Teppei Akao

Neuronal Activity in the Caudal Frontal Eye Fields of Monkeys during Memory-Based Smooth Pursuit Eye Movements: Comparison with the Supplementary Eye Fields

Recently, we examined the neuronal substrate of predictive pursuit during memory-based smooth pursuit and found that supplementary eye fields (SEFs) contain signals coding assessment and memory of visual motion direction, decision not-to-pursue (“no-go”), and preparation for pursuit. To determine whether these signals were unique to the SEF, we examined the discharge of 185 task-related neurons in the caudal frontal eye fields (FEFs) in 2 macaques. Visual motion memory and no-go signals were also present in the caudal FEF but compared with those in the SEF, the percentage of neurons coding these signals was significantly lower. In particular, unlike SEF neurons, directional visual motion responses of caudal FEF neurons decayed exponentially. In contrast, the percentage of neurons coding directional pursuit eye movements was significantly higher in the caudal FEF than in the SEF. Unlike SEF inactivation, muscimol injection into the caudal FEF did not induce direction errors or no-go errors but decreased eye velocity during pursuit causing an inability to compensate for the response delays during sinusoidal pursuit. These results indicate significant differences between the 2 regions in the signals represented and in the effects of chemical inactivation suggesting that the caudal FEF is primarily involved in generating motor commands for smooth-pursuit eye movements.

Neurons in the Caudal Frontal Eye Fields of Monkeys Signal Three‐Dimensional Tracking

To maintain optimal clarity of objects moving in three dimensions, precise coordination of binocular eye movements is required in frontal‐eyed primates. Caudal parts of the frontal eye fields (FEFs) contain smooth pursuit neurons and the discharge of the majority of them is related to vergence eye movements as well. However, whether or not those pursuit neurons carry true binocular signals has not been tested critically. Using dichoptic stimuli that dissociate horizontal movements of the left and right eyes, we found that all pursuit‐related, FEF neurons tested carried binocular signals.

Predictive signals in the pursuit area of the monkey frontal eye fields.

In order to pursue a moving target with our eyes, visual motion-signals are converted into eye movement commands. Because of delays in processing visual information, prediction is necessary to compensate for those response-delays and maintain target images on the foveae. Previous studies showed that the majority of FEF pursuit neurons receive visual signals related to actual and predicted target motion. However, in those studies, discharge related to the memory of visual motion could not be separated from that related to prediction. To distinguish the two, while fixating a stationary spot, monkeys were required to memorize the direction of random dot motion (cue-1). After a delay (delay-1), a second cue (cue-2) instructed the monkeys to prepare either pursuit in the memorized direction or to maintain fixation. After a second delay (delay-2), the monkeys selected the correct response. In virtually all tested neurons that showed a visual motion-response to cue-1, the response was not maintained during the delay-1. The majority of responsive neurons were modulated during cue-2 and delay-2. Changing the delay-2 duration also changed the duration of discharge modulation, suggesting that delay-2 modulation was predictive. These results suggest that activity related to visual motion-memory was not conveyed by the discharge of caudal FEF pursuit neurons.

Vergence eye movement signals in the cerebellar dorsal vermis.

We examined simple-spike activity of Purkinje cells (P-cells) that responded during a search task which required both vergence- and frontal-pursuit. Of a total of 100 responding P-cells, 16% discharged only for frontal-pursuit, 43% only for vergence-pursuit, and 41% for both. Thus, the majority of vermal pursuit P-cells modulated their activity during vergence-pursuit. These P-cells also discharged for vergence eye movements induced by step target-motion in-depth. The majority of vergence related P-cells carried convergence signals with both eye velocity and position sensitivities, and they discharged before the onset of convergence eye movements. Muscimol infusion into the sites where convergence P-cells were recorded resulted in a reduction of peak convergence eye velocity, of initial convergence eye acceleration, and of frontal-pursuit eye velocity. These results suggest specific involvement of the dorsal vermis in vergence eye movements.

