Influence of the globus pallidus on arm movements in monkeys. III. Timing of movement-related information

Monkeys were trained to make a visually triggered arm-reaching movement to a lighted button in a simple reaction-time paradigm, during which the reaction time (RT) and movement time (MT) were measured. Stimulus trains of varying duration were applied at various times before and during the movement at locations in the globus pallidus where application of long stimulus trains caused increased MTs. A critical stimulus period was identified during which stimulus application effectively prolonged MTs. The activity of pallidal neurons was examined during performance of the same behavioral task. More than 60% of the neurons examined showed task-related changes in activity that began before or during the reaching movement. For 45% of these cells, the initial change in firing occurred during the critical stimulus period, 50-150 ms before mechanically detected movement. Comparison of the critical stimulus period, the time of task-related changes in the discharge of pallidal neurons, and the time of EMG activity in muscles acting at the back, shoulder, elbow, and wrist revealed that both the critical stimulus period and changes in neuronal discharge occurred at or after initial muscle activation and during the buildup of EMG activity. These data are consistent with a model in which the globus pallidus plays a role in scaling the magnitude of muscle activity that determines movement velocity without affecting the initiation or sequential organization of the programmed motor output.     

Activity of neurons in cerebellar-receiving and pallidal-receiving areas of the thalamus of the behaving monkey.

1. Thalamic neurons that receive synaptic input from the globus pallidus or the cerebellar nuclei were identified in awake monkeys trained to perform an arm-reaching task. The location of electrophysiologically identified cerebellar-receiving (CR) and pallidal-receiving (PR) neurons was used to identify a total of 264 thalamic neurons in cerebellar (CB) or pallidal (GP) regions of the thalamus. 2. Stimulation in the brachium conjunctivum or white matter adjacent to the cerebellar nuclei excited 85 neurons in the thalamus at short latencies. These CR neurons were located in the oral portion of the ventral posterolateral nucleus (VPLo), in caudal portions of the ventral lateral nucleus (VLc), and in area X. 3. Stimulation in the internal globus pallidus (GPi) inhibited 10 thalamic neurons at short latency. These PR neurons were located in rostral portions of VLc, in the oral part of the ventral lateral nucleus (VLo), and in the parvicellular part of the ventral anterior nucleus (VApc). 4. There was no clear single somatotopic organization of neurons in CB and GP regions of the thalamus, as defined by "free-form" responses to passive manipulation and observation of eye movements. There was, in fact, a tendency for two representations, each, of the head/eye/mouth cells and cells with modifications of activity in response to manipulation of the arm. 5. During the hold period before illumination of a visual target, the mean firing rates and variability of discharge of arm-related CR and PR neurons did not differ significantly. This was also true for the total sample of arm-related neurons in the CB versus GP regions. 6. The activity of many neurons in both the CB and GP regions began to change before the reaching movement and, for some, before the earliest recorded changes in electromyographic (EMG) activity. The initial change was an increase in discharge for greater than 75% of the cells studied in both the CB and GP regions. 7. During the reaching task, there also was no significant difference in the time of the initial change in discharge of neurons in the CB versus GP regions of the thalamus. 8. These data are consistent with the hypothesis that the initial task-related change in discharge of PR thalamic neurons is dominated by input from the cerebral cortex and that pallidal input modulates later phases of their movement-related changes in activity.     

Motor cortical activity during drawing movements: single-unit activity during sinusoid tracing.

1. This study examines the neuronal activity of motor cortical cells associated with the production of arm trajectories during drawing movements. Three monkeys were trained to perform two tasks. The first task ("center----out" task) required the animal to move its arm in different directions from a center start position to one of eight targets spaced at equal angular intervals and equal distances from the origin. Movements to each target were in a constant direction, and the average rate of neuronal discharge with movements to different targets varied in a characteristic pattern. A cosine tuning function was used to map each cell's discharge rate to the direction of arm movement. This function spanned all movement directions, with a peak firing rate in the cell's preferred direction. 2. The second task ("tracing" task) required the animal to trace curved figures consisting of sine waves of different spatial frequencies and amplitudes. Both the speed and direction changed continuously throughout these movements. The cosine tuning function derived from the center----out task was used to model the activity of the cell during the tracing of sinusoids in the second task. Sinusoidal data were divided into 20-ms bins; instantaneous direction, speed, and discharge rate were analyzed bin by bin. This provided a way to compare directly the tuning parameters during a task with constant direction to a task where the direction varied continuously. 3. Movement direction as it changed during the tracing task was an important factor in the discharge pattern of cells that had discharge patterns that could be represented by the cosine tuning function. 4. The modulation of discharge rate during figure tracing depended on both the cell's preferred direction and the orientation of the figure. The activity of cells with preferred directions perpendicular to the axis of the sinusoidal figure was most modulated, whereas the activity of those cells with preferred directions aligned to the figure's axis was least modulated. 5. The cells with modulated activity tended to have firing rates that differed from the predicted cosine tuning function during the sinusoidal movements for those portions of the trajectory where the movement direction was in the cell's preferred direction. 6. Finger speed during figure tracing varied inversely with path curvature with the same relation that has been found during human drawing. To assess the relation of instantaneous speed to discharge rate, the component of the discharge pattern related to direction was subtracted from the total discharge.(ABSTRACT TRUNCATED AT 400 WORDS)     

