Normalizing motor-related brain activity: subthalamic nucleus stimulation in Parkinson disease.

OBJECTIVE: To test whether therapeutic unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson disease (PD) leads to normalization in the pattern of brain activation during movement execution and control of movement extent. METHODS: Six patients with PD were imaged off medication by PET during performance of a visually guided tracking task with the DBS voltage programmed for therapeutic (effective) or subtherapeutic (ineffective) stimulation. Data from patients with PD during ineffective stimulation were compared with a group of 13 age-matched control subjects to identify sites with abnormal patterns of activation. Conjunction analysis was used to identify those areas in patients with PD where activity normalized when they were treated with effective stimulation. RESULTS: For movement execution, effective DBS caused an increase of activation in the supplementary motor area (SMA), superior parietal cortex, and cerebellum toward a more normal pattern. At rest, effective stimulation reduced overactivity of SMA. Therapeutic stimulation also induced reductions of movement related "overactivity" compared with healthy subjects in prefrontal, temporal lobe, and basal ganglia circuits, consistent with the notion that many areas are recruited to compensate for ineffective motor initiation. Normalization of activity related to the control of movement extent was associated with reductions of activity in primary motor cortex, SMA, and basal ganglia. CONCLUSIONS: Effective subthalamic nucleus stimulation leads to task-specific modifications with appropriate recruitment of motor areas as well as widespread, nonspecific reductions of compensatory or competing cortical activity.

Target-, limb-, and context-dependent neural activity in the cingulate and supplementary motor areas of the monkey.

Very little is known about the role of the cingulate motor area (CMA) in visually guided reaching compared to other cortical motor areas. To investigate the hierarchical role of the caudal CMA (CMAc) during reaching we recorded the activity of neurons in CMAc in comparison to the supplementary motor area proper (SMA) while a monkey performed an instructed delay task that required it to position a cursor over visual targets on a computer screen using two-dimensional (2D) joystick movements. The direction of the monkey's arm movement was dissociated from the direction of the visual target by periodically reversing the relationship between the direction of movement of the joystick and that of the cursor. Neurons that responded maximally with a particular limb movement direction regardless of target location were classified as limb-dependent, whereas neurons that responded maximally to a particular target direction regardless of the direction of limb movement were classified as target-dependent. Neurons whose activity was directional in one of the two visuomotor mapping conditions and non-directional or inactive in the other were categorized as context-dependent. Limb-dependent activity was observed more frequently than target-dependent activity in both CMAc and SMA proper during both the delay period (preparatory activity; CMAc, 17%; SMA, 31%) and during movement execution (CMAc, 49%, SMA, 48%). A modest percentage of neurons with preparatory activity were target-dependent in both CMAc (11%) and SMA proper (8%) and a similar percentage of neurons in both areas demonstrated target-dependent, movement activity (CMAc, 8%; SMA, 10%). The surprising finding was that a very large percentage of neurons in both areas displayed context-dependent activity either during the preparatory (CMAc, 72%; SMA, 61%) or movement (CMAc, 43%, SMA 42%) epochs of the task. These results show that neural activity in both CMAc and SMA can directly represent movement direction in either limb-centered or target-centered coordinates. The presence of target-dependent activity in CMAc, as well as SMA, suggests that both are involved in the transformation of visual target information into appropriate motor commands. Target-dependent activity has been found in the putamen, SMA, CMAc, dorsal and ventral premotor cortex, as well as primary motor cortex. This indicates that the visuomotor transformations required for visually guided reaching are carried out by a distributed network of interconnected motor areas. The large proportion of neurons with context-dependent activity suggests, however, that while both CMAc and SMA may play a role in the visuomotor transformation of target information into movement parameters, their activity is not solely coding parameters of movement, since their involvement in this process is highly condition-dependent.

Neural activity correlated with the preparation and execution of visually guided arm movements in the cingulate motor area of the monkey.

