Enhancement of the vestibulo-ocular reflex by prior eye movements.

We investigated the effect of visually mediated eye movements made before velocity-step horizontal head rotations in eleven normal human subjects. When subjects viewed a stationary target before and during head rotation, gaze velocity was initially perturbed by approximately 20% of head velocity; gaze velocity subsequently declined to zero within approximately 300 ms of the stimulus onset. We used a curve-fitting procedure to estimate the dynamic course of the gain throughout the compensatory response to head rotation. This analysis indicated that the median initial gain of compensatory eye movements (mainly because of the vestibulo-ocular reflex, VOR) was 0. 8 and subsequently increased to 1.0 after a median interval of 320 ms. When subjects attempted to fixate the remembered location of the target in darkness, the initial perturbation of gaze was similar to during fixation of a visible target (median initial VOR gain 0.8); however, the period during which the gain increased toward 1.0 was >10 times longer than that during visual fixation. When subjects performed horizontal smooth-pursuit eye movements that ended (i.e., 0 gaze velocity) just before the head rotation, the gaze velocity perturbation at the onset of head rotation was absent or small. The initial gain of the VOR had been significantly increased by the prior pursuit movements for all subjects (P < 0.05; mean increase of 11%). In four subjects, we determined that horizontal saccades and smooth tracking of a head-fixed target (VOR cancellation with eye stationary in the orbit) also increased the initial VOR gain (by a mean of 13%) during subsequent head rotations. However, after vertical saccades or smooth pursuit, the initial gaze perturbation caused by a horizontal head rotation was similar to that which occurred after fixation of a stationary target. We conclude that the initial gain of the VOR during a sudden horizontal head rotation is increased by prior horizontal, but not vertical, visually mediated gaze shifts. We postulate that this "priming" effect of a prior gaze shift on the gain of the VOR occurs at the level of the velocity inputs to the neural integrator subserving horizontal eye movements, where gaze-shifting commands and vestibular signals converge.     

Eye movements during combined pursuit, optokinetic and vestibular stimulation in macaque monkey

 During natural behaviour in a visual environment, smooth pursuit eye movements (SP) usually override the vestibular-ocular reflex (VOR) and the optokinetic reflex (OKR), which stem from head-in-space and scene-relative-to-eye motion, respectively. We investigated the interaction of SP, VOR, and OKR, which is not fully understood to date. Eye movements were recorded in two macaque monkeys while applying various combinations of smooth eye pursuit, vestibular and optokinetic stimuli (sinusoidal horizontal rotations of visual target, chair and optokinetic pattern, respectively, at 0.025, 0.05, 0.1, 0.2, 0.4, and 0.8 Hz, corresponding to peak stimulus velocities of 1.25–40°/s for a standard stimulus of ±8°). Slow eye responses were analysed in terms of gain and phase. During SP at mid-frequencies, the eyes were almost perfectly on target (gain 0.98 at 0.1 Hz), independently of a concurrent vestibular or optokinetic stimulus. Pursuit gain at lower frequencies, although being almost ideal (0.98 at 0.025 Hz with pursuit-only stimulation), became modified by the optokinetic input (gain increase above unity when optokinetic stimulus had the same direction as target, decrease with opposite direction). At higher stimulus frequencies, pursuit gain decreased (down to 0.69 at 0.8 Hz), and the pursuit response became modified by vestibular input (gain increase during functionally synergistic combinations, decrease in antagonistic combinations).Thus, the pursuit system in monkey dominates during SP-OKR-VOR interaction, but it does so effectively only in the mid-frequency range. The results can be described in the form of a simple dynamic model in which it is assumed that the three systems interact by linear summation. In the model SP and OKR dominate VOR in the low- to mid-frequency/velocity range, because they represent closed loop systems with high internal gain values (>>1) at these frequencies/velocities, whereas the VOR represents an open loop system with about unity-gain (up to very high frequencies). SP dominance over OKR is obtained by allowing an ’attentional/volitional’ mechanism to boost SP gain and a predictive mechanism to improve its dynamics. Received: 27 November 1998 / Accepted: 8 March 1999     

