with the language specialists very prominent in the field,
+
+and he would state that a null hypothesis is in
+
+this area.
+
+A five is fundamentally a motor area that is capable
+
+of supporting sensory motor associations that are relevant to action
+
+selection.
+
+As I said before, one of these areas that is
+
+involved in generative frames of reference potential, the motor plans
+
+that we can execute this selection.
+
+So encourage you to read those things and we'll leave
+
+that idea of whether or not we're going to contribute
+
+fundamentally provision for thanks and how good they can click.
+
+Click, click, click here to read more effective.
+
+Problems.
+
+With you.
+
+Take me back to the current context in which you
+
+can contribute to that.
+
+I could take some time to.
+
+Come up with something specifically at the control.
+
+Group.
+
+That's one of the things that we suspect virtually all.
+
+Of the.
+
+Idea.
+
+But I don't think to.
+
+Make the point that medical technicians and.
+
+An important part of.
+
+The process.
+
+Of critical thinking about this is something that even.
+
+When I'm writing.
+
+The basic hypothesis.
+
+Is that there's a lot of activity.
+
+Quickly.
+
+Actually get.
+
+Effective.
+
+So it just doesn't make any difference whether.
+
+Or not the significant.
+
+Activity in this market.
+
+Commercial activity.
+
+But you might find indications of.
+
+What it looks like.
+
+It's going to.
+
+Be very difficult to keep.
+
+Up with.
+
+The idea.
+
+That an activity.
+
+By.
+
+Virtue of that are active but actually taking place.
+
+I see.
+
+Okay.
+
+Thank you for taking my question, please.
+
+Okay.
+
+I guess it's like if you read the study as
+
+well, but just.
+
+The active when it's objects moving towards the mouse.
+
+That's what I'm trying to say, but only when they're
+
+moving ahead of the target.
+
+So it's much more different from anything.
+
+Yeah, it's so interesting.
+
+Question Is there any.
+
+More than what is it.
+
+Going to take that we know that we know psychologically,
+
+that whole thing for.
+
+Actions.
+
+Whether that specific you know, whether specific structure can afford
+
+to do for specific.
+
+Comparisons as any work is done in the executive there?
+
+But it's a good question.
+
+I don't think it's coming back.
+
+But I don't know.
+
+But with all the time it takes to do something
+
+like this happens, but it seems to be generated, they're
+
+more expensive.
+
+But again, we recognise that.
+
+People.
+
+Keep working on.
+
+It could be difficult to predict what's going to happen
+
+in Texas because that's not something that's going to come
+
+to grips with the fact that people are killed by.
+
+In particular for the focus groups which are protected in
+
+the construction of the company as well as collaborations.

raw_transcripts/lecture_9.txt

@@ -0,0 +1,2443 @@
+All right.
+
+Good morning.
+
+You know, I have a mini stroke or did I
+
+say some names outside before anyone else say some names?
+
+Oh, no.
+
+No.
+
+Okay.
+
+Maybe I just had a mini stroke.
+
+Okay.
+
+I'm just trying to work out what happened there.
+
+So it's really my pleasure to raise a volume.
+
+So.
+
+Is that better?
+
+I can't tell from down here.
+
+Okay.
+
+It's my pleasure to try and take you through this
+
+today.
+
+When I was a young graduate student, actually, this field
+
+had just started.
+
+And one of the papers I'll introduce you to.
+
+Was a real key moment in that development.
+
+I remember talking to one of the authors of that
+
+paper and.
+
+Been blown away by the idea that perhaps we could
+
+track.
+
+The evolution of a decision in the brain.
+
+I think we think it's fairly commonplace to look at
+
+this now, but back then this seemed like there's something
+
+beyond.
+
+Our abilities.
+
+So in the last couple of lectures, what I hope
+
+I hope you understand is that signals from the senses,
+
+like the eye I communicated to the brain along parallel
+
+pathways of showing you that these signals are represented in
+
+early brain areas, the primary cortical areas, for example, in
+
+the form of topographic maps of the sensory periphery.
+
+I'm telling you also the higher brain areas are called
+
+high brain areas seem to transform those topographic maps of
+
+the century periphery into frames or reference frames in which
+
+we can make actions frames that are behaviour useful more
+
+so those now probable graphic maps.
+
+I've also shown you to some degree that Apple Motor
+
+areas can use these spatial representations to guide movement bands.
+
+So what we skipped over and what is still really
+
+one of the fundamental unknowns about neuroscience is what's in
+
+between these two things.
+
+I illustrated to you that there are some cells that
+
+we will call sensory motor neurones that give both sensory
+
+input and have motor related glands activity.
+
+They seem to be particularly important in this process.
+
+And in this lecture we'll go through a particular class,
+
+those neurones that sit in this whole area of the
+
+brain called the lateral imprint area, which we discovered a
+
+little bit in the last lecture.
+
+And the question really is how do we decide which
+
+action to execute?
+
+There are many different actions we could possibly execute.
+
+How do we decide among these options?
+
+What I want to try and introduce you to is
+
+the idea that we can actually practice evolution decisions.
+
+We still don't know how we do decide, I should
+
+say, but we're getting closer and closer to understanding that
+
+fundamental point about behaviour.
+
+To try and illustrate this, we have to settle on
+
+a on a definition of a decision that we can
+
+actually explore experimentally.
+
+And I'm just going to take you through that in
+
+the next couple of slides.
+
+There are many different ways we can think about decisions,
+
+but we need to think about ones in which we
+
+can try and work out what is the neural basis
+
+of this decision.
+
+This slide represents two possible kinds of decisions that you
+
+might make by commonly in the top in going to
+
+a restaurant, in this case a pizza restaurant, you look
+
+at the menu, you're trying to work out what it
+
+is you would like to eat.
+
+You surveyed the different options you take into account your
+
+previous experience and biases.
+
+You look for evidence in the form of the different
+
+ingredients in the in the menu.
+
+For example, you deliberate about what it is you would
+
+like.
+
+I'm asking my mom, in which case you just get
+
+the same thing every time.
+
+You learn what's available.
+
+Understand the differences and deliberate.
+
+This is a decision that we could perhaps explore.
+
+Similarly, if you're a goalkeeper in football and it's your
+
+job to try and save a penalty, then that task
+
+to try and stop that ball going into the goal,
+
+by the way, it takes about 0.3 of a second
+
+for the ball to get from the penalty spot past
+
+the goalkeeper, but not very long at all.
+
+Your task is to try and evaluate the sensory evidence
+
+or maybe the pattern of steps that kick the ball
+
+is going to is using the direction that they're coming
+
+from.
+
+Maybe analyse that, that that particular player before and you've
+
+worked out that they like to kick it up in
+
+the top right of the net.
