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Putamen

From: Neuropsychiatry, Neuropsychology, Clinical Neuroscience
by Rhawn Joseph, Ph.D.
(Academic Press, New York, 2000)




Putamen

PUTAMEN,

By Rhawn Joseph, Ph.D.

Structural Overview

The basal ganglia is composed of several major nuclei which include the corpus (or dorsal) striatum ("striped bodies") i.e., the caudate and putamen which are extensively interconnected and which project to a variety of brain areas including the immediately adjacent globus pallidus ("pale globe"). The dorsal globus pallidus although related to the hypothalamus and midbrain, is in many respects coextensive and appears to merge with the putamen giving the entire structure the appearance of a camera lens. Hence the globus pallidus and the putamen are referred to as the lenticular nucleus ("lens"). The dorsal striatum also continues to be intimately related to the amgydala, receiving massive input from this structure but providing little in return.

The striatum, receives much of its input from the neocortex (Jones & Powell, 1970; Pandya & Vignolo, 1971), and the amygdala, and to a mimimal extent the hippocampus. The majority of these incoming fibers are excitatory and terminate in the corpus striatum and subthalamic nucleus. Specifically, the anterior portion of the frontal lobes projects to the head of the caudate whereas the more posterior putamen receives converging and overlapping input from the primary and secondary motor and somesthetic cortices (Jones & Powell, 1970; Pandya & Vignolo, 1971). This structure does not receive any direct input from the peripheral sensory or motor systems.

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The main avenue of output is via the globus pallidus (and in the brainstem, the substantia nigra) which projects to the thalamus and the brainstem via the "extra-pyramidal system". The basal ganglia does not project directly to the spinal cord. The majority of these outgoing axons arise from "spiny" neurons, and these are responsible for transmitting striatal impulses to the globus pallidus (GP). These are predominantly inhibitory and employ GABA (and various peptides, e.g. substance P) as neurotransmitters.

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The GP transmits to the brainstem and to the motor thalamus and subthalamic nucleus (Mink & Thach, 1991; Parent & Hazrati 1995). The motor thalamus in turn projects to the frontal motor areas i.e. the primary, secondary, supplementary motor areas and frontal eye fields, including the anterior frontal lobe.

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The subthalamic nucleus, is directly linked with the hypothalamus and midbrain, and receives excitatory input from all frontal motor areas; Unlike the globus pallidus, output from the subthalamic nucleus is excitatory, and it in fact projects back to the globus pallidus.

The GP, therefore, receives diffuse exitatory input from the subthalamic nucleus, and converging inhibitory input from the striatum, and the transmits the bulk of its inhibitory impulses to the motor thalamus which acts on the frontal neocortical motor areas. Thus a complex feedback loop involving inhibitory and excitatory circuits is maintained in this area--feedback which presumably assists in the guidance of movements directly controlled by the frontal motor areas, as well as those initiated internally vs externally (Schultz & Romo, 1992).

Conversely, disturbances in this feedback loop, or in the neurotransmitters which maintain it, can result in a host of motor disturbances, ranging from the rigidity of Parkinson's disease and catatonia to chorea, hemiballismus, or "restless leg syndrome." Restless leg syndrome, for example, is a chronic condition which presumably afflicts about 5% of the population, and is characterized by a constant, sometimes painful urge to move the limbs which is only relieved by walking (e.g. Tergau, et al., 1999; Turjanski, et al., 1999). Functional imaging indicates that this disorder is directly related to disturbances in striatal dopamine binding and uptake, particularly in the caudate and putamen (Turjanski, et al., 1999). Presumably, this disturbances is thus a function of abnormal activity in these structures which begin to fire in the absence of any desire to move, thus inducing an urge to move, coupled with excessive activity in the frontal motor areas (e.g., Tergau, et al., 1999)

In this regard it is noteworthy that neurons in the striatum begin firing prior to movement, 20 ms on average. They increase their rate of firing at the start of specific movements, and cease to fire following movement (Montgomery & Bucholz, 1991; Schultz & Romo, 1992). Moreover, neurons related to movement are somatotopically organized such that those that represent the leg, face or arm, cluster together within the striatum, and increase their activity prior to and during movements of the leg, face or arm, etc.,

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The corpus striatum, GP, and subthalamic nucleus, however, represent only the dorsal aspect of the "basal ganglia." Ventral to and intimately associated with the dorsal striatum is the limbic striatum, portions of which have also been referred to as the "extended amygdala." Indeed, the amygdala is a major component of the "basal ganglia," and these structures function as a cohesive interacting unit for the purposes of defensive and other affective behaviors regarding gross body movements, such as kicking, flailing, running, and kicking.

