Importance of the temporal structure of movement sequences on the ability of monkeys to use serial order information.

The capacity to acquire motor skills through repeated practice of a sequence of movements underlies many everyday activities. Extensive research in humans has dealt with the importance of spatial and temporal factors on motor sequence learning, standing in contrast to the few studies available in animals, particularly in nonhuman primates. In the present experiments, we studied the effect of the serial order of stimuli and associated movements in macaque monkeys overtrained to make arm-reaching movements in response to spatially distinct visual targets.

The role of striatal tonically active neurons in reward prediction error signaling during instrumental task performance.

The detection of differences between predictions and actual outcomes is important for associative learning and for selecting actions according to their potential future reward. There are reports that tonically active neurons (TANs) in the primate striatum may carry information about errors in the prediction of rewards. However, this property seems to be expressed in classical conditioning tasks but not during performance of an instrumental task.

Modulation of neuronal activity in the monkey putamen associated with changes in the habitual order of sequential movements.

The striatum, especially its dorsolateral part, plays a major role in motor skill learning and habit formation, but it is still unclear how this contribution might be mediated at the neuronal level. We recorded single neurons in the posterior putamen of two monkeys performing an overlearned sequence of arm reaching movements to examine whether task-related activities are sensitive to manipulations of the serial order of stimulus-target locations. The monkeys' capacity to learn sequential regularities was assessed by comparing arm movement latencies and saccadic ocular reactions when a fixed repeating sequence was replaced with a random sequence.

Tonically active neurons in the striatum differentiate between delivery and omission of expected reward in a probabilistic task context.

Tonically active neurons (TANs) in the primate striatum are responsive to rewarding stimuli and they are thought to be involved in the storage of stimulus-reward associations or habits. However, it is unclear whether these neurons may signal the difference between the prediction of reward and its actual outcome as a possible neuronal correlate of reward prediction errors at the striatal level. To address this question, we studied the activity of TANs from three monkeys trained in a classical conditioning task in which a liquid reward was preceded by a visual stimulus and reward probability was systematically varied between blocks of trials.

Influence of spatial information on responses of tonically active neurons in the monkey striatum.

Previous studies have demonstrated that tonically active neurons (TANs) in the primate striatum play an important role in the detection of rewarding events. However, the influence of the spatial features of stimuli or actions required to obtain reward remains unclear. Here, we examined the activity of TANs in the striatum of monkeys trained to make spatially directed movements elicited by visual stimuli presented ipsilaterally or contralaterally to the moving arm.

Reward-related neuronal activity in the subthalamic nucleus of the monkey.

The subthalamic nucleus is a key structure for motor information processing in the basal ganglia. Little is known about its involvement in other aspects of behavior such as motivation. We investigated neuronal activity in the subthalamic nucleus while a monkey performed arm-reaching movements to obtain a liquid reward.

Responses of tonically active neurons in the monkey striatum discriminate between motivationally opposing stimuli.

The striatum is involved in the control of appetitively motivated behavior. We found previously that tonically active neurons (TANs) in the monkey striatum show discriminative responses to different stimuli that are appetitive or aversive. However, these differential responses may reflect the sensory qualities of the stimulus rather than its motivational value.

[Spatial orienting of attention: a study of reaction time during pointing movement].

Aim: The aim of this study was to investigate how advance information both explicit and implicit provided prior to movement may affect the spatial orientation and the internal attention control processes in normal adult subjects. The originality of this work compared to the test of Posner, lies essentially in the methodology used to study the attentional systems. The use of three procedures of reaction time (RT) allowed us to study the setting concerned of the specific and non-specific components of the attention in the motor preparation.

Reward unpredictability inside and outside of a task context as a determinant of the responses of tonically active neurons in the monkey striatum.

Tonically active neurons (TANs) in the monkey striatum are involved in detecting motivationally relevant stimuli. We recently provided evidence that the timing of conditioned stimuli strongly influences the responsiveness of TANs, the source of which is likely to be the monkey's previous experience with particular temporal regularities in sequential task events. To extend these findings, we investigated the relationship of TAN responses to a primary liquid reward, the timing of which is more or less predictable to the monkey either outside of a task or during instrumental task performance.

[Effects of spatial orientation on attention reaction time during pointing movement towards visual direction].

