Term
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Definition
plans,
initiates, directs—voluntary
movements |
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Term
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Definition
sensorimotor
coordination of ongoing
movement—fine tuning |
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Term
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Definition
| gating/timing and proper initiation of movement, changing direction of movement |
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Term
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Definition
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Term
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Definition
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Term
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Definition
| Now, all of the things that are in the diagram are there, of course, because nothing in the brain is working in isolation. Everything is connected to everything else. So you have to have the thalamus. We have the brainstem and the motor nuclei, which are embedded in the brain stem. And all of these may give rise to descending pathways, such as the rubrospinal, tectospinal, the corticospinal, and so on. |
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Term
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Definition
| Cortex, Cerebellum, and Basal Ganglia |
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Term
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Definition
So we begin with the motor cortex. So what we have here is a dorsal view of the human brain. And the blue arrow is pointing to the primary motor cortex area four. It's located in the precentral gyrus, so that's right before reaching the central sulcus. So you have this is the front, the front of the brain. The eyes would be around here. And then this is the back. The cerebellum would be sitting here. You don't see the cerebellum.
And this is the superior frontal gyrus, medial frontal gyrus, inferior frontal gyrus. And here we already mentioned an important area called Broca's. Broca's area, that is responsible for Broca's aphasia if it has a lesion. So motor cortex is isocortex is neocortex, therefore, is a six layer type of cortex that we also mention already. |
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Term
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Definition
Remember, in the motor cortex, and in the somatosensory cortex, we have maps of our bodies. And those maps are called homunculi, homunculus in singular. So here you have the somatosensory homunculus. And in here, you have, on the right-hand side, the motor homunculus. The reason the map looks distorted is because we need different amounts of real estate. We have different amounts of neurons to take care of the functions that are done by these different body structures.
A lot of cells are dedicated to the hand and to the face. And we don't do many motor things, let's say, with the back or with our backs or our shoulders. So you don't need that many cells to be involved in movement. So these are, again, maps of the body. |
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Term
| Corticobulbar (C-Nuclear) Pathways |
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Definition
Descending control and
modulation of sensory and
motor nuclei of cranial nerves
• First order widespread areas of
cerebral cortex
• Second order in pontine and
medullary reticular formation
and nuclei of cranial nerves
• Crossed and uncrossed for
most
• Only crossed for lower face
(VII), mostly crossed for XII
• Only uncrossed for XI |
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Term
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Definition
| Now, from the motor cortex, we have commands, motor commands, going both to the spinal cord, as well as to different places in the brain stem. So this, which are stopping at the brain stem, we call corticobulbar or corticonuclear. And remember, the reason for this is that we have a whole lot of different motor cranial nerve nuclei that are also receiving information from the motor cortex. |
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Term
| Lateral and Anterior Corticospinal Pathways |
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Definition
First order neuron: layer
V of motor cortex
• Second order: ventral
horn layers VII, VIII, and
IX
• Third order: ventral horn
layer IX
• Lateral crosses in lower
medulla-pyramidal
decuss
• Anterior crosses at
spinal segmental levels |
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Term
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Definition
So these fibers, most of them are usually to both sides. So they are ipsilateral and contralateral. Now let's, just for a second, take a look at the important pyramidal pathways and what we call lateral and anterior corticospinal pathways. So on the left here, you have a pathway that is starting with a motor neuron in the primary motor cortex. It's sending the axon down to give a motor command to some motor neuron, which is down here in the spinal cord.
And what you'll notice is descending [? behind ?] the posterior limb of the internal capsule at this level, which is mid-brain, is traveling in the basis of the mid-brain. This little hole that you have in here is the aqueduct. I'm telling you this for reference. So this is the tectum. The middle is the tagmentum. And this is the basis. The space in here is called the interpeduncular fossa in between the two peduncles. So these are the cerebral peduncles.
