 So we'll mention relations. We'll talk about primary visual cortex a because it's crucial to understand vision But also because it is in some respect a typical cortical area and not in all respects And so it's useful to learn about it as a representative So I don't know how many of you have actually ever seen a brain This is a facsimile of a brain of a human brain. So it's it has almost a texture. It's a little bit harder I mean real human brain once you remove the the skins it sort of it's quite soft It really literally is a bit like an overcooked. I mean doesn't quite fall apart like an overcooked cauliflower But like a cooked cauliflower and this is actually the size of the brain. You can see So this is the thing that this is this is your world This is where everything comes from at least so we believe all your thoughts your memory your ideas your compassion your love your hate they all reside in here and Specifically we're gonna be caught talking about cortex of course cortex isn't the entire brain It's what makes us you uniquely human But they of course as much more to the brain than just cortex or cortex is this big sheet here or neocortex It's this big sheet here and it's something. I mean it's by far the greatest expansion in if you look at the animal kingdom is in it's in in in In vertebrates in particular in mammals so that it's one of the hallmarks greatly extended neocortex Sixth layer neocortex is one of the hallmarks of mammalian evolution But of course there's lots of other things that that's responsible for for for keeping us alive and We'll talk about some of them enabling us to move to make fine movements But most of us believe that those things that end that specific sensations specific sense Senses the fact that I can see blue I can smell or I can hear and certainly things like reasoning and doing science and moral judgment And memories all of those are tied up specifically in neocortical circuit that they might need a lot of the support structure of Outside the neocortex, but that the neocortex and associated structures particularly the thalamus and the basal ganglia And the amygdala and hippocampus together those are known as a forebrain This is a term that comes from development that the forebrain really generates everything that makes us Most everything about our mental lives and our experiences of the world So we have to understand this. We have to understand the substance if you want to come up later on and look at it It's a it's a quite nice brain Also have a real brain, but that's sort of a layout and that's in Clays in in in closed in plastic and you can't really look at it. This is sort of more can get some feeling for its size How many have ever done it an anatomy course? Who's ever done a human brain anatomy course? Oh, quite a number. So some of you have dissected human brains Okay They're remarkable Homogeneous, right? I mean it's difficult to see anything much in them was quite disappointed first time I saw a human brain So here you see it high-scale This is a this is a brain from a from a monkey But it's it's smaller it in principle is no different from the brain of a of a human and what you recognize One of the key features about brains about cortex is that it's a two-dimensional tech It's a two-dimensional structure or as I mentioned before 2 plus epsilon dimensional Epsilon that conveys a sense that the that the width of this structure is much much much smaller than the extent of it So I think I mentioned it's already its insurance. It's roughly hundreds thousand square centimeters one cortex in a macaque monkey Our model system is more like a hundred square centimeters for a hundred square centimeters That's like a you know peanut butter cookie while I think in us. It's more like I think of what is it of 1428? It's something like a to 14 inch pizza No, like this and you've got two of them and they all scrunched up and put into into your skull and This dimension here ranges from let's see two to three or 3.5 millimeters in us and in in in a macaque It's remarkable constant in a mouse. It might be thinner in a mouse It may be one to one point five millimeters, but you know compared to us. It's it's two or three or four millimeters So the this dimension is very very little what this dimension has been very enormously So if you go to a tree shoe or something like that, it's maybe a square. It's a square centimeter macaque It's a thousand and and and human brain is sorry macaque is a hundred and a human brain is a thousand Of course, we are not the biggest brain. We do not have the biggest brains Right that that's our distinction goes to mammals like like dolphins or whales They have bigger brains, but typical human brain will weigh between I don't know 1200 1400 1500 grams Dolphin a brain can weigh or some whale brains can weigh five kilograms and so it's really important to understand that it's it's a really it Structure that involved in two dimension and the evolution seemed what happens in evolution that it Extra areas get added rather than anything here in the in in the width of the of the of this sheet of this Computational of the sheet of of neurons changes substantially In fact, there's a there's a nice anatomy paper published 20 years ago What people make the observation that if you look at a cause different species from? mice to rats to Cats monkeys and shoe some human material the number of neurons below a square millimeter of cortex It's roughly constant on the order of 80 to 100,000 neurons So the D is that if you look at across these different animals that have slightly different ways not a lot Maybe factor two or so that the number of neurons in a column of by one by one millimeter You know from layer one to layer six is roughly the same on the out of hundred thousand That's a very good number to remember and there's some exception like primary visual cortex It happens to have roughly twice the number of neurons to 200,000 particularly in its input layers because it needs to represent The visual world, but that seems to mean that's where V1 sort of seems to be exceptional compared to other areas So they're up on the order of 100,000 neurons per square millimeter and like I said, they are on the order of 10 to the 5 square millimeter in a in a in a Human cortex and you have two of them. So if you add up all those numbers I think you come something like 20 billion. It's a rough estimate of neurons in the human cortex 20 billion Two times ten to the ten of course in the cerebellum. They're more they're probably like 50 billion neurons Nobody quite knows what they do. So the estimates on the order of hundred billion neurons in there in the human brain So what you can see here already? That sort of this structure doesn't this cardio sheet is not homogeneous It seemed to be layering and that's a very important observation that it's not it's not totally homogeneous It has these layers and you can zoom in on them and then you can discover some substructure This is a This is all in the front in the back matter of my book and I got it from an Anatomist who's going to give you a talk in Monday at Caltech at Callaway who's at the Salk Institute So he shows two things here a he uses a stain called a nissel stain And this will stain that shows up every single cell body There's some some something in the nucleus that stain that's picked that stain by this particular chemical procedure And so you can see every single neuron in here Now and what he's done superimposed he's superimposed six neurons at using a different technique He actually reconstructed that then not only the cell body, but the entire the entire Dendritic tree and some of its axonal tree So you have to imagine that each one of those points when you expand it expands to something like this So you can imagine it's a quite it's a very very very dense tissue So let's look at some of these so first of all if you look at this the predominant Feeling you get it's the same feeling you should have when you walk through a forest Well, what I mean is that you have this vertical organization. It's very typical You know, you know if you have you have this vertical organization It's not to say that they aren't like here branches that extend horizontally But again the predominant orientation seems to be from top to bottom This is the top up So this is layer one on top of layer one you have the various brain skin skins But they appear in the Duomata and the Arachnoidae and then you have the liquid and then you know Somewhere up here you would have a skull this incidentally is taken from from a portion here in v1 Okay, and then here this is this is sort of the gray matter the provodial gray matter and then here What starts here below layer six is a white matter and what you see there the white matter is mainly the myelin the Isolation sheath of axon so axons are isolated electrically the isolated using this structure called myelin that enables the Insulation enables the action potential these pulses to zip along at much faster speed than if you wouldn't have this Isolation so that's where I mean that's that seems to be the key the key purpose of that so So, you know all of this here would be sort of the the wiring The white matter So between the top and the white matter you have this you have these cortical layers Typically in neocortex you have six layers sometimes in older part of cortic cortex like alia cortex or olfactory cortex You're only a three layers, but sort of the highly evolved Modern neocortex is has six layers although sometimes people define and if you read the literature You'll find it's very confusing because sometimes people have ten or even twelve layers and you know They're looking at the same brain and it's like anything else if it's complicated enough You know different people you know different people even though they're reasonable can can sort of see different structures in here So here for instance you have more than six You have sort of these sub layers 3a and 3b and 4b and for C and then C or sometimes it's further split up into alpha and beta Okay, but one key point is you have this vertical organization So let's see let's look at one of this cell here. So this is one of these typical cells a pyramidal cell It's called pyramidal because roughly it has a pyramid shape and 70% of all cells of this ill pyramidal cells So you have a lot of them and in fact when people talk about their gray cells Typically that's what they mean here pyramidal cells So it has a cell body here. That's here and Somewhere here. This is the axon. The I can't see where that leaves and then it makes these local branches So this is the purple here. So it's the axon the local axon or terminal So it's like this this action goes out It sends the action down here that then disappears it isn't stained anymore disappears into the white matter and goes Who knows where for example? It might cross to the other side of the brain It might cross into the you know through the colossal collection into the V1 on the other side It might go down to the superior colliculus. I mean we and we don't know where that goes But then it's like it all it's like you put a CC on there's also a carbon copy of this message It's sent out to local to local