Signals that modulate gain control for smooth pursuit eye movements in monkeys

The generation of primate smooth pursuit eye movements involves two processes. One process transforms the direction and speed of target motion into a motor command and the other regulates the strength, or "gain," of the visual-motor transformation. We have conducted a behavioral analysis to identify the signals that modulate the internal gain of pursuit. To test whether the modulatory signals are related to eye velocity in the orbit or in the world (gaze velocity), we used brief perturbations of target motion to probe the gain of pursuit during tracking conditions that used head rotation to dissociate eye and gaze velocity. We found that the responses to perturbations varied primarily as a function of gaze velocity. To further understand the gaze velocity signals that control internal pursuit gain, we used adaptive modification of the gain of the vestibulo-ocular reflex (VOR) to dissociate physical gaze velocity from the component of gaze velocity that is driven by visual inputs. After VOR adaptation, perturbation responses were altered; the smallest perturbation responses now occurred during tracking conditions that required nonzero physical gaze velocity. However, perturbation responses during tracking conditions that mimicked the modified VOR were still enhanced relative to those obtained during fixation. We conclude that the signals that modulate the internal gain of pursuit are modified by VOR adaptation so that they are rendered intermediate between physical and visually driven gaze velocity. Similar changes in the gaze velocity signal have been reported in the cerebellar floccular complex following adaptive modification of the VOR and could be present in other brain areas that carry putative gaze velocity signals.     

Latency of vestibular responses of pursuit neurons in the caudal frontal eye fields to whole body rotation

The smooth pursuit system and the vestibular system interact to keep the retinal target image on the fovea by matching the eye velocity in space to target velocity during head and/or whole body movement. The caudal part of the frontal eye fields (FEF) in the fundus of the arcuate sulcus contains pursuit-related neurons and the majority of them respond to vestibular stimulation induced by whole body movement. To understand the role of FEF pursuit neurons in the interaction of vestibular and pursuit signals, we examined the latency and time course of discharge modulation to horizontal whole body rotation during different vestibular task conditions in head-stabilized monkeys. Pursuit neurons with horizontal preferred directions were selected, and they were classified either as gaze-velocity neurons or eye/head-velocity neurons based on the previous criteria. Responses of these neurons to whole body step-rotation at 20 degrees/s were examined during cancellation of the vestibulo-ocular reflex (VOR), VOR x1, and during chair steps in complete darkness without a target (VORd). The majority of pursuit neurons tested (approximately 70%) responded during VORd with latencies <80 ms. These initial responses were basically similar in the three vestibular task conditions. The shortest latency was 20 ms and the modal value was 24 ms. These responses were also similar between gaze-velocity neurons and eye/head-velocity neurons, indicating that the initial responses (<80 ms) were vestibular responses induced by semicircular canal inputs. During VOR cancellation and x1, discharge of the two groups of neurons diverged at approximately 90 ms following the onset of chair rotation, consistent with the latencies associated with smooth pursuit. The shortest latency to the onset of target motion during smooth pursuit was 80 ms and the modal value was 95 ms. The time course of discharge rate difference of the two groups of neurons between VOR cancellation and x1 was predicted by the discharge modulation associated with smooth pursuit. These results provide further support for the involvement of the caudal FEF in integration of vestibular inputs and pursuit signals.     

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°/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. Electronic Publication     

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)     

Anticipatory VOR suppression induced by visual and nonvisual stimuli in humans

We compared the predictive behavior of smooth pursuit (SP) and suppression of the vestibuloocular reflex (VOR) in humans by examining anticipatory smooth eye movements, a phenomenon that arises after repeated presentations of sudden target movement preceded by an auditory warning cue. We investigated whether anticipatory smooth eye movements also occur prior to cued head motion, particularly when subjects expect interaction between the VOR and either real or imagined head-fixed targets. Subjects were presented with horizontal motion stimuli consisting of a visual target alone (SP), head motion in darkness (VOR), or head motion in the presence of a real or imagined head-fixed target (HFT and IHFT, respectively). Stimulus sequences were delivered as single cycles of a velocity sinusoid (frequency: 0.5 or 1.0 Hz) that were either cued (a sound cue 400 ms earlier) or noncued. For SP, anticipatory smooth eye movements developed over repeated trials in the cued, but not the noncued, condition. In the VOR condition, no such anticipatory eye movements were observed even when cued. In contrast, anticipatory responses were observed under cued, but not noncued, HFT and IHFT conditions, as for SP. Anticipatory HFT responses increased in proportion to the velocity of preceding stimuli. In general, anticipatory gaze responses were similar in cued SP, HFT, and IHFT conditions and were appropriate for expected target motion in space. Anticipatory responses may represent the output of a central mechanism for smooth-eye-movement generation that operates during predictive SP as well as VOR modulations that are linked with SP even in the absence of real visual targets.     

