Cell column	Muscles
Ventromedial (all segments)	Erector spinae
Dorsomedial (T1–L2)	Intercostals, abdominals
Ventrolateral (C5–C8, L2–S2)	Arm/thigh
Dorsolateral (C6–C8, L3–S3)	Forearm/leg
Retrodorsolateral (C8, T1, S1–S2)	Hand/foot
Central (C3–C5)	Diaphragm

Cell types

Large, α (alpha) motor neurons supply the extrafusal fibers of the skeletal muscles. Interspersed among them are small, γ (gamma) motor neurons supplying the intrafusal fibers of neuromuscular spindles.

• In execution of the withdrawal reflex described in Chapter 14, large numbers of excitatory, ‘flexor reflex’ internuncials are activated over several spinal segments on the same side as the stimulus, as well as inhibitory internuncials supplying motor neurons to antagonist muscles.

• Renshaw cells.

A reciprocal list can be drawn up for extensor motor neurons, with substitution of extensor thrust inputs for flexor reflex internuncials.

Descending Motor Pathways

Important pathways descending to the spinal cord are the following:

• corticospinal (pyramidal)

• reticulospinal (extrapyramidal)

Corticospinal tract

The corticospinal tract is the great voluntary motor pathway. About 40% of its fibers take their origin from the primary motor cortex in the precentral gyrus. Other sources include the supplementary motor area on the medial side of the hemisphere, the premotor cortex on the lateral side, the somatic sensory cortex, the parietal lobe, and the cingulate gyrus (Figure 16.2). The contributions from the two sensory areas mentioned terminate in sensory nuclei of the brainstem and spinal cord, where they modulate sensory transmission.

Figure 16.2 Pyramidal tract visualized from the left side. The supplementary motor area is on the medial surface of the hemisphere. Arrow indicates level of pyramidal decussation. Non-motor neurons are shown in blue.

The corticospinal tract descends through the corona radiata and posterior limb of the internal capsule to reach the brainstem. It continues through the crus of the midbrain and the basilar pons to reach the medulla oblongata (Figure 16.3). Here it forms the pyramid (hence the synonym, pyramidal tract).

Figure 16.3 Coronal section of embalmed brain, following treatment with copper sulfate (Mulligan’s stain) showing unstained corticospinal fibers displacing nuclei pontis en route to the pyramid.

(Illustration kindly provided by Professor David Yew, University of Hong Kong.)

During its descent through the brainstem, the corticospinal tract gives off fibers which activate motor cranial nerve nuclei, notably those serving the muscles of the face, jaw, and tongue. These fibers are called corticonuclear (Figure 16.4). (The term ‘corticobulbar’ is sometimes used, but ‘bulb’ is open to different interpretations.)

Figure 16.4 The pyramidal tract. ACST, anterior corticospinal tract; LCST, lateral corticospinal tract. Note: Only the motor components are shown; the parietal lobe components are omitted.

Just above the spinomedullary junction (Figure 16.5):

• About 80% of the fibers cross the midline in the pyramidal decussation.

• These fibers descend on the contralateral side of the spinal cord as the lateral corticospinal tract (crossed corticospinal tract, LCST).

• About 10% enter the anterior corticospinal tract, which occupies the anterior funiculus at cervical and upper thoracic levels. These fibers cross in the white commissure and supply motor neurons serving muscles in the anterior and posterior abdominal walls.

• About 10% of the pyramidal fibers enter the lateral corticospinal tract on the same side.

Figure 16.5 Ventral view of medulla oblongata and upper spinal cord, showing the three spinal projections of the left pyramid.

The corticospinal tract contains about one million nerve fibers. The average conduction velocity is 60 m/s, indicating an average fiber diameter of 10 µm (‘rule of six’ in Ch. 6). About 3% of the fibers are extra large (up to 20 µm); they arise from giant neurons (cells of Betz), located mainly in the leg area of the motor cortex (Ch. 26). All corticospinal fibers are excitatory and appear to use glutamate as their transmitter substance.

