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The cell bodies of the lower neurons are located in the ventral horn of the spinal cord gray matter and in the motor nuclei of the cranial nerves in the brainstem. These neurons (also called α motor neurons) send axons directly to skeletal muscles via the ventral roots and spinal peripheral nerves or, in the case of brainstem motor nuclei, via cranial nerves.

The spatial and temporal pat- terns of activation of lower motor neurons are determined primarily by local circuits located within the spinal cord and brainstem

The local circuit neurons that innervate the lower motor neurons receive sensory inputs as well as descending pro- jections from higher centers. The circuits they form provide much of the coordination between different muscle groups that is essential for organized movement. Even after the spinal cord is disconnected from the brain in an experi- mental animal, appropriate stimulation of local circuits in the isolated spinal cord can elicit involuntary but highly coordinated limb movements that resemble walking.

The neural centers responsible for the control of movement can be divided into four distinct but highly interactive subsystems, each of which makes a unique contribu- tion to motor control (Figure 16.1). The first of these subsystems is located within the gray matter of the spinal cord and the tegmentum of the brainstem. The relevant cells include the lower motor neurons, which send their axons out of the brainstem and spinal cord to innervate the skeletal muscles of the head and body, respectively, and the local circuit neurons, which are the major source of synaptic input to all lower motor neurons

The second motor subsystem consists of the upper motor neurons , whose cell bodies lie in the brainstem or cerebral cortex, and whose axons descend to synapse with the local circuit neurons or (more rarely) with the lower motor neurons directly

The upper motor neuron pathways that arise in the cortex are essential for the ini- tiation of voluntary movements and for complex spatio- temporal sequences of skilled movements

Upper motor neurons originating in the brainstem are re- sponsible for regulating muscle tone and for orienting the eyes, head, and body with respect to vestibular, somatic, auditory, and visual sensory information

The third and fourth subsystems are massive, complex neural circuits with output pathways that have no direct access to either the local circuit neurons or the lower mo- tor neurons. Instead, they control movement indirectly by regulating the activity of the upper motor neurons in the cerebral cortex and brainstem

The cerebellum mediates both real-time and long-term reductions in these inevitable motor errors (the latter being a form of motor learning)

The basal ganglia prevent upper motor neurons from initiating unwanted movements and prepare the mo- tor circuits for the initiation of movements.

Despite much effort, the sequence of events that lead from thought and emotion to movement is still poorly understood. The picture is clearest, however, at the level of control of the skeletal muscles themselves

An orderly relationship between the locations of motor neuron pools and the muscles they innervate is evident both along the length of the spinal cord and across the me- dial-to-lateral dimension of the cord, an arrangement that, in effect, provides a spatial map of the body’s musculature

Motor neurons that innervate the axial musculature (i.e., the postural muscles of the trunk) are located most medially in the ventral horn of the spinal cord, whereas neurons that innervate the muscles of the shoulders (or pelvis in the lumbar spinal cord; see Figure 16.2) are lateral to the axial neurons. Lower motor neurons that innervate the proximal muscles of the arm are the next most lateral, while those that innervate the distal parts of the extremi- ties, including the hands and fingers, lie farthest from the midline (Figure 16.3)

Thus, medial lower motor neuron pools that govern postural control and the maintenance of balance receive input from upper motor neurons in the brainstem vestibular nuclei and reticular formation. They comprise long pathways that run in the medial and an- terior (ventral) white matter of the spinal cord

The more lateral lower motor neuron pools that innervate the dis- tal extremities are often concerned with the execution of skilled behavior; this is especially true of the lateral motor neurons of the cervical enlargement that innervate muscles of the forearm and hand in primates. These laterally placed lower motor neurons are governed by projections from mo- tor divisions of the cerebral cortex that, in primates, run through the lateral white matter of the spinal cord.

The medial local circuit neurons, which supply the lower motor neurons in the medial ventral horn, have axons that project to many spinal cord segments. Indeed, some projections run be- tween the cervical and lumbar enlargements and partic- ipate in the coordination of rhythmic movements of the upper and lower limbs (see the section “Spinal Cord Cir- cuitry and Locomotion” later in this chapter), while other axons terminate along the entire length of the cord and help mediate posture

In contrast, local circuit neurons in the lateral region of the intermediate zone have shorter axons that typically extend fewer than five segments and are predom- inantly ipsilateral.

Two types of lower motor neurons are found in the mo- tor neuron pools of the ventral horn. Large motor neurons are called α motor neurons ; they innervate the striated muscle fibers that actually generate the forces needed for posture and movement. Interspersed among the α-motor neurons are smaller γ motor neurons , which innervate specialized muscle fibers that, in combination with the nerve fibers that innervate them, are actually sensory receptors arranged in parallel with the force-generating striated muscle fibers

The intrafusal muscle fibers are innervated by sensory axons that send information to the spinal cord and brainstem about the length of the muscle. The function of the γ motor neurons is to regulate this sensory input by setting the intrafusal muscle fibers to an appropriate length (see the section “The Spinal Cord Circuitry Un- derlying Muscle Stretch Reflexes” later in this chapter)

Most extrafusal skeletal muscle fibers in mature mammals are innervated by only a single α motor neuron (immature muscle fibers are innervated by several α motor neurons; see Chapter 23).

