BARR'S The Human Nervous System: An anatomical viewpoint, 9th Edition

PART 2 - Regional Anatomy of the Central Nervous System

Chapter 12

Corpus Striatum

Important Facts

  • The corpus striatum is the telencephalic gray matter associated with the lateral ventricle. It is composed of the striatum (caudate nucleus, nucleus accumbens, and putamen) and the pallidum (globus pallidus), which is composed of external and internal divisions.
  • In clinical and physiological usage, basal gangliarefers collectively to the corpus striatum, subthalamic nucleus, and substantia nigra. The best-understood functions of the basal ganglia are in the production of movements, but extensive connections with the temporal and anterior frontal cortex indicate involvement in memory, emotion, and other cognitive functions.
  • The striatum, subthalamic nucleus, and substantia nigra receive excitatory afferents from the cerebral cortex. Dopaminergic neurons in the substantia nigra and ventral tegmental area excite some striatal neurons and inhibit others.
  • The major output of the striatum is to the pallidum, and it is inhibitory. Excitatory input to the pallidum comes from the subthalamic nucleus.
  • The output of the pallidum, which is also inhibitory, is to various thalamic nuclei. The thalamic nuclei project to and excite the premotor and supplementary motor areas of the cerebral cortex, cortical areas concerned with eye movements, and parts of the prefrontal and temporal cortex.
  • Other pallidal efferents inhibit the subthalamic nucleus, superior colliculus, and pedunculopontine nucleus. The pedunculopontine nucleus, which is located in the reticular formation, has extensive projections that influence descending motor pathways, the waking state, and (by way of the basal cholinergic forebrain nuclei) neuronal activity throughout the cerebral cortex.
  • At rest, neurons in the striatum are quiescent, and those in the pallidum are active, thereby inhibiting the thalamic excitation of the motor cortex. Before and during a movement, the striatum becomes active and inhibits the pallidum, allowing more excitation of the motor thalamic nuclei and cortex.
  • The corpus striatum may normally be the site in which instructions for parts of learned movements are remembered and from which they are transmitted to the motor cortex for assembly and eventual execution by corticospinal and reticulospinal pathways to the motor neurons. Comparable circuitry exists for the control of movements of the eyes.
  • The nucleus accumbens and the most ventral parts of the pallidum are active in behavioral responses to a wide variety of rewarding or pleasurable stimuli. Conditioned reflexes passing through these nuclei and their associated cortical areas have been implicated in drug addiction.
  • Disorders of the motor circuitry of the basal ganglia (dyskinesias) include Parkinson's disease (degeneration of nigral dopaminergic neurons), Huntington's chorea (degeneration in the striatum), and ballism (damage to subthalamic nucleus). Some features of these disorders can be explained from knowledge of the disrupted neuronal pathways.
  • The basal cholinergic nuclei of the forebrain are ventral to the corpus striatum, within the anterior perforated substance. Their axons are distributed to the whole cerebral cortex. Afferents to the basal nuclei are from the amygdala, the pallidum, and the reticular formation of the brain stem. Subcortical cholinergic neurons degenerate in patients with Alzheimer's disease and some other forms of dementia.

The corpus striatum is a substantial region of gray matter near the base of each cerebral hemisphere. It consists of the caudate nucleus and the lentiform nucleus, with the latter divided into the putamen and the globus pallidus. Traditionally, the corpus striatum, claustrum, and amygdaloid body were referred to by anatomists

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as the basal nuclei or “ganglia” of the telencephalon. The caudate nucleus and putamen together constitute the striatum, and the globus pallidus is referred to as the pallidum.Nearby structures include the claustrum (a thin sheet of gray matter situated between the putamen and the cortex of the insula) and the amygdaloid body or amygdala in the temporal lobe, which is a component of the olfactory and limbic systems (see Chapters 17 and 18).

Clinically, the term basal ganglia is usually applied to the corpus striatum (Fig. 12-1), subthalamic nucleus, and substantia nigra. These neuronal populations are grouped under this common heading because they are interconnected to form a functional unit, and destructive lesions in any of the components result in disorders of motor control characterized by akinesia (i.e., a poverty of voluntary movement), rigidity, or dyskinesias (in which purposeless involuntary movements take place).

