Eye movement and visual motion perception in schizophrenia I: Apparent motion evoked smooth pursuit eye movement reveals a hidden dysfunction in smooth pursuit eye movement in schizophrenia

To date, smooth pursuit eye movement in schizophrenia has only been investigated using a target stimulus in continuous motion. However, smooth pursuit can also be evoked by an oscillating jumping dot that appears to be in apparent motion and although there is no continuous motion on the retinal surface this apparently moving stimulus can effortlessly elicit smooth-pursuit eye movement. In the first of two experiments smooth pursuit eye movement was evoked by target stimuli in continuous (real) motion at seven target velocities from 5.0 to 35.0 deg/s, and in a second experiment it was measured in response to an oscillating jumping dot in apparent motion at eight target velocities from 5.0 to 25.0 deg/s in a group with mixed-symptoms in schizophrenia and in a control group. The results of Experiment 1 provided no evidence for a dysfunction in continuous motion evoked smooth pursuit eye movement in the group with schizophrenia. However, following the removal of saccadic eye movements in smooth pursuit, the group with schizophrenia showed significantly lower smooth pursuit eye velocity at target velocities from 20.0 to 35.0 deg/s. The results of Experiment 2 revealed that apparent motion evoked smooth pursuit eye velocity in the group with schizophrenia was significantly lower in comparison with normal observers at all target velocities up to 25.0 deg/s with the inclusion or exclusion of saccadic eye movements. The findings demonstrate that overall smooth pursuit eye movement evoked in response to a continuous (real) motion target in the group with schizophrenia may nevertheless contain a hidden temporal resolution and integration dysfunction that is revealed when smooth pursuit eye movement is evoked in response to an oscillating jumping dot in apparent motion. The findings also demonstrate that normal smooth pursuit eye movement in normal observers can be made to resemble the dysfunctional smooth pursuit eye movement that is naturally found in some people with schizophrenia by using a target stimulus in apparent motion.     

Prediction in the timing of pursuit eye movement initiation revealed by cross-axis vestibular–pursuit training in monkeys

The smooth-pursuit system interacts with the vestibular system to maintain the image of a moving target on the fovea. Efficient tracking performance requires information about the velocity and the initiation of target motion. Previous studies in monkeys have shown that training with orthogonal pursuit and whole body rotation results in adapted eye movement direction during chair rotation. In addition, the latency of the pursuit shortens and initial eye velocity increases in a task-dependent manner. To examine whether these adapted eye movements are predictive pursuit, we studied whether our monkeys could predict the timing of smooth eye movement initiation during chair rotation. Two young Japanese monkeys were rotated horizontally in a trapezoidal waveform (20°/s, ±10°) with random inter-trial intervals. A laser spot was moved vertically with the same trajectory at a constant delay ranging from 100 to 700 ms after the onset of the chair motion. The monkeys were required to pursue the spot. After this training, the latencies of pursuit eye movements following the onset of chair motion were examined in the presence of the target motion. The target was also briefly (for 500–700 ms) extinguished at 80 ms after the onset of chair rotation. Pursuit eye movements after training were initiated before the onset of target motion and the latencies were proportional to the delays used for training. The latencies and response magnitudes of pursuit with or without target blanking were similar. The auditory–pursuit training did not induce an initial pursuit response similar to that induced by vestibular–pursuit training. These results indicate that smooth eye movements during the chair rotation after the vestibular–pursuit training included a predictive pursuit component. The monkeys’ estimate of the delays revealed by the latencies of pursuit was shorter by 22–36% than the actual delays.     

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.     

Volitional control of anticipatory ocular pursuit responses under stabilised image conditions in humans