Activity of neurons of the subthalamic nucleus in relation to motor performance in the cat

The activity of subthalamic nucleus neurons related to motor performance was studied in three unrestrained cats operantly conditioned to perform a lever-release movement. The movement was initiated either rapidly after the trigger stimulus (a brief sound) in a simple reaction-time paradigm or after a delay in trials identified by a tone cue. These paradigms were randomly presented. The activity of 171 neurons was recorded in the contralateral and in the ipsilateral subthalamic nucleus, with respect to the performing limb. The mean spontaneous activity of cells in the ipsilateral side (18.5±13.8 imp/s, mean±SD) was higher than that in the contralateral side (8.5±8.1 imp/s). A total of 145 cells (85%) presented significant changes in activity in relation to the lever-release movement (task-related cells). The remaining 26 cells were either related to other events of the task (n=15; lever-press or reinforcement occurrence) or not related at all to the task performance (n=11). The majority of changes of activity of task-related cells were initial increases in discharge, which started on average, 127 ms before movement onset and lasted several hundreds of milliseconds. These increases in discharge were more frequent in the contralateral side (75 of 80 task-related cells, 94%) than in the ipsilateral side (43 of 65 task-related cells, 66%). The changes in activity, either increases or decreases, occurred early after the trigger stimulus, since 62% of them had a latency of less than 100 ms. Although the mean latency of initial increases was rather similar in both sides (97 ms contralateral versus 104 ms ipsilateral), the contralateral side was characterized by a high proportion of very early responses (less than 20 ms). For most neurons, the early changes in activity described above were absent after the trigger stimulus in the delayed condition. For certain neurons, the changes in activity prior to movement were different in reactiontime condition and in delayed condition, showing that the pattern of activity preceding movement might depend on the temporal requirements for motor initiation. The results suggest that a significant proportion of subthalamic cells are involved in the preparation and the initiation phases of the lever-release movement studied, although other hypotheses (e.g. stimulus-related responses) cannot be definitely ruled out. The timings and patterns of the changes in activity observed in the subthalamic nucleus in the present study, and in the pallidal complex previously, cannot be explained easily by the classical scheme where the external pallidum inhibits the subthalamic nucleus. The results suggest rather that the subthalamic nucleus, driven by a yet-to-be-determined excitatory input, exerts an excitatory influence on the pallidum and plays a crucial role in the control of the basal ganglia output neurons.     

The role of putamen and pallidum in motor initiation in the cat

The participation of basal ganglia in motor initiation was studied in six cats operantly trained to perform a ballistic flexion movement, triggered after a brief sound in a simple reaction time condition or delayed after the same sound in the presence of a tone cue. The activity of 356 neurons was recorded in the putamen and in the pallidum (globus pallidus and entopeduncular nucleus). A total of 19.4% of the neurons were not related to the conditioned flexion movement: they were either unrelated to the task (10.1%) or related to other periods of the motor performance such as trial beginning or reward delivery (9.3%). About 60% of the remaining neurons — defined as task-related — exhibited changes in firing rate that occurred, in the reaction time condition, less than 100 ms after the go signal and therefore began prior to movement onset. For most neurons, in the delayed condition, these early changes were absent, suggesting that their occurrence in the reaction time condition was not a sensory response but rather was related to the movement initiation. In addition, for many neurons these changes shifted in time, remaining time-locked to the movement. Correlations between these early changes in activity and motor parameters were demonstrated, suggesting that these changes were movement-related. For most neurons the firing levels observed during intertrial intervals and during foreperiod were similar. The mean discharge rate during the foreperiod was 19.2 impulses/s. Three patterns of activity were observed before movement: increases in discharge rate (61% of task-related neurons), transient decreases followed by increases (11%), or prolonged decreases (28%). Only minor differences were found between the characteristics of the populations of neurons recorded in the three sites under study: on average the neurons recorded in the globus pallidus were more active than the neurons recorded in the putamen or in the entopeduncular nucleus. The fact that, for certain neurons, the changes of activity prior to movement were different in reaction time condition and in delayed condition showed that the pattern of activity preceding movement might depend on the temporal requirements for motor initiation. Taken together with the motor effects obtained in the same task following GABA-receptor activation with muscimol microinjections in these structures, the present results suggest that putamen and pallidal neurons participate in the initiation of the conditioned movement under study.     

