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BIOL 4315 Neuroscience Mo Wed 4-5.30pm - NEURO Lecture 22 Brain maps, Imaging, and 3 CLues To Brain Connectivity
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00:02 This is lecture 22 of neuroscience, hmm. This is lecture 22 of
00:17 . We developed this concept of brain when we talked about multiple things in
00:24 course. But we talked about maps calcium fluctuations at the synapse. And
00:31 talked about synaptic transmission and we talked barrel cortex and somatosensory barrel cortex and
00:40 . And how you when you activate whisker you see a map of
00:45 So there's a structure that represents that barrel and there's activity within that barrel
00:52 represents a matter of sensory or touch on that single whisker. And we
00:59 that these maps and some out of cortex if they start from a single
01:04 those maps of activity. They spread the adjacent interconnected brain regions. The
01:12 of activity can be described as a wave or a wave of traveling electrochemical
01:21 through the interconnected neuronal networks. We looked at the examples of brain maps
01:32 the olfactory system and what happens when is proceeding certain smiles. We saw
01:40 certain structure of the olfactory epithelium. had a variety of receptor cells.
01:49 receptor cells that all expressed a slightly receptor protein and that receptor protein was
02:02 to certain odors in the environment. we have a variety of these specific
02:11 protein receptor cells. In fact we cells that process these olfactory stimuli.
02:21 talked about how Alana bell factors stimuli Turpin's and they can be synthetic molecules
02:30 most of our environments. Most of experiences we encounter a lot of organic
02:37 nature produced our beans and that there a whole map and that map exists
02:44 the level of bill factory, both the glimmering light where you will have
02:51 sense, producing a different map of minty versus fruity within the olfactory evolved
03:00 the glamorous life. That information is throughout the cortex. Mhm. And
03:09 the interconnected brain regions. And that's we talked about how smells. Although
03:17 will say it's a psychological effect of smell, you're clearly seeing that there's
03:22 physiological effect on the brain activity which further influence your mood will influence your
03:32 . We'll tell you I'm going to this and we'll tell you maybe I
03:36 this person or not. So it not just psychological, it actually will
03:42 a lot of new motor output physiology the brain which is intertwined with physiology
03:50 the body. So we have this maps or smell maps and when we
04:02 in the olfactory evolves here. The technique that was used was calcium
04:10 And that's an important technique especially within olfactory evolved because most of the deep
04:16 and the olfactory receptor cells comes from dependent chloride channels. And when you
04:24 calcium, you measure activity. So measure calcium in this case you measure
04:32 only increases in calcium but you're also the deep polarization of the membrane
04:43 So these maps that are created and waves in which they travel are similar
04:54 they're unique in all of us. smells and how we perceive the smells
04:59 dependent upon what we've learned. Not the structure that we have built
05:05 but also the environments that we have exposed. Two. And I was
05:12 telling you about the smell maps of city, which is an artistic
05:21 But I challenge the class yesterday saying if blind people had an additional map
05:32 their environments of their community, of city? And those were the smell
05:40 maps that they could read in So what maps do blind people read
05:51 ? Oh there is no sound map , there is no tape that I
05:59 up or recording or app that tells this is the sound, the map
06:04 you of age, it doesn't So there is braille maps but braille
06:14 are pretty complicated. There's a lot things in there and this is a
06:20 simplified smell map that could be laid the city braille map also in
06:26 So when we talk about these things you think, oh it's just fun
06:30 , that could be really serious signs it could be helping another tool for
06:36 people. For example, if they a smell map of the building,
06:40 they could also rely in addition to spatial map because maybe they're special orientation
06:47 upset. So they are not sure direction they really turn and with those
06:55 then smelling, having another sense and on that is another tool that they
07:02 basically live by. So yeah, what is the threat of the wind
07:08 ? That's a great point. So the direction of minimal change and
07:16 you're inside, you know, sometimes heater will kick in and sometimes
07:20 C. And this will change maybe the smell. So the way
07:24 move through the vans. Yeah, there will be variability for sure.
07:30 then at the same time, you that you have the locations of sewage
07:36 and those typically don't change. And this is this is there permanently.
07:42 some infrastructural things that have strong gardens and maybe you could say in
07:49 springtime this will smell like flowers and the fall of this will smell like
07:55 , you know, something like So I think there's there's something to
08:00 . I'm just throwing all of these out there for you guys because you're
08:04 future of this world and you're gonna doing all of these things in the
08:08 . Now. Go away, please you. Yeah. Alright, so
08:16 we're going to look at another very technique that also allows you to experimentally
08:24 activity, neuronal activity, neuronal number deep polarization, hyper polarization. And
08:33 technique is called voltage sensitive dye And before I explained to you this
08:40 , I wanted to tell you that general when we talk about imaging,
08:45 talking about multiple levels at which this can be imaged. So when we're
08:52 about macroscopic level, we're talking about Primary Somatosensory Cortex S one Activity And
09:06 Visual Cortex V one Activity. This macroscopic. Or if you may holistic
09:14 of the large area swats of the that are activated, then if you
09:22 into one region like the one you now at this mezza SKOp IQ
09:31 And if you know and recall the of B1, there's a certain structure
09:37 the cortex recall that cortex is a layer structure so laminar and also it
09:44 columns so it's columnar laminar and columnar . And within the cortex you also
09:52 a certain circuit and arrangement. 80-90% the cells in the new cortex are
10:01 to Graham in all cells, 10-20% inhibitory into neurons. But you've also
10:08 early in this course that the diversity the cellular subtype population comes from the
10:16 cells. So excited to results are excited to re long range production cells
10:25 interconnect different regions of the brain and cells are locally controlling these excitatory cells
10:34 there is a variety of these inhibitory and how they can control the excitatory
10:39 and how that output is going to communicated. This approach is circuits
10:45 so for circuit centric approach, you to know the players that are involved
10:51 subtypes that are involved connectivity and the by which that circuit functions a rule
11:00 example of feedback inhibition. When there a lot of excitation, there's unsanitary
11:08 will activate inhibitory cells and the inhibitory will inhibit the same excitatory cells.