The fiber is traveling in the cerebral peduncle and now is positioned towards the middle. And now it has formed the pyramids because of the shape. So this is a pyramidal tract. And that pyramidal tract is going to-- a lot of the fibers are going to cross to the other side. This is the pyramidal decussation. To decussate means to cross. So now the fibers have crossed to the other side and have positioned themselves in this lateral part here. So it is there a lateral corticospinal. Corticospinal, from the cortex to the spine. The name is telling you the direction.
So again, it's now going to give a command to cells which are motor cells down here that will go and be the effectors, the ones that are going to go and communicate with the muscle. About 85% of the fibers cross to the other side. About 15% of the fibers do not cross, at least not at the beginning. But the pathway is exactly the same. They go down via the posterior limb of the internal capsule. They are here in the peduncle, the basis. They are in the pyramids. And then they continue going down. And they stay ipsilateral.
At the end, when they reach their target location at different levels in the spinal cord, they usually send a collateral to the other side. So they communicate with the other side of the body. This lateral corticospinal pathway is called lateral because of the position of the fibers when they travel in the spinal cord in the white matter. And this anterior corticospinal pathway is called anterior because of the position here anterior, in the anterior spinal cord.
85% of the fibers, versus about 15% of the fibers. This is the reason why we say that the left side of the brain controls the motor control lateral side of the body because 85% of the fibers have gone to the other side. And so if your patient has, for instance, and infarct on the left side, the paralysis will appear on the right side of the body. |
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Term
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Definition
| This information is going to be repeated. I'm going to show you the exactly same thing, different flavors again, so that maybe it will be easier to understand. Here I haven't changed anything. It's exactly the same thing. The same pathways are going down. And in here you have a depiction of 85% of the fibers moving to the other side, 15% of the fibers going down ipsilateral. The ones which stay ipsilateral constitute the anterior corticospinal tract and the ones that go to the other side the lateral corticospinal tract. |
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Term
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Definition
Then again, the same information now showing you different details. [INAUDIBLE], for instance, on the left-hand side at the bottom, that eventually the idea is that the lower motor neuron that received the command from the motor cortex is going to communicate with the muscle-- could be a gland, also-- and it's going to have an effect. So this is the effected neuron. Now something's going to move. Something's going to happen.
Here is, again, the same thing, including some areas that have to do with the homunculus. So this is important for diagnosis. When you have and infarct, for instance, in this area, you should expect lesions that are affecting that part of the body that corresponds to that area in the homunculus. This brings us to the end of this first part about voluntary motor control. |
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Term
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Definition
This is cerebellum. This is not cerebellum. This is the thalamus, OK? It's just there for orientation as well. But these are the different parts of the cerebellum. And this is the posterior part. This is anterior, of course. So here you have the vermis, the anterior lobe and so on. The folia-- Latin for the foldings, the different layers that you can see.
And in here, the cerebellum has been cut. And what you look at is the floor of the four ventricles. This couple of little bumps that you see in there constitute the facial colliculus. And here you have the superior cerebellar peduncle, the middle cerebellar peduncle, and the inferior cerebellar peduncle that have been cut again, to remove the cerebellum.
So this is the cerebellum when you look at it from underneath. So this is a ventral view. This is the posterior lateral fissure in here. This in purple and a little bit red and blue correspond to the connections of these different peduncles that were cut in the middle, the superior and inferior, OK?
So that's as much as I want to tell you about anatomy |
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Term
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Definition
Let me go into the circuitry. If you needed to remember one single thing about circuitry, remember that all of these fibers that are coming into the cerebellum are excitatory, and they are going to the cerebellar cortex.
And then something happens in terms of computation. And these computations go and inform the deep cerebellar nuclei. And then the output goes-- again, it's excitatory. So what you have is excitatory then inhibitory to the deep cerebellar nuclei, and then excitatory as well. |
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Term
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Definition
If you want to look at more details in terms of the connections and the different types of cells and so on, this is a good example. And so here you have climbing fibers, inputs from the olive, and mossy fibers inputs. And you have important Golgi cells, and you have Purkinje cells. You have many different types of cells in the cerebellum, the basket cells and so on, granule.