Terminology

The following correlations may be helpful in understanding the terminology of the corpus striatum and “basal ganglia”:

 

FIGURE 12-1 Lateral aspect of the right corpus striatum, showing also the thalamus and amygdala. The globus pallidus is concealed by the larger putamen.

  • Corpus striatum: Lentiform and caudate nuclei, including the nucleus accumbens
  • Lentiform nucleus: Putamen and globus pallidus (the latter has external and internal divisions)
  • Striatum: Putamen, caudate nucleus, and nucleus accumbens
  • Pallidum: Globus pallidus (It is composed of external and internal divisions; the substantia nigra pars reticulata belongs functionally with the internal pallidum.)
  • Basal ganglia (clinical and physiological usage): Corpus striatum, substantia nigra, and subthalamic nucleus

Lentiform and Caudate Nuclei

The configuration and relations of the lentiform and caudate nuclei contribute to the topography of the lateral ventricle and the cerebral white matter, which are described inChapter 16. This anatomy is best appreciated by dissection. For understanding the afferent and efferent connections, the pallidum and striatum are the more functionally relevant divisions of the corpus striatum.

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LENTIFORM NUCLEUS

The lentiform nucleus is wedge shaped and has been described as having the approximate size and form of a Brazil nut (Figs. 12-2 and 12-3). The narrow part of the wedge, facing medially, is occupied by the globus pallidus, which is divided into external and internal parts by a lamina of white matter. The putamen is the lateral part of the lentiform nucleus, and it extends beyond the globus pallidus in all directions except at the base of the nucleus. The external pallidum is separated from the putamen by another lamina of white matter.

The lentiform nucleus is bounded laterally by a thin layer of white matter that constitutes the external capsule (see Figs. 12-2 and 12-3). This is followed by the claustrum, which is a thin sheet of gray matter coextensive with the lateral surface of the putamen. The best-documented connections of the claustrum are reciprocal connections with the cortices of the frontal, parietal, and temporal lobes, but their functional significance is unknown. The extreme capsule separates the claustrum from the insula (island of Reil), an area of cortex buried in the depths of the lateral sulcus of the cerebral hemisphere. The medial surface of the lentiform nucleus lies against the internal capsule. The ventral surface is close to structures at the base of the hemisphere, such as the anterior perforated substance, optic tract, and amygdaloid body (see Fig. 12-3).

 

FIGURE 12-2 Horizontal section of the cerebrum stained to differentiate gray matter (dark) from white matter (light), showing the components and relations of the corpus striatum and internal capsule.

CAUDATE NUCLEUS

The caudate nucleus consists of an anterior portion or head, which tapers into a slender tail. The tail extends backward and then forward into the temporal lobe (see Fig. 12-1), where it terminates at the amygdaloid body.

The head of the caudate nucleus bulges into the frontal horn of the lateral ventricle, and the first part of the tail lies along the lateral margin of the central part of the ventricle (seeFigs. 12-2 and 12-3). The tail follows the contour of the lateral ventricle into the roof of its temporal horn. Two structures lie along the medial side of the tail of the caudate nucleus. These are the stria terminalis, a bundle of axons that originates in the amygdaloid body and the

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thalamostriate vein (vena terminalis), which drains the caudate nucleus, thalamus, internal capsule, and nearby structures (see Fig. 11-12). Groups of neuronal cell bodies within the stria terminalis constitute the bed nucleus of the stria terminalis, which belongs functionally with certain nuclei of the amygdala.

 

FIGURE 12-3 Coronal section of the cerebrum anterior (rostral) to the thalamus, stained to differentiate gray matter (dark) from white matter (light), showing the components and relations of the corpus striatum.

The anterior limb of the internal capsule intervenes between the head of the caudate nucleus and the lentiform nucleus. The tail of the caudate nucleus is medial to the internal capsule as the latter merges with the central white matter of the hemisphere. The cortical afferent and efferent fibers that constitute the internal capsule do not completely separate the two components of the striatum. The head of the caudate nucleus and the putamen are continuous with each other through a bridge of gray matter beneath the anterior limb of the internal capsule (see Fig. 12-1). In addition, numerous strands of gray matter join the caudate nucleus with the putamen by cutting across the internal capsule (see Fig. 12-3). The most ventral part of the striatum in this region is called the nucleus accumbens, also known as the ventral striatum.

