Chapter 12: Reflex & Voluntary Control of Posture & Movement

After studying this chapter, you should be able to:

• Describe the elements of the stretch reflex and how the activity of γ-motor neurons alters the response to muscle stretch.

• Describe the role of Golgi tendon organs in control of skeletal muscle.

• Describe the elements of the withdrawal reflex.

• Define spinal shock and describe the initial and long-term changes in spinal reflexes that follow transection of the spinal cord.

• Describe how skilled movements are planned and carried out.

• Compare the organization of the central pathways involved in the control of axial (posture) and distal (skilled movement, fine motor movements) muscles.

• Define decerebrate and decorticate rigidity, and comment on the cause and physiologic significance of each.

• Identify the components of the basal ganglia and the pathways that interconnect them, along with the neurotransmitters in each pathway.

• Explain the pathophysiology and symptoms of Parkinson disease and Huntington disease.

• Discuss the functions of the cerebellum and the neurologic abnormalities produced by diseases of this part of the brain.

Somatic motor activity depends ultimately on the pattern and rate of discharge of the spinal motor neurons and homologous neurons in the motor nuclei of the cranial nerves. These neurons, the final common paths to skeletal muscle, are bombarded by impulses from an immense array of descending pathways, other spinal neurons, and peripheral afferents. Some of these inputs end directly on α-motor neurons, but many exert their effects via interneurons or via γ-motor neurons to the muscle spindles and back through the Ia afferent fibers to the spinal cord. It is the integrated activity of these multiple inputs from spinal, medullary, midbrain, and cortical levels that regulates the posture of the body and makes coordinated movement possible.

The inputs converging on motor neurons have three functions: they bring about voluntary activity, they adjust body posture to provide a stable background for movement, and they coordinate the action of the various muscles to make movements smooth and precise. The patterns of voluntary activity are planned within the brain, and the commands are sent to the muscles primarily via the corticospinal and corticobulbar systems. Posture is continually adjusted not only before but also during movement by information carried in descending brainstem pathways and peripheral afferents. Movement is smoothed and coordinated by the medial and intermediate portions of the cerebellum (spinocerebellum) and its connections. The basal ganglia and the lateral portions of the cerebellum (cerebrocerebellum) are part of a feedback circuit to the premotor and motor cortex that is concerned with planning and organizing voluntary movement.

This chapter considers two types of motor output: reflex (involuntary) and voluntary. A subdivision of reflex responses includes some rhythmic movements such as swallowing, chewing, scratching, and walking, which are largely involuntary but subject to voluntary adjustment and control.

The basic unit of integrated reflex activity is the reflex arc. This arc consists of a sense organ, an afferent neuron, one or more synapses within a central integrating station, an efferent neuron, and an effector. The afferent neurons enter via the dorsal roots or cranial nerves and have their cell bodies in the dorsal root ganglia or in the homologous ganglia of the cranial nerves. The efferent fibers leave via the ventral roots or corresponding motor cranial nerves.

Activity in the reflex arc starts in a sensory receptor with a receptor potential whose magnitude is proportional to the strength of the stimulus (Figure 12–1). This generates all-or-none action potentials in the afferent nerve, the number of action potentials being proportional to the size of the receptor potential. In the central nervous system (CNS), the responses are again graded in terms of excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) at the synaptic junctions. All-or-none responses (action potentials) are generated in the efferent nerve. When these reach the effector, they again set up a graded response. When the effector is smooth muscle, responses summate to produce action potentials in the smooth muscle. In contrast, when the effector is skeletal muscle, the graded response is adequate to produce action potentials that bring about muscle contraction. The connection between the afferent and efferent neurons is in the CNS, and activity in the reflex arc is modified by the multiple inputs converging on the efferent neurons or at any synaptic station within the reflex arc.

The stimulus that triggers a reflex is generally very precise. This stimulus is called the adequate stimulus for the particular reflex. A dramatic example is the scratch reflex in the dog. This spinal reflex is adequately stimulated by multiple linear touch stimuli such as those produced by an insect crawling across the skin. The response is vigorous scratching of the area stimulated. If the multiple touch stimuli are widely separated or not in a line, the adequate stimulus is not produced and no scratching occurs. Fleas crawl, but they also jump from place to place. This jumping separates the touch stimuli so that an adequate stimulus for the scratch reflex is not produced.

Reflex activity is stereotyped and specific in that a particular stimulus elicits a particular response. The fact that reflex responses are stereotyped does not exclude the possibility of their being modified by experience. Reflexes are adaptable and can be modified to perform motor tasks and maintain balance. Descending inputs from higher brain regions play an important role in modulating and adapting spinal reflexes.

The α-motor neurons that supply the extrafusal fibers in skeletal muscles are the efferent side of many reflex arcs. All neural influences affecting muscular contraction ultimately funnel through them to the muscles, and they are therefore called the final common pathway. Numerous inputs converge on α-motor neurons. Indeed, the surface of the average motor neuron and its dendrites accommodates about 10,000 synaptic knobs. At least five inputs go from the same spinal segment to a typical spinal motor neuron. In addition to these, there are excitatory and inhibitory inputs, generally relayed via interneurons, from other levels of the spinal cord and multiple long-descending tracts from the brain. All of these pathways converge on and determine the activity in the final common pathways.

The simplest reflex arc is one with a single synapse between the afferent and efferent neurons, and reflexes occurring in them are called monosynaptic reflexes. Reflex arcs in which interneurons are interposed between the afferent and efferent neurons are called polysynaptic reflexes. There can be anywhere from two to hundreds of synapses in a polysynaptic reflex arc.

When a skeletal muscle with an intact nerve supply is stretched, it contracts. This response is called the stretch reflex or myotatic reflex. The stimulus that initiates this reflex is stretch of the muscle, and the response is contraction of the muscle being stretched. The sense organ is a small encapsulated spindlelike or fusiform-shaped structure called the muscle spindle, located within the fleshy part of the muscle. The impulses originating from the spindle are transmitted to the CNS by fast sensory fibers that pass directly to the motor neurons that supply the same muscle. The neurotransmitter at the central synapse is glutamate. The stretch reflex is the best known and studied monosynaptic reflex and is typified by the knee jerk reflex (Clinical Box 12–1).

STRUCTURE OF MUSCLE SPINDLES

Each muscle spindle has three essential elements: (1) a group of specialized intrafusal muscle fibers with contractile polar ends and a noncontractile center, (2) large diameter myelinated afferent nerves (types Ia and II) originating in the central portion of the intrafusal fibers, and (3) small diameter myelinated efferent nerves supplying the polar contractile regions of the intrafusal fibers (Figure 12–2A). It is important to understand the relationship of these elements to each other and to the muscle itself to appreciate the role of this sense organ in signaling changes in the length of the muscle in which it is located. Changes in muscle length are associated with changes in joint angle; thus muscle spindles provide information on position (ie, proprioception).