Because an action potential generated by a motor neuron typically brings to contraction threshold all of the muscle fibers the neuron contacts, the single α motor neuron and its associated muscle fibers constitute the smallest unit of force that can be activated by the muscle

Small α motor neurons innervate relatively few muscle fibers to form motor units that generate small forces, whereas large motor neurons innervate larger, more powerful motor units.

In most skeletal muscles, the smaller motor units comprise small “red” muscle fibers that contract slowly and generate relatively small forces; but because of their rich myoglobin content, plentiful mi- tochondria, and rich capillary beds, these small red fibers are resistant to fatigue. These small units are called slow ( S ) motor units and are especially important for activi- ties that require sustained muscular contraction, such as maintaining an upright posture

Larger α motor neurons innervate larger, pale muscle fibers that generate more force; however, these fibers have sparse mitochondria and are therefore easily fatigued. These units are called fast fatigable ( FF ) motor units and are especially important for brief exertions that require large forces, such as run- ning or jumping

A third class of motor unit has properties in between those of the other two. These fast fatigue- resistant ( FR ) motor units are of intermediate size and are not quite as fast as FF motor units. They generate about twice the force of a slow motor unit and, as the name im- plies, are resistant to fatigue (Figure 16.6).

In most muscles, small, slow motor units have lower thresholds for acti- vation than do the larger units and are tonically active during motor acts that require sustained effort (standing, for instance). The thresholds for the large, fast motor units are reached only during rapid movements requiring great force, such as jumping

Increasing or decreasing the number of motor units active at any one time changes the amount of force produced by a muscle. In the 1960s, Elwood Henneman and his colleagues at Harvard Medical School found that pro- gressive increases in muscle tension could be produced by progressively increasing the activity of axons that provide input to the relevant pool of lower motor neu- rons. This gradual increase in tension results from the recruitment of motor units in a fixed order, according to their size

Thus, as the synaptic activity driving a motor neuron pool increases, low-threshold S motor units are recruited first, then FR motor units, and finally, at the highest levels of activity, the FF motor units.

The frequency of the action potentials generated by mo- tor neurons also contributes to the regulation of muscle tension

The muscle fibers are activated by the next action potential before they have time to completely relax, and so the forces generated by the temporally over- lapping contractions are summed (Figure 16.8)

As already mentioned, the sensory signal for the stretch reflex originates in muscle spindles, the sensory receptors embedded within most muscles. The spindles comprise eight to ten intrafusal fi- bers arranged in parallel with the force-generating extra- fusal fibers that make up the bulk of the muscle (Figure 16.10A).

Two classes of intrafusal fibers can be distinguished by differences in their structure and function: nuclear bag fi- bers and nuclear chain fibers (the nuclear bag fibers can be subdivided further into two subclasses, dynamic and static; see below). The two classes differ in the arrange- ment of their nuclei (giving rise to their nomenclature, bag and chain fibers), the intrinsic architecture of their myofibrils, and their dynamic sensitivity to stretch

Large-diam- eter sensory axons (group Ia afferents; see Table 9.1) are coiled around the middle region of each class of intrafusal fiber, forming so-called annulospiral primary endings (see Figure 16.10A). Nearly as large in diameter are the group II afferents, which form secondary endings, mainly on nu- clear chain fibers; these are referred to as “flower-spray” endings because of their short, petal-like contacts just out- side the middle region of the fiber

Group Ia afferents tend to respond phasically to small stretches. This is because Ia afferent activity is dominated by signals transduced by the dynamic subtype of nuclear bag fiber whose biomechanical properties are sensitive to the velocity of fiber stretch. Group II afferents, which inner- vate static nuclear bag fibers and the nuclear chain fibers, signal the level of sustained fiber stretch by firing tonically at a frequency proportional to the degree of stretch, with little dynamic sensitivity.

The centrally projecting branch of the sensory neuron forms monosynaptic excitatory connections with those α motor neurons in the ventral horn of the spinal cord that innervate the same (homonymous) muscle and, via intervening GABAergic local circuit neurons (called reciprocal-Ia-inhibitory interneurons), forms inhibitory connections with those α motor neurons that innervate antagonistic (heteronymous) muscles

This monosynaptic reflex arc is variously referred to as the “stretch,” “deep tendon,” or “myotatic” reflex, and it is the basis of the knee, ankle, jaw, biceps, or triceps response tested in a routine physical examination. The tap of the reflex hammer on the tendon stretches the muscle, which evokes an afferent volley of activity in the Ia sensory axons that innervate the muscle spindles.

