Neuronal activity in medial superior temporal area (MST) during memory-based smooth pursuit eye movements in monkeys

We examined recently neuronal substrates for predictive pursuit using a memory-based smooth pursuit task that distinguishes the discharge related to memory of visual motion-direction from that related to movement preparation. We found that the supplementary eye fields (SEF) contain separate signals coding memory and assessment of visual motion-direction, decision not-to-pursue, and preparation for pursuit. Since medial superior temporal area (MST) is essential for visual motion processing and projects to SEF, we examined whether MST carried similar signals. We analyzed the discharge of 108 MSTd neurons responding to visual motion stimuli. The majority (69/108 = 64%) were also modulated during smooth pursuit. However, in nearly all (104/108 = 96%) of the MSTd neurons tested, there was no significant discharge modulation during the delay periods that required memory of visual motion-direction or preparation for smooth pursuit or not-to-pursue. Only 4 neurons of the 108 (4%) exhibited significantly higher discharge rates during the delay periods; however, their responses were non-directional and not instruction specific. Representative signals in the MSTd clearly differed from those in the SEF during memory-based smooth pursuit. MSTd neurons are unlikely to provide signals for memory of visual motion-direction or preparation for smooth pursuit eye movements

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 (Fukushima et al. in: J Neurophysiol 83:563–587, 2000). Responses of these neurons to whole body step-rotation at 20°/s were examined during cancellation of the vestibulo-ocular reflex (VOR), VOR ×1, and during chair steps in complete darkness without a target (VORd). The majority of pursuit neurons tested (∼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 ×1, discharge of the two groups of neurons diverged at ∼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 ×1 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

Submovement Composition of Head Movement

Limb movement is smooth and corrections of movement trajectory and amplitude are barely noticeable midflight. This suggests that skeletomuscular motor commands are smooth in transition, such that the rate of change of acceleration (or jerk) is minimized. Here we applied the methodology of minimum-jerk submovement decomposition to a member of the skeletomuscular family, the head movement. We examined the submovement composition of three types of horizontal head movements generated by nonhuman primates: head-alone tracking, head-gaze pursuit, and eye-head combined gaze shifts. The first two types of head movements tracked a moving target, whereas the last type oriented the head with rapid gaze shifts toward a target fixed in space. During head tracking, the head movement was composed of a series of episodes, each consisting of a distinct, bell-shaped velocity profile (submovement) that rarely overlapped with each other. There was no specific magnitude order in the peak velocities of these submovements. In contrast, during eye-head combined gaze shifts, the head movement was often comprised of overlapping submovements, in which the peak velocity of the primary submovement was always higher than that of the subsequent submovement, consistent with the two-component strategy observed in goal-directed limb movements. These results extend the previous submovement composition studies from limb to head movements, suggesting that submovement composition provides a biologically plausible approach to characterizing the head motor recruitment that can vary depending on task demand

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

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° right ear down and between upright and 40° left ear down were 6° (±6°) and 5° (±5°), 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

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

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

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

Memory and Decision Making in the Frontal Cortex during Visual Motion Processing for Smooth Pursuit Eye Movements

Cortical motor areas are thought to contribute "higher-order processing" but what that processing might include is unknown. Previous studies of the smooth pursuit-related discharge of supplementary eye field (SEF) neurons did not distinguish activity associated with the preparation for pursuit from discharge related to processing or memory of the target motion signals. Using a new, memory-based task, which was designed to separate these components, we show that the SEF contains signals coding retinal image-slip-velocity, memory and assessment of visual motion-direction, the decision of whether or not to pursue, and the preparation for pursuit eye movements. Bilateral muscimol injection into SEF resulted in directional errors in smooth pursuit, errors of whether or not to pursue, and impairment of initial correct eye movements. These results suggest an important role for the SEF in memory and assessment of visual motion-direction and the programming of appropriate pursuit eye movements

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