Recent anatomical and physiological studies have suggested that parts of the cingulate cortex are involved in the control of movement. These areas have been collectively termed the cingulate motor area (CMA). Currently almost nothing is known, however, about how neurons in the CMA actually participate in the control of movement. Therefore, we investigated the role of cells in the dorsal and ventral banks of the CMA (CMAd and CMAv, respectively) in the preparation and execution of visually guided arm movements. We recorded the activity of neurons while a monkey performed a visually guided, two-dimensional instructed delay task. A monkey was required to operate a joystick that moved a cursor from a centrally located hold target to one of four peripheral targets. Neurons were classified as exhibiting preparatory activity if the neural discharge during the postinstruction delay period was significantly higher than the preinstruction activity. Neurons were classified as exhibiting movement activity if the neural discharge was significantly elevated around the time of the movement. Of the 115 task-related neurons studied, 18 (16%) exhibited only preparatory activity, 48 (42%) exhibited only movement activity, and 49 (43%) exhibited both preparatory and movement activity. Neurons were further classified in terms of their directional tuning. For 51% of neurons with preparatory activity, that activity was directional. A significantly larger proportion of movement-related activity was directional (78%). For neurons with both directional preparatory and movement activity, the preferred directions were highly correlated (r=0.83). The median onset of movement activity was 10 ms before the beginning of movement (range -200 to 200 ms). The patterns and directionality of task-related activity of CMA neurons observed in this study are similar to those previously reported for other cortical motor areas. Together, these data provide preliminary evidence that neurons in CMAd and CMAv play a role in both the preparation and execution of visually guided arm movements.

From the Oklahoma State Department of Health. CDC recommendations for diagnosis and initial management of hepatitis C virus infection.

Hepatitis C is a growing public health concern in the United States. All physicians should be aware of who should be tested for HCV, based upon risk factors for infection, as well as how to manage persons found to have positive screening tests. The following recommendations focus primarily on the role of the primary care physician in the initial evaluation and management of persons who test positive for HCV and are excerpted from the Centers for Disease Control document "Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease," Oct. 16, 1998/47(RR19); 1-39.

Functional architecture of basal ganglia circuits: neural substrates of parallel processing.

Concepts of basal ganglia organization have changed markedly over the past decade, due to significant advances in our understanding of the anatomy, physiology and pharmacology of these structures. Independent evidence from each of these fields has reinforced a growing perception that the functional architecture of the basal ganglia is essentially parallel in nature, regardless of the perspective from which these structures are viewed. This represents a significant departure from earlier concepts of basal ganglia organization, which generally emphasized the serial aspects of their connectivity. Current evidence suggests that the basal ganglia are organized into several structurally and functionally distinct 'circuits' that link cortex, basal ganglia and thalamus, with each circuit focused on a different portion of the frontal lobe. In this review, Garrett Alexander and Michael Crutcher, using the basal ganglia 'motor' circuit as the principal example, discuss recent evidence indicating that a parallel functional architecture may also be characteristic of the organization within each individual circuit.

Preparation for movement: neural representations of intended direction in three motor areas of the monkey.

1. The purpose of this study was to compare the functional properties of neurons in three interrelated motor areas that have been implicated in the planning and execution of visually guided limb movements. All three structures, the supplementary motor area (SMA), primary motor cortex (MC), and the putamen, are components of the basal ganglia-thalamocortical "motor circuit." The focus of this report is on neuronal activity related to the preparation for movement. 2. Five rhesus monkeys were trained to perform a visuomotor step-tracking task in which elbow movements were made both with and without prior instruction concerning the direction of the forthcoming movement. To dissociate the direction of preparatory set (and limb movement) from the task-related patterns of tonic (and phasic) muscular activation, some trials included the application of a constant torque load that either opposed or assisted the movements required by the behavioral paradigm. Single-cell activity was recorded from the arm regions of the SMA, MC, and putamen contralateral to the working arm. 3. A total of 741 task-related neurons were studied, including 222 within the SMA, 202 within MC, and 317 within the putamen. Each area contained substantial proportions of neurons that manifested preparatory activity, i.e., cells that showed task-related changes in discharge rate during the postinstruction (preparatory) interval. The SMA contained a larger proportion of such cells (55%) than did MC (37%) or the putamen (33%). The proportion of cells showing only preparatory activity was threefold greater in the SMA (32%) than in MC (11%). In all three areas, cells that showed only preparatory activity tended to be located more rostrally than cells with movement-related activity. Within the arm region of the SMA, the distribution of sites from which movements were evoked by microstimulation showed just the opposite tendency: i.e., microexcitable sites were largely confined to the caudal half of this region. 4. The majority of cells with task-related preparatory activity showed selective activation in anticipation of elbow movements in a particular direction (SMA, 86%; MC, 87%; putamen, 78%), and in most cases the preparatory activity was found to be independent of the loading conditions (80% in SMA, 83% in MC, and 84% in putamen).(ABSTRACT TRUNCATED AT 400 WORDS)

Movement-related neuronal activity selectively coding either direction or muscle pattern in three motor areas of the monkey.

