Guyton and Hall Textbook of Medical Physiology, 12th Ed

CHAPTER 56

Contributions of the Cerebellum and Basal Ganglia to Overall Motor Control

image Aside from the areas in the cerebral cortex that stimulate muscle contraction, two other brain structures are also essential for normal motor function. They are the cerebellum and the basal ganglia. Yet neither of these two can control muscle function by themselves. Instead, they always function in association with other systems of motor control.

The cerebellum plays major roles in the timing of motor activities and in rapid, smooth progression from one muscle movement to the next. It also helps to control the intensity of muscle contraction when the muscle load changes and controls the necessary instantaneous interplay between agonist and antagonist muscle groups.

The basal ganglia help to plan and control complex patterns of muscle movement, controlling relative intensities of the separate movements, directions of movements, and sequencing of multiple successive and parallel movements for achieving specific complicated motor goals. This chapter explains the basic functions of the cerebellum and basal ganglia and discusses the overall brain mechanisms for achieving intricate coordination of total motor activity.

Cerebellum and Its Motor Functions

The cerebellum, illustrated in Figures 56-1 and 56-2, has long been called a silent area of the brain, principally because electrical excitation of the cerebellum does not cause any conscious sensation and rarely causes any motor movement. Removal of the cerebellum, however, causes body movements to become highly abnormal. The cerebellum is especially vital during rapid muscular activities such as running, typing, playing the piano, and even talking. Loss of this area of the brain can cause almost total incoordination of these activities even though its loss causes paralysis of no muscles.

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Figure 56-1 Anatomical lobes of the cerebellum as seen from the lateral side.

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Figure 56-2 Functional parts of the cerebellum as seen from the posteroinferior view, with the inferiormost portion of the cerebellum rolled outward to flatten the surface.

But how is it that the cerebellum can be so important when it has no direct ability to cause muscle contraction? The answer is that it helps to sequence the motor activities and also monitors and makes corrective adjustments in the body’s motor activities while they are being executed so that they will conform to the motor signals directed by the cerebral motor cortex and other parts of the brain.

The cerebellum receives continuously updated information about the desired sequence of muscle contractions from the brain motor control areas; it also receives continuous sensory information from the peripheral parts of the body, giving sequential changes in the status of each part of the body—its position, rate of movement, forces acting on it, and so forth. The cerebellum then compares the actual movements as depicted by the peripheral sensory feedback information with the movements intended by the motor system. If the two do not compare favorably, then instantaneous subconscious corrective signals are transmitted back into the motor system to increase or decrease the levels of activation of specific muscles.

The cerebellum also aids the cerebral cortex in planning the next sequential movement a fraction of a second in advance while the current movement is still being executed, thus helping the person to progress smoothly from one movement to the next. Also, it learns by its mistakes—that is, if a movement does not occur exactly as intended, the cerebellar circuit learns to make a stronger or weaker movement the next time. To do this, changes occur in the excitability of appropriate cerebellar neurons, thus bringing subsequent muscle contractions into better correspondence with the intended movements.

Anatomical Functional Areas of the Cerebellum

Anatomically, the cerebellum is divided into three lobes by two deep fissures, as shown in Figures 56-1 and 56-2: (1) the anterior lobe, (2) the posterior lobe, and (3) the flocculonodular lobe. The flocculonodular lobe is the oldest of all portions of the cerebellum; it developed along with (and functions with) the vestibular system in controlling body equilibrium, as discussed in Chapter 55.

Longitudinal Functional Divisions of the Anterior and Posterior Lobes

From a functional point of view, the anterior and posterior lobes are organized not by lobes but along the longitudinal axis, as demonstrated in Figure 56-2, which shows a posterior view of the human cerebellum after the lower end of the posterior cerebellum has been rolled downward from its normally hidden position. Note down the center of the cerebellum a narrow band called the vermis, separated from the remainder of the cerebellum by shallow grooves. In this area, most cerebellar control functions for muscle movements of the axial bodyneckshouldersand hips are located.

To each side of the vermis is a large, laterally protruding cerebellar hemisphere, and each of these hemispheres is divided into an intermediate zone and a lateral zone.

The intermediate zone of the hemisphere is concerned with controlling muscle contractions in the distal portions of the upper and lower limbs, especially the hands and fingers and feet and toes.

The lateral zone of the hemisphere operates at a much more remote level because this area joins with the cerebral cortex in the overall planning of sequential motor movements. Without this lateral zone, most discrete motor activities of the body lose their appropriate timing and sequencing and therefore become incoordinate, as we discuss more fully later.

Topographical Representation of the Body in the Vermis and Intermediate Zones

In the same manner that the cerebral sensory cortex, motor cortex, basal ganglia, red nuclei, and reticular formation all have topographical representations of the different parts of the body, so also is this true for the vermis and intermediate zones of the cerebellum. Figure 56-3 shows two such representations. Note that the axial portions of the body lie in the vermis part of the cerebellum, whereas the limbs and facial regions lie in the intermediate zones. These topographical representations receive afferent nerve signals from all the respective parts of the body, as well as from corresponding topographical motor areas in the cerebral cortex and brain stem. In turn, they send motor signals back to the same respective topographical areas of the cerebral motor cortex, as well as to topographical areas of the red nucleus and reticular formation in the brain stem.

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Figure 56-3 Somatosensory projection areas in the cerebellar cortex.

Note that the large lateral portions of the cerebellar hemispheres do not have topographical representations of the body. These areas of the cerebellum receive their input signals almost exclusively from the cerebral cortex, especially from the premotor areas of the frontal cortex and from the somatosensory and other sensory association areas of the parietal cortex. It is believed that this connectivity with the cerebral cortex allows the lateral portions of the cerebellar hemispheres to play important roles in planning and coordinating the body’s rapid sequential muscular activities that occur one after another within fractions of a second.

Neuronal Circuit of the Cerebellum

The human cerebellar cortex is actually a large folded sheet, about 17 centimeters wide by 120 centimeters long, with the folds lying crosswise, as shown in Figures 56-2 and 56-3. Each fold is called a folium.Lying deep beneath the folded mass of cerebellar cortex are deep cerebellar nuclei.

Input Pathways to the Cerebellum

Afferent Pathways from Other Parts of the Brain

The basic input pathways to the cerebellum are shown in Figure 56-4. An extensive and important afferent pathway is the corticopontocerebellar pathway, which originates in the cerebral motor and premotor cortices and also in the cerebral somatosensory cortex. It passes by way of the pontile nuclei and pontocerebellar tracts mainly to the lateral divisions of the cerebellar hemispheres on the opposite side of the brain from the cerebral areas.

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Figure 56-4 Principal afferent tracts to the cerebellum.

In addition, important afferent tracts originate in each side of the brain stem; they include (1) an extensive olivocerebellar tract, which passes from the inferior olive to all parts of the cerebellum and is excited in the olive by fibers from the cerebral motor cortex, basal ganglia, widespread areas of the reticular formation, and spinal cord; (2) vestibulocerebellar fibers, some of which originate in the vestibular apparatus itself and others from the brain stem vestibular nuclei—almost all of these terminate in the flocculonodular lobe and fastigial nucleus of the cerebellum; and (3) reticulocerebellar fibers, which originate in different portions of the brain stem reticular formation and terminate in the midline cerebellar areas (mainly in the vermis).

