Brain control of Movement

Question 1

What does the motor cortex consist of?

Answer 1

The motor cortex is a circumscribed region of the frontal lobe. Area 4 lies just anterior to the central sulcus on the precentral gyrus, and area 6 lies just anterior to area 4.

Question 2

What demonstrated that these areas constitute motor cortex in humans?

Answer 2

Penfield electrically stimulated the cortex in patients who were undergoing surgery to remove bits of brain thought to be inducing epileptic seizures. The stimulation was used in an attempt to identify which regions of cortex were so critical that they should be spared from the knife. In the course of these operations, Penfield discovered that weak electrical stimulation of area 4 in the precentral gyrus would elicit a twitch of the muscles in a particular region of the body on the contralateral side. Systematic prob- ing of this region established that there is a somatotopic organization in the human precentral gyrus much like that seen in the somatosensory areas of the postcentral gyrus

Question 3

What other name has been given to Area 4?

Answer 3

Area 4 is now often referred to as primary motor cortex or M1.

Question 4

What role is associated with area 6?

Answer 4

Penfield’s studies 50 years later supported the conjecture that this was a “higher” motor area in humans by showing that electrical stimulation of area 6 could evoke complex movements of either side of the body.

Question 5

How is area 6 often referred to now? (2) How are these similar and different?

Answer 5

Penfield found two somatotopically organized motor maps in area 6: one in a lateral region he called the premotor area (PMA) and one in a medial region called the supplementary motor area (SMA).

These two areas appear to perform similar functions but on different groups of muscles. While the SMA sends axons that innervate distal motor units directly, the PMA connects primarily with reticulospinal neurons that innervate proximal motor units.

Question 6

What contributions to motor control appear to come from the posterior parietal cortex?

Answer 6

Before someone goes to pitch a ball in baseball, he must have information about the current position of his body in space and how it relates to the positions of the batter and the catcher. This mental body image seems to be generated by somatosensory, proprioceptive, and visual in- puts to the posterior parietal cortex.

Question 7

Name two areas of particular interest in the posterior parietal cortex and from where they receive input

Answer 7

area 5, which is a target of inputs from the primary somatosensory cortical areas 3, 1, and 2; and area 7, which is a target of higher order visual cortical areas such as MT

Question 8

What occurs in human patients with lesions in these areas of the parietal lobes, as can occur after a stroke?

Answer 8

They show bizarre abnormalities of body image and the perception of spatial relations. In its most extreme manifestation, the patient will simply neglect the side of the body, and even the rest of the world, opposite the parietal lesion.

Question 9

What role is thought of the prefrontal cortex in motor planning?

Answer 9

The parietal lobes are extensively interconnected with regions in the anterior frontal lobes that in humans are thought to be important for abstract thought, decision making, and anticipating the consequences of action. These “prefrontal” areas, along with the posterior parietal cortex, represent the highest levels of the motor control hierarchy, where deci- sions are made about what actions to take and their likely outcome (a curve ball followed by a strike).

Question 10

What is the proposed function of area 6 in the motor hierarchey?

Answer 10

The prefrontal cortex and parietal cortex both send axons that converge on cortical area 6. Recall that areas 6 and 4 together contribute most of the axons to the descending corticospinal tract.

Thus, area 6 lies at the junction where signals encoding what actions are converted into signals that specify how the actions will be carried out.

Question 11

Using a method developed in the late 1960s by Edward Evarts at the National Institutes of Health, researchers have recorded the activity of neurons in the motor areas of awake, behaving animals

What results were found regarding the SMA?

Answer 11

Cells in the SMA typically increase their discharge rates about a second before the execution of a hand or wrist movement, consistent with their proposed role in planning movement.

An important feature of this activity is that it occurs in advance of the movements of either hand, suggesting that the supplementary areas of the two hemispheres are closely linked via the corpus callosum.

Question 12

What is observed in people and monkeys with lesions to the SMA?

Answer 12

Movement deficits observed following an SMA lesion on one side, in both monkeys and humans, are particularly pronounced for tasks requiring the coordinated actions of the two hands, such as buttoning a shirt.

