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All right. Um Hello and thank you for very much for joining this evening on Zoom. This time, we er realized we couldn't use metal, but thank you as we continued our exploration of neuroanatomy working out from the spinal cord brain stem and now our subcortical structures. Last week, we had a talk on the pituitary gland and this week it's my pleasure to introduce doctor Michael Shu who will be covering the basal ganglia. Michael Shur is an attending physician, a neurosurgeon and associate professor. He's also co founder and chief, chief medical officer at Omniscent Neurotechnology. And I'm excited to hand over to him now. Yes. So I'm gonna try to, I'm gonna give a talk. It's a variation on the talk that you guys were probably expecting. But what we're gonna answer is a simple question, right? If you go to the anatomy of the basal ganglia, it basically is a fairly simple collection of deep structures. Now, on the cytoarchitecture standpoint, when you look at the, the stratum, the caudate potamon, these other structures, there's really, really deep dense cytoarchitecture. But the key thing about it is that the basal ganglia is fairly repetitive. So if I look along the, the axis of the caudate nucleus, for example, it basically is uh is the same circuit over and over and over and over and over again. Now, the question is, it does a lot of diverse things and it's part of a lot of different processes. Most importantly, it, it's part of what most famously, it's part of motor regulation. And what that basically means is, you know, it, it do, it doesn't necessarily drive direct motion. You don't make a decision to move from the basal ganglia from what we know. But what it's doing often is changing the gains of motor areas to guarantee fluid and smooth movement. It's also inhibiting movement when you're not uh when you're at basal rest. But the interesting thing is like when we were, we go to medical school when I went to medical school, which is now 25 years ago and learned this, um We basically just were taught, hey, there's this loop, the direct and indirect pathway and they're part of motor regulation. And I'll take a step back just to make sure that we, that I'm not talking over people's heads since I did skip to the advanced stuff. Um And in part is I had a really good slide deck on this and I don't have it anymore from what I can tell and I apologize about this, but let's just look at the, on the fly, the direct and indirect pathways of the, of the brain. So most of us who have attended medical school at some point in neuro neuroanatomy, neuroscience, et cetera have learned a loop that looks like that. OK. Think about this as the canonical loop. So what does that, what does that mean? There's, we can't, we can't, II don't know if this. I think this might be an issue on our side. We can't see the loop. Oh OK. OK. I see. What? Yeah. Let me um can you see you? Uh maybe I did. Uh Are you, you still, you still see my slides? Yeah. Slide suicides. OK. Let me share full screen here cause that might be the problem. All right. There we go. OK. So it would be a month. Yeah. Yeah. II normally try to not share just a tab. OK. So if you look over here on the right, right. And again, it only took me 10 seconds to find this, right. Think about this as the canonical loop. OK. So what the basal ganglia is doing is it gets in from, it's a cortical basal thalamic cortical loop. OK. Now, that underlies a much more complicated anatomy. But remember that this loop is repeated in different forms in different parts of, for different systems, we know the motor system the best because it's where we put electrodes for DBS for, for, for um Parkinson's disease. And it's also where we do medications, we aim it at specific areas of the basal ganglia that ha have, for example, dopamine circuits. But if we start looking at the at if we understand this loop, understand that the cognitive and emotional parts of this of this system are just re reusing different aspects of the same loop. So the loop goes soter like this, there's an area of cortex that sends a signal down to the stratum. The stratum is the Potamon and the, and the uh Globus Pallidus, the or sorry. Yeah, Potamon and Globus Pallidus, caudate, et cetera, right? The external portion, the internal portion of it is the pallidum. And what, what's happening when the information comes into the stratum is it's sent along two pathways. One goes to the to some deeper lower structures like the S TN, the other goes to the GP the globus pus externa. And then ultimately, there's a comparison. There's a comparison being done at the Globus Pallidus interna which communicates to some nucleus of the thalamus and then it sends a signal up to the cortex. And in the case of motor, this signal to the cortex is inhibitory. OK. So you have this loop. No, the issue is II is why do you need to do this? OK. Well, the answer to some degree is people don't know. But what we do know is that what happens when you miss parts of this circuit and ultimately, you either have abnormal spontaneous movements or you have the inability to make movements or you have movements that behave not smoothly. And so, ultimately, similar to the cerebellum, there's a comparison being performed between 11 aspect of the circuit and another aspect of the circuit. Um And ultimately, that is going to, you know, compare, you know two sets of impulses and give a final feedback ex outside loop. In this case, that comparison is done with the GPI, it's gonna disinhibit the thalamus. OK. So when you inhibit the GPI, you in you, you inhibit the thalamus which disinhibit the cortex and causes something to happen at the cortical level. Usually this involves modulating what the cortex is doing. OK. Now, a lot of reasons why you might wanna do this part of it is that ultimately number one is that you want to coordinate movements and prevent certain, you know, extreme deviations. OK. So that's one theory on that. So in the motor system, this would be we don't want jerky movements that injure your joints or make your joints move in certain different directions. So there's a benefit to that. Now, it's important to understand this with motor because when you get the cognition or reward, this gets a lot harder to understand. So you need to use analogies. But if you think about it, the other thing it's doing is it's allowing you to tone the gain up and down based on other inputs in the motor system. It's less clear why that's beneficial. Why do you need the S TN and the circuit in the reward system, it's absolutely clear why we have this. But the bottom line is that ultimately what these, these are doing is it's balancing things out. It's preventing. First thing is preventing a, you know, extreme deviation from uh uh uh you know, normal functions, right? You know, it's homeostasis. Another reason why that's helpful to have this kind of loop is that one of the big challenges of the mammalian brain that didn't really happen in, you know, lower animals, it wasn't as much of an issue, but they have these structures. It's, it's the the necessity to coordinate areas that are very far apart from each other, the bigger your brain gets, the harder it is to do that and uh the benefits of higher cognition, you know, what, what is hiro cognition doing it's coordinating areas of the brain that have are doing totally different things to have AAA thought that involves emotional input, cognitive input, abstract thinking, three dimensional space, touch, sound smells and have them all be a single event in your head. OK. That's hard to do. And so you need systems that can work across different brain regions and coordinate them. And so ultimately, whenever the basal ganglia principle function and why it's so important it comes down to being able to coordinate and integrate lots of different input pulses to lead to a single event in a domain, no, what's why I went through that is that if we wanna understand everything else it's doing the loops are different. So the, if you look on here, you have AAA frontal loop, which is a cognitive loop and that's gonna use different structures. So it uses more of the caudate, less of the putamen. It uses um for its deeper structures. The ventral striatum, it uses the medial dorsal nucleus and not the ventrolateral as in in the motor system. But ultimately, it's basically integrating different areas and the circuit is relatively preserved. So while we talk about the, you know, ventral striatum and ventral pallidum as being these distinct structures, they're really very similar. And ultimately, where the embryologic origin of this is we'll talk about embryology and why the brain functions the way it does it's radial. So to show you what I mean by that, let me pull up a, a slide for.