parts of the brain in its neighborhood. This is a quarter of a millimeter So, you know this axon here. Let's see within a millimeter. It makes lots of Lots of terminals the terminals are not shown on here But the synaptic terminals would be these little things called boutons It would be distributed on here and then in those in turn contact the dentrility of other neurons And you can see let's see same thing here this pyramidal cell Another parameter cell so it makes law lots and lots of axons here contacts here some contacts here And then I guess it also has an axon that disappears This is an input axon the black one here is an input axon remember the LGN the lateral geniculate nucleus So this is this relay station between the retina pretty much halfway between the retina and prime visual cortex So it sits somewhere down here conceptually in the basement comes up here and then turn it into this zone It's specific. It goes into layer 4c. So although this looks relatively random There's a lot of and the more people look with better and better techniques particular with molecular techniques the more specificity they see So It typically the input here comes is confined to this layer 4c, which is maybe like 150 micrometer This way this is typically where the LGN input goes not only it can also sometimes go here But most the bulk of it goes here into layer 4c So typically layer 4 is the input is input to cortex So it's the layering is very important and if you read the literature people constantly talk about layer They say well, this is a layer 2 cell or it's a layer 5 cell and it's important because it gives the layering seems to convey What the new what what sort of the input to the neuron the output to the neuron where it projects to a lot of that Is tied up where in which layer it is So it's important to know and once again the take-home message is neurons are not just sort of excitatory and inhibiting Otherwise they are in their random net like many neural networks have them, but there's a great deal of specificity in the more We look the more specificity we see Okay, let's see what else Here you have these you have these pyramidal cells this is an interneuron an inhibitory interneuron and this is an interneuron I Think this is probably an excitatory interneuron. This is probably a spiny stellate cell So there are some cells. They are called spiny stellate. They look like Paramele cell except except they lost a big apical den right so what's characteristic for an apical for paramele neuron Is that it has this big den right here here or here? That's very typical and some you don't have that so like these and typically they they they remain projections remain inside Caught inside their local cortical region, which is why they called interneurons You have excitatory interneurs and inhibit your neurons for the vast majority of output from cortex out of out of cortex proper sit down to the thalamus or to Collequilosa other structure involves axons from the pyramidal neurons or Intra cortical communication from one cortical area to another cortical area all that typically seems to involve almost always axons from pyramidal neurons, so they are the big projection you and they project elsewhere So they whatever computation you have to do And rapidly communicate to other parts of the brain. It has to involve these these these neurons As I mentioned in my first lecture, this is the the main problem of all field theories of of Consciousness was just reviewing one so theories that claim that this consciousness field and this sort of this Collective this field that sort of encodes or represents sort of the neural activity of the entire Gestalt of the entire holistic brain That's what communicates a specific conscious content and the trouble is if I mentioned there's no carrier for that The only physical carrier that you have in terms of exocellent potential is tiny is much less than a Millivolt if you want to communicate information from one cortical area like v1 to another cortical area Let's see an area empty which we'll talk about it's a it's another cortical area That seems to be specifically involved in motion It's called empty in the middle temple area The way you have to do it You have to excite these neurons and these neurons send output Generate action potential and those action potential get sent along their acts their axons and then terminate just like this one does Terminate in layer four of that next cortical area in this case empty and excite new unfair So these all these terminations are excited re so they From that synaptic term as they release a neurotransmitter typically almost always glutamate and that may mix a contact with Sign ups is on the dendrites of these neurons and excites them and you have this cascade of of of events that Percolate that percolate through the system It's not true. It's all the brain but certain cortex all the project not only is most of the output mediated by Parameter but it's always excitatory It's always excitatory cortex itself the only inhibition is always local inhibition There's inhibition quite a bit of it, but it's local to cortex what gets sent outside always seems to be an excitatory message Yeah, so it's just pretty stagnant if you think that each one of these points here You know expands into one of these neurons with all that dendritic tree in axon So the dendritic trees is right here That's sort of where all the input is summed We have all the synapses the synapses, you know generate electrical signals passive actively then they interact in very complicated ways I've read for those UK have written this big textbook biophysics of computation when we talk about that and then finally All that information sort of ultimately gives rise to an action to one or more action Potentials that are patterned in time and they are then sent along the the axons and then they are distributed those action potentials Sometimes not always invades those branches and they give cause a release of a neurotransmitter and that's how that's how the information is passed along This is not actually human this is human brain We know of course much less about human brain at this microstructure level for obvious reason than than an animal brain So this is from a human brain again. You've got pretty much the same structure Here as I mentioned before you have these sub layers that you have that's typical for primates for the alpha and for the beta In fact, remember last time I mentioned in the retina that there are two types of and that that 90% of Ganglion cells that make up the optic nerve. They're actually two subclasses. They are magna cellular and there are powers I'm supposed to stand here They are marked on power cell anions and remember 70% of cells are power cell cells They convey information about color and they seem to convey information about how a spatial fidelity and they They specifically make synapses in layer 4c beta and Then the big cells at any given eccentricity retina that have sort of large dendritic tree that have big axons Send go go to the LGN and then they in term go to go to 4c alpha And this I don't know and this is probably like three millimeters from here I don't have a scale down here probably like two and a half to three millimeters So this is a collage. It's a collage Brack sort of he specialized in Germany specialized in sort of recovering in these different neuron types from from human brain Postmortem tissue you can see he has lots of different cell types Depending where they sit and where they project to and where they have spines or not spines the majority of Paramount cells and then you have these sort of interneurons here with local neurons Yeah, I should mention really interesting stuff that came couple of years ago out. You can ask at the hardware level What I say, you know if you compare this guy for example with you know Macintosh 20 years ago or with you know Eliza or Eniac or maniac or some of those computers 40 years ago After the transistor revolution the basic switching components always the same They've just become smaller and smaller and smaller and you know still silicon and still CMOS Now You can also ask the question if you compare different animals What are the differences at the micro level? I mean the obviously difference at the at the at the micro level But what are the difference at the micro level if you're a human or you look at a monkey or you go back you look at them A mouse or you go back and look at them. Let's see a fly or something like that And it's very difficult sort of to come up with I mean there are few things like spines and Mylinization that mainly occur in in the vertebrate kingdom not exclusively but mainly There's a set mylinization. That's a great thing. It speeds up axonal propagation So one way you can get faster axonal propagation is by having a bigger bigger wire The biophysics conspires to make that action potential go much faster But another way is to put myelin this insulation around it and in general that seems to be something that vertebrate So that that's one of the things that vertebrate have otherwise it's different certainly was in primates or certainly was Sorry was in mammals. It's difficult to find at the hardware level something that's sort of unique Let's see two primates or just to us There's one exception though that people have now discovered So it's a cell type that was actually first recognized by well I think Golgi the kachal just mentioned it and from a corner mode describes it very explicitly in 1925 or something these are called spindle cells and they seem to be present only in two places in the brain in cortex in a high-level part of the brain in Part of the new cortex called insular and the anterior singlet and there are small numbers They are on the order of couple of hundred thousand If you want to know more you should talk to John almonds and see he he he was involved in the study What the study showed a couple of years back that these cells are seem to be unique to us and to some closely related species which is Bonomo, I mean the picnic chimp Chimps and either gorilla or an utan one of the one of those two You don't find them in a monkey. You don't find them in a cat. You don't find them in a mouse You don't find them lots of other mammals they've looked and that's exceedingly interesting to me because I mean You know as biologists we always stress the commonality of all living things but clearly their differences, right? I mean if you've ever tried to talk to a mouse You very quickly find out that we're not exactly the same and so it is always interesting to look for For at the at the lower hardware level, you know, and we're differences So this I find terrible interesting although we have no idea right now what it what these cells are involved with these are cells Like I said, they only occur in two play places in the brain In the cortex in a very high level part of the brain that's involved in attention volitional control things like that They are in layer 5 so layer 5 is one of the output structures that provides output Just like layer 4 is where the most of the input comes in layer 5 and layer 6 is typically Particularly a 5 is where the cortex sense output actions outside the outside