Directional asymmetry in smooth ocular tracking in the presence of visual background in young and adult primates

The smooth pursuit system moves the eyes in space accurately while compensating for visual inputs from the moving background and/or vestibular inputs during head movements. To understand the mechanisms underlying such interactions, we examined the influence of a stationary textured visual background on smooth pursuit tracking and compared the results in young and adult humans and monkeys. Six humans (three children, three adults) and six macaque monkeys (five young, one adult) were used. Human eye movements were recorded using infrared oculography and evoked by a sinusoidally moving target presented on a computer monitor. Scleral search coils were used for monkeys while they tracked a target presented on a tangent screen. The target moved in a sinusoidal or trapezoidal fashion with or without whole body rotation in the same plane. Two kinds of backgrounds, homogeneous and stationary textured, were used. Eye velocity gains (eye velocity/target velocity) were calculated in each condition to compare the influence of the textured background. Children showed asymmetric eye movements during vertical pursuit across the textured (but not the homogeneous) background; upward pursuit was severely impaired, and consisted mostly of catch-up saccades. In contrast, adults showed no asymmetry during pursuit across the different backgrounds. Monkeys behaved similarly; only slight effects were observed with the textured background in a mature monkey, whereas upward pursuit was severely impaired in young monkeys. In addition, VOR cancellation was severely impaired during upward eye and head movements, resulting in residual downward VOR in young monkeys. From these results, we conclude that the directional asymmetry observed in young primates may reflect a different neural organization of the vertical, particularly upward, pursuit system in the face of conflicting visual and vestibular inputs that can be associated with pursuit eye movements. Apparently, proper compensation matures later. Electronic Publication     

Directional asymmetry in vertical smooth-pursuit and cancellation of the vertical vestibulo-ocular reflex in juvenile monkeys

Young primates exhibit asymmetric eye movements during vertical smooth-pursuit across a textured background such that upward pursuit has low velocity and requires many catch-up saccades. The asymmetric eye movements cannot be explained by the un-suppressed optokinetic reflex resulting from background visual motion across the retina during pursuit, suggesting that the asymmetry reflects most probably, a low gain in upward eye commands (Kasahara et al. in Exp Brain Res 171:306–321, 2006). In this study, we examined (1) whether there are intrinsic differences in the upward and downward pursuit capabilities and (2) how the difficulty in upward pursuit is correlated with the ability of vertical VOR cancellation. Three juvenile macaques that had initially been trained only for horizontal (but not vertical) pursuit were trained for sinusoidal pursuit in the absence of a textured background. In 2 of the 3 macaques, there was a clear asymmetry between upward and downward pursuit gains and in the time course of initial gain increase. In the third macaque, downward pursuit gain was also low. It did not show consistent asymmetry during the initial 2 weeks of training. However, it also exhibited a significant asymmetry after 4 months of training, similar to the other two monkeys. After 6 months of training, these two monkeys (but not the third) still exhibited asymmetry. As target frequency increased in these two monkeys, mean upward eye velocity saturated at ∼15°/s, whereas horizontal and downward eye velocity increased up to ∼40°/s. During cancellation of the VOR induced by upward whole body rotation, downward eye velocity of the residual VOR increased as the stimulus frequency increased. Gain of the residual VOR during upward rotation was significantly higher than that during horizontal and downward rotation. The time course of residual VOR induced by vertical whole body step-rotation during VOR cancellation was predicted by addition of eye velocity during pursuit and VOR x1. These results support our view that the directional asymmetry reflects the difference in the organization of the cerebellar floccular region for upward and downward directions and the preeminent role of pursuit in VOR cancellation.     

Analysis of a naturally occurring asymmetry in vertical smooth pursuit eye movements in a monkey.

