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Relationship between sensorimotor adaptation and cognitive functions in younger and older subjects.

We investigated whether deficits of adaptive improvement in seniors are related to an age-dependent decay of the brain's executive functions. Younger and older subjects completed a battery of cognitive tests, and preformed aimed arm movements before and during exposure to rotated visual feedback. In accordance with previous work, we found that adaptive improvement during exposure was degraded in seniors, while the transfer of adaptation to a new motor task was not. This pattern of findings confirms that strategic control but not sensorimotor recalibration is affected by old age. Using multiple linear regression (MLR) to extract separate executive components from our test battery, we found that basic response speed and decision-making, but not the inhibition of prepotent responses or mental flexibility, were degraded in our older subjects. Again using MLR, we found that degraded adaptive improvement in our seniors was partly related to the decay of basic response speed and decision-making, and partly to age-dependent phenomena not addressed by our cognitive-test battery. Finally, we observed that interindividual variability of cognition and adaptive improvement was larger in old than in young subjects, which could explain why some previous studies found degraded adaptation in seniors while others did not.

Adaptation, Physiological↗

The effect of rest breaks on human sensorimotor adaptation.

We have studied the effect of rest breaks on sensorimotor adaptation to rotated visual feedback in a pointing task. Adaptive improvement was significantly poorer after 1-s breaks than after 5-40-s breaks, with no significant difference among the latter break durations. The benefit of >1-s breaks emerged soon after the onset of adaptation, and then remained steady throughout the adaptation, retention (next day), and persistence (no feedback) phases. This pattern of findings indicates that break-induced facilitation is not a result of strategic adjustments, motivation, or recovery from fatigue, but rather to consolidation of previously acquired sensorimotor recalibration rules.

Adaptation, Physiological↗

Time series analysis of magnetoencephalographic data during copying.

We used standard time series modeling to analyze magnetoencephalographic (MEG) data acquired during three tasks. Each task lasted 45 s, for a total data acquisition period of 135 s. Ten healthy human subjects fixated their eyes on a central blue point for 45 s (fixation only, "F" task). Then a pentagon (visual template) appeared surrounding the fixation point which simultaneously became red (fixation + template, "FT" task). After 45 s, the fixation point changed to green, which was the "go" signal for the subjects to begin continuously copying the pentagon for 45 s using a joystick and without visual feedback of their movement trajectory (fixation + template + copying, "FTC" task). MEG data were acquired continuously from 248 axial gradiometers at a sampling rate of 1017.25 Hz. After removal of cardiac artifacts and rejection of records with eyeblink artifacts, a Box-Jenkins autoregressive integrative moving average (ARIMA) analysis was applied to the unsmoothed, unaveraged MEG time series for model identification and estimation within 25 time lags (approximately 25 ms). We found that an ARIMA model of 25th order autoregressive, first order differencing, and first order moving average (p=25, d=1, q=1) adequately modeled the series and yielded residuals practically stationary with respect to their mean, variance, and autocorrelation structure. These "prewhitened" residuals were then used for assessing pairwise associations between series using crosscorrelation analysis with +/-25 time lags (approximately +/-25 ms). The cross-correlograms thus obtained revealed rich and consistent patterns of interactions between series with respect to positive and/or negative correlations. The overall prevalence of these patterns was very similar in the three tasks used, and, for particular sensor pairs, they tended to be preserved across tasks.

Adult↗

Bilateral basal ganglia activation associated with sensorimotor adaptation.

Sensorimotor adaptation tasks can be classified into two types. When subjects adapt movements to visual feedback perturbations such as in prism lens adaptation, they perform kinematic adaptations. When subjects adapt movements to force field perturbations such as with robotic manipulanda, they perform kinetic adaptations. Neuroimaging studies have shown basal ganglia involvement in kinetic adaptations, but have found little evidence of basal ganglia involvement in kinematic adaptations, despite reports of deficits in patients with diseases of the basal ganglia, such as Parkinson's and Huntington's disease, in these. In an effort to resolve such apparent discrepancy, we used FMRI to focus on the first few minutes of practice during kinematic adaptation. Human subjects adapted to visuomotor rotations in the context of a joystick aiming task while lying supine in a 3.0 T MRI scanner. As demonstrated previously, early adaptive processes were associated with BOLD activation in the cerebellum and the sensory and motor cortical regions. A novel finding of this study was bilateral basal ganglia activation. This suggests that, at least for early learning, the neural correlates of kinematic adaptation parallel those of other types of skill learning. We observed activation in the right globus pallidus and putamen, along with the right prefrontal, premotor and parietal cortex, which may support spatial cognitive processes of adaptation. We also observed activation in the left globus pallidus and caudate nucleus, along with the left premotor and supplementary motor cortex, which may support the sensorimotor processes of adaptation. These results are the first to demonstrate a clear involvement of basal ganglia activation in this type of kinematic motor adaptation.

