Frontal Eye Fields Pursuit Neurons Research Articles

Vestibular-Related Frontal Cortical Areas and Their Roles in Smooth-Pursuit Eye Movements: Representation of Neck Velocity, Neck-Vestibular Interactions, and Memory-Based Smooth-Pursuit

Smooth-pursuit eye movements are voluntary responses to small slow-moving objects in the fronto-parallel plane. They evolved in primates, who possess high-acuity foveae, to ensure clear vision about the moving target. The primate frontal cortex contains two smooth-pursuit related areas; the caudal part of the frontal eye fields (FEF) and the supplementary eye fields (SEF). Both areas receive vestibular inputs. We review functional differences between the two areas in smooth-pursuit. Most FEF pursuit neurons signal pursuit parameters such as eye velocity and gaze-velocity, and are involved in canceling the vestibulo-ocular reflex by linear addition of vestibular and smooth-pursuit responses. In contrast, gaze-velocity signals are rarely represented in the SEF. Most FEF pursuit neurons receive neck velocity inputs, while discharge modulation during pursuit and trunk-on-head rotation adds linearly. Linear addition also occurs between neck velocity responses and vestibular responses during head-on-trunk rotation in a task-dependent manner. During cross-axis pursuit–vestibular interactions, vestibular signals effectively initiate predictive pursuit eye movements. Most FEF pursuit neurons discharge during the interaction training after the onset of pursuit eye velocity, making their involvement unlikely in the initial stages of generating predictive pursuit. Comparison of representative signals in the two areas and the results of chemical inactivation during a memory-based smooth-pursuit task indicate they have different roles; the SEF plans smooth-pursuit including working memory of motion–direction, whereas the caudal FEF generates motor commands for pursuit eye movements. Patients with idiopathic Parkinson’s disease were asked to perform this task, since impaired smooth-pursuit and visual working memory deficit during cognitive tasks have been reported in most patients. Preliminary results suggested specific roles of the basal ganglia in memory-based smooth-pursuit.

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.

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.

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 degrees/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 degrees/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.

Otolith inputs to pursuit neurons in the frontal eye fields of alert monkeys

The smooth-pursuit system must interact with the vestibular system to maintain the accuracy of eye movements in space during head movement. Maintenance of a target image on the foveae is required not only during head rotation which activates primarily semi-circular canals but also during head translation which activates otolith organs. The caudal part of the frontal eye fields (FEF) contains pursuit neurons. The majority of them receive vestibular inputs induced by whole body rotation. However, it has not been tested whether FEF pursuit neurons receive otolith inputs. In the present study, we first classified FEF pursuit neurons as belonging to one of three groups (vergence + fronto-parallel pursuit, vergence only, fronto-parallel pursuit only) based on their responses during fronto-parallel pursuit and mid-sagittal vergence-pursuit. We, then, tested discharge modulation of these neurons during fore/aft and/or right/left translation by passively moving the whole body sinusoidally at 0.33 Hz (+/-10 cm, peak velocity 19 cm/s; 0.04g). The majority of FEF pursuit neurons in all three groups were activated by fore/aft and right/left translation without a target in complete darkness. There was no correlation between the magnitude of discharge modulation and translational vestibulo-ocular reflex (VOR). Preferred directions of translational responses were distributed nearly evenly in front of the monkeys. Discharge modulation was also observed when a target moved together with whole body, requiring the monkeys to cancel the translational VOR. These results indicate that the discharge modulation of FEF pursuit neurons during whole body translation reflected otolith inputs.

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 degrees, peak target velocity 12.5-75.0 degrees/s). Gains of downward pursuit were 0.8-0.9 at 0.2-1.0 Hz, and peak downward eye velocity increased up to approximately 60 degrees/s linearly with target velocity, whereas peak upward eye velocity saturated at 15-20 degrees/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 approximately 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.

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.

Activity of pursuit neurons in the caudal part of the frontal eye fields during static roll-tilt

The smooth-pursuit system and vestibular system interact to keep the retinal target image on the fovea during head and/or whole body movements. The caudal part of the frontal eye fields (FEF) in the fundus of arcuate sulcus contains pursuit neurons and the majority of them respond to vestibular stimulation induced by whole-body rotation, that activates primarily semi-circular canals, and by whole-body translation, that activates otoliths. To examine whether coordinate frames representing FEF pursuit signals are orbital or earth-vertical, we compared preferred directions during upright and static, whole-body roll-tilt in head- and trunk-restrained monkeys. Preferred directions (re monkeys' head/trunk axis) of virtually all pursuit neurons tested (n = 21) were similar during upright and static whole-body roll-tilt. The slight shift of preferred directions of the majority of neurons could be accounted for by ocular counter-rolling. The mean (+/-SD) differences in preferred directions between upright and 40 degrees right ear down and between upright and 40 degrees left ear down were 6 degrees (+/-6 degrees) and 5 degrees (+/-5 degrees), respectively. Visual motion preferred directions were also similar in five pursuit neurons tested. To examine whether FEF pursuit neurons could signal static whole-body roll-tilt, we compared mean discharge rates of 29 neurons during fixation of a stationary spot while upright and during static, whole-body roll-tilt. Virtually all neurons tested (28/29) did not exhibit a significant difference in mean discharge rates between the two conditions. These results suggest that FEF pursuit neurons do not signal static roll-tilt and that they code pursuit signals in head/trunk-centered coordinates.