1. We have investigated the mechanism of a directional deficit in vertical pursuit eye movements in a monkey that was unable to match upward eye speed to target speed but that had pursuit within the normal range for downward or horizontal target motion. Except for a difference in the axis of deficient pursuit, the symptoms in this monkey were similar to those seen with lesions in the frontal or parietal lobes of the cerebral cortex in humans or monkeys. Our evaluation of vertical pursuit in this monkey suggests a new interpretation for the role of the frontal and parietal lobes in pursuit. 2. The up/down asymmetry was most pronounced for target motion at speeds greater than or equal to 2 degree/s. For target motion at 15 or 30 degree/s, upward step-ramp target motion evoked a brief upward smooth eye acceleration, followed by tracking that consisted largely of saccades. Downward step-ramp target motion evoked a prolonged smooth eye acceleration, followed by smooth, accurate tracking. 3. Varying the amplitude of the target step revealed that the deficit was similar for targets moving across all locations of the visual field. Eye acceleration in the interval 0-20 ms after the onset of pursuit was independent of initial target position and was symmetrical for upward and downward target motion. Eye acceleration in the interval 60-80 ms after the onset of pursuit showed a large asymmetry. For upward target motion, eye acceleration in this interval was small and did not depend on initial target position. For downward target motion, eye acceleration depended strongly on initial target position and was large when the target started close to the position of fixation. 4. We next attempted to understand the mechanism of the up/down asymmetry by evaluating the monkey's vertical motion processing and vertical eye movements under a variety of tracking conditions. For spot targets, the response to upward image motion was similar to that in normal monkeys if the image motion was presented during downward pursuit. In addition, the monkey with deficient upward pursuit was able to use upward image motion to make accurate saccades to moving targets. We conclude that the visual processing of upward image motion was normal in this monkey and that an asymmetry in visual motion processing could not account for the deficit in his upward pursuit. 5. Upward smooth eye acceleration was normal when the spot target was moved together with a large textured pattern.(ABSTRACT TRUNCATED AT 400 WORDS)     

Discharge of pursuit-related neurons in the caudal part of the frontal eye fields in juvenile monkeys with up–down pursuit asymmetry

The smooth-pursuit system uses retinal image-slip-velocity information of target motion to match eye velocity to actual target velocity. The caudal part of the frontal eye fields (FEF) contains neurons whose activity is related to direction and velocity of smooth-pursuit eye movements (pursuit neurons), and these neurons are thought to issue a pursuit command. During normal pursuit in well-trained adult monkeys, a pursuit command is usually not differentiable from the actual eye velocity. We examined whether FEF pursuit neurons signaled the actual eye velocity during pursuit in juvenile monkeys that exhibited intrinsic differences between upward and downward pursuit capabilities. Two, head-stabilized Japanese monkeys of 4 years of age were tested for sinusoidal vertical pursuit of target motion at 0.2–1.2 Hz (±10°, peak target velocity 12.5–75.0°/s). Gains of downward pursuit were 0.8–0.9 at 0.2–1.0 Hz, and peak downward eye velocity increased up to ~60°/s linearly with target velocity, whereas peak upward eye velocity saturated at 15–20°/s. The majority of downward FEF pursuit neurons increased the amplitude of their discharge modulation almost linearly up to 1.2 Hz. The majority of upward FEF pursuit neurons also increased amplitude of modulation nearly linearly as target frequency increased, and the regression slope was similar to that of downward pursuit neurons despite the fact that upward peak eye velocity saturated at ~0.5 Hz. These results indicate that the responses of the majority of upward FEF pursuit neurons did not signal the actual eye velocity during pursuit. We suggest that their activity reflected primarily the required eye velocity.     

Purkinje cells of the cerebellar dorsal vermis: simple-spike activity during pursuit and passive whole-body rotation

