| 00:08 | mhm. This is lecture 22 of . We developed this concept of brain |
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| 00:15 | when we talked about multiple things in course. But we talked about maps |
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| 00:21 | calcium fluctuations at the synapse and we about synaptic transmission and we talked about |
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| 00:29 | cortex and somatosensory barrel cortex and rodents how you, when you activate a |
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| 00:37 | you see a map of activity. there's a structure that represents that whisker |
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| 00:43 | and there's activity within that barrel that a matter of sensory or touch sensation |
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| 00:50 | that single whisker. And we saw these maps and some out of sensor |
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| 00:56 | if they start from a single those maps of activity, they spread |
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| 01:03 | the adjacent interconnected brain regions. The of activity can be described as a |
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| 01:10 | wave or a wave of traveling electrochemical through the interconnected neuronal networks. We |
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| 01:20 | looked at the examples of brain maps the olfactory system and what happens when |
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| 01:31 | is proceeding certain smiles and we saw certain structure of the olfactory epithelium. |
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| 01:38 | had a variety of receptor cells olfactory cells that all expressed a slightly different |
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| 01:50 | protein and that receptor protein was responsive certain voters in the environment. So |
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| 02:01 | have a variety of these specific receptor receptor cells. In fact we receptor |
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| 02:09 | that process these olfactory stimuli. We about how a lot of bill factors |
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| 02:19 | our Turpin's and they can be synthetic and most of our environments. Most |
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| 02:27 | our experiences we encounter a lot of or nature produced our beans and that |
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| 02:35 | is a whole map and that map at the level of the olfactory, |
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| 02:42 | in the glimmering light where you will different sense producing a different map of |
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| 02:49 | minty versus fruity within the olfactory involved the glamorous life. That information is |
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| 02:59 | throughout the cortex and into the interconnected regions. And that's why we talked |
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| 03:08 | how smells. Although people will say a psychological effect of the smell, |
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| 03:15 | clearly seeing that there's a physiological effect the brain activity which will further influence |
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| 03:22 | mood, will influence your decision. tell you I'm going to eat this |
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| 03:29 | we'll tell you maybe I like this or not. So it is not |
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| 03:34 | psychological, it actually will determine a of new motor output physiology in the |
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| 03:41 | which is intertwined with the physiology of body. So we have this beautiful |
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| 03:50 | or smell maps and when we looked the olfactory evolves here. The imaging |
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| 04:00 | that was used was calcium imaging. that's an important technique especially within the |
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| 04:07 | evolved because most of the deep polarization the olfactory receptor cells comes from calcium |
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| 04:14 | chloride channels. And when you measure , you measure activity. So you |
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| 04:23 | calcium in this case you measure not increases in calcium but you're also measuring |
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| 04:30 | deep polarization of the membrane potential. these maps that are created and the |
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| 04:43 | in which they travel are similar, they're unique in all of us. |
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| 04:51 | smells and how we perceive the smells dependent upon what we've learned, not |
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| 04:57 | the structure that we have built but also the environments that we have |
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| 05:01 | exposed two. And I was also you about the smell maps of the |
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| 05:11 | , which is an artistic rendition. I challenge the class yesterday saying what |
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| 05:22 | blind people had an additional map of environments of their community, of their |
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| 05:32 | ? And those were the smell smell that they could read in braille. |
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| 05:40 | what maps do blind people read So there is no sound map |
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| 05:52 | there is no tape that I pick or recording or app that tells me |
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| 05:57 | is the sound map for you of , it doesn't exist. So there |
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| 06:03 | braille maps. But braille maps are complicated. There's a lot of things |
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| 06:13 | there and this is a very simplified map that could be laid on the |
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| 06:18 | , braille map also in braille. when we talk about these things and |
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| 06:22 | think, oh it's just fun that could be really serious signs behind |
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| 06:27 | could be helping another tool for disabled . For example, if they had |
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| 06:32 | smell map of the building, but could also rely in addition to the |
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| 06:37 | map because maybe they're special orientation is . So they are not sure which |
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| 06:45 | they really turned and with those people smelling having another sense and relying on |
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| 06:54 | is another tool that they could basically by. So yeah. So what |
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| 07:00 | the change? That's a great Yes. So the direction of minimal |
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| 07:09 | and if you're inside you know sometimes heater will kick in and sometimes |
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| 07:14 | C. And this will change Maybe the smell. So the way |
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| 07:19 | move through the vans. Yeah, there will be variability for sure. |
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| 07:24 | then at the same time, you that you have the locations of sewage |
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| 07:30 | and those typically don't change. And this is this is there permanently so |
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| 07:36 | infrastructural things that have strong smells, and maybe you could say in the |
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| 07:44 | this will smell like flowers and then fall it this will smell like |
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| 07:49 | you know something like that. So think there's there's something to it. |
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| 07:55 | just throwing all of these ideas out for you guys because you're the future |
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| 07:58 | this world and you're gonna be doing of these things in the future. |
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| 08:03 | go away, please thank you. . Alright, so now we're going |
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| 08:11 | look at another very interesting technique that allows you to experimentally measure activity, |
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| 08:20 | activity, neuronal number in deep hyper polarization. And this technique is |
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| 08:29 | voltage sensitive dye images. And before explained to you this technique, I |
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| 08:34 | to tell you that in general when talk about imaging, we're talking about |
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| 08:41 | levels at which this activity can be . So when we're talking about macroscopic |
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| 08:50 | , we're talking about imaging primary somatosensory S. S one activity And Primary |
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| 09:01 | Cortex V one Activity. This is . Or if you may holistic image |
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| 09:09 | the large area swaths of the brain are activated, then if you tune |
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| 09:16 | one region like the one you are at this Mezza Skop IQ level. |
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| 09:25 | if you know and recall the anatomy B1, there's a certain structure in |
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| 09:31 | cortex recall that cortex is a six structure so laminar and also it has |
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| 09:40 | . So it's columnar laminar and columnar . And within the cortex you also |
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| 09:46 | a certain circuit and arrangement. 80-90% the cells in the new cortex are |
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| 09:55 | to program in all cells 10-20% are into neurons. But you've also learned |