Since muscles are always under some degree of stretch, this reflex circuit, mediated largely by group II afferents, is typically responsible for the steady level of tension in muscles called muscle tone . Changes in muscle tone occur in a variety of pathological conditions, and these changes are assessed by examination of deep tendon reflexes (see Box 17D)

As described earlier, when the muscle is stretched, the spindle is also stretched and the rate of dis- charge in the afferent fibers is increased. When the muscle shortens, the spindle is relieved of tension (“unloaded”), and the sensory axons that innervate the spindle might therefore be expected to fall silent, but in fact they remain active. The γ motor neurons terminate on the contractile poles of the intrafusal fibers, and the activation of these neurons causes intrafusal fiber contraction—in this way, maintaining the tension on the middle, or equatorial re- gion, of the intrafusal fibers where the sensory axons ter- minate

Just as there are the dynamic and static functional classes of intrafusal muscle fibers, there are dynamic and static classes of γ motor neurons. When dynamic γ motor neurons fire, the dynamic response of the group Ia affer- ent is markedly enhanced. In contrast, when static γ motor neurons are activated, the dynamic response of the group Ia afferent is reduced and the static response is increased; the static response of the group II afferent likewise is en- hanced under these conditions. Thus, co-activation of α and γ motor neurons allows spindles to function (i.e., send information centrally) at all muscle lengths during move- ment and postural adjustment

The level of γ motor neuron activity is often referred to as γ bias, or gain, and can be adjusted by upper motor neuron pathways as well as by local reflex circuitry

If the gain of the reflex is high, then a small amount of stretch applied to the intrafusal fibers will produce a large increase in the number of α motor neurons recruited and a large increase in their firing rates; this, in turn, will lead to a large increase in the amount of tension produced by the extrafusal fibers

Thus, under the various demands of voluntary (and in- voluntary) movement, α and γ motor neurons are often co-activated by higher centers to prevent muscle spindles from being unloaded or overactivated (Figure 16.11).

In addition, the level of γ motor neuron activity can be modulated independently of α motor neuron activity to al- low fine adjustments in movements. In general, the baseline activity level of γ motor neurons is high if a movement is relatively difficult and demands rapid and precise execution.

However, γ motor neuron activity is not the only factor that sets the gain of the stretch reflex. The gain also depends on the level of excitability of the α motor neurons that serve as the efferent side of this reflex loop

Many of these neuromodulatory projec- tions release biogenic amine neurotransmitters that bind to G-protein-coupled receptors and mediate long-lasting effects on the gain of segmental circuits in the spinal cord

Another sensory receptor that is important in the reflexive regulation of motor unit activity is the Golgi tendon or- gan. Golgi tendon organs are encapsulated afferent nerve endings located at the junction of a muscle and a tendon (Figure 16.12A). Each tendon organ is innervated by a sin- gle group Ib sensory axon (Ib axons are slightly smaller than the Ia axons that innervate the muscle spindles; see Table 9.1)

Activation of the non-selective, cationic mechanosensitive ion channels in the nerve endings of the Golgi tendon organ results in a generator potential that, if suprathreshold, triggers gen- eration of action potentials that are propagated along the group Ib axon to the spinal cord

The Golgi ten- don circuit is thus a negative feedback system that regu- lates muscle tension; it decreases the activation of a muscle when exceptionally large forces are generated and, in this way, protects the muscle

The same Ib afferents also make synaptic connections with excitatory interneurons that in- crease the excitability of α motor neurons that innervate the antagonistic muscle

The Ib in- hibitory interneurons receive synaptic inputs from several other sources, including upper motor neurons, cutaneous receptors, muscle spindles, and joint receptors.

From the preceding discussion, it should be evident that muscle spindles and Golgi tendon organs serve in a com- plementary fashion to help regulate motor performance through the operations of distinct spinal cord reflexes

In short, the muscle spindle system is a feedback system that monitors and maintains muscle length, and the Golgi tendon system is a feedback system that monitors and maintains muscle force

Under normal conditions, a noxious stimulus is required to evoke the flexion reflex; following damage to descending pathways, however, other types of stimu- lation, such as squeezing a limb, can sometimes produce the same response

Studies of rhythmic movements, such as locomotion and swimming in animal models (Box 16B), have demonstrated that local circuits in the spinal cord, called central pattern generators , are fully capable of controlling the timing and coordination of such complex patterns of movement, and of adjusting them in response to altered circumstances

Given the precise timing of the movements of individual limbs and the necessity of coordinating these movements, it is natural to assume that locomotion is accomplished by higher centers that organize the spatial and temporal ac- tivity patterns of the individual limbs. Indeed, activation of centers in the brainstem, such as the mesencephalic locomotor region (also see Chapter 17), can trigger loco- motion and change the speed and pattern of the movement by changing the level of activity delivered to the spinal cord

These and other observations in experimental animals show that the rhythmic patterns of limb movement during locomotion are not dependent on sensory input, nor are they wholly dependent on input from descending projec- tions from higher centers. Rather, local circuitry provides for each limb a central pattern generator responsible for the al- ternating flexion and extension of the limb during locomo- tion. This central pattern generator comprises local circuit neurons that include excitatory glutamateric neurons cou- pled to one another and a variety of inhibitory GABAergic and glycinergic neurons (Figure 16.15D)