And all of them are going to be doing computations. Some of them are excitatory. Here you have it color-coded, excitatory versus inhibitory. |
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Term
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Definition
But remember, the important thing here is that at the end, the output-- and most of the outputs are via the superior cerebellar peduncle-- are going to be excitation again. So innervation is internal.
cerebellum cells and fibers |
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Term
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Definition
OK, now for the circuitry that has to do with the motor function directly with what we are talking about, here you have the different deep nuclei. This is fastigial, globose, emboliform, and dentate. And I am going medial to lateral. One thing that I want you to notice-- I'm going to present the same thing several times-- just different deep nuclei which are involved.
And we begin with this one. The more lateral you go-- so if you begin with the dentate, the inputs are going to be contralateral. The outputs are going to be contralateral. If you go more to the middle, to the center, then it will be both ipsilateral and contralateral. The emboliform and globose put together are called interposed And in humans, it's better to call it interposed. It's usually difficult to separate into components, except of course if you happen to do research, and then you are very familiar with the composition.
So here you have the dentate sending inputs to areas of the thalamus, and then from the thalamus, to the motor cortex |
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Term
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Definition
If we move to the next one, we go to the middle part here, to interposed nucleus. So remember, interpose, we have put two of them together. Now they are still sending information to the thalamus, thalamus to the cortex.
And now we are going to complicate things a little bit. We are showing also the information coming back, OK? This is information now coming from the motor cortex. And it's going via the pyramidal decussation So this is descending in the posterior limb of the internal capsule. This is part of the pyramidal track. Therefore it's closing here at the pyramidal deccusation. And it's going to be part of the lateral corticospinal tract.
At the same time, they are showing here the rubrospinal tract. Rubrospinal is initiated in the red nucleus, and it closes right away, and it goes down as well. So things get complicated, of course. And we cannot show every single pathway at the same time, because there are too many of them, and nothing will make sense. So that's why we go sort of one by one. |
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Term
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Definition
When we go to the middle here to nuclei, to the fastigial nucleus, and I told you it's both ipsilateral and contralateral, here you have contralateral and ipsilateral again. Going to the thalamus and collecting information, sending to the motor cortex. Now remember, it is not here-- but remember from the motor cortex, it's going to go down. And it's going to cross over, and it's going to be part of the pyramid tract, the lateral corticospinal or the anterior corticospinal if it happens not to cross.
So every time it's possible to add and add more details-- here you have another detail, the flocculonodular lobe and inferior vermis sending information to the vestibular nucleus. Remember, vestibular nuclei in the brain stem are not really part of the cerebellum. They have something different. But keep in mind, the vestibular system is always in both.
The vestibular system has to receive information about all types of movement, reflexes, involuntary movements. Because the vestibular system has to make quick adjustments to everything that is happening, that is changing your position in space, and the center of gravity and so on. Otherwise, whenever we move a little bit, we will not balance, and lose balance and fall. |
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Term
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Definition
| Now in the cerebellum there is also a homunculus. And this is what we call the cerebellar homunculus. And here very, very [INAUDIBLE] homunculus color-coded the neck and the hand in yellow. So hand areas are here. Most of what is known in humans that has to with the cerebellar homunculus-- for that matter, also with the motor and somatosensory-- have come mostly from lesion studies that happen naturally, of course. Because we cannot experiment in that manner with humans. And this presentation of the cerebellar peduncle brings us to the end of this part of our lecture. |
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Term
Functions:
1. Motor cortex: xxxx?, yyyy?,
wwww?—voluntary movements
2. Cerebellum: sensorimotor
xxxxxx of ongoing movement—
wwwwww?
3. Basal ganglia: gating/timing
and proper xxxx? of movement,
changing direction of movement
• Brainstem centers: xxxx?
control
• Vestibular system: xxxxx?
Can you fill in the missing
information? |
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Definition
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Term
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Definition
Let's get to talk about basal ganglia. So basal ganglia is this set of nuclei that are underneath the cortex. They have, for instance, the caudate nucleus and the putamen. Together they are called the striatum because of the characteristics that it has.