Task-related coding of stimulus and response in cat red nucleus

Summary In the present study we recorded the activity of single neurons in the forelimb area of red nucleus (RN) during performance of three step-tracking tasks designed to dissociate the coding of stimulus and response variables in the discharge of recorded neurons. In two of these tasks, the standard and stimulus-reversal arm tasks, elbow flexion and extension were elicited by different stimuli enabling us to distinguish activity correlated with the forelimb response from the stimulus eliciting it. The third task (neck task) allowed us to determine whether neuronal modulation was related to an unconditioned orienting response that occurred concurrently with the forelimb response. We have previously reported that these three tasks separate neurons in MCx whose modulation precedes the response (lead cells) into three distinct classes in which task-related activity either is correlated with the direction of the forelimb response, correlated with the stimulus, or not correlated with either (Martin and Ghez 1985). All lead cells, however, remained timed to the stimulus rather than to the response. The present results show that RN lead cells can be subdivided into the same three classes as those in MCx and their discharge was also contingent on the subsequent production of a behavioral response. (1) Force-direction neurons (35%; n = 16) showed changes in activity correlated with the production of forearm force in a particular direction suggesting that they could participate in selecting the appropriate forelimb response. The onset of task-related modulation of activity was better timed to the response, in contrast to force-direction neurons in MCx, which were better timed to the stimulus. (2) Stimulus-direction neurons (18%; n = 8) modulated their activity in relation to a particular stimulus evoking either flexor or extensor responses and during neck task performance. These neurons could be involved in processing stimulus information or in the production of neck torque. The task-related discharge of these lead cells was better timed to the stimulus than to either the forelimb or the neck response. (3) Nondirectional neurons (47%; n = 21) modulated their activity during all tasks examined. Their discharge did not correlate with any specific feature of the stimulus or response, and as a group, was better timed to the stimulus than to the response. Nondirectional neurons may participate in some aspect of motor preparation. To determine the relative contributions of RN and MCx lead cells to response initiation, we compared the amount of response latency variance that could be explained by variation in the latency of the unit modulation to the stimulus for the present data and the data in the earlier MCx study (Martin and Ghez 1985). Between 38% and 53% of response latency variance (for trials examined during performance of the standard arm and stimulus reversal tasks) was accounted for by the latency variations of RN force direction neurons; in contrast, 8% and 11% for MCx force-direction neurons. Variations in timing of stimulus-direction neurons in both RN and MCx account for less than 10% of response latency variance. Our findings suggest that, in the tasks examined, RN force-direction neurons play a more direct role than MCx force-direction neurons in initiating and selecting responses to stimuli. We hypothesized that this subcortical control reflects the high degree of stereotypy of the motor response examined.     

Cerebellar neuronal activity related to whole-arm reaching movements in the monkey

1. Three monkeys were trained to make whole-arm reaching movements from a common central starting position toward eight radially arranged targets disposed at 45 degrees intervals. A sample of 312 cerebellar neurons with proximal-arm receptive fields or discharge related to shoulder or elbow movements was studied in the task. The sample included 69 Purkinje cells, 115 unidentified cortical cells, 65 interpositus neurons, and 63 dentate units. 2. The reaching task was divided into three movement-related epochs: a reaction time, a movement time, and holding over the target. All neurons demonstrated significant changes in discharge during one or more of these three epochs. Almost all of the cells (95%) showed a significant change in activity during the movement, whereas 68-69% of the cells showed significant changes from premovement activity during the reaction time and holding periods. 3. During the combined reaction time-movement period, 231/312 cells were strongly active in the task. Of these, 151 cells (65.4%) demonstrated unimodal directional responses. Sixty-three had a reciprocal relation to movement direction, whereas 88 showed only graded increases or decreases in activity. A further 37 cells (16.0%) were nondirectional, with statistically uniform changes in discharge in all eight directions. The remaining 43 cells (18.6%) showed significant differences in activity for different directions of movement, but their response patterns were not readily classifiable. 4. The proportion of directional versus nondirectional cells was consistent across the four cell populations. However, graded response patterns were more common and reciprocal responses less common among Purkinje and dentate neurons than among unidentified cortical cells and interpositus neurons. 5. The distribution of preferred directions of the population of cerebellar neurons covered all possible movement directions away from the common central starting position in the horizontal plane. When the preferred direction of each cell in the sample population was aligned, the mean direction-related activity of the cerebellar population formed a bell-shaped tuning curve for the activity recorded during both the reaction time and the movement, as well as during the time the arm maintained a fixed posture over the targets. A vector representation also showed that the overall activity of the cerebellar population during normal reaching arm movements generated a signal that varied with movement direction. 6. These results demonstrate that the cerebellum generates a signal that varies with the direction of movement of the proximal arm during normal aimed reaching movements and is consistent with a role in the control of the activity of muscles or muscle groups generating these movements.     

