Welcome to this tutorial about the Modulation of Movement by the Basal Ganglia. Our core concepts, as this concept relates to the field of neuroscience. Again, confronts the complexity of the human brain and in particular, the complexity. Of the motor system, and how voluntary movements are initiated through circuitry of the Basal Ganglia. We'll be talking about circuits that are the product of our genetic instructions and most of the time those instructions are read out correctly and the proper circuits are constructed. but sometimes there are genetic errors that can lead to dysfunction and disability. And, we'll talk about some, dysfunctions of the circuitry of the Basal Ganglia. That, at least, in some cases, seem to have a genetic component to it. But thankfully, the circuitry of the brain can change. The brain is plastic and our life experiences can change the structure and function of the nervous system. So, I hope as we move on in our studies of the motor system you'll see powerful evidence that, that is in fact the case. So this tutorial on the Basal Ganglia is going to be broken into several parts. And I'd like to begin with part one, a discussion of the circuitry of the Basal Ganglia from an anatomical perspective. And then we'll move on, in part two, and talk about function, and then dysfunction. So my learning objective for you in part one is that I want you to be able to master the anatomy of the Basal Ganglia, basically. I want you to to identify the major components of the Basal Ganglia including parts of what we'll call a dorsal motor stream and a ventral limbic stream. This word stream, as you'll see, is a word that we sometimes use in neuroanatomy to talk about a pathway or a circuit that processes information from one station to another. All right. So I'll show you again this illustration that we've seen before. And use it as a way of helping you appreciate how the Basal Ganglia fits in to our broader motor system. So you all know now that the final common path for the expression of voluntary movement are the lower motor neurons. And these exist in the spinal cord and the ventral horn, and in our cranial nerve nuclei of the brain stem. These lower motor neurons, are motivated by upper motor neurons. And these upper motors, neurons, exist in this, in the motor cortex, in the posterior frontal lobe. And in brain stem centers, such as the reticular formation, and the vestibular nuclei. So, these descending systems of upper motor neurons are responsible for motivating the output of the lower motor neurons. They provide the go signal, if you will, that actually expresses the movement. They don't micromanage the movement. That's worked out at the level of our lower motor circuits in the spinal cord and brainstem, but rather they provide the command signals for the execution of that behavior. Now notice how the Basal Ganglia fits in to all of this. The Basal Ganglia are off here to the side. The Basal Ganglia interact not directly with lower motor neurons, but they interact with upper motor neurons. So when it comes to identifying the anatomical pathways that are involved in Basal Ganglia function. We're going to be concerned with understanding how does the Basal Ganglia get information about the intention for movement. And then, how does the output of the Basal Ganglia influence the function of these upper motor neurons? To illustrate the function of the Basal Ganglia, I want to bring up a component of our Sylvius anatomical software, to illustrate what does it take to actually execute a movement. So what I've done is I've gone into Sylvius and I've opened up our pathways unit and selected from our animated pathways the corticospinal tract. And what we've created here is obvious is just say very quick demonstration of what it takes to send a signal from our upper motor neurons in the pre-central gyrus to the spinal cord, for the execution of a voluntary movement. So, this involves the signaling of these upper motor neurons,[SOUND] the propagation of an action potential and a synaptic connection, and the eventual horn at the spinal chord, with lower motor neurons that then go on the express the behavior. Well perhaps you didn't know that synapses make noise of course synapses don't make noise. That's just a little feature that we put into Sylvius. In order to emphasize for you that there is, indeed, a synaptic connection between the axons of the upper motor neuron and the lower motor neuron. Alright, so I'll probably play this a few more times just because I sort of like the sound of that little synaptic connection. okay, so the upper motor neurons send signals down the cortical spinal tract, for the execution of the movement. I think we've enough experience now with the cerebral cortex to know that if the cerebral cortex is going to generate a signal. In this case a signal that is propagated down the cortical spinal tract, there is probably some thalamic region that is providing an important trigger signal for the processing that's