Targets of the lateral corticospinal tract

Distal limb motor neurons

In the anterior gray horn, LCST axons synapse upon the dendrites of α and γ motor neurons supplying limb muscles, notably in the upper limb. A unique property of these corticomotoneuronal fibers of LCST is that of fractionation, whereby small groups of neurons can be selectively activated. This is most obvious in the case of the index finger, which can be flexed or extended quite independently, although three of its long tendons arise from muscle bellies devoted to all four fingers. Fractionation is essential for the execution of skilled movements such as buttoning a coat or tying shoe laces. Skilled movements are lost, and seldom recover completely, following damage to the corticomotoneuronal system anywhere from motor cortex to spinal cord.

Although fractionation is a manifestly important function, even simple voluntary movements, such as flexion of the elbow or abduction of the shoulder, are initiated by corticomotoneuronal fibers.

As mentioned already in Chapter 10, the α and γ motor neurons are coactivated by the LCST during a given movement, so that spindles in the prime movers are signaling active stretch while those in the antagonists are signaling passive stretch.

Renshaw cells

The number of possible functions served by LCST synapses on Renshaw cells is large because some of the cells synapse mainly upon Ia inhibitory internuncials, and others upon other Renshaw cells. Probably the most important function is to permit co-contraction of prime movers and their antagonists, in order to fix one or more joints, e.g. when a chopping or shoveling action is required of the hand. Co-contraction is achieved by inactivation of Ia inhibitory internucials by Renshaw cells.

Excitatory internuncials

In the intermediate gray matter and the base of the anterior horn, motor neurons supplying axial (vertebral) and proximal limb muscles are recruited mainly indirectly by the LCST, by way of excitatory internuncials.

Ia inhibitory internuncials

Also located in the intermediate gray matter are the Ia inhibitory internuncials, and these are the first neurons to be activated by the LCST during voluntary movements. Activity of the Ia internuncials causes the antagonist muscles to relax before the prime movers (agonists) contract. In addition, it renders the antagonists’ motor neurons refractory to stimulation by spindle afferents passively stretched by the movement. The sequence of events is shown in Figure 16.6 and its caption for voluntary flexion of the knee.

Figure 16.6 Sequence of events in a voluntary movement (flexion of the knee). (1) Activation of Ia internuncials to inhibit antagonist α motor neurons (αMN); (2) activation of agonist α and γ motor neurons; (3) activation of extrafusal and intrafusal muscle fibers; (4) feedback from actively stretched spindles increases excitation of agonist α motor neurons and inhibition of antagonist α motor neuron; (5) Ia fibers from passively stretched antagonist spindles will find the respective α motor neurons refractory. Note: The sequence γ motor neuron–Ia fiber–α motor neuron is known as the gamma loop.

(Note on terminologies: During quiet standing, the knees are ‘locked’ in slight hyperextension and the quadriceps is inactive, as indicated by the patellae being ‘loose’. Any tendency of one or both knees to go into flexion is counteracted by a twitch of quadriceps in response to passive stretching of dozens of muscle spindles there. Because the flexion movement is resisted in this way, the reflex concerned is called a resistance reflex. During voluntary flexion of the knee, on the other hand, the movement is helped along in the manner described in the caption to Figure 16.6, through an assistance reflex. The change of sign, from negative to positive, is called reflex reversal.)

Presynaptic inhibitory neurons serving the stretch reflex

Consider a sprinter. At each stride, gravity pulls the body out of the air onto a knee extended by the quadriceps muscle. At the moment of impact, all of the muscle spindles in the contracted quadriceps are thrown into active stretch. The obvious danger is that the quadriceps may rupture. Golgi tendon endings (Ch. 10) offer some protection through autogenetic inhibition, but the main protection seems to be through presynaptic inhibition by the LCST of spindle afferents close to their contact points with motor neurons. At the same time, preservation of the ankle jerk is advantageous in this situation, giving immediate recruitment of calf motor neurons for the next take-off. The extent of suppression of the stretch reflex by the LCST in fact appears to depend upon the particular motor program being executed.