Ocular pursuit responses have been examined in humans in three experiments in which the pursuit target image has been fully or partially stabilised on the fovea by feeding a recorded eye movement signal back to drive the target motion. The objective was to establish whether subjects could volitionally control smooth eye movement to reproduce trajectories of target motion in the absence of a concurrent target motion stimulus. In experiment 1 subjects were presented with a target moving with a triangular waveform in the horizontal axis with a frequency of 0.325 Hz and velocities of ± 10–50°/s. The target was illuminated twice per cycle for pulse durations (PD) of 160–640 ms as it passed through the centre position; otherwise subjects were in darkness. Subjects initially tracked the target motion in a conventional closed-loop mode for four cycles. Prior to the next target presentation the target image was stabilised on the fovea, so that any target motion generated resulted solely from volitional eye movement. Subjects continued to make anticipatory smooth eye movements both to the left and the right with a velocity trajectory similar to that observed in the closed-loop phase. Peak velocity in the stabilised-image mode was highly correlated with that in the prior closed-loop phase, but was slightly less (84% on average). In experiment 2 subjects were presented with a continuously illuminated target that was oscillated sinusoidally at frequencies of 0.2–1.34 Hz and amplitudes of ± 5–20°. After four cycles of closed-loop stimulation the image was stabilised on the fovea at the time of peak target displacement. Subjects continued to generate an oscillatory smooth eye velocity pattern that mimicked the sinusoidal motion of the previous closed-loop phase for at least three further cycles. The peak eye velocity generated ranged from 57–95% of that in the closed-loop phase at frequencies up to 0.8 Hz but decreased significantly at 1.34 Hz. In experiment 3 subjects were presented with a stabilised display throughout and generated smooth eye movements with peak velocity up to 84°/s in the complete absence of any prior external target motion stimulus, by transferring their attention alternately to left and right of the centre of the display. Eye velocity was found to be dependent on the eccentricity of the centre of attention and the frequency of alternation. When the target was partially stabilised on the retina by feeding back only a proportion (K _f = 0.6–0.9) of the eye movement signal to drive the target, subjects were still able to generate smooth movements at will, even though the display did not move as far or as fast as the eye. Peak eye velocity decreased as K _f decreased, suggesting that there was a continuous competitive interaction between the volitional drive and the visual feedback provided by the relative motion of the display with respect to the retina. These results support the evidence for two separate mechanisms of smooth eye movement control in ocular pursuit: reflex control from retinal velocity error feedback and volitional control from an internal source. Arguments are presented to indicate how smooth pursuit may be controlled by matching a voluntarily initiated estimate of the required smooth movement, normally derived from storage of past re-afferent information, against current visual feedback information. Such a mechanism allows preemptive smooth eye movements to be made that can overcome the inherent delays in the visual feedback pathway.     

Eye movement and visual motion perception in schizophrenia II: global coherent motion as a function of target velocity and stimulus density

Coherent global motion is a compelling illusion of visual motion that is seen as the result of spatially and successively presented stimuli that are, in fact, stationary. In the present study the threshold perception of global coherent motion was measured using random-dot kinematograms in a group of normal observers and a group with mixed symptoms in schizophrenia who also participated in a companion study on smooth pursuit eye movement (Slaghuis et al. in Exp Brain Res, 2007). The velocity of coherent motion target stimuli was produced by varying the spatial step-size (Δs) between dots to create three target velocities (6.0, 12.0 and 24.0 deg/s) which were measured at three target stimulus densities (100, 200, and 400 dots/deg²). A staircase procedure was used to determine the threshold for the number of target dots that was needed to move in the same direction to detect the direction of motion and which were plotted amongst a field of randomly moving visual noise dots. The findings demonstrate that in comparison with normal observers, the threshold for the perception of coherent motion in the group with schizophrenia was significantly higher at the lowest target velocity of 6.0 deg/s but not at target velocities of 12.0 and 24.0 deg/s. Stimulus density was found to have a significant effect on the perception of coherent motion, but it had no differential effect on performance in the groups. An examination of relationships between coherent motion and smooth pursuit eye movement in the companion study (Slaghuis et al. in Exp Brain Res, 2007) revealed significant, negative, correlations between coherent motion and apparent motion smooth pursuit eye velocity at target velocities of 6.0, 12.0 and 24.0 deg/s in the group with schizophrenia, but no such relationship was found in normal observers. It was concluded that the significant reduction in sensitivity for the perception of coherent motion at the lowest target velocity of 6.0 deg/s in the group with schizophrenia is consistent with an impairment in the detection of visual motion at a local level and in parallel for all parts of the image at striate and extrastiate levels of visual processing.     

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     

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.     