The intrafusal fibers are positioned in parallel to the extrafusal fibers (the regular contractile units of the muscle) with the ends of the spindle capsule attached to the tendons at either end of the muscle. Intrafusal fibers do not contribute to the overall contractile force of the muscle, but rather serve a pure sensory function. There are two types of intrafusal fibers in mammalian muscle spindles. The first type contains many nuclei in a dilated central area and is called a nuclear bag fiber (Figure 12–2B). There are two subtypes of nuclear bag fibers, dynamic and static. The second intrafusal fiber type, the nuclear chain fiber, is thinner and shorter and lacks a definite bag. Typically, each muscle spindle contains two or three nuclear bag fibers and about five nuclear chain fibers.

There are two kinds of sensory endings in each spindle, a single primary (group Ia) ending and up to eight secondary (group II) endings (Figure 12–2B). The Ia afferent fiber wraps around the center of the dynamic and static nuclear bag fibers and nuclear chain fibers. Group II sensory fibers are located adjacent to the centers of the static nuclear bag and nuclear chain fibers; these fibers do not innervate the dynamic nuclear bag fibers. Ia afferents are very sensitive to the velocity of the change in muscle length during a stretch (dynamic response); thus they provide information about the speed of movements and allow for quick corrective movements. The steady-state (tonic) activity of group Ia and II afferents provide information on steady-state length of the muscle (static response). The top trace in Figure 12–2C shows the dynamic and static components of activity in a Ia afferent during muscle stretch. Note that they discharge most rapidly while the muscle is being stretched (shaded area of graphs) and less rapidly during sustained stretch.

The spindles have a motor nerve supply of their own. These nerves are 3–6 μm in diameter, constitute about 30% of the fibers in the ventral roots, and are called γ-motor neurons. There are two types of γ-motor neurons: dynamic, which supply the dynamic nuclear bag fibers and static, which supply the static nuclear bag fibers and the nuclear chain fibers. Activation of dynamic γ-motor neurons increases the dynamic sensitivity of the group Ia endings. Activation of the static γ-motor neurons increases the tonic level of activity in both group Ia and II endings, decreases the dynamic sensitivity of group Ia afferents, and can prevent silencing of Ia afferents during muscle stretch (Figure 12–2C).

CENTRAL CONNECTIONS OF AFFERENT FIBERS

Ia fibers end directly on motor neurons supplying the extrafusal fibers of the same muscle (Figure 12–3). The time between the application of the stimulus and the response is called the reaction time. In humans, the reaction time for a stretch reflex such as the knee jerk is 19–24 ms. Weak stimulation of the sensory nerve from the muscle, known to stimulate only Ia fibers, causes a contractile response with a similar latency. Because the conduction velocities of the afferent and efferent fiber types are known and the distance from the muscle to the spinal cord can be measured, it is possible to calculate how much of the reaction time was taken up by conduction to and from the spinal cord. When this value is subtracted from the reaction time, the remainder, called the central delay, is the time taken for the reflex activity to traverse the spinal cord. The central delay for the knee jerk reflex is 0.6–0.9 ms. Because the minimum synaptic delay is 0.5 ms, only one synapse could have been traversed.

FUNCTION OF MUSCLE SPINDLES

When the muscle spindle is stretched, its sensory endings are distorted and receptor potentials are generated. These in turn set up action potentials in the sensory fibers at a frequency proportional to the degree of stretching. Because the spindle is in parallel with the extrafusal fibers, when the muscle is passively stretched, the spindles are also stretched, referred to as “loading the spindle.” This initiates reflex contraction of the extrafusal fibers in the muscle. On the other hand, the spindle afferents characteristically stop firing when the muscle is made to contract by electrical stimulation of the α-motor neurons to the extrafusal fibers because the muscle shortens while the spindle is unloaded (Figure 12–4).

The muscle spindle and its reflex connections constitute a feedback device that operates to maintain muscle length. If the muscle is stretched, spindle discharge increases and reflex shortening is produced. If the muscle is shortened without a change in γ-motor neuron discharge, spindle afferent activity decreases and the muscle relaxes.

Dynamic and static responses of muscle spindle afferents influence physiologic tremor. The response of the Ia sensory fiber endings to the dynamic (phasic) as well as the static events in the muscle is important because the prompt, marked phasic response helps dampen oscillations caused by conduction delays in the feedback loop regulating muscle length. Normally a small oscillation occurs in this feedback loop. This physiologic tremor has low amplitude (barely visible to the naked eye) and a frequency of approximately 10 Hz. Physiologic tremor is a normal phenomenon that affects everyone while maintaining posture or during movements. However, the tremor would be more prominent if it were not for the sensitivity of the spindle to velocity of stretch. It can become exaggerated in some situations such as when we are anxious or tired or because of drug toxicity. Numerous factors contribute to the genesis of physiologic tremor. It is likely dependent on not only central (inferior olive) sources but also peripheral factors including motor unit firing rates, reflexes, and mechanical resonance.

EFFECTS OF γ-MOTOR NEURON DISCHARGE

Stimulation of γ-motor neurons produces a very different picture from that produced by stimulation of the α-motor neurons. Stimulation of γ-motor neurons does not lead directly to detectable contraction of the muscles because the intrafusal fibers are not strong enough or plentiful enough to cause shortening. However, stimulation does cause the contractile ends of the intrafusal fibers to shorten and therefore stretches the nuclear bag portion of the spindles, deforming the endings, and initiating impulses in the Ia fibers (Figure 12–4). This in turn can lead to reflex contraction of the muscle. Thus, muscles can be made to contract via stimulation of the α-motor neurons that innervate the extrafusal fibers or the γ-motor neurons that initiate contraction indirectly via the stretch reflex.

If the whole muscle is stretched during stimulation of the γ-motor neurons, the rate of discharge in the Ia fibers is further increased (Figure 12–4). Increased γ-motor neuron activity thus increases spindle sensitivity during stretch.

In response to descending excitatory input to spinal motor circuits, both α- and γ-motor neurons are activated. Because of this “α–γ coactivation,” intrafusal and extrafusal fibers shorten together, and spindle afferent activity can occur throughout the period of muscle contraction. In this way, the spindle remains capable of responding to stretch and reflexively adjusting α-motor neuron discharge.

CONTROL OF γ-MOTOR NEURON DISCHARGE

The γ-motor neurons are regulated to a large degree by descending tracts from a number of areas in the brain that also control α-motor neurons (described below). Via these pathways, the sensitivity of the muscle spindles and hence the threshold of the stretch reflexes in various parts of the body can be adjusted and shifted to meet the needs of postural control.

Other factors also influence γ-motor neuron discharge. Anxiety causes an increased discharge, a fact that probably explains the hyperactive tendon reflexes sometimes seen in anxious patients. In addition, unexpected movement is associated with a greater efferent discharge. Stimulation of the skin, especially by noxious agents, increases γ-motor neuron discharge to ipsilateral flexor muscle spindles while decreasing that to extensors and produces the opposite pattern in the opposite limb. It is well known that trying to pull the hands apart when the flexed fingers are hooked together facilitates the knee jerk reflex (Jendrassik maneuver), and this may also be due to increased γ-motor neuron discharge initiated by afferent impulses from the hands.