11:15 there is arrangement, cellular arrangement, in that circuit. And there are
11:23 by which these circuits function. There's ultimate, there's inhibition, gaba,
11:31 color laura been Afrin serotonin and there rules by which these circuits function.
11:39 you can get to the circuit centric and understanding understanding what understanding what these
11:48 do during a particular phenomenon. Let's your visual cortex is activated by an
11:57 and you want to know what are inhibitory subtypes of cells doing when they're
12:04 when they're silent, What are they ourselves doing at what time and when
12:09 that information being communicated and propagated into adjacent interconnected brain regions. If you
12:19 that level of understanding on a circuit , the connectivity, the communication between
12:25 cells. You can now go down the cellular level. So there are
12:33 techniques that will allow you to go to a single cell level that is
12:41 because you can image activity in one and unlike recording electrically from two or
12:51 maximum, I think the record is simultaneously wholesale recordings individual and the slides
12:58 eight cells simultaneously is the record. believe in the world. Although it's
13:02 in the Guinness world records. If are doing imaging when you're imaging circuits
13:10 you get down to cellular level with imaging techniques you have capability of tracking
13:16 and hundreds of cells at the same and thousands of cells at the same
13:21 . That's something that the recording electrode do. You simply cannot stick 200
13:28 underneath a small objective and you certainly do it in vivo. You cannot
13:35 so many electrodes to pick up intracellular . I'm not talking that there is
13:41 electrode erase of going to the If you follow some of the multi
13:47 eraser called it would be implanted. will have hundreds of electrodes for experimental
13:53 . But here we're talking imaging imaging and hundreds of thousands of units if
14:03 even have greater resolution. And if have certain dyes certain tools and you
14:12 certain dyes and certain tools you can to the sub cellular level you can
14:18 to a level of a single synapse a synaptic button, of the synapse
14:27 a dumb drive of a dendritic spine you can get to that sub cellular
14:35 . So you need to use really microscopes. If on the macro side
14:42 don't really need to magnify you know talking about four x four times magnifying
14:50 signal that you're looking at. So magnification on this sub cellular side.
14:57 you have to have really powerful microscopes can have very high spatial resolution.
15:08 so when you talk about functional neural imaging, you will often hear this
15:16 of space or temporal resolution or spatial pattern of activity special and temporal.
15:28 you're talking about resolution, spatial temporal , you're looking at resolution in
15:35 How powerful are these microscopes? How are the cameras connected to the
15:44 It's not only the microscope that image through a camera, a digital camera
15:50 is connected to a computer so that can visualize these beautiful images on the
15:57 . So how powerful is the How many pixels does the camera
16:03 In other words, how powerful is objective is on the microscope? You're
16:10 right? It's an objective your magnifying times your magnifying 100 times your magnifying
16:16 times now you're getting down into the cellular level. But how good is
16:22 camera? How many pixels? The mounted on your microscope? How many
16:27 does it have? Is it about pixels. What does it mean if
16:31 camera has 10 pixels there is an of an apple and it has like
16:38 interesting things here and some color blah blah blah. Maybe this is like
16:46 , Some image. Right? And you have your camera that has
16:57 10, 11, 12 pixels. means whatever is in this pixel is
17:02 get averaged over and you're not gonna much of the detail that was buried
17:09 have a camera that has a lot pixels. You will get much higher
17:18 resolution. So how many megapixels does iphone have anybody bothered to know?
17:26 not the last five years. Nobody . But you used to buy these
17:31 expensive cameras like Canon pay $500,000 To like 12 megapixels and things like
17:44 And it has been replaced by cell cameras that approximately the same resolution.
17:51 way of thinking it is the less resolution that has the blurrier than the
17:55 gets, The more spatial resolution the more detail you can see.
18:01 that's for spatial resolution. Now this that is processing the spatial information also
18:10 to have speed sampling speed. What what is your video camera sample on
18:17 phone? Phone has like 2000 We only use three, we don't
18:24 know what it does. So um 30 frames per second. You will
18:30 30 FPs that stands 30 frames per . What does that mean? That
18:36 that whatever happens in one second of is segmented into 30 windows. So
18:45 I'm reaching over one second alright, will be segmented into 30 samples of
18:53 image like that and very slow. have a 60 frames per second is
19:01 to be twice as fast you have T. V. Maybe you
19:08 What's some things there's this program, mythbusters. It's somewhat scientific but they
19:14 different myths and they have super fast resolution cameras so they can show you
19:20 plumes of smoke or explosions of breaking . Can you see that with 30
19:27 per second? No, you need super fast cameras. So the things
19:34 have to match if you're imaging fast , if you're imaging fast activity on
19:40 single cell level, you better have really powerful microscope. You better have
19:44 good spatial resolution If you want to electrical activity, actual potentials.