Presynaptic inhibition of first-order afferents

In the posterior gray horn, there is some suppression of sensory transmission into the spinothalamic pathway during voluntary movement. This is brought about by activation of inhibitory internuncials synapsing upon primary afferent nerve terminals.

Modulation is more subtle at the level of the gracile and cuneate nuclei, where pyramidal tract fibers (after crossing) are capable of either enhancing sensory transmission during slow, exploratory movements, or reducing it during rapid movements.

Upper and lower motor neurons

In the context of disease, clinicians refer to the corticospinal (and corticonuclear) neurons as upper motor neurons (Clinical Panel 16.1), and those of the brainstem and spinal cord as lower motor neurons (Clinical Panel 16.2).

Clinical Panel 16.1 Upper motor neuron disease

Upper motor neuron disease is a clinical term used to denote interruption of the corticospinal tract somewhere along its course. If the lesion occurs above the level of the pyramidal decussation, the signs will be detected on the opposite side of the body; if it occurs below the decussation, the signs will be detected on the same side.

Sudden interruption of the corticospinal tract is characterized by the following features:

1 The affected limb(s) show an initial flaccid (floppy) paralysis with loss of tendon reflexes. Normal muscle tone – defined as the resistance to passive movement (e.g. flexion/extension of the knee by the examiner) – is lost.

2 After several days or weeks, some return of voluntary motor function can be expected. At the same time, muscle tone increases progressively. The typical long-term effect on muscle tone is one of spasticity, with abnormally brisk reflexes (hyperreflexia). Classically, spasticity in the leg is ‘claspknife’ in character: after initial strong resistance to passive flexion of the knee, the joint gives way.

3 Clonus can often be elicited at the ankle/wrist. It consists of rhythmic contraction of the flexor muscles 5–10 times per second in response to sudden passive dorsiflexion.

4 Babinski sign (extensor plantar response) consists of dorsiflexion of the great toe and fanning of the other toes in response to a scraping stimulus applied to the sole of the foot. The normal response is flexion of the toes (Figure CP 16.1.1).

5 The abdominal reflexes are absent on the affected side. A normal abdominal reflex consists of brief contraction of the abdominal muscles when the overlying skin is scraped.

The above features are most commonly observed after a vascular stroke interrupting the corticospinal tract on one side of the cerebrum or brainstem. The usual picture here is one of initial flaccid hemiplegia (‘half-paralysis’), followed by a permanent spastic hemiparesis (‘half-weakness’). As illustrated in Clinical Panel 35.3, the spasticity following a stroke characteristically affects the antigravity muscles. In the lower limb, these are the extensors of the knee and the plantar flexors of the foot; in the upper limb, they are the flexors of the elbow and of the wrist and fingers. Following complete transection of the spinal cord, on the other hand, there may be a paraplegia in flexion of the lower limbs, owing to concurrent interruption of the vestibulospinal tract (Clinical Panel 16.3).

The ‘positive’ signs listed under 2, 3, and 4 cannot be explained on the basis of interruption of the corticospinal tract alone. In the rare cases in which the human pyramid has been transected surgically, spasticity and hyperreflexia have not been prominent later on, although a Babinski sign has been present.

Spasticity and hyperreflexia are largely explained by the fact that stretch reflexes in spastic muscle groups are hyperactive. Electromyography (EMG) records of spastic muscles show enhanced motor unit activity in response to relatively slow rates of stretch, e.g. slow passive elbow extension. However, this is not the sole basis of explanation. In patients with spastic hemiparesis, the ankle flexors show increased tone (resistance to passive dorsiflexion) even with very slow rates of stretch—too slow to elicit any EMG response. The resistance takes several weeks to become pronounced. It is called passive stiffness and may be caused by progressive accumulation of collagen within the muscles affected. In addition, biochemical changes within paretic muscle lead to increasing change of fast-twitch to slow-twitch fibers, accounting for progressively greater difficulty in execution of rapid movements.