RECIPROCAL INNERVATION

When a stretch reflex occurs, the muscles that antagonize the action of the muscle involved (antagonists) relax. This phenomenon is said to be due to reciprocal innervation. Impulses in the Ia fibers from the muscle spindles of the protagonist muscle cause postsynaptic inhibition of the motor neurons to the antagonists. The pathway mediating this effect is bisynaptic. A collateral from each Ia fiber passes in the spinal cord to an inhibitory interneuron that synapses on a motor neuron supplying the antagonist muscles. This example of postsynaptic inhibition is discussed in Chapter 6, and the pathway is illustrated in Figure 6–6.

Up to a point, the harder a muscle is stretched, the stronger is the reflex contraction. However, when the tension becomes great enough, contraction suddenly ceases and the muscle relaxes. This relaxation in response to strong stretch is called the inverse stretch reflex. The receptor for the inverse stretch reflex is in the Golgi tendon organ (Figure 12–5). This organ consists of a netlike collection of knobby nerve endings among the fascicles of a tendon. There are 3–25 muscle fibers per tendon organ. The fibers from the Golgi tendon organs make up the Ib group of myelinated, rapidly conducting sensory nerve fibers. Stimulation of these Ib fibers leads to the production of IPSPs on the motor neurons that supply the muscle from which the fibers arise. The Ib fibers end in the spinal cord on inhibitory interneurons that in turn terminate directly on the motor neurons (Figure 12–3). They also make excitatory connections with motor neurons supplying antagonists to the muscle.

Because the Golgi tendon organs, unlike the spindles, are in series with the muscle fibers, they are stimulated by both passive stretch and active contraction of the muscle. The threshold of the Golgi tendon organs is low. The degree of stimulation by passive stretch is not great because the more elastic muscle fibers take up much of the stretch, and this is why it takes a strong stretch to produce relaxation. However, discharge is regularly produced by contraction of the muscle, and the Golgi tendon organ thus functions as a transducer in a feedback circuit that regulates muscle force in a manner analogous to the spindle feedback circuit that regulates muscle length.

The importance of the primary endings in the spindles and the Golgi tendon organs in regulating the velocity of the muscle contraction, muscle length, and muscle force is illustrated by the fact that section of the afferent nerves to an arm causes the limb to hang loosely in a semiparalyzed state. The interaction of spindle discharge, tendon organ discharge, and reciprocal innervation determines the rate of discharge of α-motor neurons (Clinical Box 12–2).

MUSCLE TONE

The resistance of a muscle to stretch is often referred to as its tone or tonus. If the motor nerve to a muscle is severed, the muscle offers very little resistance and is said to be flaccid. A hypertonic (spastic) muscle is one in which the resistance to stretch is high because of hyperactive stretch reflexes. Somewhere between the states of flaccidity and spasticity is the ill-defined area of normal tone. The muscles are generally hypotonic when the rate of γ-motor neuron discharge is low and hypertonic when it is high.

When the muscles are hypertonic, the sequence of moderate stretch → muscle contraction, strong stretch → muscle relaxation is clearly seen. Passive flexion of the elbow, for example, meets immediate resistance as a result of the stretch reflex in the triceps muscle. Further stretch activates the inverse stretch reflex. The resistance to flexion suddenly collapses, and the arm flexes. Continued passive flexion stretches the muscle again, and the sequence may be repeated. This sequence of resistance followed by a sudden decrease in resistance when a limb is moved passively is known as the clasp-knife effect because of its resemblance to the closing of a pocket knife. It is also known as the lengthening reaction because it is the response of a spastic muscle to lengthening.

Polysynaptic reflex paths branch in a complex manner. The number of synapses in each of their branches varies. Because of the synaptic delay at each synapse, activity in the branches with fewer synapses reaches the motor neurons first, followed by activity in the longer pathways. This causes prolonged bombardment of the motor neurons from a single stimulus and consequently prolonged responses. Furthermore, some of the branch pathways turn back on themselves, permitting activity to reverberate until it becomes unable to cause a propagated transsynaptic response and dies out. Such reverberating circuits are common in the brain and spinal cord.

The withdrawal reflex is a typical polysynaptic reflex that occurs in response to a noxious stimulus to the skin or subcutaneous tissues and muscle. The response is flexor muscle contraction and inhibition of extensor muscles, so that the body part stimulated is flexed and withdrawn from the stimulus. When a strong stimulus is applied to a limb, the response includes not only flexion and withdrawal of that limb but also extension of the opposite limb. This crossed extensor response is properly part of the withdrawal reflex. Strong stimuli can generate activity in the interneuron pool that spreads to all four extremities. This spread of excitatory impulses up and down the spinal cord to more and more motor neurons is called irradiation of the stimulus, and the increase in the number of active motor units is called recruitment of motor units.

IMPORTANCE OF THE WITHDRAWAL REFLEX

Flexor responses can be produced by innocuous stimulation of the skin or by stretch of the muscle, but strong flexor responses with withdrawal are initiated only by stimuli that are noxious or at least potentially harmful (ie, nociceptive stimuli). The withdrawal reflex serves a protective function as flexion of the stimulated limb gets it away from the source of irritation, and extension of the other limb supports the body. The pattern assumed by all four extremities puts one in position to escape from the offending stimulus. Withdrawal reflexes are prepotent; that is, they preempt the spinal pathways from any other reflex activity taking place at the moment.

Many of the characteristics of polysynaptic reflexes can be demonstrated by studying the withdrawal reflex. A weak noxious stimulus to one foot evokes a minimal flexion response; stronger stimuli produce greater and greater flexion as the stimulus irradiates to more and more of the motor neuron pool supplying the muscles of the limb. Stronger stimuli also cause a more prolonged response. A weak stimulus causes one quick flexion movement; a strong stimulus causes prolonged flexion and sometimes a series of flexion movements. This prolonged response is due to prolonged, repeated firing of the motor neurons. The repeated firing is called after-discharge and is due to continued bombardment of motor neurons by impulses arriving by complicated and circuitous polysynaptic paths.

As the strength of a noxious stimulus is increased, the reaction time is shortened. Spatial and temporal facilitation occurs at synapses in the polysynaptic pathway. Stronger stimuli produce more action potentials per second in the active branches and cause more branches to become active; summation of the EPSPs to the threshold level for action potential generation occurs more rapidly.

FRACTIONATION & OCCLUSION

Another characteristic of the withdrawal response is the fact that supramaximal stimulation of any of the sensory nerves from a limb never produces as strong a contraction of the flexor muscles as that elicited by direct electrical stimulation of the muscles themselves. This indicates that the afferent inputs fractionate the motor neuron pool; that is, each input goes to only part of the motor neuron pool for the flexors of that particular extremity. On the other hand, if all the sensory inputs are dissected out and stimulated one after the other, the sum of the tension developed by stimulation of each is greater than that produced by direct electrical stimulation of the muscle or stimulation of all inputs at once. This indicates that the various afferent inputs share some of the motor neurons and that occlusion occurs when all inputs are stimulated at once.

The responses of animals and humans to spinal cord injury (SCI) illustrate the integration of reflexes at the spinal level. The deficits seen after SCI vary, of course, depending on the level of the injury. Clinical Box 12–3 provides information on long-term problems related to SCI and recent advancements in treatment options.

In all vertebrates, transection of the spinal cord is followed by a period of spinal shock during which all spinal reflex responses are profoundly depressed. Subsequently, reflex responses return and become hyperactive. The duration of spinal shock is proportional to the degree of encephalization of motor function in the various species. In frogs and rats it lasts for minutes; in dogs and cats it lasts for 1–2 h; in monkeys it lasts for days; and in humans it usually lasts for a minimum of 2 weeks.

