Smooth Pursuit Eye Movements In Monkeys Research Articles

Modulation of Complex-Spike Duration and Probability during Cerebellar Motor Learning in Visually Guided Smooth-Pursuit Eye Movements of Monkeys.

Activation of an inferior olivary neuron powerfully excites Purkinje cells via its climbing fiber input and triggers a characteristic high-frequency burst, known as the complex spike (CS). The theory of cerebellar learning postulates that the CS induces long-lasting depression of the strength of synapses from active parallel fibers onto Purkinje cells, and that synaptic depression leads to changes in behavior. Prior reports showed that a CS on one learning trial is linked to a properly timed depression of simple spikes on the subsequent trial, as well as a learned change in pursuit eye movement. Further, the duration of a CS is a graded instruction for single-trial plasticity and behavioral learning. We now show across multiple learning paradigms that both the probability and duration of CS responses are correlated with the magnitudes of neural and behavioral learning in awake behaving monkeys. When the direction of the instruction for learning repeatedly was in the same direction or alternated directions, the duration and probability of CS responses decreased over a learning block along with the magnitude of trial-over-trial neural learning. When the direction of the instruction was randomized, CS duration, CS probability, and neural and behavioral learning remained stable across time. In contrast to depression, potentiation of simple-spike firing rate for ON-direction learning instructions follows a longer time course and plays a larger role as depression wanes. Computational analysis provides a model that accounts fully for the detailed statistics of a complex set of data.

Learned Timing of Motor Behavior in the Smooth Eye Movement Region of the Frontal Eye Fields

Proper timing is a critical aspect of motor learning. We report a relationship between a representation of time and an expression of learned timing in neurons in the smooth eye movement region of the frontal eye fields (FEF(SEM)). During prelearning pursuit of target motion at a constant velocity, each FEF(SEM) neuron is most active at a distinct time relative to the onset of pursuit tracking. In response to an instructive change in target direction, a neuron expresses the most learning when the instruction occurs near the time of its maximal participation in prelearning pursuit. Different neurons are most active, and undergo the most learning, at distinct times during pursuit. We suggest that the representation of time in the FEF(SEM) drives learning that is temporally linked to an instructive change in target motion, and that this may be a general function of motor areas of the cortex.

Precision of speed discrimination and smooth pursuit eye movements

Several studies have shown that the precision of smooth pursuit eye speed can match perceptual speed discrimination thresholds during the steady-state phase of pursuit [Kowler, E., & McKee, S. (1987). Sensitivity of smooth eye movement to small differences in target velocity. Vision Research, 27, 993–1015; Gegenfurtner, K., Xing, D., Scott, B., & Hawken, M. (2003). A comparison of pursuit eye movement and perceptual performance in speed discrimination. Journal of Vision, 3, 865–876]. Recently, Osborne et al. [Osborne, L. C., Lisberger, S. G., & Bialek, W. (2005). A sensory source for motor variation. Nature, 437, 412–416; Osborne, L. C., Hohl, S. S., Bialek, W., & Lisberger S. G. (2007). Time course of precision in smooth-pursuit eye movements of monkeys. Journal of Neuroscience, 27, 2987–2998] claimed that pursuit precision during the initiation phase of pursuit also matches the sensory variability, implying that there is no motor noise added during pursuit initiation. However, these results were derived from a comparison of monkey pursuit data to human perceptual data from the literature, which were obtained with different stimuli. To directly compare precision for perception and pursuit, we measured pursuit and perceptual variability in the same human observers using the same stimuli. Subjects had to pursue a Gaussian blob in a step-ramp paradigm and give speed judgments on the same or in different trials. Speed discrimination thresholds were determined for different presentation durations. The analysis of pursuit precision was performed for short intervals containing the initiation period only and also for longer intervals including steady-state pursuit. In agreement with published studies, we found that the Weber fractions for psychophysical speed discrimination were fairly constant for different presentation durations, even for the shortest presentation duration of 150ms. Pursuit variability was 3–4 times as high for the analysis interval (300ms) containing the open-loop phase only. For pursuit analysis intervals of 400–500ms, pursuit variability approached perceptual variability. Our results show that, for the stimuli we used, the motor system contributes at least 50% to the total variability of smooth pursuit eye movements during the initiation phase.

Evidence for object permanence in the smooth-pursuit eye movements of monkeys.