Why are motor neurons hyperexcitable?

In paraplegic patients, spasticity and hyperreflexia are often accompanied by increased cutaneomuscular reflex excitability, through polysynaptic propriospinal pathways. Pulling on a pair of trousers may be enough to produce spasms of the hip and knee flexors, sometimes accompanied by autonomic effects (sweating, hypertension, emptying of the bladder). Where the requisite technical facilities exist, the situation can be dramatically improved by perfusion of the lumbar CSF cistern with minute amounts of baclofen, a GABA-mimetic (imitative) drug. The first inference is that the drug diffuses through the pia–glial membrane of the spinal cord, activates GABA receptors located on the surface of primary afferent nerve terminals, and dampens impulse traffic by means of presynaptic inhibition. The second inference is that the resident population of GABA neurons in the substantia gelatinosa has fallen silent in these cases through loss of tonic supraspinal ‘drive’. The normal source of supraspinal drive seems to derive in part from the corticospinal tract, and in part from corticoreticulospinal fibers that reach the spinal cord via the tegmentum of the brainstem rather than via the pyramids.

Figure CP 16.1.2 shows the distribution of inhibitory nerve endings derived from Renshaw cells. Not alone do they normally have a tonic breaking action on α and γ motor neurons at their own segmental level: they also tonically inhibit heteronymous motor neurons (i.e. those serving other muscle groups). For example, they act simultaneously upon motor neurons controlling knee and ankle movements, as part of the executive arm of central motor programs regulating successive muscle engagements and disengagements during locomotion. Locomotion is controlled by reticulospinal rather than corticospinal neurons, and any reduction in reticulospinal drive will render motor neurons hyperexcitable, and accounts for the frequent occurrence of ill-timed contractions produced by heteronymous motor neurons.

How do voluntary movements recover?

Multiple explanations are discussed in the final Clinical Panel in the final chapter.

References

Dietz V. Spastic gait disorder. In: Bronstein AM, Brandt T, Woollacott M, editors. Clinical disorders of balance posture and gait. London: Arnold; 1996:1-17.

Nielsen JB, Crone C, Hultborn H. The spinal pathophysiology of spasticity—from a basic science point of view. Acta physiol. 2007;189:171-180.

Singermann J, Lee L. Consistency of the Babinski reflex and its variants. J Neurol. 2008;15:960-964.

Figure CP 16.1.1 The plantar reflex.

Figure CP 16.1.2 Impaired Renshaw cell activity in spasticity. MN, motor neurons.

Clinical Panel 16.2 Lower motor neuron disease

Disease of lower motor neurons may be caused by a variety of infectious agents – notably the virus of poliomyelitis. The term motor neuron disease, or MND, is used to describe a symptom complex characterized by degeneration of upper and lower motor neurons in late middle age.

During the first year or two, lower motor neurons alone may be involved, especially in the upper limbs. This phase is called progressive muscular atrophy and it has the following manifestations:

1 Weakness of the muscles affected, together with

2 Wasting. The wasting is not merely a disuse atrophy but results from loss of a trophic (nourishing) factor produced by motor neurons and conveyed to muscle by axonal transport.

3 Loss of tendon reflexes (areflexia) in the wasted muscles.

4 Fasciculations, which are visible twitchings of small groups of muscle fibers in the early stage of wasting. They arise from spontaneous discharge of motor neurons with activation of motor units, as described in the context of electromyography in Clinical Panel 12.2

5 Fibrillations, which are minute contractions detectable only by needle electromyography, also described in Clinical Panel 12.2.