Question 13

What name is given to this disorder of an inability to perform complex (but not simple) motor acts?

Answer 13

Apraxia

Question 14

A monkey performed a task requiring a specific arm movement to a target. The monkey was first given an instruction stimulus informing him what the target would be (“Get set, monkey!”), followed after a variable delay by a trigger stimulus informing the monkey that it was OK to move (“Go, monkey!”). Successful performance of the task (i.e., waiting for the “go” signal and then making the movement to the appropriate target) was rewarded with a sip of juice.

Describe the brain activity recorded from this study

Answer 14

They monitored the discharge of a neuron in the PMA. . The neuron in the PMA began firing if the instruction was to move the arm to the left, and it continued to discharge until the trigger stimulus came on and the movement was initiated. If the instruction was to move to the right, this neuron did not fire (presumably another population of PMA cells became active under this condition). Thus, the activity of this PMA neuron reported the direction of the upcoming movement and continued to do so until the movement was made.

Question 15

What role do these studies suggest the PMA plays?

Answer 15

Although we do not yet under- stand the details of the coding taking place in the SMA and PMA, the fact that neurons in these areas are selectively active well before movements are initiated is consistent with a role in planning the movement.

Question 16

Describe mirror neurons

Answer 16

Mirror neurons seem to represent particular motor acts, such as reaching, grasping, holding, or moving objects, regardless of whether a monkey actually performs the act or merely observes others doing it. Each cell has very specific movement preferences; a mirror neuron that responds when its monkey grasps a food tidbit will also respond to the sight of another monkey making a similar grasp of a tidbit but not when either monkey waves its hand.

Many mirror neurons even respond to the unique sounds another monkey produces during a specific movement (e.g., cracking open a peanut), as well as to the sight of that movement. In general, mirror neurons seem to encode the specific goals of motor acts rather than particular sensory stimuli.

Question 17

What may the function be for mirror neurons?

Answer 17

Mirror neurons may be part of an extensive brain system for understanding the actions and even the intentions of others. This implies that we use the same motor circuits both for planning our own movements and for understanding the actions and goals of others.

Question 18

A baseball pitcher has made the decision to throw a curve ball, but the batter abruptly walks away from the plate to adjust his helmet. The pitcher stands motionless on the mound, muscles tensed. He knows the batter will return, so he waits.

Describe the neural activity as he stands waiting

Answer 18

The pitcher is “set”; a select population of neurons in the premotor and supplementary motor cortex (the cells that are planning the curve ball movement sequence) are firing away in anticipation of the throw. Then the batter steps up to the plate, and an internally generated “go” command is given. This command appears to be implemented with the participation of a major subcortical input to area 6

Question 19

Where does the major subcortical input to area 6 arise?

Answer 19

In a nucleus of the dorsal thalamus, called the ventral lateral (VL) nucleus.

Question 20

Where does the input to this part of VL, called VLo arise? Where does THAT receive input and what does this create?

Answer 20

the basal ganglia buried deep within the telencephalon. The basal ganglia, in turn, are targets of the cerebral cortex, particularly the frontal, prefrontal, and parietal cortex. Thus, we have a loop where information cycles from the cortex through the basal ganglia and thalamus and then back to the cortex, particularly the supplementary motor area

Question 21

What is the proposed function of this loop?

Answer 21

One of the functions of this loop appears to be the selection and initiation of willed movements.

Question 22

What does the basal ganglia consist of

Answer 22

The basal ganglia consist of the caudate nucleus, the putamen, the globus pallidus (consisting of an internal segment, GPi, and an external segment, GPe), and the subthalamic nucleus. In addition, we can add the substantia nigra, a midbrain structure that is reciprocally connected with the basal ganglia of the forebrain

Question 23

What is the target of the cortical input to the basal ganglia?

Answer 23

The caudate and putamen together are called the striatum, which is the target of the cortical input to the basal ganglia.

Question 24

What structure is a source of output to the thalamus?

Answer 24

The globus pallidus is the source of the output to the thalamus.