cortex proper If you want to go for example To activate in motor cortex you want to move, you know I want to move my fingers then I activate a motor neurons in in layer 5 that sent sorry I act activate paranormal cells. You have a special name Bet cells and those go down to the motor neurons or if you want to if I want to move my eyes Let's say in v1 or in mt. I activate Another set of cells called minor cells again They sit in layer 5 and they project to to coliculose every time I want to do something in the world effectively I have to involve Neons in layer 5 so I do find it very fascinating Although we have no idea what it does that they are these cells that are unique to us and to a few closely related species And even those species like the bonomone chimp. They're present in many lower numbers than in in us So I find that pretty fascinating Otherwise at the hardware level as I mentioned before there's very little difference between you know If I just give you a cubic millimeter as homework, you know You each get to carry a little cubic millimeter of brain tissue and then you know if you if you would whatever tools Available to you, you know supposed to decide whether this is monkey or human brain or mouse brain. It's gonna be very very difficult Oh, yeah, I should give you some numbers so In a cubic millimeter So that's like this by this by this you know coming out What you know coming out in pretty space one cubic millimeter they're in this is in mouse I mean these things gonna differ but in mouse. They are on the all of 80,000 cells and 810 a million synapses You know So call it 10 to the 5 neurons and 10 to the 9 synapses per cubic millimeter and So that's roughly one sign ups. You can think with like a crystalline array where you have one sign ups every micrometer that's a lot of Lot of synapses and synapses of course where the communication happens and we think memory occurs there in the memory patterns encoded In the strength of those synapses where they're you know to sign up a sign up between two neurons is strong or weak And so you've got a lot of a lot of sign ups there even if you compare that against current sort of Technologies like you know your modern your most modern chip, which is probably now the transistor The gate of a transistor has a line width on the order of point Point one five or point one two micrometers. I think it's constant of the art for memory I think it's point one two and for CPU it's point one eight line with so the transistor gate will be two or three times that So but here you have an entire sign ups It has a lot of a lot of computational Elements in it and probably has you know maybe on the order of a thousand different proteins associated with it You've got a billion of those on the order of a billion of them per cubic millimeter And you've got what was it two point four kilometers of wiring in a cubic millimeter? That's a lot. I mean two point four kilometers. That's from you know, that's from here to the base of the mountain of axons So these are pretty thin Then right the thicker you have 240 meters of dendrites per cubic millimeter distributed over those 80,000 neurons This is again this shows from a real. This is from a ferret. I think this shows Is this a subset of all these are I think almost all pyramidal neurons the tenth of a millimeter here and this shows this at higher scale Paramount cell again and an interneon. This is an inhibitory interneon. So as I said they have Axons here that make local synapses in this case within maybe you know a quarter of a millimeter This is a pyramidal neuron another one Quite famous now. It's called Johnny for it's used in many textbooks So this put this goes to layer one and here terminates here's layer one and sort of you would have the top of the brain here layer one is almost pretty much devoid of Neurons itself. It's a very self-poor layer But you have a lot of the feedback that goes from high level from high level From a high level area in the brain down to lower area very often it terminates in layer one and layer two So when you you know when there's a high level message that's being sent from a high area to a lower area Very often that that has to involve synapses in this part of in this part of Cortex in the top in the superficial layers. These are also called superficial layers layer one two and three and For a because they are superficial to the main input layer and then these are called the the deep layers Or lower layers layer five and layer six. This is a how do you call it it's a From the pilot. No, how do you call it in the movie when you see him one minute trailer? Trailer will never understand why trailer shown at the beginning trailer would seem to imply Yeah. Oh Okay, well that makes sense. Okay. Well, this is a trailer I guess for movie my I'm doing with my brother who's a was a company in Paris Paris, France and We had some we have some really cool ideas about flying through the brain anyhow so the here you fly through you fly through Cortex and I think this isn't Somewhat unhappy with the artistic rendition each of those balls supposed to be in action potential The dips up and down the these axons and the dint really tree So I think and of course here we only show I can't remember that But it's only a very small like one or two percentage of all the news in that area that are shown there But I think it sort of it's an it's nice. I like it In your sin, I mean coming to a cinema soon Yeah, my brother's company specializes in doing a high-end scientific realization mainly molecular stuff This will be the first we've gotten a French and I'm a director to French Belgian director to write the storyboard It's pretty cool. It's about an alien who looks who looks inside people's brain. I mean the idea is to it's for a large audience It's supposed to ultimately in I max movie It's you know, it's an idea. It's a weight It's supposed to be fought into 15 minutes little movie for people to get a more emotional engagement So it's a nice story. It's dark. I mean, this is France, right? So it's a very dark summer mood and First they wanted to kill off the hero at the end. I said, no, no, no We're supposed to run in America. You can't do that. You can't kill off your hero at the end anyhow, so and then and then During the course of this movie and there are lots of chases, etc We we show various things inside the brain how it looks from the perspective of this guy who's being chased around How sort of how these images project on this retina onto v1 what happens in different parts of the brain? Okay Next year, hopefully so cell types. So as I said, there are many different cell types. I've asked I said this already in the retina People can estimate even 50 cell type 50 cell types and you would imagine when the retina all I really need photoreceptors And then you know like in a CMOS camera and then I okay Then I do some local processing and then I send it out over one output But even that isn't true There are lots of different types and they are as I said 8 or 10 8 to 10 Or maybe even more different types of output that project to cortex Depending on whether they signal the positive part of the signal or the negative part depending on whether the signal motion Or whether they signal high spatial frequency information or color and then there's some more specialized channel that go down to the To the midbrain to the brain stem involved in doing sort of household function like changing the pupil diameter and you know Making my eye moves etc in cortex. So if you think Retina's maybe like 200 micrometers thick cortex is 2 millimeters thick So if you apply the same principle you can already guess there could be many many more cell types And now depending and for those you're interested like on Monday There's a stalker at Callaway is going to talk more about it depends how you count and it's still it's still very early on But it could easily be that the hundred or couple of hundred maybe a thousand different cell types And those cell types might differ from one area to the next or there could be great We know ready their gradients We know ready if you look at a layered three pyramids in v1 And you look at a layer three pyramids in an intimate in a part of the brain called infratemple cortex Which is going to be very important for us and you look at layer three pyramids in front of part of the brain You see already that they are much more complicated up front the same type of neurons. They look much more complicated They have more spines. They have more sign after they are more a densely branch So certainly you have your big gradients cortex. So it's not that the machinery is everywhere homogeneous and Historically over the last hundred years there always has been this this debate this Dialogue between you know split as a lumpus between those people who think cortex essentially uniform It's a universal computation machinery that evolution came up with and then essentially the same in whether it's auditory or visual cortex Or prefrontal or factory cortex and people who say well overall It's roughly the same but then it has lots of variability how many layers it has how many cell types What is it what is the project to and you know, it's like anything else is truth is probably both There's a it's interesting hypothesis that relates to cell types Which is proposed by Francis Crick a number of years back which is called the tiling hypothesis and it says well If you believe the brain is efficient then and then in the visual domain you see well Each cell type should cover if the brain is efficient each cell type should only cover every spot in the visual field Exactly once because why be redundant if the brain is really efficient then you don't need huge redundancy Okay, and then and so then you can say well how many neurons does it take to cover one particular part of the of the Cortex, you know how big is the new on how big is its it's sort of its girls and then And then you know you average you average that with entire brain area and then you see well if they're more new And they probably do different things that what one you know one one cell type It should exactly tile the brain once and then it whatever does motion or color or stereo whatever does it can do it doesn't need 1010 10 of its kind if you assume this tiling hypothesis So the idea that the brain is tired in these in these neurons and each new on type tiles the brain as he wants Then again you come numbers on the all of a hundred to a thousand So even if you say okay, the brain is a little bit efficient in efficient Maybe two, you know you need two neurons per type still you come up with cell types on the out of hundreds And in the retina there of course tiling is much more established now because there you can count because there we know much We have a much precise understanding what the individual function of the neurons and there it is you true Indeed you can see that cell types typically one cell type will cover a particular spot in the visual field once or twice so that the take-home message here is There could be many many different cell types and we're very very far away from understanding what to do We're very far away from that probably women ecologist