Although locomotor movements can also be elicited in humans following damage to descending pathways, these are considerably less effective than the movements seen in the cat. The reduced ability of the transected spinal cord to mediate rhythmic stepping movements in humans presum- ably reflects an increased dependence of local circuitry on upper motor neuron pathways and the cortical and subcor- tical circuits that govern and modulate their output (Figure 16.16). Perhaps bipedal locomotion carries with it require- ments for postural control greater than can be accommo- dated by spinal cord circuitry alone

Once activity is initiated, cortical systems play a relatively minor role in sustaining central pattern generation. Cortical control is most relevant for conveying motor intention (e.g., spatial navigation; walking or running) and visual guid - ance of locomotion through complex environments (e.g., step- ping over or avoiding obstacles)

Damage to lower motor neurons also entails a loss of muscle tone, since tone is dependent in part on the monosynaptic reflex arc that links the muscle spindles to the lower motor neurons (see Box 17D)

The muscles involved may also exhibit fibril- lations and fasciculations, which are spontaneous twitches characteristic of single denervated muscle fibers or motor units, respectively.

These phenomena arise from changes in the excitability of single denervated muscle fibers in the case of fibrillation, and from pathological activity of injured α motor neuron units in the case of fasciculations.

The sources of these upper motor neuron pathways include several brainstem centers and multiple cortical areas in the frontal lobe

Most upper motor neurons, regardless of their source, influence the generation of movements by modulating the activity of the local circuits in the brainstem and spinal cord. Upper motor neurons in the cortex also control movement indirectly, via pathways that project to motor control centers in the brainstem, which in turn proj- ect to the local organizing circuits in the brainstem and spinal cord. These indirect pathways mediate the automatic adjustments in the body’s posture that occur during cortically initiated voluntary movements

The local circuit neurons, which lie primarily in the intermediate zone of the spinal cord and supply much of the direct input to the lower motor neurons, are also topographically arranged.

Thus, most upper motor neurons that project to the medial part of the ventral horn also project to the medial region of the intermediate zone. The axons of these upper motor neurons course through the anteri- or-medial white matter of the spinal cord and give rise to collateral branches that terminate over many spinal cord segments among medial cell groups on both sides of the spinal cord. The sources of these projections are located primarily in the brainstem, and as their terminal zones in the medial spinal cord gray matter suggest, they are con- cerned primarily with proximal muscles that control pos- ture, balance, orienting mechanisms, and the initiation and regulation of stereotyped, rhythmic behavior (see Figure 17.1B)

In contrast, the large majority of axons that project from the motor cortex to the spinal cord course through the lateral white matter of the spinal cord and terminate in lateral parts of the ventral horn, with terminal fields that are restricted to only a few spinal cord segments.

The primary motor cortex can be distinguished from a complex mosaic of adjacent “premotor” areas both cytoarchitecton- ically (it is area 4 in Brodmann’s nomenclature; see Figure 27.1) and by the low intensity of current necessary to elicit movements by electrical stimulation in this region. The low threshold for eliciting movements is an indicator of a rel- atively large and direct pathway from the primary area to the lower motor neurons of the brainstem and spinal cord

The pyramidal cells of cortical layer 5 are the upper motor neurons of the primary motor cortex. Among these neurons are the conspicuous Betz cells, which are the largest neurons (by soma size) in the human CNS (Figure 17.3)

The remaining upper motor neurons are the smaller, non-Betz pyramidal neurons of layer 5 that are found in the primary motor cortex and in each division of the premotor cortex. The axons of these upper motor neurons descend in the corticobulbar and cortico- spinal tracts , terms that are used to distinguish axons that terminate in the brainstem (“bulbar” refers to the brainstem) or spinal cord

Most corticobulbar axons that govern the cranial nerve motor nuclei (see the Appendix) terminate bilater- ally on local circuit neurons embedded in the brainstem reticular formation (see the section “Motor Control Centers in the Brainstem” later in this chapter), rather than directly on the lower motor neurons in the motor nuclei. These local circuit neurons, in turn, coordinate the output of different groups of lower motor neurons in the cranial nerve motor nuclei. The consequence of the bilateral corticobulbar innervation is that damage to the corticobulbar fibers on only one side does not result in dramatic deficits in function

There are three notable exceptions to the pattern of symmetrical, bilateral cortical innervation of the local cir- cuits controlling cranial nerve motor nuclei. For each of these exceptions, corticobulbar inputs to the relevant local circuits arise from both cerebral hemispheres; but there is significant bias in favor of inputs from the contralateral motor cortex. Specifically, the local circuits that organize the output of lower motor neurons in the hypoglossal nu- cleus (which governs tongue protrusion), the trigeminal motor nucleus (which governs chewing), and the part of the facial motor nucleus that innervates the lower face each receive corticobulbar input primarily from the contralat- eral motor cortex