The globus pallidus, of which we have external and internal segments. And putamen and globus pallidus, you can call lenticular nucleus. Then we have the subthalamic nucleus and the substantia nigra.
These are practically accepted by all researchers and clinicians. There are, however, people that would like to include other areas, such as the nucleus accumbens and the ventral pallidum in even parts of the amygdala. The reason for this has to do with continuity of a structure, similarities in the function, and just if you bear with me for one second, it's difficult because of continuity structure sometimes to put a limit between one structure and the other. And so they deviate.
If there is a deviation, it might have to do exactly with that, with areas which might be in transition. And so researchers might disagree on how to classify them. And so this is how the nucleus accumbens and ventral pallidum may, for some authors, should be part of the basal ganglia.
However, we will stick with what is more recognized. Caudate, putamen, globus pallidus, subthalamic nucleus, and substantia nigra. Substantia nigra, both reticulata and compacta. It has two parts, [INAUDIBLE] the globus pallidus external and internal segments. |
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Term
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Definition
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Term
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Definition
If we look at the same information in a coronal section in one hemisphere only, this is the way it looks. So here you have several cortex, of course. These are the white matter tracks. Corpus callosum down here.
Here you have the caudate. And then you have the putamen. Remember, caudate and putamen together are the called the striatum.
And then you have the external and internal segments of the globus pallidus. OK. That's basal ganglia. Here you have substantia nigra, of which you have pars reticulata, in particular, at this level.
And this is the thalamus. Of course, thalamus is thalamus. It's not part of the basal ganglia. But a lot of things, almost everything is connected to the thalamus. So the thalamus is a good landmark to have in all of these different representations. |
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Term
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Definition
Next I'm going to show you a pathway. The direct vessels, indirect pathways in the basal ganglia. And what I want to do is an exercise in which I'm going to explain the difference between the direct pathway and indirect pathway in terms of all the components, everything which is happening.
Now, of course, again, cortex is cortex. Thalamus is thalamus. And so all of this other stuff in here is what's considered basal ganglia. Here you have a striatum. So we are putting caudate and putamen together.
Globus pallidus external segment. Subthalamic nucleus. GPI is the Globus Pallidus Internal segment, which is put here together with the substantia nigra.
Pars reticulata. Because they can consist of the output. They are in the output pathways of the basal ganglia. They are sending information to the thalamus. And here you have the substantia nigra pars compacta.
Of course, substantia nigra, pars compacta and pars reticulata anatomically are next to each other. But for the purposes of explaining how the circuity works, we have done it this way.
OK. So before I even begin, let's just recognize some of the different components, because that will make it easier to follow the information. This glu is glutamate. And the cells that contain glutamate are pyramidal cells in the cortex, which are going to be sending information down to the striatum.
This little blue dot in here that sends an axon out represents a medium spiny cell. It's one of the main cells in the striatum, perhaps the main cell, the projection cell. Medium because it's medium in size. Spiny because the dendrites have spines.
On the other hand, this ACh is acetylcholine. So these are cholinergic giant inter neurons. Giant, again, because of the size. cholinergic because they release acetylcholine.
In the globus pallidus you have GABA cells. In the subthalamic nucleus you have glutamatergic cells.
So remember, GABA is inhibitory. Gamma aminobutyric acid. Glutamate is excitatory.
GPI and substantia nigra pars reticulata, GABA cells. And then in the thalamus you have glutamate.
This glutamate from the thalamus is going to go back to the cortex. What we are going to find out is the direct pathway that is from the cortex to the striatum, to the globus pallidus internal segment in substantia nigra pars reticulata, to the thalamus, and from the thalamus back to the cortex is going to be excitatory to the cortex.
On the other hand, the indirect pathway, which is indirect because it's taking a detour via the globus pallidus external segment in the subthalamic nucleus, this is what makes it indirect. And this, you will see, is like a switch that would allow the information to then turn off. And this is necessary to have a balance between excitation and envervation.