Vestibuloocular reflex inhibition and gaze saccade control characteristics during eye-head orientation in humans

1. In natural conditions, gaze (i.e., eye + head) orientation is a complex behavior involving simultaneously the eye and head motor systems. Thus one of the key problems of gaze control is whether or not the vestibuloocular reflex (VOR) elicited by head rotation and saccadic eye movement linearly add. 2. Kinematics of human gaze saccades within the oculomotor range (OMR) were quantified under different conditions of head motion. Saccades were visually triggered while the head was fixed or passively moving at a constant velocity (200 deg/s) either in the same direction as, or opposite to, the saccade. Active eye-head coordination was also studied in a session in which subjects were trained to actively rotate their head at a nearly constant velocity during the saccade and, in another session, during natural gaze responses. 3. When the head was passively rotated toward the visual target, both maximum and mean gaze velocities increased with respect to control responses with the head fixed; these effects increased with gaze saccade amplitude. In addition, saccade duration was reduced so that corresponding gaze accuracy, although poorer than for control responses, was not dramatically affected by head motion. 4. The same effects on gaze velocity were present during active head motion when a constant head velocity was maintained throughout saccade duration, and gaze saccades were as accurate as with the head fixed. 5. During natural gaze responses, an increased gaze velocity and a decreased saccade duration with respect to control responses became significant only for gaze displacement larger than 30 degrees, due to the negligible contribution of head motion for smaller responses. 6. When the head was passively rotated in the opposite direction to target step, gaze saccades were slower than those obtained with the head fixed; but their average accuracy was still maintained. 7. These results confirm a VOR inhibition during saccadic eye movements within the OMR. This inhibition, present in all 16 subjects studied, ranged from 40 to 96% (for a 40 degree target step) between subjects and increased almost linearly with target step amplitude. Furthermore, the systematic difference between instantaneous VOR gain estimated at the time of maximum gaze velocity and mean VOR gain estimated over the whole saccadic duration indicates a decay of VOR inhibition during the ongoing saccade. 8. A simplified model is proposed with a varying VOR inhibition during the saccade. It suggests that VOR inhibition is not directly controlled by the saccadic pulse generator.(ABSTRACT TRUNCATED AT 400 WORDS)     

The human vertical vestibulo-ocular reflex during combined linear and angular acceleration with near-target fixation

The purpose of this study was to examine the effect of fixation target distance on the human vestibuloocular reflex (VOR) during eccentric rotation in pitch. Such rotation induces both angular and linear acceleration. Eight normal subjects viewed earth-fixed targets that were either remote or near to the eyes during wholebody rotation about an earth-horizontal axis that was either oculocentric or 15 cm posterior (eccentric) to the eyes. Eye and head movements were recorded using magnetic search coils. Using a servomotor-driven chair, passive whole-body rotations were delivered as trains of single-frequency sinusoids at frequencies from 0.8 to 2.0 Hz and as pseudorandom impulses of acceleration. In the light, the visually enhanced VOR (VVOR) was recorded while subjects were asked to fixate targets at one of several distances. In darkness, subjects were asked to remember targets that had been viewed immediately prior to the rotation. In order to eliminate slip of the retinal image of a near target when the axis of rotation of the head is posterior to the eyes, the ideal gain (compensatory eye velocity divided by head velocity) of the VVOR and VOR must exceed 1.0. Both the VOR and VVOR were found to have significantly enhanced gains during sinusoidal and pseudorandom impulses of rotation (P<0.05). Enhancement of VVOR gain was greatest at low frequencies of head rotation and decreased with increasing frequency. However, enhanced VOR gain only slightly exceeded 1.0, and VVOR gain enhancement was significantly lower than the expected ideal values for the stimulus conditions employed (P<0.05). During oculocentric rotations with near targets, both the VOR and VVOR tended to exhibit small phase leads that increased with rotational frequency. In contrast, during eccentric rotations with near targets, there were small phase lags that increased with frequency. Visual tracking contributes during ocular compensatory responses to sustained head rotation, although the latency of visual tracking reflexes exceeds 100 ms. In order to study initial vestibular responses prior to modification by visual tracking, we presented impulses of head acceleration in pseudorandom sequence of initial positions and directions, and evaluated the ocular response in the epoch from 25 to 80 ms after movement onset. As with sinusoidal rotations, pseudorandom eccentric head rotation in the presence of a near, earth-fixed target was associated with enhancement of VVOR and VOR gains in the interval from 25 to 80 ms from movement onset. Despite the inability of visual tracking to contribute to these responses, VVOR gain significantly exceeded VOR gain for pseudorandom accelerations. This gain enhancement indicates that target distance and linear motion of the head are considered by the human ocular motor system in adjustment of performance of the early VOR, prior to a contribution by visual following reflexes. Vergence was appropriate to target distance during all VVOR rotations, but varied during VOR rotations with remembered targets. For the 3-m target distance, vergence during the VOR was stable over each entire trial but slightly exceeded the ideal value. For the 0.1-m near target, instantaneous vergence during the VOR typically declined gradually in a manner not corresponding to the time course of instantaneous VOR gain change; mean vergence over entire trials ranged from 60 to 90% of ideal, corresponding to target distances for which ideal gain would be much higher than actually observed. These findings suggest a dissociation between vergence and VOR gain during eccentric rotation with near targets in the frequency range from 0.8 to 2.0 Hz.     

