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Dr. David Berson: The Logic & Function of Your Brains Circuits | Episode 50
Dr. David Berson: The Logic & Function of Your Brains Circuits | Episode 50

Dr. David Berson: The Logic & Function of Your Brains Circuits | Episode 50

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David Berson, Andrew Huberman
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Dec 13, 2021
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Episode Transcript
0:00
Welcome to the huberman Lab podcast, where we discuss science and science based tools for everyday life. I'm Andrew huberman, and I'm a professor of neurobiology and Ophthalmology at Stanford school of medicine. Today. My guest is dr. David Burson, professor of Medical Science neurobiology and Ophthalmology at Brown University. Dr. Burton's laboratory is credited with discovering the cells, in the eye, that set your circadian rhythms. These are the so-called intrinsically.
0:30
Photosensitive melanopsin cells. And while that's a mouthful, all you need to know for sake of this introduction is that those are the cells that inform your brain and body about the time of day. Dr. Burton's laboratory has also made a number of other important discoveries about how we convert our perceptions of the outside world into motor action. More personally, doctor Burson has been my go-to resource for all things, Neuroscience for, nearly two decades. I knew of his reputation as a spectacular researcher.
1:00
Or for a long period of time. And then many years ago. I cold called him out of the blue. I basically Corral them into a long conversation over the phone after which he invited me out to Brown and we've been discussing neuroscience and how the brain works and the emerging new technologies and the emerging new Concepts in Neuroscience for a very long time. Now, you're going to realize today why dr. Burton is my go-to source. He has an exceptionally clear and organized view of how the nervous system.
1:30
Steam Works, there are many, many parts of the nervous system, different nuclei, and connections, and circuits, and chemicals, and so forth. But it takes a special kind of person to be able to organize that information into a structured and logical framework that can allow us to make sense of how we function. In terms of what we feel, what we experienced, how we move through the world. Dr. Bearson is truly one-of-a-kind in his ability to synthesize and organize and communicate that information. And I give him credit as one of my mentors.
2:00
And one of the people that I respect most in the field of science and medical science generally today. Dr. Burton takes us on a journey from the periphery of the nervous system. Meaning from the outside, deep into the nervous system layer by layer structure by structure, Circuit by Circuit making clear to us how each of these individual circuits work and how they work together as a whole. It's a really magnificent description that you simply cannot get from any textbook from any popular book. And frankly, as far as I know.
2:30
From any podcast that currently exists out there. So it's a real gift to have this opportunity to learn from. Dr. Burson again. I consider him my mentor in the field of learning and teaching neuroscience and I'm excited for you to learn from him. One thing is for certain, by the end of this podcast. You will know far, more about how your nervous system works. Then, the vast majority of people out there including many expert biologist and neuroscientists before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles.
3:00
At Stanford, it is however part of my desire and effort to bring zero cost to Consumer information about science and science related tools to the general public in keeping with that theme. I'd like to thank the sponsors of today's podcast. Our first sponsor is athletic greens. Athletic greens is an all-in-one vitamin mineral, probiotic drink. I've been taking athletic greens every day since 2012. So I'm delighted that they're sponsoring the podcast. The reason I started taking athletic greens. And the reason I still take athletic greens is that it covers all of my vitamin mineral and
3:30
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5:00
It is also brought To Us by inside tracker inside tracker is a personalized nutrition platform. The analyzes data from your blood and DNA to help. You better understand your body and help you reach your health goals. I've long been a believer in getting regular blood work done. For the simple reason that many of the factors that impact your immediate and long-term Health can only be analyzed from a quality blood test. And now with the Advent of modern DNA test, you can also get information about how your specific genes are impacting your immediate and long-term Health. Now, a problem with a lot of
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Al's, another feature of the inside tracker has is their inner age test. This test shows you what your biological age is and Compares that to your chronological age and what you can do to improve your biological age, which of course, is the important number. If you'd like to try inside tracker, you can visit inside tracker dot, coms huberman, to get 25% off any of inside trackers plans. Also, an interview I did with longevity, research, Doctor, and inside trackers founder. Dr. Gill blender is out. Now on their podcast, the longevity by Design podcast and a
6:30
Into that interview can be found in today's show notes. Today's episode is also brought To Us by Magic spoon. Magic spoon is a zero sugar, grain-free, keto friendly cereal. I don't follow a ketogenic diet. The way that I eat is basically geared toward feeling alert, when I want to be alert and feeling sleepy. When I want to go to sleep, which for me means fasting until about 11 a.m. Or noon. Most days then I eat low carb during the day. So I'll have some meat or fish, or chicken, and some salad. That's what works for me. And in the afternoon. I remain on a more or less.
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Berman to get five dollars off and now for my discussion with dr. David Burson. Welcome. Thank you. So nice to be here. Great to have you.
8:10
For more than 20 years. You've been my go-to source for all things nervous system, how it works, how its structured. So today I want to ask you some questions about that. I think people would gain a lot of insight into this machine that makes them think and feel and see etcetera.
8:28
If you would. Could you tell us how we see, you know,
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a photon of light enters the
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eye, what happens, right?
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I mean, how is it that I look outside? I see.
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Truck drive by or I look on the wall. I see a photo of my dog.
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How does that work? Right. So this is an old question, obviously. And clearly in the end. The reason you have a visual experience is that your brain is got some pattern of activity that is associated with the input from the periphery, but you can have a visual experience with no input from the periphery as well. When you're dreaming. You're seeing things
9:06
that aren't coming through. Your eyes, are those memories?
9:09
I would say in
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A sense, they may reflect your visual experience. They're not necessarily specific visual memories. But of course they can be but the point is that the experience of seeing is actually a brain phenomenon.
9:22
But of course, under normal circumstances, we see the world because we're looking at it, and we're using our eyes to look at it and fundamentally when we're looking at the exterior world. It's what the retina is telling the brain that matters. So there are cells called ganglion cells. These are neurons that are the key cells for communicating between eye and brain. The eye is like the camera. It's protecting the initial image doing some initial processing and then that signal gets sent back to the brain proper and of
9:52
It's there, the level of the cortex that we have this conscious visual experience there. Many other places in the brain that you had visual input as well doing other things with that kind of
10:01
information. So, I get a lot of questions about color vision. If you would, could you explain, how is it that we can perceive Reds, and greens and
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blues, and things of that sort. Right? So the first thing to understand about light is that it's just a form of electromagnetic radiation. It's vibrating.
10:22
It's oscillating. But late of say
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it's vibrating its oscillating. You mean that photons are
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actually moving. Well, in a sense, photons are certainly moving through space. We think about photons as particles, and that's one way of thinking about light, but we can also think of it as a wave, like a radio. Wave either way is acceptable and the radio, waves have frequencies like the frequencies on that your radio dial and certain frequencies in the electromagnetic spectrum can be detected by neurons in the retina. Those are the things we see.
10:52
But they're still different wavelengths. Within the light that can be seen by the eye and those different wavelengths are unpacked in a sense or decoded by the nervous system to lead to our experience of color, essentially, different wavelengths. Give us the sensation of different colors through, the auspices of
11:13
different neurons that are
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tuned to different wavelengths of
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light. So when a photon, so, when a little bit of light hits my eye.
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II goes in the photoreceptors convert that into electrical signal, right? How is it that a given? Photon of light, gives me the perception eventually leads the perception of red versus green versus blue,
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right? So if you imagine that in the first layer of the retina where this transformation occurs from electromagnetic radiation into neural signals,
11:46
That you have different kinds of sensitive cells that are expressing their making different molecules within themselves. Fourth is Express purpose of absorbing photons, which is the first step in the process of seeing how it turns out that all together. There are
12:04
about five
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proteins, like this, that we need to think about in the typical retina, but for seeing color really it's three of them, so they're three different proteins. Each absorbs light with the different prefer.
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Frequency, and then the nervous system keeps track of those signals.
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Compares and contrasts them to extract some understanding of the wavelength composition of light. So you can see just by looking at a landscape. So it must be late in the day because things are looking golden. That's all, you
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know, a function of are absorbing
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the light that's coming from the world and interpreting that with our brain because of the different composition of the the light that's reaching our eyes.
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Is it fair to assume that, my perception of red is the same as your perception of red? Well, that's a great question.
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That mine is better. I'm just kidding. I'm just kidding.
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It's a great question. So deep philosophical. Question is a question that really probably can't even ultimately be answered
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by the usual
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empirical scientific processes because it's really about, you know, an individual's experience. What we can say is that the biological mechanisms that we think are important for seeing color. For example, seem to be very highly similar from one individual to the next whether
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Be human beings or other animals. And so, we think that the physiological process looks very similar on the front end. But, you know, once you're at the level of perception or understanding or experience, that's something that's a little bit tougher to nail down with the sorts of, you know, scientific approaches that we approach biological Vision. Let's say you
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mentioned that there are five different cone types. Essentially, the cones, being the cells that
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Light of different wavelengths. I often wondered when I had my dog, what he saw and how his vision differs from our vision. And certainly, there are animals that can see things that we can't see, right? What are some of the more outrageous examples of
14:07
that? I've seen things are things.
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And in the extreme, right, you know dogs. I'm guessing. See Reds more as oranges. Is that right? Because they don't have these the same array of neurons.
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Is that we have 44 seeing color, right? So the first thing
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is it's not really five types of cones. They're really three types of cones. And if you look at the way that color vision is thought to work, you can sort of see that it has to be three different signals. There are a couple of other types of pigments. One is really mostly for dim light vision. When you're walking around in a moonless night and you're seeing things with very low light. That's the rod cell that uses own pigment, and then there's another class of
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We'll probably talk about a little bit later. This melanopsin pigment. I
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thought you were referring to the ultraviolet and infrared and and riots or right. So in the case of a
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typical, well, let's put it this way in human beings. Most of us have three coin types and we can see colors that we that stem from that in most mammals, including your
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dog or your
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cat. There really are only two cone types and that limits the kind of vision that they
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Can have in the domain of wavelength or color as you would say. So really a dog sees the world kind of like a particular kind of color. Blind, blind human might see the world because instead of having three channels to compare and contrast, they only have two channels and that makes it much more difficult to figure out exactly, which wavelength you're, you're looking at
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do colorblind, people suffer much as a consequence of being color blind.
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Well, you know, we're it's like so many other disabilities. We are, you know, the the the world is built for
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People of the most common type. So in some cases, the expectation can be there that somebody can see something that they won't be able to if they're missing
16:02
one of their cone types.