Ventral to the nucleus accumbens is the substantia innominata, which contains the most ventral part of the globus pallidus (the ventral pallidum) and the basal cholinergic nuclei of the forebrain, which are described at the end of this chapter.

CONNECTIONS

The major neuronal connections of the parts of the corpus striatum are summarized in Figures 12-4 and 12-5 and explained in the following paragraphs.

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FIGURE 12-4 Afferent (blue) and efferent (red) connections of the striatum.

STRIATUM

The striatum receives afferent fibers from the cerebral cortex, thalamus, and substantia nigra (see Fig. 12-4). Corticostriate fibers, which are excitatory, originate in the cortex of all four lobes, but especially the frontal and parietal lobes. The corticostriate fibers are topographically organized. The somatosensory and motor areas project to the putamen; the cingulate gyrus and temporal lobe cortex (including the parahippocampal gyrus) project to the nucleus accumbens or ventral striatum, and other cortical areas project mainly to the caudate nucleus. Most of these fibers enter the striatum from the internal capsule, although a substantial number enter the putamen from the external capsule. The amygdala (see also Chapter 18) is a source of afferents to the nucleus accumbens and the caudate nucleus. Some of the amygdalostriate fibers pass through the substantia innominata; others arrive by way of the stria terminalis. Thalamostriate fibers, also excitatory, originate in the intralaminar nuclei of the thalamus, especially the centromedian nucleus. Nigrostriate fibers from the pars compacta of the substantia nigra use dopamine as a transmitter; they excite some striatal neurons and inhibit others. In Parkinson's disease, discussed later in this chapter, degeneration of neurons in the pars compacta deprives the striatum of its dopaminergic input. Dopaminergic

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afferents of the nucleus accumbens arise from the ventral tegmental area, which is medial to the substantia nigra (see Fig. 7-15).

 

FIGURE 12-5 Afferent (blue) and efferent (red) connections of the pallidum. (The projection to the superior colliculus is not included in the diagram.)

The axons that leave the striatum are striopallidal, bringing both segments of the globus pallidus under the influence and control of the striatum and strionigral, which pass through the globus pallidus before entering the midbrain and terminating in both parts of the substantia nigra. (The pars reticulata of the substantia nigra, which is ventral to the pars compacta, has connections similar to those of the internal division of the globus pallidus.)

Striatal efferent projections are all inhibitory, with γ-aminobutyric acid (GABA) as their transmitter. Different populations of striatal principal cells contain various peptides and calciumbinding proteins in addition to GABA. The striatum also contains many interneurons, which use GABA, acetylcholine, and several peptides as their neuro-transmitters. Histochemical studies reveal “patches” or “striosomes,” separated by a “matrix.”

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Corticostriate and nigrostriate fibers terminate throughout the striatum, but afferents from the intralaminar thalamic nuclei end only in the matrix.

PALLIDUM

The globus pallidus contains the myelinated axons of its own neurons together with great numbers of myelinated striopallidal and strionigral fibers. The abundance of myelin accounts for the somewhat pale appearance of the region in fresh sections and for the name “globus pallidus.” The pallidum is notable in that it receives GABA-ergic inhibitory input from the striatum and its own principal neurons are also GABA-ergic and inhibitory. The substantia nigra pars reticulata in the midbrain has connections similar to those of the globus pallidus and is best thought of as a caudally displaced part of the pallidum.

The inhibitory GABA-ergic striopallidal fibers noted previously are the principal afferents to the globus pallidus (see Fig. 12-5). They end in the external and internal segments. In the following discussion, the word “pallidofugal” applies to efferents of the globus pallidus, ventral pallidum, and substantia nigra pars reticulata.