19:50 P. S. P. What's the duration of an action
19:54 Mm hmm millisecond to milliseconds. How is that? A second? One
20:03 is 1001 1000s of a second. means if you wanted to capture that
20:11 millisecond. Long action potential, you to have at least twice at
20:19 You have to take two samples of action potential. And that would be
20:25 samples. So two kilohertz. if you wanted to see all of
20:29 details as many points along this action . If you just took two
20:35 it might be here in here, on your speed. This is your
20:41 rate. If you increase the sampling . Now you can track the action
20:47 . It's every. What are these . Okay now now you will have
20:54 really beautiful representation. So you have match that whatever you're gonna put in
21:00 system whenever dies you're gonna use that dyes can track as fast with
21:09 electrical activity in the movement of the . That the cameras can pick it
21:13 and the cameras can process it. the other thing that happens is that
21:18 you collected the data and a lot these experiments are very difficult and 10
21:24 and you have to have die. these dyes are genetically expressed in
21:31 You have to have tissue prepared You know, it's usually 23 people
21:36 hours of work to get there. know, another eight hours to get
21:41 done. We're going home exhausted. have four hours of data. It's
21:48 probably take you five times as long analyze that data at least to extract
21:56 most meaningful information. So after you , after you matched everything up there
22:01 post experimental processing of data. You want to filter the noise out in
22:08 signals. You may want to filter noise out in optical signals. You
22:11 want to zoom in on an area interest and zoom in on another area
22:16 interest. If you zoom in, you want to go down to single
22:20 resolution, if you have that data and the speeds that are necessary for
22:27 to understand that date. Yeah. these are different levels of imaging.
22:33 this is one advantage of genetically encoded indicators imaging is that it can cover
22:42 spatial scales, resolution coverage raging from whole brain to dendritic spines. So
22:49 are certain dies. And in this it's genetically expressed voltage die.
22:55 so let's let's understand. What are voltage dies and how they work.
23:01 these voltage dies are really great for cortical dynamics. And you can image
23:09 cortical dynamics in vivo, which is the whole animal. And in vitro
23:15 you're imaging activity using these voltage sensitive , you're still typically imaging activity from
23:24 100 to 200 micro meters off the after activity. Now you will say
23:32 . But what if I had a powerful microscope and that microscope can go
23:39 and image deeper? Well, if had come focal microscopy you could go
23:44 a little bit deeper and you can in on a certain focal plane.
23:49 called in the microscope a little bit . But still, most of the
23:53 that you're going to observe is going be on the surface. And so
23:58 when we saw these beautiful orientation, columns and their colors blue,
24:05 yellow. And I said that these all of the different styles reacting to
24:09 orientations in the optical columns in the cortex. Those experiments were done with
24:15 imaging with imaging voltage sensitive dyes. the way this works is these
24:21 they can be genetically expressed within the or in this example in this
24:28 And another one that I will show . These dyes are embedded into the
24:32 membrane. So you can apply the on the surface of the cortex so
24:36 can apply the dye on the surface beautician. And those guys are like
24:40 little squiggly warms and they will penetrate the plasma membranes of the cells and
24:47 squiggly worms, they have a certain to them and they have certain reflective
24:54 absorptive properties. That means that if shine a light on it like a
24:58 light, it's gonna reflect at a wavelength which indicates it's confirmation all
25:05 Now, once voltage crosses through the channels and there is deep polarization across
25:13 membrane, these dies in the plasma will change their confirmation. The warm
25:20 gonna bend in a different direction. as they change their confirmation, the
25:26 properties are going to change. So deep polarization they will change their confirmation
25:32 one direction and the reflected is going increase. So the areas where there's
25:38 polarization and the conformational change are going be indicated optically as active areas.
25:46 then when the cell hyper polarizes this dies will change into a different
25:53 And as you shine the light they reflect it in a different way,
25:58 that there's cu essence or silence or in those particular areas. So the
26:07 thing here that has shown is that is a blue trace and the red
26:15 in this diagram here and the blue the red traits are virtually indistinguishable.
26:23 , one of these traces is an potential recording with an electrode. Just
26:29 we studied traditional electro physiological recordings of . P. S. P.
26:34 . And action potentials throughout this The second color recording is an optical
26:40 that is picked up by this very camera. So what that tells you
26:48 and I'm not gonna ask him to which one is which, because I
26:50 remember which one is which. The is that both its sensitive died imaging
26:59 directly correlated to the changes of the member and potential. And it's very
27:10 . So it can pick up a PS. It can even pick up
27:15 potentials, individual action potentials. And this is a an image where you
27:21 a macroscopic. So you're not really it that much. In this case
27:26 not as much worried about a single resolution. But you want to see
27:31 pinwheel cortical Structures and neurons that are to one Orientation vs the other.
27:39 now you have a window, you an electrode. This is your electrical
27:45 into the tissue into neuron and you the microscope which is only a portion
27:53 the microscope that has shown here that imaging inside this window here and the
28:00 that is being collected by this fast . So those cameras to capture action
28:07 activity again. Think about the speed the scales would be in kilohertz.