+
+You have to try and make a rapid a very
+
+rapid decision.
+
+You have to execute that decision within about 50 or
+
+80 milliseconds of holding it very, very quickly and strongly
+
+that the evidence you have for the hypothesis that you
+
+are testing it quickly to make that decision.
+
+So these are two forms of decision, the latter where
+
+there's very little action leaping left or leaping right or
+
+staying put is an easier one to study in the
+
+context of operating systems and the kind of decision that
+
+we're going to try and explore in this lecture.
+
+So a definition of the kinds of decisions that I
+
+would like to use is that a decision, is a
+
+commitment to a proposition or the selection of an action,
+
+a process that results in the overt act of choosing
+
+based on evidence of prior knowledge and belief.
+
+Overt is easier.
+
+Is a decisions that we can look at objectively rather
+
+than just subjectively.
+
+As Jeffrey saw, one of the pioneers of this field
+
+is puts it where choice refers directly to the final
+
+commitment, the one among the alternative actions, decisions referred most
+
+directly to the deliberation preceding the action.
+
+So it's not the actual action we choose, but the
+
+process of deliberating among the possible actions that we undertake.
+
+Or as Golden seven.
+
+Mike Catlin is another leader, as is his former.
+
+First of all, decision is the deliberative process that results
+
+in the commitment to categorical propositions that the right an
+
+apt analogy for judge or jury that may take time
+
+to weigh evidence for Internet of interpretations and or possible
+
+ramifications before settling on a verdict.
+
+In these kinds of definitions is that these decisions take
+
+time.
+
+You accumulate evidence and you take time to make them
+
+be deliberate.
+
+And the fact that we're taking time to make them
+
+means that we can look for the signals of that
+
+process in the brain.
+
+If there was no time in which you needed to
+
+make that decision, you wouldn't know what to look for
+
+in the brain.
+
+But it takes time to accumulate evidence, and that's something
+
+we can can't find.
+
+So this is one way of trying to think about
+
+the basic components of most of these kinds of decisions.
+
+On the top is the context in which the decision
+
+is being made.
+
+On the bottom is kind of the architecture of the
+
+process that helps that decision to be made.
+
+For example, you may need a task and motivation and
+
+will get to a very specific task and motivation in
+
+the moment.
+
+You need to generate hypotheses about the world.
+
+You need to incorporate your beliefs and prior knowledge.
+
+That's all the context of the task.
+
+And the context of this kind of sensory guided motor
+
+actions and the kinds of decisions that we're going to
+
+make require you to take some sensory input, evaluate it,
+
+transform that sensory input into a useful form of evidence,
+
+something that you can act upon.
+
+You need to generate what we will call a decision
+
+variable.
+
+That is a point at which after which you have
+
+committed to a particular decision.
+
+We'll go through this in the next episode.
+
+You need to apply that decision rule that you need
+
+to execute the motor out.
+
+I challenge you to describe decisions and reforms that don't
+
+fit into this general framework.
+
+It doesn't cover every type of decision, but most of
+
+these things are the key component that you think, well,
+
+one thing that shouldn't fail.
+
+And we're going to try and fill out these boxes
+
+in terms of specific tasks that an animal or human
+
+might do and which they have done for the last
+
+20 years, ad infinitum.
+
+So what I hope we will discover in the sector
+
+is that humans and other animals accumulate evidence for decision
+
+over time.
+
+That decision is made when the accumulated evidence reaches a
+
+criterion.
+
+Consequently, harder decisions take longer to get right.
+
+That by adjusting bias in criterion, we can change the
+
+process of decision making from being safe and slow growing
+
+fast.
+
+And I'm going to show you that there's your signatures.
+
+That is new activity that reflects these different parts of
+
+the process and that you see this is a key
+
+way that evidence can be identified early in the processing
+
+hierarchy.
+
+And and actually, Frank, Larry, as we discover among neurones
+
+that both respond to sensory stimuli and predict motor outputs,
+
+that is sensory motor neurones, these are the kinds of
+
+neurones we explored in IP.
+
+I said to, for example, that respond in both the
+
+sensory stimulus that was being shown to the animal and
+
+predicted the motor action that they were got from the.
+
+So most of this work, especially in the early stages,
+
+has been conducted in the context of moving your eyes.
+
+This is something we do 2 to 3 times every
+
+second of every day that we are waiting.
+
+We move our eyes around.
+
+We make seconds.
+
+These are ballistic eye movements, very rapid eye movements that
+
+move eye around so that we can bring some kind
+
+of growth onto the central region of our eye over
+
+here.
+
+And we bring it on to the central region of
+
+the eye, because that's where the high intensity of odour
+
+receptors are, and that's where we would like to analyse
+
+the visual image.
+
+So we were very good at making these eye movements.
+
+We make them very rapidly and we make them very
+
+frequently.
+
+There's a lot of the brains devoted to trying to
+
+make them in the most optimal way possible.
+
+This is one example of a kind of pass that
+
+a monkey might do or a human might do in
+
+trying to search the city.
+
+Here the ice starts off in the centre of the
+
+image.
+
+Their task is simply to find out, see and to
+
+look at that to.
+
+Now, when you look at the centre of these things
+
+in the periphery, they're quite hard to detect.
+
+It's very hard to tell whether something is an Al
+
+or a T when they can be repeated in whichever
+
+way.
+
+And so monkeys tend to enter humans and make eye
+
+movements to see sequentially surveil the image.
+
+And so these little movements between each of these objects
+
+are these two kinds.
+
+And in this case, the monkey eventually finds that he,
+
+in fact, actually makes an eye movement away from the
+
+team and come back to the team.
+
+So these are these are the kinds of movements you
+
+make all the day when you're reading, for example, or
+
+looking at someone's face.
+
+My kids do it as well, and they're very good
+
+at it just as we are.
+
+That in itself is still a quite a hard path
+
+to try and pick apart because the eye is moving
+
+around all over the place.
+
+There's many different potential stimuli that could be present.
+
+It's still pretty tricky.
+
+We need to find simplify that task even further.
+
+And a lot of the field over the last ten
+
+years is settled on this equal task and you will
+
+encounter it a lot in the literature.
+
+So I want to take you through the task a
+
+little bit.
+
+It is still a decision making process.
+
+There will be some sensory input.
+
+There will be a motor output and there is some
+
+decision making process in between those two things.
+
+However, the task in this case is going to be.
+
+Estimate which way this field of random dots will see
+
+them in a second reading and then make an eye
+
+movement accordingly.
+
+So the dots are moving to the left, making eye
+
+movement to the left.
+
+The dots are moving to the right, making eye movement
+
+to the right.
+
+That is the simplest possible task with moments involved.