Question 25

name the structures in the direct pathway of the motor loop in the Basal ganglia

Answer 25

Cortex → Striatum → GPi → VLo → Cortex (SMA)

Question 26

Describe how this direct pathway works

Answer 26

The motor loop through the basal ganglia originates with excitatory connections from the cortex.
In the direct pathway through the basal ganglia, synapses from cortical cells excite cells in the putamen,
which make inhibitory synapses on neurons in the globus pallidus,
which in turn make inhibitory connections with the cells in VLo.
The thalamocortical connection (from VLo to SMA) is excitatory and facilitates the discharge of movement-related cells in the SMA.

Neurons in the internal segment of the globus pallidus are spontaneously active at rest, and therefore they tonically inhibit VL:
Cortical activation (1) excites putamen neurons, which (2) inhibit GPi neurons, which (3) release the cells in VLo from inhibition, allowing them to become active. The activity in VLo boosts the activity of the SMA.

Question 27

What does this direct pathway allow the basal ganglia to do?

Answer 27

In general, the direct pathway allows the basal ganglia to enhance the initiation of desired movements. Cortical activation of the putamen leads to excitation of the SMA by VL.

Neurons in the internal segment of the globus pallidus are spontaneously active at rest, and therefore they tonically inhibit VL. Cortical activation (1) excites putamen neurons, which (2) inhibit GPi neurons, which (3) release the cells in VLo from inhibition, allowing them to become active. The activity in VLo boosts the activity of the SMA.

This part of the circuit acts as a positive-feedback loop that may serve to focus, or funnel, the activation of widespread cortical areas onto the supplementary motor area of cortex. We can speculate that the “go” signal for an internally generated movement occurs when activation of the SMA is boosted beyond some threshold amount by the activity reaching it through this basal ganglia “funnel.”

Question 28

What does the indirect pathway tend to do?

Answer 28

Antagonize the motor functions of the direct pathway. Whereas activation of the direct pathway by the cortex tends to facilitate the thalamus and information passing through it, activation of the indirect pathway by the cortex tends to inhibit the thalamus.

Question 29

What are the most unique features of the indirect pathway? (2)

Answer 29

The most unique features of the indirect pathway are the GPe and the subthalamic nucleus. Striatal neurons inhibit cells of the GPe, which then inhibit cells of both the GPi and subthalamic nucleus.

The subthalamic nucleus is also excited by axons from the cortex, and its projections excite the neurons of the GPi, which of course inhibit thalamic neurons.

Question 30

What two disorders are associated with the basal ganglia motor functions? Describe their symptoms

Answer 30

Parkinson’s disease is characterized by hypokinesia. Its symptoms include slowness of movement (bradykinesia), difficulty in initiating willed movements (akinesia), increased muscle tone (rigidity), and tremors of the hands and jaw, which are most prominent at rest when the patient is not attempting to move. Many patients also suffer deficits of cognition as the disease progresses.

Huntington’s disease is a hereditary, progressive, inevitably fatal syndrome characterized by hyperkinesia and dyskinesias (abnormal movements), dementia (impaired cognitive abilities), and a disorder of personality. People with Huntington’s disease exhibit changes in mood, personality, and memory. The most characteristic sign of the disease is chorea—spontaneous, uncontrollable, and purposeless move- ments with rapid, irregular flow and flicking motions of various parts of the body.

Question 31

What is the organic basis of parkinsons disease?

Answer 31

The degeneration of certain substantia nigra neurons and their inputs to the striatum. These inputs use the neurotransmitter dopamine (DA). The actions of DA are complex because it binds to multiple types of striatal DA receptors that mediate quite different effects. Dopaminergic synapses terminate on striatal neurons closely adjacent to the synaptic inputs from the cortex, and DA can enhance the cortical inputs to the direct pathway.

DA facilitates the direct motor loop by activating cells in the putamen (which releases VLo from GPi-induced inhibition). In essence, the depletion of dopamine in Parkinson’s disease closes the funnel that feeds activity to the SMA via the basal ganglia and VLo. At the same time, DA inhibits the neurons in the striatum that send inhibitory outputs, via the indirect pathway, to the GPe.

Question 32

What do most therapies for parkinsons disease consist of?