Cessation of tonic bombardment of spinal neurons by excitatory impulses in descending pathways (see below) undoubtedly plays a role in development of spinal shock. In addition, spinal inhibitory interneurons that normally are themselves inhibited may be released from this descending inhibition to become disinhibited. This, in turn, would inhibit motor neurons. The recovery of reflex excitability may be due to the development of denervation hypersensitivity to the mediators released by the remaining spinal excitatory endings. Another contributing factor may be sprouting of collaterals from existing neurons, with the formation of additional excitatory endings on interneurons and motor neurons.

The first reflex response to appear as spinal shock wears off in humans is often a slight contraction of the leg flexors and adductors in response to a noxious stimulus (ie, the withdrawal reflex). In some patients, the knee jerk reflex recovers first. The interval between cord transection and the return of reflex activity is about 2 weeks in the absence of any complications, but if complications are present it is much longer. Once the spinal reflexes begin to reappear after spinal shock, their threshold steadily drops.

Circuits intrinsic to the spinal cord can produce walking movements when stimulated in a suitable manner even after spinal cord transection in cats and dogs. There are two locomotor pattern generators in the spinal cord: one in the cervical region and one in the lumbar region. However, this does not mean that spinal animals or humans can walk without stimulation; the pattern generator has to be turned on by tonic discharge of a discrete area in the midbrain, the mesencephalic locomotor region, and, of course, this is only possible in patients with incomplete spinal cord transection. Interestingly, the generators can also be turned on in experimental animals by administration of the norepinephrine precursor L-dopa (levodopa) after complete section of the spinal cord. Progress is being made in teaching humans with SCI to take a few steps by placing them, with support, on a treadmill.

To voluntarily move a limb, the brain must plan a movement, arrange appropriate motion at many different joints at the same time, and adjust the motion by comparing plan with performance. The motor system “learns by doing” and performance improves with repetition. This involves synaptic plasticity. Damage to the cerebral cortex before or during childbirth or during the first 2–3 years of development can lead to cerebral palsy, a disorder that affects muscle tone, movement, and coordination (Clinical Box 12–4).

There is considerable evidence for the general motor control scheme shown in Figure 12–6. Commands for voluntary movement originate in cortical association areas. The movements are planned in the cortex as well as in the basal ganglia and the lateral portions of the cerebellar hemispheres, as indicated by increased electrical activity before the movement. The basal ganglia and cerebellum funnel information to the premotor and motor cortex by way of the thalamus. Motor commands from the motor cortex are relayed in large part via the corticospinal tracts to the spinal cord and the corresponding corticobulbar tracts to motor neurons in the brainstem. However, collaterals from these pathways and a few direct connections from the motor cortex end on brainstem nuclei, which also project to motor neurons in the brainstem and spinal cord. These pathways can also mediate voluntary movement. Movement sets up alterations in sensory input from the special senses and from muscles, tendons, joints, and the skin. This feedback information, which adjusts and smooths movement, is relayed directly to the motor cortex and to the spinocerebellum. The spinocerebellum projects in turn to the brainstem. The main brainstem pathways that are concerned with posture and coordination are the rubrospinal, reticulospinal, tectospinal, and vestibulospinal tracts.

PRIMARY MOTOR CORTEX

The reader can refer to Figure 8–8 for the locations of the major cortical regions involved in motor control. The primary motor cortex (M1) is in the precentral gyrus of the frontal lobe, extending into the central sulcus. By means of stimulation experiments in patients undergoing craniotomy under local anesthesia, this region was mapped to show where various parts of the body are represented in the precentral gyrus. Figure 12–7 shows the motor homunculus with the feet at the top of the gyrus and the face at the bottom. The facial area is represented bilaterally, but the rest of the representation is generally unilateral, with the cortical motor area controlling the musculature on the opposite side of the body. The cortical representation of each body part is proportional in size to the skill with which the part is used in fine, voluntary movement. The areas involved in speech and hand movements are especially large in the cortex; use of the pharynx, lips, and tongue to form words and of the fingers and opposable thumbs to manipulate the environment are activities in which humans are especially skilled.

Modern brain imaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have been used to map the cortex to identify motor areas. Figure 12–8 shows activation of the hand area of the motor cortex while repetitively squeezing a ball with either the right or left hand.

The cells in the cortical motor areas are arranged in a columnar organization. The ability to elicit discrete movements of a single muscle by electrical stimulation of a column within M1 led to the view that this area was responsible for control of individual muscles. More recent work has shown that neurons in several cortical columns project to the same muscle; in fact, most stimuli activate more than one muscle. Moreover, the cells in each column receive fairly extensive sensory input from the peripheral area in which they produce movement, providing the basis for feedback control of movement. Some of this input may be direct and some is relayed from other parts of the cortex. The current view is that M1 neurons represent movements of groups of muscles for different tasks.

SUPPLEMENTARY MOTOR AREA

The supplementary motor area is on and above the superior bank of the cingulate sulcus on the medial side of the hemisphere. It projects to the primary motor cortex and also contains a map of the body; but it is less precise than in M1. The supplementary motor area may be involved primarily in organizing or planning motor sequences, while M1 executes the movements. Lesions of this area in monkeys produce awkwardness in performing complex activities and difficulty with bimanual coordination.

When human subjects count to themselves without speaking, the motor cortex is quiescent, but when they speak the numbers aloud as they count, blood flow increases in M1 and the supplementary motor area. Thus, both regions are involved in voluntary movement when the movements being performed are complex and involve planning.

PREMOTOR CORTEX

The premotor cortex is located anterior to the precentral gyrus, on the lateral and medial cortical surface; it also contains a somatotopic map. This region receives input from sensory regions of the parietal cortex and projects to M1, the spinal cord, and the brainstem reticular formation. This region may be concerned with setting posture at the start of a planned movement and with getting the individual prepared to move. It is most involved in control of proximal limb muscles needed to orient the body for movement.

POSTERIOR PARIETAL CORTEX

The somatic sensory area and related portions of the posterior parietal lobe project to the premotor cortex. Lesions of the somatic sensory area cause defects in motor performance that are characterized by inability to execute learned sequences of movements such as eating with a knife and fork. Some of the neurons are concerned with aiming the hands toward an object and manipulating it, whereas other neurons are concerned with hand–eye coordination. As described below, neurons in this posterior parietal cortex contribute to the descending pathways involved in motor control.

PLASTICITY

A striking discovery made possible by PET and fMRI is that the motor cortex shows the same kind of plasticity as already described for the sensory cortex in Chapter 8. For example, the finger areas of the contralateral motor cortex enlarge as a pattern of rapid finger movement is learned with the fingers of one hand; this change is detectable at 1 week and maximal at 4 weeks. Cortical areas of output to other muscles also increase in size when motor learning involves these muscles. When a small focal ischemic lesion is produced in the hand area of the motor cortex of monkeys, the hand area may reappear, with return of motor function, in an adjacent undamaged part of the cortex. Thus, the maps of the motor cortex are not immutable, and they change with experience.