In the present study, it was consequently proposed to investigate how the spatial orientation of attention made by the explicit and implicit components of advance information, affected the reaction time (RT) performances. Subjects performed a simple RT task with an orientation cue and two choice RT situations, the one with a neutral cue and the other with a primed cue. The motor task to be performed consisted of pointing towards a visual target.

Influence of the predicted time of stimuli eliciting movements on responses of tonically active neurons in the monkey striatum.

Changes in activity of tonically active neurons of the primate striatum are determined both by the behavioural significance of stimuli and the context in which stimuli are presented. We investigated how the responses of these neurons are modified by the temporal predictability of stimuli eliciting learned behavioural reactions. Single neurons were recorded from the caudate nucleus and putamen of two macaque monkeys performing a visual reaction time task under conditions in which the timing of the trigger stimulus was made more or less predictable.

Tonically active neurons in the monkey striatum do not preferentially respond to appetitive stimuli.

The tonically active neurons in the monkey striatum respond to stimuli presented during the performance of appetitively motivated behavior. To test whether these neurons are selectively responsive to the appetitive properties of stimuli, we studied their responsiveness to three different stimuli presented in an unsignalled manner to monkeys not performing any behavioral tasks: (1) an appetitive liquid, eliciting licking movements; (2) an aversive air puff directed towards the face, eliciting eyelid closure and facial movements; (3) a neutral sound, eliciting no overt behavioral reactions. The great majority of the tonic striatal neurons tested in two monkeys showed pronounced responses to the delivery of liquid (338 of 388 neurons, 87%) or the onset of the air puff stimulus (168 of 204, 82%).

Influence of predictive information on responses of tonically active neurons in the monkey striatum.

Influence of predictive information on responses of tonically active neurons in the monkey striatum. J. Neurophysiol.

[Effects of advance information given by sensory cues on the duration and precision of a pointing movement in Parkinson's disease].

The aim of the present study was to investigate Parkinsonians' ability to process and use the explicit and implicit advance information available about a motor task they are preparing to perform. For this purpose, the performances of 13 Parkinsonians were compared with those of 11 control subjects in a double stimulus reaction time task. The explicit information was provided by a preparatory auditory signal (S1), and the implicit information was conveyed by the probability that the imperative signal (S2) would be consistent with S1 in a given series of trials.

The use of advance information for motor preparation in Parkinson's disease: effects of cueing and compatibility between warning and imperative stimuli.

The ability of 13 Parkinsonian patients and 11 age-matched control subjects to process and use two components of the information given prior to a voluntary movement was studied using reaction time (RT) tasks. This advance information about the direction of a pointing movement was given using a double stimulation paradigm with an auditory warning signal (WS) which occurred prior to a visual imperative signal (IS). The first component of the information was given by the WS at the beginning of each trial, and the second component was the WS-IS compatibility during series of trials.

Spatio-temporal and kinematic analysis of pointing movements performed by cerebellar patients with limb ataxia.

Three patients with cerebellar limb ataxia and three age-matched controls performed arm-pointing movements towards a visual stimulus during an experimental procedure using a double-step paradigm in a three-dimensional space. Four types of trajectories were defined: P1, single-step pointing movement towards the visual stimulus in the initial position S1; P2, double-step pointing movement towards S1; P3, double-step straight pointing movement towards the second position S2; and P4, double-step pointing movement towards S2 with an initial direction towards S1. We found that the cerebellar patients, as well as the controls, were able to modify their motor programs, but with impaired timing, severe anomalies in the direction and amplitude of the changed movement trajectories and alteration of the precision of the pointing movements.

Responses of tonically discharging neurons in the monkey striatum to primary rewards delivered during different behavioral states.

In the primate striatum, the tonically discharging neurons respond to conditioned stimuli associated with reward. We investigated whether these neurons respond to the reward itself and how changes in the behavioral context in which the reward is delivered might influence their responsiveness. A total of 286 neurons in the caudate nucleus and putamen were studied in two awake macaque monkeys while liquid reward was delivered in three behavioral situations: (1) an instrumental task, in which reward was delivered upon execution of a visually triggered arm movement; (2) a classically conditioned task, in which reward was delivered 1 s after a visual signal; (3) a free reward situation, in which reward was delivered at irregular time intervals outside of any conditioning task.

Responses of tonically discharging neurons in monkey striatum to visual stimuli presented under passive conditions and during task performance.