Catatonia, Parkinson's Disease, & Psychosis.

Lesions to the corpus striatum and lenticular nucleus (putamen and globus pallidus) can attenuate one's capacity to motorically express their emotions via the musculature; e.g. the face may become frozen and mask-like. These latter motor disturbances are well known symptoms associated with Parkinson's disease, a disturbance directly linked to dopamine deficiency (Fahn, 1999) and neuronal degeneration not only in the putamen (Goto, et al. 1990; Kish, et al. 1988; see also Hauser et al., 1999), but within the limbic striatum, i.e. the nucleus accumbens (see Rolls & Williams, 1987), as well as in the supplementary motor areas and medial frontal lobe -which maintains rich interconnections with the striatum.

However, when chemical or structural lesions extend beyond the basal ganglia and come to include the medial frontal lobe, not only might an individual suffer motor rigidity, they may become catatonic and experience extreme difficulty responding to external or internally mediated impulses (Joseph, 1999a). Various aspects of this symptom complex also characterize those with Parkinson's disease (see below).

Other disturbances associated with striatal abnormalities include Huntington's chorea, ballismus, restless leg syndrome, sensory neglect and apathy, obsessive compulsive disorders, mania, depression, "schizophrenia" and related psychotic states (Aylward et al. 1994; Baxter et al. 1992; Caplan, et al. 1990; Castellanos et al. 1994; Chakos et al. 1994; Davis, 1958; Deicken et al. 1995; Ellison, 1994; Rauch et al. 1994; Richfield, et al. 1987; Turjanski, et al., 1999). Severe memory loss and social-emotional agnosia and an inability to recongize friends or loved ones is also characteristic of striatal abnormalities, particularly disturbances involving the limbic striatum.

Thus although the basal ganglia is often viewed and described as a major motor center (detailed below), the functional capacities and symptoms associated with this group of nuclei are quite diverse, and vary depending on the nuclei and chemical neurotransmitters involved as well as the laterality, location, and extent of any lesion.

THE CORPUS STRIATUM

PATCHES & MATRIX

The caudate and putamen are tightly interlinked and in some respects are indistinguishable and possess a similar internal compartmental structure of patches and matrix (Graybiel 1986; Gerfen, 1984). This is why a gross analysis of the the mammalian caudate and putamen reveals a striated (patchlike) appearance.

The patches and matrix are biochemically distinct and receive projections from different regions of the neuroaxis (Gerfen, 1984, 1987; Graybiel 1986). For example, the patches contain dense concentration of opiate receptors (Graybiel, 1986) and receive projections from the amygdala, hippocampus, and other limbic tissue and maintain interconnections with the DA neurons in the substantia nigra. The patches in fact form a continuous labyrinth which snakes throughout the striatum.

The surrounding matrix also receives projections from the cingulate gyrus, the motor thalamus, and from throughout the neocortex and maintains interconnections with GABA and DA neurons in the substantia nigra (Gerfen, 1987). The matrix also contains large amounts of acetylcholinesterase.

MOTOR FUNCTIONS

Although tightly linked and similar in structural organization, the caudate appears to exert more influence and provide more input to the putamen, than vice versa. However, like the caudate, the putamen also receives considerable input from the medial frontal, supplementary, secondary and primary motor cortex, as well as areas 5 and 7 of the parietal lobe (Jones & Powell, 1970; Pandya & Vignolo, 1971).

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As per motor functioning, presumably the putamen, in conjunction with the caudate, transmits this information to the globus pallidus which in turn projects to the motor thalamus, brainstem reticular formation, as well as to the motor neocortex, thus creating a very elaborate feedback loop (see Mink & Thach, 1991; Parent & Hazrati 1995) whose origin may begin in the medial frontal lobes (Alexander & Crutcher, 1990; Crutcher & Alexander, 1990) or perhaps the limbic system, e.g. anterior cingulate, amygdala.