happening in the cerebral cortex. And indeed that will be the case for the motor-cortex in the posterior part of the frontal lobe. There is a division of the thalamus in here, that provides input to the motor-cortex. You may remember from a previous tutorial, it's called the ventral anterior, and ventral lateral complex of the thalamus. So this thalamic region sends signals up into the motor cortex that provide an excitatory trigger for the execution of the movement. So, how do the Basal Ganglia factor in? Well, the Basal Ganglia are sitting in the deep part of the forebrain. And they provide an output to the motor thalamus, which is inhibitory. So the Basal Ganglia is really key for the thalamic trigger to be sent up to the motor cortex that ultimately leads in the execution of this behavior. Okay. So, really, the point that I'm trying to make here, is that. In order for the motor cortex to send out a command signal. It has to be triggered to do so by the thalamic input. And one way to control the output of the cortex is to regulate the thalamic input. And this is the function of the Basal Ganglia. The Basal Ganglia has inhibitory control over the motor thalamus, and that is a wonderful phenomenon, because it keeps our movements in check. It prevents us from making all kinds of movements that we might otherwise express. So this inhibitory lock on the thalamus helps us regulate the expression of voluntary movement. Well, you may, you may be wondering well how then do we move, if the basal ganglia, inhibits the thalamus. Well, the way we move is by temporarily removing that inhibition from the Basal Ganglia. And that's where the complicated circuitry comes in that links one part of the Basal Ganglia to another. So, as we begin to get deeper into this tutorial you're probably wondering well what are the Basal Ganglia? I've heard that before, I remember watching some videos from the neuroanatomy lab where I pointed out the Basal Ganglia but really, where are they? So let me tell you. The Basal Ganglia are a collection of nuclei that are found deep in the base of the fore brain. They are developed from the telencephalon, the same part of the developing nervous system that formed the cerebral cortex. Except the neurons of the Basal Ganglia didn't migrate out to the expanding outer sphere of the developing telencephalon, rather the cells that formed the Basal Ganglia stayed close to the base of the, of the ventricular system. Which is why the Basal Ganglia in the adult brain, end up being very close to the lateral ventricles. Well, these Basal Ganglia then, they are a collection of nuclei that relate to the functions of the cerebral cortex. The Basal Ganglia receive input from widespread regions of the cerebral cortex. There are then several stages of processing within the circuitry of the Basal Ganglia. And then the output of the Basal Ganglia doesn't go directly back to cortex, but rather it goes to the thalamus. And then the thalamus, in turn, is what modulates the output of the cerebral cortex. In this case, the, delivery of a command signal down the cortical spinal tract. Now there are other pathways to the Basal Ganglia that send their output to targets in the brainstem, and I'll mention them in just a moment. But for the most part, I want you to understand that the major function of the Basal Ganglia is to modulate thalamo-cortical activity. And what I mean is, the way the thalamus interacts with the cortex. In the case of the expression of voluntary movement, this is critical. Because the thalamus provides a trigger signal that leads typically to the expression of movement as the motor cortical circuits then send signals down the cortical spinal pathway and cortical bulbar pathway. So to control the expression of movement it makes great sense to want to control the motor division of the thalamus and that's what the Basal Ganglia do. So they play an important role in the initiation of voluntary movement, the initiation of behavior. And the suppression of behavior. That is the suppression of movements that are inappropriate, or unwanted. So keep these concepts in mind as we work through this tutorial. The Basal Ganglia are involved in the initiation of movement and the suppression of movement and we'll look at the details of how that happens. Now, we've encountered this concept of parallel pathways numerous places so far in our studies our sensory motor systems so here's yet another example of parallel pathways through the brain. In the Basal Ganglia, we tend to call these processing streams. And what we really mean are a set of parallel pathways. And neuroanatomists have recognized actually quite a large number of processing streams that run through the Basal Ganglia. So we don't need to worry about, all of the various ways that anatomists and physiologists have recognized parallel processing streams. rather we can focus on what's common about them, and then recognize some key streams that we do want to focus on today. So what's common about