Volitional control of anticipatory ocular smooth pursuit after viewing, but not pursuing, a moving target: evidence for a re-afferent velocity store

 Although human subjects cannot normally initiate smooth eye movements in the absence of a moving target, previous experiments have established that such movements can be evoked if the subject is required to pursue a regularly repeated, transient target motion stimulus. We sought to determine whether active pursuit was necessary to evoke such an anticipatory response or whether it could be induced after merely viewing the target motion. Subjects were presented with a succession of ramp target motion stimuli of identical velocity and alternating direction in the horizontal axis. In initial experiments, the target was exposed for only 120 ms as it passed through centre, with a constant interval between presentations. Ramp velocity was varied from ±9 to 45°/s in one set of trials; the interval between ramp presentations was varied from 640 to 1920 ms in another. Subjects were instructed either to pursue the moving target from the first presentation or to hold fixation on another, stationary target during the first one, two or three presentations of the moving display. Without fixation, the first smooth movement was initiated with a mean latency of 95 ms after target onset, but with repeated presentations anticipatory smooth movements started to build up before target onset. In contrast, when the subjects fixated the stationary target for three presentations of the moving target, the first movement they made was already anticipatory and had a peak velocity that was significantly greater than that of the first response without prior fixation. The conditions of experiment 1 were repeated in experiment 3 with a longer duration of target exposure (480 ms), to allow higher eye velocities to build up. Again, after three prior fixations, the anticipatory velocity measured at 100 ms after target onset (when visual feedback would be expected to start) was not significantly different to that evoked after the subjects had made three active pursuit responses to the same target motion, reaching a mean of 20°/s for a 50°/s target movement. In a further experiment, we determined whether subjects could use stored information from prior active pursuit to generate anticipatory pursuit in darkness if there was a high expectancy that the target would reappear with identical velocity. Subjects made one predictive response immediately after target disappearance, but very little response thereafter until the time at which they expected the target to reappear, when they were again able to re-vitalise the anticipatory response before target appearance. The findings of these experiments provide evidence that information related to target velocity can be stored and used to generate future anticipatory responses even in the absence of eye movement. This suggests that information for storage is probably derived from a common pre-motor drive signal that is inhibited during fixation, rather than an efference copy of eye movement itself. Furthermore, a high level of expectancy of target appearance can facilitate the release of this stored information in darkness. Received: 14 January 1997 / Accepted: 30 April 1997     

Purkinje cell activity in the flocculus of vestibular neurectomized and normal monkeys during optokinetic nystagmus (OKN) and smooth pursuit eye movements

Summary 1. Single unit activity was recorded in the primate flocculus after the vestibular nerves were cut (bilateral vestibular neurectomy) during optokinetic nystagmus (OKN), smooth pursuit eye movements (SP) and whole field visual stimulation with gaze fixed on a stationary target light (OKN-suppression). Following vestibular neurectomy monkeys had no vestibular responses and no optokinetic after-nystagmus (OKAN) in the horizontal plane. However, OKN slow phases still reached steady state velocities of up to 100 deg/s. 2. After neurectomy, simple spike (SS) activity of Purkinje cells (P-cells) was modulated in relation to eye velocity, regardless of whether eye velocity was induced by a small target light moving in darkness (SP) or by a moving visual surround (OKN). In over 90% of the P-cells firing rate increased with eye velocity to the ipsilateral side and decreased with velocities to the contralateral side. Modulation in firing rate increased monotonically with increasing eye velocity. The strength of modulation was similar during SP and OKN for the same eye velocity. 3. The change in firing rate of P-cells in response to a sudden change in optokinetic stimulus velocity contained a component related to eye velocity and a component related to eye acceleration. Only a few P-cells were also modulated with image slip velocity during OKN-suppression. 4. The modulation of P-cells during SP and OKN was compared in normal and vestibular neurectomized monkeys. The sensitivity of floccular P-cells to eye velocity during SP was 1.14 imp·s^–1/deg·s^–1 in normal monkey and 1.28 imp·s^–1/deg·s^–1 after neurectomy. The similarity of eye velocity sensitivities demonstrates that neurectomy does not change the characteristics of floccular P-cell modulation during SP. In contrast, during OKN modulation of P-cells is quite different in normal and neurectomized monkey. In normal monkey, P-cells are modulated during steady state OKN for eye velocities above 40–60 deg/s only. This threshold velocity corresponds approximately to the maximal initial OKAN velocity (i.e. OKAN saturation velocity). After neurectomy, the threshold velocity is 0 deg/s and P-cells are modulated during steady state OKN also over ranges of eye velocities that do not cause a response in normal monkey. Sensitivities of P-cells to eye velocity during OKN for eye velocities above the threshold velocity are 1.0 imp·s^–1/deg·s^–1 in neurectomized monkey and 1.43 imp·s^–1/deg·s^–1 in normal monkey. 5. The hypothesis has been put forward that OKN slow phase velocity in normal monkey has two dynamically different components, a fast and a slow component. The results strongly suggest that the two components depend on different neuronal populations. Firing rate of floccular P-cells is modulated in relation to the fast component only. The results furthermore support the idea that it is the smooth pursuit system which may generate the fast component in the OKN slow phase velocity response.Supported by Swiss National Foundation for Scientific Research (Nr. 3.718-0.80 and 3.593-0.84)     