Afferent Pathways from the Periphery

The cerebellum also receives important sensory signals directly from the peripheral parts of the body mainly through four tracts on each side, two of which are located dorsally in the cord and two ventrally. The two most important of these tracts are shown in Figure 56-5: the dorsal spinocerebellar tract and the ventral spinocerebellar tract. The dorsal tract enters the cerebellum through the inferior cerebellar peduncle and terminates in the vermis and intermediate zones of the cerebellum on the same side as its origin. The ventral tract enters the cerebellum through the superior cerebellar peduncle, but it terminates in both sides of the cerebellum.

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Figure 56-5 Spinocerebellar tracts.

The signals transmitted in the dorsal spinocerebellar tracts come mainly from the muscle spindles and to a lesser extent from other somatic receptors throughout the body, such as Golgi tendon organs, large tactile receptors of the skin, and joint receptors. All these signals apprise the cerebellum of the momentary status of (1) muscle contraction, (2) degree of tension on the muscle tendons, (3) positions and rates of movement of the parts of the body, and (4) forces acting on the surfaces of the body.

The ventral spinocerebellar tracts receive much less information from the peripheral receptors. Instead, they are excited mainly by motor signals arriving in the anterior horns of the spinal cord from (1) the brain through the corticospinal and rubrospinal tracts and (2) the internal motor pattern generators in the cord itself. Thus, this ventral fiber pathway tells the cerebellum which motor signals have arrived at the anterior horns; this feedback is called the efference copy of the anterior horn motor drive.

The spinocerebellar pathways can transmit impulses at velocities up to 120 m/sec, which is the most rapid conduction in any pathway in the central nervous system. This extremely rapid conduction is important for instantaneous apprisal of the cerebellum of changes in peripheral muscle actions.

In addition to signals from the spinocerebellar tracts, signals are transmitted into the cerebellum from the body periphery through the spinal dorsal columns to the dorsal column nuclei of the medulla and then relayed to the cerebellum. Likewise, signals are transmitted up the spinal cord through the spinoreticular pathway to the reticular formation of the brain stem and also through the spino-olivary pathway to the inferior olivary nucleus. Then signals are relayed from both of these areas to the cerebellum. Thus, the cerebellum continually collects information about the movements and positions of all parts of the body even though it is operating at a subconscious level.

Output Signals from the Cerebellum

Deep Cerebellar Nuclei and the Efferent Pathways

Located deep in the cerebellar mass on each side are three deep cerebellar nuclei—the dentate, interposed, and fastigial. (The vestibular nuclei in the medulla also function in some respects as if they were deep cerebellar nuclei because of their direct connections with the cortex of the flocculonodular lobe.) All the deep cerebellar nuclei receive signals from two sources: (1) the cerebellar cortex and (2) the deep sensory afferent tracts to the cerebellum.

Each time an input signal arrives in the cerebellum, it divides and goes in two directions: (1) directly to one of the cerebellar deep nuclei and (2) to a corresponding area of the cerebellar cortex overlying the deep nucleus. Then, a fraction of a second later, the cerebellar cortex relays an inhibitory output signal to the deep nucleus. Thus, all input signals that enter the cerebellum eventually end in the deep nuclei in the form of initial excitatory signals followed a fraction of a second later by inhibitory signals. From the deep nuclei, output signals leave the cerebellum and are distributed to other parts of the brain.

The general plan of the major efferent pathways leading out of the cerebellum is shown in Figure 56-6 and consists of the following:

1. A pathway that originates in the midline structures of the cerebellum (the vermis) and then passes through the fastigial nuclei into the medullary and pontile regions of the brain stem. This circuit functions in close association with the equilibrium apparatus and brain stem vestibular nuclei to control equilibrium, as well as in association with the reticular formation of the brain stem to control the postural attitudes of the body. It was discussed in detail in Chapter 55 in relation to equilibrium.

2. A pathway that originates in (1) the intermediate zone of the cerebellar hemisphere and then passes through (2) the interposed nucleus to (3) the ventrolateral and ventroanterior nuclei of the thalamus and then to (4) the cerebral cortex, to (5) several midline structures of the thalamus and then to (6) the basal ganglia and (7) the red nucleus and reticular formation of the upper portion of the brain stem. This complex circuit helps to coordinate mainly the reciprocal contractions of agonist and antagonist muscles in the peripheral portions of the limbs, especially in the hands, fingers, and thumbs.

3. A pathway that begins in the cerebellar cortex of the lateral zone of the cerebellar hemisphere and then passes to the dentate nucleus, next to the ventrolateral and ventroanterior nuclei of the thalamus, and, finally, to the cerebral cortex. This pathway plays an important role in helping coordinate sequential motor activities initiated by the cerebral cortex.

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Figure 56-6 Principal efferent tracts from the cerebellum.

Functional Unit of the Cerebellar Cortex— the Purkinje Cell and the Deep Nuclear Cell

The cerebellum has about 30 million nearly identical functional units, one of which is shown to the left in Figure 56-7. This functional unit centers on a single, very large Purkinje cell and on a corresponding deep nuclear cell.

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Figure 56-7 The left side of this figure shows the basic neuronal circuit of the cerebellum, with excitatory neurons shown in red and the Purkinje cell (an inhibitory neuron) shown in black. To the right is shown the physical relationship of the deep cerebellar nuclei to the cerebellar cortex with its three layers.

To the top and right in Figure 56-7, the three major layers of the cerebellar cortex are shown: the molecular layer, Purkinje cell layer, and granule cell layer. Beneath these cortical layers, in the center of the cerebellar mass, are the deep cerebellar nuclei that send output signals to other parts of the nervous system.

Neuronal Circuit of the Functional Unit

Also shown in the left half of Figure 56-7 is the neuronal circuit of the functional unit, which is repeated with little variation 30 million times in the cerebellum. The output from the functional unit is from a deep nuclear cell. This cell is continually under both excitatory and inhibitory influences. The excitatory influences arise from direct connections with afferent fibers that enter the cerebellum from the brain or the periphery. The inhibitory influence arises entirely from the Purkinje cell in the cortex of the cerebellum.

The afferent inputs to the cerebellum are mainly of two types, one called the climbing fiber type and the other called the mossy fiber type.

The climbing fibers all originate from the inferior olives of the medulla. There is one climbing fiber for about 5 to 10 Purkinje cells. After sending branches to several deep nuclear cells, the climbing fiber continues all the way to the outer layers of the cerebellar cortex, where it makes about 300 synapses with the soma and dendrites of each Purkinje cell. This climbing fiber is distinguished by the fact that a single impulse in it will always cause a single, prolonged (up to 1 second), peculiar type of action potential in each Purkinje cell with which it connects, beginning with a strong spike and followed by a trail of weakening secondary spikes. This action potential is called the complex spike.