Precentral unit activity related to control of arm movements

Summary 1. Precentral neural activity was studied in relation to steady loads in a Cebus monkey trained to make self-paced elbow flexions and extensions into learned target positions in which the arm had to be held steady between movements. The same steady loads were applied in about 15 successive trials. 2. Single unit records were analyzed from 75 task-related precentral cortical cells. Out of 57 activated neurons, 18 reached peak discharge before or at movement onset, 31 after movement onset, and 8 had gradually rising discharge throughout holding and movement. 3. Different steady loads were tested adequately for 52 neurons. Of these 13 displayed a clear increase of the static discharge rate during the hold phase; a weak trend in the same direction was seen in additional 11 neurons. Four neurons appeared to be related to position rather than to load, and 24 neurons did not change their static discharge rate under different loads. 4. Increasing load produced also dynamic changes of firing frequency in 8 neurons: an increase of the peak frequency, a shortening of the rise time to peak, and advanced onset time. Increased peak frequency was positively correlated with increased peak acceleration of the movement. 5. It is likely that these dynamic changes occurring before or shortly after movement onset are programmed and not the consequence of proprioceptive feedback.Supported in part by the Medical Research Council of Canada (MT-4465) and the U. S. Public Health Servic (NS-10311)     

Striatal neuronal activity during the initiation and execution of hand movements made in response to visual and vibratory cues

Summary Recordings were obtained from 146 neurons in the neostriatum of rhesus monkeys while they performed wrist movements in response to visual and vibratory cues. Of these, 75 putamen and 29 caudate neurons exhibited changes in firing rate that were temporally related to the onset of the wrist movements and that began prior to movement onset. This premovement activity (PMA) usually was directionally specific, in that the magnitude or direction of change in firing rates was different during flexion trials as compared to trials involving wrist extension. PMA onset usually preceded movement onset by more than 100 ms and in most instances preceded the average onset of task-related changes in electromyographic (EMG) activity in muscles of the wrist and forelimb. For most neurons. the changes in neuronal activity that began prior to movement were maintained during movement execution. However, approximately one-third of the neurons that exhibited PMA changed their firing rate in the opposite direction, relative to their PMA and to their baseline rate of activity, once the movement began. Several other neurons either exhibited PMA only or they altered their discharge rates during movement execution but did not exhibit PMA. These observations suggest that, despite the close temporal relationship between the onset of PMA and the onset of wrist movement, the neuronal mechanisms mediating the PMA may differ from those that occur during movement execution. The PMA onset of neostriatal neurons occurred earlier in visually cued than in vibratory cued trials. These differences were statistically significant only for flexion trials, however, in which movements were made against a load and in the same direction as the palmar vibratory stimulus. For trials involving wrist extension, PMA onsets for visually cued as compared with vibratory cued trials were not statistically different. These findings contrast with data obtained previously from somatosensory cortical neurons during performance of the same behavioral task. On average, PMA in the putamen began earlier, relative to movement onset, than it did in the somatosensory cortex. Moreover, in the somatosensory cortex, PMA onset occurred earlier in vibratory cued than in visually cued trials, irrespective of movement direction (Nelson 1988; Nelson and Douglas 1989). For putamen neurons, but not for caudate or cortical neurons, the onset of PMA also occurred significantly earlier during extension trials than flexion trials, irrespective of the modality of the go-cue. These modality-dependent and direction-dependent differences in the PMA onset of neostriatal neurons may reflect the responsiveness of these neurons to somatosensory inputs (e.g., load conditions and vibratory stimulation) that were associated with the behavioral task. These data confirm observations made by other investigators that a substantial proportion of neurons in the putamen exhibit movement-related changes in discharge rate that are initiated prior to task-related changes in EMG activity, and they further suggest that this PMA may be initiated sufficiently early to influence even the earliest task-related activity of cortical neurons.     

Deep brain stimulation reduces neuronal entropy in the MPTP-primate model of Parkinson's disease

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) or internal segment of the globus pallidus is a clinically successful treatment for the motor symptoms of Parkinson's disease. However, the mechanisms by which HFS alleviates these symptoms are not understood. Whereas initial studies focused on HFS-induced changes in neuronal firing rates, recent studies suggest that changes in patterns of neuronal activity may correlate with symptom alleviation. We hypothesized that effective STN HFS reduces the disorder of neuronal firing patterns in the basal ganglia thalamic circuit, minimizing the pathological activity associated with parkinsonism. Stimulating leads were implanted in the STN of two rhesus monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Action potentials were recorded from neurons of the internal and external globus pallidus and the motor thalamus (ventralis anterior, ventralis lateralis pars oralis, and ventralis posterior lateralis pars oralis) during HFS that reduced motor symptoms and during clinically ineffective low-frequency stimulation (LFS). Firing pattern entropy was calculated from the recorded spike times to quantify the disorder of the neuronal activity. The firing pattern entropy of neurons within each region of the pallidum and motor thalamus decreased in response to HFS (n > or = 18 and P < or = 0.02 in each region), whereas firing rate changes were specific to pallidal neurons only. In response to LFS, firing rates were unchanged, but firing pattern entropy increased throughout the circuit (n > or = 24 and P < or = 10(-4) in each region). These data suggest that the clinical effectiveness of HFS is correlated with, and potentially mediated by, a regularization of the pattern of neuronal activity throughout the basal ganglia thalamic circuit.     