where maybe at the turn of the last century 1900s Because we can now record from these neurons, but typically we do not do not know from which new and we're recording from so all we can Tell okay, I'm you know blinding recording now here somewhere in you know area x and you know I know in a if I record you know consecutive times 50% of the cells seem to be doing that and 10% of the cells doing this But I don't know you know which type of new and I'm recording from and that's like doing molecular biology Or chemistry without knowing what you know what what what what molecule what what chemical reagent I'm I'm interacting with which Probably not a good idea But it's it's very difficult to do that sort of experiments to record from a neuron and Simultaneously discover what type it is where it projects to it's technically very very demanding So to a large extent we're still sort of in the dark Very much in the dark Okay, this is going to be part of the homework number What one is it now for Free Okay, it's next week. So we'll talk about And you can get all the background there in the homework. We'll talk about the representation of visual space in Cortex so as I mentioned already If you look at the photoreceptor distribution It's highly highly uneven the fovea that covers let's see 1% or less than 1% the central fovea of the visual field It's hugely over represented in terms of the in terms of photoreceptors in terms of cones not in terms of rods and this goes on and I mean If you look at it at every stage that sort of sent that emphasis on the central part of the visual field becomes If either just transmitted on or even further amplified until in the brain you come to the following picture So here what we do what what we do what hot and hot did so you have to be one is roughly this size It's on the odd of 20 or 25 square centimeters. So it's it's a little bit like this It's a little bit bigger, but not much now. You've got two of these you left and your right brain and in fact We do have a picture No, I don't Okay, so in fact Most of primary visual cortex so all the algae and output Remember the retina 90% projects to the LGN in the thalamus 10% 10% project to colliculus and other Small nucleus in the brain stem the majority goes to the LGN the LGN on block projects to just one area in humans and cats is different in to primary visual cortex of V1 now V1 sort of sits Well, so it's sort of here in this running in this in this In this canyon in this sulcus and it's a little bit like So if you take the medial side, you know, here at the back, this is the back right? So it's like like this Here and then you take what you take this calcium fissure. That's what's called calcium fissure and Sort of you open it up and flatten it out That's what you get and the horizontal median is down in the depth of this canyon So for if you just sort of cut open my brain, you see sort of this is the inner side This is sort of the the lower in the upper lip of the canyon And then if you want to go to the horizontal radiance buried here in the depth of the canyon and here what I do computation I just flattened out that representation okay So it's a flattened representation for our viewing convenience. This is at the outside of the of the of the cortex I mean if you remove the skull and the brain skin and this is sort of Inside and you can see this like six or four here like six or seven centimeters This is the visual field and I mentioned already, of course This is mapping the right visual field gets mapped on to the left part of my brain in the left visual field Okay, so the left part of Both left and right eyes get mapped to the right visual field This is cross over which is true for almost all sensory modalities this crossing So here look at so this is a radial and Radial coordinate system so it starts here in the middle and then all of this half field gets mapped onto the on to the right Side of the brain Horizontal meridian is this and vertical meridian is this So the you have this transformation from here to here and it turns out to be a logarithmic one Which has some interesting computation property. So The fovea gets mapped onto this part of the brain on the outside And you see already this huge expansion the central two and a half degree Occupy roughly one third of primary visual cortex. So in me that my thumb at arm lengths is one point five degrees So two and a half degrees like this So two one third of my visual of the prime visual cortex is is occupied it's just dealing with the central part of the visual space and Roughly half is dealing with like five degrees, you know this area half of my prime visual cortex It's just dedicated to analyzing stuff in this part of the this part of the visual field Then all the periphery so this is the monocular crests and right So this is mine. This is my nose and so with my let's see. This is the right visual field Okay, so I should do it here. So everything here. I can only see with my right eye right my left eye Because my nose I can't see this so that's the so-called monocular crests and right so over here. It's everything Here I can see but beyond here. I cannot see with my right eye anymore. That's a monocular crest and all of that part Look at it sort of you know, it's taking you know this little part of the of the brain He is dedicated with all of that You can see again. This is huge over representation over emphasis on the central part of the visual field And that's you see that in all subsequent structures. You always see this This is called a retinotopic mapping It's a topographic mapping which means that two points outside in the visual field to neighboring points map onto neighboring points in In the cortex and furthermore retinotopic that it vastly over emphasize the central structure It has some nice properties logarithmic So folks and this is logarithmically related to the to the radial dimension and in principle if it would be a perfect log Mapping you would have these things that at straight lines, but it's not quite and this is a blind spot representation So which gets nuanced which gets information from the from the other eye and as I said new on city I mean here you you do find neurons. It's not that there are no nuance here Just that those neurons correspond to nuance that's that sit around here in the neighborhood here. I because there's no Visual input at this at the blind spot itself because that's where the axons the optic nerve axon to leave the eye and Then of course, there's also this so this is and this inversion is also the left the Up up down inversion that the Because just because the optics of the lens the upper part of the visual field get mapped to the lower part of the brain And the lower part of the visual field get mapped to the upper part of my brain Right to this part here this quadrant This is this one corner here gets mapped onto the upper part So this is would be towards the top here and this quadrant here gets mapped to the lower part This apparently cause people endless problems in the 16th and 17th 18th century at the time of Descartes Because they were always wondering how that their harmonious wouldn't see everything upside down because they realized about the Opics that the picture at the level of the retinas inverted so that all these fancy argument why Why the why we don't see the world upside down? Because we don't see the world upside down because there is no harmonious They're hanging from the trees or something all we need is relationships and although we once had one patient a very interesting one Who had what's the clinical term? He had a stroke. No, he had a There was an accident. It was unclear what happened, but The end result was he had a bullet in his head that remained there. It's not good. Let me tell you and Then he finally recovered first he was blind in the first day or two following this this this mishap and then He is slowly recovered. He was like an early like 50 year old maybe gentlemen. He recovered, but then he insisted That everything was upside down He insisted that everything was upside down that the world was just upside down now when we saw and this was like a year and a Half after this accident and you know, he did all you know, he didn't when you say hi to him He didn't do this, you know, I mean it's not that you know, it's not like a slapstick But that of course very easy to account. I did this myself once in Switzerland I bought these reversing prison glasses that reverse left right or up down and you can very quickly adapt to that I was in a couple of hours sort of you know early on you make mistakes Let's see if you wear prison glasses shift everything over by 10 degrees early on, you know, you make mistakes You're just you know, you're misaligned, but your motor system very quickly learns and competates for that So he didn't have any of these obvious These obvious deficit, but he did claim And we tied very hard to test them But we could never find any conclusive evidence on it and he wasn't hysteric There wasn't any secondary gain to be gotten from that and we turn out there were a few cases in the literature When people claim that things are upside down very often they involve lesion to the bridal cortex Which might have to do with a sense of balance that could have been that his sense of Balance was and he also had trouble walking very straight lines. So maybe it has to do something with that Anyhow apart from that there's no there's no harmonious inside your head that hangs upside down to correct for the obvious deficit because right how I mean your neurons inside your brain don't care about the absolute direction what's out there, right? All the news inside they can just see, you know, other new old signals And there's no reason that the that the map in the brain has to have the same orientation as a map outside there I mean none whatsoever In the computer they don't what I mean, why should they have why should they have this relationship in the brain? So it seems fairly obvious today, so I don't quite understand why where the deep problem was in the 17th century Okay, now each of these these are all neurons of course, right? So Each of you know in each point here, there are many many neurons people actually visualize this directly using a radioactive technique called 2DG So you can actually do experiments where they saw this sort of pattern where they had them where they showed the monkey Radial symmetry they had sort of radial patterns and then they used a technique that essentially tracks Metabolic uptake uptake of these neurons with this radioactive sugar and then they could later on You know when they kill the animal they could look at they could take photographs and see where it was sustained up taken up And then they could see and they could see sort of this structure here it directly visualized it So now what we're going to do we're going to zoom in on one of these neurons anywhere here in this in In the in the visual cortex in primal visual cortex Now as I mentioned you last time For many years people to the first exploration of the brain with electrodes was done Mainly I mean not only in this country in England, but mainly in this country during and after the war and first what people