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| 10:03 | in this course that the diversity in cellular subtype population comes from the inhibitory |
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| 10:12 | . So excited to results are mostly to re long range production cells that |
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| 10:19 | different regions of the brain and inhibitory are locally controlling these excitatory cells and |
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| 10:28 | is a variety of these inhibitory cells how they can control the excitatory cells |
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| 10:33 | how that output is going to be . This approach is circuits centric, |
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| 10:40 | for circuit centric approach, you want know the players that are involved self |
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| 10:46 | that are involved connectivity and the rules which that circuit functions a rule for |
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| 10:56 | of feedback inhibition when there is a of excitation. Those unsanitary cells will |
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| 11:03 | inhibitory cells and the inhibitory cells will the same excitatory cells. So there |
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| 11:10 | arrangement cellular arrangement, connectivity in that . And there are rules by which |
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| 11:18 | circuits function. There's excitation limit, inhibition Gaba, there's color, |
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| 11:27 | pan, african, serotonin and there rules by which these circuits function. |
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| 11:33 | you can get to this circuit centric and understanding understanding what understanding what these |
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| 11:42 | do during a particular phenomenon. Let's your visual cortex is activated by an |
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| 11:51 | and you want to know what are inhibitory subtypes of cells doing when they're |
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| 11:58 | when they're silent. What are you ourselves doing at what time and when |
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| 12:03 | that information being communicated and propagated into adjacent interconnected brain regions. If you |
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| 12:13 | that level of understanding on a circuit , the connectivity, the communication between |
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| 12:19 | cells. You can now go down the cellular level. So there are |
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| 12:27 | techniques that will allow you to go to a single cell level, that |
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| 12:35 | huge because you can image activity in neuron and unlike recording electrically from two |
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| 12:44 | three maximum, I think the record recording simultaneously. Also recordings in vitro |
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| 12:51 | the slides from eight cells simultaneously is record. I believe in the |
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| 12:56 | Although it's not in the Guinness world . If we are doing imaging when |
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| 13:03 | imaging circuits and you get down to you the level with the imaging techniques |
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| 13:08 | have capability of tracking activity and hundreds cells at the same and thousands of |
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| 13:14 | at the same time. That's something the recording electrode cannot do. You |
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| 13:19 | cannot stick 200 electorates underneath a small and you certainly cannot do it in |
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| 13:28 | . You cannot stick so many electrodes pick up intracellular activity. I'm not |
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| 13:34 | that there is no electrode race of to the brain. If you follow |
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| 13:40 | of the multi electrode eraser called, would be implanted, they will have |
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| 13:45 | of electrodes for experimental purposes. But we're talking imaging imaging activity and hundreds |
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| 13:52 | thousands of units if you even have resolution. And if you have certain |
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| 14:03 | , certain tools you have certain dyes certain tools you can get to the |
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| 14:09 | cellular level, you can get to level of a single synapse of a |
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| 14:18 | button. Of the synapse of the drive of the dendritic spine and you |
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| 14:27 | get to that sub cellular level. you need to use really powerful |
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| 14:34 | If on the macro side, you really need to magnify you know, |
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| 14:40 | talking about four x four times magnifying signal that you're looking at. So |
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| 14:46 | magnification on this sub cellular side now have to have really powerful microscopes that |
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| 14:56 | have very high spatial resolution. And when you talk about functional neural activity |
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| 15:08 | , you will often hear this term space or temporal resolution or spatial temporal |
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| 15:17 | of activity special. And temporal when talking about resolution, spatial temporal resolution |
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| 15:26 | looking at resolution in space. How are these microscopes? How powerful are |
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| 15:34 | cameras connected to the microscopes? It's only the microscope that image comes through |
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| 15:42 | camera, a digital camera that is to a computer so that you can |
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| 15:47 | these beautiful images on the computer. how powerful is the camera? How |
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| 15:55 | pixels does the camera have? In words, how powerful is the objective |
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| 16:01 | on the microscope? You're magnifying It's an objective. Your magnifying four |
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| 16:07 | your magnifying 100 times your magnifying 1000 now you're getting down into the sub |
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| 16:13 | level. But how good is your ? How many pixels the camera mounted |
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| 16:19 | your microscope? How many pixels does have? Does it have 10 |
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| 16:24 | What does it mean if the camera 10 pixels here is an image of |
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| 16:30 | apple and it has like some interesting here and some color blah blah blah |
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| 16:37 | . Maybe this is like something some Right? And now you have your |
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| 16:46 | because 1, 2, 3, , 5, 6, 7, |
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| 16:51 | , 10, 11, 12 It means whatever is in this pixel |
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| 16:56 | gonna get averaged over and you're not see much of the detail that was |
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| 17:02 | here. Have a camera that has lot more pixels. You will get |
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| 17:11 | higher spatial resolution. So how many does your iphone have anybody bothered to |
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| 17:20 | ? Probably not the last five Nobody bothered. But you used to |
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| 17:24 | these really expensive cameras like Canon Pay To get like 12 megapixels and things |
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| 17:37 | that. And it has been replaced cell phone cameras that approximately the same |
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| 17:44 | . Another way of thinking it is less spatial resolution that has the blurrier |
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| 17:49 | the image gets, The more spatial has the more detail you can |
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| 17:55 | So that's for spatial resolution. Now camera that is processing the spatial information |
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| 18:04 | has to have speed sampling speed. is what is your video camera sample |
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| 18:11 | the phone? Phone has like 2000 . We only use three. We |
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| 18:18 | even know what it does. So probably 30 frames per second. You'll |
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| 18:24 | 30 FPs that stands 30 frames per . What does that mean? That |
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| 18:30 | that whatever happens in one second of is segmented into 30 windows. So |
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| 18:39 | I'm reaching over one second alright it be segmented into 30 samples of this |
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| 18:49 | . What's that? And very slow have a 60 frames per second is |
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| 18:56 | to be twice as fast you have T. V. Maybe you guys |
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| 19:03 | some things there's this program the It's somewhat scientific but they take different |
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| 19:09 | and they have super fast high resolution so they can show you the plumes |
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| 19:15 | smoke or explosions of breaking glass. you see that with 30 frames per |
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| 19:22 | ? No you need super super fast . So the things that have to |
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| 19:29 | if you're imaging fast activity, if imaging fast activity on the single cell |