Control strategies in directing the hand to moving targets

Summary We have evaluated the use of visual information about the movement of a target in two tasks tracking and interceptions — involving multi-joint reaching movements with the arm. Target velocity was either varied in a pseudorandom order (random condition) or was kept constant (predictable condition) across trials. Response latency decreased as target velocity increased in each condition. A simple model that assumes that latency is the sum of two components — the time taken for target motion to be detected, and a fixed processing time — provides a good fit to the data. Results from a step-ramp experiment, in which the target stepped a small distance immediately preceding the onset of the ramp motion, were consistent with this model. The characteristics of the first 100 ms of the response depended on the amount of information about target motion available to the subject. In the tracking task with randomly varied target velocities, the initial changes in hand velocity were largely independent of target velocity. In contrast, when the velocity was predictable the initial hand velocity depended on target velocity. Analogously, the initial changes in the direction of hand motion in the interception task were independent of target velocity in the random condition, but depended on target velocity in the predictable condition. The time course for development of response dependence was estimated by controlling the amount of visual information about target velocity available to the subject before the onset of limb movement. The results suggest that when target velocity was random, hand movement started before visual motion processing was complete. The response was subsequently adjusted after target velocity was computed. Subjects displayed idiosyncratic strategies during the catch-up phase in the tracking task. The peak hand velocity depended on target velocity and was similar for all subjects. The time at which the peak occurred, in contrast, varied substantially among subjects. In the interception task the hand paths were straighter in the predictable than in the random condition. This appeared to be the result of making adjustments in movement direction in the former condition to correct for initially inappropriate responses.     

The natural discharges of Purkinje cells in paravermal regions of lobules V and VI of the monkey's cerebellum.

1. Conscious monkeys were trained with food rewards to perform movement tasks with the left hand and to accept manipulation of the joints and muscles and natural non-noxious stimulation of the skin of both forelimbs.2. Recordings were made from 230 Purkinje cells situated in the paravermal region of lobules V and VI or immediately adjacent folia of the left cerebellum in a region from 2 to 7 mm from the mid line. These neurones were all in a zone which was demonstrated to receive inputs from the ipsilateral hand and which is known to receive projections, via the pontine nuclei from the ;arm area' of motor cortex in the right hemisphere.3. Modulation of the natural activity of 182 of these 230 Purkinje cells (79%) occurred in a reproducible manner in temporal association, each with a particular phase of the self-paced movement tasks performed by the animal using the ipsilateral arm and hand. The patterns of modulation of Purkinje cell firing in this limited zone of cerebellar cortex could be classified into one of four groups, and each cell's discharge was associated with a particular aspect of movement such as general arm flexion, shoulder retraction, elbow extension or elbow flexion whenever it occurred.4. The cells were spontaneously active at rest. Most commonly, marked accelerations of the discharge were related to one direction of the particular aspect of movement and a reduction of activity or even total silence accompanied movement in the opposite direction.5. Variation of the amount of discharge demonstrated during a movement performance with which this discharge was characteristically associated could be related to the range of the movement or its duration, more activity being characteristic of more prolonged movement performance through larger angles of joint displacement.6. Both simple spikes and complex spikes of some cells showed characteristic modulation of their activity during the monkey's self-initiated movements. Cells whose simple spikes did not change in frequency during the movement task, also showed no modification of complex spike discharge.7. Of the 182 neurones whose discharges changed during active movement performance, 105 (roughly 60%) were demonstrated to be in receipt of an input from peripheral receptors in the hand which could be activated by brisk tapping of the skin or brushing of hairs. In contrast, none of the Purkinje cells whose discharges were unchanged during arm movements could be demonstrated to receive such an input.8. Movement of joints through their full range and prodding of muscles were completely ineffective stimuli for causing changes in Purkinje cell firing in this zone of the cerebellar cortex while the animal was passive and relaxed. Imposed perturbations of movement performance injected unexpectedly during the execution of a movement task were also ineffective in modifying the discharge of these Purkinje cells in relation to the task.     

Neuronal activity related to visually guided saccadic eye movements in the supplementary motor area of rhesus monkeys.