Vestibular catch-up saccades in labyrinthine deficiency

During rapid head rotations, saccades ipsiversive with compensatory vestibulo-ocular reflex (VOR) slow phases may augment the deficient VOR and assist gaze stabilization in space. The present experiments compared these vestibular catch-up saccades (VCUSs) with visually and memory-guided saccades. To characterize VCUSs and their relationship to deficiency of the initial VOR, we delivered random, whole-body transients of 1000 and 2800 degrees/s2 peak yaw acceleration around four different eccentric vertical axes in eight unilaterally and one bilaterally vestibulopathic subjects, as well as nine age-matched normal subjects. Eye and head movements were sampled at 1200 Hz using magnetic search coils. Subjects fixed targets at either 500 or 15 cm distance immediately before unpredictable onset of rotation in darkness. Under all testing conditions, normal subjects exhibited only compensatory vestibular slow phases and occasional anticompensatory quick phases. This behavior was also typical of unilaterally vestibulopathic subjects rotated contralesionally. When rotated ipsilesionally, however, vestibulopathic subjects had deficient slow-phase VOR gain with prolonged latency, and six of the nine exhibited saccadic movements in the compensatory direction (VCUSs). Higher head accelerations preferentially evoked VCUSs, but there were no preferred combinations of target distances and eccentric rotation axes. Peak velocities and durations of VCUSs increased with saccade amplitude. The latency distribution for VCUSs peaked around 70 ms, substantially shorter than reported for either visually guided express saccades or vestibular memory contingent saccades. The latency of each VCUS was highly correlated with the gaze error prior to that VCUS. The amplitude of VCUSs was calibrated to gaze position error, such that VCUSs reduced gaze error by an average of 37%. Thus when VOR slow-phase responses cannot compensate fully for head rotation, vestibular gaze position error can nevertheless calibrate the programming of VCUSs to augment the deficient VOR, much like catch-up saccades substitute for deficient visual pursuit.     

Voluntary modulation of the vestibuloocular reflex in humans and its relation to smooth pursuit

Summary Human subjects attempted to modify their vestibuloocular reflex (VOR) in the dark by fixating imagined targets while experiencing predictable (SIN) sinusoidal (0.01–2.5 Hz) and unpredictable (SSN) sum of sines rotational stimuli (0.02–1.9 Hz). Modification was attempted under 2 instructional sets: VOR enhancement, ie tracking an imaginary earth-fixed target; VOR suppression, ie fixation of a chair fixed target. When compared to gain characteristics exhibited during the relax state with the same stimuli, subjects were able to alter VOR gain under both experimental conditions, raising it during the enhance paradigm and lowering it during the suppress paradigm. While ability to suppress the VOR was dependent on stimulus frequency, decreasing as frequency of rotation increased, subjects were equally able to modify their responses to the unpredictable and the predictable stimuli. Response phase did not change and was maintained close to 180 deg, regardless of instructional set, predictability, or frequency of stimulation for frequencies greater than 0.1 Hz. At frequencies below 0.1 Hz, a phase lead developed that was similar for all paradigms and rotational stimuli. In contrast, when subjects attempted to pursue visual targets that matched closely the velocities and frequencies of the chair rotation during predictable (SIN) and unpredictable stimulation (SSN), success was dependent on predictability of the stimulus. SSN target motion caused a significant decrease in pursuit velocity as compared to results using SIN target motion. Phase characteristics for both types of stimuli were similar, demonstrating a slight lead at lower frequencies and lagging as frequency of target oscillation increased. The results suggest that voluntary modulation of the VOR is not mediated by a neural control mechanism that is based on prediction. In addition, pursuit does not appear to contribute significantly to ability to cancel VOR. Instead, VOR modulation may be a cognitive event that involves use of a mechanism that produces simple parametric gain changes.Supported by Coleman, Hearst and Regenstein Foundation grants and National Institute of Handicapped Research grant no. G008300079     

Behavior of the position vestibular pause (PVP) interneurons of the vestibuloocular reflex during head-free gaze shifts in the monkey