28:13 want to have four kilohertz, 10 of optical imaging. You want to
28:20 thousands of pixels of resolution in that data files thousands of pixels, 10
28:30 of imaging data for two minutes. like a two GB of data.
28:37 running an experiment for four hours. can you can you can count how
28:41 data storage you need in the computers files and transfers and backups and things
28:47 that. So it's a lot of . But so now this is an
28:52 and you have a visual stimulator for animal. And instead of just recording
28:58 an individual cell like you would in orientation columns, spoke in one
29:03 What is this cell responsive to this of that orientation? Okay. The
29:08 day I'm gonna poke another cell. me eight hours to get there.
29:12 orientation without orientation. So this was evolution of understanding the primary visual cortex
29:18 understanding orientation columns. Is literally poking by cell one by one until we
29:25 imaging techniques until the intrinsic optical signal the ocular dominance columns. Until you
29:32 more spatial resolution in the microscopes and cameras and faster dies that we're able
29:37 reveal the orientation column structure and the that we saw in the visual
29:43 And so this is the precise experiments these are the multi sensitive dyes that
29:49 talking about. Let me make sure have. So now we're going to
29:59 Movie number one as I call. and Movie number one is called epileptic
30:03 waves. And these are the recordings were done in the movie that was
30:07 by me and my students. And will comment as we watch this movie
30:11 you should be able to recognize some the structures like the hippocampus stimulation of
30:19 and you can read along. Thank you. 40 Hz stimulation of
30:38 . This black thing is a stimulating will produce currents of stimulus rather than
30:53 . Okay okay so it travels in certain despise what we call the temporal
31:02 . Green is like clumps of cells don't have a single resolution err So
31:07 little mountains represent to too few cells per pixel. Now it's the same
31:13 but it's apoplectic condition, it's the stimulus that gets produced. But the
31:20 the environment of the tissue has been the chemical e convulsive pro epileptic bro
31:28 same stimulus. Now you can see first of all you're seeing a lot
31:35 red which is a lot of signal lot of activity here. That signal
31:44 massive. It's huge. It's no very precise. It's spatially temporally has
31:50 recognized reorganized into a big med puddle activity. This is electrical activity looking
31:57 have and it's persistent that way to there, the stimulus was the same
32:05 stimulus is in the first image. now you can see this persistent epileptic
32:11 of activity standing, this is without . Without stimulation. You can observe
32:19 activity. You will see that there's burst of activity that generates right there
32:27 it propagates over there. This is hippocampus, this is dente gyros,
32:34 is C. A. Three and is C A C A one area
32:37 we looked at earlier in the course we studied the diversity of the
32:41 this is individual cortex. You guys the structure of the cortex? Let
32:47 remind you. This is the superficial . So this would be layer one
32:52 is the most deep layers. This be layer six. What happens here
32:57 activity comes from sub cortical layers and moves up the column because you have
33:03 column of structures, if you recall have inter cortical loops and it will
33:08 activity coming into four going into What happens in 23. Activity spreads
33:15 . Okay, it spreads laterally. can then travel back into the
33:19 Can get communicated back into the This is an epileptic form condition but
33:24 highlights the cortical connectivity that we talked the course. And so now you
33:30 this burst originating deep, it's traveling the column, It's spreading laterally through
33:37 23. This activity it's going back the column. Okay? And as
33:44 goes back into the column, it up into little pieces. So if
33:50 is a map or smell or different , there's also a map for regular
33:57 . There's a map for thoughts, a map for emotions and there's a
34:03 for epilepsy and seizures. And this a map of epilepsy and seizures.
34:11 can be a lot of mathematical studying can be done on these maps.
34:17 example, you can overlay the contours activity over the structure. This is
34:26 the contours of that previous activity and traveled the most dominant activity. You
34:32 make a drawing underneath it of the structures of the layers and the
34:37 You can mathematically reduce, Deduce these . There are very fast waves of
34:46 . Excitatory and inhibitory activity that travel ? Mhm. Red blue, red
35:03 excitation inhibition, excitation inhibition, excitation . These waves are passing and finally
35:12 is a little bit of artistic chaotic orchestra of ripples, ripples are
35:20 very fast waves of activity That happened 200 Hz per second. But we
35:27 different rhythms of activity. We have slower waves of activity and faster waves
35:32 activity depending on whatever you're processing whatever thought pattern maybe or the output
35:38 Well just imagine that these are your and these are your brain maps in
35:44 artistic rendition as you listen to this , this would be our auditory neurons
36:09 activated auditory cortex being activated. These being translated swished around between different areas
36:17 the brain. So that's the end this and I have to give credit
36:31 uh mostly to my graduate student who these experiments in Newcomb has ra he
36:38 his PhD in my lab here using . And these fast voltage imaging sensitive
36:46 sensitive dyes, they're called voltage sensitive because they're sensitive to voltage. So
36:51 imaging the voltage because these dyes are to voltage. So he perfected and
36:58 these techniques here that you have a then did his postdoc at thomas Jefferson
37:04 and moved back to India where he originally from as a faculty.
37:11 so this is uh the aluminum knows still playing this video to to the
37:20 . So thank you very much. you very much. Um This video
37:27 the third place here at U. H. For three dimensional renditions of
37:32 data. So we we we came with this video because we wanted to
37:38 in the competition and we won the place with it, which was really
37:43 and it was completely different from everybody's else's three dimensional graphs and models that
37:50 presented and I think maybe the music does get the third place.