1. The purpose of this study was to describe the response properties of neurons in the supplementary motor area (SMA), including the supplementary eye fields (SEF) of three rhesus monkeys (Macaca mulatta) performing visually guided eye and forelimb movements. Seven hundred thirty single units were recorded in the dorsomedial agranular cortex while monkeys performed a go/no-go visual tracking task. The unit activity associated with rewarded, task-related movements was compared with that associated with unrewarded, spontaneous movements executed in the intertrial interval or when the task was not running. A number of neuronal response types were identified. 2. Sensory cells were characterized by their response to the visual and/or auditory target stimuli combined with no discharge associated with eye or forelimb movements. New information was provided about the receptive fields of the visual cells; they varied in size and, although many included the ipsilateral hemifield, they tended to emphasize the contralateral. A significant proportion of the visually responsive cells had receptive fields restricted to within 8 degrees of the fovea. The response latency was relatively long (greater than 90 ms) and variable. 3. Preparatory set cells were activated from the appearance of the target until the presentation of the go/no-go cue. This subpopulation ceased firing 50-100 ms before the movement was initiated. These cells tended to respond best in relation to contralateral movements. The response latency was similar to that of the sensory cells, although some of these units began to discharge in anticipation of predictable target presentations. These neurons were not active before unrewarded, spontaneous saccades. 4. Sensory-movement cells comprised the largest population of neurons identified in SMA. They were active from the appearance of the target until after the execution of the saccade. These neurons tended to respond preferentially in association with contraversive saccades. The latency of response to the target was significantly longer than that of the sensory cells. There was a large amount of variability in the time to reach the peak level of activation, and this population of units generally became inactivated shortly after the saccade was initiated. Although there were counterexamples, most sensory-movement cells responded equally in association with visually and auditory guided movements. In addition, these neurons were not active in relation to self-generated eye movements made during the intertrial intervals. 5. Pause-rebound cells were identified by their suppression at the appearance of the target and subsequent discharge associated with the saccade. These units tended to respond preferentially to contralateral targets.(ABSTRACT TRUNCATED AT 400 WORDS)     

Contrasting properties of monkey somatosensory and motor cortex neurons activated during the control of force in precision grip

1. Single cell activity was investigated in the precentral motor (MI) and postcentral somatosensory (SI) cortex of the monkey to compare the neuronal activity related to the control of isometric force in the precision grip and to assess the participation of SI in motor control. 2. Three monkeys (Macaca fascicularis) were trained in a visual step-tracking paradigm to generate and precisely maintain force on a transducer held between thumb and index finger. Great care was taken to have the monkeys use only their fingers without moving the wrist or proximal joints. In two monkeys electromyographic (EMG) activity was checked in 23 muscles over several sessions. 3. Five similar classes of task-related firing patterns were found in both SI and MI cortical hand and finger representations, but their relative proportions differed. The majority of the SI neurons were phasically or phasic-tonically active (61%), whereas in MI the neurons that decreased their firing rate with force were most frequent (42%). 4. The timing of activity changes related to the onset of force increase from low to higher levels strongly differed in the two neuronal populations. In SI, only 14% of the task-related neurons increased or decreased their firing rate before the onset of force increase, in contrast to 56% in MI. Only 3% of the SI neurons showed changes before the earliest EMG activation. 5. In both SI and MI neurons with tonic and phasic-tonic, increasing or decreasing discharge patterns disclosed a relationship between neuronal activity and static force. Distinction was made between neurons modulating their activity in a monotonic way and those that were active only at one force level and had a kind of recruitment or deactivation threshold. The latter ones were more frequent in MI than in SI, and in the neuron population with decreasing firing patterns. For the neurons with increases in activity, statistically significant linear correlations between firing rate and force were found more frequently in MI than in SI, where the proportion of nonsignificant correlations was relatively high (35% vs. 15% in MI). In SI the indexes of force sensitivity, calculated from the slopes of the regression lines, covered a wider range than in MI; and their distribution was bimodal, with one mean of 30 Hz/N and the other of 155 Hz/N. In contrast, the mean rate-force slope in MI was 69 Hz/N.(ABSTRACT TRUNCATED AT 400 WORDS)     

Parietal area 5 activity does not reflect the differential time-course of motor output kinetics during arm-reaching and isometric-force tasks

Many single-neuron recording studies have examined the degree to which the activity of primary motor cortex (M1) neurons is related to the kinematics and kinetics of various motor tasks. This has not been explored as extensively for arm movement-related neurons in posterior parietal cortex area 5. We recorded the activity of 78 proximal arm-related neurons in area 5 of two monkeys while they used their whole arm to make reaching movements toward eight targets on a horizontal plane against an inertial load or to generate isometric forces at the hand in the same eight horizontal directions. The overall range of measured output forces was similar in the two tasks. The forces increased monotonically in the desired direction in the isometric task. In the movement task, in contrast, they showed a rapid initial increase in the direction of movement, followed by a transient reversal of forces as the hand approached the target. Many task-related area 5 neurons were tuned for the direction of motor output in the tasks, but most area 5 neurons were more strongly active or exclusively active in the movement task than in the isometric task. Furthermore, their activity at either the single cell or population level did not reflect the transient reversal of output forces during movement. In contrast, M1 neuronal activity was typically strong in both tasks and showed task-related changes that reflected the differences in the time course and directionality of force outputs between both tasks, including the transient reversal of forces in the movement task. These results show that area 5 neurons are less strongly related to the time-course of task kinetics than M1 during isometric and arm-movement tasks.     