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| 19:35 | , you better have a really powerful , you better have really good spatial |
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| 19:40 | . If you want to image electrical action potentials E. P. |
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| 19:44 | P. S. What's the duration an action potential millisecond to milliseconds. |
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| 19:52 | many is that a second? One is 1001. of a second. |
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| 20:03 | means if you wanted to capture that millisecond. Long action potential you have |
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| 20:09 | have at least twice at least. have to take two samples of that |
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| 20:15 | potential And that would be 2000 So two kilohertz. Now if you |
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| 20:23 | to see all of the details as points along this action potential. If |
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| 20:28 | just took two measurements it might be in here depending on your speed. |
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| 20:34 | is your sampling rate. If you the sampling rate. Now you can |
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| 20:39 | the action potential. It's every what these sports? Now? Now you |
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| 20:48 | have this really beautiful representation. So have to match that whatever you're gonna |
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| 20:54 | in the system whenever dies you're gonna . But these guys can track as |
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| 21:01 | with activity electrical activity in the movement the dye that the cameras can pick |
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| 21:07 | up and the cameras can process it . The other thing that happens is |
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| 21:12 | after you collected the data and a of these experiments are very difficult and |
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| 21:18 | eunice and you have to have Sometimes these dyes are genetically expressed in |
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| 21:25 | . You have to have tissue prepared . You know, it's usually 23 |
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| 21:30 | , eight hours of work to get , you know, another eight hours |
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| 21:34 | get experiment done. We're going home . You have four hours of |
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| 21:42 | It's gonna probably take you five times long to analyze that data at least |
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| 21:50 | extract the most meaningful information. So you acquired after you matched everything up |
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| 21:55 | is post experimental processing of data. may want to filter the noise out |
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| 22:02 | electrical signals. You may want to the noise out in optical signals. |
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| 22:06 | may want to zoom in on an of interest and zoom in on another |
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| 22:10 | of interest. If you zoom maybe you want to go down to |
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| 22:14 | cell resolution. If you have that stored and the speeds that are necessary |
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| 22:21 | you to understand that data. So these are different levels of |
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| 22:27 | And this is one advantage of genetically voltage indicators, imaging is that it |
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| 22:36 | cover multiple spatial scales, resolution coverage from the whole brain to dendritic |
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| 22:42 | So there are certain dies. And this case it's genetically expressed voltage |
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| 22:49 | Yeah. So let's let's understand. are these voltage dies and how they |
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| 22:55 | . And these voltage dies are really for imaging cortical dynamics. And you |
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| 23:02 | image these cortical dynamics in vivo, is in the whole animal. And |
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| 23:07 | vitro when you're imaging activity using these sensitive dyes, you're still typically imaging |
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| 23:16 | from approximately 100 to 200 micro meters the surface after activity. Now you |
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| 23:26 | say okay. But what if I a really powerful microscope and that microscope |
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| 23:32 | go down and image deeper? if you had come focal microscopy you |
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| 23:37 | go down a little bit deeper and can focus in on a certain focal |
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| 23:43 | . It's called in the microscope a bit deeper. But still most of |
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| 23:47 | things that you're going to observe is to be on the surface. And |
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| 23:52 | remember when we saw these beautiful orientation columns and their colors blue red, |
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| 24:00 | . And I said that these are of the different cells reacting to different |
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| 24:04 | in the optical columns in the visual . Those experiments were done with voltage |
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| 24:10 | with imaging voltage sensitive dyes. So way this works is these dyes, |
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| 24:16 | can be genetically expressed within the membranes in this example in this experiment. |
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| 24:22 | another one that I will show you dyes are embedded into the plasma |
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| 24:27 | So you can apply the dye on surface of the cortex so you can |
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| 24:31 | the dye on the surface of the . And those guys are like these |
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| 24:35 | squiggly warms and they will penetrate into plasma membranes of the cells and these |
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| 24:41 | warms. They have a certain confirmation them and they have certain reflective or |
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| 24:49 | properties. That means that if you a light on it like a fluorescent |
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| 24:52 | it's gonna reflect at a certain wavelength indicates it's confirmation all state. Now |
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| 25:01 | voltage crosses through the ion channels and is deep polarization across plasma membrane, |
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| 25:09 | dyes and the plasma membrane will change confirmation. The warm is gonna bend |
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| 25:15 | a different direction and as they change confirmation, the reflective properties are going |
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| 25:22 | change. So with deep polarization they change their confirmation in one direction and |
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| 25:28 | reflected is going to increase. So areas where there's deep polarization and the |
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| 25:34 | change are going to be indicated optically active areas. And then when the |
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| 25:41 | hyper polarizes, this quickly dies will into a different confirmation. And as |
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| 25:47 | shine the light they will reflect it different ways indicating that there is co |
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| 25:54 | or silence or inhibition in those particular . So the wonderful thing here that |
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| 26:02 | shown is that there is a blue and the red trace in this diagram |
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| 26:11 | and the blue and the red traits virtually indistinguishable. However, one of |
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| 26:18 | traces is an electrical potential recording with electrode. Just like we studied traditional |
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| 26:26 | physiological recordings of E. P. . P. S. And action |
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| 26:29 | throughout this course. The second color is an optical recording that is picked |
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| 26:36 | by this very fast camera. So that tells you is and I'm not |
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| 26:43 | ask him to test which one is , because I can't remember which one |
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| 26:46 | which. The fact is that both sensitive dye imaging is directly correlated to |
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| 26:56 | changes of the electrical membrane potential. it's very fast. So it can |
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| 27:05 | up a PS PS. It can pick up action potentials, individual action |
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| 27:12 | . And so this is a an where you have a macroscopic. So |
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| 27:18 | not really magnifying it that much. this case, you're not as much |
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| 27:22 | about a single cell resolution, but want to see those pinwheel cortical Structures |
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| 27:28 | neurons that are responsive to one Orientation the other. So now you have |
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| 27:34 | window, you insert an electrode, is your electrical recording into the tissue |
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| 27:41 | neuron. And you have the microscope is only a portion of the microscope |
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| 27:48 | has shown here that is imaging inside window here and the data that is |
