[Spatial orienting of attention: a study of reaction time during pointing movement]. / Orientation spatiale de l'attention: étude des temps de réaction lors du mouvement de pointage.

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. By associating of these three procedures of RT, we have evaluated the effects of the explicit and implicit components of advance information on motor preparation. The use of advance information to the movement requires the implication of the attentional systems. MATERIAL AND METHODS: Experiments were carried out using a simple reaction time (RT) procedure involving the use of an orientation cue and two choice reaction time situations: one with a neutral preparatory cue and one with a priming cue giving the likelihood of the preparatory stimulus (S1) being compatible with the imperative stimulus (S2). The mechanisms underlying the subjects' vigilance and the orientation of their attention were studied by assessing the effects on their reaction times of the preparatory signal and those of the cue giving the likelihood of S1 and S2 being compatible. The preparatory signal was designed to explicitly attract the subjects' attention towards the position of the forthcoming pointing target, whereas the cue giving the compatibility between S1 and S2 was intended to mobilize the subject's attention more implicitly. Prior to performing the pointing movement towards a visual target, the subjects' attention was therefore mobilized by the advance information containing two components: the explicit information about the position of S1 and the implicit information about the probability of S1 and S2 being compatible. RESULTS AND CONCLUSION: The results obtained here on 17 normal adult subjects show that the subjects significantly improved their RTs by using the explicit component of the information provided. The implicit information available was also used in the choice reaction situations: a priming effect was found to occur, which resulted in the shortening of the primed "compatible cue" reaction times in comparison with the "neutral cue" reaction times, and in the correlation which was found to exist between the reaction time performances and the degree of compatibility between the preparatory signal and the imperative signal. These results suggest that various components of the attentional system may participate in processing the advance information provided prior to the movement in reaction time tasks of the kind used here. The explicit information provided prior to the movement may mobilize the subject's vigilance and spatially orients his attention; whereas the implicit information available may rather subserve the internal control of the subject's attention.

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. Reward predictability was indexed by the timing characteristics of the mouth movements. The responsiveness of TANs to reward increased with the range and variability of time periods before reward, notably when the liquid was delivered outside of a task. A change in the temporal order of events in a task context produced an increase of response to reward, suggesting an influence of the predicted nature of the event in addition to its time of occurrence. By contrast, we observed no substantial changes in neuronal activity at the expected time of reward when this event failed to occur, suggesting that these neurons do not appear to carry information about an error in reward prediction. These results demonstrate that TANs constitute a neuronal system that is involved in detecting unpredicted reward events, irrespective of the specific behavioral situation in which such events occur. The responses influenced by stimulus prediction may constitute a neuronal basis for the notion that striatal processing is crucial for habit learning.

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. The monkeys' ability to predict the trigger onset was assessed by measuring arm movement reaction times and saccadic ocular reactions. Of 171 neurons responding to the unsignalled presentation of the trigger stimulus, 32% lost their response when an instruction cue preceded the trigger by a highly practised 1.5 s interval, and the response reappeared when this interval was varied randomly from 1 to 2.5 s or prolonged to 3 or 4. 5 s. Although 43% of the neurons remained responsive irrespective of task condition, the responses were stronger with longer intervals than with the accustomed 1.5 s interval. In addition, a number of neurons responding to the instruction lost their response when the trigger appeared more distant from the instruction. These findings demonstrate that neuronal responses to a movement-triggering signal become more numerous and pronounced when the degree of temporal predictability of that signal was decreased. We conclude that tonic striatal neurons are sensitive to temporal aspects of stimulus prediction.

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%). In contrast, few neurons (15 of 68, 22%) were modulated by the sound. The majority (80%) of the neurons tested with appetitive and aversive stimuli (n=189) responded to both types of stimulus. The characteristics of neuronal responses to the liquid were generally not similar to those described for the air puff in terms of response pattern and response duration. This suggests the existence of differences in the encoding of the affective significance of stimuli. It is concluded that tonic striatal neurons might function to differentiate stimuli that are important to the animal from those that are not, regardless of the specific motivational attributes of relevant stimuli.