+
+So an animal or a human can be looking at
+
+an evening monitor to see a field of dots on
+
+a moving and then have two potential outputs.
+
+Move left and move right.
+
+And look at these two different dots.
+
+And indeed, after the dance, the emotion seems has gone
+
+away.
+
+They're allowed to move their eyes and make that appropriate
+
+decision.
+
+This is perhaps the simplest task we can look at,
+
+and it has proved enormously fruitful to understand the very
+
+basic aspects of decision making.
+
+So if you go back to this general context of
+
+what a decision might look like and then we try
+
+to put this past in that in that framework, you
+
+get something like the of the animal, the animal or
+
+the human.
+
+The task is simply are the dots moving left or
+
+right?
+
+And the motivation for animals is reward often also the
+
+motivation for humans.
+
+Amazon.
+
+Humans generate two hypotheses on the basis of the sensory
+
+evidence hypothesis.
+
+One dog moving that told to the moving right.
+
+And I can bring in to this task, although we
+
+won't discuss it equally here.
+
+They believe some families set up example.
+
+You could train and even or train a monkey on
+
+a task such that the you over represent the probability
+
+of the adults moving right and perhaps the monkey will
+
+learn or even will learn that it's more likely to
+
+go right.
+
+That might be a prior belief.
+
+That's not the general structure of these parts, but that's
+
+something you might do to fiddle with the context and
+
+biases, and I will bring it into a decision.
+
+So that's the context of the past.
+
+The decision making process is to analyse that visual motion,
+
+which direction of the dots going.
+
+Then transform that into a useful form of evidence generating
+
+decision variable, apply a decision rule and then move your
+
+eyes to the left or the right, and the path
+
+to the next few slides is fine.
+
+Go through this.
+
+To be able to do that.
+
+I need to tell you a couple of little things
+
+about how we represent motion in the brain digital motion.
+
+Then we're going to use this task, these dots that
+
+you'll see moving into the next slide.
+
+They've become very common.
+
+The reason these dots are so common in these parts
+
+is there are a large field of dots that can
+
+move.
+
+Either every dot moves to the left, for example, to
+
+the right together.
+
+That would we would call that a 100% coherence.
+
+All the dots are moving in the same direction.
+
+You can see that represented on the right here for
+
+each of those dots as a little arrow and they're
+
+all going in the same direction.
+
+This is actually output Explorer.
+
+So all adults can move together or only some of
+
+the dots can move.
+
+So you might vary the fraction moving in a particular
+
+direction or if example, maybe 50% of the dots open
+
+it up automatically.
+
+Right.
+
+And the other 50% adults.
+
+Those dots are moving randomly.
+
+And so those dots, they provide noise.
+
+So by bearing the number of dots in a moving
+
+in the same direction, we can vary the signal to
+
+noise ratio with English.
+
+This is very important.
+
+Some decisions which are very easy to do and this
+
+is very easy.
+
+For example, 100% coherence are actually really hard to do
+
+when there's only a small amount of signalling there.
+
+So by adding noise, we can make this decision harder
+
+and we can track things over a longer period of
+
+time, for example, and we can ask how animals or
+
+humans accumulate the evidence that they're about right.
+
+Now, these dots were developed as a stimulus to explore
+
+the responses of neurones in a very particular part of
+
+the brain called Area MP, sometimes referred to as B
+
+five.
+
+This area, which was first discovered by senators that he
+
+who is emeritus professor at UCL and at the time
+
+I think was working over in Queen Square in the
+
+history of neurology.
+
+E contemporaneously with some researchers in the US in the
+
+early 1970s discovered this tiny little part of the brain
+
+that is several millimetres in size in monkeys where every
+
+neurone in that part of the brain seemed to be
+
+selected for the direction of motion of a visual stimulus.
+
+In Sammy's work, this was in contradiction.
+
+Its most effective area, he found, next to an area
+
+that seemed to be selected for colour.
+
+He was describing how different types of as different information
+
+about the outside world had been encoded by visual cortex.
+
+He found areas that responsive to motion, areas that were
+
+supposed to be responsive to colour by not fluid depth
+
+and other forms of information, which you will only learn
+
+about later.
+
+But the purpose here, our interest is in this area
+
+empty.
+
+By the way, the doublet empty stands for a middle
+
+temporal area because on some in some monkeys, this part
+
+of the brain is found in the middle temporal area.
+
+In mechanics and humans.
+
+It's found in a small suitcase inside of the brain.
+
+You can't really see it here.
+
+It's actually this little bit here.
+
+This little area gets direct input from V1, the primary
+
+visual cortex.
+
+It is one of the most highly conserved parts of
+
+the brain in primates.
+
+Every single primate seems to have this part of the
+
+cortex dedicated to being selected for visual motion.
+
+And if you measure it from neurones in that part
+
+of the brain, you get something like this activity shown
+
+here.
+
+If you're using a very strong stimulus, understand coherent dots.
+
+The neurones are very selective for the direction and motion
+
+of those dots.
+
+These dashes here are meant to indicate the time of
+
+appearances and action potential on one file of the stimulus
+
+and can see that these neurones respond very well when
+
+these talks are all moving together in one direction.
+
+They are tuned for the direction of motion.
+
+That is, even if the dots are moving in another
+
+direction, they aren't responsive.
+
+And they're also sensitive to the signal to noise ratio.
+
+That is, if there are fewer dogs moving in the
+
+same direction, they become progressively weaker.
+
+And their response?
+
+These are neurones in every empty.
+
+They are based on neurones that we discover in a
+
+second.
+
+They don't seem to communicate much information about what an
+
+animal would do with that signal.
+
+They just represent a visual motion in the outside world.
+
+We study these neurones that 15 or 20 years ourselves
+
+in our lab.
+
+It's an amazing part of the brain to report from.
+
+What you will see here is actually the kinds of
+
+stimuli that are used in the lab with different it's
+
+quite hard to represent these moving stimuli.
+
+So videos only really work.
+
+One project is a little bit you need a high
+
+frame rate presentation device to see it properly.
+
+You see hopefully dots moving in one direction or another
+
+direction down to left or up to the right, and
+
+the fraction of dogs that are moving in the same
+
+direction varies and find the file.
+
+Well, you can.
+
+Here is actually this is a video taken lots of
+
+monkeys doing this task.
+
+You can hear all the audio tones which indicate when
+
+the start and finish is the monkey.
+
+And in the background you hear the action potentials of
+
+cells and area and to.
+
+This.
+
+So those are the action potentials that you hear about
+
+recording played through an amplifier so the experiment can listen
+
+to them.
+
+That, by the way, is not available for the monkey
+
+to do in the past.
+
+It's in a soundproof chamber outside of this room.