Sooner or later, signs of upper motor neuron disease appear. The lower limbs become weak, with increased muscle tone and brisk reflexes. This condition is called amyotrophic lateral sclerosis (ALS). Motor cranial nerve nuclei in the pons and medulla oblongata may be involved from the start (progressive bulbar palsy, Ch.18) or only terminally. Death, from respiratory complications, usually occurs within 5 years of onset.

The search for etiological clues is intense. Damage to motor neurons by free radicals has long been suspected, and it is of interest that mutation of a free-radical scavenging enzyme has been detected in some of the 10% of patients who inherit MND in an autosomal dominant mode. Because it is known that retrograde transport of neurotrophins is essential for long-term neuronal survival, recent research has focused upon retrograde transport of signaling endosomes. In particular, failure of the dynein retrograde motor (Ch. 6) has been implicated in the development of several neurodegenerative disorders.

Reference

Wijesekera LC, Leigh PN. Amyotrophic lateral sclerosis. Orphanet journal of rare diseases. 2009;10:1150-1172.

Reticulospinal tracts

The reticulospinal tracts originate in the reticular formation of the pons and medulla oblongata. They are partially crossed.

The pontine reticulospinal tract descends ipsilaterally in the anterior funiculus, and the medullary reticulospinal tract descends, partly crossed, in the lateral funiculus (Figure 16.7). Both tracts act, via internuncials shared with the corticospinal tract, upon motor neurons supplying axial (trunk) and proximal limb muscles. Information from animal experiments indicates that the pontine reticulospinal tract acts upon extensor motor neurons and the medullary reticulospinal tract upon flexor motor neurons. Both pathways exert reciprocal inhibition.

The reticulospinal system is involved in two different kinds of motor behavior: locomotion and postural control.

Locomotion

Walking and running are rhythmical events involving all four limbs. Movements of the two sides are reciprocal with respect to flexor and extensor contractions and relaxations. In lower animals, locomotion is regulated by a hierarchical system in which the lowest members are internuncial neurons on both sides at cervical and lumbosacral levels, activating the flexors and extensors of the individual limbs. They are called pattern generators. Coordinating the pattern generators for the individual limbs is a further generator situated in the intermediate gray matter at the upper end of the spinal cord; it is capable of initiating rhythmical movements after section of the neuraxis at the spinomedullary junction. Locomotion is initiated from a locomotor center located in the lower midbrain of humans, in the pons in laboratory animals. In anesthetized cats, electrical stimulation of the locomotor center with pulses of increasing frequency produces walking movements, then trotting, and finally, galloping.

Although the basic locomotor patterns are inbuilt, they are modulated by sensory feedback from the terrain. Overall control of the motor output resides in the premotor cortex, which has direct projections to the brainstem neurons that give rise to the reticulospinal tracts. The tracts are used to steer the animal as it walks or runs and to override the spinal generators, e.g. in scaling a wall.

Human locomotion is less ‘spinal’ than that of quadrupeds. However, the general neuroanatomical framework has been conserved during higher evolution, and the basic physiology seems to be in place as well. In particular, a bilaterally organized motor system controlling proximal and axial muscles must exist to account for the return of near-perfect locomotor function following removal of an entire cerebral hemisphere during childhood or adolescence. Such people never recover manual skill on the contralateral side, and this reinforces the belief among physical therapists that two distinct pathways are involved in motor control: pyramidal and ‘extrapyramidal’. The latter term denotes the reticulospinal pathway and its controls upstream in the cerebral cortex and basal ganglia.

Higher-level locomotor controls are described in Chapter 24.

Posture

Definitions of posture vary with the context in which the term is used. In the general context of standing, sitting, and recumbency, posture may be defined as the position held between movements. In the local context of a single hand or foot, the term signifies postural fixation – the immobilization of proximal limb joints by co-contraction of the surrounding muscles, leaving the distal limb parts free to do voluntary business. As will be noted in Chapter 29, there is reason to believe that the human premotor cortex is programmed to select appropriate proximal muscle groups by way of the reticulospinal tracts, to set the stage for any particular movement of the hand or foot.