37:57 so we're we're venturing into this really understanding of the brain connectivity of the
38:04 maps. We already talked about We already talked about development. Critical
38:11 of development. We talked about tonight sensory information. We talked about learned
38:19 that you learned during the plasticity. we're gonna watch today to talk.
38:23 about 20 minutes longer. 25 23 minutes long. So it may
38:28 talk much during the talk. I review what we watch today but it's
38:34 three symptoms syndromes and I will write down the step as he discusses
38:40 Perhaps one of the best ted talks neuroscience today by dr Ramachandran. Mm
38:50 . Mhm. Um what is um pointed out, I study the human
38:55 the functions and structure of the human and I just want you to think
39:02 um chris pointed out, I study human brain the functions and structure of
39:06 human brain and I just want you think for a minute about what this
39:11 Here is this Mass of Jelly, of Jelly, you can hold in
39:17 palm of your hand and it can the vastness of interstellar space. It
39:22 contemplate the meaning of infinity and it contemplate itself contemplating on the meaning of
39:29 . And there is this peculiar recursive that we call self awareness which I
39:34 is the holy Grail of neuroscience of and hopefully someday we'll understand how that
39:42 . Okay, so how do you this mysterious organ? I mean,
39:45 have 100 billion nerve cells, little of protoplasm interacting with each other and
39:52 this activity emerges the whole spectrum of that we call human nature and human
39:57 . How does this happen? there are many ways of approaching the
40:02 of the human brain. One approach one we use mainly is to look
40:06 patients who have sustained damage to a region of the brain. There's been
40:10 genetic change in a small region of brain. What then happens is not
40:15 across the board, reduction in all mental capacities, that sort of blunting
40:19 your cognitive ability. What you get a highly selective loss of one function
40:24 other functions being preserved intact. And gives you some confidence in asserting that
40:29 part of the brain is somehow involved mediating that function. So you can
40:32 map function onto structure and then find what the circuitry is doing to generate
40:38 particular function. So that's what we're to do. So let me give
40:42 a few striking examples of this. fact, I'm giving you three examples
40:46 minutes each during this talk. The example is an extraordinary syndrome called cop
40:51 syndrome. If you look at the slide then that's the temporal lobes,
40:56 lobes, parietal lobes, ok. lobes that constitute the brain. And
41:01 you look tucked away inside the inner of the temporal lobes, you can't
41:06 that is a little structure called the to form gyros and that's been called
41:10 face area in the brain because when damaged, you can no longer recognize
41:14 faces, you can still recognize them their voice. Say, oh
41:18 that's joe. But you can't look their face and know who it is
41:22 you can't even recognize yourself in the . I mean, you know,
41:25 is, it's you because when you it may winks and you know,
41:27 a mirror, but you don't really yourself as as yourself. Okay,
41:33 that syndrome is well known is caused damage to the face of interest.
41:36 there's another rare syndrome, so rare fact that very few physicians have heard
41:41 it, Not even neurologists, this called the cab graph delusion and that
41:46 a patient who's otherwise completely normal to a head injury comes out of
41:51 otherwise completely normal. He looks at mother and says, this looks exactly
41:56 my mother, this woman, but an impostor, she's some other woman
42:00 to be my mother. Now, does this happen? Why would somebody
42:04 this person is perfectly lucid and intelligent all other respects. But when he
42:07 his mother, his delusion kicks and it's not mother. Now, the
42:11 common interpretation of this, which you in older psychiatry textbooks is a Freudian
42:17 and that is that this chap and same argument applies to women by the
42:21 . But I'll just talk about guys you were a little baby, when
42:25 young baby, you had a strong attraction to your mother, This is
42:28 so called Oedipus complex of Freud. not saying I believe this, but
42:32 is the starting standard Freudian view. then as you grow up, the
42:37 develops and inhibits these latent sexual urges your mother. Thank God. Otherwise
42:42 all be sexually aroused when you saw mother. And then what happens is
42:47 a blow to your head, damaging cortex, allowing these latent sexual urges
42:53 emerge flaming to the surface. And and inexplicably you find yourself being sexually
42:58 by your mother. He said, God, if this is my
43:00 how come I'm being sexually turned She's some other woman. She's an
43:05 . It's the only interpretation that makes to your damaged brain. This never
43:10 much sense to me this argument, very ingenious as all Freudian arguments are
43:16 hmm. It didn't make money Much sense. Because I have seen
43:20 same delusion, A patient having the delusion about his pet poodle. He'll
43:26 doctor, this is not Fifi. looks exactly like Fifi. But it's
43:30 other dog. Right now you try the Freudian explanation that you have.
43:35 have to start talking about the latent and all humans or some such
43:40 which is quite absurd, of Now, what's really going on?
43:44 , to explain this curious disorder. you look at the structure and functions
43:48 the normal visual pathways in the Normally, visual signals come in into
43:52 eyeballs, go to the visual areas the brain that are in fact 30
43:56 in the back of your brain concerned just vision. And after processing all
44:00 , the message goes to a small called effusive form gyros um where you
44:06 faces. There are neurons there that sensitive to faces. You can call
44:09 the face area of the brain. ? I talked about that earlier.