1. Movement-related neuronal activity in the supplementary motor area (SMA), primary motor cortex (MC), and putamen was studied in monkeys performing a visuomotor tracking task designed to determine 1) the extent to which neuronal activity in each of these areas represented the direction of visually guided arm movements versus the pattern of muscle activity required to achieve those movements and 2) the relative timing of different types of movement-related activity in these three motor areas. 2. A total of 455 movement-related neurons in the three motor areas were tested with a behavioral paradigm, which dissociated the direction of visually guided elbow movements from the accompanying pattern of muscular activity by the application of opposing and assisting torque loads. The movement-related activity described in this report was collected in the same animals performing the same behavioral paradigm used to study preparatory activity described in the preceding paper. Of the total sample, 87 neurons were located within the arm region of the SMA, 150 within the arm region of the MC, and 218 within the arm region of the putamen. 3. Movement-related cells were classified as "directional" if they showed an increase in discharge rate predominantly or exclusively during movements in one direction and did not have significant static or dynamic load effects. A cell was classified as "muscle-like" if its directional movement-related activity was associated with static and/or dynamic load effects whose pattern was similar to that of flexors or extensors of the forearm. Both directional and muscle-like cells were found in all three motor areas. The largest proportion of directional cells was located in the putamen (52%), with significantly smaller proportions in the SMA (38%) and MC (41%). Conversely, a smaller proportion of muscle-like cells was seen in the putamen (24%) than in the SMA (41%) or MC (36%). 4. The time of onset of movement-related discharge relative to the onset of movement ("lead time") was computed for each cell. On average, SMA neurons discharged significantly earlier (SMA lead times 47 +/- 8 ms, mean +/- SE) than those in MC (23 +/- 6 ms), which in turn were earlier than those in putamen (-33 +/- 6 ms). However, the degree of overlap of the distributions of lead times for the three areas was extensive.(ABSTRACT TRUNCATED AT 400 WORDS)

Neural representations of the target (goal) of visually guided arm movements in three motor areas of the monkey.

1. This study was designed to determine whether the supplementary motor area (SMA), the primary motor cortex (MC), and the putamen, all of which are components of the basal ganglia-thalamocortical "motor circuit," contain neural representations of the target or goal of a movement, independent of specific features of the movement itself. Four rhesus monkeys were trained to perform two visuomotor delayed step-tracking tasks in which the subject used a cursor to track targets on a display screen by making flexion and extension movements of the elbow. Single-cell activity was recorded from the SMA, MC, and putamen while the monkeys performed the two tasks. In the Standard task, the cursor and the forearm moved in the same direction. The Cursor/Limb Inversion task was identical to the Standard task except that there was an inverse relationship between the directions of movement of the forearm and cursor. Together, these tasks dissociated the spatial features of the target or goal of the movement from those of the movement itself. Both tasks also included features that made it possible to distinguish neuronal activity related to the preparation for movement from that related to movement execution. A total of 554 directionally selective, task-related neurons were tested with both tasks (SMA, 207; MC, 198; putamen, 149). 2. Two types of directionally selective preparatory activity were seen in each motor area. Cells with target-dependent preparatory activity showed selective discharge prior to all preplanned movements of the cursor toward one of the side targets (right or left), irrespective of whether the limb movement involved extension or flexion of the elbow. Comparable proportions of target-dependent preparatory cells were seen in the SMA (36%), MC (40%), and putamen (38%). Cells with limb-dependent preparatory activity showed selective discharge prior to all preplanned elbow movements in a particular direction (extension or flexion), irrespective of whether the target to which the cursor was moved was located on the right or left side of the display. The SMA contained a higher proportion of limb-dependent preparatory cells (40%) than either MC (15%) or putamen (9%). 3. Two types of directionally selective movement-related activity were also seen in each motor area.(ABSTRACT TRUNCATED AT 400 WORDS)

Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions.