Adaptation, Physiological↗

How active gaze informs the hand in sequential pointing movements.

Visual information is vital for fast and accurate hand movements. It has been demonstrated that allowing free eye movements results in greater accuracy than when the eyes maintain centrally fixed. Three explanations as to why free gaze improves accuracy are: shifting gaze to a target allows visual feedback in guiding the hand to the target (feedback loop), shifting gaze generates ocular-proprioception which can be used to update a movement (feedback-feedforward), or efference copy could be used to direct hand movements (feedforward). In this experiment we used a double-step task and manipulated the utility of ocular-proprioceptive feedback from eye to head position by removing the second target during the saccade. We confirm the advantage of free gaze for sequential movements with a double-step pointing task and document eye-hand lead times of approximately 200 ms for both initial movements and secondary movements. The observation that participants move gaze well ahead of the current hand target dismisses foveal feedback as a major contribution. We argue for a feedforward model based on eye movement efference as the major factor in enabling accurate hand movements. The results with the double-step target task also suggest the need for some buffering of efference and ocular-proprioceptive signals to cope with the situation where the eye has moved to a location ahead of the current target for the hand movement. We estimate that this buffer period may range between 120 and 200 ms without significant impact on hand movement accuracy.

Adult↗

Movement-dependent positioning errors in human elbow joint movements.

Healthy adult humans performed elbow movements in a horizontal plane under a small external extending torque (2.1-3.3 Nm). Test movements (TMs) consisted of slow ramp-and-hold flexions in the absence of visual feedback, with the target joint angle to be remembered from a preceding conditioning movement (CM). The CM was produced by matching two beams on the monitor screen: (1) command representing the target position (a straight line); and (2) a signal from the sensor of the elbow joint angle. Two kinds of CM were applied, which had the same target position (50 degrees in most experiments) but differed in initial positions: (1) fully extended joint (0 degrees, P1 CMs); (2) flexed joint (100 degrees, P2 CMs). In a group of 25 subjects, the target in TMs was usually overshot, with the position errors depending on the CMs: 2.7 +/- 0.6 degree (mean +/- SEM) for P1 CMs, and 10.9 +/- 0.7 degree (P < 0.001) for P2 CMs. Vibration of the elbow flexors substantially diminished the difference between the position errors, amounting to--0.31 +/- 0.5 degree and 2.33 +/- 0.6 degrees, respectively. It is suggested that the observed position errors resulted from after-effects in the activity of muscle spindles in agonist and antagonist muscles, but influence of differences in dynamic components of the afferent signals during oppositely directed approaches to the target cannot be excluded.

Adult↗

Speed-accuracy trade-off in the performance of pointing movements in different directions in two-dimensional space.

Nine healthy subjects performed 2D pointing movements using a joystick that controlled a screen cursor. Continuous visual feedback was provided until movement completion. Three variables were systematically manipulated: (1) target distance, (2) target size and (3) target direction. A four-way factorial ANOVA was used to analyze the effects of these fixed factors and of the random factor of subject on several movement parameters. Movement time increased with increasing distance and decreasing target size and as predicted from Fitts' law. The target direction did not affect movement time. In contrast the direction, distance and size of the target significantly affected the movement time until the first zero crossing on the speed record reflecting the time to bring the arm into the vicinity of the target. Movements on the lateral axis of the horizontal plane (horizontal movements) resulted in a decrease in initial movement time compared to movements on the anterior axis of the horizontal plane (vertical movements). A significant effect of target distance and direction but not target size was observed for the magnitude of maximum acceleration, maximum speed and maximum deceleration. Horizontal movements had a larger maximum acceleration, speed and deceleration. Furthermore the maximum speed and deceleration occurred earlier in time for these horizontal movements. Finally the number of secondary peaks on the speed record increased with decreasing target size and was not affected by the target distance or target direction. In conclusion our results indicate that different movement parameters are affected by target distance, size and direction. The crucial distinction was between parameters affected by target size and direction. These parameters did not overlap. Target direction affects the first part of movement execution while target size affects the final part of movement execution. Thus a clear segmentation of movement execution in two phases is supported by these results. The implications of these results for theoretical models of speed-accuracy trade-off are discussed.