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. 80: 3341-3344, 1998. We investigated how the expectation of a signal of behavioral significance influences the activity of tonically active neurons in the striatum of two monkeys performing a simple reaction time task under two conditions, an uncued condition in which the trigger stimulus occurred randomly in time and a cued condition in which the same trigger was preceded by an instruction stimulus serving as a predictive signal for the forthcoming signal eliciting an immediate behavioral reaction. Both monkeys benefited from the presence of the instruction stimulus to reduce their reaction time, suggesting an increased ability to predict the trigger onset during cued trials compared with uncued trials. A majority of neurons (199/272, 73%) showed a phasic reduction in activity after the onset of the trigger stimulus in the uncued condition, whereas only 38% responded to the same stimulus when it was preceded by the instruction. Furthermore, magnitudes of trigger responses in the uncued condition were significantly higher than in the cued condition. Fifty-seven percent of the neurons responded to the instruction stimulus, and one-half of the neurons losing their response to the trigger in the cued condition responded to the instruction stimulus. These findings suggest that responses of tonic striatal neurons to a trigger stimulus for movement were influenced by predictive information.

[Effects of advance information given by sensory cues on the duration and precision of a pointing movement in Parkinson's disease]. / Effets de l'information préalable donnée par des indices sensoriels sur la durée et la précision d'un mouvement de pointage dans la maladie de Parkinson.

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. Each subject performed 3 successive RT tasks under the following conditions: an oriented cue condition, a neutral cue condition and a primed condition. The results show that the movement times of the Parkinsonians were longer than those of the control subjects, and that they lengthened with the clinical evolution of the disease. Neither the explicit nor the implicit advance information had any effect on the control subjects' performance variables; nor did they affect the Parkinsonians' movement times or pointing areas. The Parkinsonians' systematic errors increased however in the case of primed responses. The fact that the patients' bradykinesia was associated with fairly accurate pointing performances suggests that in Parkinson's disease, a change of voluntary movement performance strategy may occur, involving greater reliance on visual cues.

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. The subjects were tested with three RT paradigms: a cued simple (CS) task, a cued choice (NC) task, and a priming choice (P) task. The results show that the normal subjects used both the lateral cue and the WS-IS compatibility to shorten their RTs, whereas the Parkinsonian patients were able to use the lateral warning signal, but their ability to use the degree of compatibility stimuli was impaired. These data suggest that when dealing with lateral cues in a RT task, Parkinsonian patients have no difficulty in identifying a stimulus and selecting the appropriate response, but that this is no longer so in the case of stimulus compatibility. This impairment may be due to attentional disorders involving a dysfunction affecting the medial premotor system, which includes the basal ganglia and may be responsible for the feedforward movement control deficits associated with Parkinson's disease.

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.

[Effects of spatial orientation on attention reaction time during pointing movement towards visual direction]. / Effets de l'orientation spatiale de l'attention sur le temps de réaction lors du mouvement de pointage sur une cible visuelle.

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. The mechanisms involved in the orientation of attention were studied on the one hand by analysing the effects of the preparatory signal, which explicitly oriented the subjects' attention towards the forthcoming target position, and on the other hand, by examining whether the reinforced probability of warning stimulus(WS) and imperative stimulus (IS) being compatible affected the subjects' performances, i.e., whether they detected and made use of the information implicitly conveyed that there existed a bias in favour of the probability that IS would appear in the direction predicted by WS. The results of this study show that the subjects shortened their RTs by using both the explicit(auditory) and the implicit(probability-related) information with which they were provided prior to performing the movement. These data on the effects of the oriented auditory signal on the reaction times indicate that in our experiments, by orienting their attention depending on the position of the stimuli, the subjects were able to reduce their reaction times. The significant correlation found to exist here between the level of probability associated with the position of the WS and the choice RT values indicates that also the implicit information as to the WS-IS compatibility was taken into account by the subjects in all the situations.