The mossy fibers are all the other fibers that enter the cerebellum from multiple sources: from the higher brain, brain stem, and spinal cord. These fibers also send collaterals to excite the deep nuclear cells. Then they proceed to the granule cell layer of the cortex, where they, too, synapse with hundreds to thousands of granule cells. In turn, the granule cells send extremely small axons, less than 1 micrometer in diameter, up to the molecular layer on the outer surface of the cerebellar cortex. Here the axons divide into two branches that extend 1 to 2 millimeters in each direction parallel to the folia. There are many millions of these parallel nerve fibers because there are some 500 to 1000 granule cells for every 1 Purkinje cell. It is into this molecular layer that the dendrites of the Purkinje cells project and 80,000 to 200,000 of the parallel fibers synapse with each Purkinje cell.

The mossy fiber input to the Purkinje cell is quite different from the climbing fiber input because the synaptic connections are weak, so large numbers of mossy fibers must be stimulated simultaneously to excite the Purkinje cell. Furthermore, activation usually takes the form of a much weaker short-duration Purkinje cell action potential called a simple spike, rather than the prolonged complex action potential caused by climbing fiber input.

Purkinje Cells and Deep Nuclear Cells Fire Continuously Under Normal Resting Conditions

One characteristic of both Purkinje cells and deep nuclear cells is that normally both of them fire continuously; the Purkinje cell fires at about 50 to 100 action potentials per second, and the deep nuclear cells at much higher rates. Furthermore, the output activity of both these cells can be modulated upward or downward.

Balance Between Excitation and Inhibition at the Deep Cerebellar Nuclei

Referring again to the circuit of Figure 56-7, note that direct stimulation of the deep nuclear cells by both the climbing and the mossy fibers excites them. By contrast, signals arriving from the Purkinje cells inhibit them. Normally, the balance between these two effects is slightly in favor of excitation so that under quiet conditions, output from the deep nuclear cell remains relatively constant at a moderate level of continuous stimulation.

In execution of a rapid motor movement, the initiating signal from the cerebral motor cortex or brain stem at first greatly increases deep nuclear cell excitation. Then, another few milliseconds later, feedback inhibitory signals from the Purkinje cell circuit arrive. In this way, there is first a rapid excitatory signal sent by the deep nuclear cells into the motor output pathway to enhance the motor movement, but this is followed within another small fraction of a second by an inhibitory signal. This inhibitory signal resembles a “delay-line” negative feedback signal of the type that is effective in providing damping. That is, when the motor system is excited, a negative feedback signal occurs after a short delay to stop the muscle movement from overshooting its mark. Otherwise, oscillation of the movement would occur.

Other Inhibitory Cells in the Cerebellum

In addition to the deep nuclear cells, granule cells, and Purkinje cells, two other types of neurons are located in the cerebellum: basket cells and stellate cells. These are inhibitory cells with short axons. Both the basket cells and the stellate cells are located in the molecular layer of the cerebellar cortex, lying among and stimulated by the small parallel fibers. These cells in turn send their axons at right angles across the parallel fibers and cause lateral inhibitionof adjacent Purkinje cells, thus sharpening the signal in the same manner that lateral inhibition sharpens contrast of signals in many other neuronal circuits of the nervous system.

Turn-On/Turn-Off and Turn-Off/Turn-On Output Signals from the Cerebellum

The typical function of the cerebellum is to help provide rapid turn-on signals for the agonist muscles and simultaneous reciprocal turn-off signals for the antagonist muscles at the onset of a movement. Then on approaching termination of the movement, the cerebellum is mainly responsible for timing and executing the turn-off signals to the agonists and turn-on signals to the antagonists. Although the exact details are not fully known, one can speculate from the basic cerebellar circuit of Figure 56-7 how this might work, as follows.

Let us suppose that the turn-on/turn-off pattern of agonist/antagonist contraction at the onset of movement begins with signals from the cerebral cortex. These signals pass through noncerebellar brain stem and cord pathways directly to the agonist muscle to begin the initial contraction.

At the same time, parallel signals are sent by way of the pontile mossy fibers into the cerebellum. One branch of each mossy fiber goes directly to deep nuclear cells in the dentate or other deep cerebellar nuclei; this instantly sends an excitatory signal back into the cerebral corticospinal motor system, either by way of return signals through the thalamus to the cerebral cortex or by way of neuronal circuitry in the brain stem, to support the muscle contraction signal that had already been begun by the cerebral cortex. As a consequence, the turn-on signal, after a few milliseconds, becomes even more powerful than it was at the start because it becomes the sum of both the cortical and the cerebellar signals. This is the normal effect when the cerebellum is intact, but in the absence of the cerebellum, the secondary extra supportive signal is missing. This cerebellar support makes the turn-on muscle contraction much stronger than it would be if the cerebellum did not exist.

Now, what causes the turn-off signal for the agonist muscles at the termination of the movement? Remember that all mossy fibers have a second branch that transmits signals by way of the granule cells to the cerebellar cortex and eventually, by way of “parallel” fibers, to the Purkinje cells. The Purkinje cells in turn inhibit the deep nuclear cells. This pathway passes through some of the smallest, slowest-conducting nerve fibers in the nervous system: that is, the parallel fibers of the cerebellar cortical molecular layer, which have diameters of only a fraction of a millimeter. Also, the signals from these fibers are weak, so they require a finite period of time to build up enough excitation in the dendrites of the Purkinje cell to excite it. But once the Purkinje cell is excited, it in turn sends a strong inhibitory signal to the same deep nuclear cell that had originally turned on the movement. Therefore, this helps to turn off the movement after a short time.

Thus, one can see how the complete cerebellar circuit could cause a rapid turn-on agonist muscle contraction at the beginning of a movement and yet cause also a precisely timed turn-off of the same agonist contraction after a given time period.

Now let us speculate on the circuit for the antagonist muscles. Most important, remember that throughout the spinal cord there are reciprocal agonist/antagonist circuits for virtually every movement that the cord can initiate. Therefore, these circuits are part of the basis for antagonist turn-off at the onset of movement and then turn-on at termination of movement, mirroring whatever occurs in the agonist muscles. But we must remember, too, that the cerebellum contains several other types of inhibitory cells besides Purkinje cells. The functions of some of these are still to be determined; they, too, could play roles in the initial inhibition of the antagonist muscles at onset of a movement and subsequent excitation at the end of a movement.

All these mechanisms are still partly speculation. They are presented here especially to illustrate ways by which the cerebellum could cause exaggerated turn-on and turn-off signals, controlling the agonist and antagonist muscles, as well as the timing.

The Purkinje Cells “Learn” to Correct Motor Errors—Role of the Climbing Fibers

The degree to which the cerebellum supports onset and offset of muscle contractions, as well as timing of contractions, must be learned by the cerebellum. Typically, when a person first performs a new motor act, the degree of motor enhancement by the cerebellum at the onset of contraction, the degree or inhibition at the end of contraction, and the timing of these are almost always incorrect for precise performance of the movement. But after the act has been performed many times, the individual events become progressively more precise, sometimes requiring only a few movements before the desired result is achieved, but at other times requiring hundreds of movements.

How do these adjustments come about? The exact answer is not known, although it is known that sensitivity levels of cerebellar circuits themselves progressively adapt during the training process, especially the sensitivity of the Purkinje cells to respond to the granule cell excitation. Furthermore, this sensitivity change is brought about by signals from the climbing fibers entering the cerebellum from the inferior olivary complex.