Within the brainstem and spinal cord, pathways and neurons that are concerned with the control of skeletal muscles of the trunk (axial) and proximal portions of the limbs are located medially or ventrally, whereas pathways and neurons that are concerned with the control of skeletal muscles in the distal portions of the limbs are located laterally. The axial muscles are concerned with postural adjustments and gross movements, whereas the distal limb muscles mediate fine, skilled movements. Thus, for example, neurons in the medial portion of the ventral horn innervate proximal limb muscles, particularly the flexors, whereas lateral ventral horn neurons innervate distal limb muscles. Similarly, the ventral corticospinal tract and medial descending brainstem pathways (tectospinal, reticulospinal, and vestibulospinal tracts) are concerned with adjustments of proximal muscles and posture, whereas the lateral corticospinal and rubrospinal tracts are concerned with distal limb muscles and, particularly in the case of the lateral corticospinal tract, with skilled voluntary movements. Phylogenetically, the lateral pathways are newer.

CORTICOSPINAL & CORTICOBULBAR TRACTS

The somatotopic organization just described for the motor cortex continues throughout the pathways from the cortex to the motor neurons. The axons of neurons from the motor cortex that project to spinal motor neurons form the corticospinal tracts, a large bundle of about 1 million fibers. About 80% of these fibers cross the midline in the medullary pyramids to form the lateral corticospinal tract (Figure 12–9). The remaining 20% make up the ventral corticospinal tract, which does not cross the midline until it reaches the level of the spinal cord at which it terminates. Lateral corticospinal tract neurons make monosynaptic connections to motor neurons, especially those concerned with skilled movements. Many corticospinal tract neurons also synapse on spinal interneurons antecedent to motor neurons; this indirect pathway is important in coordinating groups of muscles.

The trajectory from the cortex to the spinal cord passes through the corona radiata to the posterior limb of the internal capsule. Within the midbrain they traverse the cerebral peduncle and the basilar pons until they reach the medullary pyramids on their way to the spinal cord.

The corticobulbar tract is composed of the fibers that pass from the motor cortex to motor neurons in the trigeminal, facial, and hypoglossal nuclei. Corticobulbar neurons end either directly on the cranial nerve nuclei or on their antecedent interneurons within the brainstem. Their axons traverse through the genu of the internal capsule, the cerebral peduncle (medial to corticospinal tract neurons), to descend with corticospinal tract fibers in the pons and medulla.

The motor system can be divided into lower and upper motor neurons. Lower motor neurons refer to the spinal and cranial motor neurons that directly innervate skeletal muscles. Upper motor neurons are those in the cortex and brainstem that activate the lower motor neurons. The pathophysiologic responses to damage to lower and upper motor neurons are very distinctive (Clinical Box 12–5).

ORIGINS OF CORTICOSPINAL & CORTICOBULBAR TRACTS

Corticospinal and corticobulbar tract neurons are pyramidal shaped and located in layer V of the cerebral cortex (see Chapter 14). The cortical areas from which these tracts originate were identified on the basis of electrical stimulation that produced prompt discrete movement. About 31% of the corticospinal tract neurons are from the primary motor cortex. The premotor cortex and supplementary motor cortex account for 29% of the corticospinal tract neurons. The other 40% of corticospinal tract neurons originate in the parietal lobe and primary somatosensory area in the postcentral gyrus.

ROLE IN MOVEMENT

The corticospinal and corticobulbar system is the primary pathway for the initiation of skilled voluntary movement. This does not mean that movement—even skilled movement—is impossible without it. Nonmammalian vertebrates have essentially no corticospinal and corticobulbar system, but they move with great agility. Cats and dogs stand, walk, and run after complete destruction of this system. Only in primates are relatively marked deficits produced.

Careful section of the pyramids producing highly selective destruction of the lateral corticospinal tract in laboratory primates produces prompt and sustained loss of the ability to grasp small objects between two fingers and to make isolated movements of the wrists. However, the animal can still use the hand in a gross manner and can stand and walk. These deficits are consistent with loss of control of the distal musculature of the limbs, which is concerned with fine-skilled movements. On the other hand, lesions of the ventral corticospinal tract produce axial muscle deficits that cause difficulty with balance, walking, and climbing.

As mentioned above, spinal motor neurons are organized so that those innervating the most proximal muscles are located most medially and those innervating the more distal muscles are located more laterally. This organization is also reflected in descending brainstem pathways (Figure 12–10).

MEDIAL BRAINSTEM PATHWAYS

The medial brainstem pathways, which work in concert with the ventral corticospinal tract, are the pontine and medullary reticulospinal, vestibulospinal, and tectospinal tracts. These pathways descend in the ipsilateral ventral columns of the spinal cord and terminate predominantly on interneurons and long propriospinal neurons in the ventromedial part of the ventral horn to control axial and proximal muscles. A few medial pathway neurons synapse directly on motor neurons controlling axial muscles.

The medial and lateral vestibulospinal tracts are involved in vestibular function and are described in Chapter 10. The medial tract originates in the medial and inferior vestibular nuclei and projects bilaterally to cervical spinal motor neurons that control neck musculature. The lateral tract originates in the lateral vestibular nuclei and projects ipsilaterally to neurons at all spinal levels. It activates motor neurons to antigravity muscles (eg, proximal limb extensors) to control posture and balance.

The pontine and medullary reticulospinal tracts project to all spinal levels. They are involved in the maintenance of posture and in modulating muscle tone, especially via an input to γ-motor neurons. Pontine reticulospinal neurons are primarily excitatory and medullary reticulospinal neurons are primarily inhibitory.

The tectospinal tract originates in the superior colliculus of the midbrain. It projects to the contralateral cervical spinal cord to control head and eye movements.

LATERAL BRAINSTEM PATHWAY

The main control of distal muscles arise from the lateral corticospinal tract, but neurons within the red nucleus of the midbrain cross the midline and project to interneurons in the dorsolateral part of the spinal ventral horn to also influence motor neurons that control distal limb muscles. This rubrospinal tract excites flexor motor neurons and inhibits extensor motor neurons. This pathway is not very prominent in humans, but it may play a role in the posture typical of decorticate rigidity (see below).

In the intact animal, individual motor responses are submerged in the total pattern of motor activity. When the neural axis is transected, the activities integrated below the section are cut off, or released, from the control of higher brain centers and often appear to be accentuated. Release of this type, long a cardinal principle in neurology, may be due in some situations to removal of an inhibitory control by higher neural centers. A more important cause of the apparent hyperactivity is loss of differentiation of the reaction so that it no longer fits into the broader pattern of motor activity. Research using animal models has led to information on the role of cortical and brainstem mechanisms involved in control of voluntary movement and posture. The deficits in motor control seen after various lesions mimic those seen in humans with damage in the same structures.