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

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

The vestibular-related frontal cortex and its role in smooth-pursuit eye movements and vestibular-pursuit interactions

In order to see clearly when a target is moving slowly, primates with high acuity foveae use smooth-pursuit and vergence eye movements. The former rotates both eyes in the same direction to track target motion in frontal planes, while the latter rotates left and right eyes in opposite directions to track target motion in depth. Together, these two systems pursue targets precisely and maintain their images on the foveae of both eyes. During head movements, both systems must interact with the vestibular system to minimize slip of the retinal images. The primate frontal cortex contains two pursuit-related areas; the caudal part of the frontal eye fields (FEF) and supplementary eye fields (SEF). Evoked potential studies have demonstrated vestibular projections to both areas and pursuit neurons in both areas respond to vestibular stimulation. The majority of FEF pursuit neurons code parameters of pursuit such as pursuit and vergence eye velocity, gaze velocity, and retinal image motion for target velocity in frontal and depth planes. Moreover, vestibular inputs contribute to the predictive pursuit responses of FEF neurons. In contrast, the majority of SEF pursuit neurons do not code pursuit metrics and many SEF neurons are reported to be active in more complex tasks. These results suggest that FEF- and SEF-pursuit neurons are involved in different aspects of vestibular-pursuit interactions and that eye velocity coding of SEF pursuit neurons is specialized for the task condition.

Visual and vergence eye movement-related responses of pursuit neurons in the caudal frontal eye fields to motion-in-depth stimuli

The caudal parts of the frontal eye fields (FEF) contain smooth-pursuit related neurons. Previous studies show that most FEF pursuit neurons carry visual signals in relation to frontal spot motion and discharge before the initiation of smooth-pursuit. It has also been demonstrated that most FEF pursuit neurons discharge during vergence tracking. Accurate vergence tracking requires information about target motion-in-depth. To further understand the role of the FEF in vergence tracking and to determine whether FEF pursuit neurons carry visual information about target motion-in-depth, we examined visual and vergence eye movement-related responses of FEF pursuit neurons to sinusoidal spot motion-in-depth. During vergence tracking, most FEF pursuit neurons exhibited both vergence eye position and velocity sensitivity. Phase shifts (re target velocity) of most neurons remained virtually constant up to 1.5 Hz. About half of FEF pursuit neurons exhibited visual responses to spot motion-in-depth. The preferred directions for visual responses of most neurons were similar to those during vergence tracking. Visual responses of most of these neurons exhibited sensitivity to the velocity of spot motion-in-depth. Phase shifts of most of the responding neurons remained virtually constant up to 2.0 Hz. Neurons that exhibited visual responses in-depth were mostly separate from neurons that showed visual responses in the frontal plane. To further examine whether FEF pursuit neurons could participate in initiation of vergence tracking, we examined latencies of neuronal responses with respect to vergence eye movements induced by step target motion-in-depth. About half of FEF pursuit neurons discharged before the onset of vergence eye movements with lead times longer than 20 ms. These results together with previous observations suggest that the caudal FEF carries visual signals appropriate to be converted into motor commands for pursuit in depth and frontal plane.

Role of Vestibular Signals in the Caudal Part of the Frontal Eye Fields in Pursuit Eye Movements in Three‐Dimensional Space

For accurate visual information about objects of interest moving slowly in three-dimensional (3D) space, primates with binocular fields use both frontal smooth-pursuit (frontal-pursuit) and vergence eye movements (i.e., depth pursuit) to maintain the images of the objects precisely on the foveae of left and right eyes. Moreover, during head or whole-body movement, both frontal- and depth-pursuit systems must interact with the vestibular system to minimize slip of the retinal images that degrades image quality considerably. The caudal part of the frontal eye fields (FEF) contains many frontal-pursuit neurons. Previous studies have shown that a majority of pursuit neurons there discharge for both frontal pursuit and vergence and carry pursuit-in-3D signals. To understand how vestibular inputs interact with pursuit-in-3D signals, three different experiments that examined the nature of vestibular signals in the caudal FEF are described in this review. A majority of caudal FEF pursuit neurons responded to whole-body rotation with preferred directions similar to frontal-pursuit directions and carried frontal gaze (eye-in-space) velocity signals. They were activated in association with adaptive pursuit eye movements induced by cross-axis pursuit-vestibular interactions. During fore/aft and right/left translation in complete darkness, they were also modulated with preferred directions of many neurons similar to pursuit-preferred directions. Previous studies showed that caudal FEF pursuit neurons also receive visual signals about target motion. Taken together, these results suggest that the caudal FEF coordinates its various inputs to provide signals for accurate eye-movement-in-space commands.

Discharge Characteristics of Pursuit Neurons in MST During Vergence Eye Movements

For small objects moving smoothly in space close to the observer, smooth pursuit and vergence eye movements maintain target images near the foveae to insure high-resolution processing of visual signals about moving objects. Signals for both systems must be synthesized for pursuit-in-three-dimensions (3D). Recent studies have shown that responses of the majority of pursuit neurons in the frontal eye fields (FEF) code pursuit-in-3D. This area is known to have reciprocal connections with the medial superior temporal area (MST) where frontal pursuit neurons are found. To examine whether pursuit-in-3D signals are already present in MST and how MST neurons discharge during vergence-tracking induced by a small spot, we examined discharge of MST pursuit neurons in 2 monkeys. Of a total of 219 pursuit neurons examined during both frontal pursuit and vergence-tracking, 61% discharged only for frontal pursuit, 18% only for vergence-tracking, and 21% for both. A majority of vergence-related MST neurons exhibited sensitivity to vergence eye velocity. Their discharge was maintained during brief blanking of a vergence target. About 1/3 of vergence-related MST neurons exhibited visual responses to spot motion in depth. The preferred directions for visual motion and vergence-tracking were similar in half of our population. Some of the remaining neurons showed opposite preferred directions. A significant proportion (29%) of vergence-related neurons discharged before onset of eye movements with lead times longer than 20 ms. The results in this and previous studies indicate differences in discharge characteristics of FEF and MST pursuit neurons, suggesting different roles for the two in pursuit-in-3D.