Neuronal activity related to the visual representation of arm movements in the lateral cerebellar cortex

Testing the hypothesis that the lateral cerebellum forms a sensory representation of arm movements, we investigated cortical neuronal activity in two monkeys performing visually guided step-tracking movements with a manipulandum. A virtual target and cursor image were viewed co-planar with the manipulandum. In the normal task, manipulandum and cursor moved in the same direction; in the mirror task, the cursor was left-right reversed. In one monkey, 70- and 200-ms time delays were introduced on cursor movement. Significant task-related activity was recorded in 31 cells in one animal and 142 cells in the second: 10.2% increased activity before arm movements onset, 77.1% during arm movement, and 12.7% after the new position was reached. To test for neural representation of the visual outcome of movement, firing rate modulation was compared in normal and mirror step-tracking. Most task-related neurons (68%) showed no significant directional modulation. Of 70 directionally sensitive cells, almost one-half (n = 34, 48%) modulated firing with a consistent cursor movement direction, many fewer responding to the manipulandum direction (n = 9, 13%). For those "cursor-related" cells tested with delayed cursor movement, increased activity onset was time-locked to arm movement and not cursor movement, but activation duration was extended by an amount similar to the applied delay. Hence, activity returned to baseline about when the delayed cursor reached the target. We conclude that many cells in the lateral cerebellar cortex signaled the direction of cursor movement during active step-tracking. Such a predictive representation of the arm movement could be used in the guidance of visuo-motor actions.     

Arm-movement-related neurons in the primate superior colliculus and underlying reticular formation: comparison of neuronal activity with EMGs of muscles of the shoulder, arm and trunk during reaching

 Neuronal activity was recorded from the superior colliculus (SC) and the underlying reticular formation in two monkeys during an arm reaching task. Of 744 neurons recorded, 389 (52%) clearly modulated their activity with arm movements. The temporal activity patterns of arm-movement-related neurons often had a time course similar to rectified electromyograms (EMGs) of particular muscles recorded from the shoulder, arm or trunk. These reach cells, as well as the muscles investigated, commonly exhibited mono- or biphasic (less frequently tri- or polyphasic) excitatory bursts of activity, which were related to the (pre-)movement period, the contact phase and/or the return movement. The vast majority of reach cells exhibited a consistent activity pattern from trial to trial as did most of the muscles of the shoulder, arm and trunk. Similarities between the activity patterns of the neurons and the muscles were sometimes very strong and were especially notable with the muscles of the shoulder girdle (e.g. trapezius descendens, supraspinatus, infraspinatus or the anterior and medial deltoids). This high degree of co-activation suggests a functional linkage, though not direct, between the collicular reach cells and these muscles. Neuronal activity onset was compared with that of 25 muscles of the arms, shoulders and trunk. The majority of cells (78.5%) started before movement onset with a mean lead time of 149±90 ms, and 36.5% were active even before the earliest EMG onset. The neurons exhibited the same high degree of correlation (r=0.97, Spearman rank) between activity onset and the beginning of the arm movement as did the muscles (r=0.98) involved in the task. The mean neuronal reach activity (background subtracted) ranged between 7 and 193 impulses/s (mean 40.5±24.2). The mean modulation index calculated [(reach activity −background activity)/reach activity+background activity)] was 0.75±0.23 for neurons (n=358) and 0.87±0.14 for muscles (n=25). As the monkeys fixated the reach target constantly during an arm movement, neuronal activity which was modulated in this period was not related to eye movements. The three neck muscles investigated in the reach task exhibited no reach-related activity modulation comparable to that of either the reach cells or the muscles of the shoulder, arm and trunk. However, tonic neck muscle EMG was monotonically related to horizontal eye position. The clear skeletomotor discharge characteristics of arm-movement-related SC neurons revealed in this study agree with those already known from other sensorimotor regions (for example the primary motor, the premotor and parietal cortex, the basal ganglia or the cerebellum) and are consistent with the possible role of this population of reach cells in the control of arm movements. Received: 17 June 1996 / Accepted: 24 December 1996     

Precerebellar hindbrain neurons encoding eye velocity during vestibular and optokinetic behavior in the goldfish