+
+So you can see that those neurones in area and
+
+they respond very well when the when the stimulus goes
+
+up into the right side, down to the left and
+
+not at all when it goes down to the right,
+
+but different neurones in area MP will prefer different motion
+
+directions, some down to the left, some often to the
+
+right, some often to the left.
+
+Some down to the right, for example.
+
+The second part of the of this task, that's the
+
+sensory information that's coming in is representing an area MP.
+
+It's representing the action potential that neurones in that area
+
+produce.
+
+And it's possible to train a monkey to do this
+
+task to detect which or to report sorry which direction
+
+in motion these dots are going in.
+
+And this was something that was accomplished first in the
+
+late 1980s and now has become very sound parts of
+
+monkeys and humans.
+
+And you can see here that if we put on
+
+the x axis, the number of the fraction of Dr.
+
+moving coherently at 1% or 10% or 100%.
+
+This is the proportion correct on an author's choice task
+
+where the animal has to report to the left, to
+
+the right, example or two up to the right and
+
+down to the left.
+
+That as those as the number of dots moving coherently
+
+increases, so does the fraction of times that the animal
+
+gets its decision.
+
+Right.
+
+These animals are highly motivated because they are actually water
+
+regulated and they're working for juice.
+
+They just have very well, I've tried to do this
+
+task many times.
+
+I'm nowhere near as good as these monkeys.
+
+These monkeys are getting almost 100% correct, about ten or
+
+20%.
+
+That's moving in the same direction.
+
+To me, it takes 30 or 40%, 0% for.
+
+But his monkeys are highly motivated.
+
+So this is what we would call a psychometric function.
+
+It simply says that the monkey gets better as the
+
+numbers don't move in the same direction also increases.
+
+All right.
+
+So I thought then about the fact that this area
+
+empty, which seems to be responsive to these dots, provides
+
+potentially action potentials or neural activity that they may represent
+
+the motion direction of these dots.
+
+And we know that the monkey can actually detect which
+
+motion direction is going in.
+
+So then between these two things, between the sensory input
+
+and this motor output.
+
+So now I need to tell you that one of
+
+the reasons we're looking at Area A is it has
+
+a not only does it have a strong input from
+
+the primary visual cortex, it also has a strong apple
+
+to this whole area of the frontal cortex over the
+
+lateral impropriety area.
+
+And so what researchers thought back in the late 1990s,
+
+and this is when I started to see this field.
+
+Since the neurones in their empty seem to be encoding
+
+information about the visual stimulus, not about monkey's behaviour.
+
+What we should do is look at one of the
+
+areas, the area empty sensing.
+
+In this case there might be and see whether or
+
+not the same as bear.
+
+Maybe those neurones that are getting input from these neurones
+
+in MP are actually closer to the decision making process
+
+than those neurones in area.
+
+So if I was to summarise the activity of neurones
+
+in every MP, looks like then as a function of
+
+time you get something on the left.
+
+This is a schematic.
+
+When the stimulus comes on the activity, those neurones increases.
+
+And when the stimulus turns off, the activity resume decreases.
+
+So this neurone is responsive to the visual stimulus.
+
+And the amplitude of this on the number of action
+
+potentials a neurone produces depends on the emotion strength that
+
+stimulus.
+
+So there's only a few dots moving in the right
+
+direction.
+
+And if you continue to produce, if there are lots
+
+of dots moving the wrong direction, a lot of attention
+
+to produce.
+
+So these neurones encode both the direction of motion and
+
+the signal strength of the incoming stimulus.
+
+In Aria Lippi, however, he finds something quite different.
+
+Now when the stimulus comes on, instead of an immediate
+
+change in the activity of these neurones, you get a
+
+slow ramping up of activity.
+
+The slope of that ramp seems depend on how much
+
+signal there is in the visuals inlets.
+
+And that activity is actually sustained even after the stimulus
+
+is going on.
+
+So these neurones are quite different to the sensory neurones
+
+in our MP which are providing input to them.
+
+They're not as closely linked to the onset of this
+
+stimulus.
+
+Their activity persists after the offset of the stimulus.
+
+And in between, they seem to show this ramping behaviour,
+
+this accumulation of activity from low levels to high levels.
+
+That depends on the signal strength, the visual signal strength.
+
+This is the same kind of way that we've shown
+
+other cells in the previous lectures.
+
+And I'll go through the presentation here again and I
+
+can shows the activity of a real neurone.
+
+An area like a when it's recorded from in this
+
+kind of past.
+
+It's quite a busy slide, so I'll just take you
+
+through its early.
+
+First of all, the monkey in this case is looking
+
+at a screen very much like what we saw before.
+
+There are some dots moving on that screen and there
+
+are a couple of choice targets left or right, for
+
+example.
+
+And it turns out that if you measure from neurones
+
+an area like this, you find a region of the
+
+visual fields where these neurones tend to respond to the
+
+visual stimulus and also a region that these people field
+
+where neurones will predict an upcoming movement.
+
+In fact.
+
+So it's half the dots.
+
+Come on.
+
+And then they go off.
+
+When they go off, the monkey has to make an
+
+argument to the left or the right reporting which motion
+
+direction in which Lincoln.
+
+In these pictures down the bottom here.
+
+Each of these rows represents a single file in which
+
+the animals doing this asked each of those dots the
+
+time of occurrence of a single action Santa Cruz 11
+
+year on and the average activity over many trials is
+
+shown in it is found on the bottom.
+
+So large fires mean more activity from the zero.
+
+And you can see as shown in the schematic before
+
+that has a seamless turns on.
+
+In this case, there's no coherent motion and there's very
+
+little response in the neurone does start to build up,
+
+however.
+
+And indeed that build up in activity sustained until the
+
+moment that the animal makes that eye movement to the
+
+left or the right.
+
+Just before that movement is made, that activity goes away.
+
+It's as if that activity is predicting when the movement
+
+will occur.
+
+So these neurones in our area, AYP, which is I
+
+showing in the second have some sensory input, are also
+
+predicting when an eye movement occur and indeed which location
+
+visual space I'm moving towards.
+
+So you can vary the signal as visual motion streamers
+
+in the on the screen.
+
+In this case, if you move it, for example, in
+
+one direction, it's to say to the left.
+
+Which would inform the animal that the eye movement should
+
+be to the left that is away from the part
+
+of visual space that these neurones represent.
+
+Then you find actually that the activity of these neurones
+
+is very low.
+
+And indeed, when they make an eye movement, nothing much
+
+changes.
+
+If, on the other hand, you put a lot of
+
+thoughts moving in that direction to the right, predicting that
+
+the movement should go to the right, which is also
+
+happens before this neurone.
+
+The preferred location of the eye movement is a good
+
+deal.
+
+You find that the activity goes up substantially, is sustained
+
+through the time by movement and then dies away.