To test whether the responsiveness of tonically discharging neurons from monkey striatum is dependent on the motor or rewarding features of the conditioned stimuli, we studied the responses of these neurons to visual stimuli presented under two behavioral conditions: during an operant task in which the stimulus triggered a movement to obtain a reward, and in a non-performing state in which the stimulus was consistently followed by a reward outside of a task. Most of the neurons tested (110/158) responded to the stimuli presented in both conditions, while a relatively small number of neurons (35/158) showed selective responses in one or other of the conditions. A gradual disappearance of neuronal responses occurred in the passive state when presenting a stimulus which was never followed by reward.

Quantitative behavioral study of the acute and long-term effects of two-stage bilateral 6-OHDA-induced lesions of the nigrostriatal dopaminergic system in monkeys.

Bilateral lesions of the nigrostriatal dopaminergic system (2-stage lesions separated by 5-6 months) were induced in 3 monkeys trained to initiate forelimb-reaching movements toward a visual target. After each lesion, analysis of the task performance over several months of regular testing showed that the latency to initiate the movement was permanently prolonged in monkeys showing 90% or more striatal dopamine depletion, whereas animals with less severe depletion completely recovered the task performance. Several months after a unilateral nigrostriatal damage, a lesion on the other side produced impairments only on the side of the body contralateral to that second lesion and did not reinstate the deficits on the side previously affected by the first lesion.

Planning and execution of pointing movements in cerebellar patients.

Twelve patients with cerebellar dysfunction including a limb ataxia and 12 age-matched controls performed pointing movements with an arm. In one condition, the task was a simple reaction time (RT) movement directed toward a spatially defined target. The other two conditions involved choice tasks in which the amplitude and direction of movement were varied.

Bilateral and side-related reaction time impairments in patients with unilateral cerebral lesions of a medial frontal region involving the supplementary motor area.

Human subjects (nine patients with unilateral brain lesions of a medial frontal region involving the supplementary motor area, SMA, and 10 controls) performed two reaction time (RT) tasks in response to the presentation of a luminous signal: an aimed movement towards a spatially defined target involving hand lifting and pointing with the index finger, and a no-aimed movement consisting of the hand lifting phase completed by the stabilization of the limb posture without any pointing. When compared with controls, the patients exhibited a bilateral RT increase which was more pronounced in the hand contralateral to the lesion. Moreover, comparison between the two tasks showed that this contralateral RT impairment was more marked in the no-aiming than in the aiming task.

Methods of motor performance evaluation: application to a primate model for basal ganglia pathology.

In studies on the motor impairments induced in monkeys by performing lesions of various kinds on the central nervous system, it is necessary to be able to exactly quantify the motor deficits. The battery of tests described in the present paper (simple and choice reaction-time procedures, goal-directed pointing movement, digital manipulation task) provide a systematic means of analysing the motor performances involving movement control. Central nervous dysfunction can be induced by either reversibly or permanently excluding specific structures.

Globus pallidus and motor initiation: the bilateral effects of unilateral quisqualic acid-induced lesion on reaction times in monkeys.

The results of many experimental studies have shown that the globus pallidus (GP) is involved in the control of motor activities, particularly during motor execution. Whether or not the GP is involved in the initiation phase is still a matter of controversy, however. This question was investigated in the present study in Papio papio monkeys after GP lesion using a simple reaction time (RT) task, focusing particularly on the initiation phase.

Neglect of contralateral visual stimuli in monkeys with unilateral striatal dopamine depletion.

Unilateral lesions of the nigrostriatal dopaminergic system were induced by injecting 6-hydroxydopamine into the substantia nigra of three monkeys trained to initiate arm movements in response to stimuli randomly presented at various locations in their immediate visual space. This procedure resulted in partial reduction of dopamine content, as compared to intact side, in both the putamen and caudate nucleus, with the exception of the putamen in one monkey. A concomitant reduction in the level of dihydroxyphenylacetic acid was observed, but less systematically than the dopamine decrease in the same striatal regions.

Motor impairments and neurochemical changes after unilateral 6-hydroxydopamine lesion of the nigrostriatal dopaminergic system in monkeys.

Unilateral lesions of the nigrostriatal dopaminergic system were induced in five monkeys by intranigral injections of the neurotoxin 6-hydroxydopamine. Following the lesion, all monkeys showed a transient reluctance in using the contralateral forelimb, accompanied, in two monkeys by semi-flexed posture of the disabled forelimb. Three of the monkeys that had been conditioned to perform a visually triggered goal-directed arm movement, showed an increase in latency and duration of contralateral arm movements.