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| 27:55 | collected by this fast camera. So cameras to capture action potential activity |
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| 28:03 | Think about the speed and the scales be in kilohertz. You want to |
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| 28:08 | four kilohertz, 10 kilohertz of optical . You want to have thousands of |
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| 28:16 | of resolution in that the data files of pixels, 10 kHz of imaging |
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| 28:26 | for two minutes. It's like a GB of data. You're running experiment |
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| 28:32 | four hours. You can you can can count how much data storage you |
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| 28:36 | in the computers and files and transfers backups and things like that. So |
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| 28:43 | a lot of data. But so this is an experiment and you have |
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| 28:47 | visual stimulator for the animal and instead just recording from an individual cell like |
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| 28:54 | would in the orientation columns, spoke one cell. What is this cell |
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| 28:58 | to this orientation or that orientation? . The following day and I'm going |
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| 29:03 | focus on other sell it takes me hours to get there this orientation without |
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| 29:08 | . So this was the evolution of the primary visual cortex and understanding orientation |
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| 29:14 | is literally poking cell by cell one one. Until we had imaging techniques |
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| 29:21 | the intrinsic optical signal revealed the ocular columns. Until you had more spatial |
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| 29:27 | in the microscopes and the cameras and dyes that were able to reveal the |
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| 29:33 | column structure and the cortex that we in the visual cortex. And so |
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| 29:39 | is the precise experiment. And these the multi sensitive dyes that we're talking |
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| 29:46 | . Let me make sure I So now we're going to watch movie |
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| 29:54 | one as I call. Okay and number one is called epileptic brain |
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| 29:57 | And these are the recordings that were in the movie that was produced by |
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| 30:02 | and my student. And I will as we watch this movie. But |
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| 30:06 | should be able to recognize some of structures like the hippocampus stimulation of hippocampus |
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| 30:13 | you can read along too 40 hertz stimulation up in the competition. This |
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| 30:33 | thing is a stimulating electric. It produce currents of stimulus through the spread |
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| 30:43 | the activity. It travels in a despise what we call the temporal |
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| 30:57 | Green is like clumps of cells. don't have a singing resolution here. |
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| 31:01 | these little mountains represent to too few each per pixel. Now it's the |
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| 31:07 | stimulation but it's a pill epic It's the same stimulus that gets |
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| 31:13 | But the tissue, the environment of tissue has been made to be chemically |
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| 31:20 | pro epileptic broken balls. Same Now you can see that. First |
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| 31:28 | all you're seeing a lot of red is a lot of signal. A |
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| 31:36 | of activity here. That signal is . It's huge. It's no more |
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| 31:41 | precise. It's spacious temporarily has been , reorganized into a big med puddle |
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| 31:49 | activity. This is electrical activity and persistent that way to standing there students |
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| 31:59 | the same duration stimulus as a first . But now you can see this |
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| 32:04 | epileptic wave of activity. Standing this without stimulation without stimulation you can observe |
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| 32:13 | activity. You will see that there's burst of activity that generates right there |
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| 32:22 | it propagates over there. This is hippocampus, this is dente gyros, |
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| 32:28 | is C. A. Three and is C A C A one area |
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| 32:31 | we looked at earlier in the course we studied the diversity of the |
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| 32:35 | This is individual cortex. You guys the structure of the cortex? Let |
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| 32:41 | remind you. This is the superficial . So this would be layer |
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| 32:46 | This is the most deep layers. would be layer six. What happens |
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| 32:51 | is activity comes from sub cortical layers it moves up the column because you |
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| 32:57 | a column of structures. If you you have inter cortical loops and it |
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| 33:01 | be activity coming into four going into . What happens in two? Three |
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| 33:08 | spreads laterally. Okay, it spreads . It can then travel back into |
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| 33:12 | column. Can get communicated back into cortex. This is an epileptic form |
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| 33:18 | but it highlights the cortical connectivity that talked throughout the course. And so |
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| 33:24 | you have this burst originating deep, traveling up the column, it's spreading |
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| 33:31 | through layers 23. This activity it's back into the column and as it |
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| 33:38 | back into the column it breaks up little pieces. So if there is |
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| 33:45 | map or smell or different odors, also a map for regular activity. |
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| 33:52 | a map for thoughts. There's a for emotions and there's a map for |
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| 33:58 | and seizures. And this is a of epilepsy and seizures. There can |
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| 34:06 | a lot of mathematical studying that can done on these maps. For |
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| 34:12 | you can overlay the contours of activity the structure. This is just the |
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| 34:21 | of that previous activity and we're traveled most dominant activity. You can make |
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| 34:27 | drawing underneath it of the cortical structures the layers and the columns. You |
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| 34:32 | mathematically reduce, deduce these things. are very fast waves of activity excited |
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| 34:41 | an inhibitor activity that travel. yeah. Red, blue, red |
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| 34:57 | excitation inhibition, excitation, inhibition, inhibition. These waves are passing and |
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| 35:06 | this is a little bit of artistic , chaotic orchestra of ripples, ripples |
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| 35:14 | these very fast waves of activity That about 200 Hz per second. But |
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| 35:21 | have different rhythms of activity. We some slower waves of activity and faster |
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| 35:26 | of activity depending on whatever you're processing the thought pattern maybe or the output |
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| 35:32 | . Well just imagine that these are thoughts and these are your brain maps |
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| 35:38 | this artistic rendition as you listen to music. Mm hmm mm hmm mm |
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| 35:46 | hmm hmm hmm hmm hmm hmm hmm hmm hmm hmm hmm hmm hmm hmm |
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| 35:50 | hmm hmm hmm hmm. This would our auditory neurons being activated, auditory |
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| 36:06 | being activated. These waves being translated around between different areas of the |
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| 36:20 | So that's the end of this. I have to give credit to uh |
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| 36:26 | to my graduate student who performed these in New Palm Hazara. He did |
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| 36:33 | PhD in my lab here using electrophysiology these fast voltage imaging sensitive voltage sensitive |
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| 36:41 | . They're called voltage sensitive dyes because sensitive to voltage. So you're imaging |
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| 36:46 | voltage because these dyes are sensitive to . So he perfected and performed these |
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| 36:53 | here that you have a judge then his postdoc at thomas Jefferson University and |
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| 36:59 | back to India where he is originally as a faculty. So, so |
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| 37:06 | is the mom knows I'm still playing video to to the students. Thank |