Under resting conditions, the climbing fibers fire about once per second. But they cause extreme depolarization of the entire dendritic tree of the Purkinje cell, lasting for up to a second, each time they fire. During this time, the Purkinje cell fires with one initial strong output spike followed by a series of diminishing spikes. When a person performs a new movement for the first time, feedback signals from the muscle and joint proprioceptors will usually denote to the cerebellum how much the actual movement fails to match the intended movement. And the climbing fiber signals in some way alter long-term sensitivity of the Purkinje cells. Over a period of time, this change in sensitivity, along with other possible “learning” functions of the cerebellum, is believed to make the timing and other aspects of cerebellar control of movements approach perfection. When this has been achieved, the climbing fibers no longer need to send “error” signals to the cerebellum to cause further change.

Function of the Cerebellum in Overall Motor Control

The nervous system uses the cerebellum to coordinate motor control functions at three levels, as follows:

1. The vestibulocerebellum. This consists principally of the small flocculonodular cerebellar lobes that lie under the posterior cerebellum and adjacent portions of the vermis. It provides neural circuits for most of the body’s equilibrium movements.

2. The spinocerebellum. This consists of most of the vermis of the posterior and anterior cerebellum plus the adjacent intermediate zones on both sides of the vermis. It provides the circuitry for coordinating mainly movements of the distal portions of the limbs, especially the hands and fingers.

3. The cerebrocerebellum. This consists of the large lateral zones of the cerebellar hemispheres, lateral to the intermediate zones. It receives virtually all its input from the cerebral motor cortex and adjacent premotor and somatosensory cortices of the cerebrum. It transmits its output information in the upward direction back to the brain, functioning in a feedback manner with the cerebral cortical sensorimotor system to plan sequential voluntary body and limb movements, planning these as much as tenths of a second in advance of the actual movements. This is called development of “motor imagery” of movements to be performed.

Vestibulocerebellum Functions in Association with the Brain Stem and Spinal Cord to Control Equilibrium and Postural Movements

The vestibulocerebellum originated phylogenetically at about the same time that the vestibular apparatus in the inner ear developed. Furthermore, as discussed in Chapter 55, loss of the flocculonodular lobes and adjacent portions of the vermis of the cerebellum, which constitute the vestibulocerebellum, causes extreme disturbance of equilibrium and postural movements.

We still must ask the question, what role does the vestibulocerebellum play in equilibrium that cannot be provided by other neuronal machinery of the brain stem? A clue is the fact that in people with vestibulocerebellar dysfunction, equilibrium is far more disturbed during performance of rapid motions than during stasis, especially when these movements involve changes in direction of movement and stimulate the semicircular ducts. This suggests that the vestibulocerebellum is important in controlling balance between agonist and antagonist muscle contractions of the spine, hips, and shoulders during rapid changes in body positions as required by the vestibular apparatus.

One of the major problems in controlling balance is the amount of time required to transmit position signals and velocity of movement signals from the different parts of the body to the brain. Even when the most rapidly conducting sensory pathways are used, up to 120 m/sec in the spinocerebellar afferent tracts, the delay for transmission from the feet to the brain is still 15 to 20 milliseconds. The feet of a person running rapidly can move as much as 10 inches during that time. Therefore, it is never possible for return signals from the peripheral parts of the body to reach the brain at the same time that the movements actually occur. How, then, is it possible for the brain to know when to stop a movement and to perform the next sequential act when the movements are performed rapidly? The answer is that the signals from the periphery tell the brain how rapidly and in which directions the body parts are moving. It is then the function of the vestibulocerebellum to calculate in advance from these rates and directions where the different parts will be during the next few milliseconds. The results of these calculations are the key to the brain’s progression to the next sequential movement.

Thus, during control of equilibrium, it is presumed that information from both the body periphery and the vestibular apparatus is used in a typical feedback control circuit to provide anticipatory correction of postural motor signals necessary for maintaining equilibrium even during extremely rapid motion, including rapidly changing directions of motion.

Spinocerebellum—Feedback Control of Distal Limb Movements by Way of the Intermediate Cerebellar Cortex and the Interposed Nucleus

As shown in Figure 56-8, the intermediate zone of each cerebellar hemisphere receives two types of information when a movement is performed: (1) information from the cerebral motor cortex and from the midbrain red nucleus, telling the cerebellum the intended sequential plan of movement for the next few fractions of a second, and (2) feedback information from the peripheral parts of the body, especially from the distal proprioceptors of the limbs, telling the cerebellum what actual movements result.

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Figure 56-8 Cerebral and cerebellar control of voluntary movements, involving especially the intermediate zone of the cerebellum.

After the intermediate zone of the cerebellum has compared the intended movements with the actual movements, the deep nuclear cells of the interposed nucleus send corrective output signals (1) back to the cerebral motor cortexthrough relay nuclei in the thalamus and (2) to the magnocellular portion (the lower portion) of the red nucleus that gives rise to the rubrospinal tract. The rubrospinal tract in turn joins the corticospinal tract in innervating the lateral most motor neurons in the anterior horns of the spinal cord gray matter, the neurons that control the distal parts of the limbs, particularly the hands and fingers.

This part of the cerebellar motor control system provides smooth, coordinate movements of the agonist and antagonist muscles of the distal limbs for performing acute purposeful patterned movements. The cerebellum seems to compare the “intentions” of the higher levels of the motor control system, as transmitted to the intermediate cerebellar zone through the corticopontocerebellar tract, with the “performance” by the respective parts of the body, as transmitted back to the cerebellum from the periphery. In fact, the ventral spinocerebellar tract even transmits back to the cerebellum an “efference” copy of the actual motor control signals that reach the anterior motor neurons, and this is also integrated with the signals arriving from the muscle spindles and other proprioceptor sensory organs, transmitted principally in the dorsal spinocerebellar tract. Similar comparator signals also go to the inferior olivary complex; if the signals do not compare favorably, the olivary-Purkinje cell system along with possibly other cerebellar learning mechanisms eventually corrects the motions until they perform the desired function.

Function of the Cerebellum to Prevent Overshoot of Movements and to “Damp” Movements

Almost all movements of the body are “pendular.” For instance, when an arm is moved, momentum develops, and the momentum must be overcome before the movement can be stopped. Because of momentum, all pendular movements have a tendency to overshoot. If overshooting does occur in a person whose cerebellum has been destroyed, the conscious centers of the cerebrum eventually recognize this and initiate a movement in the reverse direction attempting to bring the arm to its intended position. But the arm, by virtue of its momentum, overshoots once more in the opposite direction, and appropriate corrective signals must again be instituted. Thus, the arm oscillates back and forth past its intended point for several cycles before it finally fixes on its mark. This effect is called an action tremor,or intention tremor.

But, if the cerebellum is intact, appropriate learned, subconscious signals stop the movement precisely at the intended point, thereby preventing the overshoot and the tremor. This is the basic characteristic of a damping system. All control systems regulating pendular elements that have inertia must have damping circuits built into the mechanisms. For motor control by the nervous system, the cerebellum provides most of this damping function.