The central theme of the "segregated circuits" hypothesis is that structural convergence and functional integration occurs within, rather than between, each of the identified circuits. Admittedly, the anatomical evidence upon which this scheme is based remains incomplete. The hypothesis continues to be predicated largely on comparisons of anterograde and retrograde labeling studies carried out in different sets of animals. Only in the case of the "motor" circuit has evidence for the continuity of the loop been demonstrated directly in individual subjects; for the other circuits, such continuity is inferred from comparisons of data on different components of each circuit obtained in separate experiments. Because of the marked compression of pathways leading from cortex through basal ganglia to thalamus, comparisons of projection topography across experimental subjects may be hazardous. Definitive tests of the hypothesis of maintained segregation await additional double- and multiple-label tract-tracing experiments wherein the continuity of one circuit, or the segregation of adjacent circuits, can be examined directly in individual subjects. It is worthy of note, however, that the few studies to date that have employed this methodology have generated results consistent with the segregated circuits hypothesis. Moreover, single cell recordings in behaving animals have shown striking preservation of functional specificity at the level of individual neurons throughout the "motor" and "oculomotor" circuits. It is difficult to imagine how such functional specificity could be maintained in the absence of strict topographic specificity within the sequential projections that comprise these two circuits. This is not to say, however, that we expect the internal structure of functional channels (e.g., the "arm" channel within the "motor" circuit) to have cable-like, point-to-point topography. When the grain of analysis is sufficiently fine, anatomical studies have shown repeatedly that the terminal fields of internuclear projections (e.g., to striatum, pallidum, nigra, thalamus, etc.) often appear patchy and highly divergent, suggesting that neighboring groups of projection cells tend to influence interdigitating clusters of postsynaptic neurons. While more intricate and complex than simple point-to-point topography, however, this type arrangement should also be capable of maintaining functional specificity. As discussed briefly above, it is not yet clear to what extent the inputs to the "motor" circuit from the different precentral motor fields (e.g., MC, SMA, APA) are integrated in their passage through the circuit. It now appears that at the level of the putamen such inputs remain segregated.(ABSTRACT TRUNCATED AT 400 WORDS)

Cognitive spatial-motor processes. 3. Motor cortical prediction of movement direction during an instructed delay period.

We studied the activity of 123 cells in the arm area of the motor cortex of three rhesus monkeys while the animals performed a 2-dimensional (2-D) step-tracking task with or without a delay interposed between a directional cue and a movement triggering signal. Movements of equal amplitude were made in eight directions on a planar working surface, from a central point to targets located equidistantly on a circle. The appearance of the target served as the cue, and its dimming, after a variable period of time (0.5-3.2 s), as the "go" stimulus to trigger the movement to the target; in a separate task, the target light appeared dim and the monkey moved its hand towards it without waiting. Population histograms were constructed for each direction after the spike trains of single trials were aligned to the onset of the cue. A significant increase (3-4x) in the population activity was observed 80-120 ms following the cue onset; since the minimum delay was 500 ms and the average reaction time approximately 300 ms, this increase in population activity occurred at least 680-720 ms before the onset of movement. A directional analysis (Georgopoulos et al. 1983, 1984) of the changes in population activity revealed that the population vector during the delay period pointed in the direction of movement that was to be made later.

Primate globus pallidus and subthalamic nucleus: functional organization.