The part of the facial motor nucleus that innervates the upper face is supplied more equally by the corticobulbar inputs from the two sides; this is an import- ant clinical point that is also relevant for understanding facial expressions of emotion (Clinical Applications)

Near the caudal end of the medulla, nearly all of the fibers in the medullary pyramids are corticospinal axons. Just before entering the spinal cord, about 90% of these axons cross the midline—decussate—to enter the lateral columns of the spinal cord on the opposite side, where they form the lateral corticospinal tract . The remaining 10% of the pyramidal tract fibers enter the spinal cord without crossing; these axons, which constitute the ventral ( ante- rior ) corticospinal tract , terminate bilaterally. Collateral branches of these axons cross the midline via the ventral white commissure of the spinal cord to reach the opposite ventral horn

The ventral corticospinal pathway arises pri- marily from dorsal and medial regions of the motor cortex that serve trunk and proximal limb muscles—the same divisions of the motor cortex that give rise to projections to the reticular formation (see the section “Motor Control Centers in the Brainstem”).

Some of these axons (including those derived from Betz cells) synapse directly on α motor neurons that govern the distal extremities (see Figures 17.1 and 17.4). However, this privileged synaptic contact on lower motor neurons is restricted to a subset of α motor neurons that supply the muscles of the forearm and hand; most axons of the lateral corticospinal tract, in contrast, terminate among pools of local circuit neurons that coordinate the activities of the lower motor neurons in the lateral cell columns of the ventral horn that innervate different muscles

Although selective damage to this pathway in humans is rarely seen, evidence from experimental studies in non-hu- man primates indicates that direct projections from the motor cortex to the spinal cord are essential for the perfor- mance of discrete finger movements. This evidence helps explain the limited recovery in humans after damage to the motor cortex or some component of this pathway

Until recently, it was assumed that this pattern of inferior facial paresis with su- perior facial sparing could be attributed t o (presumed) bilateral projections from the face representation in the lateral portion of the primary motor cortex to the facial motor nucleus; in this concep- tion, the intact ipsilateral corticobulbar p rojections were considered sufficient to motivate the contractions of the superi- or muscles of the face. However, recent p athway-tracing studies in non-human primates have suggested a different ex- planation

First, the corticobulbar projec- tions of the primary motor cortex are di- rected predominantly toward the lateral c ell columns in the contralateral facial motor nucleus, which control the move- ments of the perioral musculature. Thus, t he more dorsal cell columns in the facial motor nucleus that innervate superior fa- cial muscles do not receive significant i nput from the primary motor cortex. Sec- ond, these dorsal cell columns are gov- erned by premotor areas in the anterior ci ngulate gyrus, a cortical region that is associated with emotional processing (see Chapter 31). Therefore, strokes in- volving the middle cerebral artery spare t he superior aspect of the face because the relevant upper motor neurons are in the cingulate gyrus, which is supplied by the anterior cerebral artery

Strokes involving the ante- rior cerebral artery or subcortical lesions t hat interrupt the corticobulbar projec- tion (lesion B in the figure) seldom pro- duce significant paresis of the superior f acial muscles. Superior facial sparing in these situations may arise because these cingulate motor areas (see Fig- ure 17.9) send descending projections thr ough the corticobulbar pathway that bifurcate and innervate dorsal facial motor cell columns on both sides of the brainstem. Thus, the superior muscles of facial expression are controlled by sym - metrical inputs from the cingulate motor a reas in both hemispheres. These same cingulate motor areas also provide some measure of corticobulbar innerva- tion to the dorsolateral facial motor nu- cleus, which governs the upper perioral m usculature. This likely explains why indi- viduals with injury to the lateral precen- tral gyrus (or the portion of the cortico- bulbar tract originating there) are often s till able to express a genuine emotional smile despite voluntary weakness (see Box 31A)

Interestingly, the corti- cospinal projection to the ventral horn is largest in verte- brates that have the most complex repertoire of fraction- ated movements with their hands or forepaws. In animals with little ability to execute skilled movements with their forepaws, the corticospinal projection is predominantly di- rected toward the dorsal horn, where it modulates sensory input to the brain and spinal cord

In contrast to the precise and detailed representation of the contralateral b ody in the primary somatosensory cortex (see Figure 9.11), the somatotopy of the primary motor cortex is much more coarse

Although intracortical stimulation generally confirmed Penfield’s spatial map in the motor cortex, it also showed that the finer organization of the map is rather different from what most neuroscientists had imagined. For exam- ple, when microstimulation was combined with record- ings of muscle electrical activity, even the smallest cur- rents capable of eliciting a response initiated the excitation of several muscles (and the simultaneous suppression of others), suggesting that organized movements rather than individual muscles are represented in the map (Box 17A).