Cerebellar Control of Ballistic Movements

Most rapid movements of the body, such as the movements of the fingers in typing, occur so rapidly that it is not possible to receive feedback information either from the periphery to the cerebellum or from the cerebellum back to the motor cortex before the movements are over. These movements are called ballistic movements, meaning that the entire movement is preplanned and set into motion to go a specific distance and then to stop. Another important example is the saccadic movements of the eyes, in which the eyes jump from one position to the next when reading or when looking at successive points along a road as a person is moving in a car.

Much can be understood about the function of the cerebellum by studying the changes that occur in these ballistic movements when the cerebellum is removed. Three major changes occur: (1) The movements are slow to develop and do not have the extra onset surge that the cerebellum usually provides, (2) the force developed is weak, and (3) the movements are slow to turn off, usually allowing the movement to go well beyond the intended mark. Therefore, in the absence of the cerebellar circuit, the motor cortex has to think extra hard to turn ballistic movements on and again has to think hard and take extra time to turn the movement off. Thus, the automatism of ballistic movements is lost.

Considering once again the circuitry of the cerebellum, one sees that it is beautifully organized to perform this biphasic, first excitatory and then delayed inhibitory function that is required for preplanned rapid ballistic movements. One also sees that the built-in timing circuits of the cerebellar cortex are fundamental to this particular ability of the cerebellum.

Cerebrocerebellum—Function of the Large Lateral Zone of the Cerebellar Hemisphere to Plan, Sequence, and Time Complex Movements

In human beings, the lateral zones of the two cerebellar hemispheres are highly developed and greatly enlarged. This goes along with human abilities to plan and perform intricate sequential patterns of movement, especially with the hands and fingers, and to speak. Yet the large lateral zones of the cerebellar hemispheres have no direct input of information from the peripheral parts of the body. Also, almost all communication between these lateral cerebellar areas and the cerebral cortex is not with the primary cerebral motor cortex itself but instead with the premotor area and primary and association somatosensory areas.

Even so, destruction of the lateral zones of the cerebellar hemispheres along with their deep nuclei, the dentate nuclei, can lead to extreme incoordination of complex purposeful movements of the hands, fingers, and feet and of the speech apparatus. This has been difficult to understand because of lack of direct communication between this part of the cerebellum and the primary motor cortex. However, experimental studies suggest that these portions of the cerebellum are concerned with two other important but indirect aspects of motor control: (1) the planning of sequential movements and (2) the “timing” of the sequential movements.

Planning of Sequential Movements

The planning of sequential movements requires that the lateral zones of the hemispheres communicate with both the premotor and the sensory portions of the cerebral cortex, and it requires two-way communication between these cerebral cortex areas with corresponding areas of the basal ganglia. It seems that the “plan” of sequential movements actually begins in the sensory and premotor areas of the cerebral cortex, and from there the plan is transmitted to the lateral zones of the cerebellar hemispheres. Then, amid much two-way traffic between cerebellum and cerebral cortex, appropriate motor signals provide transition from one sequence of movements to the next.

An interesting observation that supports this view is that many neurons in the cerebellar dentate nuclei display the activity pattern for the sequential movement that is yet to come while the present movement is still occurring. Thus, the lateral cerebellar zones appear to be involved not with what movement is happening at a given moment but with what will be happening during the next sequential movement a fraction of a second or perhaps even seconds later.

To summarize, one of the most important features of normal motor function is one’s ability to progress smoothly from one movement to the next in orderly succession. In the absence of the large lateral zones of the cerebellar hemispheres, this capability is seriously disturbed for rapid movements.

Timing Function

Another important function of the lateral zones of the cerebellar hemispheres is to provide appropriate timing for each succeeding movement. In the absence of these cerebellar zones, one loses the subconscious ability to predict how far the different parts of the body will move in a given time. Without this timing capability, the person becomes unable to determine when the next sequential movement needs to begin. As a result, the succeeding movement may begin too early or, more likely, too late. Therefore, lesions in the lateral zones of the cerebellum cause complex movements (such as those required for writing, running, or even talking) to become incoordinate and lacking ability to progress in orderly sequence from one movement to the next. Such cerebellar lesions are said to cause failure of smooth progression of movements.

Extramotor Predictive Functions of the Cerebrocerebellum

The cerebrocerebellum (the large lateral lobes) also helps to “time” events other than movements of the body. For instance, the rates of progression of both auditory and visual phenomena can be predicted by the brain, but both of these require cerebellar participation. As an example, a person can predict from the changing visual scene how rapidly he or she is approaching an object. A striking experiment that demonstrates the importance of the cerebellum in this ability is the effects of removing the large lateral portions of the cerebellum in monkeys. Such a monkey occasionally charges the wall of a corridor and literally bashes its brains because it is unable to predict when it will reach the wall.

We are only now beginning to learn about these extramotor predictive functions of the cerebellum. It is quite possible that the cerebellum provides a “time-base,” perhaps using time-delay circuits, against which signals from other parts of the central nervous system can be compared; it is often stated that the cerebellum is particularly helpful in interpreting rapidly changing spatiotemporal relations in sensory information.

Clinical Abnormalities of the Cerebellum

Destruction of small portions of the lateral cerebellar cortex seldom causes detectable abnormalities in motor function. In fact, several months after as much as one half of the lateral cerebellar cortex on one side of the brain has been removed, if the deep cerebellar nuclei are not removed along with the cortex, the motor functions of the animal appear to be almost normal as long as the animal performs all movements slowly. Thus, the remaining portions of the motor control system are capable of compensating tremendously for loss of parts of the cerebellum.

To cause serious and continuing dysfunction of the cerebellum, the cerebellar lesion usually must involve one or more of the deep cerebellar nuclei—the dentate, interposed, or fastigial nuclei.

Dysmetria and Ataxia

Two of the most important symptoms of cerebellar disease are dysmetria and ataxia. In the absence of the cerebellum, the subconscious motor control system cannot predict how far movements will go. Therefore, the movements ordinarily overshoot their intended mark; then the conscious portion of the brain overcompensates in the opposite direction for the succeeding compensatory movement. This effect is called dysmetria, and it results in uncoordinated movements that are called ataxia. Dysmetria and ataxia can also result from lesions in the spinocerebellar tracts because feedback information from the moving parts of the body to the cerebellum is essential for cerebellar timing of movement termination.

Past Pointing

Past pointing means that in the absence of the cerebellum, a person ordinarily moves the hand or some other moving part of the body considerably beyond the point of intention. This results from the fact that normally the cerebellum initiates most of the motor signal that turns off a movement after it is begun; if the cerebellum is not available to do this, the movement ordinarily goes beyond the intended mark. Therefore, past pointing is actually a manifestation of dysmetria.

Failure of Progression

Dysdiadochokinesia—Inability to Perform Rapid Alternating Movements

When the motor control system fails to predict where the different parts of the body will be at a given time, it “loses” perception of the parts during rapid motor movements. As a result, the succeeding movement may begin much too early or much too late, so no orderly “progression of movement” can occur. One can demonstrate this readily by having a patient with cerebellar damage turn one hand upward and downward at a rapid rate. The patient rapidly “loses” all perception of the instantaneous position of the hand during any portion of the movement. As a result, a series of stalled attempted but jumbled movements occurs instead of the normal coordinate upward and downward motions. This is called dysdiadochokinesia.