Eye-Pursuit and Reafferent Head Movement Signals Carried by Pursuit Neurons in the Caudal Part of the Frontal Eye Fields during Head-Free Pursuit

Eye and head movements are coordinated during head-free pursuit. To examine whether pursuit neurons in frontal eye fields (FEF) carry gaze-pursuit commands that drive both eye-pursuit and head-pursuit, monkeys whose heads were free to rotate about a vertical axis were trained to pursue a juice feeder with their head and a target with their eyes. Initially the feeder and target moved synchronously with the same visual angle. FEF neurons responding to this gaze-pursuit were tested for eye-pursuit of target motion while the feeder was stationary and for head-pursuit while the target was stationary. The majority of pursuit neurons exhibited modulation during head-pursuit, but their preferred directions during eye-pursuit and head-pursuit were different. Although peak modulation occurred during head movements, the onset of discharge usually was not aligned with the head movement onset. The minority of neurons whose discharge onset was so aligned discharged after the head movement onset. These results do not support the idea that the head-pursuit–related modulation reflects head-pursuit commands. Furthermore, modulation similar to that during head-pursuit was obtained by passive head rotation on stationary trunk. Our results suggest that FEF pursuit neurons issue gaze or eye movement commands during gaze-pursuit and that the head-pursuit–related modulation primarily reflects reafferent signals resulting from head movements.

Further evidence for selective difficulty of upward eye pursuit in juvenile monkeys: effects of optokinetic stimulation, static roll tilt, and active head movements

The smooth-pursuit system moves the eyes in space accurately to track slowly moving objects of interest despite visual inputs from the moving background and/or vestibular inputs during head movements. Recently, our laboratory has shown that young primates exhibit asymmetric eye movements during vertical pursuit across a textured background; upward eye velocity gain is reduced. To further understand the nature of this asymmetry, we performed three series of experiments in young monkeys. In Experiment 1, we examined whether this asymmetry was due to an un-compensated downward optokinetic reflex induced by the textured background as it moves across the retina in the opposite direction of the pursuit eye movements. For this, we examined the monkeys’ ability to fixate a stationary spot in space during movement of the textured background and compared it with vertical pursuit across the stationary textured background. We also examined gains of optokinetic eye movements induced by downward motion of the textured background during upward pursuit. In both task conditions, gains of downward eye velocity induced by the textured background were too small to explain reduced upward eye velocity gains. In Experiment 2, we examined whether the frame of reference for low-velocity, upward pursuit was orbital or earth vertical. To test this, we first applied static tilt in the roll plane until the animals were nearly positioned on their side in order to dissociate vertical or horizontal eye movements in the orbit from those in space. Deficits were observed for upward pursuit in the orbit but not in space. In Experiment 3, we tested whether asymmetry was observed during head-free pursuit that requires coordination between eye and head movements. Asymmetry in vertical eye velocity gains was still observed during head-free pursuit although it was not observed in vertical head velocity. These results, taken together, suggest that the asymmetric eye movements during vertical pursuit are specific for upward, primarily eye pursuit in the orbit.

Involvement of the Frontal Oculomotor Areas in Developmental Compensation for the Directional Asymmetry in Smooth‐Pursuit Eye Movements in Young Primates

The smooth pursuit system moves the eyes in space to accurately track objects of interest and maintain their images on the foveae while compensating for conflicting visual inputs from the moving background and/or vestibular inputs during head movements. Under demanding task conditions, young (but not mature) primates have difficulty with upward smooth gaze (eye in space) movement; pursuit breaks down, and they perform the task with saccades. Proper compensation matures later, after preadolescence. Chemical inactivation of the supplementary eye fields in compensated monkeys reproduced the directional asymmetry that had been compensated developmentally, suggesting that the supplemental eye fields may be involved in the compensation.