Most behavioral studies indicate that the efficacy (gain) of the vestibuloocular reflex (VOR) in primates is modulated during the voluntary head movements that accompany large shifts in the direction of gaze. However, the timing and degree of this modulation is the subject of some debate. The neurophysiological substrate for this apparent gain reduction has been sought in the behavior of the type I position vestibular pause (PVP) neuron, a well-known type of interneuron in the direct VOR pathway. With the head fixed, PVPs increase their firing rates with contraversive eye position and with ipsiversive passive head rotation and also cease firing (pause) for the duration of ipsiversive saccades. During head-free ipsiversive gaze shifts, the eyes and head move in the same direction. If the vestibular signal carried by PVPs provides the primary drive for the VOR, the vestibular signal should be present during ipsiversive gaze shifts to the degree that the VOR is present. Of 25 type I PVPs recorded, 21 ceased their discharge for the entire duration of the rapid, eye-saccade component of an ipsiversive gaze shift. The resumption of activity occurred, on average, 13 ms after the end of the saccade. These results suggest that the activity of the vast majority of PVP neurons do not reflect the state of the VOR, but rather PVPs are completely eliminated from participation in the reflex during head-free gaze movements. We conclude that if any modulation of the VOR does exist, it must occur through other, probably longer-latency, pathways.     

Gaze-, eye-, and head-movement dynamics during closed- and open-loop gaze pursuit

Horizontal step-ramp stimuli were used to examine gaze-, eye-, and head-movement dynamics during head-unrestrained pursuit in two rhesus monkeys. In a first series of experiments, we characterized and compared head-restrained (HR) and -unrestrained (HU) pursuit responses to unpredictable, nonperiodic, constant velocity (20-80 degrees/s) stimuli. When the head was free to move, both monkeys used a combination of eye and head motion to initially fixate and then pursue the target. The pursuit responses (i.e., gaze responses) were highly stereotyped and nearly identical among the HR and HU conditions for a given step-ramp stimulus. In the HU condition, initial eye and initial head acceleration tended to increase as a function of target velocity but did not vary systematically with initial target eccentricity. In a second series of experiments, step-ramp stimuli (40 degrees/s) were presented, and, approximately 125 ms after pursuit onset, a constant retinal velocity error (RVE) was imposed for a duration of 300 ms. In each monkey, HR and HU gaze velocity was similarly affected by stabilizing the target with respect to the monkey's fovea (i.e., RVE = 0 degrees/s) and by moving the target with constant retinal velocity errors (i.e., RVE = +/- 10 degrees/s). In the HU condition, changes in both eye and head velocity trajectories contributed to the observed gaze velocity responses to imposed RVEs. We conclude that eye and head movements are not independently controlled during HU pursuit but rather are controlled, at least in part, by a shared upstream controller within the pursuit pathways.     

Activity of smooth pursuit-related neurons in the monkey periarcuate cortex during pursuit and passive whole-body rotation

Smooth pursuit and vestibularly induced eye movements interact to maintain the accuracy of eye movements in space (i.e., gaze). To understand the role played by the frontal eye fields in pursuit-vestibular interactions, we examined activity of 110 neurons in the periarcuate areas of head-stabilized Japanese monkeys during pursuit eye movements and passive whole-body rotation. The majority (92%) responded with the peak of their modulation near peak stimulus velocity during suppression of the vestibuloocular reflex (VOR) when the monkeys tracked a target that moved with the same amplitude and phase and in the same plane as the chair. We classified pursuit-related neurons (n = 100) as gaze- velocity if their peak modulation occurred for eye (pursuit) and head (VOR suppression) movements in the same direction; the amplitude of modulation during one less than twice that of the other; and modulation was lower during target-stationary-in-space condition (VOR x1) than during VOR suppression. In addition, we examined responses during VOR enhancement (x2) in which the target moved with equal amplitude as, but opposite direction to, the chair. Gaze-velocity neurons responded maximally for opposite directions during VOR x2 and suppression. Based on these criteria, the majority of pursuit-related neurons (66%) were classified as gaze-velocity with preferred directions uniformly distributed. Because the majority of the remaining cells (32/34) also responded during VOR suppression, they were classified as eye/head-velocity neurons. Thirteen preferred pursuit and VOR suppression in the same direction; 13 in the opposite direction, and 6 showed biphasic modulation during VOR suppression. Eye- and gaze-velocity sensitivity of the two groups of cells were similar; mean (+/- SD) was 0.53 +/- 0.30 and 0.50 +/- 0.44 spikes/s per degrees /s, respectively. Gaze-velocity (but not eye/head-velocity) neurons showed significant correlation between eye- and gaze-velocity sensitivity, and both groups maintained their responses when the tracking target was extinguished briefly. The majority of pursuit-related neurons (28/43 = about 65%) responded to chair rotation in complete darkness. When the monkeys fixated a stationary target, more than half of cells tested (21/40) discharged in proportion to the velocity of retinal motion of a second laser spot (mean velocity sensitivity = 0.20 +/- 0.16 spikes/s per degrees /s). Preferred directions of individual cells to the second spot were similar to those during pursuit. Visual responses to the second spot movement were maintained even when it was extinguished briefly. These results indicate that both retinal image- and gaze-velocity signals are carried by single periarcuate pursuit-related neurons, suggesting that these signals can provide target-velocity-in-space and gaze-velocity commands during pursuit-vestibular interactions.     