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Let's say, so in those moments that can be a real problem, you know, if there's a lack of contrast to their visual system, they will be blind to that in general. It's a fairly modest visual limitation as things go, you know, for example, if
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Not being able to see, acutely can be much more damaging, not being able to read fine print for
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example, suppose if I had to give up the ability to see certain colors or give up the ability to see clearly, I certainly trade out color for clarity. Right? Of course, colors, very meaningful to us as human
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beings, you know, so we would hate to give it up, but obviously dogs and cats and all kinds of other mammals do perfectly well in the world.
16:48
Yeah, because we take care of them. I spend most of my time thinking care of that.
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You took care of me, too. Let's talk about the that odd photo pigment photopigment. Of course, being thing that absorbs light of a particular wavelength. And let's talk about these specialized ganglion cells,
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that communicate
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certain types of information from eye to the brain. That are so important for so many things. What I'm referring to here, of course, is your code discovery of the so-called intrinsically.
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Sensitive cells, the neurons in the eye that do so many of the things that don't actually have to do with perception. But have to do with important biological
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functions. What I would love for you to do is
17:32
explain to me. Why once I heard you say, we have a bit of fly. I our
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I yeah. And you showed this
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slide of like a giant fly from a horror movie. Yeah. Trying to attack this woman. Yeah, and maybe it was an eye also. So what does it mean that we have a bit of a fly?
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In our eye.
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Yeah, so this is this last pigment is a really peculiar one it when you can think about it as really the initial sensitive element in a system that's designed to tell your brain about how bright things are in your
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world.
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And the thing
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that's really peculiar about this pigment is that it's in the wrong place. In a sense when you think about the structure of the retina, you think about a layer cake, essentially, you've got to this thin membrane at the back of your eye, but it's actually a stack of thin layers and the outermost of those layers is where these photoreceptors you were talking about earlier sitting. That's where the film of your camera is. Essentially that's where the photons do their magic with the photo pigments and turn it into a neural
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signal. I like that. I've never really thought of the photoreceptors is the
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Some of the camera but that makes sense or like the
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sensitive chip on you know, CCD chip in your in your cell phone. It's the surface on which the light pattern is imaged by the Optics of the eye. And now you've got an array of sensors. That's capturing that information in creating a bitmap essentially, but now it's in neural signals distributed across the surface of the retina. So all of that was known to be going on 150 years ago. A couple of types of photoreceptors cones and rods. If you look a little
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Bit more closely, three types of cones. That's where the transformation from electromagnetic, radiation to do neural signals was thought to take place, but it turns out that this last photo pigment is in the other end of the retina, the innermost part of the retina, that's where the so-called ganglion cells. Are. Those are the cells that talk to the brain. The ones that actually can communicate directly, what information comes to them from the photoreceptors. And here you've got a case where actually
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Of the output neurons that we didn't think have any business being directly sensitive to light. We're actually making this photopigment absorbing light and converting that to neural
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signals and send it to the brain.
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So that made it pretty surprising and unexpected. But there are many surprising things about these
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cells. So and what is the relationship to the fly? I the right? So the link
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there is that if you ask how the photopigment now,
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Medicates, Downstream from the initial absorption event, to get to the electrical signal. That's a complex cellular process involves, many chemical steps. And if you look at how photoreceptors in our eyes work, you can see what that Cascade is, how that chain works. If you look in the eyes of flies or other insects or other invertebrates, there's a very similar kind of chain that. But the specifics of how the signal
20:41
from the absorption event by the pigment to the electrical response that the nervous system can understand are characteristically different between
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Fuzzy furry creatures like us and insects, for example, like the fly. I say, so he's funny extra photoreceptors that are in the wrong layer doing something, completely different are actually using it chemical Cascade. That looks much more like what you would see in a fly photoreceptor than what you would see in a human photoreceptor Roderick own, for
21:13
example, so it sounds like it's a very primitive part of primitive aspect of biology that we
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maintain.
21:20
Exactly, right, you know,
21:21
Zach and despite the fact that dogs can't see as many colors as we can and cats can't see as many colors as we can. We have all this extravagant stuff for seeing color and then you got this other Pigman sitting in the wrong not wrong, but in a different part of the I sending processing light very differently, right? And sending that information into the brain. So what do these cells do? I mean, presumably they're there for a reason they are
21:48
and the
21:50
Interesting thing is that one cell type like this carrying one kind of signal, which I would call a brightness signal. Essentially can do many things in the
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brain, when you say brightness signal, you mean that it like right now, I have these cells have these soldiers. I do. It's not like I'm joking. I hope I have these cells in my and they're paying attention to how bright it is overall, but they're not paying attention, for instance, to the edge of your ear or what else is going on in the room, right? So, so
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it's the difference between knowing what the objects are.
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The table and knowing whether it's bright enough to be daylight right now. So what, why does your nervous system to need? Need to know whether it's daylight right now? Well, one thing that needs to know that is your circadian clock if you could travel across time zones to Europe. Now your internal clock thinks it's California time, but the rotation of the earth is, you know, for a different part of the planet, you're the rising and setting of the sun is not at all. What your body is anticipating. So you've
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an internal representation of the rotation of the earth in your own brain. That's your circadian system is keeping time. But now you've played a trick on your nervous system. You put yourself in a different place where the sun is rising. It the quote, wrong time. Well, that's not good for you. Right? So you got to get back on track. One of the things this system does is sends a, oh, it's daylight now signal to the brain, which Compares with its internal clock. And if that's not right it, tweaks the clock gradually.
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You get over your jet lag and you feel back on track again. So
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the jetlag case, makes a lot of sense to me, but presumably these elements didn't evolve for jet lag. Right? So what, what are they doing on a day-to-day
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basis? Right? Well, one way to think about this is that the clock that you have in, not just your brain in all the cell's, be warm, almost all of the cells of your body. They're all oscillating or all, you know, they got a little cockeyed, little clocks.
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In themselves, they're all they're all clocks, you know, they need to be synchronized appropriately and the whole thing has to be built in biological Machinery. This is actually a beautiful story about how gene expression can control gene expression. And if you set it up, right, you can set up a little thing that just sort of homes along at a particular frequency, in our case is humming along at 24 hours, because that's how our Earth.
24:20
Is and it's all built into our biology. So this is great. But the reality is that the clock can only be so good. I mean, we're talking about biology or it's not Precision Engineering and so it can be a little bit
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off. Also. It doesn't it's in our brain. So it doesn't have access to any regular unerring signal.
24:39
Well if in the absence of the rising and setting of the sun, it doesn't if you put someone in a cave, their biological clock will keep time to within a handful of minutes of
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24 hours, that's no problem for one day. But if this went on without any correction, eventually, you'd be out of phase. And this is actually one of the things that blind patients often complain about. They've got retinal, blindness, is insomnia,
25:07
and or seasonal stream? That organized
25:10
exactly. They're not synchronize. Our clock is there, but they're drifting out of phase because their clocks only good to, you know, twenty four point two hours or 23.
25:20
In eight hours, though by little and they're drifting. So you need a synchronization signal. So even if you never across time zones, and of course, we didn't back on the savanna. We stayed within walking distance of where we were. You still need a synchronizer because otherwise you have nothing to actually confirm
25:39
one, the rising in the setting
25:40
of the sun is that's what you're trying to synchronize yourself to.
25:44
I'm fascinated by the circadian
25:46
clock and the
25:48
fact that all the cells of our body have,
25:50
Essentially a 24-hour ish clock in them, right? We hear a lot about these circadian rhythms and circadian. Clocks fact that we need light input from these special neurons in order to set the clock, but I've never really heard. It described how the clock itself works and how the clock signals to all the rest of the body. When, you know, the livers should be doing, one thing about the stomach should be doing another. I know you've done some work on the clock. So if you would just maybe,
26:20
We describe where the clock is, what it does and some of the, you know, top Contour of
26:27
how it tells the cells of the body, what to do. Right? So the first thing to say is that he's you said, the clock is all over the place. Most of the tissues in your body have clocks.
26:37
We probably have what millions of clocks. Yeah, but
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I would say, that's probably fair. You have millions of cell types. You might be have millions of clause that the role of the central pacemaker for the Circadian system is,
26:50
To coordinate all of these. And this is there's a little nucleus, a little collection of nerve cells in your brain. This called the suprachiasmatic nucleus, the scn, and it is sitting in a funny place for the rest of the structures in the nervous system to get direct retinal input. It's sitting in the hypothalamus, which you can think about is sort of the great coordinator of drives and the
27:18
source of all our pleasures and all our
27:20
Right? And most are problems. Yes,
27:22
it really is, but it's sort of, you know, deep in your brain, things that drive you to do things. If you're freezing cold, you put on a code, you
27:30
you shivery all these things are coordinated by the
27:32
hypothalamus. So this pathway it we're talking about from the retina and from these peculiar cells that are encoding light intensity or sending signals directly into
27:44
A center that's surrounded by all of these centers that control autonomic nervous system and your hormonal systems. So this is a part of the your visual system that doesn't really reach the level of Consciousness. It's not something you think about. It's happening under the radar kind of all the time and the signal is working its way into this Central clock coordinating Center.
28:13
now what happens then is not that well understood but it's clear that this is a neural Center that has the same ability to communicate with other parts of your brain as any other neural Center and clearly there are
28:27
circuits that involve connections between neurons that, you know, are conventional. But in addition is quite clear that there are also sort of humoral effects that things are being losing out of the cells in the center, and maybe into the circulation or just diffusing through the brain, to some extent. They can also affect neurons, all square, but the hypothalamus uses everything to control the rest of the bodies. And that's true. The suprachiasmatic nucleus, this this circuit.
28:57
And Center as well. It can get its fingers into the autonomic nervous system, the humoral system, and of course, up to the centers of the brain, that organized coordinated rational
29:10
Behavior. So if I understand correctly, we have this group of cells, the suprachiasmatic nucleus. It's got a 24-hour Rhythm it. That rhythm is more or less matched to what's going on in our external World by the specialized set of neurons in our eye, but then the
29:27
The Master Clock itself, the scn releases things in the blood humoral, signals that go out, various places in the body and he said to the autonomic system, which is regulating more or less our alert or calm. We are as well as our thinking in our cognition. So the I'd love to talk to you about the autonomic part. Presumably that's through,
29:51
melatonin. It's through
29:54
adrenaline. How is it that this clock?
29:57
Is impacting. How the autonomic system? How alert or calm? We feel
30:02
right? So there are there are Pathways by which the suprachiasmatic nucleus can access both the parasympathetic and sympathetic nervous
30:11
system. Just so people know the sympathetic nervous system is the one that tends to make us more alert and the parasympathetic nervous system is the portion of the autonomic nervous system makes us feel more calm right in
30:22
broadcast first. Yeah, to First approximation, right? So this is both
30:27
both of these systems are within the grasp of the Circadian system through hypothalamic circuits. One of the circuits that will be I think of particular interest to some of your listeners is a pathway that involves this sympathetic branch of the autonomic nervous system, the fight or flight system that is actually through a very circuitous route innervating. The pineal gland which is sitting in the middle of your brain, the so-called third eye, right?