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| 37:16 | very much. Thank you very Um this video won the third place |
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| 37:23 | at U. Of H for three renditions of scientific data. So we |
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| 37:29 | we came up with this video because wanted to participate in the competition and |
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| 37:34 | won the third place with it which really cool and it was completely different |
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| 37:39 | everybody's everybody else's three dimensional graphs and that were presented and I think maybe |
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| 37:46 | music helped us get the third Okay. So we're we're venturing into |
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| 37:54 | really detailed understanding of the brain connectivity the brain maps. We already talked |
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| 38:01 | plasticity. We already talked about critical period of development. We talked |
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| 38:08 | some amount of sensory information. We about learned things that you learned during |
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| 38:14 | plasticity and we're gonna watch today to . It's about 20 minutes longer, |
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| 38:20 | minutes, 23 minutes long. So may not talk much during the |
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| 38:24 | I may review what we watch but it's the three symptoms syndromes and |
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| 38:31 | will write them down to stop as discusses them. Perhaps one of the |
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| 38:36 | ted talks in neuroscience today by dr . Um what is um chris pointed |
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| 38:48 | , I study the human brain the and structure of the human brain and |
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| 38:52 | just want you to think for a about what this entails Here is this |
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| 38:57 | of Jelly, Mass of Jelly, can hold in the palm of your |
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| 39:02 | and it can contemplate the vastness of space. It can contemplate the meaning |
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| 39:08 | infinity, and it can contemplate itself on the meaning of infinity. And |
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| 39:13 | is this peculiar recursive quality that we self awareness which I think is the |
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| 39:19 | Grail of neuroscience of neurology and hopefully we'll understand how that happens. |
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| 39:26 | so how do you study this mysterious ? I mean, you have 100 |
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| 39:31 | nerve cells, little wisps of protoplasm with each other and from this activity |
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| 39:37 | the whole spectrum of abilities that we human nature and human consciousness. How |
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| 39:42 | this happen? Well, there are ways of approaching the functions of the |
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| 39:46 | brain. One approach. The one use mainly is to look at patients |
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| 39:51 | have sustained damage to a small region the brain. There's been a genetic |
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| 39:55 | in a small region of the What then happens is not and across |
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| 40:00 | board, reduction in all your mental , a sort of blunting of your |
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| 40:04 | ability. What you get is a selective loss of one function with other |
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| 40:08 | being preserved intact. And this gives some confidence in asserting that that part |
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| 40:13 | the brain is somehow involved in mediating function. So you can then map |
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| 40:17 | onto structure and then find out what circuitry is doing to generate that particular |
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| 40:23 | . So that's what we're trying to . So let me give you a |
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| 40:26 | striking examples of this. I'm giving three examples six minutes each during this |
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| 40:32 | . The first example is an extraordinary called Cat Grass syndrome. If you |
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| 40:37 | at the first slide, then that's temporal lobes, frontal lobes, parietal |
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| 40:42 | gave the lobes that constitute the And if you look tucked away inside |
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| 40:48 | inner surface of the temporal lobes, can't see that is a little structure |
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| 40:52 | effusive form gyros and that's been called face area in the brain because when |
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| 40:56 | damaged, you can no longer recognize faces, you can still recognize them |
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| 41:01 | their voice. Oh yeah, that's but you can't look at their face |
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| 41:05 | know who it is that you can't recognize yourself in the mirror. I |
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| 41:09 | , you know it is, it's because when you wink it may winks |
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| 41:11 | you know it's a mirror, but don't really recognize yourself as as |
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| 41:17 | Okay, now that syndrome is well is caused by damage to the face |
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| 41:20 | Honduras. But there's another rare so rare in fact, that very |
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| 41:24 | physicians have heard about it, Not neurologists, this is called the cab |
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| 41:28 | delusion and that is a patient who's completely normal to have a head injury |
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| 41:34 | out of coma otherwise completely normal. looks at his mother and says this |
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| 41:40 | exactly like my mother, this but she's an impostor, she's some |
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| 41:43 | woman pretending to be my mother. why does this happen? Why would |
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| 41:48 | that this person is perfectly lucid and in all other respects. But when |
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| 41:51 | sees his mother, his delusion kicks says not mother. Now, the |
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| 41:55 | common interpretation of this, which you in older psychiatry textbooks is a Freudian |
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| 42:01 | and that is that this chap and same argument applies to women by the |
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| 42:05 | , but I'll just talk about guys you were a little baby and a |
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| 42:09 | baby. You had a strong sexual to your mother. This is the |
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| 42:12 | called EuroPass complex of Freud. I'm saying I believe this, but this |
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| 42:16 | the standard Freudian view. And then you grow up, the cortex develops |
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| 42:22 | inhibits these latent sexual urges towards your . Thank God. Otherwise we'd all |
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| 42:27 | sexually aroused when you saw your And then what happens is there's a |
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| 42:32 | to your head, damaging the allowing these latent sexual urges to emerge |
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| 42:38 | to the surface and suddenly and inexplicably find yourself being sexually aroused by your |
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| 42:43 | . He said, my God, this is my mom, how come |
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| 42:45 | being sexually turned on? She's some woman, She's an impostor. The |
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| 42:49 | interpretation that makes sense to your damaged . This never made much sense to |
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| 42:55 | this argument. It's very ingenious as Freudian arguments are okay, didn't make |
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| 43:02 | sense, much sense because I have the same delusion, a patient having |
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| 43:06 | same delusion about his pet poodle, say doctor, this is not |
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| 43:12 | it looks exactly like Fifi, but some other dog right now you try |
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| 43:17 | the Freudian explanation that you have to talking about the latent bestiality and all |
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| 43:23 | or some such thing, which is absurd. Of course. Now, |
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| 43:27 | really going on? So to explain curious disorder, we look at the |
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| 43:31 | and functions of the normal visual pathways the brain. Normally visual signals come |
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| 43:36 | into the eyeballs go to the visual in the brain. There are in |
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| 43:39 | 30 areas in the back of your concerned with just vision. And after |
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| 43:43 | all that, the message goes to small structure called effusive form Gyros um |
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| 43:49 | you perceive faces. There are neurons that are sensitive to faces. You |
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| 43:53 | call it the face area of the , right? I talked about that |
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| 43:57 | . Now, when that area's you lose the ability to see |