+
+So these neurones encoding three different things.
+
+They seem to be encoding aspects of the visual stimulus,
+
+the coherence of the dots and when and where the
+
+eyes move.
+
+They are sensory motor neurones like those we discussed in
+
+Area 80 on Friday.
+
+So this activity predicts the direction of the movement, as
+
+I showed you here, which.
+
+If the animal was making it immune to the right.
+
+In this case, the activity is high because making my
+
+move to the left, the activity is low.
+
+The activity signals the direction of the eye movement.
+
+It signals also the time of the current, the eye
+
+movement.
+
+And also the activity also depends on the actual strength
+
+of the visual signal.
+
+If there was a lot of speed in the same
+
+direction, the activity is not.
+
+The activity is lower.
+
+So these new ones are really integrating lots of different
+
+types of things, integrating visual sensory information and predicting where
+
+an eye when and where an eye will move.
+
+They are that boundary, the interface between sensation and motor
+
+output.
+
+Despite his own father.
+
+The simple decision is whether I should be moved right
+
+or left.
+
+We'll hear his indistinguishable in his past.
+
+But a visual motion into the Michael, where I've also
+
+said to you that neurones in our IP may participate
+
+in making decisions about where to move the ice.
+
+And the logic, the reasons for making that claim that
+
+these neurones in our area may participate in making these
+
+decisions.
+
+Is that they are not sensory neurones because their activity
+
+build up slowly and is continued after the cessation of
+
+the visual stimulus.
+
+They also are not sensory neurones because their activity predicts
+
+the time and direction of a subsequent eye movement.
+
+Even when the sensory information is ambiguous.
+
+I didn't show you here.
+
+But those neurones are also not just motor neurones because
+
+their activity depends on the visual stimulus.
+
+So if example this number of dots moving in the
+
+same direction changes the.
+
+I give you the neurones that I have a sensory
+
+representation.
+
+And what I only alluded to here and haven't really
+
+shown to you that the differences in their activity emerged
+
+early on in the response way before my movement was
+
+actually made.
+
+So these two different sets of evidence that you can
+
+see in this one task said if these neurones are
+
+neither sensory neurones nor motor neurones, but something at the
+
+interface between them.
+
+And for that reason they are hypothesised to be closely
+
+involved in the formation of decisions about where to move
+
+the eyes because they integrate.
+
+They say that the bridge between sensory and motor activity.
+
+So we just come out of size and go back
+
+to the semantic illustration of what these two areas are
+
+providing.
+
+In this particular past year.
+
+The area Empty streets.
+
+Visual Sensory Stimulus Responses to visual Motion.
+
+I've suggested the area.
+
+Let me instead show you something that's more related to
+
+the behaviour output, or at least the interface between sensory
+
+and behaviour.
+
+So how does this fit into the kinds of parts
+
+that we were describing for?
+
+We can start to think about the activity in aerospace
+
+as potentially representing the decision variables.
+
+So.
+
+I said that there needs to be a decision variable.
+
+When we make a decision, we need to collapse that
+
+decision onto something as simple, as simple enough space in
+
+which we can make a decision, for example.
+
+We may want to say simply that if I produced
+
+at least five action potentials, that I am confident about
+
+the sensory input and I would like to make the
+
+decision to move my eyes around.
+
+In that case, the number of action tools that I
+
+produce is a decision variable.
+
+It is not enough of them.
+
+I won't make that decision.
+
+It is too many of them.
+
+There's more than enough of them.
+
+I will make that decision.
+
+The decision variable.
+
+So we could argue that the activity of neurones in
+
+LP is actually a decision variable itself.
+
+And further, we could say that when we apply criteria
+
+to that decision variable, that is a particular threshold, let's
+
+say five action potentials.
+
+Once I pass that bacteria, I will make that decision.
+
+So we go back to this description of what a
+
+decision might look like.
+
+We have, as I said before, the task is moving
+
+left and right some hypotheses that we generate some belief
+
+and find knowledge that we're not really going into.
+
+And here we have the analysis of visual motion and
+
+a decision in the end to move the eyes left
+
+or right.
+
+It should be.
+
+Another thing here is useful form of evidence is actually
+
+the output of every empty decision.
+
+Variable is potentially the activity of neurones in every LP,
+
+and the decision rule is simply that when the activity
+
+of neurones in area LP exceed a certain value, then
+
+I move my direction in my eyes and the direction
+
+indicated by those neurones.
+
+So this is a simple architecture for making a very
+
+simple decision.
+
+But we start to learn some really interesting things from
+
+this.
+
+For example, in the next few slides.
+
+What I want to show you is that the predictions
+
+of this kind of model.
+
+Are the simple decisions in the course of simple decisions
+
+and hard decisions.
+
+There are compromises between the speed and accuracy of the
+
+decision.
+
+I showed you this graph before it.
+
+In the context of these tasks, monkeys and humans are
+
+very capable of making correct decisions when the number of
+
+dots moving in the right direction is enough and we
+
+get it right 100% of the time, and when it's
+
+not enough, we get it right on time, which is
+
+chance.
+
+And in between we have a graded performance.
+
+What I didn't show you was that if you looked
+
+at the reaction time and given all monkeys that it
+
+takes the time it takes to make these decisions.
+
+The report was moving left to right.
+
+This also varies if the motion hearings.
+
+It takes longer.
+
+That's at the left.
+
+It takes longer to make the decision when there's very
+
+few dots moving in the right direction and takes less
+
+time to make decision when there's a lot of moving.
+
+And we might think that the difference between the minimum
+
+amount of time it takes to make a response, it
+
+might be simply in our time, it takes me to
+
+trigger a motor action.
+
+That difference between the minimum and maximum amount of time
+
+make a decision for people thinking we're deliberating about what
+
+the information is.
+
+The evidence is that is provided by those you can
+
+the spring.
+
+And in the context of the model I'm showing you,
+
+we can think of then evidence being accumulated over time.
+
+We require a threshold to be reached, after which we'll
+
+make the decision.
+
+And when the sequence is moving, a lot of thoughts
+
+are moving in the same direction.
+
+That threshold is reached relatively quickly, or when only a
+
+few dots are moving in the right direction, that threshold
+
+is reached.
+
+We slowly.
+
+So this model, which is often called the drift diffusion
+
+model or accumulation model or rate model, or is it
+
+about faulty compounds or it simply predicts that hard decisions
+
+take longer because the rate of accumulation of the decision
+
+variable, the evidence is slower when when a stimulus has
+
+less signal to noise ratio.
+
+You can even step.
+
+We can even start to dig down a bit further
+
+into in this module about how the decisions actually might
+
+be made.
+
+I showed you that owns an area and keep people
+
+in motion directions.
+
+What?