Acceleration↗

Selective enhancement of motoneurone short-term synchrony during an attention-demanding task.

Recent experiments on monkeys suggest that attention-related changes in the synchronous activity of neurones occur in the motor cortex. In humans, the clinical data available suggest that the weak synchronization of the motor unit firing observed during voluntary contraction might reflect the activity of the motoneurone cortico-spinal afferents. The present study was therefore designed to investigate how the synchronous motor-unit activity might depend on the attention required in performing a motor task. Twenty-five motor unit pairs were tested in the right extensor carpi radialis muscles of five right-handed subjects, who were instructed to keep both motor units firing tonically while trying to maintain the extension force as constant as possible using visual feedback set either at low or high gain. Fifteen motor unit pairs (60%) showed a greater amount of synchronous activity, without any consistent changes in the motor unit firing rates, when the subjects were monitoring the force at high gain. In addition, the mean value and the steadiness of the force did not differ significantly between the two tasks. The amplitude of the motor units' contractile force extracted by spike-triggered averaging did not change consistently despite the slight increase in the synchronous impulse probability observed under the high-gain conditions. Changes in synchrony affected slowly contracting, low-threshold motor units as well as fast-contracting, high-threshold motor units. The most noteworthy finding was that these changes actually focused on a narrow component of the synchronous activity (within a period of less than 4 ms) in keeping with the short-term synchronization process. This suggests that common inputs, possibly of cortical origin, may have contributed more greatly to controlling the motoneurone firing pattern in the motor task which required the subjects to pay more attention.

Adult↗

Vision of the hand and environmental context in human prehension.

Previous findings on the role of visual contact with the hand in the control of reaching and grasping have been contradictory. Some studies have shown that such contact is largely irrelevant, while more recent ones have emphasised its importance. In contrast, information arising from the surrounding environment has received relatively little attention in the study of prehensile actions. In order to identify the roles of both sources of information, we made kinematic comparisons between three conditions. In the first, reaching was performed in a dimly lit room and compared with a second condition in which reaches in the dark, but with the thumb and first finger illuminated, were made to a luminous object. This contrast allows the effects of environmental context to be identified. A comparison between the second and a third condition, in which both vision of the hand and the environment was removed, but the object was still visually available, enabled the assessment of how and when vision of the hand plays a role. Removing environmental cues had effects both early and late in the reach, while vision of the hand was only crucial in the period after peak deceleration. In addition, removal of both sources of information resulted in larger grip apertures. Differences and similarities between our findings and those of other studies are discussed, as is the ongoing debate about the relative importance of visual feedback of the hand in the control and co-ordination of prehensile actions. We conclude with suggestions for further research based on the set-up used in the present study.

Adult↗

Fast, anticipatory smooth-pursuit eye movements appear to depend on a short-term store.

Anticipatory smooth pursuit before the expected appearance of a moving target can reduce the initial retinal blur caused by the 100-ms delay of visual feedback. Humans, though, can only voluntarily generate smooth velocities up to about 5 degrees/s without a moving target. However, previous experiments have shown that repetitive brief presentations of a moving target every few seconds appear to charge an internal store, the contents of which can later be released to generate higher velocity anticipatory movements. This store's longevity was assessed here by repetitively presenting a moving target for 500 ms at different known intervals up to 7.2 s. Target motion at 25 degrees/s or 50 degrees/s was tested, with presentations in alternate directions or the same direction. Anticipatory velocity, measured 100 ms after target onset, decreased with increasing interval for all target motion conditions. A decrease was still seen when accurate timing cues were given before each presentation, suggesting that the drive for anticipatory pursuit is held in a short-term store lasting a few seconds which can enhance the low velocities produced by volition alone. The results also demonstrate that high-velocity anticipatory pursuit helps to overcome the temporal delays in the system and allows target velocity to be matched at an earlier time.