DECEREBRATION

A complete transection of the brainstem between the superior and inferior colliculi permits the brainstem pathways to function independent of their input from higher brain structures. This is called a midcollicular decerebration and is diagramed in Figure 12–11 by the dashed line labeled A. This lesion interrupts all input from the cortex (corticospinal and corticobulbar tracts) and red nucleus (rubrospinal tract), primarily to distal muscles of the extremities. The excitatory and inhibitory reticulospinal pathways (primarily to postural extensor muscles) remain intact. The dominance of drive from ascending sensory pathways to the excitatory reticulospinal pathway leads to hyperactivity in extensor muscles in all four extremities which is called decerebrate rigidity. This resembles what ensues after uncal herniation due to a supratentorial lesion. Uncal herniation can occur in patients with large tumors or a hemorrhage in the cerebral hemisphere. Figure 12–12A shows the posture typical of such a patient. Clinical Box 12–6 describes complications related to uncal herniation.

In midcollicular decerebrate cats, section of dorsal roots to a limb (dashed line labeled B in Figure 12–11) immediately eliminates the hyperactivity of extensor muscles. This suggests that decerebrate rigidity is spasticity due to facilitation of the myotatic stretch reflex. That is, the excitatory input from the reticulospinal pathway activates γ-motor neurons which indirectly activate α-motor neurons (via Ia spindle afferent activity). This is called the gamma loop.

The exact site of origin within the cerebral cortex of the fibers that inhibit stretch reflexes is unknown. Under certain conditions, stimulation of the anterior edge of the precentral gyrus can cause inhibition of stretch reflexes and cortically evoked movements. This region, which also projects to the basal ganglia, has been named the suppressor strip.

There is also evidence that decerebrate rigidity leads to direct activation of α-motor neurons. If the anterior lobe of the cerebellum is removed in a decerebrate animal (dashed line labeled C in Figure 12–11), extensor muscle hyperactivity is exaggerated (decerebellate rigidity). This cut eliminates cortical inhibition of the cerebellar fastigial nucleus and secondarily increases excitation to vestibular nuclei. Subsequent dorsal root section does not reverse the rigidity, thus it was due to activation of α-motor neurons independent of the gamma loop.

DECORTICATION

Removal of the cerebral cortex (decortication; dashed line labeled D in Figure 12–11) produces decorticate rigidity which is characterized by flexion of the upper extremities at the elbow and extensor hyperactivity in the lower extremities (Figure 12–12B). The flexion can be explained by rubrospinal excitation of flexor muscles in the upper extremities; the hyperextension of lower extremities is due to the same changes that occur after midcollicular decerebration.

Decorticate rigidity is seen on the hemiplegic side after hemorrhages or thromboses in the internal capsule. Probably because of their anatomy, the small arteries in the internal capsule are especially prone to rupture or thrombotic obstruction, so this type of decorticate rigidity is fairly common. Sixty percent of intracerebral hemorrhages occur in the internal capsule, while 10% occur in the cerebral cortex, 10% in the pons, 10% in the thalamus, and 10% in the cerebellum.

ORGANIZATION OF THE BASAL GANGLIA

The term basal ganglia (or basal nuclei) is applied to five interactive structures on each side of the brain (Figure 12–13). These are the caudate nucleus, putamen, and globus pallidus (three large nuclear masses underlying the cortical mantle), the subthalamic nucleus, and substantia nigra. The caudate nucleus and putamen collectively form the striatum; the putamen and globus pallidus collectively form the lenticular nucleus.

The globus pallidus is divided into external and internal segments (GPe and GPi); both regions contain inhibitory GABAergic neurons. The substantia nigra is divided into a pars compacta, which uses dopamine as a neurotransmitter, and a pars reticulata, which uses GABA as a neurotransmitter. There are at least four neuronal types within the striatum. About 95% of striatal neurons are medium spiny neurons that use GABA as a neurotransmitter. The remaining striatal neurons are all aspiny interneurons that differ in terms of size and neurotransmitters: large (acetylcholine), medium (somatostatin), and small (GABA).

Figure 12–14 shows the major connections to and from and within the basal ganglia along with the neurotransmitters within these pathways. There are two main inputs to the basal ganglia; they are both excitatory (glutamate), and they both terminate in the striatum. They are from a wide region of the cerebral cortex (corticostriate pathway) and from intralaminar nuclei of the thalamus (thalamostriatal pathway). The two major outputs of the basal ganglia are from GPi and substantia nigra pars reticulata. Both are inhibitory (GABAergic) and both project to the thalamus. From the thalamus, there is an excitatory (presumably glutamate) projection to the prefrontal and premotor cortex. This completes a full cortical-basal ganglia-thalamic-cortical loop.

The connections within the basal ganglia include a dopaminergic nigrostriatal projection from the substantia nigra pars compacta to the striatum and a GABAergic projection from the striatum to substantia nigra pars reticulata. There is an inhibitory projection from the striatum to both GPe and GPi. The subthalamic nucleus receives an inhibitory input from GPe, and in turn the subthalamic nucleus has an excitatory (glutamate) projection to both GPe and GPi.

FUNCTION

Neurons in the basal ganglia, like those in the lateral portions of the cerebellar hemispheres, discharge before movements begin. This observation, plus careful analysis of the effects of diseases of the basal ganglion in humans and the effects of drugs that destroy dopaminergic neurons in animals, have led to the idea that the basal ganglia are involved in the planning and programming of movement or, more broadly, in the processes by which an abstract thought is converted into voluntary action (Figure 12–6). They influence the motor cortex via the thalamus, and the corticospinal pathways provide the final common pathway to motor neurons. In addition, GPi projects to nuclei in the brainstem, and from there to motor neurons in the brainstem and spinal cord. The basal ganglia, particularly the caudate nuclei, also play a role in some cognitive processes. Possibly because of the interconnections of this nucleus with the frontal portions of the neocortex, lesions of the caudate nuclei disrupt performance on tests involving object reversal and delayed alternation. In addition, lesions of the head of the left but not the right caudate nucleus and nearby white matter in humans are associated with a dysarthric form of aphasia that resembles Wernicke aphasia (see Chapter 15).

DISEASES OF THE BASAL GANGLIA IN HUMANS

Three distinct biochemical pathways in the basal ganglia normally operate in a balanced manner: (1) the nigrostriatal dopaminergic system, (2) the intrastriatal cholinergic system, and (3) the GABAergic system, which projects from the striatum to the globus pallidus and substantia nigra. When one or more of these pathways become dysfunctional, characteristic motor abnormalities occur. Diseases of the basal ganglia lead to two general types of disorders: hyperkinetic and hypokinetic. The hyperkinetic conditions are those in which movement is excessive and abnormal, including chorea, athetosis, and ballism. Hypokinetic abnormalities include akinesia and bradykinesia.

Chorea is characterized by rapid, involuntary “dancing” movements. Athetosis is characterized by continuous, slow writhing movements. Choreiform and athetotic movements have been likened to the start of voluntary movements occurring in an involuntary, disorganized way. In ballism, involuntary flailing, intense, and violent movements occur. Akinesia is difficulty in initiating movement and decreased spontaneous movement. Bradykinesia is slowness of movement.

In addition to Parkinson disease, which is described below, there are several other disorders known to involve a malfunction within the basal ganglia. A few of these are described in Clinical Box 12–7. Huntington disease is one of an increasing number of human genetic diseases affecting the nervous system that are characterized by trinucleotide repeat expansion. Most of these involve cytosine-adenine-guanine (CAG) repeats (Table 12–1), but one involves CGG repeats and another involves CTG repeats (T refers to thymine). There is also preliminary evidence that increased numbers of a 12-nucleotide repeat are associated with a rare form of epilepsy.