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. The monkeys' uncertainty about the time at which reward will be delivered was assessed by monitoring their mouth movements. A larger proportion of neurons responsive to reward was observed in the free reward situation (86%) than in the classically conditioned (57%) and instrumental tasks (37%). Among the neurons tested in all situations (n = 78), 24% responded to reward regardless of the situation and 65% in only one or two situations. Responses selective for one particular situation occurred exclusively in the free reward situation. When the reward was delivered immediately after the visual signal in the classically conditioned task, most of the neurons reduced or completely lost their responses to reward, and other neurons remained responsive. Conversely, neuronal responses invariably persisted when reward was delivered later than 1 s after the visual signal. This is the first report that tonic striatal neurons might display responses directly to primary rewards. The neuronal responses were strongly influenced by the behavioral context in which the animals received the reward. An important factor appears to be the timing of reward. These neurons might therefore contribute to a general aspect of behavioral reactivity of the subject to relevant stimuli.

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. These results provide evidence that tonic striatal neurons may be involved in detecting stimuli predicting reward, regardless of the behavioral contingency of those stimuli.

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. This suggests that the remaining intact nigrostriatal dopaminergic system may not be involved in the long-term behavioral recovery observed in monkeys with a unilateral 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. The variables recorded were: movement latency determined by measuring the RT, duration of movement and the terminal accuracy of pointing as reflected in the movement time (MT), pointing surfaces (PS), and systematic errors. RTs and MTs were found to be significantly longer in cerebellar patients than in controls. In both groups the choice RT increased significantly as compared to simple RT, but no significant difference between patients and controls was found for the mean increase of the choice RT as compared with the mean increase for simple RT. A strong correlation between MTs and PSs was found in the controls. The cerebellar patients showed no correlation between MTs and PSs. The results are discussed in relation to the ability in cerebellar patients to program and execute voluntary movements.

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. These results suggest that unilateral lesions of a medial frontal region involving the SMA cause two types of RT impairment in these motor tasks. The first may concern a supramotor function which acts bilaterally and initiates the motor programme of the limb movement as the first step of preparatory processes. The second component of this RT impairment would concern a supplementary motor function which consists of the feed forward control of the coupling between the hand lifting and the appropriate posture, just before the triggering of the limb movement. This interpretation leads to the hypothesis that the SMA region, and the medial motor system in general, may have a dual motor function.

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. An example of the motor impairments observed after lesion of the substantia nigra is given which provides an animal model for hemi-parkinsonism.

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. The monkeys were trained to perform this task, which consisted of raising their hand as quickly as possible in response to a visual signal. The RT and its premotor and motor components were measured. In addition, the distribution of the RTs was analyzed in order to assess the number of long latency responses. After making unilateral GP cell lesions by locally injecting small amounts of the excitatory amino acid quisqualic acid, a bilateral increase was observed in RT. This lengthening involved both the premotor and the motor phases of the RT when the task was performed with the contralateral limb and only the premotor phase when it was performed with the ipsilateral one. A significant increase was observed in the percentage of long latency responses recorded in the contralateral limb after the GP lesion but not in the ipsilateral one. Increases in the RT and in the percentage of long latency responses are thought to constitute two indices of the akinesia observed in our task involving speed constraints, which suggests that the GP may participate in motor initiation. A complete recovery of the RT was observed within one month, whereas the increase in the percentage of long latency responses persisted. These two indices of akinesia seemed therefore to result from an impairment involving both motor and nonmotor processes. These data suggest that the GP may be involved in the control of postural adjustment, motivation, and/or the control of the initial isometric part of movements. The time course of the recovery from the deficits observed after GP lesion shows the existence of mechanisms which seem to have been operative particularly in the case of impairments affecting motor processes.