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| 44:00 | right? But from that area, message cascades into a structure called the |
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| 44:05 | in the limbic system, the emotional of the brain and that structure called |
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| 44:10 | amygdala gauges the emotional significance of what looking at. Is it prey? |
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| 44:14 | it predator? Is it mate? is it something absolutely trivial? Like |
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| 44:19 | piece of lint or a piece of or or I don't want to point |
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| 44:22 | that but or a shoe or something that. Okay. Which you can |
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| 44:26 | ignore. So if the amygdala is and there's something important, the messages |
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| 44:31 | cascade into the autonomic nervous system. heart starts beating faster, You start |
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| 44:36 | to dissipate the heat that you're going create from exerting muscular exertion. And |
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| 44:41 | fortunate because you can put two electrodes your palm and measure the change in |
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| 44:45 | resistance produced by sweating. So I determine when you're looking at something whether |
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| 44:50 | excited or whether you're aroused or Ok. And I'll get to that |
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| 44:54 | a minute. So my idea was this chap looks at an object, |
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| 45:00 | he looks at his any object for matter, it goes to the visual |
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| 45:04 | and however and it's processed in the injuries and you recognize it as a |
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| 45:08 | plant or a table or your mother that matter. Okay. And then |
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| 45:13 | message cascades into the amygdala and then down the autonomic nervous system. But |
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| 45:18 | in this chap, that wire that from the amygdala to the limbic |
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| 45:22 | the emotional core of the brain is by the accident. So because the |
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| 45:27 | farmers intact the chap can still recognize mother and says, oh yeah, |
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| 45:31 | looks like my mother. But because wire is cut to the emotional |
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| 45:35 | But how come it was my I don't experience a warmth or terror |
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| 45:40 | the case may be. Right, . And therefore he says, how |
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| 45:46 | I account for this inexplicable lack of . This can't be my mother with |
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| 45:50 | strange woman pretending to be my How do you test this? |
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| 45:53 | what you do is if you take one of you here and put you |
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| 45:56 | front of a screen and measure your skin response and show pictures on the |
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| 46:01 | , I can measure how you sweat you see an object like a table |
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| 46:05 | an umbrella, of course you don't . If I show you a picture |
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| 46:08 | a lion or a tiger or a , you start sweating right and believe |
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| 46:13 | or not? If I show you picture of your mother, I'm talking |
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| 46:16 | normal people. You start sweating. don't even have to be jewish. |
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| 46:20 | hmm. Now what happens? What if you show this patient, you |
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| 46:26 | the patient and show him pictures on screen and measure his galvanic skin response |
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| 46:31 | and chairs and lint. Nothing As in normal people. But when |
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| 46:36 | show him a picture of his the galvanic skin response is flat. |
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| 46:40 | no emotional reaction to his mother because wire going from the visual areas to |
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| 46:45 | emotional centers is cut so his vision normal because the visual areas are |
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| 46:50 | his emotions are normal. He'll he'll cry and so on and so |
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| 46:53 | . But the wire from vision to is cut and therefore he has this |
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| 46:58 | that his mother is an impostor. a lovely example of what the sort |
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| 47:01 | thing. We do take a seemingly incomprehensible neuro psychiatrist syndrome and say |
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| 47:07 | the standard Freudian view is wrong. in fact, you can come up |
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| 47:10 | a precise explanation in terms of no anatomy of the brain. By the |
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| 47:14 | , if this patient then goes and phones from an adjacent room phones him |
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| 47:21 | he picks up the phone and wow, mom, how are |
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| 47:24 | Where are you? There's no delusion the phone, then she approaches him |
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| 47:28 | an hour. He says, who you? You look just like my |
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| 47:31 | . Okay. The reason is there's separate pathway going from the hearing centers |
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| 47:35 | the brain to the emotional centers and not being cut by the accident. |
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| 47:40 | this explains why with a phone he his mother. No problem. When |
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| 47:44 | sees it in person, he he says, it's an impostor. |
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| 47:49 | , how is all this complex circuit he set up in the brain? |
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| 47:52 | it nature genes or is it And we approach this problem by considering |
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| 47:56 | curious syndrome called phantom limb. And all know what a phantom limb is |
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| 48:02 | an arm is amputated or a leg amputated for gangrene or you lose it |
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| 48:06 | war. For example, in the war, it's now a serious |
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| 48:10 | You continue to vividly feel the presence that missing arm and that's called a |
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| 48:14 | arm or a phantom leg. In , you can get a phantom with |
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| 48:17 | any part of the body, believe or not, Even with internal |
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| 48:21 | I've had patients with the uterus removed who have a phantom uterus, including |
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| 48:29 | menstrual cramps at the appropriate time of month. And in fact, one |
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| 48:34 | asked me the other day do they phantom PMS subject ripe for scientific |
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| 48:40 | but we haven't pursued that. now, the next question is, |
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| 48:44 | can you learn about phantom limbs by experiments. One of the things we |
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| 48:48 | was about half the patients with phantom claim that they can move the |
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| 48:52 | It'll pat his brother on the It'll answer the phone when it |
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| 48:56 | it'll wave goodbye. These are very , vivid sensations. Patient's not |
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| 49:01 | He knows that the arm is not , but nevertheless, it's a compelling |
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| 49:05 | experience for the patient. But about half the patients, this doesn't |
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| 49:10 | . The phantom limb, they'll But doctor, the phantom limb is |
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| 49:14 | , it's fixed in a clenched spasm excruciatingly painful. If only I could |
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| 49:18 | it, maybe the pain will be . Now why would a phantom limb |
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| 49:22 | paralyzed? It sounds like an When we look at the case |
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| 49:27 | what we found was these people with paralyzed phantom limbs. The original arm |
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| 49:32 | paralyzed because of the peripheral nerve The actual nerve supplying the arm was |
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| 49:38 | was cut by, say, a accident. So the patient had an |
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| 49:41 | arm which is painful in a sling a few months or a year. |
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| 49:46 | then in a misguided attempt to get of the pain and the arm, |
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| 49:49 | sergeant amputate the arm and then you a phantom arm with the same |
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| 49:54 | Right? And this is a serious problem patients become depressed? Some of |
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| 49:59 | are driven to suicide. Okay, how do you treat this syndrome. |
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| 50:04 | , why do you get a paralyzed limb? And I looked at the |
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| 50:06 | sheet. I found that they had actual arm. The nerves supplying the |