Dysarthria—Failure of Progression in Talking

Another example in which failure of progression occurs is in talking because the formation of words depends on rapid and orderly succession of individual muscle movements in the larynx, mouth, and respiratory system. Lack of coordination among these and inability to adjust in advance either the intensity of sound or duration of each successive sound causes jumbled vocalization, with some syllables loud, some weak, some held for long intervals, some held for short intervals, and resultant speech that is often unintelligible. This is called dysarthria.

Intention Tremor

When a person who has lost the cerebellum performs a voluntary act, the movements tend to oscillate, especially when they approach the intended mark, first overshooting the mark and then vibrating back and forth several times before settling on the mark. This reaction is called an intention tremor or an action tremor, and it results from cerebellar overshooting and failure of the cerebellar system to “damp” the motor movements.

Cerebellar Nystagmus—Tremor of the Eyeballs

Cerebellar nystagmus is tremor of the eyeballs that occurs usually when one attempts to fixate the eyes on a scene to one side of the head. This off-center type of fixation results in rapid, tremulous movements of the eyes rather than steady fixation, and it is another manifestation of failure of damping by the cerebellum. It occurs especially when the flocculonodular lobes of the cerebellum are damaged; in this instance it is also associated with loss of equilibrium because of dysfunction of the pathways through the flocculonodular cerebellum from the semicircular ducts.

Hypotonia—Decreased Tone of the Musculature

Loss of the deep cerebellar nuclei, particularly of the dentate and interposed nuclei, causes decreased tone of the peripheral body musculature on the side of the cerebellar lesion. The hypotonia results from loss of cerebellar facilitation of the motor cortex and brain stem motor nuclei by tonic signals from the deep cerebellar nuclei.

Basal Ganglia—Their Motor Functions

The basal ganglia, like the cerebellum, constitute another accessory motor system that functions usually not by itself but in close association with the cerebral cortex and corticospinal motor control system. In fact, the basal ganglia receive most of their input signals from the cerebral cortex itself and also return almost all their output signals back to the cortex.

Figure 56-9 shows the anatomical relations of the basal ganglia to other structures of the brain. On each side of the brain, these ganglia consist of the caudate nucleus, putamen, globus pallidus, substantia nigra, and subthalamic nucleus. They are located mainly lateral to and surrounding the thalamus, occupying a large portion of the interior regions of both cerebral hemispheres. Note also that almost all motor and sensory nerve fibers connecting the cerebral cortex and spinal cord pass through the space that lies between the major masses of the basal ganglia, the caudate nucleus and the putamen. This space is called the internal capsule of the brain. It is important for our current discussion because of the intimate association between the basal ganglia and the corticospinal system for motor control.

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Figure 56-9 Anatomical relations of the basal ganglia to the cerebral cortex and thalamus, shown in three-dimensional view.

(Redrawn from Guyton AC: Basic Neuroscience: Anatomy and Physiology. Philadelphia: WB Saunders, 1992.)

Neuronal Circuitry of the Basal Ganglia

The anatomical connections between the basal ganglia and the other brain elements that provide motor control are complex, as shown in Figure 56-10. To the left is shown the motor cortex, thalamus, and associated brain stem and cerebellar circuitry. To the right is the major circuitry of the basal ganglia system, showing the tremendous interconnections among the basal ganglia themselves plus extensive input and output pathways between the other motor regions of the brain and the basal ganglia.

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Figure 56-10 Relation of the basal ganglial circuitry to the corticospinal-cerebellar system for movement control.

In the next few sections we concentrate especially on two major circuits, the putamen circuit and the caudate circuit.

Function of the Basal Ganglia in Executing Patterns of Motor Activity—the Putamen Circuit

One of the principal roles of the basal ganglia in motor control is to function in association with the corticospinal system to control complex patterns of motor activity. An example is the writing of letters of the alphabet. When there is serious damage to the basal ganglia, the cortical system of motor control can no longer provide these patterns. Instead, one’s writing becomes crude, as if one were learning for the first time how to write.

Other patterns that require the basal ganglia are cutting paper with scissors, hammering nails, shooting a basketball through a hoop, passing a football, throwing a baseball, the movements of shoveling dirt, most aspects of vocalization, controlled movements of the eyes, and virtually any other of our skilled movements, most of them performed subconsciously.

Neural Pathways of the Putamen Circuit

Figure 56-11 shows the principal pathways through the basal ganglia for executing learned patterns of movement. They begin mainly in the premotor and supplementary areas of the motor cortex and in the somatosensory areas of the sensory cortex. Next they pass to the putamen (mainly bypassing the caudate nucleus), then to the internal portion of the globus pallidus, next to the ventroanterior and ventrolateral relay nuclei of the thalamus, and finally return to the cerebral primary motor cortex and to portions of the premotor and supplementary cerebral areas closely associated with the primary motor cortex. Thus, the putamen circuit has its inputs mainly from those parts of the brain adjacent to the primary motor cortex but not much from the primary motor cortex itself. Then its outputs do go mainly back to the primary motor cortex or closely associated premotor and supplementary cortex. Functioning in close association with this primary putamen circuit are ancillary circuits that pass from the putamen through the external globus pallidus, the subthalamus, and the substantia nigra—finally returning to the motor cortex by way of the thalamus.

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Figure 56-11 Putamen circuit through the basal ganglia for subconscious execution of learned patterns of movement.

Abnormal Function in the Putamen Circuit: Athetosis, Hemiballismus, and Chorea

How does the putamen circuit function to help execute patterns of movement? The answer is poorly known. However, when a portion of the circuit is damaged or blocked, certain patterns of movement become severely abnormal. For instance, lesions in the globus pallidus frequently lead to spontaneous and often continuous writhing movements of a hand, an arm, the neck, or the face—movements called athetosis.

A lesion in the subthalamus often leads to sudden flailing movements of an entire limb, a condition called hemiballismus.

Multiple small lesions in the putamen lead to flicking movements in the hands, face, and other parts of the body, called chorea.

Lesions of the substantia nigra lead to the common and extremely severe disease of rigidity, akinesia, and tremors known as Parkinson’s disease, which we discuss in more detail later.

Role of the Basal Ganglia for Cognitive Control of Sequences of Motor Patterns—the Caudate Circuit

The term cognition means the thinking processes of the brain, using both sensory input to the brain plus information already stored in memory. Most of our motor actions occur as a consequence of thoughts generated in the mind, a process called cognitive control of motor activity. The caudate nucleus plays a major role in this cognitive control of motor activity.

The neural connections between the caudate nucleus and the corticospinal motor control system, shown in Figure 56-12, are somewhat different from those of the putamen circuit. Part of the reason for this is that the caudate nucleus, as shown in Figure 56-9, extends into all lobes of the cerebrum, beginning anteriorly in the frontal lobes, then passing posteriorly through the parietal and occipital lobes, and finally curving forward again like the letter “C” into the temporal lobes. Furthermore, the caudate nucleus receives large amounts of its input from the association areas of the cerebral cortex overlying the caudate nucleus, mainly areas that also integrate the different types of sensory and motor information into usable thought patterns.

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Figure 56-12 Caudate circuit through the basal ganglia for cognitive planning of sequential and parallel motor patterns to achieve specific conscious goals.