Fibers leaving the globus pallidus initially take either of two routes (see Fig. 12-5). Some cross the internal capsule and appear as the lenticular fasciculus (field H2 of Forel) in the subthalamus, dorsal to the subthalamic nucleus. Other pallidofugal fibers curve around the medial edge of the internal capsule, forming the ansa lenticularis. These two fasciculi (shown in Figs. 11-9 and 11-10) consist mainly of pallidothalamic fibers, which originate in the internal segment of the globus pallidus. They enter the prerubral area of the subthalamus (field H of Forel), turn laterally into the thalamic fasciculus (field H1 of Forel), and terminate in at least three thalamic nuclei. The anterior division of the ventral lateral nucleus (VLa) projects to the premotor area of cortex in the frontal lobe and to the contiguous part of the medial surface of the hemisphere that is designated the supplementary motor area (see Chapters 15 and 24). The ventral anterior nucleus projects to these motor areas as well as to the frontal eye field and parts of the prefrontal cortex, which covers the frontal pole and the orbital surface of the frontal lobe. The mediodorsal nucleus consists of subnuclei; most of these project to the prefrontal cortex and anterior end of the cingulate gyrus, but one contains neurons connected with the frontal eye field. The regions of the VL thalamic nucleus that receive pallidal afferents (VLa) are largely separate from those that receive input from the cerebellum (VLp), although some overlap exists.

A few pallidofugal fibers accompany the main outflow to the thalamus but continue into the stria medullaris thalami and terminate in the habenular nuclei. Through this connection, the corpus striatum is potentially able to modify the descending output of the limbic system, which exerts control over autonomic and other involuntary activities.

Other pallidofugal fibers (mostly from the substantia nigra pars reticulata) go to the superior colliculus, which has numerous connections with other nuclei involved in the control of eye movements.

Although the efferent fasciculi of the internal (medial) segment of the globus pallidus project principally to the VLa, ventral anterior (VA), and mediodorsal (MD) nuclei of the thalamus, some pallidofugal fibers turn caudally and end in the pedunculopontine nucleus, which is one of the cholinergic groups of reticular nuclei (see Chapter 9) in the brain stem. Fibers from the pedunculopontine nucleus proceed caudally to the central nuclei of the reticular formation and rostrally to the substantia nigra pars compacta, subthalamic nucleus, intralaminar thalamic nuclei, pallidum, striatum, and basal cholinergic forebrain nuclei.

The external segment of the globus pallidus has an inhibitory projection to the subthalamic nucleus, consisting of axons that pass across the internal capsule in the subthalamic fasciculus (see Fig. 12-5). This bundle also contains the axons of neurons of the subthalamic nucleus, which end in the internal segment of the globus pallidus and in the closely related pars reticulata of the substantia nigra.

Physiology and Neurochemistry of the Basal Ganglia

THE DIRECT AND INDIRECT LOOPS

Knowledge of the excitatory and inhibitory synapses in the basal ganglia may explain some clinical features of disorders of the system and has

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provided indications for therapy with drugs that mimic or inhibit the neurotransmitters. Figure 12-6 shows some of the connections with their actins and the known or suspected transmitters.

Fibers from motor and other areas of the cerebral cortex end in the striatum (corticostriate fibers), subthalamic nucleus (corticosubthalamic fibers), and pars compacta of the substantia nigra (corticonigral fibers). These cortical projections are excitatory, with glutamate as the neurotransmitter.

Pallidal neurons are spontaneously active. The medial segment of the globus pallidus and the substantia nigra pars reticulata receive additional excitatory drive from the glutamatergic neurons of the subthalamic nucleus. Thus, increased activity in the subthalamic nucleus results in reduced activity of thalamocortical neurons.

The striatum inhibits both divisions of the pallidum, and pallidofugal neurons inhibit thalamocortical neurons. In both cases, the inhibitory transmitter is GABA. The different connections of the external and internal divisions of the globus pallidus provide two loops of connected neurons that have opposite effects on the cerebral cortex. The direct loopbegins with neurons in the striatum that contain GABA and substance P (SP). Increased activity of these striatal neurons leads to disinhibition of thalamic neurons and, consequently, increased stimulation of the cerebral cortex. Different striatal neurons, containing GABA and enkephalin (ENK), participate in the indirect loop, which includes the subthalamic nucleus. Activity of the striatal GABA-ENK neurons results in inhibition of the thalamus and reduced stimulation of the cortex. The nigrostriate input excites the GABA-ENK neurons and inhibits the GABA-SP neurons because of different types of dopamine receptors on the surfaces of the cells. Both these actions of dopamine lead to increased activity of thalamocortical neurons.