44:13 , when that area's damaged, you the ability to see faces,
44:17 But from that area, the message into a structure called the amygdala in
44:22 limbic system, the emotional core of brain, and that structure called the
44:26 gauges the emotional significance of what you're at. Is it prey? Is
44:31 predator? Is it mate? Or it something absolutely trivial? Like a
44:35 of lint or a piece of Or or I don't want to point
44:38 that, but or a shoe or like that. Okay. Which you
44:41 completely ignore. So, if the is excited and this is something
44:46 the messages then cascade into the autonomic system. Your heart starts beating
44:50 You start sweating to dissipate the heat you're going to create from exerting muscular
44:57 . And that's fortunate because you can two electrodes on your palm and measure
45:00 skin change in skin resistance produced by . So I can determine when you're
45:05 at something, whether you're excited or you're aroused or not. Ok.
45:09 I'll get to that in a So my idea was when this chap
45:14 at an object when he looks at any object for that matter, it
45:18 to the visual areas and however and processed in the future from the
45:22 And you recognize it as a pea or a table or your mother for
45:27 matter. Okay. And then the cascades into the amygdala and then goes
45:32 the autonomic nervous system. But maybe this chap, that wire that goes
45:36 the amygdala to the limbic system, emotional core of the brain is cut
45:40 the accident. So because the future intact, the chap can still recognize
45:45 mother and says, oh yeah this like my mother. But because the
45:49 is cut to the emotional centers is how come it was my mother?
45:53 don't experience a warmth or terror as case may be right. And therefore
46:01 says, how do I account for inexplicable lack of emotions. This can't
46:04 my mother. It's some strange woman to be my mother. How do
46:08 test this? Well what you do you if you take any one of
46:11 here and put you in front of screen and measure your galvanic skin response
46:16 show pictures on the screen. I measure how you sweat when you see
46:20 object like a table or an Of course you don't sweat. If
46:23 show you a picture of a lion a tiger or a pinup, you
46:26 sweating right and believe it or if I show you a picture of
46:30 mother, I'm talking about normal you start sweating. You don't even
46:34 to be jewish. Now. What ? What happens if you show this
46:42 ? You take the patient and show pictures on the screen and measure his
46:45 skin response tables and chairs and Nothing happens as in normal people.
46:52 when you show him a picture of mother, the galvanic skin response is
46:56 . There's no emotional reaction to his because that wire going from the visual
47:01 to the emotional centers is cut so vision is normal because the visual areas
47:05 normal. His emotions are normal. laugh, he'll cry so on and
47:09 forth. But the wire from vision emotions is cut. And therefore he
47:13 this delusion that his mother is an . It's a lovely example of what
47:16 sort of thing we do take a , seemingly incomprehensible neuro psychiatrist syndrome and
47:22 that the standard Freudian view is That in fact you can come up
47:26 a precise explanation in terms of the neuro anatomy of the brain. By
47:30 way, If this patient then goes mother phones from an adjacent room,
47:36 him and he picks up the phone says, wow, mom, how
47:39 you? Where are you? There's delusion through the phone. Then she
47:44 him after an hour he says, are you? You look just like
47:46 mother. Okay. The reason is a separate pathway going from the hearing
47:51 in the brain to the emotional centers that's not being cut by the
47:55 So this explains why with the he recognizes his mother. No
48:00 When he sees it in person. says it's a he says it's an
48:03 . Ok, how is all this circuitry set up in the brain?
48:08 it nature genes or is it And we approach this problem by considering
48:12 curious syndrome called phantom limb. And all know what a phantom limb is
48:18 an arm is amputated or a leg amputated for gangrene or you lose it
48:22 war. For example, in the war, it's now a serious
48:26 You continue to vividly feel the presence that missing arm and that's called a
48:30 arm or a phantom leg. In , you can get a phantom with
48:33 any part of the body, believe or not even with internal viscera?
48:37 had patients with the uterus removed hysterectomy have a phantom uterus including phantom menstrual
48:46 at the appropriate time of the And in fact, one student asked
48:50 the other day do they get phantom subject ripe for scientific inquiry but we
48:56 pursued that. Okay, now, next question is, what can you
49:01 about phantom limbs By doing experiments? of the things we found was about
49:05 the patients with phantom limbs claim that can move the phantom. It'll pat
49:09 brother on the shoulder. It'll answer phone when it rings it'll wave
49:13 These are very compelling, vivid Patient's not delusional. He knows that
49:17 arm is not there. But nevertheless a compelling sensory experience for the
49:22 But however, about half the this doesn't happen. The phantom limb
49:27 say. But doctor the phantom limb paralyzed. It's fixed in a clenched
49:31 . It is excruciatingly painful. If I could move it, maybe the
49:35 will be relieved. Now why would phantom limb be paralyzed? It sounds
49:39 an oxymoron When we look at the sheets. What we found was these
49:44 with the paralyzed phantom limbs. The arm was paralyzed because of the peripheral
49:50 injury. The actual nerve supplying the was severed was cut by say,
49:54 motorcycle accident. So the patient had actual arm which is painful in a
50:00 for a few months or a And then in a misguided attempt to
50:03 rid of the pain and the The surgeon amputated the arm and then
50:07 get a phantom arm with the same right and this is a serious clinical
50:13 patients become depressed. Some of them driven to suicide. Okay so how
50:18 you treat this syndrome now? Why you get a paralyzed phantom limb?