Answer 32

A central goal of most therapies for Parkinson’s disease is to en- hance the levels of dopamine delivered to the caudate nucleus and pu- tamen. This is most easily done by administering the compound L-dopa, which is a precursor to dopamine. L-dopa crosses the blood–brain barrier and boosts DA synthesis in the cells that remain alive in the substantia nigra, thus al- leviating some of the symptoms. DA agonists are also useful drugs in the treatment of Parkinson’s disease.

Question 33

How effective are L-dopa and dopamine agonists in treating Parkinson’s disease

Answer 33

They are useful but treatments with L-dopa or DA agonists do not alter the progressive course of the disease, nor do they alter the rate at which substantia nigra neurons degenerate. They also have significant side effects.

Question 34

Describe two alternative ways of treating parkinsons

Answer 34

The symptoms of some Parkinson’s dis- ease patients can also be improved with brain surgery and stimulation. There are also a variety of experimental treatment strategies. One of them is to graft DA-producing cells into the basal ganglia. A promising possibility is to use human stem cells that have been manipulated developmentally or genetically to produce DA.

Question 35

What is the most obvious pathology of huntingtons disease?

Answer 35

The most obvious pathology of their brains is a profound loss of neurons in the caudate nucleus, putamen, and globus pallidus, with additional cell loss in the cerebral cortex and elsewhere

Question 36

Give an example of how kyperkinesia can also result from other types of lesions that affect the basal ganglia

Answer 36

One example is ballism, which is characterized by violent, flinging movements of the extremities (somewhat like our baseball pitcher unintentionally throwing the ball while sitting in the dugout). The symptoms usually occur on just one side of the body, and the condition is then called hemiballismus. As with Parkinson’s disease, the cellular mechanisms associated with ballism are known; it is caused by damage to the subthalamic nucleus (usually resulting from an interruption of its blood supply caused by a stroke).

The subthalamic nucleus, part of another side loop within the basal ganglia, excites neurons in the globus pallidus that project to VLo. Remember that excitation of the globus pallidus inhibits VLo. Thus, a loss of excitatory drive to the globus pallidus facilitates VLo, in effect opening the funnel of activity to the SMA.

Question 37

SMA does not automatically trigger movement. The initiation of voluntary movement also requires activation of what brain area?

Answer 37

Area 4, primary motor cortex (M1). This area has the lowest threshold for the elicitation of movement by electrical stimulation. In other words, stimulation intensities that are unable to evoke movement in other cortical areas are still effective in evoking movement when applied to area 4, meaning that area 4 has dense, strong synaptic connections with the motor neurons and the spinal interneurons that drive them.

Question 38

As we discussed earlier, the somatic musculature is mapped systematically in this area. What is this part (‘map’) of the cortex called?

Answer 38

This ribbon of cortex that stretches the full length of the precentral gyrus is sometimes also called the motor strip.

Question 39

In which cortical layer does the pathway by which motor cortex activates lower motor neurons originate?

Answer 39

The pathway by which motor cortex activates lower motor neurons originates in cortical layer V

Question 40

Describe the neurons in Layer V

Answer 40

Layer V has a population of pyramidal neurons, some of which can be quite large (soma diameters approaching 0.1 mm). The largest cells were first described as a separate class by Russian anatomist Vladimir Betz in 1874 and are therefore called Betz cells.

In humans, many of the large corticospinal cells of layer V project to pools of lower motor neurons and excite them monosynaptically. The same corticospinal axons can also branch and excite local inhibitory interneurons. By controlling selected groups of motor neurons and interneurons, a single corticospinal neuron may generate coordinated effects on antagonist muscles. This is similar to the reciprocal inhibition that we saw in the spinal reflex circuitry

Question 41

Where do the layer V pyramidal cells in M1 receive their inputs primarily from? (2)

Answer 41

The layer V pyramidal cells in M1 receive their inputs primarily from two sources: other cortical areas and the thalamus.

Question 42

From which cortical areas does the main input to the layer V pyramidal cells in M1 come from?

Answer 42

The major cortical inputs originate in the areas adjacent to area 4: area 6 immediately anterior; and areas 3, 1, and 2 immediately posterior

Question 43

From which parts of the thalamus does the main input to the layer V pyramidal cells in M1 come from?