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. All monkeys displayed a predominant contralateral arm hypokinesia consisting of a slowness in initiating movements, little or not affected by the hemispace of presentation of the trigger stimulus. Conversely, when the monkeys responded with the arm ipsilateral to the lesion, the movement was initiated more slowly when the trigger stimulus was presented to the hemispace contralateral to the striatal dopaminergic depletion as compared to the ipsilateral hemispace. The results suggest that the visual neglect is more conspicuous when monkeys performed with the arm ipsilateral to the damaged nigrostriatal system. This neglect may be described as a disorder in the ease with which stimuli presented to the side contralateral to the impaired dopaminergic transmission are able to elicit behavioral responses, possibly as the result of a lack of selective attention or defective movement initiation.

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. Task performance recovered spontaneously to preoperative levels within four months in two monkeys despite significant reductions of endogenous dopamine and dihydroxyphenylacetic acid contents in the caudate nucleus, putamen and globus pallidus ipsilateral to the neurotoxic nigral injection. The third monkey exhibited a persistent increase in movement latency associated with a near complete loss of dopamine in both the putamen and the caudate nucleus. In all cases, an increase the dihydroxyphenyl-acetic acid to dopamine ratio was detected in the striatum and pallidum suggesting a compensatory increase in dopamine turnover in remaining intact dopaminergic nerve terminals. The level of serotonin was changed in all monkeys consisting of either a decrease or an increase, depending on the striatopallidal regions studied. Changes in choline acetyltransferase and glutamic acid decarboxylase activities in the same regions were only seen in some cases. The present results show that 6-hydroxydopamine-induced partial unilateral lesion of nigral dopaminergic neurons produced predominantly contralateral hypokinesia, accompanied by reductions of dopamine content in the ipsilateral striatum and pallidum. The use of this locally applied neurotoxin appears to be a suitable method for investigating neurophysiological mechanisms underlying hypokinesia since deficits in both initiating and executing movements can be expressed independently of other behavioral symptoms. The results show more persistent deficits in starting movements than in their execution and thus suggest that motor initiation is more dependent upon the functional integrity of the nigrostriatal dopamine system than movement completion.

The role of visual reafferents during a pointing movement: comparative study between open-loop and closed-loop performances in monkeys before and after unilateral electrolytic lesion of the substantia nigra.

In order to elucidate the compensatory role of visual feedback during movement, two experiments were designed to compare the motor performances of Papio papio baboons depending on whether the animals were able to visually control the limb trajectory (visual closed-loop condition) or not (visual open-loop condition). The visuomotor task used consisted of making trained pointing movements towards a stationary target. In experiment A, the baboons were successively presented with these two experimental conditions. The abolition of visual control was found to cause no change in either reaction time (RT) or movement time (MT), but brought about extensive pointing errors. It was also associated with a conspicuous increase in the mean velocity and the mean length of the trajectories. In experiment B, two groups of baboons were used. The monkeys in the first group were required to perform under closed loop conditions. The second group performed the pointing movement under open loop conditions. Once criterion was reached by each animal, a unilateral electrolytic lesion of the substantia nigra (SN) was performed. A comparison between the post operative performances of the animals in the two groups showed that suppression of visual cues resulted in a lengthening of the RT and a slowing of the movement speed. Moreover when visual feedback was lacking, the amplitude of the movement decreased and the finger fell short of the target. During the last post operative period, suppression of visual feedback brought about a more rapid return of RTs to their preoperative level and a more durable slowing of movement speed than with normal vision. The discussion deals with the role of visual feed-back in the control of movement preparation and execution, and with the change in mode of motor control caused by lesion of the SN. Partial exclusion of the SN might bring about a shift from the feedforward to a feedback mode relying more heavily on visual cues.

Differential time-course of reaction time recovery depending on variations in the amplitude of a goal-directed movement after nigrostriatal lesion in monkeys.

Unilateral striatal dopamine depletion induced by 6-hydroxydopamine injections into the substantia nigra of behaving monkeys was found to increase the latency of a visually guided pointing movement performed by the contralateral forelimb. The time-course of recovery of the movement latency was faster in small displacements of the limb than in movements with larger amplitudes. The efficiency of putative compensatory mechanisms that may develop progressively in response to the striatal dopamine deficit depends on the amplitude of the movement to be initiated.