After the signals pass from the cerebral cortex to the caudate nucleus, they are next transmitted to the internal globus pallidus, then to the relay nuclei of the ventroanterior and ventrolateral thalamus, and finally back to the prefrontal, premotor, and supplementary motor areas of the cerebral cortex, but with almost none of the returning signals passing directly to the primary motor cortex. Instead, the returning signals go to those accessory motor regions in the premotor and supplementary motor areas that are concerned with putting together sequential patterns of movement lasting 5 or more seconds instead of exciting individual muscle movements.

A good example of this would be a person seeing a lion approach and then responding instantaneously and automatically by (1) turning away from the lion, (2) beginning to run, and (3) even attempting to climb a tree. Without the cognitive functions, the person might not have the instinctive knowledge, without thinking for too long a time, to respond quickly and appropriately. Thus, cognitive control of motor activity determines subconsciously, and within seconds, which patterns of movement will be used together to achieve a complex goal that might itself last for many seconds.

Function of the Basal Ganglia to Change the Timing and to Scale the Intensity of Movements

Two important capabilities of the brain in controlling movement are (1) to determine how rapidly the movement is to be performed and (2) to control how large the movement will be. For instance, a person may write the letter “a” slowly or rapidly. Also, he or she may write a small “a” on a piece of paper or a large “a” on a chalkboard. Regardless of the choice, the proportional characteristics of the letter remain nearly the same.

In patients with severe lesions of the basal ganglia, these timing and scaling functions are poor; in fact, sometimes they are nonexistent. Here again, the basal ganglia do not function alone; they function in close association with the cerebral cortex. One especially important cortical area is the posterior parietal cortex, which is the locus of the spatial coordinates for motor control of all parts of the body, as well as for the relation of the body and its parts to all its surroundings. Damage to this area does not produce simple deficits of sensory perception, such as loss of tactile sensation, blindness, or deafness. Instead, lesions of the posterior parietal cortex produce an inability to accurately perceive objects through normally functioning sensory mechanisms, a condition called agnosia.Figure 56-13 shows the way in which a person with a lesion in the right posterior parietal cortex might try to copy drawings. In these cases, the patient’s ability to copy the left side of the drawings is severely impaired. Also, such a person will always try to avoid using his or her left arm, left hand, or other portions of his or her left body for the performance of tasks, or even wash this side of the body (personal neglect syndrome), almost not knowing that these parts of his or her body exist.

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Figure 56-13 Illustration of drawings that might be made by a person who has neglect syndrome caused by severe damage in his or her right posterior parietal cortex compared with the actual drawing the patient was requested to copy. Note that the person’s ability to copy the left side of the drawings is severely impaired.

Because the caudate circuit of the basal ganglial system functions mainly with association areas of the cerebral cortex such as the posterior parietal cortex, presumably the timing and scaling of movements are functions of this caudate cognitive motor control circuit. However, our understanding of function in the basal ganglia is still so imprecise that much of what is conjectured in the last few sections is analytical deduction rather than proven fact.

Functions of Specific Neurotransmitter Substances in the Basal Ganglial System

Figure 56-14 demonstrates the interplay of several specific neurotransmitters that are known to function within the basal ganglia, showing (1) dopamine pathways from the substantia nigra to the caudate nucleus and putamen, (2) gamma-aminobutyric acid (GABA) pathways from the caudate nucleus and putamen to the globus pallidus and substantia nigra, (3) acetylcholine pathways from the cortex to the caudate nucleus and putamen, and (4) multiple general pathways from the brain stem that secrete norepinephrine, serotonin, enkephalin, and several other neurotransmitters in the basal ganglia, as well as in other parts of the cerebrum. In addition to all these are multiple glutamate pathways that provide most of the excitatory signals (not shown in the figure) that balance out the large numbers of inhibitory signals transmitted especially by the dopamine, GABA, and serotonin inhibitory transmitters. We have more to say about some of these neurotransmitter and hormonal systems in subsequent sections when we discuss diseases of the basal ganglia, as well as in subsequent chapters when we discuss behavior, sleep, wakefulness, and functions of the autonomic nervous system.

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Figure 56-14 Neuronal pathways that secrete different types of neurotransmitter substances in the basal ganglia. Ach, acetylcholine; GABA, gamma-aminobutyric acid.

For the present, it should be remembered that the neurotransmitter GABA always functions as an inhibitory agent. Therefore, GABA neurons in the feedback loops from the cortex through the basal ganglia and then back to the cortex make virtually all these loops negative feedback loops, rather than positive feedback loops, thus lending stability to the motor control systems. Dopamine also functions as an inhibitory neurotransmitter in most parts of the brain, so it also functions as a stabilizer under some conditions.

Clinical Syndromes Resulting from Damage to the Basal Ganglia

Aside from athetosis and hemiballismus, which have already been mentioned in relation to lesions in the globus pallidus and subthalamus, two other major diseases result from damage in the basal ganglia. These are Parkinson’s disease and Huntington’s disease.

Parkinson’s Disease

Parkinson’s disease, known also as paralysis agitans, results from widespread destruction of that portion of the substantia nigra (the pars compacta) that sends dopamine-secreting nerve fibers to the caudate nucleus and putamen. The disease is characterized by (1) rigidity of much of the musculature of the body; (2) involuntary tremor of the involved areas even when the person is resting at a fixed rate of three to six cycles per second; and (3) serious difficulty in initiating movement, called akinesia; (4) postural instability caused by impaired postural reflexes, leading to poor balance and falls; and (5) other motor symptoms including dysphagia (impaired ability to swallow), speech disorders, gait disturbances, and fatigue.

The causes of these abnormal motor effects are unknown. However, the dopamine secreted in the caudate nucleus and putamen is an inhibitory transmitter; therefore, destruction of the dopaminergic neurons in the substantia nigra of the parkinsonian patient theoretically would allow the caudate nucleus and putamen to become overly active and possibly cause continuous output of excitatory signals to the corticospinal motor control system. These signals could overly excite many or all of the muscles of the body, thus leading to rigidity.

Some of the feedback circuits might easily oscillate because of high feedback gains after loss of their inhibition, leading to the tremor of Parkinson’s disease. This tremor is quite different from that of cerebellar disease because it occurs during all waking hours and therefore is an involuntary tremor, in contradistinction to cerebellar tremor, which occurs only when the person performs intentionally initiated movements and therefore is called intention tremor.

The akinesia that occurs in Parkinson’s disease is often much more distressing to the patient than are the symptoms of muscle rigidity and tremor, because to perform even the simplest movement in severe parkinsonism, the person must exert the highest degree of concentration. The mental effort, even mental anguish, that is necessary to make the desired movements is often at the limit of the patient’s willpower. Then, when the movements do occur, they are usually stiff and staccato in character instead of smooth. The cause of this akinesia is still speculative. However, dopamine secretion in the limbic system, especially in the nucleus accumbens, is often decreased along with its decrease in the basal ganglia. It has been suggested that this might reduce the psychic drive for motor activity so greatly that akinesia results.

Treatment with L-Dopa

Administration of the drug L-dopa to patients with Parkinson’s disease usually ameliorates many of the symptoms, especially the rigidity and akinesia. The reason for this is believed to be that L-dopa is converted in the brain into dopamine, and the dopamine then restores the normal balance between inhibition and excitation in the caudate nucleus and putamen. Administration of dopamine itself does not have the same effect because dopamine has a chemical structure that will not allow it to pass through the blood-brain barrier, even though the slightly different structure of L-dopa does allow it to pass.