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| 50:11 | had been cut and the actual arm been paralyzed and lying in a sling |
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| 50:16 | several months before the amputation. And pain then gets carried over into the |
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| 50:24 | itself. Why does this happen when arm was intact but paralyzed? The |
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| 50:29 | sends commands to the arm, the of the brain saying move, but |
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| 50:32 | getting visual feedback, saying no no move, no move, |
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| 50:38 | And this gets wired into the circuitry the brain and we call this learned |
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| 50:44 | . The brain learns because of this in associative link, that the comm |
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| 50:49 | command to move the arm creates a of a paralyzed arm. And then |
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| 50:54 | you populate the arm, this learned carries over into the into your body |
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| 51:00 | and into your phantom. Okay, how do you help these patients? |
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| 51:05 | do you unlearn the learned paralysis so can relieve him of this excruciating clenching |
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| 51:11 | of the phantom arm. Well we what if you now send the command |
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| 51:16 | the phantom but give him visual feedback it's obeying his commands. Maybe you |
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| 51:21 | relieve the phantom pain. The phantom . How do you do that? |
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| 51:25 | , virtual reality, but that costs of dollars. So I hit on |
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| 51:28 | way of doing this for $3. don't tell my funding agencies. |
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| 51:35 | what you do is you create what call a mirror box. You have |
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| 51:38 | cardboard box with a mirror in the and then you put the phantom. |
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| 51:42 | my first patient derek came in. had his arm amputated 10 years |
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| 51:46 | He had a break in revulsion. the nerves were cut and the arm |
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| 51:50 | paralyzed lying in a sling for a . And then the arm was |
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| 51:53 | He had a phantom arm excruciatingly painful he couldn't move. It was a |
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| 51:57 | phantom long. So he came there I gave him a mirror like that |
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| 52:01 | a box, okay? Which I the mirror box, right? And |
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| 52:05 | patient puts his phantom left arm which clenched and inspire them on the left |
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| 52:10 | of the mirror and the normal hand the right side of the mirror and |
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| 52:13 | the same posture, The clenched posture looks inside the mirror. And what |
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| 52:19 | the experience? He looks at the being resurrected because he's looking at the |
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| 52:24 | of the normal arm in the mirror it looks like this phantom has been |
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| 52:28 | . Now, I said, now wiggle your phantom your real fingers or |
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| 52:33 | your real fingers while looking in the . He's going to get the visual |
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| 52:37 | that the phantom is moving right, obvious. But the astonishing thing is |
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| 52:41 | patient then says, oh my my phantom is moving again and the |
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| 52:45 | . The clenching phantom is relieved. remember my first patient who came |
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| 52:50 | Okay, my first patient came in he looked in the mirror and I |
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| 52:57 | , look at your reflection of your . He's and he started giggling so |
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| 53:01 | can see my phantom. But he's stupid. He knows it's not |
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| 53:04 | He knows it's a mirror reflection, it's a vivid sensory experience. |
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| 53:08 | I said, move your normal hand phantom, He said, oh, |
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| 53:11 | can't move my phantom. You know it's painful. I said move your |
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| 53:14 | hand. And he says, oh God, my phantom is moving |
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| 53:17 | I don't believe this. And my is being relieved. Ok? And |
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| 53:21 | I said close your eyes and close eyes and move your normal hand. |
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| 53:24 | , nothing ! It's clenched again. , open your eyes ! Oh my |
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| 53:27 | ! Oh my God, it's moving . So, he's like a kid |
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| 53:29 | a candy store. So I OK, this proves my theory about |
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| 53:35 | paralysis and the critical role of visual . But I'm not going to get |
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| 53:38 | nobel prize for getting somebody to move phantom limb. Mm hmm. Completely |
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| 53:45 | ability. If you think about But then I started realizing maybe other |
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| 53:50 | of paralysis that you see. In in in neurology like stroke focal |
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| 53:56 | So there may be a learned component this, which you can overcome with |
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| 53:59 | simple device of using a mirror. I said, look, derek. |
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| 54:03 | , first of all, the guy just go around carrying a mirror to |
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| 54:06 | his pain. I said, Derek, take it home and practice |
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| 54:09 | it for a week or two, after repeated practice, you can dispense |
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| 54:13 | the mirror, unlearn the paralysis and moving your paralyzed arm and then relieve |
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| 54:18 | of pain. So he said, . And he took it home. |
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| 54:20 | said, Look, it's after $2, take it home. So |
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| 54:23 | took it home and after two weeks phones me and he said, |
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| 54:26 | you're not gonna believe this. I what? He said, it's |
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| 54:30 | I said, what's gone? I maybe the mirror box was gone. |
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| 54:34 | said, No, No, You know this phantom I've had for |
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| 54:36 | last 10 years it's disappeared. And said, I got worried. I |
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| 54:41 | , my God, I mean, changed this guy's body image. What |
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| 54:44 | human subjects, ethics, and all that? And I said, |
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| 54:46 | does this bother you? He said , last three days I've not had |
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| 54:50 | phantom arm and therefore no phantom elbow , no clenching, no phantom forearm |
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| 54:56 | . All those pains are gone But the problem is I still have |
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| 54:59 | phantom fingers dangling from the shoulder and box doesn't reach. So can you |
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| 55:05 | the design and put it on my so I can, you know, |
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| 55:08 | this and eliminate my phantom fingers. thought it was some kind of |
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| 55:13 | This happened is because the brain is with tremendous sensory conflict. It's getting |
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| 55:18 | from vision saying the phantom is On the other hand, there's no |
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| 55:21 | reception, muscle signals saying that there no arm, right? And your |
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| 55:26 | command saying there is an arm. because of this conflict, the brain |
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| 55:30 | to hell with it, There is phantom, there is no arm, |
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| 55:32 | ? It goes into a sort of . It gates the signals. And |
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| 55:35 | the arm disappears, the bonus is pain disappears because you can't have disembodied |
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| 55:41 | floating out there in space. that's the bonus. Now, this |
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| 55:45 | has been tried on dozens of patients other groups in Helsinki. So it |
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| 55:48 | prove to be valuable as a treatment phantom pain and indeed people have tried |
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| 55:53 | for stroke rehabilitation stroke you normally think as damage to the fibers, nothing |
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| 55:58 | can do about it. But it out some component of stroke paralysis is |
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| 56:02 | learned paralysis and maybe that component can overcome using mirrors. This has also |
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| 56:08 | through clinical trials, helping lots and of patients. Okay, let me |