 

FIGURE 12-6 General plan of the neuronal circuitry of the basal ganglia showing neurotransmitters and their actions. Neurons in the direct loop are blue and those of the indirect loop are green. (+ indicates excitation; -, inhibition; DA, dopamine; ENK, enkephalin; GABA, γ-aminobutyrate; GLU, glutamate; SP, substance P.)

MOTOR FUNCTIONS

The best-understood functions of the corpus striatum are those related to movement. The neurons of the striatum are quiescent, and those of the pallidum are active when no movements are being made. Shortly before and during a movement, the situation is reversed. Removal of pallidal inhibition allows the VLa and VA thalamic nuclei to be stimulated by other afferent fibers, most of which come from the premotor and supplementary motor areas of the cerebral cortex. The thalamocortical neurons are excitatory to the same motor cortical areas.

Nigrostriatal dopaminergic neurons are active all the time; their rates of firing increase with activity of the contralateral musculature.

Clinical observations and animal experiments indicate that the corpus striatum is probably a

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repository of instructions for fragments of learned movements. When a movement is to be carried out, the instructions encoded by the corpus striatum are presumably transmitted from the pallidum to the thalamus (VLa and VA) and then sent on to the supplementary motor area and the premotor cortex. Corticospinal, corticoreticular, and reticulospinal projections then modulate the motor neurons. The pallidal projection to the pedunculopontine nucleus provides another functional connection with the central nuclei of the reticular formation, which are the source of the reticulospinal tracts. Degenerative diseases of the basal ganglia result in unwanted movements, and it has been suggested that the circuitry of the corpus striatum normally allows choices to be made in the types of motor responses rather than making stereotyped movements in response to stimuli.

OTHER FUNCTIONS OF THE CORPUS STRIATUM

The topographical projections of different cortical areas with parts of the striatum are associated with parallel but separate channels through the pallidum and thalamus. Four such channels are usually recognized; these are summarized in Table 12-1.

TABLE 12-1 Parallel Circuits (“Channels”) Involving the Corpus Striatum

Channel

Sources of
Cortical Input
to Striatum

Striatal
Nuclei

Pallidal
Nuclei

Thalamic
Nuclei Relaying
Pallidal Input
to Cortex

Cortical Areas
Receiving
Thalamic Input

Motor

Primary somatic sensory and motor areas; premotor area

Putamen

Globus pallidus

Ventral lateral and ventral anterior nuclei

Supplementary and primary motor areas and premotor area

Ocular motor

Prefrontal and posterior parietal cortex

Caudate nucleus (tail)

Globus pallidus; substantia nigra pars reticulata

Ventral anterior and mediodorsal nuclei

Frontal eye fields

Prefrontal

Premotor area and posterior parietal cortex

Caudate nucleus (head)

Globus pallidus

Ventral anterior and mediodorsal nuclei

Prefrontal cortex

Limbic

Temporal lobe; hippocampal formation; amygdala

Nucleus accumbens

Ventral pallidum

Mediodorsal nucleus

Cingulate gyrus and orbital prefrontal cortex

The great size of the human corpus striatum indicates collaboration with the cerebral cortex in aspects of memory and thought that are more complex than formulation of the component parts of movements. These higher functions probably involve the connections of the striatum and pallidum with the mediodorsal thalamic nucleus and with the prefrontal, cingulate, and temporal cortex. Despite the numerous known connections of the basal ganglia, it is not possible to ascribe simple functions to the four channels summarized in Table 12-1. Diseases that affect the basal ganglia result principally in the motor disorders described later in this chapter.

An animal with an electrode implanted in either the ventral tegmental area or the lateral hypothalamus derives gratification from delivering small electrical stimuli to these regions and will press the switch repeatedly to the exclusion of such activities as eating and drinking. The ventral tegmental area is the source of dopaminergic axons that pass through the lateral hypothalamic area (medial forebrain bundle) en route to the nucleus accumbens. Numerous other experiments implicate the dopaminergic projection to the nucleus accumbens in behavioral responses to stimuli that are perceived as rewards. Drugs of addiction activate the system. Thus, amphetamines enhance dopamine release from presynaptic terminals, cocaine potentiates the action of dopamine by blocking its reuptake by presynaptic terminals, and opiates act on neurons in the ventral tegmental area and the striatum. Nicotine and ethanol have also been shown to induce elevated levels of dopamine in the nucleus accumbens.