Treatment with L-Deprenyl

Another treatment for Parkinson’s disease is the drug L-deprenyl. This drug inhibits monoamine oxidase, which is responsible for destruction of most of the dopamine after it has been secreted. Therefore, any dopamine that is released remains in the basal ganglial tissues for a longer time. In addition, for reasons not understood, this treatment helps to slow destruction of the dopamine-secreting neurons in the substantia nigra. Therefore, appropriate combinations of L-dopa therapy along with L-deprenyl therapy usually provide much better treatment than use of one of these drugs alone.

Treatment with Transplanted Fetal Dopamine Cells

Transplantation of dopamine-secreting cells (cells obtained from the brains of aborted fetuses) into the caudate nuclei and putamen has been used with some short-term success to treat Parkinson’s disease. However, the cells do not live for more than a few months. If persistence could be achieved, perhaps this would become the treatment of the future.

Treatment by Destroying Part of the Feedback Circuitry in the Basal Ganglia

Because abnormal signals from the basal ganglia to the motor cortex cause most of the abnormalities in Parkinson’s disease, multiple attempts have been made to treat these patients by blocking these signals surgically. For a number of years, surgical lesions were made in the ventrolateral and ventroanterior nuclei of the thalamus, which blocked part of the feedback circuit from the basal ganglia to the cortex; variable degrees of success were achieved, as well as sometimes serious neurological damage. In monkeys with Parkinson’s disease, lesions placed in the subthalamus have been used, sometimes with surprisingly good results.

Huntington’s Disease (Huntington’s Chorea)

Huntington’s disease is a hereditary disorder that usually begins causing symptoms at age 30 to 40 years. It is characterized at first by flicking movements in individual muscles and then progressive severe distortional movements of the entire body. In addition, severe dementia develops along with the motor dysfunctions.

The abnormal movements of Huntington’s disease are believed to be caused by loss of most of the cell bodies of the GABA-secreting neurons in the caudate nucleus and putamen and of acetylcholine-secreting neurons in many parts of the brain. The axon terminals of the GABA neurons normally inhibit portions of the globus pallidus and substantia nigra. This loss of inhibition is believed to allow spontaneous outbursts of globus pallidus and substantia nigra activity that cause the distortional movements.

The dementia in Huntington’s disease probably does not result from the loss of GABA neurons but from the loss of acetylcholine-secreting neurons, perhaps especially in the thinking areas of the cerebral cortex.

The abnormal gene that causes Huntington’s disease has been found; it has a many-times-repeating codon, CAG, that codes for multiple extra glutamine amino acids in the molecular structure of an abnormal neuronal cell protein called huntington that causes the symptoms. How this protein causes the disease effects is now the question for major research effort.

Integration of the Many Parts of the Total Motor Control System

Finally, we need to summarize as best we can what is known about overall control of movement. To do this, let us first give a synopsis of the different levels of control.

Spinal Level

Programmed in the spinal cord are local patterns of movement for all muscle areas of the body—for instance, programmed withdrawal reflexes that pull any part of the body away from a source of pain. The cord is the locus also of complex patterns of rhythmical motions such as to-and-fro movement of the limbs for walking, plus reciprocal motions on opposite sides of the body or of the hindlimbs versus the forelimbs in four-legged animals.

All these programs of the cord can be commanded into action by higher levels of motor control, or they can be inhibited while the higher levels take over control.

Hindbrain Level

The hindbrain provides two major functions for general motor control of the body: (1) maintenance of axial tone of the body for the purpose of standing and (2) continuous modification of the degrees of tone in the different muscles in response to information from the vestibular apparatuses for the purpose of maintaining body equilibrium.

Motor Cortex Level

The motor cortex system provides most of the activating motor signals to the spinal cord. It functions partly by issuing sequential and parallel commands that set into motion various cord patterns of motor action. It can also change the intensities of the different patterns or modify their timing or other characteristics. When needed, the corticospinal system can bypass the cord patterns, replacing them with higher-level patterns from the brain stem or cerebral cortex. The cortical patterns are usually complex; also, they can be “learned,” whereas cord patterns are mainly determined by heredity and are said to be “hard wired.”

Associated Functions of the Cerebellum

The cerebellum functions with all levels of muscle control. It functions with the spinal cord especially to enhance the stretch reflex, so when a contracting muscle encounters an unexpectedly heavy load, a long stretch reflex signal transmitted all the way through the cerebellum and back again to the cord strongly enhances the load-resisting effect of the basic stretch reflex.

At the brain stem level, the cerebellum functions to make the postural movements of the body, especially the rapid movements required by the equilibrium system, smooth and continuous and without abnormal oscillations.

At the cerebral cortex level, the cerebellum operates in association with the cortex to provide many accessory motor functions, especially to provide extra motor force for turning on muscle contraction rapidly at the start of a movement. Near the end of each movement, the cerebellum turns on antagonist muscles at exactly the right time and with proper force to stop the movement at the intended point. Furthermore, there is good physiologic evidence that all aspects of this turn-on/turn-off patterning by the cerebellum can be learned with experience.

The cerebellum functions with the cerebral cortex at still another level of motor control: it helps to program in advance muscle contractions that are required for smooth progression from a present rapid movement in one direction to the next rapid movement in another direction, all this occurring in a fraction of a second. The neural circuit for this passes from the cerebral cortex to the large lateral zones of the cerebellar hemispheres and then back to the cerebral cortex.

The cerebellum functions mainly when muscle movements have to be rapid. Without the cerebellum, slow and calculated movements can still occur, but it is difficult for the corticospinal system to achieve rapid and changing intended movements to execute a particular goal or especially to progress smoothly from one rapid movement to the next.

Associated Functions of the Basal Ganglia

The basal ganglia are essential to motor control in ways entirely different from those of the cerebellum. Their most important functions are (1) to help the cortex execute subconscious but learned patterns of movement and (2) to help plan multiple parallel and sequential patterns of movement that the mind must put together to accomplish a purposeful task.

The types of motor patterns that require the basal ganglia include those for writing all the different letters of the alphabet, for throwing a ball, and for typing. Also, the basal ganglia are required to modify these patterns for writing small or writing very large, thus controlling dimensions of the patterns.

At a still higher level of control is another combined cerebral and basal ganglia circuit, beginning in the thinking processes of the cerebrum to provide overall sequential steps of action for responding to each new situation, such as planning one’s immediate motor response to an assailant who hits the person in the face or one’s sequential response to an unexpectedly fond embrace.

What Drives Us to Action?

What is it that arouses us from inactivity and sets into play our trains of movement? We are beginning to learn about the motivational systems of the brain. Basically, the brain has an older core located beneath, anterior, and lateral to the thalamus—including the hypothalamus, amygdala, hippocampus, septal region anterior to the hypothalamus and thalamus, and even old regions of the thalamus and cerebral cortex themselves—all of which function together to initiate most motor and other functional activities of the brain. These areas are collectively called the limbic system of the brain. We discuss this system in detail in Chapter 58.

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