A non-visual mechanism for voluntary cancellation of the vestibulo-ocular reflex

Summary Squirrel monkeys were trained to cancel their vestibulo-ocular reflex (VOR) by fixating a visual target that was head stationary during passive vestibular stimulation. The monkeys were seated on a vestibular turntable, and their heads were restrained. A small visual target (0.2°) was projected from the vestibular turntable onto a tangent screen. The monkeys' ability to suppress their VOR by fixating a head stationary target while the turntable was moving was compared to their ability to pursue the target when it was moved in the same manner.Squirrel monkeys were better able to suppress their VOR when the turntable was moved at high velocities than they were able to pursue targets that were moving at high velocities. The gaze velocity gain during VOR cancellation began to decrease when the head velocity was above 80°/s, and was greater than 0.6 when the head velocity was above 150°/s. However, gaze velocity gain during smooth pursuit decreased significantly when the target velocity was greater than 60°/s, and was less than 0.4 when the target velocity was 150°/s or more.The latency of VOR suppression was significantly shorter than the latency of smooth pursuit while the monkey was cancelling its VOR. When an unpredictable step change in head acceleration was generated while the monkey was cancelling its VOR, the VOR evoked by the head acceleration step began to be suppressed shortly after the initiation of the step ( 30 ms). On the other hand, the latency of the smooth pursuit eye movement elicited when the visual target was accelerated in the same manner during VOR cancellation was 100 ms. The comparison between these two results suggests that the monkeys did not use visual information related to target motion to suppress their VOR at an early latency.The monkeys' ability to suppress the VOR evoked by an unexpected change in head acceleration depended on the size of the head acceleration step. The VOR evoked by unexpected step changes in head acceleration was progressively less suppressed at an early latency as the size of the acceleration step increased, and was not suppressed at an early latency when the step change in head acceleration was greater than 500°/s².During smooth pursuit eye movements, unexpected step changes in head acceleration evoked a VOR that was suppressed at an early latency ( 50 ms) if the head movement was in the same direction as the ongoing smooth pursuit eye movement. The amount of early VOR suppression increased as the pursuit eye velocity increased.We conclude that squirrel monkeys utilize a fast, non-visual mechanism for cancelling their VOR while they are fixating a visual target and their head is moving. This non-visual mechanism appears to be turned on when the head is moving and the monkey is fixating a head stationary target. The mechanism probably utilizes a voluntarily gated vestibular signal to cancel the signals in VOR pathways at the level of the extraocular motorneurons. Although the VOR cancellation mechanism is not capable of completely suppressing the VOR evoked by large unexpected changes in head acceleration, we suggest that it is capable of suppressing the VOR generated by most voluntary head movements during combined eye and head gaze pursuit and that the function of this gated VOR cancellation system is to extend the range and accuracy of eye-head tracking movements.     

Transformation of vestibular signals into motor commands in the vestibuloocular reflex pathways of monkeys

Parallel pathways mediate the rotatory vestibuloocular reflex (VOR). If the VOR undergoes adaptive modification with spectacles that change the magnification of the visual scene, signals in one neural pathway are modified, whereas those in another are not. By recording the responses of vestibular afferents and abducens neurons for vestibular oscillations at frequencies from 0.5 to 50 Hz, we have elucidated how vestibular signals are processed in the modified versus unmodified VOR pathways. For the small stimuli we used (+/- 15 degrees/s), the afferents with the most regular spontaneous discharge fired throughout the cycle of oscillation even at 50 Hz, whereas afferents with more irregular discharge showed phase locking. For all afferents, the firing rate was in phase with stimulus head velocity at low frequencies and showed progressive phase lead as frequency increased. Sensitivity to head velocity increased steadily as a function of frequency. Abducens neurons showed highly regular spontaneous discharge and very little evidence of phase locking. Their sensitivity to head velocity during the VOR was relatively flat across frequencies; firing rate lagged head velocity at low frequencies and shifted to large phase leads as stimulus frequency increased. When afferent responses were provided as inputs to a two-pathway model of the VOR, the output of the model reproduced the responses of abducens neurons if the unmodified and modified VOR pathways had frequency-dependent internal gains and included fixed time delays of 1.5 and 9 ms. The phase shifts predicted by the model provide fingerprints for identifying brain stem neurons that participate in the modified versus unmodified VOR pathways.     