Adult↗

Changes in motor cortical activity during visuomotor adaptation.

We examined neuronal activity in three motor cortical areas while a rhesus monkey adapted to novel visuomotor transforms. The monkey moved a joystick that controlled a cursor on a video screen. Each trial began with the joystick centered. Next, the cursor appeared in one of eight positions, arranged in a circle around a target stimulus at the center of the screen. To receive reinforcement, the monkey moved the joystick so that the cursor contacted the target continuously for Is. The video monitor provided continuous visual feedback of both cursor and target position. With those elements of the task constant, we modified the transform between joystick movement and that of the cursor at the beginning of a block of trials. Neuronal activity was studied as the monkey adapted to these novel joystick-cursor transforms. Some novel tasks included spatial transforms such as single-axis inversions, asymmetric double-axis inversions and angular deviations (also known as rotations). Other tasks involved changes in the spatiotemporal pattern and magnitude of joystick movement. As the monkey adapted to various visuomotor tasks, 209 task-related neurons (selected for stable background activity) showed significant changes in their task-related activity: 88 neurons in the primary motor cortex (M1), 32 in the supplementary motor cortex (M2), and 89 in the caudal part of the dorsal premotor cortex (PMdc). Slightly more than half of the sample in each area showed significant changes in the magnitude of activity modulation during adaptation, with the number of increases approximately equaling the number of decreases. These data support the prediction that changes in task-related neuronal activity can be observed in M1 during motor adaptation, but fail to support the hypothesis that M1 and PMdc differ in this regard. When viewed in population averages, motor cortex continued to change its activity for at least dozens of trials after performance reached a plateau. This slow, apparently continuing change in the pattern and magnitude of task-related activity may reflect the initial phases of consolidating the motor memory for preparing and executing visuomotor skills.

Adaptation, Physiological↗

Hand and joint paths during reaching movements with and without vision.

This study examines whether the kinematics of pointing movements are altered by the sensory systems used to select spatial targets and to guide movement. Hand and joint paths of visually guided reaching movements of human subjects were compared with two non-visual conditions where only proprioception was available: (1) movements of the same subjects with blindfolds, and (2) movements by congenitally blind subjects. While hand-path curvatures were overall quite small, sighted subjects wearing a blindfold showed a statistical increase in hand-path curvature compared with their visually guided movements. Blindfolded subjects also showed greater hand-path curvature than blind subjects. These increases in hand-path curvature for blindfolded subjects did not always lead to a decrease in joint-path curvature. While there were differences between blind subjects and sighted subjects using vision for some movement directions, there was no systematic difference between these two groups. The magnitude of joint-path curvature showed much greater variation than hand-path curvature across the movement directions. We found variation in joint-path curvature to be correlated to two factors, one spatial and one geometrical. For all subject groups, joint-path curvature tended to be smaller for sagittal-plane movements than for transverse or diagonal movements. As well, we found that the magnitude of joint-path curvature was also related to the relative motion at each joint. Joint-path curvature tended to increase when movements predominantly involved changes in shoulder angle and was minimal when movements predominantly involved elbow motion. The consistently small curvatures of hand trajectory across blind and sighted subjects emphasize the powerful tendency of the motor system to generate goal-directed reaching movements with relatively straight hand trajectories, even when deprived of visual feedback from very early in life.

Adult↗

Comparison of variability of initial kinematics and endpoints of reaching movements.

The accuracy of reaching movements to memorized visual target locations is presumed to be determined largely by central planning processes before movement onset. If so, then the initial kinematics of a pointing movement should predict its endpoint. Our study examined this hypothesis by testing the correlation between peak acceleration, peak velocity, and movement amplitude and the correspondence between the respective spatial positions of these kinematic landmarks. Subjects made planar horizontal reaching movements to targets located at five different distances and along five radially arrayed directions without visual feedback during the movements. The spatial dispersion of the positions of peak acceleration, peak velocity, and endpoint all tended to form ellipses oriented along the movement trajectory. However, whereas the peaks of acceleration and velocity scaled strongly with movement amplitude for all of the movements made at the five target distances in any one direction, the correlations with movement amplitude were more modest for trajectories aimed at each target separately. Furthermore, the spatial variability in direction and extent of the distribution of positions of peak acceleration and peak velocity did not scale differently with target distance, whereas they did for endpoint distributions. Therefore, certain features of the final kinematics are evident in the early kinematics of the movements as predicted by the hypothesis that they reflect planning processes. However, endpoint distributions were not completely predetermined by the Initial kinematics. In contrast, multivariate analysis suggests that adjustments to movement duration help compensate for the variability of the initial kinematics to achieve desired movement amplitude. These compensatory adjustments do not contradict the general conclusion that the systematic patterns in the spatial variability observed in this study reflect planning processes. On the contrary, and consistent with that conclusion, our results provide further evidence that direction and extent of reaching movements are planned and determined in parallel over time.