50:21 I looked at the case sheet. found that they had an actual arm
50:25 the nerves supplying the arm had been and the actual arm had been paralyzed
50:31 lying in a sling for several months the amputation. And this pain then
50:37 carried over into the phantom itself. does this happen when the arm was
50:43 but paralyzed? The brain sends commands the arm, the front of the
50:47 saying move. But it's getting visual saying no move, no move,
50:53 move, No. And this gets into the circuitry of the brain and
50:57 call this learned paralysis. Okay. brain learns because of this heavy in
51:03 link that the comeere command to move arm creates a sensation of a paralyzed
51:09 . And then when you rotate the , this learned paralysis carries over into
51:14 into your body image and into your . Okay now how do you help
51:20 patients? How do you unlearn the paralysis so you can relieve him of
51:24 excruciating clenching spasm of the phantom Well we said what if you now
51:32 the command to the phantom but give visual feedback that it's obeying his command
51:37 ? Maybe you can relieve the phantom . The phantom cramp, How do
51:40 do that? Well, virtual reality that costs millions of dollars. So
51:44 hit on a way of doing this $3. But don't tell my funding
51:50 okay. What you do is you what I call a mirror box.
51:54 have a cardboard box with a mirror the middle and then you put the
51:58 . So my first patient Derek came . He had his arm amputated 10
52:02 ago. He had a break in . So the nerves were cut and
52:06 arm was paralyzed lying in a sling a year and then the arm was
52:10 . He had a phantom arm excruciatingly and he couldn't move. It was
52:13 paralyzed phantom limb. So he came and I gave him a mirror like
52:17 in a box okay? Which I the mirror box right? And the
52:22 puts his phantom left arm which is and in spasm on the left side
52:26 the mirror and the normal hand on right side of the mirror and makes
52:30 same posture. The clenched posture and inside the mirror. And what is
52:35 experience? He he looks at the being resurrected because he's looking at the
52:40 of the normal arm in the mirror it looks like this phantom has been
52:45 . Now I said now look wiggle phantom your real fingers or move your
52:49 fingers while looking in the mirror. going to get the visual impression that
52:53 phantom is moving, right, that's . But the astonishing thing is the
52:58 then says, oh my God, phantom is moving again. And the
53:01 , the clenching spasm is relieved. remember my first patient who came
53:07 my first patient came in and he in the mirror and I said,
53:14 at your reflection of your phantom. and he started giggling so I can
53:17 my phantom, but he's not He knows it's not real, he
53:21 it's a mirror reflection, but it's vivid sensory experience. Now, I
53:25 , move your normal hand and he said, oh, I can't
53:28 my phantom, you know that it's . I said move your normal
53:31 And he says, oh my my phantom is moving again. I
53:33 believe this. And my pain is relieved, OK? And then I
53:37 close your eyes and close his eyes move your normal hand. Oh,
53:41 ! It's clenched again, Okay, your eyes ! Oh my God !
53:44 my God, it's moving again. it was like a kid in a
53:46 store. So I said, this proves my theory about learned paralysis
53:52 the critical role of visual input, I'm not going to get a nobel
53:55 for getting somebody to move his phantom completely useless ability if you think about
54:03 . But then I started realizing maybe kinds of paralysis that you see in
54:09 in in neurology, like stroke focal . So there may be a learned
54:14 to this which you can overcome with simple device of using a mirror.
54:18 I said, look Derek. first of all, the guy can't
54:20 go around carrying a mirror to alleviate pain. I said, look,
54:24 take it home and practice with it a week or two, maybe after
54:27 practice, you can dispense with the , unlearn the paralysis and start moving
54:31 paralyzed arm and then relieve yourself of . So he said, OK.
54:36 he took it home. I Look, it's after all, $2
54:38 it home. So he took it and after two weeks he phones me
54:41 he said doctor, you're not gonna this? I said what? He
54:45 , it's gone. I said, gone? I thought maybe the mirror
54:48 was gone. Okay. He said , No, No. You know
54:51 phantom I've had for the last 10 it's disappeared. And I said,
54:56 got worried. I said, my , I mean, I've changed this
54:59 body image. What about human ethics and all of that? And
55:02 said, Derek, does this bother ? He said no. Last three
55:05 . I've not had a phantom arm therefore no phantom elbow pain. No
55:11 no phantom forearm pain. All those are gone away. But the problem
55:15 I still have my phantom fingers dangling the shoulder and your box doesn't
55:20 So can you change the design and it on my forehead so I can
55:24 know, do this and eliminate my fingers. He thought it was some
55:28 of magician. Does this happen? because the brain is faced with tremendous
55:32 conflict. It's getting messages from vision the phantom is back. On the
55:37 hand, there's no appropriate reception, signals, saying that there is no
55:41 , right? And your motor command there is an arm. And because
55:44 this conflict, the brain says to with it, there is no
55:48 there is no arm, right? goes into a sort of denial.