30:57
So this is a lot to get back to why it's called the third eye because yeah, that's an interesting call seeing the third eye and not and just, you know,
31:05
just leave it there. Leave it there. Right? Right. Anyway, this is the major source of melatonin your body.
31:11
So light comes in to my eye. Yes. Passed off to the suprachiasmatic nucleus. Essentially not the light itself, but the the signal representing the light. Sure. Then. The scn the suprachiasmatic nucleus can impact the Melatonin system, right?
31:27
But via the pineal, right? The way this
31:29
is seen, is that if you were to measure your melatonin level over the course of the day, if you could do this, you know, hour by hour, you'd see that it's really low during the day, very high at night. But if you get up in the middle, the night and go to the bathroom and turn on the bright folder fluorescent light, your melatonin level is slammed to the floor. Light is directly impacting your hormonal levels through this mechanism that we just described. So this
31:57
One of the routes by which light can act on your hormonal status through Pathways, that are completely beyond what you normally would think about. Right? You're thinking about this, the things in the bathroom. Oh, there's the toothbrush. There's the tube of toothpaste. But meanwhile, this other system is just counting photons and saying, oh, well, that's a lot of photons right now. Let's shut down, the Melatonin release.
32:22
This is one of the main reasons why I've encouraged people to avoid bright light exposure in the
32:27
Middle of the night, not just blue light, but bright light of any wavelength because there's this myth out there that blue light because it's the optimal signal for activating. This pathway in shutting down. Melatonin is the only wavelength of light that can shut it down. But am I correct in thinking that if a light is bright enough, right? It doesn't matter. If it's blue, light, green, light, purple light, even red light. You're going to slam melatonin down to the ground, which is not a good thing to happen in the middle of the
32:57
Right, right. Yeah, I mean any any light will affect the system to some extent? The blue light is somewhat more effective, but don't fool yourself to into thinking that. If you use red light, that means you're, you know, you're avoiding the effect you street. It's certainly still there. And certainly, if it's very bright. It'll be more effective in driving the system than dim blue, light would be interesting.
33:20
A lot of people wear blue blockers and in a kind of odd, Twist of misinformation out there.
33:27
There are a lot of people wear blue blockers during the middle of the day, which basically makes no sense. Because during the middle of the day is, when you want to get a lot of bright light and
33:37
including blue light into your eyes, correct? Absolutely. And not, just for the reasons we've been talking about in terms of circadian effects. There are major effects of light, on mood and seasonal affective disorder apparently is essentially a reflection of this same system in Reverse. If you living in the northern
33:57
He
33:57
climbs and you know, you're not getting that much light during the middle of the winter in Stockholm. You might be prone to depression and phototherapy might be just the ticket for you. And that's because there's a direct effect of light on mood. Does there's an example where if you don't have enough light, it's a problem. So I think you're exactly right. It's not about his like good or bad for you. It's about what kind of light and when then that makes the
34:24
difference, the general rule of thumb that I've been living by his to
34:27
Get as much bright light in my eyes. Ideally from sunlight anytime. I want to be alert, right? And doing exactly the opposite when I want to be asleep. Yeah, we're getting
34:36
drowsy and there are aspects of this that spin out Way Beyond the conversation. We're having now, two things like this. It turns out that the incidence of myopia or nearsightedness nearsightedness right is strongly related to the amount of time that kids spend outdoors
34:56
and what direction of
34:57
The more they spend time Outdoors, the less nearsightedness they have. So
35:02
this is that because they're viewing things at a distance R because they're getting a lot of blue light, this
35:06
sunlight. It's a great question. It is not fully resolved. What the epidemiological with the basis of that epidemiological finding is one possibility, is the amount of Light, which would make me think about this melanopsin system again, but it might very well be a question of accommodation. That is the process by which you focus on near or far things if you're never out doors, everything is
35:27
Nearby, if you're Outdoors, you're focusing
35:29
far. So this is your, on your phone. Right? Exactly, which there's a tremendous amount of Interest these days in, you know, watches and things that count steps beginning to realize that we should probably have a device that can count photons during the day, right? And can also count photons at night and tell us how you're getting too many photons. You're going to shut down your melatonin and I adore. You're not getting enough photons today. You didn't get enough bright light whether or not some artificial liner from sunlight that I guess, the
35:57
Would you put a zebra on top of your head or you probably want it someplace outward-facing? Right? It probably what
36:04
you need is his many photons over as much of the retina as possible to recruit as much of this system, you know as possible
36:11
in thinking about other effects of this non-image forming pathway that involves these special cells in the eye and the scn. You had a paper a few years ago, looking at
36:23
retinal imput to an area of the brain which has a fancy name,
36:29
the Perry habenula, but names don't necessarily
36:32
matter that had some important effects on mood and other aspects of light, what maybe you could tell us a little bit about what is the Perry
36:41
habenula? Oh, wow. So, you know, that's a fancy term. But I think the way to think about this is as a chunk of the brain, that is sitting as part of a bigger chunk. That's
36:53
Really the Linker between peripheral sensory input of all kinds, more virtually all kinds, whether it's auditory input or tactile input or visual input to the region of your brain. The cortex that allows you to think about these things and make plans around them and to integrate them in that kind of thing. So, you know, we've known about a pathway
37:22
That gets from the retina through this sort of linker Center called the thalamus and then on us like a train station. Exactly. But you want to arrive at the destination. Right now, your Grand Central and now you can do your thing as you're up at the cortex. So this is the standard pattern. You have the sensory input coming from the periphery. You've got these peripheral elements that are doing the initial stages of
37:45
the the I do
37:47
skin of your fingertips, right, you know the taste buds on your tongue, they're taking.
37:52
Raw information in and they're doing some pre-processing maybe, or, you know, the early circuits are. But eventually most of these signals have to pass through the gateway to the cortex, which is the thalamus. And we've known for years for decades many decades, what the major, throughput pathway from the retina to the cortex is, and where it ends up ins up in the visual cortex, you know, you passed the back of your head. That's where the, where the receiving? The center is for the main pathway from
38:22
Retina to Cortex. But wait a minute. There's more. There's this little side pathway that goes to a different part of that linking Thalamus. Center. The gateway to that were like a
38:32
local train. Yeah. From Grand Central to
38:35
instant a weird part of the Nero it, right. It's a completely different. It's like a little trunk line that branches off and goes out into the Hinterlands, and it's going to the part of this Linker Center. That's talking to a completely different part of Cortex way. Up front frontal lobe.
38:51
Which is much more involved in things like planning or self-image
38:56
or South Edge. Literally, how one
38:59
views oneself in. Did you feel good about yourself? Or you know, what's your plan for next Thursday? You know, it's it's a it's a very high level Center in the highest level of your nervous system. And this is the region that is getting input from this pathway, which is mostly worked out in this function by Samurai.
39:21
Muslim, I know you had human the
39:22
podcast. We didn't talk about this path, this
39:24
path way at all, right, so, Daniel, Fernandez, and, and samarin the folks that work with them were able to show that this pathway doesn't just exist and get you to a weird place. But if you activate it at kind of the wrong time of day,
39:43
Animals can become depressed. And if you silence it under the right circumstances, then weird lighting cycles, that would normally make them act sort of depressed. No longer have that effect. So it
39:57
sounds to me like, there's this pathway from I to this unusual. Train route through the structure. We call the thalamus, then up to the front of the brain, that relates to things of self perception, kind of higher level functions.
40:12
And I find that really interesting because most of what I think about when I think about these fancy, well, or these primitive rather neurons, that don't pay attention to the shapes of things. But instead to brightness, I think of well, it regulates Melatonin circadian clock, mood hunger, the really kind of vegetative life if you will, right. And this is interesting because I think a lot of people experience depression, not just people that live at the, you know, in Scandinavia, in the middle of winter and
40:42
And we are very much divorced from our normal interactions with light. It also makes me realize that these intrinsically photosensitive cells that set the clock Etc are involved in a lot of things. I mean, they seem to regulate a dozen or more different basic functions. I want to ask you about a different aspect of the visual system now, which is the one that relates to our sense of balance. So I love boats, but I
41:12
Being on them. Love the ocean from Shore because I get incredibly seasick. Just it's awful. I think I'm gonna get seasick if I think about it too much, and once I went on a boat trip, I came back and I actually got I got motion sick or wasn't seasick, because I would rafting. So there's a system that somehow gets messed up. They always tell us if you're feeling sick to look at the Horizon, etc. Etc. So, what is the link between our visual system and our balance system and why does it make us nauseous?
41:42
Times when the world is moving in a way that we're not accustomed to, right. I realize this is a big question because it involves eye movement, Etc. But let's maybe just walk in at the simplest layers Vision, vestibular so-called balanced system. And then maybe we can piece this system together for people so that they can understand. And then also we should give them some tools for adjusting their knowledge. They do. When they're when they're vestibular system is out of
42:10
whack. Cool, so
42:12
I mean, I think the first thing to think about is that the vestibular system is designed to allow you to see how, your or detect, sense, how you're moving in the world, through the world.
42:31
It's a funny one because it's about your movement in relationship to the world in a sense. And yet it's sort of interoceptive in the sense that it is really, in the end, sensing the movement of your own body.
42:46
Okay. So interoception, we should probably delineate for people is when you're focusing on your internal State as opposed to something outside you, right? But is it, is it a? It's a gravity sensing?
42:54
It's well, it's partly a gravity sensing system in the sense that
43:00
Gravity is a force that's acting on you as if you were moving through the world in the opposite direction.
43:06
All right. Now you got to explain that one to
43:09
me. Okay. So basically the idea is that if we leave gravity aside, we're just sitting in, in a in a car in the passenger seat and the driver hits the accelerator and you start moving forward. You sense that if your eyes were closed, you'd sense it. If your ears were plugged in.
43:29
Eyes were closed. You'd still know it.
43:31
And many people take off on the plane like this, third reading the flight, and they know when it's the plane is, taking off,
43:36
sure. That's your vestibular system talking because anything that jostles you out of the current position. You're in right now, will be detected by the vestibular system pretty much. So this is a complicated system, but it's basically in your inner ear, very close to where you're hearing. They put it there.
43:56
There was, and I don't know who is going to ride. You know, I'm just kidding. There's a to steal our friend. Russ van gelder's explanation. We weren't consulted the design phase and no one. That's, that's a great idea. That's a great line, but it's interesting. It's in
44:10
the ear. Yeah. It's yeah, it's deep in there and it served by the same nerve actually that serves the hearing system. One way to think about it is both the hearing system and this vestibular self motion sensing.