Elucidating the causal role of head and eye movement signaling during cerebellar-dependent oculomotor behavior and plasticity is contingent on knowledge of precerebellar structure and function. To address this question, single-unit extracellular recordings were made from hindbrain Area II neurons that provide a major mossy fiber projection to the goldfish vestibulolateral cerebellum. During spontaneous behavior, Area II neurons exhibited minimal eye position and saccadic sensitivity. Sinusoidal visual and vestibular stimulation over a broad frequency range (0.1-4.0 Hz) demonstrated that firing rate mirrored the amplitude and phase of eye or head velocity, respectively. Table frequencies >1.0 Hz resulted in decreased firing rate relative to eye velocity gain, while phase was unchanged. During visual steps, neuronal discharge paralleled eye velocity latency (approximately 90 ms) and matched both the build-up and the time course of the decay (approximately 19 s) in eye velocity storage. Latency of neuronal discharge to table steps (40 ms) was significantly longer than for eye movement (17 ms), but firing rate rose faster than eye velocity to steady-state levels. The velocity sensitivity of Area II neurons was shown to equal (+/- 10%) the sum of eye- and head-velocity firing rates as has been observed in cerebellar Purkinje cells. These results demonstrate that Area II neuronal firing closely emulates oculomotor performance. Conjoint signaling of head and eye velocity together with the termination pattern of each Area II neuron in the vestibulolateral lobe presents a unique eye-velocity brain stem-cerebellar pathway, eliminating the conceptual requirement of motor error signaling.     

Natriuretic peptides, but not nitric oxide donors, elevate levels of cytosolic guanosine 3',5'-cyclic monophosphate in ependymal cells ex vivo

We examined how children with Spastic Hemiparetic Cerebral Palsy (SHCP) perform interceptive actions they experience in daily life. Children were required to walk towards and intercept a stationary ball or a moving ball, with either their impaired or non-impaired arm. In the stationary ball condition the child was free to determine the speed of their response (internal timing), whereas in the moving ball condition there was a restricted time available (external timing). It was found that the reach movements of the non-impaired arm were different to the impaired arm, and were characterized by some of the typical movement limitations imposed by SHCP. However, there was no evidence of increased contribution from trunk motion or a lengthening of reach movement time or deceleration time. Instead, there was a coordinated change with the walking kinematics, whereby the children spent proportionately more time slowing down as they approached the point of interception when reaching with the impaired arm. There were also several differences in the response when intercepting a moving ball compared to a stationary ball. When the timing constraints were imposed externally (moving ball) rather than internally (stationary ball), children reached with a reduced movement time and deceleration time, and an increased peak wrist velocity and elbow excursion. These adaptations to behaviour were necessary to deal with the restricted time available to make the interception in the moving ball condition compared to when the ball was stationary, and reveal how children with SHCP coordinate walking and reaching when performing natural interceptive actions.     

Relations of motor cortex neural discharge to kinematics of passive and active elbow movements in the monkey

1. Bedingham and Tatton recently reported that in cats trained not to resist imposed limb perturbations, some motor cortex (area 4) neurons responded predominantly to acceleration or jerk (the third derivative of position). The questions arose whether motor cortex neurons responding to higher derivatives of limb displacement exist in the primate in a resist-perturbation task and, if so, whether discharge of such neurons responds to the same kinematics in active (voluntary) movements. 2. To answer these questions we studied the discharge patterns of 203 motor cortex neurons that responded to torque pulse perturbations about the elbow and fired during active elbow flexions and extensions in four monkeys. Detailed analysis was performed on 66 neurons that responded reciprocally in both situations. 3. Reciprocal neurons discharged at short latency (20-40 ms) for one direction of arm perturbation. For the opposite direction they were initially silent or inhibited and then discharged at a variety of latencies but in apparent relation to limb kinematics. Based on the timing and overall pattern of their discharge the majority of neurons (68%) were classified as being acceleration-like. 4. Twenty-four (36%) of these reciprocal neurons had only sensory (kinematic)-like properties in active movements, i.e., they discharged after (and not before) movement onset. Discharge of these neurons followed the timing, but not the magnitude, of acceleration (20 neurons) or velocity (4 neurons). The discharge of these neurons also had a static component as the arm was held stationary. 5. Twenty-nine (44%) of reciprocal neurons commenced firing before movement onset for one direction of active movement, while for the opposite direction their discharge occurred after movement onset. Thus their discharge appeared to be muscle-related: both when the muscle was contracting as an agonist and stretched as an antagonist. 6. Although in these tasks discharge of MCNs could be generated either by sensory feedback or by motor responses, the strong response sensitivity of many neurons to acceleration supports the hypothesis that feedback based on higher derivatives of limb displacement could represent a "predictive" control system for accurate regulation of limb motion.