For example, when anticipating or preparing to make a movement, but prior to the actual movement, neuronal activity will first begin and then dramatically increase in the medial supplementary motor areas (SMA), as well as in the striatum (Montgomery & Buchholz, 1991; Schultz & Romo, 1992) followed by activity in the secondary and then the primary motor area (see chapter 19), and then again in the caudate, putamen and globus pallidus which become increasingly active prior to and then during movement and ceasing their activity once the movement is completed (Alexander & Crutcher, 1990; Mink & Thach, 1991; Schultz & Romo, 1992).

Hence, these areas, including the "motor" thalamus, in many respects act in a coordinated fashion so as to mediate purposeful movement. As noted in chapter 12, this was a principle role of the basal ganglia long before the evolution of the neocortex and frontal motor areas.

It is perhaps important to point out that some investigators have argued there are at least five different motor circuits involving the basal ganglia which are segregated to varying degrees (Alexander et al. 1990). The dorsal striatal motor circuit also consists of at least two separate systems involving the putamen and medial (internal) globus pallidus, and the putamen and lateral (external) globus pallidus (reviewed in Marsden & Obeso, 1994; Parent & Hazrati 1995).

FUNCTIONAL DIFFERENTIATION OF THE CAUDATE & PUTAMEN

Over the course of evolutionary metamorphosis, the corpus striatum and the motor thalamus began to develop in tandem and became increasingly interlinked in order to subserve motoric and related activities, including the processing and analysis of sensory information and the expression of feeling states via specific motor activities. That is, the corpus striatum initially served not only the motor functions and related information requirements of the limbic system but in many respects performed (at a rudimentary levels) some of the same "analytical" and perceptual functions that would later be subsumed by the neocortex.

With the continued expansion of the the neocortex and the exponential increase in the capacity to analyze and respond to divergent sensory information, the corpus striatum essentially was split in two by the tremendous proliferation of thalamic axons (i.e. the internal capsule, or rather, the thalamic radiations) that not only terminated on striatal dendrites, but which swept forward and radiated outward to innervate the frontal lobes (Kemp & Powell, 1970). Thus the putamen and caudate nucleus were formed and began to receive differential input from the thalamus as well as from the neocortex and therefore began to subserve somewhat different functions.

For example, although both nuclei contain significant amounts of DA, 5HT, ACH, and GABA (reviewed in Ellison, 1994; Parent & Hazrati 1995; Stoof et al. 1992) and receive input from the amygdala, hippocampus, and motor and somatosensory perceptual data (Haber et al. 1985; Van Hoesen, et al. 1981; Whitlock & Nauta, 1956), the putamen is the recipient of considerable bilateral and topographical input, such that a motor and sensory map of the body (particularly the face, mouth, leg, and arm) is maintained in this region (Delong et al. 1983; Parent & Hazrati 1995). Axonal projections from the motor and sensory neocortex which are concerned with the arm converge in one area of the putamen, whereas those concerned with the leg converge in another.

When coupled with the symptoms and experiments describes below, it is suspected that the putamen is concerned with integrating sensory with intended motor actions and coordinating the movement of the limbs and body in visual space via projections maintained with the medial and lateral globus pallidus as well as the parietal lobe.

In contrast, the caudate nucleus is dominated by axons from association cortices including the inferior temporal lobe and anterior cingulate (Percheron, et al. 1987), the amygdala (Ammaral et al. 1992; Heimer & Aheid, 1991) and the frontal motor areas. The caudate appears to be more involved in multi-modal motor, emotional and sensory integration, analysis and inhibitory functions. Consequently lesions to the caudate can produce sensory neglect and unresponsiveness, or conversely, loss of inhibitory control over the musculature; depending on the extent and laterality of the lesion.

NEOCORTICAL, THALAMIC, & STRIATAL MOVEMENT FEEDBACK LOOPS

THE SMA, PUTAMEN, AND GLOBUS PALLIDUS

Some studies have indicated that those with Parkinson's disease demonstrate the greatest amounts of DA depletion and related DA neuronal degeneration within the putamen. Hence, many authors have argued that Parkinson's symptoms are a consequence of damage to this nuclei (e.g. Goto et al.1990), which in turn can result in the production of unwanted movements such as tremor. Presumably, in these instances, the medial (internal) globus pallidus (which receives putamen input) ceases to inhibit irrelevant motor activity.