44:25
System are really detecting the signal in the same way. They are hairy cells and they were exciting hair. Yeah, sort of they got little cilia sticking up off the surfaces and depending on which way you bend, those is cells, will either be inhibited or excited? They're not even neurons, but then they talked to neurons with a neuron like process and off you go. Now, you've got an auditory signal. If you're sensing things bouncing around in your cochlea, which is sound ways sympathetically, that bouncing of your
44:55
Um, which is in sympathetically, the sound waves in the world, but in the case of the vestibular apparatus evolution is built a system that detects the motion of a fluid going by those hairs. And if you put a sensor like that in a tube, that's fluid-filled. Now, you've got a sensor that will be activated. When you rotate that tube around the axis that passes through the middle of it. Those were just listening. Well, when people are, you
45:22
know, I think usually says, I was think of it as three. Hula hoops, right?
45:25
Hold on standing up, one lying down on the ground, right? The, you know, the other one, the other
45:30
way, three directions, you know, the people who fly will talk about roll pitch, and yaw, all that kind of thing. So, three axes of encoding just like in the
45:39
chords of the, yes, the know and then I would say it's and then the puppy had told ya that puppy Hotel the US. That's the other one. So the point is that your
45:48
brain is eventually going to be able to unpack, what these sensors are telling you, about how you just
45:55
Stated your head in very much the way that the three types of cones. We were talking about before are reading the incoming photons in the wavelength domain differently. And if your degree here in good, yeah, you think wearing trust, you get Redwing blue. So it seemed basic idea. If you have three sensors and you were Rea them properly. Now, you can tell if you're rotating your head left or right up or down. That's the sensory signal coming back into your brain.
46:23
Confirming that you've just made a movement that you will.
46:26
But what about on the plane? Because when I'm on the plane, I'm completely stationary the planes moving, right? My head doesn't move, right. So I'm just moving forward. Gravity is constant exactly how so I know I'm
46:37
accelerating. So what's happening now is your brain is sensing the motion.
46:42
And the brain is smart enough. Also to ask itself, did I will that movement or did that come from the outside? So now in terms of sort of understanding what the vestibular signal means? It's got to be embedded in the context of what you tried to do, or what about your other sensories systems, are telling you about what's happening. I see. So,
47:03
it's very interesting. I but it's not conscious or at least if it's conscious it's very it not conscious. It's definitely very fast, right. The moment that
47:12
Starts moving. I know that I didn't get up on my chair and run forward, right? But I'm not really thinking about getting up out of my chair.
47:18
I think, you know, I guess the way I think about it is that the nervous system is quota. We're at many levels.
47:27
When it gets all the way up to the cortex, and we're thinking about it, you're talking about it, you know, that's cortical. But the lower levels of the brain that don't require you to actually actively think about it. They're just doing their thing are also made aware. Right? A lot of this is happening under the surface of what you're thinking. These are reflexes,
47:48
okay.
47:50
So we've got this gravity sensing system, right for, I'm nodding for those that are listening for a YES Movement of the head and no movement of the head or the tilting of the head from side to side. Right? And then you said that knowledge about whether or not activation of that system comes from my own movements or something acting upon me like the plane moving, right? Has to be combined with other signals. And so, how is the visual information?
48:19
More information about the visual world combined with balance information,
48:22
right? So I mean, I guess maybe the best way to think about how these two systems work together is to think about what happens when you suddenly rotate your head to the left.
48:35
When you suddenly rotate your head to the left, your eyes are actually rotating to the right automatically it. You do this in complete darkness. If you had an IR infrared camera and watched yourself in complete darkness, you can't see anything, rotating your head to the left, your eyes, would rotate to the right. That's your vestibular system saying.
48:55
It's I'm going to try to compensate for the head rotation. So my eyes are still looking in the same place. Why is that useful? Well, if it's always doing that, then the image of the world on your retina will be pretty stable, most of the time and that actually helps Vision. If they built this into
49:15
cameras for image stabilization because when I move, when I take a picture with my phone, it's blurry. It's not, it's not clear. Well, actually,
49:23
you know, you might want to get a better phone.
49:25
Because now what they have is software in the better ABS that will do a kind of image stabilization post hoc by doing a registration of the images that are bouncing around. They say this, the edge of the house was here. So let's get that aligned in each of your images. So you may not be aware. If you're using a good new phone that if you walk around landscape and hold your phone that, you know, there's all this image stabilization going on, but it's built into standard.
49:55
Cinematic, you know technology now because we tried to do a handheld camera, things would be bouncing around. Things would be unwatchable. You wouldn't be able to really understand what's going on in the scene. So the brain works really hard to mostly stabilize the image of the world on your end. And of course, you're moving through the world so you can't stabilize everything. But the more you can stabilize most of the time, the better you can see. And that's why, when we're scanning a scene.
50:22
Looking around at things, we're making very rapid eye movements for very short periods of time. And then we did a rest, but we're not the only ones that do that. If you ever watch a hummingbird, it does exactly the same thing at a feeder, right? Such as if this body jolting is going to make a quick movement.
50:39
And then it's going to be stable. And when you watch a pigeon walking on the sidewalk, it does this funny, head-bobbing thing. But what is really doing, is racking his head back on its neck, while its body goes forward. So that the image of the visual World stays static, is that whether doing jealous and you've seen the funny chicken videos on YouTube, right? You've taken chicken, move it up and down the head stays in one place. It's all the same thing. All of these animals are trying hard to keep the image of the world stable on their retina as much of the time.
51:09
They possibly can. And then when they've got to move, make it fast, make it quick and then stabilize. Again. That's one of the pigeons of their head back ideas. Yeah. Wow. Yeah, I mean if you can just, you know, pause
51:20
there for a second and digest that amazing case people aren't well, there's no reason why people would know what we're doing here. But essentially what we're doing is we're building up from sensory, you know light onto the eye color to what the brain does with that. The
51:39
Integration of that, circadian clock, melatonin cetera. And now what we're doing is we're talking about multi-sensory, where multimodal, combining one sense Vision with another sense, balance, right? And it turns out that pigeons know more about this than I do, because pigeons know to keep their head back as they walk forward, right? All right, so, that gets us to this issue of motion sickness, right? And if you don't have to go out on a boat, any time I go to New York. I sit in an Uber, or in a cab, in the back.
52:09
I'm looking at my phone, while the car is driving. I feel nauseous by time. I arrive at my destination, right? I always try and look out the front of the windshield because I'm told that helps, but it's a little tiny window. Right? And I end up feeling slightly less sick if I do that. So what's going on with the vision and balance system? That causes a kind of a nausea? And actually if I keep talking about the setting Ali look at so I don't throw up easily, but
52:39
But for some reason, motion sickness is a real thing for. It's a problem for a
52:43
lot of people. I mean, I think the fundamental problem, typically, when you get motion sick is what they call Visual vestibular conflict. That is, you have to sensory systems that are talking to your brain about how you're moving through the world. And as long as they agree, you're fine. So if you're driving, you know, your body senses that you're moving forward? Your vestibular systems, you know, is is
53:09
Hang up this acceleration of the car. And your visual system is seeing the consequences of Forward Motion in the sweeping of the scene past you, everything is hunky-dory, right? No problem, but when you are headed forward, but you're looking at your cell phone. What is your retina seeing your retina, seeing the stable image of the screen? There's absolutely no
53:31
motion.
53:33
In that or the motion is just or some other emotion, that's among virology. If you're playing a game or you're
53:38
watching a video of football game, you know, the motion is uncoupled with what's actually happening to your body. Your brain doesn't like that, your brain likes everything to be, you know, a line. And if it's not, it's going to
53:49
complain to you. So give me feel not. Make
53:51
me feel nauseous, and maybe you'll change your behavior. So you're getting, I'm getting punished. Yeah, for for setting it up. So you're single so I can click right by the vestibular. You'll learn visual system.
54:04
In time, I love it. I love the idea of reward signals and we've done a lot of discussion about this on this podcast of things like dopamine reward and things but also punishment signals and
54:15
I love this
54:16
example. Well, maybe marching a little bit further along this pathway. Visual input is combined with balanced input. Where does that occur? And maybe, because I have some hint of where it occurs, you could tell us.
54:32
A little bit about this kind of mysterious little mini brain that they call the cerebellum.
54:38
Yeah. So, you know, the way I tried to describe the cerebellum to my students is that it serves, sort of like the air traffic control system functions in air travel. So that it's a system is very complicated and it's really dependent on great information. So it's taking in information.
55:02
Everything that's happening everywhere. Not only through your sensory systems, but is listening into all the little centers elsewhere in your brain that are Computing. What you're going to be doing next and so forth. So it's just ravenous for that kind of
55:15
information. So it really is like a little mini brain. It is
55:18
it's got access to all those signals and it really has an important role in in coordinating and shaping movements, but, you know, if you
55:32
Suddenly eliminated, the air traffic control system, planes could still take off and land, but you might have some unhappy accidents in the, in the process. So the cerebellum is kind of like that. It's not that you would be paralyzed if your cerebellum was gone because you still have motor neurons. You still have ways to talk to your muscles. You still have reflux centers and it's not like you would have any sensory laws because you still have your cortex getting all of those beautiful.
56:02
Those that you can think about but you wouldn't be coordinating things. So well anymore, the timing between input and output might be off or if you were trying to practice a new athletic Move Like an overhead serve in tennis, you'd be just terrible at learning but all the sequences of muscle movements and the feedback from your sensor. He's a press that would let you really hit that ball exactly where you wanted to after the nth rep, right?
56:32
I knew thousands rep or something, you get much better at it. So the cerebellum is all involved in things like
56:40
Motor learning and refining the precision's of movement so that they get you where you want to go. If you reach for a glass of champagne that you don't knock it over or stop short. That's what he's good at people
56:54
who have selective damage to the cerebellum. Absolutely. And, and what I come familiar with Will Korsakoff's is different, right? Isn't that a B vitamin deficiency from in chronic alcoholics, right? And they have a
57:08
Tend to walk kind of bowlegged and they can't coordinate their movements is that that has some that not sure a Mercedes but also cerebellum,
57:16
I'm not sure about the cerebellar involvement there. But you know, the typical thing would be a patient who has a cerebral or stroke or tumor. For example, might be not that steady on their feet, you know, if the, you know, dynamics of the situation you standing on a street corner
57:38
Car with your new, with Noah and go pull the whole onto, they might not be as good at adjusting all the little movements of the car, you know, there's a kind of tremor that can occur as they're reaching for things because the reach a little too far and then they overcorrect and come back things like that. So it's very common neurological phenomenon. Actually cerebellar Ataxia. This is what the neurologist call it and it can happen. Not just with cerebellar.