Individual pyramidal tract a xons are now known to terminate on sets of spinal motor neurons that inner- vate different muscles. This relationship i s evident even for neurons in the hand representation of the motor cortex, the region that controls the most discrete, fractionated movements

Thus, while the somatotopic maps in the motor cortex generated by early studies are correct in their overall to - pography, the fine structure of the map i s far more abstract.

Their micro- stimulation studies of awake, behaving m onkeys suggest that the topographic representations of movement in the mo- tor cortex are organized around etho- logically relevant categories of motor b ehavior

New studies of the mirror motor system raise the intriguing possibility that what is actually represent - ed in the motor cortex is the intention of m ovement or action goal, rather than movement per se

Evarts and his group found that the force generated by contracting muscles changed as a function of the firing rate of upper motor neurons. Moreover, the firing rates of the active neurons often changed prior to movements involving very small forces. Evarts therefore proposed that the primary motor cortex contributes to the initial phase of recruitment of lower motor neurons involved in the generation of finely controlled movements. Additional experiments showed that the activity of primary motor neurons is correlated not only with the magnitude, but also with the direction of the force produced by muscles. Thus, some neurons show progressively less activity as the vector of the movement deviates from the neuron’s “preferred direction.”

These observations, which confirmed that single upper motor neurons contact several lower motor neuron pools, are consistent with the general conclusion that the activity of the upper motor neurons in the cortex controls movements, rather than individual muscles.

Indeed, it is problematic to represent the motor map in the form of a homunculus car- toon that would be analogous to the somatosensory ho- munculus in the postcentral gyrus (see Figure 9.11), since the representation of muscle movement is not organized at the level of individual muscles or body parts, and the distribution of muscle fields among neighboring cortical neurons is neither spatially continuous nor temporally fixed

These observations showed that the discharges of individual upper motor neurons cannot specify the direc- tion of an arm movement, simply because they are tuned too broadly (likely reflecting the summed tuning of in- puts from other upper motor neurons).

The Premotor Cortex A complex mosaic of interconnected frontal lobe areas that lie rostral to the primary motor cortex also contributes to motor functions (see Figure 17.2). This functional division of the motor cortex includes Brodmann’s areas 6, 8, and 44/45 on the lateral surface of the frontal lobe and parts of areas 23 and 24 on the medial surface of the hemisphere

Indeed, over 30% of the axons in the corticospinal tract arise from neurons in the premotor cortex. Thus, past argu- ments that the premotor cortex occupies a higher position in a cortical hierarchy of motor control by operating through feedforward signals to the primary motor cortex are no lon- ger tenable. Rather, a variety of experiments indicate that the premotor cortex uses information from other cortical regions to select movements appropriate to the context and goal of the action (see Chapter 32)

Rather than directly commanding the initiation of a movement, these neurons appear to encode the monkey’s intention to perform a particular movement; thus, they seem to be particularly involved in the selection of movements based on external events

Recent studies have demonstrated that some mirror motor neurons show suppression of firing during action observa- tion, even if the same neurons fire during action execution. Such neuronal activities may contribute to the suppression of imitation. Taken together, these findings suggest that the mirror motor system is involved in encoding the intention to make a specific movement based on the observation of the behaviorally relevant actions of others

Similarly, patients with frontal lobe damage have difficulty learning to select a particular movement to be performed in response to a visual cue, even though they understand the instructions and can perform the movements. Individuals with lesions in the premotor cortex may also have difficulty performing move- ments in response to verbal commands

The medial division of the premotor cortex extends onto the medial aspect of the frontal lobe (including a division that has been referred to as the “supplementary motor area”). Like the lateral area, the medial premotor cortex mediates the selection of movements. However, this region appears to be specialized for initiating movements specified by internal rather than external cues (“open-loop” conditions). In contrast to lesions in the lateral premotor area, removal of the medial premotor area in a monkey reduces the number of self-initiated or “spontaneous” movements the animal makes, whereas the ability to ex- ecute movements in response to external cues remains largely intact

Among the areas of the medial premotor cor- tex are two divisions that will be considered in more detail elsewhere: a frontal eye field (see Figure 17.9) involved in directing visual gaze toward a location of interest (see also Chapter 20); and a set of areas in the depths of the cingu- late sulcus (see Figure 17.9 and Clinical Applications) that plays a role in the expression of emotional behavior (see also Chapter 31)

Many of the cells in the vestibular nuclei that receive this information are upper motor neurons with descending axons that ter- minate in the medial region of the spinal cord gray matter, although some extend more laterally to contact the neurons that control the proximal muscles of the limbs. The projec- tions from the vestibular nuclei that control axial muscles and those that influence proximal limb muscles originate from different cells and take somewhat different routes to the spinal cord (see Figure 17.12A)

Neurons in the medial vestibular nucleus give rise to a medial vestibulospinal tract that terminates bilaterally in the medial ventral horn of the cervical cord. There, the me- dial vestibulospinal tract regulates head position by reflex activation of neck muscles in response to the stimulation of the anterior semicircular canals resulting from unexpected rapid, downward rotation of the head. For example, when an individual falls forward, the medial vestibulospinal tract mediates reflexive dorsiflexion of the neck as well as exten- sion of the arms in an attempt to protect the upper body from injury.