Neuronal relations to active movements of individual body parts and neuronal responses to somatosensory stimulation were studied in the external (GPe) and internal (GPi) segments of the globus pallidus (GP) and the subthalamic nucleus (STN) of awake monkeys. In GPe (n = 249), GPi (n = 151), and STN (n = 153), 47, 29, and 28% of the cells, respectively, discharged in relation to active arm movements, 10, 11, and 15% to leg movements, and 22, 22, and 18% to orofacial movements. Of the neurons whose activity was related to arm movements, 26, 16, and 21% in GPe, GPi, and STN, respectively, discharged in relation to movements of distal parts of the limb. Of cells whose discharge was related to active limb movements, 37, 22, and 20% in GPe, GPi, and STN, respectively, also responded to passive joint rotation, which was usually specific in terms of joint and direction of movement. Only a small percentage of cells responded to muscle or joint palpation, tendon taps, or cutaneous stimulation. Short-latency, direction-specific neuronal responses to load perturbations confirmed the existence of proprioceptive driving. In both GPe and GPi, leg movement-related neurons were centrally located in the rostrocaudal and dorsoventral dimensions. In contrast, arm movement-related cells were found throughout the entire rostrocaudal extent of both segments, although in greater numbers caudally. In the central portions they were situated largely inferior and lateral to leg movement-related neurons. Neurons related to orofacial movements were largely confined to the caudal halves of both segments, where they were located largely ventral to arm movement-related cells. The STN cells whose activity was related to leg movements were observed largely in the central portions of the nucleus in the rostrocaudal and mediolateral dimensions. Cells whose activity was related to arm movements were found throughout the rostrocaudal extent of the nucleus, but were most numerous at the rostral and caudal poles. Neurons related to movements of the facial musculature and to licking and chewing movements were distributed over the entire rostrocaudal extent of the nucleus, where they generally occupied the ventrolateral regions. In all three nuclei, neurons with similar functional properties were sometimes clustered together. Within the arm and leg areas, however, there was no clear evidence for a simple organization of clusters related to different parts of the limb. These studies provide further evidence for a role of the basal ganglia in the control of limb movements.(ABSTRACT TRUNCATED AT 400 WORDS)

Old age and environmental docility: the roles of health, support and personality.

This study assessed the generalizability of Lawton and Simon's environmental docility hyopthesis across three domains of personal competence. The hypothesis was supported, in that a survey of 102 people (aged 60 to 92) found environmental press to be related significantly to adjustment only among less competent individuals in terms of (a) health (i.e., those with poor ratings of health, vision, and hearing, the old-old, and men); access to caregiving networks, (i.e., those who were unmarried, had infrequent contact with children and family, and lived in smaller communities); and (c) personality, (i.e., those with low self-esteem, and external locus of control, low assertiveness, and an inability to deal with the threat of dependency).

Single cell studies of the primate putamen. I. Functional organization.

In order to clarify the functional organization of the putamen and the nature of sensory inputs to this structure we studied the relation of single cell activity to active movements and somatosensory stimulation in the awake primate. Neurons (N = 707) were categorized on the basis of their relation to active movements or responses to sensory stimulation of individual body parts. 38% of neurons studied were related to the arm, 9% to the leg, 11% to the mouth or face, and 3% to axial portions of the body. The remaining neurons exhibited non-specific activation which could not be confidently localized to an individual body part (12%) or did not respond during the examination (26%). The high proportion of arm neurons was due to the focus of this study on cells related to arm movements. A large proportion (41%; N = 270) of the "arm" neurons was responsive to somatosensory stimulation. For these neurons the most effective stimulus (82%) was passive joint rotation. Six (5%) of the arm neurons responded to cutaneous stimulation. The putamen was found to be somatotopically organized. Neurons related to different body parts (leg, arm, and face) were segregated, and each body part was represented over a long anteroposterior extent of the nucleus. Clusters of 2-5 neurons with similar relations to active movements or responsive to passive movements of a single joint were often encountered over a 100-500 mu distance. Clusters of neurons with sensory driving were organized by joints. Rather than a single elbow or shoulder area, multiple clusters of neurons related to each joint were widely distributed over a long anteroposterior extent of the nucleus and were adjacent to clusters of neurons related to other joints of the arm. These clusters of neurons with similar functional properties may correspond to the subunits of the striatum which have been revealed by anatomic and morphologic studies. We propose that these clusters of neurons with similar functional properties represent the basic functional units of the striatum in a manner analogous to the functional columns of the neocortex.

Single cell studies of the primate putamen. II. Relations to direction of movement and pattern of muscular activity.