58:08
Damage, but damage to the tracks that feed the information
58:11
into the cerebellum or Broadway structures, actually or output from the cerebellum. And so the cerebellum is where a lot of Visual Land and balance. Information is combined in a
58:20
very key place in the cerebellum, which is it's really one of the oldest Parts in terms of applications. The flocculants, right? This is a it's a critical place in the cerebellum where Visual and vestibular information comes together for courting just the kinds of movements. We were talking about this.
58:38
Image stabilizing Network. It's all happening there, and there's learning happening there as well. So that if your vestibular apparatus is a little bit damaged, somehow your visual system is actually talking to your cerebellum. Saying there's a problem here. There's an error and your cerebellum is learning to do better by increasing the output of the vestibular system to compensate for whatever that loss was. So it's a little error correction system, that's sort of typical of cerebellar function and it
59:08
Happen in many, many different domains. This is just one of the domains of sensory motor integration that takes
59:14
place there.
59:16
So I should stay off my phone in the reverse. If I'm on a boat. I should essentially look and as much as possible act, as if I'm driving the the machine, right, that'd be weird. If I was in the passenger seat pretending. I was driving the machine, but I do always feel better. If I'm sitting in the front seat passenger, write some more
59:33
of the of the visual world that you can see. As if you were actually the one doing the motion, I would
59:38
think, but stay in the inner ear for a minute as we continue to March around the nervous system.
59:46
When you take off in the plane or when you land or sometimes the middle of their, your ears get clogged or at least my ears get clogged.
59:54
That's because of pressure buildup in the various tubes of the inner. Ear, Etc will get into this but years ago are good. Our good friend Harvey. Carton is a another world class neuroanatomist.
1:00:09
Gave a lecture and talked about how plugging your nose and blowing out versus plugging your nose and sucking in can should be done at different times depending on whether or not you're taking off or landing. And I always see people try to unpop their ears, right. And when you do scuba diving, you learn how to do this without necessarily. I can do it by just kind of moving my jaw now, because I've done a little bit of diving, but what's the story there? We don't have to get into all the
1:00:39
Francis is an atmospheric pressure Etc. But I'm taking off and my ears are plugged rub recently ascended. When I took off. My ears are plugged. Do I plug my nose and blow out or do I plug my nose in
1:00:49
suckin? Right? So the basic idea is that if your ears feel bad because you're going into an area of higher pressure. So if they pressurize the cabin more than the pressure that you have on the surface of the planet, your eardrums will be bending in and they don't like that. If you push them or they'll hurt, even
1:01:08
it's good.
1:01:09
Description that you know, that pressure goes up then, we're going to bend it
1:01:12
in. Reverse would be true. If you go into an area of low pressure. So if you know, you started to drive up the mountain side, you know, the pressure is getting lower and lower outside. Now, the inside the are behind your drum is blooming out. Yep, right? So it's just a question of are you trying to get more pressure or less pressure behind the eardrum? And there's a little tube that does that and comes down into your, you Novak your throat there. If you force pressure up that tube, you going to be putting more air?
1:01:39
Pressure into the compartment to counter it. If it's if it's not enough and if you're sucking, you're going the other way in reality, I think, as long as you open the passage way, I think the different pressure differential is going to solve your problems. I think you could actually blow in when you're not quote, supposed to.
1:01:55
Okay, so you could just blow your nose and blow air out or hold your nose and suck. In the right effect. Either way is
1:02:04
fine. I think so, I think so. Don't you
1:02:06
just? I just want $100 from every carton.
1:02:09
Thank you very much. There's a lot wheat, Harvey, and I used to teach neuroanatomy together. I was like, I don't think it matters. What? Thank you Bruce. I'll split, you know, split that with you after this is this is important stuff, but it sure you hear this, you know, so so it doesn't matter either way. Yeah.
1:02:25
I'm no expert in this area. Don't worry. Don't quote me. He's
1:02:28
not going to Vlog going to quote you. But Okay, so we've talked about the inner ear and we talked about the cerebellum. I want to talk about an area of the brain. That is rarely discussed.
1:02:38
Which is the midbrain? Yeah,
1:02:40
and for those that don't know. The midbrain is an area beneath the cortex. I guess we never really defined cortex. It was kind of the outer layers or is are the outer layers of the least mammalian, brain and human brain at, but the midbrain is super interesting because it controls a lot of unconscious stuff reflexes Etc.
1:03:05
And then there's this phenomenon even called blindsight. So could you please tell us about the midbrain about what it does? And what in the world
1:03:14
is blind sight? Yeah. So this is a there's a lot of pieces there. I think. The first thing to say is, if you imagine the nervous system in your mind's eye. You see this big honking brain and then there's this little thin little wand that dangles down into your vertebral column, the spinal
1:03:34
And that's kind of your visual impression. What you have to imagine is starting in the spinal cord and working your way up into this big magnificent brain and what you would do. As you enter. The skull is get into a little place where the spinal cord kind of thickens out. It still has that sort of long skinny trunk like
1:03:54
feelings or like a paddle or a spoon shape,
1:03:56
right? It starts spread out a little bit. That's because you're, you know, evolution is packed more interesting goodies in there, for processing information and generate.
1:04:04
Ting movement. So beyond that. Is this tween brain we were talking about. So it's link this link or been with diencephalon. Really means that the between, bro. I thought you said tween. Well, yes. Yes. No. No, he's tweeting
1:04:17
between. As I said, tween.
1:04:19
He's the between it's a between rain is is what the the name means? It's the Linker from the spinal cord in the periphery up to these Grand centers of the cortex. But this midbrain you're talking about is the last
1:04:34
Of this enlarged, sort of spinal cord anything in your skull, which is really the brain. Stem is what we call it, the last bit of that. Before you get to this relay up, to the cortex, is the midbrain. And there's a really important visual Center at their. It's called The Superior colliculus. There's a similar Center in the brains of other vertebrate animals, a frog for example, or a lizard would have this is called the optic tectum there, but it's a center.
1:05:04
Then in these non-mammalian vertebrates, is really the main visual Center. I don't really have what we would call a visual cortex. All of there's something sort of like that. But this is where most of the action is in terms of interpreting visual input. And organizing Behavior around that you can sort of think about the this region of the brain. Stem is a reflex center that can reorient the animals gays or body.
1:05:34
Or maybe even attention to particular regions of space out there around the animal and that could be all for all kinds of reasons. I mean, it might be a predator just showed up in one corner of the forest and you pick that up and you're trying to avoid it or just any movement many movement, right? It might be you know, that suddenly, you know, some things Splats on the page when you're reading a novel and your eye reflects Lee looks at it, don't have to think about that. That's a reflex.
1:06:04
Whatever you
1:06:04
throw me a ball, but I'm not expecting it. Right? I just reach up and, and try and grab it. Right? It should or not. Right? Is that handled by the midbrain? Well, that's
1:06:12
probably not the midbrain. Although, if I mean by itself because it's going to involve all these limb movements this movement of your arm and body and
1:06:23
what about ducking, if something suddenly
1:06:24
thrown ahead, sure? Right? Things like that are, will certainly have a brain stem component, a midbrain component, you know, something looms and you doc it.
1:06:34
Copy the superior colliculus, we're talking about now might be another part of the visual midbrain, but these are centers that emerged early in the evolution of a brains like ours to handle complicated visual events that have significance for the animal in terms of space. Where is it in space? And in fact, the same Center actually gets input from all kinds of other sensory systems that take information from the external World from particular locations. And where you might want to either avoid or approach things according to their
1:07:04
Significance to you. So you get input from The Touch system. You get input from the auditory system. I work for a while in rattlesnakes. They get input from a part of their warm sensors on their face. They're in these little Pits on the, on the face work on baby rattlesnakes right over there. They were adults
1:07:23
at oh I wasn't trying to diminish, the danger. I thought for some reason, they were little ones. Know why in the world would you work on
1:07:29
rattlesnakes? Well, because they have a version of an
1:07:34
Receptive sensory system that is there looking out into the world using a completely different set of sensors. They're using the same sensors. That would feel the warmth on your face. If you stood in front of a bonfire, accept evolution has given them. This very nice specialized system that lets them image where the Heats coming from. You can sort of do that anyway, right? If you walk around the fire you can feel which where the fire is from the, you know, the heat hitting your face is that they've
1:08:00
just merry way in which they detect prey.
1:08:04
Race. One of one of the major ways. And in fact, they use Vision as well. And they bring these two systems together in the same place, in this tectum regions brainstem
1:08:14
memories of a jungle reading about
1:08:16
when the snakes that I don't know. That maybe olfactory, they're made, they're sniffing the air with their tongue. Yeah, there may be
1:08:23
bullier not drive. You told me that flies actually taste things with their
1:08:27
feet. They did. Yeah. Yeah, so we have, they have, they have taste receptors and lots of funny
1:08:31
places. I want to pause here.
1:08:34
For one second before we get back into the midbrain. I think what's so interesting in all seriousness about taste receptors on feet, heat sensors tongue, shutting out of snakes and vision. And all this integration is that it really speaks to the fact that all these Sensory neurons are trying to gather information and stuff it into a system that can make meaningful decisions and actions. And that it really does.
1:09:04
Don't matter whether or not it's coming from eyes or ears or nose, or bottoms of feet because in the end it's just electricity flowing in. And so it's it sounds like it's placed on each animal. It's always feels weird to call flying animal, but they are amateurs. They are animals. It's placed in different locations on different animals depending on the particular needs of that animal, right? But how much more
1:09:27
powerful if the nervous systems can also cross-correlate across sensory?
1:09:34
So if you've got a weak signal from one sensory system, you're not quite sure. There's something there and a weak signal from another sensory system. That's telling you. The same locations is a little bit interesting. There might be something there. If you've got those two together, you've got corroboration your brain now, says, it's much more likely that that's going to, you know, be something worth paying attention to,
1:09:56
right. So, maybe I'm feeling some heat on one side of my face and I also smell
1:10:04
Something baking in the oven, right? So now there's it's neither is particularly strong. But as you said, there's some corroboration, right? And that corroboration is occurring in the midbrain,
1:10:12
right? And then, if you throw things into conflict now, the brain is confused and that may be where your, your motion sickness comes from. So it's great to have, you know, as a as a brain. It's great to have this many sources of information is you can have just like if
1:10:26
you're a, you
1:10:27
know, you're a spy or a journalist, you know, one as much information as you can get as about what's out there.
1:10:33
But if things conflict, that's problematic, right? Your sources are giving you different formation about what's going on. Now. You got a problem on your hands. What do you
1:10:40
publish?
