The electrical-grid analogy for the conscious brain

14:25studies and things like that. The N is like very low. Single digits is you're already getting a lot because human I mean you're like experimenting on human beings, right? There's tons of ethical concerns. There's not a lot of like, you know, people who are willing to do this. And so even though the data is low, the fact that it worked means that there's something going on. So that sort of rejuvenated this research and in 2010 that same author, Nicholas Schiff, he came up with something called the meso circuit hypothesis. Okay? Effectively, what he's saying is the following. The consciousness relies on a network of interactions between the cortex and the central thalamus. And that interaction is regulated by a

15:07part of the brain called the basal ganglia. We're going to focus on effectively three regions of the brain. Okay? And I'm going to use an analogy of an electrical grid. Okay? A city's electrical grid. So the cerebral cortex, this is the part that's on the outside, the most sort of recently developed in humans. This is the when we think about the brain and all the wrinkles, that's the cerebral cortex that we're seeing on the outside. And that outer layer, it's responsible for higher thought, memory, sensory processing. And in this analogy of a city's electrical grid, this is your network of homes, podcast studios, you

15:47know, businesses that consume the electricity, right? Now, the central thalamus is the deep brain relay station. That's the part that's sort of on the right over there in the pink. Just just above the brain stem? >> Just above the brain stem, okay? So, that's getting input from the cortex and it's also giving input to the cortex, okay? So, it's a two-way street. It's kind of like the primary power substation. It's pumping excitatory input to the cortex, but it's also getting excitatory input back from the cortex. So, it's relaying a bunch of electricity one way or the other. So, the ex- the when the example's being if you have solar on your house, you're sending >> Yeah, very very good. Yes. Yes. That's very good. Yes. Yes. Yes. No, that's exactly

16:29right. And this feedback loop kind of helps both run. Right. Okay? In some sense. And then finally, there's the basal ganglia and that's the striatum and the globus pallidus. That is a kind of regulatory system and it's kind of like a voltage controller that manages the flow of power in this entire network. So, when it's summer when it gets hot, they have to decide where to send energy where to not send energy in order to not overflow. Like there has to be there's somebody decides, "Okay, we're going to shut down this neighborhood because we need to power the nuclear plant." >> Yeah, yeah, it's the yeah, exactly. As a crude analogy, it's kind of routing signals and it's controlling both the power stations and the homes to make sure like nothing's Yeah, there's

17:11balance and nothing's nothing's going out of the way. Okay, so, that's how sort of the consciousness mechanism is working in healthy patients. What happens during a coma? Well, according to the meso circuit hypothesis, here's what happens. When there's widespread brain injury, Yeah. right? Like from a traumatic brain injury or a stroke, so a bunch of neurons die because they don't get oxygen and things like that. Um your power lines are going to be down on the cortex, right? So, you're going to get localized areas of power cuts, >> Yep. like we do in a um LA sometimes when somebody steals our copper >> Yes. >> from underground, >> Yes. >> okay? Yes. >> But um anyways, the the the cortex is now going to reduce its excitatory input to the thalamus. That connection is broken, as you can see on the left.

17:51>> Yes. >> The thalamus and the cortex, that's now a dotted line >> Yeah, yeah. >> instead of on the left, it's a solid line. >> Yep. Okay. The other thing is um there are these special neurons in the striatum um called medium spiny neurons, and what they do, they're super prone to metabolic stress death, meaning you like remove a little bit of oxygen and they'll they'll just die, okay? They're not very resilient. >> Mhm. They're very finicky. And if those guys die, then the striatum is going to not inhibit the part that is inhibiting the thalamus. >> Okay. >> negative now. >> Okay. Okay? So, because of that, so what it's what it's doing is usually the striatum is like