Extraction of visual motion information for the control of eye and head movement during head-free pursuit

We investigated how effectively briefly presented visual motion could be assimilated and used to track future target motion with head and eyes during target disappearance. Without vision, continuation of eye and head movement is controlled by internal (extra-retinal) mechanisms, but head movement stimulates compensatory vestibulo-ocular reflex (VOR) responses that must be countermanded for gaze to remain in the direction of target motion. We used target exposures of 50-200 ms at the start of randomised step-ramp stimuli, followed by > 400 ms of target disappearance, to investigate the ability to sample target velocity and subsequently generate internally controlled responses. Subjects could appropriately grade gaze velocity to different target velocities without visual feedback, but responses were fully developed only when exposure was > 100 ms. Gaze velocities were sustained or even increased during target disappearance, especially when there was expectation of target reappearance, but they were always less than for controls, where the target was continuously visible. Gaze velocity remained in the direction of target motion throughout target extinction, implying that compensatory (VOR) responses were suppressed by internal drive mechanisms. Regression analysis revealed that the underlying compensatory response remained active, but with gain slightly less than unity (0.85), resulting in head-free gaze responses that were very similar to, but slightly greater than, head-fixed. The sampled velocity information was also used to grade head velocity, but in contrast to gaze, head velocity was similar whether the target was briefly or continuously presented, suggesting that head motion was controlled by internal mechanisms alone, without direct influence of visual feedback.     

Computational study on monkey VOR adaptation and smooth pursuit based on the parallel control-pathway theory

Much controversy remains about the site of learning and memory for vestibuloocular reflex (VOR) adaptation in spite of numerous previous studies. One possible explanation for VOR adaptation is the flocculus hypothesis, which assumes that this adaptation is caused by synaptic plasticity in the cerebellar cortex. Another hypothesis is the model proposed by Lisberger that assumes that the learning that occurs in both the cerebellar cortex and the vestibular nucleus is necessary for VOR adaptation. Lisberger's model is characterized by a strong positive feedback loop carrying eye velocity information from the vestibular nucleus to the cerebellar cortex. This structure contributes to the maintenance of a smooth pursuit driving command with zero retinal slip during the steady-state phase of smooth pursuit with gain 1 or during the target blink condition. Here, we propose an alternative hypothesis that suggests that the pursuit driving command is maintained in the medial superior temporal (MST) area based on MST firing data during target blink and during ocular following blank, and as a consequence, we assume a much smaller gain for the positive feedback from the vestibular nucleus to the cerebellar cortex. This hypothesis is equivalent to assuming that there are two parallel neural pathways for controlling VOR and smooth pursuit: a main pathway of the semicircular canals to the vestibular nucleus for VOR, and a main pathway of the MST-dorsolateral pontine nuclei (DLPN)-flocculus/ventral paraflocculus to the vestibular nucleus for smooth pursuit. First, we theoretically demonstrate that this parallel control-pathway theory can reproduce the various firing patterns of horizontal gaze velocity Purkinje cells in the flocculus/ventral paraflocculus dependent on VOR in the dark, smooth pursuit, and VOR cancellation as reported in Miles et al. at least equally as well as the gaze velocity theory, which is the basic framework of Lisberger's model. Second, computer simulations based on our hypothesis can stably reproduce neural firing data as well as behavioral data obtained in smooth pursuit, VOR cancellation, and VOR adaptation, even if only plasticity in the cerebellar cortex is assumed. Furthermore, our computer simulation model can reproduce VOR adaptation automatically based on a heterosynaptic interaction model between parallel fiber inputs and climbing fiber inputs. Our results indicate that different assumptions about the site of pursuit driving command maintenance computationally lead to different conclusions about where the learning for VOR adaptation occurs. Finally, we propose behavioral and physiological experiments capable of discriminating between these two possibilities for the site of pursuit driving command maintenance and hence for the sites of learning and memory for VOR adaptation.     