To track a slowly moving object during whole body rotation, smooth-pursuit and vestibularly induced eye movements must interact to maintain the accuracy of eye movements in space (i.e., gaze), and gaze movement signals must eventually be converted into eye movement signals in the orbit. To understand the role played by the cerebellar vermis in pursuit-vestibular interactions, in particular whether the output of the vermis codes gaze-velocity or eye-velocity, we examined simple-spike activity of 58 Purkinje (P-) cells in lobules VI-VII of head-stabilized Japanese monkeys that were trained to elicit smooth-pursuit eye movements and cancel their vestibuloocular reflex (VOR) during passive whole body rotation around horizontal, vertical, or oblique axes. All pursuit-sensitive vermal P-cells also responded during VOR cancellation, and the majority of them had peak modulation near peak stimulus velocity. The directions of maximum modulation during these two tasks were distributed in all directions with a downward preponderance. Using standard criteria, 40% of pursuit-sensitive vermal P-cells were classified as gaze-velocity. Other P-cells were classified either as eye/head-velocity group I (36%) that had similar preferred directions during pursuit and VOR cancellation but that had larger responses during VOR x1 when gaze remained stationary, or as eye/head-velocity group II (24%) that had oppositely directed or orthogonal eye and head movement sensitivity during pursuit and VOR cancellation. Eye/head-velocity group I P-cells contained cells whose activity was correlated with eye velocity. Modulation of many P-cells of the three groups during VOR x1 could be accounted for by the linear addition of their modulations during pursuit and VOR cancellation. When monkeys fixated a stationary target, over half of the P-cells tested, including gaze-velocity P-cells, discharged in proportion to the velocity of retinal motion of a second spot. These observations are in a striking contrast to our previous results for floccular vertical P-cells. Because we used identical tasks, these differences suggest that the two cerebellar regions are involved in very different kinds of processing of pursuit-vestibular interactions.     

Lid-eye coordination during vertical gaze changes in man and monkey

1. To investigate the coordination between the upper lid and the eye during vertical gaze changes, the movements of the lid and the eye were measured by the electromagnetic search-coil technique in three humans and two monkeys. 2. In both man and monkey, there was a close correspondence between the metrics of the lid movement and those of the concomitant eye movement during vertical fixation, smooth pursuit, and saccades. 3. During steady fixation, the eye and lid assumed essentially equal average positions; however, in man the lid would often undergo small idiosyncratic movements of up to 5 degrees when the eye was completely stationary. 4. During sinusoidal smooth pursuit between 0.2 and 1.0 Hz, the gain and phase shift of eye and lid movements were remarkably similar. The smaller gain and larger phase lag for downward smooth pursuit eye movements was mirrored in a similar reduced gain and increased phase lag for downward lid movements. 5. The time course of vertical lid movements associated with saccades was generally a faithful replica of the time course of the concomitant saccade; the similarity was especially impressive when the details of the velocity profiles were compared. Consequently, lid movements associated with vertical eye saccades are called lid saccades. 6. On average, lid saccades start some 5 ms later than the concomitant eye saccades but reach peak velocity at about the same time as the eye saccade. Concurrent lid and eye saccades in the downward direction have similar amplitudes and velocities. Lid saccades in the upward direction are often smaller and slower than the concomitant eye saccades. The relation of peak velocity versus amplitude and of duration versus amplitude are similar for lid and eye saccades. 7. To investigate the neural signal responsible for lid saccades, isometric tension and EMG activity were recorded from the lids of the two authors. 8. The isometric tensions during upward lid saccades exceeded the tensions required to hold the lid in its final position.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cerebellar disease alters the axis of the high-acceleration vestibuloocular reflex

L. W. Schultheis and D. A. Robinson showed that the axis of the rotational vestibuloocular reflex (RVOR) cannot be altered by visual-vestibular mismatch ("cross-axis adaptation") when the vestibulocerebellum is lesioned. This suggests that the cerebellum may calibrate the axis of eye velocity of the RVOR under natural conditions. Thus we asked whether patients with cerebellar disease have alterations in the RVOR axis and, if so, what might be the mechanism. We used three-axis scleral coils to record head and eye movements during yaw, pitch, and roll head impulses in 18 patients with cerebellar disease and in a comparison group of eight subjects without neurologic disease. We found distinct shifts of the eye-velocity axis in patients. The characteristic finding was a disconjugate upward eye velocity during yaw. Measured at 70 ms after the onset of head rotation, the median upward gaze velocity was 15% of yaw head velocity for patients and <1% for normal subjects (P < 0.001). Upward eye velocity was greater in the contralateral (abducting) eye during yaw and in the ipsilateral eye during roll. Patients had a higher gain (eye speed/head speed) for downward than for upward pitch (median ratio of downward to upward gain: 1.3). In patients, upward gaze velocities during both yaw and roll correlated with the difference in anterior (AC) and posterior canal excitations, scaled by the respective pitch gains. Our findings support the hypothesis that upward eye velocity during yaw results from AC excitation, which must normally be suppressed by the intact cerebellum.     