them? Well for each of these processing streams, there's input from the cerebral cortex, to the Basal Ganglia. So the Basal Ganglia occupy these two middle layers in this schematic drawing. There's a division of the basal ganglia that we call striatum for anatomical reasons. That's what's shown here in this orange color. And then there is a division called the pallidum. Also, for anatomical reasons, that's show in this purple color. So, the striatum projects to the pallidum. That's fundamentally the intrinsic circuitry of the Basal Ganglia that we want to come to understand. And then the output from the Basal Ganglia. Is provided by the palladum, and again that output doesn't go directly back to the cerebral cortex rather it goes back to some division of the thalamus. So for example our motor processing stream sometimes we call these loops, because they begin in the cortex and they ultimately come back to impact activity in the cortex. So our loop for body movement is derived from cortical inputs that converge from a widespread region of the cerebral cortex, into the basal ganglia. So here's the cortical input coming into a part of the Basal Ganglia that we call the putamen. And that division part of the striatum sends signals to the globus pallidus. Another part of the Basal Ganglia that's representative of this layer of tissue and this processing that we call a pallidus. The globus pallidus in turn turns to the motor thalamus. This ventral interior ventral lateral complex. And the motor thalamus finally sends signals into the motor cortex that can either trigger the initiation of movement or, depending upon the physiology of the Basal Ganglia, suppress unwanted movements. So this same kind of theme of cortex to striatum Striatum to palladum, the palladum to thalamus and then thalamus back up to cortex is repeated in each of these processing streams. And we have something of a simplified view in front of us where we simply recognize that there are motor loops, or motor processing streams, and non-motor loops. The motor loops concern movements of, of the body and there's seem to be a dedicating processing stream for movements of the eyes. And on the non motor side we can recognize a loop that is concerned with the functions of the prefrontal cortex, we've talked about in a few tutorials. This plays an executive functioning role in cognition. And they are processing strains that seem to involve the limbic parts of the forebrain. And these are brain regions that are involved in the experience and expression of emotion. So the loops are primarily defined by the anatomical inputs from the cerebral cortex. And the kinds of functions that are carried out by those cortical areas that receive the feedback that comes from the thalamus after being modulated by the Basal Ganglia. So again, I, I would encourage you by saying don't worry about the complexity of this figure. Just understand the point that there are parallel processing streams that are concerned with the initiation and suppression of movement in one domain of physical action or mental action or emotional action or another. Well, one important means by which we've come to understand the functions of the Basal Ganglia in the normal human brain has been based on studies of individuals that have had disease or disorder in the circuitry of theBasal Ganglia. So, by understanding a neurobiological framework of disease in the Basal Ganglia. We've gained considerable insight into the normal functions of these parts of brain. So we will take some time in this tutorial, to consider two major classes of movement disorder that relate to Basal Ganglia function. As you'll come to see, we will recognize a category of movement disorder where the problem is not enough movement. We call these Hypokinetic movement disorders. And the chief representative in this category would be Parkisonsim. And we'll come to understand Parkisonsim as primarily a failure to initiate voluntary movement. Of course, there is much more to this clinical picture than just this. But for our purposes, focusing on the role of the Basal Ganglia. Parkinsonism is a failure of initiation. On the other end of the spectrum. There are Hyperkinetic movement disorders. So these are disorders that are represented by Huntington's disease and by other kinds of disorders that result in the expression of unwanted movement. So we can think of these disorders in terms of the Basal ganglia, as a failure to suppress unwanted movement. Now, what's been very exciting in recent years, is the possibility that this concept of hypokinetic disorder and hyperkinetic disorder, might also apply to some of these non motor loops that are running through the Basal Ganglia. Perhaps various affective and cognitive disorders reflect either a failure to initiate a particular behavioral program or a failure to suppress an inappropriate behavioral program. So this is an exciting hypothesis that is getting much attention and research by cognitive neuroscientists and psychiatrists.