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CLINICAL NOTE

Dyskinesias and the Corpus Striatum

Despite the central position of the corpus striatum in the neural circuitry of motor control (see Chapter 23), lesions in the basal ganglia do not cause paralysis. They result in unwanted involuntary movements.

TYPES OF DYSKINESIA

The involuntary movements seen in the dyskinesias related to the corpus striatum take various forms. Choreiform movements involve multiple muscles. They are brisk, jerky, and purposeless, resembling isolated fragments of movements that might be useful. They are irregularly timed, most pronounced in the upper limbs and face, and cannot be voluntarily inhibited. Hypotonia of the affected muscles may present when the muscles are not contracting.

Dystonic movements are sustained contractions that lead to abnormal posture or twisting of the neck, trunk, or limbs. Dystonia musculorum deformans (also called generalized dystonia) is a particularly disabling motor disturbance in which slow, writhing, involuntary movements of the axial and limb musculature are sustained, leading in rare cases to permanent contractures. The symptoms first appear in older children and young adults. Lesions may be present in the corpus striatum and elsewhere, but the pathology is poorly understood. The most common dystonia is spasmodic torticollis, with rotation and lateral flexion of the neck. Athetosis is a type of dystonia in which slow and sinuous movements occur involving the proximal and distal musculature of the limbs. The movements blend together in a continuous mobile spasm and are usually associated with varying degrees of paresis and spasticity. The muscles of the face, neck, and tongue may be affected, with grimacing, protrusion, and writhing of the tongue as well as difficulty in speaking and swallowing. The term choreoathetosis is applied to involuntary movements with both choreiform and athetoid features.

Myoclonus consists of sudden, strong contractions that may be isolated, repetitive, or rhythmic. Regularly alternating movements of small amplitude constitute tremor. Whereas stereotyped purposeless movements that occur at random are called tics or habit spasms, a generalized inability to be still, with constant motion of the limbs, is sometimes called akathisia. The largest involuntary movements are those of ballism, an exaggerated form of chorea in which the limbs make large, irregular flinging and rotational movements caused by contractions of muscles acting on the shoulder or hip joints.

The lesions responsible for dyskinesias are poorly understood. In chorea, extensive damage is present in the striatum. Some cases of dystonia are attributable to a tumor or a vascular lesion in the contralateral putamen, and myoclonus has been associated with lesions in the ventral part of the thalamus. More often than not, no pathology can be identified by clinical imaging in patients with dystonias. Ballism is usually attributed to a small destructive lesion in the contralateral subthalamic nucleus. The uncontrolled movements may be attributable to a loss of excitatory input to the internal division of the globus pallidus, which then fails to inhibit the VLa and VA nuclei of the thalamus. Excessive activity in these thalamic nuclei stimulates the premotor area of the cerebral cortex, causing excessive movement at the proximal joints of the limbs. The most common type of ballism is hemiballismus, described in Chapter 11. Lesions in the pars compacta of the substantia nigra are responsible for the tremor, bradykinesia, and other features of Parkinson's disease, described in Chapter 7.

DISEASES

Choreiform movements are a cardinal sign in numerous conditions. Huntington's chorea is a dominant hereditary disorder with onset of clinical signs in middle life. Patients have atrophy of the striatum, most conspicuous in the caudate nucleus. The choreiform movements become more severe with time, and progressive mental deterioration is also present, attributed partly to degeneration of the nonmotor parts of the striatum and partly to concurrent loss of neurons in the cerebral cortex. Sydenham's chorea (or St. Vitus' dance) is now a rare disorder. It typically occurred in childhood after an infectious disease caused by hemolytic streptococci. Because the disease was seldom fatal, the pathology of Sydenham's chorea is poorly understood. The most common findings were microscopic hemorrhages and emboli in the corpus striatum.