Cerebellar nodulectomy impairs spatial memory of vestibular and optokinetic stimulation in rabbits

Natural vestibular and optokinetic stimulation were used to investigate the possible role of the cerebellar nodulus in the regulation and modification of reflexive eye movements in rabbits. The nodulus and folium 9d of the uvula were destroyed by surgical aspiration. Before and after nodulectomy the vertical and horizontal vestibuloocular reflexes (VVOR, HVOR) were measured during sinusoidal vestibular stimulation about the longitudinal (roll) and vertical (yaw) axes. Although the gain of the HVOR (G(HVOR) = peak eye movement velocity/peak head velocity) was not affected by the nodulectomy, the gain of the VVOR (G(VVOR)) was reduced. The gains of the vertical and horizontal optokinetic reflexes (G(VOKR), G(HOKR)) were measured during monocular, sinusoidal optokinetic stimulation (OKS) about the longitudinal and vertical axes. Following nodulectomy, there was no reduction in G(VOKR) or G(HOKR). Long-term binocular OKS was used to generate optokinetic afternystagmus, OKAN II, that lasts for hours. After OKAN II was induced, rabbits were subjected to static pitch and roll, to determine how the plane and velocity of OKAN II is influenced by a changing vestibular environment. During static pitch, OKAN II slow phase remained aligned with earth-horizontal. This was true for normal and nodulectomized rabbits. During static roll, OKAN II remained aligned with earth-horizontal in normal rabbits. During static roll in nodulectomized rabbits, OKAN II slow phase developed a centripetal vertical drift. We examined the suppression and recovery of G(VVOR) following exposure to conflicting vertical OKS for 10-30 min. This vestibular-optokinetic conflict reduced G(VVOR) in both normal and nodulectomized rabbits. The time course of recovery of G(VVOR) after conflicting OKS was the same before and after nodulectomy. In normal rabbits, the head pitch angle, at which peak OKAN II velocity occurred, corresponded to the head pitch angle maintained during long-term OKS. If the head was maintained in a "pitched-up" or "pitched-down" orientation during long-term OKS, the subsequently measured OKAN II peak velocity occurred at the same orientation. This was not true for nodulectomized rabbits, who had OKAN II peak velocities at head pitch angles independent of those maintained during long-term OKS. We conclude that the nodulus participates in the regulation of compensatory reflexive movements. The nodulus also influences "remembered" head position in space derived from previous optokinetic and vestibular stimulation.     

Gravity and the vertical vestibulo-ocular reflex

Summary We studied the vertical vestibulo-ocular reflex (VOR) and vertical visual-vestibular interaction induced by voluntary pitch in the upright and onside positions in eight normal human subjects. Subjects were trained to produce sinusoidal (0.4 to 1.6 Hz) pitch head movements guided by a frequency modulated sound signal. Eye and head movements were recorded with a magnetic search coil. There was no significant difference between the pooled average gain (eye velocity/head velocity) of the vertical VOR in the upright and onside positions. Vertical VOR gain in any position could be more or less than 1.0 for individual subjects. By contrast, gain with an earth-fixed visual target was always near 1.0. Asymmetries in the gain of upward and downward VOR, pursuit and fixation suppression of the VOR were found in individual subjects, but in the group of normal subjects there was no significant difference between gain of up and down eye movements induced by vestibular, visual or visual-vestibular stimulation in any position. We conclude that during voluntary pitch otolith signals are not critical for normal functioning of the vertical VOR.     