This indirect pathway you are going to see in a second turns out to be inhibitory to the cortex.
So the arrows in color, the color is just to show [INAUDIBLE] differences between direct and indirect. If the arrow is going up, what I want to indicate is that there is excitation. If the arrow goes down, envervation.
So when we release glutamate, when the cortex is releasing glutamate into the medium spiny cells of the striatum, because it's glutamate that cell is going to get excited.
So if this cell, the medium spiny contains GABA, in the direct pathway they have GABA and something else called substance P. So that cell being excited is going to release GABA into the globus pallidus internal segment, in the substantia nigra pars reticulata.
Therefore, the cells on those structures are going to be inhibited. That's why the arrow is going down. That means that these cells which are supposed to be releasing GABA into the thalamus, since they are inhibited, they are unable to release too much GABA. They will not release GABA at all into the thalamus.
And what happens next is then the thalamus that was being inhibited by the GABA coming from this structure is now not inhibited anymore. It's likely moving the breaks from the cells in the thalamus.
And the cells in the thalamus contain glutamate. And therefore, now you are able to release more glutamate back into the cortex. And glutamate is excitatory. And so that's why you have the excitation going back. So there you have the arrow going up to indicate excitation via the direct pathway.
Now, if we do the same exercise on the indirect pathway, again, the blue just to distinguish it from the direct [INAUDIBLE] indirect pathway. But the arrow is going up. That's because it's the same glutamate.
Glutamate is glutamate. And it's having excitatory influence on these medium spiny cells. But these medium spiny cells also contain GABA. In this case they have GABA and enkephalin.
So if you were to stain using immunohistochemistry for GABA cells in the striatum, but you wanted to distinguish the ones which are involved in the direct and the ones which are involved in the indirect pathway, you wouldn't stain for GABA because they are both GABA. You would stain for substance P and enkephalin. Cause the substance P1s are direct. The enkephalin ones are in the indirect pathway.
OK. So GABA is now being released into the globus pallidus external segment. If you release GABA there, you inhibit the globus pallidus external segment cells. And once they are inhibited, they are unable to release GABA into the subthalamic nucleus. So the subthalamic nucleus cells, which are glutamatergic, get excited. Once they are excited, they are releasing glutamate into the globus pallidus internal segment in the substantia nigra pars reticulata.
GABA cells. Here you can see already the difference. This arrow is going down. This arrow is going up. So you have turned around the way in which information is being processed.
This is like a switch. This is why I said this is like turning on and off information.
And so now you have exactly the opposite effect on everything, because everything is now backwards. And that's why in the indirect pathway, you have the overall action on the cortex to be inhibitory.
Now, important to remember here is that you have [INAUDIBLE] GABA direct enervation. And via glutamate you have direct excitation. When you remove GABA from a structure that was receiving it, you allowed it to get excited.
So you don't excite it directly, because it's not direct excitation via glutamate. But because you remove the breaks, the thing that was keeping it inhibited, you allow it to go, that's called disenervation.
That, in reality, has sort of the same effect of being directly excited. There's just a fine distinction that we have to keep in mind.
So in some cases what I mentioned as excitation is not excitation, as direct excitation, but rather the removal of enervation, which is having the same effect.
Think of it in these terms. If you park a car and you are holding it in place by keeping the brakes down, when you remove the brakes, if there is an incline, the car may just move. It may just go.
Now, you are not pressing the accelerator. But the car is moving. So this is sort of the same idea.
Now, a little more detail in here. Now, we show what happens. Remember, in the middle of everything that is happening you have modulatory systems. You have [INAUDIBLE] incoming from [INAUDIBLE]. You have norepinephrine. You have a lot of other things, monoacetylcholine coming from different places in the brainstem and so on. So a lot of stuff is going on.
One thing that sometimes confuses students is what is going on with the dopamine that comes from the substantia nigra pars compacta. Substantia nigra pars compacta is here and is releasing dopamine. And they say, oh, there is a mistake.