+
+I didn't show you.
+
+But what I told you was that some of your
+
+own example coercion happened to the left and some down
+
+to the right.
+
+Up into the right.
+
+Down to the left, for example.
+
+So to make this decision, what we would like to
+
+do is compare the responses of neurones that are, say,
+
+representing often to the right with those and in the
+
+opposite direction.
+
+Right versus left, for example.
+
+So we might find you are preparing activity of neurones,
+
+preparing right with motion activity, neurones, preparing network management.
+
+The way to extract a decision variable, a useful form
+
+of evidence from these neurones is simply to find a
+
+difference in their activity.
+
+What is one minus the other?
+
+We just represent that with a minus sign and we
+
+do that.
+
+In an area of IP.
+
+We expect that to be the difference between these neurones
+
+activity, which initially starts off as zero stimulus and then
+
+after stimulus turns on gradually or rapidly.
+
+Starts to go in one direction or the other direction.
+
+So, for example, in this case, this evidence area of
+
+activity in area of IP will tend to go towards
+
+evidence for a right wing motion.
+
+So we can think of then of this area activity,
+
+an area IP representing the accumulated evidence that is seen
+
+as moving either right or left.
+
+And further that we will apply criteria to that activity
+
+generating IP such that when this activity reaches a certain
+
+level, we will decide that the dots are moving to
+
+the right or to the left.
+
+And that active you accumulate over some time.
+
+That time of accumulation will depend on the magnitude of
+
+the evidence.
+
+Yeah, so that's a really good question.
+
+So the exact mechanism for how you subtract your rooms
+
+can vary.
+
+The simplest way to think about is you think back
+
+a few lectures.
+
+If you have glutamatergic outputs from some neurones and gabaergic
+
+apples from other neurones and the Gabaergic and the glutamatergic
+
+have different signs, one is positive, one is negative.
+
+And so when you add those together, you actually have
+
+a subtraction going on.
+
+So if you inhibit activity from activity output of neurones
+
+that are going right one direction, if you inhibit them
+
+by the activity of neurones exerting liquid direction, you actually
+
+have a function.
+
+Antibody suppression.
+
+So inhibition can do this infarction for you.
+
+There are other ways of doing this, but that is
+
+the most obvious way to find.
+
+Those neurones are coming together in some form, invited together
+
+into a light.
+
+If some neurones are providing in addition to some neurone
+
+defining excitation, you can subtract one from the other and
+
+get this form of evidence.
+
+Now the schematics are showing.
+
+You going to show you the kind of real activity
+
+on a trial by trial basis and every MP.
+
+If you think about this, it's also schematic, but it's
+
+a bit more realistic.
+
+There's a lot of variability from moment to moment in
+
+the activity of neurones and area and to.
+
+So, for example, those neurones that were preferring right with
+
+motion are no longer nice straight lines, but they will
+
+be lines.
+
+And you and Fred, right?
+
+MARTIN And your friend Macklemore from Memphis.
+
+In fact, these you still in the end get towards
+
+the same value, but you got a lot of variance
+
+in the game, for example, instead of having a straight
+
+line here.
+
+Absolutely.
+
+Lines are important, first of all.
+
+Now, the consequence of this noise that's happening on each
+
+trial is variability in your firing is that sometimes you
+
+might reach this criteria more quickly on than on other
+
+times.
+
+So for example, and because of that, we need to
+
+make a decision about where we set the criterion and
+
+what decision we're making.
+
+It is evidence accumulates over time.
+
+It will, in the end get to the right place.
+
+If we make our criteria nice and high threshold, nice
+
+and high, we will only.
+
+Make a decision when the evidence is accumulated to a
+
+really safe sure bet.
+
+So we going to have a higher threshold and make
+
+sure that we don't make the wrong decision.
+
+If, on the other hand, we reduce our criteria, reduce
+
+our threshold, we become sensitive to noise variability.
+
+Some of the times that noise is fine, that variability
+
+is fine.
+
+So, for example, here we're still making the right decision
+
+is going towards the right.
+
+We're making it earlier because we're able to be more
+
+sensitive to the early phase of the activity.
+
+But we also occasionally make the wrong decision because actually
+
+because that noise, that variability, the activity, the new ordinary,
+
+empty, we're actually representing the wrong direction in motion at
+
+that point in time.
+
+So if we make our criteria really, really low, we're
+
+going to be faster to make decisions because we need
+
+less evidence to accumulate.
+
+But we're not going to make we run the risk
+
+of making the wrong decision.
+
+So we transform a safe and slow decision and go
+
+fast with every decision.
+
+Just by simply changing the criteria which will apply to
+
+activity of your.
+
+The other way that we can try and change the
+
+kind of responses we make is by adding bias to
+
+the activity.
+
+So, for example, we might come in with preconceptions and
+
+don't move to the right.
+
+We could somehow change the combinations we're making such that
+
+the activity goes right with neurones ones closer to the
+
+threshold that we've set.
+
+We will then be very capable, very capable of detecting
+
+dogs that move around very quickly.
+
+With our bias allows us to make fast decisions.
+
+Our it also runs the risk of making the wrong
+
+decision.
+
+If, for example, these double blind gear activity would have
+
+normally ended up being a st, the left was unfortunately
+
+to the right.
+
+Early on in the trial.
+
+So again, we can transform a safe and slow decision
+
+into a risky and fast decision, this time not by
+
+changing the criteria that we're applying to the activity, but
+
+by changing the bias that we put into the system
+
+in the first place.
+
+We might call this our five beliefs, our bias, or
+
+whatever it is.
+
+It's it's something that we can use to manipulate the
+
+activities.
+
+I want to spend so.
+
+But hopefully outline to you there is that in this
+
+very simple framework of understanding the decision and these very
+
+simple, neurobiological driven models of making those decisions.
+
+We actually have some profound insight about the process of
+
+making decisions that we can have these safe and slow,
+
+fast and risky ones.
+
+We've actually been able to see how neurones that bridge
+
+between sensation and motor activity might actually help revive that
+
+season, although we still don't know.
+
+How.
+
+I just want to spend a few seconds, you know,
+
+just describing some one of the other outcomes of that
+
+kind of framework.
+
+And that is one of the things we want to
+
+do when we make decisions is learn from them.
+
+We want to make better decisions in the future.
+
+And.
+
+The other thing that we want to do is and
+
+make better decisions.
+
+We kind of know how confident we were in those
+
+decisions.
+
+We also want to know.
+
+We want to associate the decisions that we make with
+
+the presence or absence of a reward that we get
+
+from students.
+
+So we all know how confident we are in the
+
+season we're making so that we can learn from those
+
+decisions.
+
+We want to know if those decisions led to a
+
+reward.
+
+Strikingly, we've been able to make some progress in that
+
+in the last ten years.