Answer 43

The thalamic input to M1 arises mainly from another part of the ventral lateral nucleus, called VLc, which relays information from the cerebellum.

Question 44

Researchers previously thought the motor cortex consisted of a detailed mapping of the individual muscles, such that the activity of a single pyramidal cell would lead to activity in a single motor neuron pool.

How has this view changed?

Answer 44

The view that has emerged from more recent work is that individual pyramidal cells can drive numerous motor neuron pools from a group of differ- ent muscles involved in moving a limb toward a desired goal. Recordings from M1 neurons in behaving animals have revealed that a burst of activity occurs immediately before and during a voluntary movement, and that this activity appears to encode two aspects of the movement: force and direction.

Question 45

This breadth of tuning is shown clearly in a type of experiment devised by Apostolos Georgopoulos and his colleagues, then working at Johns Hopkins University.

describe this study

Answer 45

Monkeys were trained to move a joystick to- ward a small light whose position varied randomly around a circle. Some M1 cells fired most vigorously during movement in one direction but also discharged during movement angles that varied considerably from the preferred direction. The coarseness in the directional tuning of the corticospinal neurons was certainly at odds with the high accuracy of the monkey’s movements, suggesting that the direction of movement could not be encoded by the activity of individual cells that command movement in a single direction.

Question 46

What did Georgopoulos deduce from this study?

Answer 46

Georgopoulos hypothesised that movement direction was encoded instead by the collective activity of a population of neurons. Recall the role of neuronal population coding in the sensory systems, where the responses of many broadly tuned neurons are used to specify the properties of a particular stimulus

Question 47

What is meant by a population vector?

Answer 47

Georgopoulos and his colleagues recorded from over 200 different neurons in M1; for each cell, they constructed a directional tuning curve. From these data, the researchers knew how vigorously each of the cells in the population responded during movement in each direction.

The activity of each cell was represented as a direction vector pointing in the direction that was best for that cell; the length of the vector represented how active that cell had been during a particular movement. The vectors representing each cell’s activity could be plotted together for each direction of movement, then averaged to yield what the researchers called a population vector.

Question 48

What observation was made about this population vector?

Answer 48

They found a strong correlation between this average vector, representing the activity of the entire population of M1 cells, and the actual direction of movement

Question 49

What three important conclusions about how M1 commands voluntary movement were suggested by these studies?

Answer 49

(1) much of the motor cortex is active for every movement,
(2) the activity of each cell represents a single “vote” for a particular direction of movement, and
(3) the direction of movement is determined by a tally (and averaging) of the votes registered by each cell in the population.

Question 50

Although this population-coding scheme remains hypothetical in M1, where has this scheme been shown to been used in the brain?

Answer 50

experiments on the superior colliculus by James McIlwain at Brown University and David Sparks at the University of Alabama showed conclusively that a population code is used by this structure to command precisely directed eye movements

Question 51

Based on this scheme for motor control, what prediction would be made from a larger population of neurons representing a type of movement? Does it hold true?

Answer 51

The larger the population of neurons representing a type of movement, the finer the possible control. From the motor map shown in Figure 14.8, we would predict that finer control should be possible for the hands and the muscles of facial expression, and indeed this is normally the case.

Question 52

Does finer movements of other muscles learned with experience have any effect on this proposed scheme?

Answer 52

The answer appears to be yes. John Donoghue, Jerome Sanes, and their students at Brown University collected evidence indicating that such plasticity of the adult motor cortex is possible. For example, in one series of experiments, they used cortical microstimulation in rats and mapped the regions of M1 that normally elicit movements of the forelimb, facial whiskers, or muscles around the eye.

Then they cut the motor nerve that supplies the muscles of the snout and its whiskers and found that regions of M1 that had evoked whisker movements now would elicit either forelimb or eye movements. The motor map had been reorganized. These neuroscientists speculated that similar types of cortical reorganization might provide a basis for learning fine motor skills.

Question 53

Which critical motor functions belong to the cerebellum?