discovered at at Kufla at Harvard and Heartline at Rockefeller Was that neurons in the retina have these radials they like things that are radial symmetric roughly so they like sports of light Small sports large sports annually things that are a little symmetric and then once people in the 50s and in the early 50s We can began to move up the visual stream into cortex They tried because that's what they used to they tried To discover the visual selectivity of neurons in visual cortex and they were not having a lot of luck So they tried the same stimuli that they knew they could drive new ones in the in the retina LGN But neurons in cortex don't much like don't much respond They don't respond at all a very low very sluggish to sort of diffuse lights or to sports of lights Until and I checked it's actually I mean she will give a tool told me the story who He and David visa got the Nobel Prize for this say it's actually true one day as they were moving So the way they they stimulated thing and the stimulated animals They had these slides where they had very you know black and then they had a cut out for some circular shape They put it in a slide projector because they didn't have you know Severe things like that put them in a slide projector to to give rise to bright target And what happened was that as they move as they move the slide into the slide projector There was this there was an uneven slide and there was a strong crack This oriented crack that up that that that ran across the slide and they moved it down and suddenly They had this very strong discharge Of course a prepared mind. I mean you need serendipity, but then you also need to prepare mine So it immediately followed up in that location on that observation and then that opens sort of the floodgate There was this paper that literally launched a thousand electrodes in dozens of labs throughout the world and it's now a classic Where where they essentially discovered that neurons are incredible selective if you use somewhat more complicated stimuli In particular what neurons like not all neurons, but many neurons in V1 like primary visual cortex like are haunted Things that are oriented and things that move and all things that move so here what you see Stimulus that can move a bother can move either to the right or to the left and if you move it in this direction doesn't respond Now what you do you you rotate it and then you find what it's diagonal it really likes that and Furthermore it really only likes if you move it in the sort of you know at one o'clock if you move with seven o'clock down here Then you're on you know hardly responds So it's tuned not only this new and it's not only tuned for orientation But it's also tuned for direction of motion in this case. In fact, they are far now the the optimal orientation of Fogman that's a very common observation here. The optimal orientation is orthogonal to the optimal direction of motion This is called a null direction. It's like This direction down here is called a null direction and this direction is called a preferred direction and There's so many many neurons have this sensitivity when they're very sent You know we're very sensitive or they're more or they're less sensitive, but they certainly care about orientation and Some neurons care about and bright on dark So they want an edge Let's see a bright edge on a dark background and some new ones just like in a retina remember on an off-sales Care about the opposite they want a dark edge on a white background Some new ones care either some new ones sort of don't discriminate if I to either edge as long as that orientation Okay, no, that's certainly not a stupid question because it's a it's a real issue. Yeah, so you have to use In fact a lot of the early paid early response were probably what's called multi-unit where they probably Looked at the response of a number of neurons and nearby neurons. So it's a bit like in human neighborhoods Oh, the question was how do how do people know that this is actually one neuron and not many neurons So and the in some papers Now today we know it but before we didn't know it People record for multiple neurons. So when they say neuronal response careful not to say whether it's a single neuron or a cluster of neurons This works often because neurons just like people cluster in neighborhoods according to social class or religious affiliation or you know Ethnic background whatever so very often if you find neurons It's a common property thought cortex that like let's see this Let's see that like motion in this direction Then the neighboring neurons will also tend to like motion in this direction and that makes your problem even more acute So the only way you can know is doing very careful test looking at the shape of the action potential for example You can tell that you know are the are the for some real new ones have what's called a refractive period So real neurons fire what when they fire an action potential they are very Unlikely to fire another action potential for the set next two three four five six seconds They're refractive for that so typically if you have neuron if you have a spy and new spikes that are you know Very close to each other. You can assume if let's see the two milliseconds close each other that that's probably from two different neurons And then depending what you want sometimes it's okay Sometimes all you say is neuronal response other times you want to make sure it's a single neuron So yes, you have to be careful But yes, they're also techniques that can tell you which one is whether it's single-newn or multiple-newns Other questions Okay Yeah, this shows the same thing people did a lot of theory we discuss this in the vision class next year But not here you can model these by Gabor functions So you can model the the spatial temple orientation of these things by by mathematical function But that's neither here nor there for this class if this shows the point that I Just alluded to in response to your question It's terribly important Neons cluster Okay, so neurons with similar properties whether it's color or orientation or stereo or even face selectivity More often than not tend to cluster in other words if you record and you see that because you can record from one electrode And you go down depending whether you go perpendicular or you know at an angle you can encounter new to similar property So this shows here. This is a monkey So it's not a monkey It's a slide of a picture of an abstract picture of a monkey caught neocortex in V1 And these are two tracks that I made by an electrode as you go through You know sort of semi tangentially through the cortex and what this shows what the electrophysiologist recorded here a is a preferred orientation So these you know, this is the preferred orientation of the neon here of the neurons here And so if you just let's just look at the orientation here's pretty much vertical I so the optimal stimulus is this and then as he goes along it shifts you can see systematically shifts Here and then here it goes back again Okay, same thing here That shifts systematically and there it goes back again And now if you look at below a column, okay, if you go, you know, if you stay in this column You can see here and here here and here Okay for layer 4 is different here and here the orientation is the same So the basic rule is and this is called a columnar property. It's really terrible important But in a column, so as I said the cortex you have this this to them plus and some dimensional Structure to imagine this is layer 1 and with my feet I'm in layer 6 and my head is in layer 2 and so the To first extend most of the neurons in there in one column tend to share one or more receptive field property So for example in v1 they all all the neurons in this column would roughly look at the same part of visual space It would roughly look at this part of visual space and they roughly have to see all these new ones here the same orientation They're not all alike They do all sorts of things and it's not to say that all their properties are they like but they always seem to share One or more property from v1 its orientation and and and receptive field location in Layer if the input layer is different layer in the new ones in the input layer for be typically Tend to be not oriented. You can see that here Here circle means those cells were not oriented now also what what the exam? This is Michael here. What he showed is that and see his color. So those are new ones that like That seem to respond to select aspect of color and again the cluster, right? They hear they occur together and then they disappear in here again You have a bunch of color new ones in here and the dashed and dog at the solid and dashed line means left or right input So the only place in the brain where Inputs are kept separate according to the right or to the left eye tends to be layer in in v1 particularly in in close to the input layers Outside v1 information is merged so that if a new on fires You don't know did it fire because it got input from a from the right eye or from the left eye and a very interesting fact that Directly pertains to that is the psychological observation that if I shine a light into my eye Shouldn't do this if I shine a light This is what seems like a simple and stupid Stupid question was if I shine a tiny light into your eye and I shine into the right on your left I do you think you can tell whether it goes into your left or into your right eye Now one way to telling it all right So let's say I have tubes and at the end of the tube There's a little light and LED either it's on and the right on my left eye and I ask you you tell me So if you're guessing it's 50% tell me whether the input came in the right or in the left eye Now one way to get that is to blink right if I blink and the light goes off and I know was the right eye So I have to rule that out and likewise, you know if I move my head I can you know do parallax have to rule that out if I'm careful enough and if I make it very bright Of course my pupil constricts the rule all of those things out it turns out humans are very bad at telling origin I have origin So it seems rather surprising that you cannot tell you know where an input came in your right in your left eye now You could argue ecologically that's okay because this doesn't really it doesn't there no natural tasks that require you to know that Explicitly I mean that's not to say that neurons in your brain don't have access to this information But if you if I'm asking you a subject was this input in the left or right? I you don't have that information. It's quite remarkable and It it's interesting because that information is accessible in v1 explicitly But it's not apparently not made consciously accessible Okay, but again the point here is Neons cluster so you have a bunch of units that get input from the left eye then from the right eye They're from the left eye so that's and again in a column this seem to be more less often of very similar types This is a very important observation Okay, actually I'm missing one picture here I should have because what you can do for example what you can do Screen what people have done they have again used radioactive Inject for example