The putamen receives much of it's input from the caudate and in particular the SMA, the secondary and primary motor cortex, as well as areas 5 and 7 of the parietal lobe (Jones & Powell, 1970; Pandya & Vignolo, 1971). Presumably the putamen, in conjunction with the caudate, transmits this information to the medial and lateral GP which in turn projects to the motor thalamus, and brainstem. However, like the caudate, the putamen and GP also project back to the motor neocortex, thus creating a very elaborate feedback loop (see Mink & Thach, 1991; Parent & Hazrati 1995) whose origin may begin in the SMA (Alexander & Crutcher, 1990; Crutcher & Alexander, 1990) or perhaps the limbic system (chapter 13).

For example, when anticipating or preparing to make a movement, but prior to the actual movement, neuronal activity will first begin and then dramatically increase in the SMA, followed by activity in the secondary and then the primary motor area (see chapter 19), and then the caudate and last of all the putamen-GP (Alexander & Crutcher, 1990; see also Mink & Thach, 1991).

Ignoring for the moment the role of the limbic system, this indicates that impulses to move first appear in the SMA and that other motor regions are temporally-sequentially recruited in a step-wise fashion; i.e. SMA - premotor - primary motor - caudate - putamen - GP - motor thalamus/frontal motor areas - brainstem...

However, the caudate nucleus also contains neurons which become active prior to, and in anticipation of making body movements, and in response to associated auditory and visual environmental cues (Rolls, et al. 1983; Rolls & Williams, 1987). This caudate neuronal activity precedes, or occurs simultaneously with excitation in the lenticular nucleus, which also results (via feedback) in SMA activation. This is because the GP and the putamen not only receive caudate and neocortical afferents, but they project back to the frontal motor areas (as well as to the motor thalamus). Hence, parallel processing also occurs.

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That is, activity in these regions quickly begins to overlap such that neurons in the motor neocortex and basal ganglia often remain activated simultaneously (Alexander & Crutcher, 1990). Moreover, the motor areas all independently send axons to the brainstem, with axons from different areas converging on the same motor neuron.

Therefore, activity in the motor areas is characterized by both temporal-sequential and parallel processing that in turn is made possible via feedback neural circuitry. Because these different networks are intimately linked and mutually interactive they make coordinated and goal directed movements possible.

Indeed, multiple feedback loops are probably also necessitated by the numerous variables and body- spatial- visual- kinesthetic- motor references, etc., that need to be computed in order to make a planned movement. Thus both temporal-sequential and parallel processing is necessitated as each area is functionally specialized to analyze specific types of information and to perform certain actions in semi-isolation as well performing other functions in parallel with yet other motor areas.

THE PUTAMEN & MEDIAL & LATERAL GLOBUS PALLIDUS

Just as different regions of the caudate appear to subserve different functions, a variety of neuronal types also characterize the lenticular nucleus. For example, preparatory and movement related neurons are segregated within the putamen (Alexander & Crutcher, 1990). This suggests that the putamen employs two different neural networks, one which executes movements, the other which prepares to make the movement; information which is normally transmitted to the GP as well as back to the motor neocortex.

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The putamen appears to act at the behest of impulses arising in the neocortical motor areas (as well as the limbic system) and then only secondarily acts to prepare for and then to participate in the guidance of movement (Mink & Thach, 1991). In conjunction with the caudate, the putamen accomplishes this via signals transmitted to the medial and lateral GP, the motor thalamus, and brainstem reticular formation (Marsden & Obeso, 1994) and then back to the motor neocortex (see also Parent & Hazrati 1995, for a related review).

As noted, the putamen and globus pallidus are also coextensive (the lenticular nucleus) and in many respects function as a prepatory motor unit involved in the guidance, and perhaps even the learning of various motor activities (Crutcher & DeLong, 1984; Kimura, 1987). For example, alterations in neuronal activity have been demonstrated in the globus pallidus and the putamen during tasks involving learned body movement (Crutcher & DeLong, 1984). Lenticular neurons also become highly active when learned facial or limb movements are triggered in response to a particular auditory or visual stimulus associated with that movement (Kimura, 1987).