We recorded the smooth-pursuit eye movements of monkeys in response to targets that were extinguished (blinked) for 200 ms in mid-trajectory. Eye velocity declined considerably during the target blinks, even when the blinks were completely predictable in time and space. Eye velocity declined whether blinks were presented during steady-state pursuit of a constant-velocity target, during initiation of pursuit before target velocity was reached, or during eye accelerations induced by a change in target velocity. When a physical occluder covered the trajectory of the target during blinks, creating the impression that the target moved behind it, the decline in eye velocity was reduced or abolished. If the target was occluded once the eye had reached target velocity, pursuit was only slightly poorer than normal, uninterrupted pursuit. In contrast, if the target was occluded during the initiation of pursuit, while the eye was accelerating toward target velocity, pursuit during occlusion was very different from normal pursuit. Eye velocity remained relatively stable during target occlusion, showing much less acceleration than normal pursuit and much less of a decline than was produced by a target blink. Anticipatory or predictive eye acceleration was typically observed just prior to the reappearance of the target. Computer simulations show that these results are best understood by assuming that a mechanism of eye-velocity memory remains engaged during target occlusion but is disengaged during target blinks.

Activation and inactivation of rostral superior colliculus neurons during smooth-pursuit eye movements in monkeys.

Neurons in the intermediate and deep layers of the rostral superior colliculus (SC) of monkeys are active during attentive fixation, small saccades, and smooth-pursuit eye movements. Alterations of SC activity have been shown to alter saccades and fixation, but similar manipulations have not been shown to influence smooth-pursuit eye movements. Therefore we both activated (electrical stimulation) and inactivated (reversible chemical injection) rostral SC neurons to establish a causal role for the activity of these neurons in smooth pursuit. First, we stimulated the rostral SC during pursuit initiation as well as pursuit maintenance. For pursuit initiation, stimulation of the rostral SC suppressed pursuit to ipsiversive moving targets primarily and had modest effects on contraversive pursuit. The effect of stimulation on pursuit varied with the location of the stimulation with the most rostral sites producing the most effective inhibition of ipsiversive pursuit. Stimulation was more effective on higher pursuit speeds than on lower and did not evoke smooth-pursuit eye movements during fixation. As with the effects on pursuit initiation, ipsiversive maintained pursuit was suppressed, whereas contraversive pursuit was less affected. The stimulation effect on smooth pursuit did not result from a generalized inhibition because the suppression of smooth pursuit was greater than the suppression of smooth eye movements evoked by head rotations (vestibular-ocular reflex). Nor was the stimulation effect due to the activation of superficial layer visual neurons rather than the intermediate layers of the SC because stimulation of the superficial layers produced effects opposite to those found with intermediate layer stimulation. Second, we inactivated the rostral SC with muscimol and found that contraversive pursuit initiation was reduced and ipsiversive pursuit was increased slightly, changes that were opposite to those resulting from stimulation. The results of both the stimulation and the muscimol injection experiments on pursuit are consistent with the effects of these activation and inactivation experiments on saccades, and the effects on pursuit are consistent with the hypothesis that the SC provides a position signal that is used by the smooth-pursuit eye-movement system.

Visual responses of Purkinje cells in the cerebellar flocculus during smooth-pursuit eye movements in monkeys. I. Simple spikes

1. We have identified a visually driven output from the flocculus of the monkey by studying the simple-spike responses of Purkinje cells (P-cells) during the initiation of smooth-pursuit eye movements. We report on two groups of P-cells that appear to be the horizontal and vertical gaze-velocity P-cells (GVP-cells) studied previously during periodic target and head motion. 2. During pursuit of periodic target motion, one group of P-cells prefers downward motion (down GVP-cells), and the other prefers motion toward the side of recording (ipsi GVP-cells). The two groups have mean directional preferences that are nearly orthogonal, but their responses during pursuit of sinusoidal target motion and sinusoidal vestibular stimulation are in other respects quantitatively similar. 3. During the initiation of pursuit to step-ramp target motion, GVP-cells show a large transient change in simple-spike firing rate followed by a sustained change in firing that persists during steady-state pursuit. 4. The transient response is directionally selective, so that GVP-cells show a pulse of simple spikes for pursuit in the ON-direction and a dip in simple-spike firing for pursuit in the OFF-direction. The amplitude of the transient response is too large to be explained by the sensitivity of GVP-cells to eye velocity measured during pursuit of sinusoidal target motion. 5. To test whether the transient change in simple-spike firing was related to a visual input or to an eye-acceleration input to the flocculus, we recorded the firing of ipsi GVP-cells during a rapid eye acceleration caused by a transient vestibular stimulus in darkness. Most GVP-cells showed little or no transient response under these conditions, even though eye acceleration was greater than during the initiation of pursuit. We conclude that the transient response at the initiation of pursuit is probably caused by visual mossy-fiber inputs to the flocculus. 6. The sustained change in simple-spike firing is also directionally selective, with large increases in simple-spike firing for pursuit in the ON-direction and smaller decreases for pursuit in the OFF-direction. For pursuit in the ON-direction, the amplitude of the sustained response is well predicted by the sensitivity of GVP-cells to eye velocity measured during pursuit of sinusoidal target motion. 7. To determine whether the sustained response was driven by visual inputs, we recorded simple-spike firing when image motion was prevented by electronically stabilizing the target image on the fovea during steady-state pursuit.(ABSTRACT TRUNCATED AT 400 WORDS)