radioactive substances into one eye and then and then that gets transported over very day or number of days to Neons in primal visual cortex and then you can stain for radioactivity And then if you sort of if you take again your v1 what you can see you can see these stripes These are called ocular dominance columns, you know, they have these they I mean they look like zebra I can't really they're very dense. I had the picture. I don't know where it is So for example these will all would be sort of these stripes Where you have a nuance that are only driven by the left eye only driven by the right eye It really looks like a zebra pattern And so that's a direct confirmation of columns in this case in the input structure mainly in the input layers mainly Or four that seem to code for one and the same for for what one in the same eye But it's also true for color color neurons cluster and it's true for orientation So you have this columnar property which France would click and I think it's critical Because it relates to this to this notion of explicit coding that that whenever you have a columnar property for something in this case Like for orientation or for a location that properties made explicit Because you can directly without a lot of further computation you can directly read off the orientation of that stimulus Or you can directly read off the location of that stimulus from pooling a nuance in them within one of those columns okay, so Yes, I'm V1 and in different parts of the brain you have columns for different things might have columns form for tones You might have columns for motion for some in this area Mt. We'll talk about you have columns for faces So in this area called Infra temple cortex Which is probably the best the location where most of the nuance that directly give rise to visual consciousness and sit You have columns you tend to have columns for for faces in other words If you record there and you find a new one that likes faces it tends to have lots of bodies They tend to be just nearby they can not be spread locally Randomly, but they are all in local neighborhoods The reason for this columnar representation probably has to do with some sort of economy of wiring principle that for developmental reasons and for wiring reasons if you want I mean you saw how dense cortex is right So you can imagine that running wires is terrible expensive and you want to minimize that all cost You want to minimize how many long-distance wire you have to run just because But right you can't make this brain any bigger anymore. It won't fit through the birth canal right so so so you really have the economies and wiring and so the argument goes if you Put things with similar properties nearby then you have lot because that's why you tend to have lots of interaction that Minimizes long-distance wiring and people have sort of had me have made computational models of that okay let me Tell you 15 minutes about because next one see we won't have lecture. It's a student faculty conference so And the left on Friday will be a short one so Because normally I will I would have finished now, but let me give you the first part of them of the next lecture so then we can Miss the one on Wednesday so I Wanted to give you So it's a very popular turn now I saw it last week in an editorial front page editorial in nature the NCC the neuronal colleagues of consciousness and What do we mean by that or what do other people now mean by that? So I wanted to talk about that Okay, gotta remember purple and blue not a good idea Not a good idea Okay, no to myself because People say well, okay, so it's all right, but they know that we're talking about correlates neuronal correlates because they're bound to be This is apology after all not physics. They're bound to be you know many, you know correlates Not guaranteed, but probably so the argument goes well We know if you don't have your heart, you're not gonna be conscious Right because we without your heart leaving aside sort of machine support systems, you know your dad was in Very quickly Well, in fact, yeah, I recently read this paper. They did this study that in 1942 okay, and This is a study that would not pass human subject committee today anymore what they did they did this in Hopefully volunteers although didn't say that The people who did this were at the Navy And what they did they ran that young man unconscious and they wanted to see how long does it take? For these people to be unconscious so what they did they applied cuff electrodes They put a couple electrodes. I'm not going to demonstrate this year around the around the neck around the carotid Externa and they choke them and Yeah, they do they Well, I mean this was at a time when you didn't have human subject review boards, etc Be that as it may they they talk about the average duration it takes these so these are all I didn't say I assume they're all recruits or sort of people in the army So they're my they're all males so they assume we're all in in good health between 18 and 22 or something So that population takes 6.9 seconds to become unconscious after they after they choke this They wake up they claim I mean in the paper they say they did not observe any long-term consequences But of course they didn't track these people for a long time Typically, they wake up within within a minute or two and have some disorientation, but then quickly quickly recover It's another this is interest okay I read this up because I was interesting how long does it take it's just a little Factor I to become unconscious what's interesting for respect to consciousness that some of these people when they wake up have vivid hallucinations This relates I was several times now on TV because people talk to me about About consciousness and near-death experiences. So near-death experiences which are now more prevalent. They're more prevalent than before not because Well, not because of any metaphysical reason, but just because the medical technology is advanced to such a degree to such an extent that people who previously You know had near death didn't have near death experience their death experiences and so they couldn't talk about them No, but today, you know with advanced medical technology a lot of these people particularly in hospital when they have their second or third heart attack they already in hospital they can survive and so they can tell us about them and Two of the things and I don't want to denigrate these experiences if you talk to these people They're very passionate about them. There's no question about them. They're not lying or they're not trying to put one over you Or they're not hysteric They have these very very vivid experiences that a they are few physiological manifestation like one is very often they go hand-in-hand with Light at the end of the tunnel syndrome The other thing has to do with the vascularization of the retina which is very dense in the fovea and much less dense in the Surround so well imagine and some people there's a second group of patient normal in normal humans sorry Air Force recruits who who They were also rendered unconscious, but as a as a side effect it spun them This is in the 60 70s in the 80s when they test when they test people for you know High perform for test pilot or for astronauts and they spin them in centrifuge and they want to know at what point Do do they become unconscious at what g-force and whether whether wearing you know full One of these body suits whether that and that helps and then you also have people some you know It's a huge viability at what g the lowest guy fainted at to the high the one guy only fainted at 7g and There people also report sometimes this this tunnel syndrome So I think that's a very simple physiological observation But the other two observation that the ones striking the one that strikes the the public in your death experiences is a very vivid imagery That every that a lot it turns out as far as far as I could tell a lot of people have this imagery But if you're now very religious now put yourself in a situation You are 70 75, you know you have some term of disease So you know you might die any moment and you're very religious and then very often this is this imagery of this Dreams that these people have tend to be of a religious nature like they saw you know God talk to them or whatever and I don't for a moment doubt the Exprate you know as Oscar Wilde famously say you can't argue with perception In the sense that I don't doubt that from their point of view This is what they experienced or at least that's the interpretation of their experience and I don't I think that's probably true I mean I had dreams like that now together it goes with a euphoric feeling with a strange euphoria not always but very but Significant number of times that when people have these experiments. They're very euphoric and so of course in a sense It's a godsend gift Maybe it's a user term It's a it's it's it's a gift because you know if you are terminal ill and you'll have this vision And then you have the half these euphoria very because very often these people then after they had this experience They sort of they seemed happy with their with with their fate So I mean that cannot be but good now as I was interested in reading both these studies one of these recruits that where they Were choked and the other set who were spun around till they fell unconscious Because a number of times both the subject groups reported when they woke up very often They had intense visual imagery and some of them had these euphoric feelings now when you're 19 and the doctor tells you Okay, we're gonna do this experiment. You might faint but don't worry And then you have imagery tend not to interpret it in you know in terms of near-death experiences because the entire Social you know religious context isn't there the thing that that I mean that to my mind could be the explanation And of course it's still back The answer why is it that when the brain wakes up so the brain is unconscious? Why because the There's not enough oxygen transported because it's due to the gravity It goes into your feet or because he choked so then the the brain cells Very quickly failed to fight. They cannot fire anymore They cannot support the gradients anymore and they cannot generate action potential anymore It's an interesting question when if you wake up what what part of the brain wake up first Is it first the brain stem and then the cortex and what order is it and? Why is it that this waking up very often goes hand-in-hand with this very intense imagery and Of course, it's something that we don't experience if I become conscious every day and I have these experiences I probably wouldn't make a big deal out of them just like dreams I mean it's remarkable if you think about it right every night you go to I mean this night I had such a vivid dream I didn't incredible intense dream and every night you wake up you you go to bed You close your eyes and you wake up in some world and you have these amazing things happen to you And if you never if those things Never happen except once in your life then of course it's something incredible special So I think that's what makes these near-death experiences so special because they don't