Neurons in the lateral vestibular nucleus are the source of the lateral vestibulospinal tract , which courses through the anterior white matter of the spinal cord in a slightly more lateral position relative to the medial vestib- ulospinal tract. Despite the modifier in its name, the lateral vestibulospinal tract terminates ipsilaterally among medial lower motor neuron pools that govern proximal muscles of the limbs. As discussed in more detail in Chapter 14, this tract facilitates the activation of limb extensor (antigravity) muscles when the otolith organs signal deviations from sta- ble balance and upright posture.

The neurons within the reticular formation serve a disparate variety of functions, including cardiovascular and respiratory control (see Chapter 21), governance of myriad sensorimotor reflexes (see Chapters 16 and 21), coordination of eye movements (see Chapter 20), regulation of sleep and wakefulness (see Chapter 28), and most important for the purpose of this discussion, the temporal and spatial coordination of limb and trunk movements, particularly those that con- trol rhythmic, stereotypical behaviors such as locomo- tion

The reticular formation is a complicated network of circuits in the core of the brainstem that extends from the rostral midbrain to the caudal medulla; it is similar in structure and function to the local circuitry in the in- termediate gray matter of the spinal cord (Figure 17.13 and Box 17C).

The descending motor control pathways from the reticular formation to the spinal cord are similar to those of the vestibular nuclei; they terminate primarily in the medial parts of the gray matter, where they influence the local circuit neurons that coordinate axial and proximal limb muscles (see Figure 17.12B). With few exceptions, reticulospinal projections are distributed bilaterally to the medial ventral horns

In contrast, the motor centers in the reticular formation are controlled largely by motor centers in the cerebral cortex, hypothalamus, or brainstem. The relevant neurons in the reticular formation initiate feedforward adjustments that stabilize posture during ongoing movements

The results of this experiment can be understood in terms of the fact that the upper motor neurons in the mo- tor cortex influence the spinal cord circuits by two routes: direct projections to the spinal cord (as discussed above) and indirect projections to brainstem centers that in turn project to the spinal cord

The forepaw movement is initiated by the direct pathway from the cortex to the spinal cord, whereas the postural adjustments are mediated via path- ways from the motor cortex that reach the spinal cord indi- rectly, after an intervening relay in the reticular formation (the so-called cortico-reticulospinal pathway; Figure 17.16)

These observations show that following damage to the direct projections from the motor cortex to the spinal cord at the level of the medulla, the indirect projections to the spinal cord from the motor cortex via the brainstem centers (or from brainstem centers alone) are capable of sustaining motor behavior that involves primarily the use of proximal muscles. In contrast, the direct projections from the motor cortex to the spinal cord provide the speed and agility of movements, and they enable a higher degree of precision in fractionated finger movements than is possible using the indirect pathways alone

The mesencephalic and rostral pontine reticular formation (yellow) mainly modulates forebrain activity and the caudal pontine and medullary retic - ular formation (red) provides premotor co ordination of lower somatic motor and visceral motor neuronal pools

Scattered among the diffuse fibers that course through the tegmentum are small clusters of neu- rons that are collectively known as the r eticular formation. With few exceptions, these clusters of neurons are difficult to recognize as distinct nuclei in standard histological preparations

First, the functions of the different clusters of neurons in the reticular formation can be grouped into two broad categories: modulatory functions and premotor functions. Second, the modu- latory functions are found primarily in the r ostral sector of the reticular formation, whereas most of the premotor functions are localized in more caudal regions

Several clusters of large (magnocel- lular) neurons in the midbrain and ros- tral pontine reticular formation partici- pate—together with certain diencephal- ic nuclei—in the modulation of con- scious states (see Chapter 28)

E xamples of this functional category include the smaller (parvocellular) neu- rons that coordinate a broad range of m otor activities, including the gaze cen- ters discussed in Chapter 20 and local ci rcuit neurons near the somatic motor and branchiomotor nuclei that organize mastication, facial expressions, and a variety of reflexive orofacial behaviors such as sneezing, hiccupping, yawning, and swallowing

The reticulospinal inputs serve to modulate the gain of segmental reflex - es involving the muscles of the trunk and p roximal limbs and to relay initiation sig- nals for certain stereotypical patterns of l imb movement, such as locomotion

An additional brainstem structure, the superior collicu- lus , which is located in the dorsal midbrain, also contributes upper motor neuron pathways that govern lower motor neu- rons in the spinal cord. Although most mammals are likely to have direct projections from neurons in deep layers of the superior colliculus to the spinal cord (comprising a so-called colliculospinal or tectospinal tract), the major output of the superior colliculus to the spinal cord is mediated by the re- ticular formation. Thus, upper motor neurons in the superior colliculus innervate neural circuits in the reticular forma- tion, which in turn give rise to reticulospinal projections that supply medial cell groups in the cervical cord. Functionally, this pathway plays a role in controlling axial musculature in the neck.