18:33inhibiting the part that is putting brakes on the thalamus, >> Mhm. okay? But now that that brake is gone, the the first brake is gone, right? The second negative is going to go even more negative, >> okay? And it's going to start inhibiting the thalamus even more. That's why that red line just got fatter, >> That makes sense. right? So, the thalamus is one not getting any input from the cortex because the power lines are down, >> Yes. and second, the part that was putting brakes on the thalamus has now gone hyperactive and putting even more brakes on the thalamus. So, the thalamus is getting inhibited. It's getting shut down more and more >> Mhm. in a coma Mhm. >> because of these very tiny defects that have happened in exactly the wrong areas. >> Yeah, the so this is this is very

19:14interesting and and what we're sort of saying here is the the the traumatic brain injuries are disrupting the normal flow >> Mhm. between these three fundamental component parts. >> Yeah. Um the cortex, which is like the end destination, the Holmes example, the thalamus, which is sort of sending and receiving, >> Mhm. and then the striatum and pallidum that are kind of controlling the amount of what is or is not being sent and where it is or is not being sent. >> Exactly. And and and it's exactly at the right part where the thalamus, which is the relay station, is just getting signal to shut down. >> yeah, yeah. Okay? And when that shuts down, now this entire circuit of consciousness is getting shut down.

19:55>> It's it's almost like the fail-safe system that happens at a substation if there's some overload, just gets stuck in the locked position. Exactly. Exactly. And there's and there's some evidence that this meso circuit hypothesis is probably correct. >> Okay. There's certain stimulant drugs, for examp- for example, um amantadine, which enhances the inhibition to that brake, like the part that's inhibiting the thalamus. Amantadine inhibits that part, so it's no longer going to inhibit the thalamus. Kind of works and it kind of wakes up patients. It's turning it to overclock mode. >> Yes. Yes, exactly. So so there there's some mechanism where these drugs are kind of working with the meso circuit hypothesis. But at

20:35the end of the day, still a hypothesis because it's not very granular, right? It's just like, oh, giant brain area. You know, like there's but the giant brain area has millions of neurons >> Right. that are all different types. What type? Right. >> What type is doing what, right? Um and also, you can't really test it directly because the bottleneck is standard animal models are really bad at mimicking um human comas. >> Mhm. This prolonged unconsciousness. And that just has to do with the fact that animal models, like rodents, the brain is structurally a very different thing, right? Even though it's still a mammal, one of the things that we think happens during traumatic brain injury that causes this kind of coma is the idea of

21:18a diffuse axonal injury. Here's the idea. You've got the cerebral cortex on the outside. There There's gray matter, which is like sort of the cell bodies, and then there's white matter. You might have heard of that, gray matter and white matter. Gray matter is kind of like the cell bodies, the white matter is the axons. These are these like cables, like you know the high-voltage cables that come from, you know, Hoover Dam to LA. The axons are kind of like that. They're the high-voltage cables. Now, if we go to a photo 14, what you'll see is the white matter is kind of in the middle, and it's like connecting these areas of gray matter. But, if you have a traumatic brain injury, let's say you got in a car crash or like boom, like your brain had severe G-forces on it.

22:00Those axons, which are the cables, those are going to rupture first, right? Now, with a small rodent, the brain is not big enough to feel that kind of G-force stress, right? Ours is big enough where like and we're like doing crazy things as humans, where like we're driving around at 70 miles an hour. We're like we're we're now subject to G-forces if something goes wrong, right? And so the our brain is just not evolved when we were hunter-gatherers in Africa like evolving, the evolution didn't think, "Hey, I should probably make this brain um you know, withstand getting hit by another 350-lb man in an NFL game.

22:41>> Yeah, exactly. Okay? So So there's a mismatch between like what the brain is designed, like the the the environment that the brain is designed in, and then what the brain was capable of creating, right? Which is like which is like human beings in cars and all this other crazy stuff, skiing and then hitting a tree and things like that, right? So >> and we simply can't test in rodent models, okay? >> And this is something we talked about on recent previous episode two about just, you know, there are a lot of opportunities to use animal models, which the purpose of which yes, for folks who