+
+But this accumulation model actually predicts that a wave representing
+
+confidence in the activity of neurones.
+
+As I said before, we can have a decision variable
+
+here which accumulates over time until we make a decision.
+
+But if we look at the activity of neurones in
+
+the brain over this period of time, we also find
+
+another feature which would be very happy to be able
+
+to answer in this context is that.
+
+The certainty that we have and the variability in the
+
+activity, those neurones changes as a function of time.
+
+So not only are we getting a change in the
+
+mean, that is the accumulation of evidence, we're also getting
+
+a change in the variability of the activity of those
+
+neurones.
+
+And the consequence of that is that early on in
+
+the trial, for example, we have a lot of variability
+
+and we have much less confidence in our choices.
+
+Much more uncertainty.
+
+Whereas later on in time we have more certainty or
+
+more confidence.
+
+Now, of course, the variability of different.
+
+We can actually measure the reduction here that we are
+
+actually more confident later on.
+
+Like more evidence because the variability reduces and the activity
+
+of neurones and towards the main.
+
+We actually measure some of these things by confidence in
+
+humans and animals.
+
+This is one really nice example of how to find
+
+it in a child in this case.
+
+We can measure the confidence the animal the child has
+
+in the decision making without even asking.
+
+And the rate at which a child will find very
+
+difficult to do.
+
+This task is really straightforward and really, really elegant.
+
+A trial has shown two boxes through which they can
+
+put their hands and is shown that there's a toy
+
+in one of those boxes.
+
+They are then required to.
+
+A delay is then interposed between being shown that and
+
+then being exposed to the two boxes again.
+
+And then the account is required to indicate whether by
+
+moving the hand towards the box which of the thing
+
+before using.
+
+And that's a simple task.
+
+That's the simplest open task that the to do.
+
+It is stunning when you do this task is to
+
+do what you see represented here on the x axis
+
+is the memorisation.
+
+The way the time between being shown the and being
+
+asked to complete the task, which ranges between three and
+
+4 seconds in this experiment.
+
+And the Y axis here is what we would call
+
+the persistence.
+
+That is how long the child leaves the hand in
+
+the box scoring for the object.
+
+The green dot here shows how long they leave the
+
+hand boxes going.
+
+By the way, he's not there.
+
+There's not public approval.
+
+When they make the correct decision and the read points
+
+indicate how long they chooses to go where there may
+
+be a decision.
+
+Now, if the child had no representation of the confidence,
+
+they hadn't made decisions.
+
+These values should be the same.
+
+You should explore as long whether you made the correct
+
+or incorrect decision, you should explore the same outcome.
+
+As strikingly, you find that the child exposed longer when
+
+they've made the correct decision and when they're waiting for.
+
+This implies that the chart has a representation of the
+
+confidence in the decision they can somehow use.
+
+Another elegant design is in monkeys, as shown here and
+
+there.
+
+And I'll just take you through this briefly.
+
+But basically that same experimental design that we saw before
+
+we realised the left or the right is now elaborated
+
+slightly with one little change in the experimental design.
+
+Now instead of just having left and right pockets to
+
+move their eyes.
+
+There's also another target that allows a monkey to make
+
+a sure bet.
+
+A sure bet is a small but consistent war.
+
+So the monkey's unsure about the decisions that they're making.
+
+They could take the show back because I know they'll
+
+get a small reward if they're more confident that this
+
+isn't the right thing.
+
+It was more like a move to the left or
+
+the right pocket, which will give a larger reward there
+
+some risk.
+
+And indeed, if you ask the monkey to do this
+
+task, you find the data.
+
+I won't go through the data particularly here, but it
+
+is, as you would expect, Monkey makes more choices when
+
+it is when the signal strength is lower and therefore
+
+he's less likely to be concerned and less sure choices.
+
+So the signal strength is higher is therefore likely to
+
+be important.
+
+So this is the probably the short target.
+
+And the probability the short target decreases with this amount
+
+of.
+
+Signal strength.
+
+Strikingly, if you look at the activity of the neurones
+
+in this area of IP actually represent whether or not
+
+the animal will choose the short target early on in
+
+the trial.
+
+This is a little bit tricky, so I'm just going
+
+to show you this and describe it to do really.
+
+This is the task here.
+
+During this time here, there's a period of time here.
+
+That's when the stimulus is on.
+
+Now the dots come on and then they turn off.
+
+And then at some point in time after that, the
+
+short target comes on.
+
+And that's from Dave on this test line.
+
+And then some time after that, the channel makes a
+
+choice by moving their eyes.
+
+You can ignore the street here for a moment and
+
+just look at this bit during the presentation.
+
+The stimulus.
+
+It turns out if you divide those files into three
+
+different parts, Monkey chooses the left target, choosing the right
+
+target, which uses a short target.
+
+The activity in this period before they even know that
+
+the short target will be available, predicts the upcoming decision.
+
+The implement.
+
+This short target is only available on 57,000 unpredictable 50%
+
+pilot.
+
+And we did not know that that tiger will be
+
+available when when this activity is developing.
+
+And yet that activity sits between this activity, the left
+
+and right eye movements, even before the animal knows the
+
+target is available.
+
+That is evidence of an activity representing the confidence the
+
+animal has in the decision to bear out or.
+
+I'm going to get this slide, but I encourage you
+
+to write.
+
+I read the papers.
+
+I just want to end this by saying.
+
+When we make a decision, we hope that that will
+
+be the correct decision.
+
+We hope to get reward for a couple of lecture
+
+lectures ago, we discussed the part of the brain that
+
+is actually important in generating rewarding signals eventual placement where.
+
+And it turns out that that little area of the
+
+brain provides broadcast signals about work and incorrect decisions to
+
+the rest of the brain, including those areas like it
+
+either involved in making these decisions.
+
+And there's a beautiful set of data in the in
+
+the in the technical area which shows.
+
+When an animal is learning a task like the kind
+
+of task of showing their.
+
+That that the activity in the rental health area which
+
+in start of encoding the reward that the animal gets
+
+transitions to encoding the stimulus that will predict the reward.
+
+And so the animal was able to use this teaching
+
+signal from the entertainment area, its own signal to learn
+
+how to make better decisions.
+
+I just explain this diagram here to help you understand
+
+what is going on.
+
+Early on in the learning process, Dan was not provided
+
+as it was.
+
+It does get a reward, maybe a reward of juice,
+
+for example.
+
+And when that reward is provided, the activity of neurones
+
+in the BTK monkey again increases.
+
+The animals and learn to associate that the terms of
+
+that reward that Jews with a previous occurrence of the
+
+stimulus that predicts that reward.
+
+This we were condition stimulus.
+
+And after a long time of learning this relationship.