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| 56:13 | gears now to the third part of talk, which is about another curious |
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| 56:17 | called synesthesia just discovered by Francis Galton the 19th century. He was a |
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| 56:22 | of Charles Darwin. He pointed out certain people in the population who are |
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| 56:27 | completely normal has the following peculiarity every they see a number. It's colored |
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| 56:33 | is blue, Seven is yellow. is chartreuse. Nine is indigo. |
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| 56:39 | , bear in mind these people are normal in other respects, or C |
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| 56:44 | . Sometimes tones evoke color. C is blue. F Sharp is |
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| 56:48 | Another tone might be yellow. Why does this happen? It's called |
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| 56:53 | Galton called it synesthesia a mingling of senses in us. All the senses |
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| 56:58 | distinct. These people muddle up their . Why does this happen? Another |
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| 57:02 | aspects of this problem are very Synesthesia runs in families. So, |
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| 57:06 | said, this is a hereditary A genetic basis, secondly, as |
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| 57:10 | as these years about, and this what gets me to my point about |
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| 57:14 | main theme of this election is about . Synesthesia is eight times more common |
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| 57:19 | artists, poets, novelists, and creative people than in the general |
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| 57:23 | Why would that be? I'm going answer that question has never been answered |
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| 57:27 | . Okay, what is synesthesia? causes it will want. There are |
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| 57:31 | theories. One theory is they're just . That's not really a scientific |
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| 57:35 | So, you can forget about Okay, Another theory Is there acid |
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| 57:38 | and potheads? Right. There may some truth to this because it's much |
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| 57:42 | common here in the Bay Area than san Diego. Okay, now, |
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| 57:47 | third theory is that, Well, ask ourselves what's really going on in |
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| 57:52 | . Alright. So, but the area and the number area right next |
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| 57:56 | each other in the brain in the form gyros. So we said there's |
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| 58:00 | accidental cross wiring between color and numbers the brain. So every time you |
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| 58:05 | a number you see a corresponding And that's why you get synesthesia now |
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| 58:11 | it. Why does this happen? would there be crossed wires? And |
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| 58:13 | people remember I said it runs in . That gives you the clue. |
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| 58:17 | that is there is an abnormal gene the gene that causes this abnormal cross |
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| 58:23 | in all of us. It turns we are born with everything wired to |
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| 58:27 | else. So every brain region is to every other region. And these |
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| 58:31 | trimmed down to create the characteristic modular of the adult brain. So there's |
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| 58:37 | gene causing this trimming. And if gene mutates then you get deficient trimming |
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| 58:42 | adjacent brain areas. And if it's number and color, you get number |
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| 58:46 | synesthesia. If it's been toned in , you get tone color synesthesia so |
|
| 58:49 | so good. Now, what if gene is expressed everywhere in the |
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| 58:53 | So everything is cross connected? think about what artists, novelists and |
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| 58:59 | have in common the ability to engage metaphorical thinking, linking seemingly unrelated ideas |
|
| 59:06 | as it is the east and Juliet the sun. But you don't say |
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| 59:09 | is the sun does that mean she's glowing ball of fire? I mean |
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| 59:13 | do that But it's a different story ? Normal people say she's warm like |
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| 59:18 | sun. She's radiant. Like the . She's nurturing like the sun instantly |
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| 59:21 | the links. Now if you assume this greater cross wiring and concepts are |
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| 59:27 | in different parts of the brain then going to create a greater propensity towards |
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| 59:32 | thinking and creativity in people with synesthesia hence the eight times more common incidence |
|
| 59:39 | synesthesia among poets, artists and Ok. It's a very chronological view |
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| 59:43 | synesthesia. The last demonstration can I one minute? Okay you're all sinister |
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| 59:52 | but you're in denial about it. what I call martian alphabet. Just |
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| 59:56 | your alphabet. A. Is B. S. B. |
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| 59:59 | S. See different shapes for different . Right here you've got martian |
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| 60:04 | One of them is kiki. One them is bouba. Which one is |
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| 60:08 | ? And which one is about how of you think that's kiki? And |
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| 60:10 | bouba. Mhm. How many of think the one on the ride is |
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| 60:17 | and this one is bouba. How do you think that this is |
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| 60:25 | Okay but raise your hands. Well one or two mutants? How many |
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| 60:33 | you think that's bouba? That's kiki your hands 99% of you now none |
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| 60:37 | you is a martian. How did do that? It's because you're all |
|
| 60:41 | a cross model synesthesia tick abstraction You're saying that that sharp inflection ki |
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| 60:48 | your auditory cortex, the hair cells excited, kiki mimics the visual |
|
| 60:54 | sudden inflection of that jagged shape. this is very important because what it's |
|
| 60:59 | you is your brain is engaging in primitive, just it looks like a |
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| 61:03 | illusion. But these photons in your are doing this shape and hair cells |
|
| 61:08 | your year are exciting the auditory pattern the brain is able to extract the |
|
| 61:14 | denominator. It's a primitive form of . And we now know this happens |
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| 61:19 | the refusal form gyrus of the brain when that's damaged these people lose the |
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| 61:25 | to engage in bouba kiki but they lose the ability to engage in |
|
| 61:30 | If you ask this guy what all glitters is not gold, what does |
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| 61:33 | mean? The patient says well if metallic and shiny it doesn't mean it's |
|
| 61:37 | . You have to measure its specific . Okay, so they completely miss |
|
| 61:41 | metaphorical meaning. So this area is eight times the size in higher, |
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| 61:47 | in humans as in lower primates. very interesting is going on here in |
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| 61:50 | angular gyrus because it's the crossroads between , vision and touch enormous in humans |
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| 61:57 | something very interesting is going on. I think it's the basis of many |
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| 62:01 | human abilities like abstraction, metaphor and . All of these questions that philosophers |
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| 62:07 | been studying for millennia. we scientists begin to explore by doing brain imaging |
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| 62:12 | by studying patients and asking the right . Thank you. Like I |
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| 62:23 | this is uh probably one of the interesting nurse ahn's ted talks that you |
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| 62:29 | ever see and it will be on exam. All of these things that |
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| 62:34 | written down here for those on You can see all of the things |
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| 62:38 | we talked about, you know, grass syndrome, plant um limp synesthesia |
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| 62:45 | areas of the brain are involved. is the explanation for the problem? |
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| 62:51 | is the technique for the solution? atlantic skin response versus mirror box versus |
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| 62:57 | of the trimming gene in synesthesia. thank you very much. I'm out |
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| 63:01 | time today and good luck on the next week. You should be seeing |
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| 63:07 | on casa, appearing in the next of days or so. Take care |
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| 63:10 | |
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