Some putamen and GP neurons also fire in response to reward but not to movement and vice versa (Kimura, et al. 1984). However, these same neurons do not respond when the same learned and rewarded movements are made spontaneously and in the absence of associated cues, or when they were no longer rewarded. These findings raise the possibility that specific neurons within these nuclei are responsive to motivational cues associated with movement and that these neurons utilizes these cues in preparation to make a movement (Kimura, 1987).

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Neurons in the GP also selectively respond and change their activity when making ballistic movements, particularly those which are visually guided (Mink & Thach, 1991). However, activation occurs too late for these neurons to be involved in the initiation or planning of the movement (Mink & Thach, 1991). Conversely, destruction or massive inhibition of the GP can result in difficulty turning off a movement (see Mink & Thach, 1991) -thus giving each movement a ballistic quality. Similarly, destruction or massive inhibition of the GP can make it exceedingly difficulty to rapidly alternate between movements and thus switch from an ongoing to a different motor program (Hore & Vilis, 1980). This loss of control over motor programming with GP impairment extends even to attempts to make purposeful ballistic reaching or stepping movements (Horak & Anderson, 1984; Hore & Vilis, 1980), and the velocity and amplitude of these movements may in fact be significantly slowed and reduced (Mink & Thach, 1991).

HUNTINGTON'S CHOREA

Chorea ("dance") is characterized by jerky, writhing, twisting, and unpredictable movements of the extremities. The two main types are Sydenham's Chorea (St. Vitus dance) and Huntington's Chorea. Sydenham's Chorea involves choreiform movements of the facial, tongue, and extremities, and is accompanied by loss of nerve cells in the caudate and putamen, as well as within the cerebral cortex, substantia nigra, and subthalamic nucleus.

Huntington's chorea is a progressive deteriorative inherited genetic disorder which is passed on by an autosomal dominant gene located on chromosome 4. It is characterized by an insidious onset that may begin during childhood or old age, with the illness beginning earlier in those who have an affected father (reviewed in Folstein et al. 1990; Young 1995). Cognitive decline, however, is gradual.

Affected individuals tend to suffer from memory and visual-spatial deficits, depression, and reduced fluent output although aphasia is not typical. Difficulty with motor coordination, planning skills, decision making, and a reduced capacity to consider alternate problem solving strategies or to shift form one mental set to another, is not uncommon (reviewed in Folstein et al. 1990). Hence, in some respects this disorder is suggestive of frontal lobe abnormalities (see chapter 19).

This syndrome is also associated with widespread neuronal loss in the caudate, putamen, brainstem, spinal cord, cerebellum, and atrophy in the GP (see Vonsattel, et al. 1987; Young 1995). Degeneration is predominantly of small striatal neurons whereas larger neurons remain intact. Opiate neurons located in the striatum are also significantly effected (Reiner et al. 1988). It is believed that the degeneration of these corpus striatal neurons, as well as the loss of GABA influences, results in reduced striatal control over the GP (see Narabayashi, 1987), thereby producing excessive movement.

It is noteworthy that some reports indicate that the posterior caudate and putamen are more severely effected than the anterior regions (Vonsattel, et al. 1987). Indeed, the posterior caudate and it's tail is usually the earliest and most severely effected part of the brain -which implicates the amygdala as a factor in the development of chorea. Indeed, in the early stages of Huntingtons chorea, atrophy and degeneration begin in the tail and spreads dorsally and anteriorally thus effecting the striatum and lenticular nucleus (Young 1995).

In this regard it is noteworthy that affective disorders and personality and mood changes are prominent early signs suggesting amygdala involvement. Indeed, disturbances of emotion may precede any motor or cognitive decline by as much as 20 years, with some patients displaying mania, depression as well as antisocial tendencies (reviewed in Folstein et al. 1990). As noted, neural degeneration tends to begin in the amygdaloid tail of the corpus striatum (Young 1995).

As per disturbances of movement, those with Huntington's disease tend to suffer from either or both voluntary and involuntary abnormalities. The involuntary aspects include the jerking and unpredictable movements of the limbs, trunk and face which may occur when at rest, walking, or while actively engaged in some task such that they may appear to be intoxicated and/or attempting to dance about.

Voluntary disorders include rigidity, slowed, clumsy, or difficulty initiating movement. Those who suffer from voluntary movement disorders are the most likely to demonstrate cognitive decline (Folstein et al. 1990).






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