Up-down asymmetry in human vertical optokinetic nystagmus and afternystagmus: contributions of the central and peripheral retinae

Summary The vertical optokinetic nystagmus (OKN) of 10 normal subjects and the optokinetic afternystagmus (OKAN) of 3 subjects were measured with the magnetic search coil technique. In order to assess the relative contributions of various retinal areas to the up-down asymmetry in OKN the central and peripheral visual fields were selectively stimulated in four OKN conditions. In the full-field OKN condition the stimulus was a 61°×64° display of moving random-dots. Overall, full-field OKN gains elicited by upward motion were significantly higher than those elicited by downward motion at stimulus velocities between 30 and 70°/s. In the periphery-only OKN condition a 3° or 6°-wide vertical band occluded the center of the full-field display. Nine of the 10 subjects displayed OKN in this condition. For 6 subjects, the addition of the 6° band to the full field resulted in an increase in the up-down asymmetry at stimulus velocities above 30°/s. For the other three subjects there was a decline in the gains of both upward and downward OKN when the 3° or 6° band was present; the result was directionally symmetric OKN gains. In the central-strip OKN condition only a 6°-wide central vertical strip of moving dots was visible. The gains of central-strip OKN were not significantly different from the full-field responses. A servo controlled centrally-located 10°× 6° moving display was used in the center-only OKN condition. In this condition both upward and downward gains were attenuated and there was no up-down asymmetry. OKAN was measured following a 50-s exposure to either the full-field or center-only OKN display. The stimulus velocity was 30°/s. After viewing the full-field display the 3 subjects displayed OKAN with slow phases upward following upward OKN but there was no downward OKAN following downward OKN. In contrast, there was no consistent directional asymmetry following exposure to the center-only display. The disappearance of the upward preponderance in OKN and OKAN with occlusion of the peripheral retina suggests that the directional asymmetry in vertical OKN exists in the slow OKN system.     

Pursuit afternystagmus asymmetry in humans

Summary It is known that prolonged unidirectional motion of a large field induces a reflexive drift of the eyes in the same direction when the stimulus is turned off. The phenomenon, which is called optokinetic afternystagmus, is known to be stronger after upward than downward stimulus motion. It is now reported that a similar anisotropy exists in the afternystagmus associated with the smooth pursuit system (PAN). The speed of the PAN reflexive drift was found to be greater following upward tracking at all times tested during a 15 s interval when compared to the values following downward tracking. A psychophysical measure of illusory motion, presumed to be generated by suppression of PAN in order to maintain fixation upon a stationary target, also showed a significantly greater amplitude and duration for the upward direction. If the directional asymmetry is a property of a velocity integrator that is believed to generate the afternystagmus, then the results are compatible with the existence of a common integrator for both optokinetic and pursuit systems.     

Asymmetry of visuo-vestibular mechanisms contributes to reversal of optokinetic after-nystagmus

When the visual background is moving while subject fixate a visual target, optokinetic eye movements (OKN) are suppressed and the after response, called optokinetic after nystagmus (OKAN), occurring at the stimuli offset is often inverted as compared to the situation when the OKN movements are allowed. In this study, we investigated whether this reversal of OKAN results from a perceptual or extra-retinal feedback in relation with the pursuit system and/or the vestibular indirect system. Optokinesis performance was studied in normal subjects in four experiments always using the same background motion (1) to characterize the OKN and OKAN performance elicited by the whole visual field motion while fixating or not a central visual target, (2) to investigate the 3D characteristics of the OKAN reversal by using different orientations of the visual stimulation, (3) to correlate the occurrence of an inverted OKAN with functional asymmetry of the visuo-vestibular system, by studying the effects of ocular fixation deviations and finally (4) to examine the effects of the depth plane of gaze fixation on the OKAN characteristics. In Experiments 1 and 2, we observed that the visual fixation during full-field motion induced either a dumping effect or an inversion of the OKAN response that could occur in the different planes of eye movements. The time constant was significantly increased in the inverted after-responses as compared to the not inverted ones. In Experiment 3, we found that the occurrence of an OKAN reversal after eye movement inhibition was significantly related to the presence of right/left asymmetrical OKAN responses. Moreover, the OKAN time constant was strikingly dependent on the eye fixation position during the visual stimulation and this time constant/eye position relation diverged between OKAN responses with and without inversion. Finally, Experiment 4 showed that the OKAN inversion tended to disappear when the visual target to fixate was in the near space as compared to the far space included in the background. These results argue in favor of an extraretinal influence in relation to the dynamics of the vestibulo-motor system, rather than for a perceptual influence on the inverted OKAN mechanisms. More precisely, we postulate that the reversal of OKAN could be linked to an inhibition issued from pursuit signals combined with an asymmetrical activity in the VSM vestibular complex. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