Athetosis and choreoathetosis often form part of a complex of neurological signs that result from metabolic disorders of the developing brain or

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from birth injury. Athetoid movements are most frequently associated with pathological changes in the striatum and the cerebral cortex, although lesions are sometimes also present in the globus pallidus and the thalamus. The term cerebral palsy refers to movement disorders caused by brain injury incurred near or at the time of birth. Spastic paresis or paralysis (caused by loss of function of descending motor pathways; see Chapter 23) is another common type of cerebral palsy.

Wilson's disease (hepatolenticular degeneration) is caused by a genetically determined error in copper metabolism. The signs of Wilson's disease usually appear between the ages of 10 and 25 years and include muscle rigidity, dystonia, tremor, impairment of voluntary movements (including those of speech), and loss of facial expression. Uncontrollable laughing or crying may be present without apparent cause, and dementia ensues if the condition is left untreated. The degenerative changes are most pronounced in the putamen and progress to cavitation of the lentiform nucleus. Cellular degeneration may take place in the cerebral cortex, thalamus, red nucleus, and cerebellum. In addition to these neurological abnormalities, affected patients have cirrhosis of the liver. The neurological and hepatic changes of Wilson's disease respond to treatment with drugs that enhance the urinary excretion of copper.

Some drugs used in psychiatry inhibit the action of dopamine in the striatum. When given for a long time, in high doses, or to unusually susceptible patients, these drugs can cause a variety of acute parkinsonian or dystonic reactions or dyskinesias. The most common of these iatrogenic disorders is known as tardive dyskinesia.

The connections of the corpus striatum indicate that the control of movement is only one of the functions of this large part of the cerebral hemisphere, but disorders other than dyskinesias are not well documented. A condition known as abulia, in which patients have a loss of willpower and initiative with long delays in answering questions, has been reported in patients with small lesions confined to the caudate nucleus. Abulia, however, is more commonly seen in patients with large bilateral frontal lobe lesions.

SUBSTANTIA INNOMINATA AND BASAL CHOLINERGIC NUCLEI

The substantia innominata is the territory ventral to the internal capsule, nucleus accumbens, and anterior commissure; dorsal to the anterior perforated substance; medial to the amygdala; and lateral to the hypothalamus. The region contains axons passing in all directions, including a large contingent on their way from the amygdala to the ventral striatum and hypothalamus. The substantia innominata also contains the ventral pallidum, small numbers of dopamine-synthesizing neurons, and the basal forebrain nuclei. The latter comprise three groups of large cholinergic neurons: the largest cholinergic cell group is the nucleus basalis of Meynert; the others are the nucleus of the diagonal band and part of the septal area. These groups of cells receive afferent fibers from the amygdala; the cortex of the temporal lobe; the insula; the orbital surface of the frontal lobe; the hypothalamus; and the central, cholinergic, and noradrenergic nuclei of the reticular formation. The cholinergic neurons in the basal forebrain nuclei have branching axons that end in all areas of the cerebral cortex as well as in the hippocampus and all components of the basal ganglia. They constitute the sole source of cholinergic innervation of the cortex, perhaps providing an important link between the limbic system and the neocortex. Amnesia can occur after surgical damage that interrupts the cholinergic projection from the basal forebrain nuclei to the hippocampal formation, indicating an involvement of this connection in learning and recall. The basal cholinergic nuclei also

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receive input from nuclei in the brain stem (see Chapter 9) and are implicated in arousal and the wakeful state.

CLINICAL NOTE

Alzheimer's Disease

The magnocellular basal forebrain nuclei are among several parts of the brain that degenerate in Alzheimer's disease. This disorder, the first manifestation of which is the failure of memory for recent events, is a common cause of mental deterioration (dementia) in elderly people. The large cholinergic neurons at the base of the forebrain degenerate, and the cortex loses its cholinergic afferent fibers. Severe degenerative changes are also seen in the entorhinal cortex, hippocampus, and locus coeruleus. In advanced Alzheimer's disease, considerable neuronal loss is also present, with shrinkage of gyri, throughout the cerebral cortex but most prominently in the temporal and parietal lobes. Fibrillary tangles in neuronal somata are present in all affected parts of the brain, together with large extracellular deposits of fibrillary material known as senile plaques. Similar pathological changes are found in several other diseases that cause dementia.

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