Velocity prediction in corrective saccades during smooth-pursuit eye movements in monkey

It has been noted in a variety of studies in both humans and monkeys that saccades made during smooth pursuit eye movements are usually quite accurate. Since saccades are known to be planned on the basis of neuronal information existing at some interval of time before the actual onset of the movement, it is generally accepted that some sort of prediction or use of visual motion velocity is combined with static position error in the execution of these saccades to moving targets. However, statistical treatment of this response in humans has provided evidence for alternative mechanisms, including a strategy of saccading ahead in the direction of target motion without any incorporation of actual speed information about target motion in the response. We reinvestigated this question quantitatively in the monkey on a large data base of saccades. We found evidence that supports the hypothesis that information about target speed per se is used in this species in the production of saccades to moving targets. Multiple linear regression analysis supported the hypothesis that information about the position error and the target velocity that exists at about 100 ms prior to the saccade onset are both required to provide a statistical explanation of saccade size during pursuit eye movements under the conditions of our experiments.

Visual responses of Purkinje cells in the cerebellar flocculus during smooth-pursuit eye movements in monkeys. II. Complex spikes

1. We report the complex-spike responses of two groups of Purkinje cells (P-cells). The cell were classified according to their simple-spike firing during smooth eye movements evoked by visual and vestibular stimuli with the use of established criteria (Lisberger and Fuchs 1978; Stone and Lisberger 1990). During pursuit with the head fixed, ipsi gaze-velocity P-cells (GVP-cells) showed increased simple-spike firing when gaze moved toward the side of the recording, whereas down GVP-cells showed increased simple-spike firing when gaze moved downward. 2. During pursuit of sinusoidal target motion, the complex-spike firing rate was modulated out-of-phase with the simple-spike firing rate. Ipsi GVP-cells showed increased complex-spike firing during pursuit away from the side of the recording, and down GVP-cells showed increased complex-spike firing during upward pursuit. The strength of the complex-spike response increased as a function of the frequency of sinusoidal target motion. 3. GVP-cells showed directionally selective complex-spike responses during the initiation of pursuit to ramp target motion. Ipsi GVP-cells had increased complex-spike firing 100 ms after the onset of contralaterally directed target motion and decreased complex-spike activity after the onset of ipsilaterally directed target motion. Down GVP-cells had increased complex-spike firing 100 ms after the onset of upward target motion and decreased firing after the onset of downward target motion. As during sinusoidal target motion, each cell's simple- and complex-spike responses had the opposite directional preferences. 4. When the monkeys fixated a stationary target during a transient vestibular stimulus, the retinal slip caused by the 14-ms latency of the vestibuloocular reflex (VOR) affected the complex-spike firing rate. For ipsi GVP-cells, ipsilateral head motion caused transient contralateral image motion and an increase in complex-spike firing. The same vestibular stimulus in darkness caused an almost identical eye movement but had no effect on complex-spike firing. We conclude that complex spikes in ipsi GVP-cells are driven by contralaterally directed image motion. 5. To determine the events surrounding complex-spike firing during pursuit, we triggered averages of eye and target velocity on the occurrence of complex spikes during pursuit of sine-wave target motion. The averages revealed a transient pulse of retinal image motion that peaked approximately 100 ms before the complex spike. We conclude that complex spikes during steady-state pursuit are driven by the retinal slip associated with imperfect pursuit.(ABSTRACT TRUNCATED AT 400 WORDS)

Topographic and directional organization of visual motion inputs for the initiation of horizontal and vertical smooth-pursuit eye movements in monkeys.