Adult↗

Pointing in 3D space to remembered targets. II. Effects of movement speed toward kinesthetically defined targets.

The accuracy of visually guided pointing movements decreases with speed. We have shown that for movements to a visually defined remembered target, the variability of the final arm endpoint position does not depend on movement speed. We put forward a hypothesis that this observation can be explained by suggesting that movements directed at remembered targets are produced without ongoing corrections. In the present study, this hypothesis was tested for pointing movements in 3D space to kinesthetically defined remembered targets. Passive versus active acquisition of kinesthetic information was contrasted. Pointing errors, movement kinematics, and joint-angle coordination were analyzed. The movements were performed at a slow speed (average peak tangential velocity of about 1.2 m/s) and at a fast speed (2.7 m/s). No visual feedback was allowed during the target presentation or the movement. Variability in the final position of the arm endpoint did not increase with speed in either the active or the passive condition. Variability in the final values of the arm-orientation angles determining the position of the forearm and of the upper arm in space was also speed invariant. This invariance occurred despite the fact that angular velocities increased by a factor of two for all the angles involved. The speed-invariant variability supports the hypothesis that there is an absence of ongoing corrections for movements to remembered targets: in the case of a slower movement, where there is more time for movement correction, the final arm endpoint variability did not decrease. In contrast to variability in the final endpoint position, the variability in the peak tangential acceleration increased significantly with movement speed. This may imply that the nervous system adopts one of two strategies: either the final endpoint position is not encoded in terms of muscle torques or there is a special on-line mechanism that adjusts movement deceleration according to the muscle-torque variability at the initial stage of the movement. The final endpoint position was on average farther from the shoulder than the target. Constant radial-distance errors were speed dependent in both the active and the passive conditions. In the fast speed conditions, the radial distance overshoots of the targets increased. This increase in radial-distance overshoot with movement speed can be explained by the hypothesis that the final arm position is not predetermined in these experimental conditions, but is defined during the movement by a feedforward or feedback mechanism with an internal delay.

Acceleration↗

Consequences of altered cerebellar input for the cortical regulation of motor coordination, as reflected in EEG potentials.

The cerebellum is certainly involved in fine coordination of movements, but has no efferences of its own to the muscles. Thus, it can exert its influence only via other cerebral areas that have those efferences. This study investigated in patients with cerebellar atrophy how cortical motor areas are affected by dysfunction of the cerebellum. The main question was whether the patients' slow cortical electroencephalogram (EEG) potentials during key-press preparation and execution would be generally altered or would be specifically altered when fine coordination was needed. In the coordination task, right- and left-hand keys had to be pressed simultaneously with different forces, under visual feedback. Control tasks were to press with both hands equally or with one hand only. The patients indeed had a performance deficit in the coordination task. Their cortical EEG potentials were already drastically reduced in the simple tasks, but were enhanced by the same amount as in healthy subjects when more coordination was needed. These results suggest that the cerebellum is not exclusively active in fine coordination, but is generally involved in any kind of preparatory and executive activity, whereas the motor cortex becomes more active with fine coordination. The role of the cerebellum might be to provide the motor cortex with information needed for coordinating movements. In cerebellar atrophy, this altered input may be sufficient for the motor cortex in controlling simple tasks, but not for complex ones.

Adult↗

Grip force dynamics in the approach to a collision.