Velocity characteristics of smooth pursuit eye movements to different patterns of target motion

Summary Horizontal smooth pursuit eye movements were recorded in normal subjects in response to different patterns of target motion that was either periodic or not. Periodic patterns were triangular and sinusoidal waves. Non-periodic patterns were ramps with either constant or sinusoidally varying velocity. In both cases, several different amplitudes and peak velocities were considered. The experimental results indicate that (a) the performance of the smooth pursuit system depends on the spatio-temporal characteristics of target motion, (b) the relationship between smooth pursuit eye velocity and target velocity during the tracking of constant velocity ramps is strongly nonlinear with a saturation depending on the amplitude of target excursion, (c) in the remaining experimental conditions, there is a linear behaviour up to target velocities of 75 deg/s with a gain of about 0.9.     

Role of retinal slip in the prediction of target motion during smooth and saccadic pursuit

Visual tracking of moving targets requires the combination of smooth pursuit eye movements with catch-up saccades. In primates, catch-up saccades usually take place only during pursuit initiation because pursuit gain is close to unity. This contrasts with the lower and more variable gain of smooth pursuit in cats, where smooth eye movements are intermingled with catch-up saccades during steady-state pursuit. In this paper, we studied in detail the role of retinal slip in the prediction of target motion during smooth and saccadic pursuit in the cat. We found that the typical pattern of pursuit in the cat was a combination of smooth eye movements with saccades. During smooth pursuit initiation, there was a correlation between peak eye acceleration and target velocity. During pursuit maintenance, eye velocity oscillated at approximately 3 Hz around a steady-state value. The average gain of smooth pursuit was approximately 0.5. Trained cats were able to continue pursuing in the absence of a visible target, suggesting a role of the prediction of future target motion in this species. The analysis of catch-up saccades showed that the smooth-pursuit motor command is added to the saccadic command during catch-up saccades and that both position error and retinal slip are taken into account in their programming. The influence of retinal slip on catch-up saccades showed that prediction about future target motion is used in the programming of catch-up saccades. Altogether, these results suggest that pursuit systems in primates and cats are qualitatively similar, with a lower average gain in the cat and that prediction affects both saccades and smooth eye movements during pursuit.     

Prediction in the oculomotor system: smooth pursuit during transient disappearance of a visual target

Summary Eye movements were recorded in human subjects who tracked a target spot which moved horizontally at constant speeds. At random times during its trajectory, the target disappeared for variable periods of time and the subjects attempted to continue tracking the invisible target. The smooth pursuit component of their eye movements was isolated and averaged. About 190 ms after the target disappeared, the smooth pursuit velocity began to decelerate rapidly. The time course of this deceleration was similar to that in response to a visible target whose velocity decreased suddenly. After a deceleration lasting about 280 ms, the velocity stabilized at a new, reduced level which we call the residual velocity. The residual velocity remained more or less constant or declined only slowly even when the target remained invisible for 4 s. When the same target velocity was used in all trials of an experiment, the subjects' residual velocity amounted to 60% of their normal pursuit velocity. When the velocity was varied randomly from trial to trial, the residual velocity was smaller; for target velocities of 5, 10, and 20 deg/s it reached 55, 47, and 39% respectively. The subjects needed to see targets of unforeseeable velocity for no more than 300 ms in order to develop a residual velocity that was characteristic of the given target velocity. When a target of unknown velocity disappeared at the very moment the subject expected it to start, a smooth movement developed nonetheless and reached within 300 ms a peak velocity of 5 deg/s which was independent of the actual target velocity and reflected a default value for the pursuit system. Thereafter the eyes decelerated briefly and then continued with a constant or slightly decreasing velocity of 2–4 deg/s until the target reappeared. Even when the subjects saw no moving target during an experiment, they could produce a smooth movement in the dark and could grade its velocity as a function of that of an imagined target. We suggest that the residual velocity reflects a first order prediction of target movement which is attenuated by a variable gain element. When subjects are pursuing a visible target, the gain of this element is close to unity. When the target disappears but continued tracking is attempted, the gain is reduced to a value between 0.4 and 0.6.Supported by grants DFG Be 783/1 and Be 783/2-1 (1), and NIH RR 00166 and EY 00745 (2)     