A comparison of the horizontal and vertical optokinetic reflexes of the rabbit

Summary The horizontal and vertical monocular optokinetic reflexes of the rabbit were measured under closed-loop and open-loop conditions. A random noise, optokinetic stimulus subtending 70×70 deg was presented to the left eye of rabbits placed in front of a rear projection tangent screen. The position of the right eye (nonstimulated) was measured using an infrared light projection technique. During open-loop optokinetic stimulation the eye position signal was fed back to sum with a time-integrated velocity command signal driving the optokinetic stimulus. The dynamics of eye movements evoked by horizontal and vertical optokinetic stimulation were different. Horizontally evoked eye movements never exceeded a deviation of 15 deg before being interrupted by resetting saccades, which returned the eye past the primary position. By contrast, vertical eye deviations greater than 20 deg were often maintained for intervals exceeding 10 s without resetting. The closed-loop gain of optokinetically evoked horizontal eye movements was higher for monocular posterior-anterior optokinetic stimulation than for anterior-posterior stimulation. The vertical optokinetic gain for up-down stimulation was slightly greater than the gain for down-up stimulation. The vertical up-down, open-loop optokinetic gain was greater than the down-up gain over a range of retinal slip velocities of 0.5–5.0 deg/s. Measurement of the horizontal vestibulo-ocular reflex during simultaneous horizontal optokinetic stimulation demonstrated that visual and vestibular information combine linearly to produce reflex eye movements. These data suggest that the higher gain of the horizontal optokinetic reflex may compensate in part for the reduced gain of the horizontal vestibulo-ocular reflex at lower angular accelerations of the head. An equivalent vertical optokinetic gain would be obviated by the contribution of the utricular otoliths to the vertical vestibulo-ocular reflex at low frequencies of head movement.This research was supported by the National Institutes of Health Grant EY00848 and the Oregon Lions Sight and Hearing Foundation     

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.     

Vertical Purkinje cells of the monkey floccular lobe: simple-spike activity during pursuit and passive whole body rotation.

To understand how the simian floccular lobe is involved in vertical smooth pursuit eye movements and the vertical vestibuloocular reflex (VOR), we examined simple-spike activity of 70 Purkinje (P) cells during pursuit eye movements and passive whole body rotation. Fifty-eight cells responded during vertical and 12 during horizontal pursuit. We classified P cells as vertical gaze velocity (VG) if their modulation occurred for movements of both the eye (during vertical pursuit) and head (during pitch VOR suppression) with the modulation during one less than twice that of the other and was less during the target-fixed-in-space condition (pitch VOR X1) than during pitch VOR suppression. VG P cells constituted only a minority of vertical P cells (19%). Other vertical P cells that responded during pitch VOR suppression were classified as vertical eye and head velocity (V/) P cells (48%), regardless of the synergy of their response direction during smooth pursuit and VOR suppression. Vertical P cells that did not respond during pitch VOR suppression but did respond during rotation in vertical planes other than pitch were classified as off-pitch V/ P cells (33%). The mean eye-velocity and eye-position sensitivities of the three types of vertical P cells were similar. One-third (2/7 VG, 2/11 V/, 6/13 off-pitch V/), in addition, showed eye position sensitivity during saccade-free fixations. Maximal vestibular activation directions (MADs) were examined during VOR suppression by applying vertical whole body rotation with the monkeys oriented in different vertical planes. The MADs for VG P cells and V/ P cells with eye and vestibular sensitivity in the same direction were distributed near the pitch plane, suggesting convergence of bilateral anterior canal inputs. In contrast, MADs of off-pitch V/ P cells and V/ P cells with oppositely directed eye and vestibular sensitivity were shifted toward the roll plane, suggesting convergence of anterior and posterior canal inputs of the same side. Unlike horizontal G P cells, the modulation of many VG and V/ P cells when the target was fixed in space (pitch VOR X1) was not well predicted by the linear addition of their modulations during vertical pursuit and pitch VOR suppression. These results indicate that the populations of vertical and horizontal eye-movement P cells in the floccular lobe have markedly different discharge properties and therefore may be involved in different kinds of processing of vestibular-oculomotor interactions.     