happen to most of us more you know Any time and it happens only to subset of people under these very very special circumstances And then they have these very ingenious in genius explanations They actually did there was a paper in Lancet This is a British medical journal where they actually because some people I mean most people who talk about them have sort of new age and very religious explanations of these including It's a related phenomena people people sometimes have which is out of body experience that can also happen there And where they do these bizarre where one doctor actually did this experiment where he actually put Information he put a letter in a big phone on top of Of a of a on top of a big How do you call it? What yeah on top of a cabinet To to make sure is it really true when the patient floats out of body the patient could look down and actually read it He said that he said and he found that the patient could not do that And then he and then he then he actually said and this amazing said well that experiments would have Would have finally shown the reality of the existence of the soul Which strikes me as I mean there's so many other explanations that you have to that you have to look at it before before you come to that conclusion anyhow Okay, how do we oh yeah, yeah, so to close several parentheses You could are you well clearly you need blood and oxygen if you don't have that you come unconscious So therefore the heart or you know is it's a colleague of conscience in that sense of course It's true. So what Francis and I mean we mean the very very specific Factors that are necessary to mediate one specific percept right now focusing the percept of this weak Purple on this on the blue back on that specific percept Not the fact that all of you unless you're sleeping you have to be a route They have to be a number of enabling factors But if you're not a route you're you're sort of you're in in coma or you know you're asleep I don't I don't think anybody's in coma here. I hope not So so these are all the enabling factors that have to be present in order for you to be conscious at all And there are a number of them and people study them They're touch of course terrible important for patients if you you know there this entire large unfortunately large group of patients who you know typically young healthy You're otherwise healthy males. You know it is a trauma mainly trauma car accidents climbing high Shooting etc. That are that have various Disturbances of conscious permanent the terms of consciousness like coma opposite or vegetative syndrome or persistent that it is syndrome But typically what happened you have damage to these structures in the in the in the in the brain stem See I just wanted So this is just a mini part So the the the brain stem tends to be through this part here You can see why it's called the stem right for an obvious reason This is human brain for all these reasons which comprise the midbrain the pawns the medulla and then here it goes into the spinal cord So typically if you have the so the remarkable point is that many people have marked I can take out a big chunk of this part of the brain here of cortex and for the most part And unless I look very careful, I won't make I won't notice a difference in you I mean if if if well one of you had you to an accident something settles cubic millimeter or cubic centimeters of cortex removed And you know then you heal it would be difficult to know from an outsider One would have to do very specific and very sophisticated text text test to find that out I mean, I believe that there unless you're sort of younger than 14 when you have a huge amount of plasticity But let's say it's certainly at my age if I now lose a couple of Square centimeters of my of my cortex there would be some deficits But I can probably compensate for that you would have to do a very careful test on the other hand you Remove very small volumes millimeter cubic millimeter of this part of the brain folks are in the midbrain or part of the thalamus particular particular part of the thalamus called intra laminar nuclei so the seller that The thalamus this structure here And contains lots of different nucleus I mentioned you one of the best known one is called the LGN the lateral geniculate nucleus It means it's a specific visual information from the retina to To primary visual cortex. There are other thalamic nuclei for vision for addition etc But then there are some so-called unspecific thalamic nuclei in one of them It's a collection of nuclei called the intra laminar nuclei You make a tiny lesion in their cubic millimeter you're in coma if you lose both on both sides You could be permanently in in coma although some of these patients do recover after a while so it is quite remarkable that that Large destruction of large part of cortex you can compensate, but destruction of small parts here in the In there in the in the brainstem can lead to very very severe and sometimes permanent deficits Which might include things you know as code in coma or persistent of a vegetative syndrome or persistent vegetative syndrome Where you sort of essentially just lie you might have you know circadian rhythm Or you might sometimes you know you might be able to follow your you know to follow the your eyes might follow sometimes But in the worst case nothing you're just there as a sort of human vegetable. Very sad Okay, so so these are all the enabling factors for some we know there's these this is mad their number of Systems in the in the brainstem This was discovered here in the 40s in party in Los Angeles called the midbrain or mesentatholic reticular formation so this is a Martly collection of 30 to 40 different nuclei that sit in this part of the brain and that put some of them project very very widely like some of Them like in Lucas Cirolio said 20,000 neurons that one you might project here here and here single axon branches everywhere and some of these structures are Terrible important they regulate sleep they regulate arousal they regulate learning and without them you're in deep deep trouble There's no question you need all these structures But those are still enabling factors you need them in order for your brain to be aroused to be awake to be able to learn It does not explain and the specific The specific content of my current visual or sensory consciousness And so that's why I introduce this term many many people particular philosophers make this distinction between content of consciousness like right now You're conscious of my voice or your conscious of this You know laser daughter you're conscious of this word or something. That's a content of consciousness and consciousness as such I Don't think I don't think it's all that useful because I'm not sure how good as a risk for a research strategy That is but but a lot of people do assist distinction And so I think these enabling factors are necessary for consciousness as such for any conscious If they're not present I'm not calm there's no content an interesting question is I Think really interesting not not even from philosophical but from a practical point of view Can you have consciousness as such without content now think this is what some meditation techniques are trying to achieve and And there's been a lot. I mean a lot of writing on that. I mean is it possible You know for if you do Zen Buddhism that that I mean if you look at a lot of these techniques often involve focusing on one thing And then sort of trying to I mean without falling asleep And then sort of trying to have even this thing sort of escapes the clutches of your minds at the end You're sort of you're conscious but not conscious of anything in particular and maybe I don't know It's sort of pure rampant speculation. Maybe that that corresponds to consciousness such without content It's not a very useful research strategy because I don't know how to do this in a monkey in a mouse I don't know how to get a monkey or mouse You know to meditate and so I've never seen any good evidence that there are specific for example that you can have a specific input from the brain stem I'll show to this for example is input from one set of two sets of neurons in the basal in the Basal for brain called the basal nucleus of my nut and he in another part of the of the mithincephalic Reticular activating system that project here and that project very widely so some of those neurons might project You know across half the brain I've never seen any evidence that folks and they can only innovate part of V1 and only in a made part of somatosensory cortex I've now I mean that might that might exist. I just have I just I just don't think there's evidence such that For that degree of specificity That's why I think you need these things in order to be aroused in order to be able to learn You know when something happens suddenly, you know, I mean and for those sorts of things or to enable me to learn I I don't think it's involved in specific content It might enable you for example it might generate might facilitate Oscillations, but it would do that throughout large parts of the brain So remember that illusion I showed you in the very first class when you sometimes see the yellow spots and sometimes not right? Again, where's the difference between the those two states and I don't think it has anything, you know Sometimes you are just conscious of the yellow spot. Sometimes you're not conscious of them I don't think that difference really add all the differences in for some of these sorts of widely broadcasting systems So then you can think of it like a broadcast on a you know on a network or something or something with the bullhorn Because these new and see a sort of widely broadcast to very large parts of the brain This shows you a functional imaging study of this. So this shows you this is pet study a positive emission tomography done in in Stockholm, I think by Per Roland on Uppsala somewhere in Sweden where they showed Where they essentially you can see that they had the ups or this they had people do different attention tasks Well, you either had to tend to a visual stimulus or you had to attempt to a tactile stimulus And then they compared that against just quietly lying in them in the in the machine without attending to anything And two parts of the brain always lit up It's maybe a little bit difficult to see here Lights all off Okay, so you can see this is so this is the thalamus here and here you can see So this is I mean these are small structures the intra inter thalamic nuclei You can see the active here and here and then here. This is sort of the The top of the midbrain segment of the midbrain the active here and here. It's a it's a different view This is just a structural MI This is pet so this just shows that that if you really need to attend to something you really need to pay attention To something again these structures seem to be active So it is it is what that probably says that was you need those structures in order to be able to attend to anything at all But it but the fact is that these are active whether you're doing visual or tactile already tells you that it doesn't relate to the Specific content of what you're attending. It just sets the baseline