Representation of Neck Velocity and Neck–Vestibular Interactions in Pursuit Neurons in the Simian Frontal Eye Fields

The smooth pursuit system must interact with the vestibular system to maintain the accuracy of eye movements in space (i.e., gaze-movement) during head movement. Normally, the head moves on the stationary trunk. Vestibular signals cannot distinguish whether the head or whole body is moving. Neck proprioceptive inputs provide information about head movements relative to the trunk. Previous studies have shown that the majority of pursuit neurons in the frontal eye fields (FEF) carry visual information about target velocity, vestibular information about whole-body movements, and signal eye- or gaze-velocity. However, it is unknown whether FEF neurons carry neck proprioceptive signals. By passive trunk-on-head rotation, we tested neck inputs to FEF pursuit neurons in 2 monkeys. The majority of FEF pursuit neurons tested that had horizontal preferred directions (87%) responded to horizontal trunk-on-head rotation. The modulation consisted predominantly of velocity components. Discharge modulation during pursuit and trunk-on-head rotation added linearly. During passive head-on-trunk rotation, modulation to vestibular and neck inputs also added linearly in most neurons, although in half of gaze-velocity neurons neck responses were strongly influenced by the context of neck rotation. Our results suggest that neck inputs could contribute to representing eye- and gaze-velocity FEF signals in trunk coordinates.

Oscillatory eye movements resembling pendular nystagmus in normal juvenile macaques

PURPOSE Juvenile monkeys being trained on smooth-pursuit tasks exhibit ocular oscillations resembling pendular nystagmus. The purpose of this study was to analyze these oscillations, the effects of gabapentin on them, and responses of cerebellar floccular neurons to understand possible neuronal mechanisms. METHODS Four monkeys were trained for horizontal and vertical smooth pursuit; in two, saccades were also tested. Frequency, peak-to-peak eye velocity, and amplitude of the ocular oscillations were measured. In one monkey, the effect of gabapentin on the oscillations was measured, and oscillation-related neuronal discharge was recorded in the cerebellar floccular region. RESULTS Ocular oscillations, with features of pendular nystagmus, appeared early during training of both horizontal and vertical pursuit in all four monkeys. Although these oscillations were observed both in the direction of pursuit and orthogonally, the velocity and amplitude of oscillation were larger in the direction of pursuit, implicating pursuit mechanisms in their generation. Corrective saccades were often superimposed on the oscillations during pursuit and fixation. Gabapentin suppressed oscillations in the monkey tested. Recordings in the floccular region revealed a subset of neurons discharged during both the oscillations and corrective saccades. Many of them exhibited burst-tonic discharge during visually guided saccades, similar to discharge of brain stem burst-tonic neurons, suggesting contributions of the neural integrator to the oscillations. CONCLUSIONS The developmentally transient ocular oscillations occurring in monkeys during pursuit training has properties resembling pendular nystagmus. Both smooth pursuit and a neural integrator may contribute to these ocular oscillations. Analysis using an efference-copy pursuit model supports the interpretation herein.

Reafferent head-movement signals carried by pursuit neurons of the simian frontal eye fields during head movements.

The smooth‐pursuit system is important to precisely track a slowly moving object and maintain its image on the foveae during movement. During whole‐body rotation, the smooth‐pursuit system interacts with the vestibular system. The caudal part of the frontal eye fields (FEF) contains smooth pursuit–related neurons that signal eye velocity during pursuit. The majority of them receives vestibular inputs and signal gaze‐velocity during passive whole‐body rotation. It was asked whether discharge modulation of FEF pursuit neurons during head rotation on the stationary trunk could be accounted for by vestibular inputs only or if both vestibular and neck proprioceptive inputs contributed to the modulation. Discharge modulation during active head pursuit, passive head rotation on the stationary trunk, passive whole‐body rotation, and passive trunk rotation against the stationary head were compared. The results indicate that both vestibular and neck proprioceptive inputs contributed to the discharge modulation of FEF pursuit neurons during head movements.