Behavioral responses of trained squirrel and rhesus monkeys during oculomotor tasks

The oculomotor system is the motor system of choice for many neuroscientists studying motor control and learning because of its simplicity, easy control of inputs (e.g., visual stimulation), and precise control and measurement of motor outputs (eye position). This is especially true in primates, which are easily trained to perform oculomotor tasks. Here we provide the first detailed characterization of the oculomotor performance of trained squirrel monkeys, primates used extensively in oculomotor physiology, during saccade and smooth pursuit tasks, and compare it to that of the rhesus macaque. We found that both primates have similar oculomotor behavior but the rhesus shows a larger oculomotor range, better performance for horizontal saccades above 10 degrees, and better horizontal smooth pursuit gain to target velocities above 15 deg/s. These results are important for interspecies comparisons and necessary when selecting the best stimuli to study motor control and motor learning in the oculomotor systems of these primates.     

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.     

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.     

Smooth pursuit eye movements in children

Smooth pursuit eye movements consists of slow eye movements that approximate the velocity of the eyes to that of a small moving target, so that target image is kept at or near the fovea. Little information on smooth pursuit is available in children. We used an infrared eye tracker to record smooth pursuit in 38 typically developing children, aged 8–19 years. Participants followed a visual target moving sinusoidally at ±10° amplitude, horizontally and vertically at 0.25 or 0.5 Hz. The mean horizontal smooth pursuit gains, the ratio of eye to target velocities, were 0.84 at 0.25 Hz and 0.73 at 0.5 Hz. Mean vertical smooth pursuit gains were 0.68 at 0.25 Hz and 0.45 at 0.5 Hz. Smooth pursuit gains were significantly lower for vertical in comparison to horizontal tracking, and for 0.5 Hz in comparison to 0.25 Hz tracking (P<0.0001). Smooth pursuit gains increased with age (P<0.01, Pearson’s correlation tests), with horizontal gains attaining reported adult values by mid adolescence. Vertical gains had large variability among participants. The median phase, the time interval between eye and target velocities, varied between 39 and 86 ms. Phase was not influenced by age. We conclude that smooth pursuit gains are lower in children than gains reported in adults. Vertical pursuit gain is significantly lower than horizontal pursuit gain. Gains improve with age and approach adult values in mid adolescence. Children have larger phases than reported adults values indicating that prediction in the smooth pursuit system is less mature in children.     

Context-dependent smooth eye movements evoked by stationary visual stimuli in trained monkeys

The appearance of a stationary but irrelevant cue triggers a smooth eye movement away from the position of the cue in monkeys that have been trained extensively to smoothly track the motion of moving targets while not making saccades to the stationary cue. We have analyzed the parameters that regulate the size of the cue-evoked smooth eye movement and examined whether presentation of the cue changes the initiation of pursuit for subsequent steps of target velocity. Cues evoked smooth eye movements in blocks of target motions that required smooth pursuit to moving targets, but evoked much smaller smooth eye movements in blocks that required saccades to stationary targets. The direction of the cue-evoked eye movement was always opposite to the position of the cue and did not depend on whether subsequent target motion was toward or away from the position of fixation. The latency of the cue-evoked smooth eye movement was near 100 ms and was slightly longer than the latency of pursuit for target motion away from the position of fixation. The size of the cue-evoked smooth eye movement was as large as 10 degrees /s and decreased as functions of the eccentricity of the cue and the illumination of the experimental room. To study the initiation of pursuit in the wake of the cues, we used bilateral cues at equal eccentricities to the right and left of the position of fixation. These evoked smaller eye velocities that were consistent with vector averaging of the responses to each cue. In the wake of bilateral cues, the initiation of pursuit was enhanced for target motion away from the position of fixation, but not for target motion toward the position of fixation. We suggest that the cue-evoked smooth eye movement is related to a previously postulated on-line gain control for pursuit, and that it is a side-effect of sudden activation of the gain-controlling element.     