In non-human primates and other mammals, a large nucleus in the tegmentum of the midbrain, termed the red nucleus, projects via the rubrospinal tract to the cervi- cal level of the spinal cord (rubro— Latin, “red”—refers to the reddish color of this nucleus in fresh tissue, presumably due to the enrichment of its neurons with iron–protein com- plexes). Unlike the other projections from the brainstem to the spinal cord discussed thus far, the rubro- spinal tract is located in the lateral white matter of the spinal cord; its axons terminate in lateral regions of the ventral horn and intermediate zone, where circuits of lower motor neurons governing the distal mus- culature of the upper extremities re- side

In the human midbrain, there are few—if any—large neurons in the red nucleus; thus, if the rubrospinal tract exists in humans (which may not be the case in some individuals), its significance for motor control is dubious. Indeed, nearly all of the neurons in the red nu- cleus in humans are small (parvocellular) and do not project to the spinal cord at all; instead, many of these neurons relay information to the inferior olive, an important source of learning signals for the cerebellum (this role of the red nucleus will be discussed in Chapter 19)

The acute manifestations tend to be most severe in the arms and legs. If the affected limb is elevated and released, it drops passively, and all reflex activity on the af- fected side is abolished. In contrast, control of trunk mus- cles is usually preserved, either by the remaining brain- stem pathways or because of the bilateral projections of the corticospinal pathway to local circuits that control midline musculature

This initial period of “hypotonia” after upper motor neuron injury is called spinal shock and reflects the decreased activity of spinal circuits suddenly deprived of input from the motor cortex and brainstem

After several days, however, the spinal cord circuits re- gain much of their function for reasons that are not fully understood, but may include the strengthening of remain- ing connections, the sprouting of new connections, and other homeostatic reactions that promote sustained neural activity in local segmental circuits

Spasticity is probably caused by disruption of the regulatory influences exerted by the cortex on the postural centers of the vestibular nuclei and re- ticular formation, which in turn serve to govern the excitability of segmental circuits in the spinal cord. In experimental animals, for instance, lesions of the vestibular nuclei ameliorate the spasticity that follows damage to the corticospinal tract. Spasticity is also eliminated by sectioning the dorsal roots, suggesting that it represents an atypical increase in the gain of the spinal cord stretch reflexes due to loss of descending suppression (see Chapter 16). This increased gain of segmental circuits is also thought to explain clonus

Muscle tone depends on the resting level of discharge of α motor neurons. Activity in muscle spindle afferents—the neurons responsible for the stretch re - flex—is the major contributor to this tonic l evel of firing. As described in Chapter 16, the γ efferent system (by its action on intrafusal muscle fibers) regulates the resting level of activity in spindle affer- ents and thus establishes the baseline l evel of α motor neuron activity in the ab- sence of muscle stretch

Damage to either the α motor neurons or the spindle affer- ents carrying sensory information to the α m otor neurons results in a decrease in muscle tone, called hypotonia.

The neural changes responsi - ble for hypertonia following damage to h igher centers are not well understood; however, at least part of this change is due to an increase in the responsiveness of α motor neurons to spindle afferent inputs. Thus, in experimental animals in which descending inputs have been severed, the resulting hypertonia can be eliminated by sectioning the dorsal roots

Hy- peractivity of the stretch reflex loop is the r eason for the increased resistance to stretch in the clasp-knife phenomenon. The physiological basis for the inhibition that causes the sudden collapse of the stretch reflex (and loss of muscle tone) may involve the activation of Golgi ten - don organs and/or inhibitory Ib interneu- rons in the spinal cord (see Chapter 16)

Cl onus refers to a rhythmic pattern of contractions (3 to 7 per second) due to the alternate stretching and unloading of the muscle spindles in a spastic mus- cle. Clonus can be demonstrated in the f lexor muscles of the leg by pushing up on the sole of an individual’s foot to dor- siflex the ankle

Although these upper motor neuron signs and symptoms may arise from damage anywhere along the descending pathways, the spasticity that follows damage to descending pathways in the spinal cord is less marked than the spas- ticity that follows damage to the cortex or internal capsule. For example, the spastic extensor muscles in the legs of a patient with spinal cord damage cannot support the in- dividual’s body weight, whereas those of a patient with damage at the cortical level often can. However, lesions that interrupt the descending pathways in the brainstem above the level of the vestibular nuclei but below the level of the red nucleus cause even greater extensor tone than that which occurs after damage to higher regions. Sher- rington, who first described this phenomenon, called the increased tone decerebrate rigidity .

The relatively greater hypertonia following damage to the nervous system above the level of the me- dulla oblongata is presumably explained by the remaining activity of the intact descending pathways from the vestib- ular nuclei and reticular formation, which evidently have a net excitatory influence on the gain of segmental reflexes that contribute to posture and equilibrium in the context of impaired cortico-reticular regulation