Senescence of human visual-vestibular interactions: smooth pursuit,optokinetic, and vestibular control of eye movements with aging

Natural aging entails progressive deterioration in a variety of biological systems. This study focuses on visual and vestibular influences on human eye movements as a function of aging. Eye movements were recorded (search-coil technique) during visual, vestibular, and combined stimuli in subjects across a broad range of ages (18–89 years). Two types of visual following were assessed: smooth pursuit (SP) of a small discrete target, and optokinetic (OKR) following of a large-field striped image. The vestibulo-ocular reflex (VOR) was studied during head rotation in darkness. Visualvestibular interactions were recorded during rotation in two ways: when the optokinetic scene was earth-fixed, resulting in visual enhancement of the VOR (VVOR), and when the visual image was head-fixed, allowing visual suppression of the VOR (VSVOR). Stimuli consisted of horizontal sinusoidal oscillations over the frequency range 0.025–4 Hz. Trials were analyzed to yield response gain (peak horizontal eye/stimulus velocities) and phase (asynchrony, in degrees, between eye and stimulus velocity signals). VOR gain in young subjects was greatest (near 0.9) at 2.5–4 Hz but declined steadily with decreasing frequency, while phase hovered near zero until 0.1 Hz and then developed a progressively increasing lead. Effects of advancing age were small, given the modest head velocities presented, and were most noticeable as an increase in phase lead and decline in gain at the lowest frequencies (0.1 Hz). The two forms of visual following and all conditions of visual-vestibular interactions displayed more prominent age-dependent changes. OKR and SP response characteristics (0.25–4 Hz) closely resembled each other. Gain was greatest at 0.25 Hz, while phase was near 0°. As frequency increased, gain declined while phase lag rose. However, both gain and phase lag tended to be slightly greater for OKR than for SP responses. Both SP and OKR response properties deteriorated progressively with increasing age, as witnessed by a progressive decline in gain and increase in phase lag, even at modest frequencies (e.g., 0.25–1.0 Hz). VVOR responses were generally closer to the ideal of 1.0 in gain and 0° in phase than either the VOR or visual following alone. A subtle but significant age-dependent decline in VVOR performance occurred at the lowest frequencies. VSVOR response characteristics were close to those of the VOR and VVOR at 4 Hz, where visual influences on eye movements are generally inconsequential. As frequency declined, visual suppression became more robust and gain dropped. The SP stimulus seemed surprisingly more effective than the OK scene in suppressing the VOR, but this effect is predicted by a linear model of visual-vestibular interactions. As age increased, visual influences on the VOR became progressively weaker, in concert with deterioration of visual following. The subjective sensation of circular vection (CV), a psychophysical measure of VVI, was assessed during optokinetic stimulation at 0.025 Hz. Interestingly, the likelihood and intensity of CV increased with aging, suggesting that visual inputs to the perception of self-motion are enhanced in the elderly. This may represent a form of visual compensation for age-dependent loss of vestibular self-rotation cues. In brief, the VOR, visual following, and their interactions display specific changes in response properties as a function of natural aging. The modifications may be interpreted as age-dependent deteriorations in the performance of systems underlying the control of human eye movements.     

Phase-plane analysis of gaze stabilization to high acceleration head thrusts: a continuum across normal subjects and patients with loss of vestibular function

We investigated the vestibulo-ocular reflex (VOR) during high-acceleration, yaw-axis, head rotations in 12 normals and 15 patients with vestibular loss [7 unilateral vestibular deficient (UVD) and 8 bilateral vestibular deficient (BVD)]. We analyzed gaze stabilization within a 200-ms window after head rotation began, using phase planes, which allowed simultaneous analysis of gaze velocity and gaze position. These "gaze planes" revealed critical dynamic information not easily gleaned from traditional gain measurements. We found linear relationships between peak gaze-velocity and peak gaze-position error when normalized to peak head speed and position, respectively. Values fell on a continuum, increasing from normals, to normals tested with very high acceleration (VHA = 10,000-20,000 degrees/s2), to UVD patients during rotations toward the intact side, to UVD patients during rotations toward the lesioned side, to BVD patients. We classified compensatory gaze corrections as gaze-position corrections (GPCs) or gaze-velocity error corrections (GVCs). We defined patients as better-compensated when the value of their end gaze position was low relative to peak gaze position. In the gaze plane this criterion corresponded to relatively stereotyped patterns over many rotations, and appearance of high velocity (100-400 degrees/s) GPCs in the gaze plane ending quadrant (150-200 ms after head movement onset). In less-compensated patients, and normals at VHA, more GVCs were generated, and GPCs were generated only after gaze-velocity error was minimized. These findings suggest that challenges to compensatory vestibular function can be from vestibular deficiency or novel stimuli not previously experienced. Similar patterns of challenge and compensation were observed in both patients with vestibular loss and normal subjects.