The interpolation of internuncial neurons between the two main motor pathways acting upon motor neurons serving axial and proximal limb muscles means that either pathway may be in command for a particular movement sequence – the extrapyramidal (reticulospinal) pathway for routine tasks such as walking along a clear path, the pyramidal pathway for tasks requiring close attention, e.g. picking one’s way along a path strewn with rubble.

Tectospinal tract

The tectospinal tract is a crossed pathway descending from the tectum of the midbrain to the medial part of the anterior gray horn at cervical and upper thoracic levels. It is strategically placed for access to axial motor neurons (Figure 16.7).

Figure 16.7 Descending pathways at upper cervical level. Notes: The anterior corticospinal tract crosses partially at lower cervical level and engages anterior horn cells supplying postural muscles of the trunk. Some 10% of lateral corticospinal tract fibers descend ipsilaterally.

This tract is an important motor pathway in the reptilian brain, being responsible for orienting the head/trunk toward sources of visual stimulation (superior colliculus) or auditory stimulation (inferior colliculus). It is likely to have similar automatic functions in humans.

Vestibulospinal tract

The vestibulospinal tract is an important uncrossed pathway whereby the tone of appropriate antigravity muscles is automatically increased when the head is tilted to one side. It descends in the anterior funiculus (Figure 16.7) and its function is to keep the center of gravity between the feet. It originates in the vestibular nucleus in the medulla oblongata. (Note: As explained in Ch. 17, there are in fact two vestibulospinal tracts on each side. The unqualified term refers to the lateral vestibulospinal tract.)

Raphespinal tract

The raphespinal tract originates in and beside the raphe nucleus situated in the midline in the medulla oblongata. It descends on both sides within the posterolateral tract of Lissauer. Its function is to modulate sensory transmission between first- and second-order neurons in the posterior gray horn – particularly with respect to pain (see Ch. 24).

Aminergic pathways

Aminergic pathways descend from specialized cell groups in the pons and medulla oblongata (Ch. 24). The principal neurotransmitters involved are norepinephrine and serotonin, both of which are classed as biogenic amines. The aminergic pathways descend in the outer parts of the anterior and lateral funiculi, and are distributed widely in the spinal gray matter. In general terms, they have inhibitory effects on sensory neurons and facilitatory effects on motor neurons.

Central autonomic pathways

Central sympathetic and parasympathetic fibers descend beside the intermediate gray matter (Figure 16.7). They originate in part from autonomic control centers in the hypothalamus and in part from several nuclear groups in the brainstem. They terminate in the intermediolateral cell columns that give rise to the preganglionic sympathetic and parasympathetic fibers of the peripheral autonomic system.

The central sympathetic pathway is required for normal baroreceptor reflex activity. If the spinal cord is crushed in a neck injury, the patient loses consciousness if raised from the recumbent position within the first week or so because a fall of blood pressure in the carotid sinus on sitting up normally causes a compensatory increase in sympathetic activity in order to maintain blood flow to the brain.

The central parasympathetic pathway is required for normal bladder (and rectal) function. The fibers concerned originate in the reticular formation, mainly at the level of the pons (Ch. 24). The pontine micturition center has a tonic inhibitory action on the sacral parasympathetic system. Severe injury to the spinal cord or cauda equina results in reflex voiding when the bladder is only half full (Clinical Panel 16.3).

Clinical Panel 16.3 Spinal cord injury

In the industrialized world, automobile accidents are the commonest cause of spinal cord injury. More than half of the victims are between 16 and 30 years old, and the cervical cord is most commonly affected. Injury at thoracic or lumbar segmental level results in paraplegia (paralysis of lower limbs). Injury at cervical level causes tetraplegia (quadriplegia), in which the extent of upper limb paralysis depends on the number or level of cervical segments involved.