PARKINSON DISEASE

Parkinson disease has both hypokinetic and hyperkinetic features. It was originally described in 1817 by James Parkinson and is named for him. Parkinson disease is the first disease identified as being due to a deficiency in a specific neurotransmitter (Clinical Box 12–8). In the 1960s, Parkinson disease was shown to result from the degeneration of dopaminergic neurons in the substantia nigra pars compacta. The fibers to the putamen (part of the striatum) are most severely affected.

The hypokinetic features of Parkinson disease are akinesia and bradykinesia, and the hyperkinetic features are cogwheel rigidity and tremor at rest. The absence of motor activity and the difficulty in initiating voluntary movements are striking. There is a decrease in the normal, unconscious movements such as swinging of the arms during walking, the panorama of facial expressions related to the emotional content of thought and speech, and the multiple “fidgety” actions and gestures that occur in all of us. The rigidity is different from spasticity because motor neuron discharge increases to both the agonist and antagonist muscles. Passive motion of an extremity meets with a plastic, dead-feeling resistance that has been likened to bending a lead pipe and is therefore called lead pipe rigidity. Sometimes a series of “catches” takes place during passive motion (cogwheel rigidity), but the sudden loss of resistance seen in a spastic extremity is absent. The tremor, which is present at rest and disappears with activity, is due to regular, alternating 8-Hz contractions of antagonistic muscles.

A current view of the pathogenesis of the movement disorders in Parkinson disease is shown in Figure 12–15. In healthy individuals, basal ganglia output is inhibitory via GABAergic nerve fibers. The dopaminergic neurons that project from the substantia nigra to the putamen normally have two effects. They stimulate the D₁ dopamine receptors, which inhibit GPi via direct GABAergic receptors; and they inhibit D₂ receptors, which also inhibit the GPi. In addition, the inhibition reduces the excitatory discharge from the subthalamic nucleus to the GPi. This balance between inhibition and excitation somehow maintains normal motor function. In Parkinson disease, the dopaminergic input to the putamen is lost. This results in decreased inhibition and increased excitation from the subthalamic nucleus to the GPi. The overall increase in inhibitory output to the thalamus and brainstem disorganizes movement.

Familial cases of Parkinson disease occur, but these are uncommon. The genes for at least five proteins can be mutated. These proteins appear to be involved in ubiquitination. Two of the proteins, α-synuclein and barkin, interact and are found in Lewy bodies. The Lewy bodies are inclusion bodies in neurons that occur in all forms of Parkinson disease. However, the significance of these findings is still unsettled.

An important consideration in Parkinson disease is the balance between the excitatory discharge of cholinergic interneurons and the inhibitory dopaminergic input in the striatum. Some improvement is produced by decreasing the cholinergic influence with anticholinergic drugs. More dramatic improvement is produced by administration of L-dopa (levodopa). Unlike dopamine, this dopamine precursor crosses the blood-brain barrier and helps repair the dopamine deficiency. However, the degeneration of these neurons continues and in 5–7 years the beneficial effects of L-dopa disappear.

The cerebellum sits astride the main sensory and motor systems in the brainstem (Figure 12–16). The medial vermis and lateral cerebellar hemispheres are more extensively folded and fissured than the cerebral cortex. The cerebellum weighs only 10% as much as the cerebral cortex, but its surface area is about 75% of that of the cerebral cortex. Anatomically, the cerebellum is divided into three parts by two transverse fissures. The posterolateral fissure separates the medial nodulus and the lateral flocculus on either side from the rest of the cerebellum, and the primary fissure divides the remainder into an anterior and a posterior lobe. Lesser fissures divide the vermis into smaller sections, so that it contains ten primary lobules numbered I–X from superior to inferior.

The cerebellum is connected to the brainstem by three pairs of peduncles that are located above and around the fourth ventricle. The superior cerebellar peduncle includes fibers from deep cerebellar nuclei that project to the brainstem, red nucleus, and thalamus. The middle cerebellar peduncle contains only afferent fibers from the contralateral pontine nuclei, and the inferior cerebellar peduncle a mixture of afferent fibers from the brainstem and spinal cord and efferent fibers to the vestibular nuclei.

The cerebellum has an external cerebellar cortex separated by white matter from the deep cerebellar nuclei. The middle and inferior cerebellar peduncles carry afferent fibers into the cerebellum where they are called mossy and climbing fibers. These fibers emit collaterals to the deep nuclei and pass to the cortex. There are four deep nuclei: the dentate, the globose, the emboliform, and the fastigial nuclei. The globose and the emboliform nuclei are sometimes lumped together as the interpositus nucleus.

ORGANIZATION OF THE CEREBELLUM

The cerebellar cortex has three layers: an external molecular layer, a Purkinje cell layer that is only one cell thick, and an internal granular layer. There are five types of neurons in the cortex: Purkinje, granule, basket, stellate, and Golgi cells (Figure 12–17). The Purkinje cells are among the biggest neurons in the CNS. They have very extensive dendritic arbors that extend throughout the molecular layer. Their axons, which are the only output from the cerebellar cortex, project to the deep cerebellar nuclei, especially the dentate nucleus, where they form inhibitory synapses. They also make inhibitory connections with neurons in the vestibular nuclei.

The cerebellar granule cells, whose cell bodies are in the granular layer, receive excitatory input from the mossy fibers and innervate the Purkinje cells (Figure 12–18). Each sends an axon to the molecular layer, where the axon bifurcates to form a T. The branches of the T are straight and run long distances; thus, they are called parallel fibers. The dendritic trees of the Purkinje cells are markedly flattened and oriented at right angles to the parallel fibers. The parallel fibers form excitatory synapses on the dendrites of many Purkinje cells, and the parallel fibers and Purkinje dendritic trees form a grid of remarkably regular proportions.

The other three types of neurons in the cerebellar cortex are inhibitory interneurons. Basket cells (Figure 12–17) are located in the molecular layer. They receive excitatory input from the parallel fibers and each projects to many Purkinje cells (Figure 12–18). Their axons form a basket around the cell body and axon hillock of each Purkinje cell they innervate. Stellate cells are similar to the basket cells but are located in the more superficial molecular layer. Golgi cells are located in the granular layer. Their dendrites, which project into the molecular layer, receive excitatory input from the parallel fibers (Figure 12–18). Their cell bodies receive excitatory input via collaterals from the incoming mossy fibers. Their axons project to the dendrites of the granule cells where they form an inhibitory synapse.

As already mentioned, the two main inputs to the cerebellar cortex are climbing fibers and mossy fibers. Both are excitatory (Figure 12–18). The climbing fibers come from a single source, the inferior olivary nuclei. Each projects to the primary dendrites of a Purkinje cell, around which it entwines like a climbing plant. Proprioceptive input to the inferior olivary nuclei comes from all over the body. On the other hand, the mossy fibers provide direct proprioceptive input from all parts of the body plus input from the cerebral cortex via the pontine nuclei to the cerebellar cortex. They end on the dendrites of granule cells in complex synaptic groupings called glomeruli. The glomeruli also contain the inhibitory endings of the Golgi cells mentioned above.