Answer 53

It is not enough to simply command the muscles to contract. Throwing a ball requires a detailed sequence of muscle contractions, each one generating exactly the right amount of force at precisely the right time. These critical motor control functions belong to the cerebellum

Question 54

How are these functions of the cerebellum plainly revealed?

Answer 54

Cerebellar lesions; movements become uncoordinated and inaccurate, a condition known as ataxia.

Question 55

Name and describe the symptoms of ataxia

Answer 55

Instead of smoothly and simultaneously moving the shoulder, elbow, and wrist to bring the finger to rest on the nose, they move each joint sequentially—first the shoulder, then the elbow, and finally the wrist. This is called dyssynergia, decomposition of synergistic multijoint movement. Another characteristic deficit shown by these patients is that their finger movement will be dysmetric; they will either come up short of the nose or shoot past it, poking themselves in the face.

Question 56

What anatomical feature does the cerebellum ‘sit’ on?

Answer 56

The cerebellum sits on stout stalks of axons called peduncles that rise from the pons; the whole structure resembles a piece of cauliflower.

Question 57

Describe the visible part of the cerebellum

Answer 57

The visible part of the cerebellum is actually a thin sheet of cortex, which is repeatedly folded. The dorsal surface is characterised by a series of shallow ridges called folia (singular: folium), which run transversely (from side to side). In addition, there are deeper transverse fissures, revealed by making a sagittal slice through the cerebellum; these divide the cerebellum into 10 lobules.

Question 58

What structures in the cerebellum relay most of the cerebellar cortical output to various brain stem structures?

Answer 58

Neurons are also embedded deep within the white matter of the cerebellum, forming the deep cerebellar nuclei, which relay most of the cerebellar cortical output to various brain stem structures.

Question 59

What are the majority of the neurons in the cerebellum? How numerous are these cells?

Answer 59

The cerebellum constitutes only about 10% of the total volume of the brain, but its cortex has an astonishingly high density of neurons. The vast majority of these are tiny excitatory neurons called granule cells, whose somata lie in the granule cell layer.

The number of granule neurons in the cerebellum is about equal to the number of other neurons in the entire CNS.

Question 60

Is the cerebellum split in half, similar to the cerebrum?

Answer 60

Unlike the cerebrum, the cerebellum is not obviously split down the middle. At the midline, the folia appear to run uninterrupted from one side to the other. The only distinguishing feature of the midline is a bump that runs like a backbone down the length of the cerebellum.

Question 61

What is this midline region called and what function does it serve?

Answer 61

This midline region is called the vermis (from the Latin for “worm”), and it separates the two lateral cerebellar hemispheres from each other. The vermis and the hemispheres represent important functional divisions. The vermis sends output to the brain stem structures that contribute to the ventromedial descending spinal pathways. The hemispheres are related to other brain structures that contribute to the lateral pathways, particularly the cerebral cortex.

Question 62

What is the simplest circuit involving the lateral cerebellum? Describe it

Answer 62

The simplest circuit involving the lateral cerebellum constitutes yet another loop: The motor loop.

Axons arising from layer V pyramidal cells in the sensorimotor cortex—frontal areas 4 and 6, somatosensory areas on the postcentral gyrus, and the posterior parietal areas—form a massive projection to clusters of cells in the pons, the pontine nuclei, which in turn feed the cerebellum. The lateral cerebellum then projects back to the motor cortex via a relay in the ventral lateral nucleus of the thalamus (VLc).

Question 63

What have we learned from lesions to this pathway in the cerebellum?

Answer 63

From the effects of lesions in this pathway, we can deduce that it is critical for the proper execution of planned, voluntary, multijoint movements. Indeed, once the cerebellum has received the signal for movement intent, its activity appears to instruct the primary motor cortex with respect to movement direction, timing, and force.

Question 64

What are these instructions based on for ballistic movements?

Answer 64

For ballistic movements, these instructions are based entirely on predictions about their outcome (because such movements are too fast for sensory feedback to be of much immediate use). Such predictions are based on past experience; that is, they are learned. Therefore, the cerebellum is another important site for motor learning; it is a place where what is intended is compared with what has happened. When this comparison fails to meet expectations, compensatory modifications are made in certain cerebellar circuits.