1. The goal of our study was to determine the properties of the visual inputs for pursuit eye movements. In a previous study we presented horizontal target motion along the horizontal meridian and showed that targets were more effective if they moved across the center of the visual field. We have now analyzed the topographic weighting of the inputs for pursuit in greater detail, using targets that moved in all directions and across a wide area of the visual field. 2. Monkeys were rewarded for tracking targets that started at 48 positions in the visual field. The initial positions were spaced equally around 4 circles that were centered at the position of fixation and had radii of 3, 6, 9, and 12 degrees. Targets moved horizontally or vertically at 30 degrees/s. We measured the smooth eye acceleration in the first 80 ms after the initiation of pursuit, before there had been time for visual feedback to affect the position or velocity of the retinal images from the target. 3. For both horizontal and vertical target motion, there were major differences between the early and late intervals in the first 80 ms of pursuit. In the first 20 ms eye acceleration was largely independent of initial target position. In later intervals eye acceleration decreased sharply as a function of initial target eccentricity. The later intervals also showed a pronounced toward/away asymmetry such that the initiation of pursuit was more vigorous for target motion toward than for motion away from the horizontal or vertical meridian. 4. Comparison of the topographic organization of the middle temporal visual area (MT) with our data on pursuit suggests that the topography of cortical maps is smoothed when the visual signals are transmitted to the pursuit system. For example, the superior visual hemifield is underrepresented in cortical motion processing areas, but target motion in the superior and inferior visual hemifields is equally effective for the initiation of pursuit. 5. We investigated the directional organization of the visual inputs for pursuit by presenting targets that started at 6 degrees eccentric and moved in 16 different directions. Horizontal target motion always evoked larger eye accelerations than did vertical target motion. Target motion in oblique directions evoked intermediate values of eye acceleration. 6. Our data show two classes of variation in pursuit performance. First, some subjects showed ideosyncratic variations that were restricted to one hemifield or one direction of target motion. We attribute these variations to differences among subjects in the physiology of visual pathways.(ABSTRACT TRUNCATED AT 400 WORDS)

Different responses to small visual errors during initiation and maintenance of smooth-pursuit eye movements in monkeys.

1. We have investigated the role of retinal and extraretinal signals in the initiation and maintenance of smooth-pursuit eye movements in trained rhesus monkeys. Visual targets were presented in open-loop conditions by using electronic feedback of eye position to form the command for target position. This allowed us to present stimuli that were stabilized with respect to the moving eye or to provide small, precisely controlled retinal position or velocity errors. 2. Pursuit was maintained with only small decreases in eye velocity if retinal errors were eliminated by stabilizing the tracking target in front of the fovea during pursuit at 15 degrees/s. This argues that the pursuit system employs "velocity memory" to maintain pursuit. We suggest that velocity memory is effected by an extraretinal signal derived from positive feedback of eye-velocity commands. 3. Small retinal position errors caused smooth eye accelerations if imposed during pursuit, but were ineffective for initiating the transition from steady fixation to pursuit. Small retinal velocity errors were effective both for initiating pursuit from steady fixation and for altering eye velocity during pursuit. 4. Retinal position errors were effective at changing smooth eye velocity in a variety of conditions that required prior activation of the pursuit system. These include pursuit with or without a stationary background, pursuit with a background that was stabilized with respect to the eye, pursuit with combined eye and head motion (cancellation of the vestibuloocular reflex), and use of pursuit to suppress optokinetic nystagmus. Position errors were ineffective during fixation of stationary targets, even if head motion was provided to evoke the smooth eye velocity of the vestibuloocular reflex. 5. We conclude that retinal position errors are effective only after the pursuit system has been activated. It follows that pursuit initiation involves an active transition from steady fixation and that this transition is normally triggered by retinal velocity errors but not by retinal position errors.

Effect of a parafoveal microlesion made with an argon laser on smooth-pursuit eye movements of monkeys

The significance of the parafoveal region in processing information about target velocity to initiate ocular pursuit was evaluated by making a small paracentral scotoma in monkeys trained to pursue a slowly moving target. In the experimental paradigms in which the image had to cross the scotoma, the small retinal lesion (>2°) gave a direct effect upon the ability of monkeys to pursue the target motion. The abnormal pursuit was characterized by a marked reduction of eye velocity. Evaluated from the initial portion of the pursuit immediately following the first corrective saccade, the eye velocity was as low as 50 to 60% of the target velocity. The abnormality was more pronounced in slow pursuit (15 to 20°/s) than in fast pursuit (25°/s). The data indicated that the small retinal region at the boundary of the macula plays an important role in sampling target velocity during the initial part of smooth-pursuit eye movement.