The major goal of this study was to determine whether the activity of single cells in the primate putamen was better related to the direction of limb movement or to the underlying pattern of muscular activity. In addition, the neural responses to load application were studied in order to determine whether the same neurons were also responsive to somatosensory stimuli. Two rhesus monkeys were trained to perform a visuomotor arm tracking task which required elbow flexion/extension movements with assisting and opposing loads in order to dissociate the direction of elbow movement from the pattern of muscular activity required for the movement. Neurons in the putamen were selected for study only if they were related both to the task and to arm movements outside the task. Most (96%) of the cells studied responded to load application: 36% of these showed short-latency (less than 50 ms), "sensory" responses. Forty-four percent of neurons had significant relations to the level of static load as the animal held the arm stationary against the steady loads: in general, static load effects were relatively weak. During the elbow flexion/extension movements in the task, 76% of cells had significant relations to the direction of movement, and 52% of neurons had significant dynamic relations to the level of load. Half of all neurons studied were primarily related to the direction of movement independent of the load. Only thirteen percent of cells in the putamen had a pattern of activity similar to that of muscles. These results indicate that neuronal activity in the putamen is predominantly related to the direction of limb movement rather than to the activity of particular muscles and that the basal ganglia may play a role in the specification of parameters of movement independent of the activity of specific muscles. These results also indicate that the basal ganglia receive proprioceptive input which may be used in the control of ongoing movement.

Role of basal ganglia in limb movements.

Recent anatomic and physiologic studies have shed new light on the functional organization of the basal ganglia and their role in movement. The basal ganglia receive topographically organized input from the entire neocortex. Influences from sensorimotor and "association" cortices appear to remain segregated in the basal ganglia. The concept of segregated parallel subcortical loops subserving "motor" and "complex" functions is discussed. Recent neurophysiologic studies in behaving primates suggest that basal ganglia output plays a role in controlling the direction and amplitude of movement but is not primarily involved in the initiation of limb movement or selection of specific muscles. These studies are generally consistent with data from patients with Parkinson's disease, which likewise indicates a deficit in the programming of movement amplitude in step-tracking tasks, with little or no change in reaction-time or pattern of muscular activity.

Functional organization of the basal ganglia: contributions of single-cell recording studies.

Studies of single-cell discharge in the basal ganglia of behaving primates have revealed: characteristic patterns of spontaneous discharge in the striatum, external (GPe) and internal (GPi) globus pallidus, pars reticulata and pars compacta of the substantia nigra, and the subthalamic nucleus (STN); phasic changes in neural discharge in relation to movements of specific body parts (e.g. leg, arm, neck, face); short-latency (sensory) neural responses to passive joint rotation; a somatotopic organization of movement-related neurons in GPe, GPi, and STN; a clustering of functionally similar neurons in the putamen and globus pallidus; greater representation of the proximal than of the distal portion of the limb; changes in neural activity in reaction-time tasks, suggesting a greater role of the basal ganglia in the execution than in the initiation of movement in this paradigm; a clear relation of neuronal activity to direction, amplitude (?velocity) of movement, and force; a preferential relation of neural activity to the direction of movement, rather than to the pattern of muscular activity. Some of these findings suggest that the basal ganglia may play a role in the control of movement parameters rather than (or independent of) the pattern of muscular activity. Loss of basal ganglia output related to amplitude may account for the bradykinesia in Parkinson's disease. The presence of somatotopic organization in the putamen and globus pallidus, together with known topographic striopallidal connections, suggests that segregated, parallel cortico-subcortical loops subserve 'motor' and 'complex' functions.

Relations between parameters of step-tracking movements and single cell discharge in the globus pallidus and subthalamic nucleus of the behaving monkey.

We describe the relations between the direction, amplitude, and velocity of step-tracking arm movements and the frequency of single cell discharge in the external (GPe) and internal (GPi) segments of the globus pallidus and the subthalamic nucleus (STN) of the behaving monkey. Statistically significant relations to the direction, amplitude, and peak velocity of the movement were found in all structures studied predominantly during the movement but also during the reaction time. For movements in a particular direction, the discharge rate was frequently a linear function of the movement amplitude and/or peak velocity. The slopes of this relation differed for different cells and comprised both positive and negative values. STN differed from both GPe and GPi in that (a) a larger proportion of neurons in STN showed significant relations to the direction of movement and (b) the onset times of changes in neural activity related to movement occurred earlier in STN than in GPe or GPi. The results of these studies suggest that cells in GPe, GPi, and STN may be involved in the control of movement parameters. Loss of the basal ganglia output related to the amplitude or velocity of movement might account for the impairments of step movements observed in Parkinsonian patients. On the other hand, deranged or excessive output related to amplitude or velocity control might result in the excesses of movement observed in other disorders, such as chorea and hemiballismus. These studies also provide direct evidence that the STN exerts a specific influence on basal ganglia output related to the control of movement parameters.