The fundamental circuits of the cerebellar cortex are thus relatively simple (Figure 12–18). Climbing fiber inputs exert a strong excitatory effect on single Purkinje cells, whereas mossy fiber inputs exert a weak excitatory effect on many Purkinje cells via the granule cells. The basket and stellate cells are also excited by granule cells via their parallel fibers; and the basket and stellate cells, in turn, inhibit the Purkinje cells (feed-forward inhibition). Golgi cells are excited by the mossy fiber collaterals and parallel fibers, and they inhibit transmission from mossy fibers to granule cells. The neurotransmitter released by the stellate, basket, Golgi, and Purkinje cells is GABA, whereas the granule cells release glutamate. GABA acts via GABA_A receptors, but the combinations of subunits in these receptors vary from one cell type to the next. The granule cell is unique in that it appears to be the only type of neuron in the CNS that has a GABA_A receptor containing the α6 subunit.

The output of the Purkinje cells is in turn inhibitory to the deep cerebellar nuclei. As noted above, these nuclei also receive excitatory inputs via collaterals from the mossy and climbing fibers. It is interesting, in view of their inhibitory Purkinje cell input, that the output of the deep cerebellar nuclei to the brainstem and thalamus is always excitatory. Thus, almost all the cerebellar circuitry seems to be concerned solely with modulating or timing the excitatory output of the deep cerebellar nuclei to the brainstem and thalamus. The primary afferent systems that converge to form the mossy fiber or climbing fiber input to the cerebellum are summarized in Table 12–2.

FUNCTIONAL DIVISIONS

From a functional point of view, the cerebellum is divided into three parts (Figure 12–19). The nodulus in the vermis and the flanking flocculus in the hemisphere on each side form the vestibulocerebellum (or flocculonodular lobe). This lobe, which is phylogenetically the oldest part of the cerebellum, has vestibular connections and is concerned with equilibrium and eye movements. The rest of the vermis and the adjacent medial portions of the hemispheres form the spinocerebellum, the region that receives proprioceptive input from the body as well as a copy of the “motor plan” from the motor cortex. By comparing plan with performance, it smooths and coordinates movements that are ongoing. The vermis projects to the brainstem area concerned with control of axial and proximal limb muscles (medial brainstem pathways), whereas the hemispheres of the spinocerebellum project to the brainstem areas concerned with control of distal limb muscles (lateral brainstem pathways). The lateral portions of the cerebellar hemispheres are called the cerebrocerebellum. They are the newest from a phylogenetic point of view, reaching their greatest development in humans. They interact with the motor cortex in planning and programming movements.

Most of the vestibulocerebellar output passes directly to the brainstem; but the rest of the cerebellar cortex projects to the deep nuclei, which in turn project to the brainstem. The deep nuclei provide the only output for the spinocerebellum and the cerebrocerebellum. The medial portion of the spinocerebellum projects to the fastigial nuclei and from there to the brainstem. The adjacent hemispheric portions of the spinocerebellum project to the emboliform and globose nuclei and from there to the brainstem. The cerebrocerebellum projects to the dentate nucleus and from there either directly or indirectly to the ventrolateral nucleus of the thalamus.

CEREBELLAR DISEASE

Damage to the cerebellum leads to several characteristic abnormalities, including hypotonia, ataxia, and intention tremor. Motor abnormalities associated with cerebellar damage vary depending on the region involved. Figure 12–20 illustrates some of these abnormalities. Additional information is provided in Clinical Box 12–9.

THE CEREBELLUM & LEARNING

The cerebellum is concerned with learned adjustments that make coordination easier when a given task is performed over and over. As a motor task is learned, activity in the brain shifts from the prefrontal areas to the parietal and motor cortex and the cerebellum. The basis of the learning in the cerebellum is probably the input via the olivary nuclei. The mossy fiber–granule cell–Purkinje cell pathway is highly divergent, allowing an individual Purkinje cell to receive input from many mossy fibers arising from different regions. In contrast, a Purkinje cell receives input from a single climbing fiber but it makes 2000–3000 synapses on it. Climbing fiber activation produces a large, complex spike in the Purkinje cell, and this spike produces long-term modification of the pattern of mossy fiber input to that particular Purkinje cell. Climbing fiber activity is increased when a new movement is being learned, and selective lesions of the olivary complex abolish the ability to produce long-term adjustments in certain motor responses.

• A muscle spindle is a group of specialized intrafusal muscle fibers with contractile polar ends and a noncontractile center that is located in parallel to the extrafusal muscle fibers and is innervated by types Ia and II afferent fibers and efferent γ-motor neurons. Muscle stretch activates the muscle spindle to initiate reflex contraction of the extrafusal muscle fibers in the same muscle (stretch reflex).

• A Golgi tendon organ is a netlike collection of knobby nerve endings among the fascicles of a tendon that is located in series with extrafusal muscle fibers and innervated by type Ib afferents. They are stimulated by both passive stretch and active contraction of the muscle to relax the muscle (inverse stretch reflex) and function as a transducer to regulate muscle force.

• The flexor withdrawal reflex is a polysynaptic reflex that is initiated by nociceptive stimuli; it can serve as a protective mechanism to present further injury.

• Spinal cord transection is followed by a period of spinal shock during which all spinal reflex responses are profoundly depressed.

• In humans, recovery begins about 2 weeks after the injury.

• The supplementary cortex, basal ganglia, and cerebellum participate in the planning of skilled movements. Commands from the primary motor cortex and other cortical regions are relayed via the corticospinal and corticobulbar tracts to spinal and brainstem motor neurons. Cortical areas and motor pathways descending from the cortex are somatotopically organized.

• The ventral corticospinal tract and medial descending brainstem pathways (tectospinal, reticulospinal, and vestibulospinal tracts) regulate proximal muscles and posture. The lateral corticospinal and rubrospinal tracts control distal limb muscles for fine motor control and skilled voluntary movements.

• Decerebrate rigidity leads to hyperactivity in extensor muscles in all four extremities; it is actually spasticity due to facilitation of the stretch reflex. It resembles what is seen with uncal herniation due to a supratentorial lesion. Decorticate rigidity is flexion of the upper extremities at the elbow and extensor hyperactivity in the lower extremities. It occurs on the hemiplegic side after hemorrhage or thrombosis in the internal capsule.

• The basal ganglia include the caudate nucleus, putamen, globus pallidus, subthalamic nucleus, and substantia nigra. The connections between the parts of the basal ganglia include a dopaminergic nigrostriatal projection from the substantia nigra to the striatum and a GABAergic projection from the striatum to substantia nigra.

• Parkinson disease is due to degeneration of the nigrostriatal dopaminergic neurons and is characterized by akinesia, bradykinesia, cogwheel rigidity, and tremor at rest. Huntington disease is characterized by choreiform movements due to the loss of the GABAergic inhibitory pathway to the globus pallidus.

• The cerebellar cortex contains five types of neurons: Purkinje, granule, basket, stellate, and Golgi cells. The two main inputs to the cerebellar cortex are climbing fibers and mossy fibers. Purkinje cells are the only output from the cerebellar cortex, and they generally project to the deep nuclei. Damage to the cerebellum leads to several characteristic abnormalities, including hypotonia, ataxia, and intention tremor.