that you can attend that you can attend So any time you really need to concentrate on something these structures are active and involved Okay, this is my last slide today so Yeah, so so it is important when you talk about correlates a there correlates and There's probably not gonna be one and want to distinguish the the enabling factors from the from the from the I think this is a right life from the specific factors And we are always looking for the specific factors that mediate because ultimately we care about the subjective feelings Where does the subjective feeling comes from this this buzz you have when you see something or smell something and hear something? right where does the pain come the awful the painful of pain comes from and I Mean in vision you have these very nice illusion where you can rapidly switch you don't have him for pain Because so that's one reason why it's so much more difficult to study the new biology of pain But it's more difficult to recruit subjects But but but you know it's so again those those things all they are necessary those Brainstorm reticular activating system and interlamina nucleus But if you want to see what one understand where the specific buzz of seeing the yellow not seeing it comes From you have to look basically you have to look in the forebrain You have to look in cortex and neocortex and thalamus and in really closely related structures Just a few points. I wanted to take off the expanded it at more depth in the in the today's chapter The the chapter that I'm talking about today right now is in next week's lecture. It's already out Once emotions so I spent a lot of time two years ago Well, I spent a couple of weekends with psychoanalyst. They're very interested in in concert They have of course always been interested in consciousness and they were trying to understand what sort of modern neuroscience has to say about some of those some of the things they interested in and The thing with emotion is that of course for humans emotions are terribly important no question about it However emotions and people are now beginning to study the emotion the new biological basis of emotion particular fear because that's easy to study in animals It's difficult to study the biological basis of happiness. Although I think that would be nicer But the basic point about emotion is they do not Fundamentally change the nature of the problem and they become and right now I think it's all about tactics trying to find the most easiest and the best model system where you can tackle these problems and the claim the the I mean our belief is that You know, let's say take us to I mean, you know, you could do the following experiment with somebody called Zeke has tried to do in London you can take for some grads undergrad students who in love and those who are not in love you try to Someone normalize for gender and you try to normalize for all sorts of other things you can think of and then you know You can try to study sort of, you know And he has done that using you know using fmi to see if there any different response to picture of the loved one You know, it's a more strong more powerful response when you look at the the object of your adulation But but fundamentally whether you're I mean folks and it's claimed that when people are in love, you know Cuz look more vibrant, right? Roses look more Roses look more red and all of that stuff. Of course, it's you know That's sort of what 90% of the airways are filled with songs about that topic I've yet to see any test of that I've yet to see actually any dispassion sort of evidence that that's actually true that you see colors differently when you're in love Then when you're not in love but furthermore, even if that's true. I think at best. It's a modulation I mean at best. It's not it's no question about it when I'm sad or happy or elated I perceive the way the words slightly different or I might pay I might pay attention to different things when I'm happy than when I'm sad But in both in all these cases, there is always feeling and the fundamental I mean, I just I've never seen any evidence that focus in this blue, you know You might see it slightly different when I'm willing to admit the possibility although not seen any test that when you're in love You see this blue is slightly different shoe than when you're not in love Okay, but at best that's going to be a basic modulation. It's not going to change the fundamental fact that you know You that you see this blue in the blue as a distinct relationship to red or for some of this illusion I showed you with the yellow spots. You're going to see that whether you're in love or not Or whether you're angry or not when you're angry you might not want to focus that a long time because you're angry something else But that's a different point So the bottom line is that emotions are incredibly important to us and we need to understand the neural basis Particularly what goes wrong and various emotional diseases, but it does not change the fundamental nature of the beats that we need to explain and doesn't provide any any good experimental paradigm to test anesthesia When I first come into the problem of consciousness twelve years ago I I had a very good friend was anesthesiologist. So I talked with him a lot In fact, we've wrote a paper together and I dug I dug in a lot of books on anesthesia So what anesthesia always do professionally they get paid a lot of money for that they're in a you unconscious, right? They're in a you unconscious in a very controlled way And in fact their task is much more difficult because the people they have to run unconscious very often already Terrible impaired they either very old and frail or they just had a near deadly experiment, you know Accident on a freeway. So so So it's a very difficult job Now most books at the time when I read Most books and anesthesiology didn't even have an index entry and a consciousness Okay, this was my first very striking observation And when I talked, you know, I went to a dentist at the time went to another doctor I you know, I tried to engage him to try to find out and they said don't worry Don't why you won't have if you won't have pain. I said, well, I that's okay, but when I understand I'm really unconscious. Don't worry. Don't worry. You won't remember a thing and that's what it comes down to So there are several books that I have now and that have been published Called awareness on anesthesia. And so this is something that the doctors are aware of as it were and are concerned with But ultimately what the anesthesiologist cares is the subject stable in other words It says, you know blood system is blood pressure, etc stable sympathetic nervous system stable Is it does he have any pain and does he have any memory and at the end and does he move because if he moves Clearly not a good idea So what you do in modern anesthesiological practice you give cocktails of multiple of multiple agents You give you know, you give something an antiparalytic comb I mean to specifically to paralyze a patient who doesn't jump off the table when you do the cut You give him and anxiety drugs. You give him drugs that knocks out memory and recall You give drugs to stabilize his his blood pressure. And so you use all these different ones But but but that is of course not identical with actually the patient being unconscious And there are lots of cases in the 30s and 40s 50s when people first discovered the use of curare You know when it came first came I guess in the 19th century from South South Africa as South America when people thought it wasn't an aesthetic comb Well, it's fact curare doesn't anesthetize you at all. It just paralyzes you, but you're still inside You want to scream but you can't because you are you can't do that anymore And so if you read these accounts of people Who wake up an anesthesia usually it is During the biggest insularity when you do the first abdominal cut because that's of course a big insult to the system You wake up usually these people don't report pain because pain is treated separately But they report an absolutely horrifying experience right you're not being told you're in general people and they've changed over the last 10 years so now they tell you ahead of time there's this possibility this might happen But so recently they didn't tell you this experience at all and you're trying to communicate desperately to the bathroom something's wrong but you can because You're paralyzed and most people have this probably don't remember it even afterwards because you're giving these drugs to not to Render you to Minimize anxiety memory recall now on the other hand I found it very Disappointing what we could learn from anesthesiology be about consciousness The reason is that all anesthetic drug so far they work globally they work at the receptor level the interview with specific receptors Specifically they put into it they potentiate garba the inhibitor neurotransmitter or they interfere with glutamate or NMDA was excitedly neurotransmitters but they do it thought large parts of the brain and So far the upshot is I mean we could give an entire lecture this on anesthesiology. We have not learned a lot about the effect the global effect of Of anesthesia on on consciousness It's not true that for example V1 is intact and some other brain areas totally shut down In fact a lot of the early exploration of visual cortex In fact even the discovery of first of the face cells, you know the cells I showed you Two lectures ago. They were in fact done in a lightly anesthetized animal So it is true that even in a lightly anesthetized animal you can get new neurons to respond You know you the monkeys asleep the anesthetize you pop open its eyes and you can get where it's sometimes quite selective responses Although the animals anesthetize so it's not true that in anesthetic for example your brain is shut down In fact today, there's not a single conscious ometer out I mean wouldn't it be nice to have a tool like dr. Spock has that you can point at a patient and you can read off sort of some sort of Scale of level of anesthesia Level of consciousness or you know you do with e.g. In general If you average or if you look across entire class of different anesthetic agent There's no no simple no single signature of consciousness that we can use in a clinical sense today That would tell us is that patient in front of me unconscious or not I can tell you or doctors can tell you for very specific type of anesthetic They all have experiences, you know for this type of for ketamine or something, you know If you do the e.g. You do spectral analysis The patient will go through these steps and at this point the patient's unconscious and that's true because it's based on 100,000 of cases, but we do not have a general signature of consciousness that they can apply in a in a in a You know that I can take a patient and attach some sort of electrodes and tell tell you this patient is unconscious I can tell you the patient is paralyzed and doesn't move and doesn't have pain and May and probably doesn't remember but of course that is not identical with being unconscious I'm leaving you with that observation to think about the next time you go have anesthesia taken