Target anticipation and impairment of smooth pursuit eye movements in schizophrenia

A reduced gain of smooth pursuit eye velocity has frequently been reported in schizophrenic patients. With respect to predictable stimuli, this could be due to a deficit in predicting the target path. To determine this contribution to smooth pursuit eye movement performance, we analyzed the ocular smooth pursuit response to a sinusoidally moving target that was suddenly stopped after some cycles of regular movement. Horizontal eye movements were recorded with infrared reflection oculography in a group of 17 schizophrenic in-patients and 16 age-matched healthy subjects for controls. The patients exhibited a reduced gain of smooth pursuit velocity, but phase lag was not different from the control group. After the unpredictable stop of target movement, predictive sinusoidal smooth pursuit was maintained for 150 to 200 ms in both groups. The resulting maximal position and velocity error was larger in the patient group. In conclusion, schizophrenic patients were able to generate a normal anticipatory component of smooth pursuit and to switch it off in response to external demands. They showed, however, an increased velocity of anticipatory pursuit, which might be used to compensate for the primary deficit of smooth pursuit velocity frequently found in schizophrenics.     

Blink effects on ongoing smooth pursuit eye movements in humans

Blinks are known to affect eye movements, e.g., saccades, slow and fast vergence, and saccade-vergence interaction, in two ways: by superimposition of blink-associated eye movements and changes of the central premotor activity in the brainstem. The goal of this study was to determine, for the first time, the effects of trigeminal evoked blinks on ongoing smooth pursuit eye movements which could be related to visual sensory or premotor neuronal changes. This was compared to the effect of a target disappearing for 100–300 ms duration during ongoing smooth pursuit (blank paradigm) in order to control for the visual sensory effects of a blink. Eye and blink movements were recorded in eight healthy subjects with the scleral search coil technique. Blink-associated eye movements during the first 50% of the blink duration were non-linearly superimposed on the smooth pursuit eye movements. Immediately after the blink-associated eye movements, the pursuit velocity slowly decreased by an average of 3.2±2.1°/s. This decrease was not dependent on the stimulus direction. The pursuit velocity decrease caused by blinks which occluded the pupil more than 50% could be explained mostly by blanking the visual target. However, small blinks that did not occlude the pupil (<10% of lid closure) also decreased smooth pursuit velocity. Thus, this blink effect on pursuit velocity cannot be explained by blink-associated eye movements or by the blink having blanked the visual input. We propose that part of this effect might either be caused by incomplete visual suppression during blinks and/or a change in the activity of omnipause neurons.     

Latency of adaptive vergence eye movements induced by vergence-vestibular interaction training in monkeys

Clear vision of objects that move in depth toward or away from an observer requires vergence eye movements. The vergence system must interact with the vestibular system to maintain the object images on the foveae of both eyes during head movement. Previous studies have shown that training with sinusoidal vergence-vestibular interaction improves the frequency response of vergence eye movements during pitch rotation: vergence eye velocity gains increase and phase-lags decrease. To further understand the changes in eye movement responses in this adaptation, we examined latencies of vergence eye movements before and after vergence-vestibular training. Two head-stabilized Japanese monkeys were rewarded for tracking a target spot moving in depth that required vergence eye movements of 10°/s. This target motion was synchronized with pitch rotation at 20°/s. Both target and chair moved in a trapezoidal waveform interspersed with random inter-trial intervals. Before training, pitch rotation in complete darkness without a target did not induce vergence eye movements. Mean latencies of convergence and divergence eye movements induced by vergence target motion alone were 182 and 169 ms, respectively. After training, mean latencies of convergence and divergence eye movements to a target synchronized with pitch rotation shortened to 65 and 53 ms, and vergence eye velocity gains (relative to vergence target velocity) at the normal latencies were 0.68 and 1.53, respectively. Pitch rotation alone without a target induced vergence eye movements with similar latencies after training. These results indicate that vestibular information can be used effectively to initiate vergence eye movements following vergence-vestibular training.