+
+The animals have eaten during the VTR no longer respond
+
+to the reward itself, but respond to the presence of
+
+the stimulus, the conditions in this.
+
+And indeed, if a reward is absent after presentation of
+
+the conditions in which you see this produce and everything
+
+approaching the EPA.
+
+So the neurones in the mental states mental area are
+
+also representing the outcomes of these decisions.
+
+They're representing whether or not a stimulus will produce or
+
+upcoming reward, and they're allowing animals to learn from that,
+
+from that rewarding and rewarding scenario.
+
+So what I hope I've shown you here then is
+
+very simple decision architecture.
+
+Face and sensory input.
+
+Making eye movement has taught us a lot about how
+
+to see the snake in the brain.
+
+We've seen that some neurones that seem to sit at
+
+the interface between sensory and motor outputs accumulate signals in
+
+a way that is inconsistent with the idea that they
+
+form in of themselves the activities of the client in
+
+making this decision and that all we need to do
+
+a set of criteria on the activity of neurones so
+
+that we subsequently make a decision.
+
+I've shown you that in addition seems to be representation
+
+of confidence in the brain, a way that we can
+
+be confident about whether or not we're making the right
+
+decisions.
+
+I'll show you also that in the reward circuits in
+
+the brain, which allow us to learn about history and
+
+experience of making those decisions.
+
+How will these things come together?
+
+This remains still a mystery.
+
+How all these things are brought together, how they invade
+
+consciousness, an awareness that only remains in these people.
+
+Those signals are there.
+
+This is what we've learnt over the last ten years,
+
+and what I would find explained to you on Friday
+
+is how those ending direct with the emotions that we
+
+feel.
+
+Thanks everyone.
+
+I was.
+
+Very.
+
+Sure about a ton.
+
+Of pressure placed on the monkeys by the experiment.
+
+Oh, that's a really good question.
+
+Right.
+
+So.
+
+So you could make these decisions in two context.
+
+One is you got all the time in the world.
+
+But make these decisions in context.
+
+One is you have all the time in the world
+
+and the other is you need to make it in
+
+a set period of time.
+
+Now, the context in this case for these animals is
+
+provided not so much by the but sort of.
+
+But these animals, there's two things that you might want
+
+to try and make it fun.
+
+First of all, the faster they make decisions, the quicker
+
+they get.
+
+And they figure they get to the next problem that
+
+they have during the 7010 problem.
+
+So that's one one plan.
+
+The other one is that the stimulus plan.
+
+So there's actually no further additional data from that.
+
+So there's there's a concept that there's no additional evidence
+
+coming in.
+
+So you've already got all the evidence.
+
+And if you make it faster decision, you get another
+
+of.
+
+So this is not like an election.
+
+It's a what.
+
+Is what what official news.
+
+We don't get comparison with what I saw.
+
+What is the model when you're on an area like
+
+that is that when they're actually reaching a certain.
+
+Probably about 16 foot about one in every six feet.
+
+That is.
+
+So whether this is some of this is certainly part
+
+of the voting.
+
+Record during the primaries.
+
+What we do know is that the.
+
+In the area like we predict.
+
+When you.
+
+And there is more or less in terms of the
+
+number of actions that an optimist sits on.
+
+Yeah, right.
+
+And also this like I don't know how this relates
+
+to the fact that the you're asking to have like
+
+a preferred coin partner.
+
+Yeah.
+
+Sorry I struggle to work out between say so.
+
+You're in the now and you were mysterious for a
+
+long time when they seemed to actually.
+
+Yeah.
+
+So the fact that.
+
+So when you want to do things to some kind.
+
+Are you finding some kind of situation in which.
+
+So it's actually.
+
+A time.
+
+Where the.
+
+But then you the event.
+
+Well.
+
+Oh.

requirements.txt

@@ -0,0 +1,7 @@
+langchain
+openai
+tiktoken
+datasets
+pypdf
+git+https://github.com/chroma-core/chroma.git@d5be7a66a8f1cb9aef7727c1e519c482dfe9df06 # chroma without torch
+gradio

summarize.py

@@ -0,0 +1,82 @@
+from langchain.chains.summarize import load_summarize_chain
+from langchain.text_splitter import CharacterTextSplitter
+from langchain import OpenAI, LLMChain, PromptTemplate
+
+from datasets import Dataset
+import textwrap
+from tqdm import tqdm
+import os 
+
+
+
+
+
+
+template = 'Write a verbose summary of the following:\n\n\n"{text}"\n\nDo not omit any information. VERBOSE SUMMARY:\n\n\n'
+prompt = PromptTemplate(template=template, input_variables=["text"])
+chain = LLMChain(prompt=prompt, llm=OpenAI(temperature=0), verbose=False)
+
+def _summarize_func(chunk):
+    chunk = chunk["chunk"]
+    summary = chain.run(chunk)
+    assert isinstance(summary, str)
+    return dict(summary=summary)
+
+
+class RecursiveSummarizer():
+
+    def __init__(
+            self,
+    ):       
+        self.splitter = CharacterTextSplitter.from_tiktoken_encoder(chunk_size=3900, chunk_overlap=0, separator=" ")
+
+    def _save_txt(self, string, lecture_number):
+
+        #string = textwrap.wrap(string, width=60)
+        #string = "\n".join(string)
+        with open(f"./data/bab/lecture_{lecture_number}.txt", "w") as f:
+            f.write(string)
+            
+    def summarize(self, text, n):
+
+        text_length = len(text)
+        print("Initial Text length: ", text_length)
+
+        i = 0
+        while text_length > 18000:
+            i += 1
+            print(f"Summarizing p{i}...")
+            # split text into chunks
+            chunks = self.splitter.split_text(text)
+            print(f"Number of chunks: {len(chunks)}")
+
+            # summarize each chunk in different threads
+            ds = Dataset.from_list([{"chunk": chunk} for chunk in chunks])
+            summaries = ds.map(_summarize_func, num_proc=len(chunks), remove_columns=["chunk"])['summary']
+
+            # join summaries
+            summary = " ".join(summaries)
+
+            text = summary
+            text_length = len(text)
+
+        self._save_txt(text, lecture_number=n)
+
+        return text
+    
+
+if __name__ == "__main__":
+    summarizer = RecursiveSummarizer()
+    
+    # scan for .txt files
+    txtfiles = [f for f in os.listdir(".") if f.endswith(".txt") if f.startswith("lecture")]
+
+    for t in tqdm(txtfiles):
+        # extract lecture number
+        n = t.split("_")[1].split(".")[0]
+        print(f"Summarizing {t}...")
+        # get text from text.txt
+        with open(t, "r") as f:
+            text = f.read()
+
+        summarizer.summarize(text, n)