Discharge of pursuit neurons in the caudal part of the frontal eye fields during cross-axis vestibular-pursuit training in monkeys

Previous studies in monkeys have shown that pursuit training during orthogonal whole body rotation results in task-dependent, predictive pursuit eye movements. We examined whether pursuit neurons in the frontal eye fields (FEF) are involved in predictive pursuit induced by vestibular-pursuit training. Two monkeys were rotated horizontally at 20°/s for 0.5 s either rightward or leftward with random inter-trial intervals. This chair motion trajectory was synchronized with orthogonal target motion at 20°/s for 0.5 s either upward or downward. Monkeys were rewarded for pursuing the target. Vertical pursuit eye velocities and discharge of 23 vertical pursuit neurons to vertical target motion were compared before training and during the last 5 min of the 25–45 min training. The latencies of discharge modulation of 61% of the neurons (14/23) shortened after vestibular-pursuit training in association with a shortening of pursuit latency. However, their discharge modulation occurred after 100 ms following the onset of pursuit eye velocity. Only four neurons (4/23 = 17%) discharged before the eye movement onset. A significant change was not observed in eye velocity and FEF pursuit neuron discharge during pursuit alone after training without vestibular stimulation. Vestibular stimulation alone without a target after training induced no clear response. These results suggest that the adaptive change in response to pursuit prediction was induced by vestibular inputs in the presence of target pursuit. FEF pursuit neurons are unlikely to be involved in the initial stage of generating predictive eye movements. We suggest that they may participate in the maintenance of predictive pursuit.     

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.     

Role of the cerebellar flocculus region in the coordination of eye and head movements during gaze pursuit

The contribution of the flocculus region of the cerebellum to horizontal gaze pursuit was studied in squirrel monkeys. When the head was free to move, the monkeys pursued targets with a combination of smooth eye and head movements; with the majority of the gaze velocity produced by smooth tracking head movements. In the accompanying study we reported that the flocculus region was necessary for cancellation of the vestibuloocular reflex (VOR) evoked by passive whole body rotation. The question addressed in this study was whether the flocculus region of the cerebellum also plays a role in canceling the VOR produced by active head movements during gaze pursuit. The firing behavior of 121 Purkinje (Pk) cells that were sensitive to horizontal smooth pursuit eye movements was studied. The sample included 66 eye velocity Pk cells and 55 gaze velocity Pk cells. All of the cells remained sensitive to smooth pursuit eye movements during combined eye and head tracking. Eye velocity Pk cells were insensitive to smooth pursuit head movements. Gaze velocity Pk cells were nearly as sensitive to active smooth pursuit head movements as they were passive whole body rotation; but they were less than half as sensitive ( approximately 43%) to smooth pursuit head movements as they were to smooth pursuit eye movements. Considered as a whole, the Pk cells in the flocculus region of the cerebellar cortex were <20% as sensitive to smooth pursuit head movements as they were to smooth pursuit eye movements, which suggests that this region does not produce signals sufficient to cancel the VOR during smooth head tracking. The comparative effect of injections of muscimol into the flocculus region on smooth pursuit eye and head movements was studied in two monkeys. Muscimol inactivation of the flocculus region profoundly affected smooth pursuit eye movements but had little effect on smooth pursuit head movements or on smooth tracking of visual targets when the head was free to move. We conclude that the signals produced by flocculus region Pk cells are neither necessary nor sufficient to cancel the VOR during gaze pursuit.     