55:50 gates the signals and when the arm , the bonus is the pain disappears
55:56 you can't have disembodied pain floating out in space. So, that's the
56:00 . Now, this technique has been on dozens of patients by other groups
56:03 Helsinki. So it may prove to valuable as a treatment for phantom
56:08 And indeed people have tried it for rehabilitation stroke you normally think of as
56:12 to the fibers, nothing you can about it. But it turns out
56:16 component of stroke paralysis is also learned and maybe that component can be overcome
56:23 mirrors. This has also gone through trials helping lots and lots of
56:28 Okay, let me switch gears now the third part of my talk,
56:31 is about another curious phenomenon called synesthesia discovered by Francis Galton in the 19th
56:38 . He was a cousin of Charles . He pointed out that certain people
56:42 the population who are otherwise completely normal the following peculiarity. Every time they
56:47 a number. It's colored, five blue, seven is yellow, Eight
56:52 chartreuse, Nine is indigo. bear in mind these people are completely
56:57 in other respects. Okay, Or Sharp. Sometimes tones evoke color.
57:02 sharp is blue. F Sharp is . Another tone might be yellow.
57:08 ? Why does this happen? It's synesthesia Galton called it synesthesia a mingling
57:12 the senses in us? All the are distinct. These people muddle up
57:16 senses. Why does this happen? two aspects of this problem, A
57:20 intriguing synesthesia runs in families. So said, this is a hereditary
57:24 A genetic basis, secondly, synesthesia about. And this is what gets
57:28 too. My point about the main of this election, which is about
57:32 . Synesthesia is eight times more common artists, poets, novelists, and
57:37 creative people than in the general Why would that be? I'm going
57:41 answer that question has never been answered . Okay, what is synesthesia?
57:46 causes it? Well, one, are many theories. One theory is
57:48 just crazy. Now, that's not a scientific theory. So you can
57:52 about it. Okay, another theory there acid junkies and potheads.
57:56 There may be some truth to this it's much more common here in the
57:59 Area than in san Diego. now the third theory is that?
58:06 , let's ask ourselves what's really going in synesthesia. Alright. But the
58:11 area and the number area right next each other in the brain in the
58:14 form Gyros. So we said there's accidental cross wiring between color and numbers
58:20 the brain. So every time you a number you see a corresponding
58:24 And that's why you get synesthesia. remember it. Why does this
58:28 Why would there be crossed wires? some people remember I said it runs
58:31 families that gives you the clue and is there is an abnormal gene and
58:36 the gene that causes this abnormal cross in all of us, it turns
58:41 we are born with everything wired to else. So every brain region is
58:46 to every other region. And these trimmed down to create the characteristic modular
58:51 of the adult brain. So there's gene causing this trimming. And if
58:55 gene mutates then you get deficient trimming adjacent brain areas. And if it's
59:00 number and color, you get number synesthesia. If it's been tone and
59:04 , you get tone color synesthesia so so good. Now what if this
59:08 is expressed everywhere in the brain. everything is cross connected. Well,
59:12 about what artists, novelists and poets in common the the ability to engage
59:18 metaphorical thinking, linking seemingly unrelated Such as it is the east and
59:24 is the sun. But you don't Juliet is the sun. Does that
59:27 she's a glowing ball of fire? mean schizophrenics do that but it's a
59:31 story, right? Normal people say warm like the sun. She's radiant
59:35 the sun. She's nurturing like the instantly form the links. Now if
59:39 assume that this greater cross wiring and are also in different parts of the
59:44 , then it's going to create a propensity towards metaphorical thinking and creativity in
59:51 with synesthesia and hence the eight times common incidence of synesthesia among poets,
59:56 and novelists. Ok. It's a friendly logical view of synesthesia. The
60:00 demonstration cannot take one minute. Okay all sinister deeds but you're in denial
60:09 it. Here's what I call martian . Just like your alphabet.
60:13 Is A B. S. C. Is C. Different shapes
60:17 different phonemes. Right here you've got alphabet. One of them is
60:22 One of them is bouba which one kiki and which one is about how
60:25 of you think that's kiki? And buba raise your hands? Well it's
60:28 or two mutants. How many of think that's bouba that's kiki raise your
60:33 99% of you now none of you a martian. How did you do
60:37 ? It's because you're all doing a model synesthesia, tick abstraction meaning.
60:42 saying that that sharp inflection ki in auditory cortex, the hair cells being
60:48 , kiki mimics the visual inflection, inflection of that jagged shape. Now
60:54 is very important because what it's telling is your brain is engaging in a
60:59 just it looks like a silly But these photons in your eye are
61:04 this shape and hair cells in your are exciting the auditory pattern. But
61:08 brain is able to extract the common . It's a primitive form of
61:14 And we now know this happens in refusal form gyrus of the brain because
61:19 that's damaged these people lose the ability engage in bouba kiki. But they
61:25 lose the ability to engage in If you ask this guy what all
61:29 glitters is not gold. What does mean? The patient says Well if
61:33 metallic and shiny it doesn't mean it's . You have to measure its specific
61:37 . Okay, so they completely miss metaphorical meaning. So this area is
61:42 eight times the size in higher, in humans as in lower primates.
61:46 very interesting is going on here in angular gyrus because it's the crossroads between
61:51 , vision and touch enormous in humans something very interesting is going on.
61:56 I think it's the basis of many human abilities like abstraction, metaphor and
62:03 . All of these questions that philosophers been studying for millennia we scientists can
62:07 to explore by doing brain imaging and studying patients and asking the right
62:12 Thank you. Sorry about
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