1:10:42
The midbrain is so fascinating. I don't want to eject us from the midbrain and go back to the vestibular system. But I do have a question that I forgot to ask about the vestibular system, which is why is it that for many people including me? There's despite my motion sickness in caps. That there's a sense of pleasure in moving through space and getting tilted, relative to the gravitational pull of the Earth. For me, growing up. It was skateboarding, but people like to corner and Cars Corner on bikes. It may be for some people.
1:11:11
It's done running or dance. But you know, what, is it about? Moving through space and getting tilted lot of surfers around here, getting tilted, that can tap into some of the pleasure centers is that we have any idea. Why that would feel I have no clothes. They're dopaminergic input to this
1:11:30
system. Well, you know, the dopaminergic system gets a lot of places, you know, it's pretty much to some extent everywhere in the cortex a lot.
1:11:41
More in the frontal lobe, of course, but, you know, that's just for starters. I mean, there's basically dopaminergic innervation most places in the central nervous system. So there's the potential for dopaminergic involvement, but I really have no clue about the tilting phenomenon. I mean, if
1:11:55
you do pay money to go on roller coasters,
1:11:58
right? Well, I think that may be as much about the thrill is anything. Sure
1:12:01
and falling is the falling reflexes. Very robust in all of us live in the visual world is going up very fast. It usually means that we're falling, right? But in some people like that, some people
1:12:10
don't write and
1:12:11
Kids, tolerate a lot more, you know, sort of vestibular, craziness spinning around until they drop.
1:12:18
And I've see, I've friends always, you know, worries me a little bit that will they throw their kids? I'm not recommending it. When do this when they're little kids, you know, like throwing the kids really far back and forth. I'm kids some kids seem to love it.
1:12:30
Yeah. Yeah. Our son loved being shaken up and down very very vigorously. He has the only thing that would come down sometimes
1:12:39
interesting. Yeah, so I'm guessing we
1:12:41
Can we can guess that? Maybe there's some activation of the reward systems from yeah. Being moving through space.
1:12:50
Well, I mean, if you think about it, you know, how rewarding it is to be able to move through space and how unhappy people are, who are used to that, who suddenly aren't able to do that. There is a sense of agency, right? If you can choose to move through the world and to tilt, that's not only you moving through the world, but you're doing with a certain amount of finesse. Maybe that's what it is. You can feel like you're the master of your
1:13:11
On movement in a way that you wouldn't, if you're going straight. I'm just blowing
1:13:16
smoke earring. Yeah, we can speculate that's fine. I couldn't help but ask the question. Okay. So if we move ourselves pun intended back into the midbrain, the mid brain is combining all these different signals for reflexive action. At what point. Does this become deliberate action? Because if I look at something I want and I want to pursue it. I'm going to go toward it and
1:13:40
many times. That's a
1:13:41
Right decision, right? So this gets very slippery. I think because what you have to try to imagine is all these different parts of the brain, working on the problem of staying alive, you know, and surviving in the world. They're working on the problem simultaneously. And there's not one right answer to how to do that. But the one way to think about it is that you have high levels of your nervous system.
1:14:11
There are very well designed to override and otherwise automatic movement if it's inappropriate, so if you imagine you've been invited to tea with the queen and she hands you, you know, very fancy Wedgwood, you know teacup very thin Wedgwood teacup. Yes with very hot tea in it and you're burning your hand. You probably will try to find a way to put that back down on the saucer rather than just dropping it on the floor. Because you're
1:14:41
If the queen, you know, you're trying to be appropriate to that. So you have ways of reining in automatic behaviors if they're going to be maladaptive, but you also want the reflex to work quickly. If it's the only thing that's going to save you the looming, you know, object coming at your head. You don't have time to think about that. So this is the interplay.
1:15:03
In these hierarchically organized centers of the nervous system at the lowest level. You've got the automatic sensors that in centers and reflux, you know, arcs that will keep you safe. Even if you don't have time to think about it. And then you've got the higher Center saying, well, maybe we could do this as well. Or maybe we shouldn't do that at all. Right. So you have all of these different levels, operating simultaneously and you need bi-directional communication between high level.
1:15:33
Cognitive centers decision-making on the one hand and these low-level very helpful reflexive centers, but there are little bit rigid, little hardwired, so they need some new ones. So there's that they're both of these things are operating in tandem in real time all the time in our brains and sometimes we listen more to one than the other. You've heard people in sports talking about
1:15:55
Messing up at the plate because they over thought it, you know, thinking too hard about it. That's partly, you've already trained your cerebellum how to hit a fastball right down the middle.
1:16:04
Right? And if you start looking for for something new or different, you're going to mess up your your reflexive
1:16:10
swing, right? If you're trying to think about the physics of the ball as is coming at you you've already missed, right? Because you, you're not using your this all those reps have built a kind of knowledge is what you want to rely on when you don't have enough time.
1:16:25
To contemplate.
1:16:28
This is important and a great segue for what I'd like to discuss next. Was it, which is the basal ganglia. This really interesting of the area of the brain that's involved in go type commands and behaviors, instructing us to do things, and no go preventing us from doing things because so much of motor learning and skill execution, and not saying the wrong thing or sitting still in class, when or as you used with the, you know,
1:16:58
Tea with the queen example, feeling discomfort involves suppressing behavior. And sometimes, it's activating Behavior, right? You know, tremendous amount of online. Attention is devoted to trying to get people motivated, you know, this isn't the main focus of our podcast. We touch on some of the underlying neural circuits of motivation dopamine and so forth. But so much of what people struggle with out. There are elements around failure to pay attention right? Or challenges in pain.
1:17:27
Attention, which is essentially the putting the blinders on there, you know, getting a soda straw view of the world and maintaining that for about of work or something of that sort and trying to get into action. So of course, this is carried out by many neural circuits, not just the basal ganglia, but what are the basal ganglia and what are their primary roles in controlling go type behavior and no go type Behavior.
1:17:51
Yeah. So I mean to the basal ganglia are sitting deep in what you would call the forebrain.
1:17:58
Should the highest levels of the brain? There are sort of cousins to the cerebral cortex, which we talked about is sort of the highest level of your brain that thing you're thinking with
1:18:09
three recorded as being the refined cousins and then you've got the right, you know, the brutes.
1:18:14
Yeah. I mean that's probably totally unfair but
1:18:17
that's alright because I like the basal ganglia. I can relate to that brutish parts of the brain. Little bit of hypothalamus. Little bit of Basil ganglia. Sure. We need
1:18:25
it all. We need it all.
1:18:27
And, you know, this area of the brain has gotten a lot bigger as the cortex has gotten bigger and it's deeply intertwined with cortical function. The cortex can't really do what it needs to do without the help of the basal ganglia and vice versa. So they're really intertwined and in a way you can think about this logically is saying, you know, if you have the ability to withhold Behavior or to execute it, how do you decide
1:18:58
Which to do while the cortex is going to have to do that. Thinking for you, you have to be looking at all the contingencies of your situation and decide. Is this a crazy move? Or is this a really smart investment right now? Or you know
1:19:10
what? I don't want to go out for a run in the morning, but I'm going to make myself go out for a run or I'm having a great time out on a run. And I know I need to get back but I kind of want to go. Another mile. I
1:19:20
mean, another great example is that, you know, the marshmallow test for the little kids, you know, they can get two marshmallows if they hold off.
1:19:27
You know, just 30 seconds initially, you know, they can have one right away. But if they can wait 30 seconds, they got to, you know, so that's the no-go because they're cortex is saying, you know, I really like to have two more than having one, but they're not going to get the two unless they can not reach for the one. So they've got a hold off the action. And that has to result from a cognitive process of the cortex is involved in this, in a major way.
1:19:57
Yes, I recall in that experiment. The kids used a variety of tools to some would distract themselves. I particularly related to the kid that would just put himself right next to the marshmallows and then what, and then some of the kids covered their eyes. Some of them would count or sing. Yeah. So that's all very cortical right. Coming up with a novel strategy, simple example that we're using here. But of course, this is at play. Anytime someone decides, they want to go watch a motivational speech or something. Just, you know, a Steve Jobs commencement speech just to get motivated to engage in their debt. I take this new
1:20:27
A job, you just got great benefits, but it's in a lousy part of the country. Why do you think that some people
1:20:33
have a harder time running these gonogo circuits? And other people seem to have very low activation energy. We would say they can just, you know, you they have a task. They just lean into the task. Right? Whereas some people getting into task completion or things of that sort is very challenging for
1:20:52
them. Yeah. I mean, I think it's really just another, it's a special case of a very general phenomenon.
1:20:57
His brains are complicated and Brands, resented rains. We have are the result of genetics and experience and my jeans are different from your jeans and my experiences are different from your experiences. So the things that are be easier, hard for us, won't necessarily be aligned. They might just happen to be just because they are. But the point is that, you know, you you're dealt a certain set of cards, you have certain set of genes. You are handed a, you know, a
1:21:27
brain, you don't choose your brain. It's handed to you, but then there's all the stuff you can do with it, you know, you can learn to, you know, to have new skills, or to act differently or to show more restraint, which is kind of relevant to what we're talking about here or maybe show less restrained. If your problem is, you're so button down. You never have any fun in life, you know, you should loosen up a little bit, right? You I appreciate that. So yeah,
1:21:55
David's always encouraging me to have a little more.
1:21:59
So basal ganglia are their kind of the disciplinarian or there's they're sort of the instructor conductor of sorts. Right? Go no-go, you know, you be quiet, you start.
1:22:11
Now. I wish I knew more about the basal ganglia Then I then I do my sense is that if you know this system is key for implementing the plans that get cooked up in the cortex, but they also influence the plans.
1:22:27
That the, you know, cortex is dishing out because this is a major source of information to the cortex. So it becomes almost impossible to figure out where the computation begins and where it ends and who's doing what, because these things are all interacting in a complex Network and it's all of it. It's the whole network. It's not, you know, one is the leader in the other
1:22:49
is the follower. Of course, you know, these are all the structures that were discussing are working in parallel, right? And there's a lot
1:22:57
of
1:22:57
Changing crosstalk. I have this somewhat sick habit, David. Oh every day. I try and do 21. No goes. So if I want to reach for my phone I try and not do it. Just to see if I can prevent myself from engaging in that behavior. If it was reflexive. It's something I want to do. Deliberate Choice, then I certainly allow myself to do it. Right? I don't tend to have too much trouble with motivation with go type functions, mostly because I'm so busy that. I wish I had more.