This is excitatory. There is a plus sign there. And this is inhibitory. But there's no mistake. The reason is that what you actually see in terms of the effect that this modulator is having-- dopamine is the modulator-- depends not only on the substance, but on the substance and the family of receptors which are being activated.
So dopamine acting via the D1 family of receptors is excitatory. But dopamine acting on the family D2 of receptors is inhibitory. So it's the substance plus the receptor that will make it excitatory or inhibitory. So that's another important caveat that needs to be kept in mind.
But dopamine is dopamine. It's the same dopamine in one system or dopamine in the other system. Remember, GABA enkephalin versus GABA substance P in D1 versus D2.
If you stain medium spiny cells team with D1 receptors and antibody to distinguish D1 receptors and D2, the D1 will be mostly in the cells which are involved in the direct pathway, and the D2 family of receptors in the pathway in the medium spiny cells in the indirect pathway.
Now, to end, let's just examine for one second what happens with a case of a hyperkinetic disorder. This, I think, makes it clear that for everything to work correctly, you need both excitation and envervation, and both of them have to be in equilibrium. What happens in problems of the basal ganglia is that there is no correct equilibrium. And so you may have too much excitation. Or you may have too much enervation. You may have too much of the direct pathway, or too much of the indirect pathway.
In this example that I'm going to give, a hyperkinetic-- hyper is too much movement. Could be Huntington's, hemiballismus, chorea. So ballistic movements, things like that. if you, for some reason, something, we don't know what something, were to kill very many of these medium spiny cells which are involved in this pathway without affecting, or affecting differentially-- so a little bit of this, but a lot of the other ones-- then you are changing the balance in the circuit. You kill these cells, and therefore, you start reversing everything that was happening there.
Now, you have the ability to have a little bit of excitation in the globus pallidus external segment, because they are not receiving as much GABA as they should be receiving.
And everything, again, is now backwards. So you are making the indirect pathway as if it was a little bit like the direct pathway. And that will result in too much activity. So it will impinge upon the cortex, a little bit of excitation. And therefore, things will be out of balance.
And with this I think I will end our explanations of the basal ganglia. |
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Term
| . Basal ganglia Hyperkinetic |
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Definition
Huntington’s disease—uncontrolled,
involuntary movements; random patterns of jerks and
twists |
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Term
| Basal ganglia Hypokinetic |
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Definition
Parkinson’s disease—rigidity, slowness,
difficulty to initiate movements |
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Term
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Definition
“lack of or order”—lack of smooth motor control,
lack of coordination, overshooting-overcorrecting
(dysmetria), wavering, abnormal timing (dysrhythmia)—
affects medial and lateral motor systems, eye movements,
balance—nausea, vomiting, vertigo, slurred speech,
unsteady gait (patient seems drunk) |
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Term
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Definition
Lesions of the precentral gyrus result in paralysis of the
contralateral side of the body—recall the UMN deficits |
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Term
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Definition
hypokinetic disorder, degeneration of the
dopamine cells in the SNc—increased activity of the indirect
pathway and decreased activity of the direct pathway—decreased movement initiation |
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Term
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Definition
subthalamic nucleus lesion—results in
uncontrolled, ballistic movement contralateral to the lesion—STn
drives the GPi and SNr to inhibit the thalamus; without the STn,
there is insufficient inhibition of thalamus |
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Term
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Definition
hyperkinetic disorder—selective loss of the
GABA/enkephalin neurons in indirect pathway, leading to excess
movement and thoughts (psychosis/dementia); as the disease
progresses, direct pathway degenerates—patient is left mute and
akinetic; this is an autosomal dominant disorder which manifests in
early middle age |
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Term
D2 agonist (e.g., apomorphine) for Parkinson’s…
problem: |
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Definition
dose okay for putamen, may be too high
for caudate -> hallucinations; pallidotomy:
dangerous, invasive |
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Term
| Schizophrenia (too much D2 signaling) -> |
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Definition
antagonist: several anti-psychotic drugs
Block D2… problem: affects motor behavior! ->
patient is lethargic, Parkinsonian! |
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