Smooth-pursuit eye-movement-related neuronal activity in macaque nucleus reticularis tegmenti pontis

Neuronal responses that were observed during smooth-pursuit eye movements were recorded from cells in rostral portions of the nucleus reticularis tegmenti pontis (rNRTP). The responses were categorized as smooth-pursuit eye velocity (78%) or eye acceleration (22%). A separate population of rNRTP cells encoded static eye position. The sensitivity to pursuit eye velocity averaged 0.81 spikes/s per degrees /s, whereas the average sensitivity to pursuit eye acceleration was 0.20 spikes/s per degrees /s(2). Of the eye-velocity cells with horizontal preferences for pursuit responses, 56% were optimally responsive to contraversive smooth-pursuit eye movements and 44% preferred ipsiversive pursuit. For cells with vertical pursuit preferences, 61% preferred upward pursuit and 39% preferred downward pursuit. The direction selectivity was broad with 50% of the maximal response amplitude observed for directions of smooth pursuit up to +/-85 degrees away from the optimal direction. The activities of some rNRTP cells were linearly related to eye position with an average sensitivity of 2.1 spikes/s per deg. In some cells, the magnitude of the response during smooth-pursuit eye movements was affected by the position of the eyes even though these cells did not encode eye position. On average, pursuit centered to one side of screen center elicited a response that was 73% of the response amplitude obtained with tracking centered at screen center. For pursuit centered on the opposite side, the average response was 127% of the response obtained at screen center. The results provide a neuronal rationale for the slow, pursuit-like eye movements evoked with rNRTP microstimulation and for the deficits in smooth-pursuit eye movements observed with ibotenic acid injection into rNRTP. More globally, the results support the notion of a frontal and supplementary eye field-rNRTP-cerebellum pathway involved with controlling smooth-pursuit eye movements.     

Activity of mesencephalic vertical burst neurons during saccades and smooth pursuit

The activity of vertical burst neurons (BNs) was recorded in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF-BNs) and in the interstitial nucleus of Cajal (NIC-BNs) in head-restrained cats while performing saccades or smooth pursuit. BNs emitted a high-frequency burst of action potentials before and during vertical saccades. On average, these bursts led saccade onset by 14 +/- 4 ms (mean +/- SD, n = 23), and this value was in the range of latencies ( approximately 5-15 ms) of medium-lead burst neurons (MLBNs). All NIC-BNs (n = 15) had a downward preferred direction, whereas riMLF-BNs showed either a downward (n = 3) or an upward (n = 5) preferred direction. We found significant correlations between saccade and burst parameters in all BNs: vertical amplitude was correlated with the number of spikes, maximum vertical velocity with maximum of the spike density, and saccade duration with burst duration. A correlation was also found between instantaneous vertical velocity and neuronal activity during saccades. During fixation, all riMLF-BNs and approximately 50% of NIC-BNs (7/15) were silent. Among NIC-BNs active during fixation (8/15), only two cells had an activity correlated with the eye position in the orbit. During smooth pursuit, most riMLF-BNs were silent (7/8), but all NIC-BNs showed an activity that was significantly correlated with the eye velocity. This activity was unaltered during temporary disappearance of the visual target, demonstrating that it was not visual in origin. For a given neuron, its ON-direction during smooth pursuit and saccades remained identical. The activity of NIC-BNs during both saccades and smooth pursuit can be described by a nonlinear exponential function using the velocity of the eye as independent variable. We suggest that riMLF-BNs, which were not active during smooth pursuit, are vertical MLBNs responsible for the generation of vertical saccades. Because NIC-BNs discharged during both saccades and pursuit, they cannot be regarded as MLBNs as usually defined. NIC-BNs could, however, be the site of convergence of both the saccadic and smooth pursuit signals at the premotoneuronal level. Alternatively, NIC-BNs could participate in the integration of eye velocity to eye position signals and represent input neurons to a common integrator.