1:23:27
Time for more goes, but so to speak. But do you think the circuits have genuine plasticity in the
1:23:35
absolutely? I mean, everybody knows how they've learned over time to wait for the two marshmallows, right? You know, you don't have to have instant gratification all the time, you know, you're willing to do a job. Sometimes it isn't your favorite job because it comes with the territory and you want the salary that comes at the end of the week or the end of the month, right? So we can defer gratification.
1:23:57
You know, we can choose not to say the thing that we know is going to inflame our partner
1:24:01
in, create a, you know, a
1:24:03
meltdown for the next week, you know, we learn this control. But I think these are skills, like any other. You can get better at them if you practice them. So I think you're choosing to do that to spontaneously is as kind of a, you know, it's a mental practice. It's a discipline. It's a way of building a skill that you want to have.
1:24:21
Yeah. I find it to be something that when I engage in a no-go type.
1:24:27
Situation, then the next time. And the next time that I find myself about to move reflexively, there's a little Gap in Consciousness that I can interpret. I can make a decision whether or not this is really the best use of my time because I sometimes wonder whether or not all this business around attention. Certainly there's the case of ADHD and clinical diagnosed ADHD, but all these the issue around focus and attention is really that people just have not really learned how to short-circuit a reflex and
1:24:57
So much of what makes us different than rattlesnakes or well actually they could be deliberate, but from the other animals and is our ability to suppress reflex.
1:25:06
Yeah. Well, that's the cortex. I'm going to order. Let's say the for brain cortex and basal ganglia working together sitting on top of this lizard. Brain, that's giving you all these great adaptive reflexes that help you survive. You. Just hope you don't get the surprising case. Where the thing that your reflux is telling you is actually exactly the wrong thing. And you make
1:25:27
Mistake right? And that's what right? So that's what the cortex is for. Its adding nuance, and context and experience past Association and in human beings obviously learning from others through, you know, communication. Well, I was
1:25:42
you went right to it and it was where I was going to go. So let's talk about the cortex. We've worked our way up. The so-called neuraxis as the physician Autos will will know, so we're in the cortex. This is the seat of our higher, Consciousness, self-image.
1:25:56
Anning and action. But as you mentioned, the cortex isn't just about that. It's got other regions that are involved in other things. So maybe we should staying with vision. Let's talk a little bit about visual cortex. You told me a story, an amazing story about visual cortex. And it was a somewhat of a sad story. Unfortunately, about someone who had a stroke to visual cortex. Maybe if you would share that story. Because I think it illustrates many important principles about what the cortex
1:26:24
does, right? So, you know,
1:26:27
The visual cortex is you could say the projection screen, the first, you know, place where this information streaming from the retina through this Thalamus, you know, connecting Linker gets played out for the highest level of your brain to see. I mean, it's a representation. It's a map of things going on in the visual world, that's in your brain and
1:26:57
When we describe a scene to a friend, we're using this chunk of our brain, to be able to put words, which are coming from a different part of our cortex to the objects and movements and colors that we see in the world. So, you know, that's a key part of your visual experience. When you, when you can describe the things you're seeing, you're looking at your visual cortex, and this is that I just as a good question.
1:27:24
So right now, because I'm looking at your face.
1:27:27
Right. As we're talking,
1:27:29
there are neurons in my brain more or less in the configuration of your face that are active as you move about. And what if I were to close my eyes and just imagine do this all the time by the way David, I'll close my eyes and I imagine David person's face. I don't tend to do that as off. Maybe I should but you get the point. I'm now using visualization, but what you look like by way of memory.
1:27:56
Right. If we were to image the neurons in my brain, would the activity of neurons resemble? The activity of neurons?
1:28:06
That's present when I open my eyes and look at your actual.
1:28:09
This is a deep question. We don't really have a full. Seems like an experiment to do that. Yes, except, you know, you're talking about looking in detail at the activity of neurons in a human brain and that's not as easy to do as it would be in a you know in some kind of animal model but you know, the bottom line is that you you have a spatial representation of the visual World late as a map of the visual.
1:28:35
The world lay down on the surface of your cortex. The thing that's surprising is that it's not one map. It's actually dozens of maps.
1:28:44
What are each of those Maps do?
1:28:46
Well, we don't really have a full accounting there either but it looks a little bit like the diversification of the output neurons of the retinal ganglion cells. We were talking about before they're different types of ganglion cells that are encoding different, kinds of information about the visual world. We talked about the ones that were encoding the brightness, but other ones are
1:29:06
Motion or color, these kinds of things. The same kinds of specializations in different representations of the visual world in the cortex, seem to be true. It's a complex story. We don't have the whole the whole picture yet, but it does look as if some parts of the brain are much more important for things, like reaching for things in the space around you and other parts of the cortex are really important for making associations between particular visual things, you're looking at now and their significance.
1:29:35
What they, what, what is that object? What can it do for me? How can I use it?
1:29:39
What about the really specialized areas of Cortex? Like the areas like neurons that respond to particular phases or neurons that I don't know. Can help me understand where I am relative to some other specific
1:29:54
object. Right? So, you know this these are our properties of neurons that are
1:30:02
Extracted from detected by recording the activity of single neurons in some experimental system. What's going on when you actually perceive your grandmother's face is a much more complicated question and you clearly involves hundreds and thousands and probably millions of neurons acting in a Cooperative way. So you can pick out any one little element in this very complicated system and see that it's responding, differentially to certain kinds of visual patterns, and you think you're seeing a glimpse,
1:30:31
Limps of some part of the process by which you recognize your grandmother's phase. But that's a long way from a complete description and it certainly isn't going to be at the level of a magic single neuron that has the special stuff to recognize your grandmother. It's going to be in some pattern of activity across many, many cells resonating in some kind of special way that will represent the internal, you know memory of your of your mother. So it was really
1:30:58
incredible. Yeah. I mean, I mean every time we do this deal
1:31:01
Dive which we do from time to time you and I would kind of like March into the nervous system and explore how different aspects of our life experiences is handled there and how its organized the it after so many decades of doing this. It's still boggles my mind that that the collection of neurons, one through seven active, in a particular sequence, gives the memory of a particular face and run backwards.
1:31:31
Then through to one, gives you a complete, you know, could be, you know, rattle, snake pit, viper heat sensing organs, right? We're talking about earlier. So it sounds is it true that there's a lot of multi purposing of the circuitry. Like we can't say, one area of the brain does a in another area of the brain does be so, you know, areas can multitask or have multiple jobs. They can
1:31:55
Moonlight right, but I think in
1:31:59
My career, the hard problem has been to square that with the fact that, you know, things are specialized that there are specific genes expressed in the specific neurons that make them make synaptic connections with only certain other neurons. And that particular synaptic Arrangement actually results in the processing of information that's useful to the animal to survive. Right? So it's not as if
1:32:30
Either a big undifferentiated network of cells and looking at anyone is never going to tell you anything. That's too extreme on the one hand nor is it the case that everything is hardwired in, every neuron has one function and this all happens in one place in the brain. It's way more complicated and interactive, and interconnected than that.
1:32:49
So we're not hardwired or softwired. Both. We're sort of, I don't know what the analogy should be. What substance would work. Best. David
1:32:57
no idea there, but you know the idea.
1:32:59
Is that it's always network activity. There's always many many neurons involved. And yet there's tremendous specificity in the neurons that might or might not be participating in any distributed function like that. Right? So you have to get your mind around the fact that it's both very specific and very nonspecific at the same time. It's a little tricky to do but I think that's kind of where the truth
1:33:22
lies, you know, and so the example that you mentioned want to me once before about a woman who had a
1:33:29
Open visual cortex, I think speaks to some of this, right? Could you share with us that story? Sure. So the point is that you
1:33:36
you all those of us who see have representations of the
1:33:42
visual World in our visual
1:33:43
cortex. What happens to somebody, when they become blind because of problems in the eye, the retina perhaps you have a big chunk of the cortex, this really valuable real estate for neural processing.
1:34:01
That has come to expect input from the visual system and there isn't any anymore. So you might think about that is fallow land, right? It's just it's on used by the nervous system and that would be a Pity. But it turns out that it is in fact used and the the case that you're talking about is of a woman who was blind from very early in her life and who had risen.
1:34:29
And through the ranks to a very high level, executive secretarial positions, in a major corporation. I and she was extremely good at Braille reading and she had a braille typewriter and that's how everything was done. And apparently she had a stroke and was discovered at were collapsed and he brought her to the hospital and apparently the neurologist who saw her, when she finally came to said, you know, I've got good news and bad news. Bad news, is he had a stroke? The good news is that it was in an area.
1:34:59
A of your brain, you're not even using its your visual cortex, and I know you're blind from birth. So there shouldn't be any issue here. The problem was she lost her ability to read Braille. So what appears to have been the case and this has been confirmed in other ways by Imaging experiments in humans is that in people who are blind from very early and birth the visual cortex gets repurposed as an eccentric for processing tactile information and especially if
1:35:29
Rain to be a good Braille reader. You're actually reallocating somehow that real estate to your fingertips, you know, a part of the cortex. It should be listening to the eyes. So that's an extreme level of plasticity. But what it shows is the visual cortex is kind of a general purpose processing machine is good at spatial information, in the skin of your fingers, is just another spatial sense, and deprived a guy, the any other input, the brains seems smart enough.
1:35:59
F, if you want to put it that way to rewire itself to use that real estate for something useful in this case reading
1:36:06
Braille, incredible somewhat tragic, but incredible, at least in that case tragic, yeah, very very informative. And of course, it can go the other way to write where people can gain function in particular, modalities, like improved hearing or tactile function in the
1:36:22
absence of vision, right, huh?
1:36:26
Tell us about connectomes, we hear about genomes proteomes microbiomes, homes these days. What's a connectome? And I was invaluable. Yeah, so so
1:36:40
connectome actually now has two meanings. So I've only refer to more than one. That is my passion right now and that is really trying to understand the
1:36:49
structure of nervous
1:36:51
tissue.
1:36:53
At a scale. That's very, very fine.
1:36:57
But smaller than a millimeter
1:36:59
way smaller than a millimeter, a nanometer or less as this a thousand times smaller or it's actually, you know, a million times smaller. So really, really tiny it. On the scale of individual synapses between individual neurons or even smaller like the individual synaptic vesicles containing a little packets of neurotransmitter that again,
1:37:22
Released to law one, neuron communicate to the next. So very, very fine. But the notion here is that you're doing this section after section at very fine. Scale. So in theory, what you have is a complete description of a chunk of nervous tissue. That is so complete. That if you took enough time to identify where the boundaries are all the cells are. You could come up with a complete description of the
1:37:52
The synaptic wiring of that chunk of nervous tissue because you have a complete description for where all the cells are and where all the synapses between are all the cells are. So now you essentially have a wiring diagram of this complicated piece of tissue. So the omics part is the exhaustive - of it rather than looking at a couple of synapses that are interesting to you from do different cell types. You're looking at all, the synapses of all of the cell types, which of course is this massive Avalanche of data.