This experiment investigated the prediction of load force (LF) in impulsive collisions inferred from anticipatory adjustments of grip force (GF) used to stabilise a hand-held object. Subjects used a precision grip to hold the object between thumb and index finger of their right hand and used the arm either: (1) to move the object to produce a collision by hitting the lower end of a pendulum, causing it to swing to one of three target angles, or (2) to hold the object still while receiving a collision produced by the experimenter releasing the pendulum from one of three angles. Visual feedback of the pendulum's trajectory was available in the production task only. In all conditions, subjects increased GF in advance of the collision. In receiving the collision without advance information, subjects set GF levels to the mid-range of the experienced forces. When subjects possessed knowledge about the maximum angle of pendulum swing - either because they were going to produce it or because they were verbally informed - magnitude of the anticipatory-GF magnitude response was scaled to the predicted LF magnitude. Furthermore, GF was scaled to LF with a higher gain when producing compared to receiving the collision. This suggests that updating forward models through a semantic route is not as powerful as when the updating is achieved through the more direct route of dynamic exploration.

Adolescent↗

Viewer-centered and body-centered frames of reference in direct visuomotor transformations.

It has been hypothesized that the end-point position of reaching may be specified in an egocentric frame of reference. In most previous studies, however, reaching was toward a memorized target, rather than an actual target. Thus, the role played by sensorimotor transformation could not be disassociated from the role played by storage in short-term memory. In the present study the direct process of sensorimotor transformation was investigated in reaching toward continuously visible targets that need not be stored in memory. A virtual reality system was used to present visual targets in different three-dimensional (3D) locations in two different tasks, one with visual feedback of the hand and arm position (Seen Hand) and the other without such feedback (Unseen Hand). In the Seen Hand task, the axes of maximum variability and of maximum contraction converge toward the mid-point between the eyes. In the Unseen Hand task only the maximum contraction correlates with the sight-line and the axes of maximum variability are not viewer-centered but rotate anti-clockwise around the body and the effector arm during the move from the right to the left workspace. The bulk of findings from these and previous experiments support the hypothesis of a two-stage process, with a gradual transformation from viewer-centered to body-centered and arm-centered coordinates. Retinal, extra-retinal and arm-related signals appear to be progressively combined in superior and inferior parietal areas, giving rise to egocentric representations of the end-point position of reaching.

Adult↗

Adaptive changes in smooth pursuit eye movements induced by cross-axis pursuit-vestibular interaction training in monkeys.

The smooth pursuit system interacts with the vestibular system to maintain the accuracy of eye movements in space. To understand neural mechanisms of short-term modifications of the vestibulo-ocular reflex (VOR) induced by pursuit-vestibular interactions, we used a cross-axis procedure in trained monkeys. We showed earlier that pursuit training in the plane orthogonal to the rotation plane induces adaptive cross-axis VOR in complete darkness. To further study the properties of adaptive responses, we examined here the initial eye movements during tracking of a target while being rotated with a trapezoidal waveform (peak velocity 30 or 40 degrees/s). Subjects were head-stabilized Japanese monkeys that were rewarded for accurate pursuit. Whole body rotation was applied either in the yaw or pitch plane while presenting a target moving in-phase with the chair with the same trajectory but in the orthogonal plane. Eye movements induced by equivalent chair rotation with or without the target were examined before and after training. Before training, chair rotation alone resulted only in the collinear VOR, and smooth eye movement-tracking of orthogonal target motion during rotation had a normal smooth pursuit latency (ca 100 ms). With training, the latency of orthogonal smooth tracking eye movements shortened, and the mean latency after 1 h of training was 42 ms with a mean gain, at 100 ms after stimulus onset, of 0.4. The cross-axis VOR induced by chair rotation in complete darkness had identical latencies with the orthogonal smooth tracking eye movements, but its gains were <0.2. After cross-axis pursuit training, target movement alone without chair rotation induced smooth pursuit eye movements with latencies ca 100 ms. Pursuit training alone for 1 h using the same trajectory but without chair rotation did not result in any clear change in pursuit latency (ca 100 ms) or initial eye velocity. When a new target velocity was presented during identical chair rotation after training, eye velocity was correspondingly modulated by just 80 ms after rotation onset, which was shorter than the expected latency of pursuit (ca 100 ms). These results indicate that adaptive changes were induced in the smooth pursuit system by pursuit-vestibular interaction training. We suggest that this training facilitates the response of pursuit-related neurons in the cortical smooth pursuit pathways to vestibular inputs in the orthogonal plane, thus enabling smooth eye movements to be executed with shorter latencies and larger eye velocities than in normal smooth pursuit driven only by visual feedback.

Adaptation, Physiological↗