1:38:22
So in genetics you have genetics and then you've genomics which is the idea of getting the whole genome all of it. And we don't really have an analogous word for genetics, but it would be connectivity and can omics. Excuse me. I'm connect homework, honey, tommix TV and
1:38:37
connectomics, right? So it's wanting at all and of course, it's crazy ambitious. But you know, that's that's where it gets fun. You know, it's it really it's a use of electron microscopy a very high resolution microscopic Imaging.
1:38:52
System on a new scale with way more payoff in terms of understanding the connectivity of the nervous system and it's just emerging. But I really think it's going to revolutionize the field because we're going to be able to query these circuits, how they actually do it. But look at the hardware in a way, that's never been possible. Before
1:39:12
the way to describe this to people is, if you were to take a chunk of cold cooked, but cold spaghetti, right? And slice it up very thin. You're trying to
1:39:22
Act up
1:39:23
each image of each
1:39:25
slice of the edge of the spaghetti as figure out, which ropes of spaghetti, belonged to which, and have it
1:39:31
complete description of where this piece of spaghetti touches that piece of spaghetti. And there's there's something special. They are
1:39:36
obviously sauces and all the other cell types and the
1:39:39
rights. Yeah, the pesto and
1:39:41
I'll wear it all is around the spaghetti because those are the other self, the blood vessels and the glial cells. And so, what's it good for? I mean, maps are great.
1:39:52
I always think of connectomics and genomics and proteomics Etc as necessary, but not
1:39:59
sufficient. Right? Right. So I mean, in many cases what you do is you go out and prove the the function and you understand how the brain does the function, by finding neurons at seem to be firing in association with with this function that you're observing and little by little your work your way in. And now you want to know what the connectivity is, maybe the anatomy could help you but this connectomics approach or at least the cereal
1:40:22
Turn microscopy, reconstruction of neurons approach. Really is allowing us to frame questions starting from the anatomy and saying, I see a synaptic circuit here. My prediction would be that these cell types would interact in a particular way. Is that right? And then you can go and probe the physiology and you might be right or you might be wrong but more often than not it looks like the structure is pointing Us in the right direction. So it my case, I'm using this to try to understand.
1:40:52
A circuit that is involved in this image stabilization Network. We're talking about keeping things stable on the retina. And this thing will only respond at certain speeds of motion these cells in the circuit like slow-motion. They won't respond to fast motion. How does that come about? Well, I was able to probe the circuitry. I knew what my cells look like, I could see which other cells were talking to it. I could categorize all the cells that might be the players here that are involved in this mechanism.
1:41:22
Tuning thing for slow speeds. And then we said it looks like it's that cell type and we went and looked and the data bore that up. But the anatomy drove the search for the particular cell type because we could see it connected in the right place to the right cells. So it's that creates the hypothesis that lets you go query the physiology, but it can go the other way as well. So it's always the Synergy between these functional and structural approaches. It gives you the most lift but
1:41:52
You know, in many cases, the anatomy is been a little bit the weak sister in this, the structure trying to work out the diagram because we haven't had the methods now, the methods exist and this whole field is expanding very quickly because people want these circuit diagrams for the particular part of the nervous system that they're working on. If you don't know this, all types and the connections, how do you really understand how the machine works?
1:42:17
Yeah. What I love about it is we don't know what we don't know, right? And scientists. We don't ask
1:42:22
As we posed hypotheses hypotheses being, of course, some prediction that you wager your time on basically, right and it either turns out to be true or not true. But if you don't know that a particular cell type is there, you could never in any configuration of life or a career where exploration of a nervous system, wager a hypothesis because you didn't know it was there. So this allows you to say, oh there's a little interesting little
1:42:52
Connection between this cell that I know is interesting in another cell, that's a little mysterious. But interesting, I'm going to hypothesize that. It's doing, blank, blank, and blank, and go test that. And in the absence of these connectomes, you would never know that. That's L was lurking there in the shadows.
1:43:06
Right? Right. Yeah, and if you're just trying to understand how information flows through this biological machine, you want to know where things are, you know, the neurotransmitters are dumped out of the terminals of one cell and they diffuse across the space between the two.
1:43:22
All of which is kind of a liquidy space and they hit some receptors on the postsynaptic cell and they have some impact. Sometimes that's not through a regular synapse. Sometimes it's through a neuromodulator like you often talk about on your podcast that are sort of go. See dopamine. Exactly losing into the space between the cells and it may be acting at some distance far away from where it was released. Right? But if you don't know where the valise is happening, and where other things are, that might respond to that release, you're groping around in the dark.
1:43:52
I love that you are doing this and I have to share with the listeners that the first time I ever met David. And every time I've ever met with him, in person, at least at his laboratory at Brown, he was in his office door closed drawing neurons and their connections. And this is somewhat unusual for somebody who's a, you know, in doubtful Professor chairman, the department etc. For many years to be doing the Hands-On work. Typically, that's the stuff that's done.
1:44:22
Technicians are graduate students or postdocs, but I think it's fair to say that you really love looking at nervous systems and drawing the accurate, Renditions of how those nervous systems are organized and thinking about how they
1:44:36
work. Yeah. It's pure joy, for me. I mean, I'm a very visual person. My wife is an artist. We look a lot of art together, just the forms of things are gorgeous in their own, right? But to know that the form is in a sense, the function that the that
1:44:52
The architecture of the connectivity is how the computation happens in the brain at some level. Even though we don't fully understand that in most contexts gives me great. Joy because I'm working on something that's both visually beautiful, but also deeply beautiful and it's sort of a
1:45:11
Higher sort of knowledge context, you know, what is it? What is it all about? Love it.
1:45:18
Well, as a final question, I get asked very often about how people should learn about Neuroscience or how they should go about pursuing, maybe an education in Neuroscience if they're at that stage of their life, or that's appropriate for their current trajectory. Do you have any advice to young people old people and anything in between about how to learn about the nervous system more maybe?
1:45:41
A
1:45:41
more formal way. I mean, obviously we have our podcast. There are other sources of Neuroscience information out there. But for the young person who thinks they want to understand the brain, they want to learn about the brain. What should we tell them?
1:45:55
Well, that's a great question and there's so many sources out there. It's almost a question of, you know, how do you deal with this Avalanche of information out there? And I think our podcast is a great way for people to learn more about the nervous system in an accessible way, but there's so much stuff out there and it's not just that, I mean, the
1:46:11
Resources are becoming more and more available for average. Folks to participate in Neuroscience research on some level. There's this famous iy project of
1:46:21
Sebastian about
1:46:22
eyewire. Yeah, so that's connectomics. And that's just a situation where a very clever scientist realized that the the physical work of doing all this reconstruction of neurons from these electron micrographs. There's a lot of time involved many, many person hours.
1:46:41
Have to go into that to come up with the map that you want of where the cells are. And he was very clever about setting up a context in which he could crowdsource this, and people who are interested in getting a little experience looking at nervous tissue in participating. In a research project, could learn how to do this and do a little bit and their living room from their living room, their language will put
1:47:02
a link to I wire that's a. It also is a great bridge between what we were just talking about connectomics and actually participating in research, write, and you don't need a graduate mentor.
1:47:11
Or anything like that, right?
1:47:12
I so, the more of this is coming and I'm actually interested in building more of this, so that people who are interested want to participate at some level, don't necessarily have the time or resources to get involved in laboratory, research can can get exposed to it, and participate and actually contribute. So, I think that's, you know, one, one thing. I mean, just asking questions of the people around you, who know a little bit more and have them point you in the right direction.
1:47:41
A book, you might like to read, there's lots of great popular books out there that are accessible, that will give you some more sense of the full range of what's out there in the neurosciences and how we can put some
1:47:52
links to a few of those that we like, right? I'm basic Neuroscience, right? Good friend dick. Naslund the late Richard people call him dick. Dick. Maslin had a good book. I forget the title at the moment. It's sitting behind me somewhere over there on the Shelf, but about vision and how nervous systems work out. A pretty accessible.
1:48:11
Bill book for the general
1:48:12
public. Right? Right. So, you know that and you know, there's so many sources out there. I mean, Wikipedia is a great way. If you had a particular question about visual function, I would say by all means, you know, he had to wikipedians and get the first look and follow the references from there, or go to your library. Or, you know, there's so many ways to get into it. It's such an exciting field. Now, there's so many, I mean, any particular realm that special to you your experience your you know, your strengths, your passions.
1:48:41
Our there's there's a field of Neuroscience devoted to that. You've got. If you know, somebody who's got a neurological problem, or a psychiatric problem. There's a branch of Neuroscience that is devoted to trying to understand that and to solve these kinds of problems down the line. So feel the feel the buzz. It's an exciting time to get involved.
1:49:03
Great. Those are great resources that people can access from anywhere zero cost as you need an internet connection, but aside from that will put the links to some
1:49:11
And I'm remembering dicks book is called, we know it when we see it. One of my heroes. Yeah, wonderful colleague. Who unfortunately, we lost a few years ago. But listen, David, this has been wonderful been a blast. We really appreciate you taking the time to do this, as people probably realize by. Now, you're an incredible wealth of knowledge about the entire nervous system. Today. We just hit the top Contour of a number of different areas to give a flavor of the different ways that the nervous system works and is organized and
1:49:41
How that's put together how these areas are talking to one another. What I love about you is that you're such an incredible educator, and I've taught so many students over the years, but also for me personally as friends, but also any time that I want to touch into the beauty of the nervous system. I rarely lose touch with it, but anytime I want to touch into it and start thinking about new problems in ways that the nervous system is doing things that I hadn't thought about I call you. So I please forgive me for the calls.
1:50:11
Past present and future, unless you change a number and even if you do, I'll be calling,
1:50:16
it's been such a blast Andy, you know, this has been a great session and it's always fun talking to. You is always
1:50:23
gets my brain
1:50:24
racing. So thank you. Thank you.
1:50:28
Thank you for joining me today for my discussion with dr. David Burson, by now. You should have a much clearer understanding of how the brain is organized, and how it works to do all the incredible things that it does, if you're in,
1:50:41
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Us and we have a patreon. It's patreon.com slash Andrew huberman. There, you can support us at any level that you like while today's discussion did not focus on supplements, many previous podcast episodes include discussions about supplements and while supplements aren't necessary for everybody many people derive benefit from them for things like sleep or Focus or Anxiety Relief. And so on one issue with the supplement industry. However, is that often times the quality will really vary across Brands. That's why we partner.
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1:52:41
Thank you for your interest in science.
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