Clinical application of eye movement tasks as an aid to understanding Parkinson's disease pathophysiology.

Parkinson's disease (PD) is a progressive neurodegenerative disorder of the basal ganglia. Most PD patients suffer from somatomotor and oculomotor disorders. The oculomotor system facilitates obtaining accurate information from the visual world. If a target moves slowly in the fronto-parallel plane, tracking eye movements occur that consist primarily of smooth-pursuit interspersed with corrective saccades. Efficient smooth-pursuit requires appropriate target selection and predictive compensation for inherent processing delays. Although pursuit impairment, e.g. as latency prolongation or low gain (eye velocity/target velocity), is well known in PD, normal aging alone results in such changes. In this article, we first briefly review some basic features of smooth-pursuit, then review recent results showing the specific nature of impaired pursuit in PD using a cue-dependent memory-based smooth-pursuit task. This task was initially used for monkeys to separate two major components of prediction (image-motion direction memory and movement preparation), and neural correlates were examined in major pursuit pathways. Most PD patients possessed normal cue-information memory but extra-retinal mechanisms for pursuit preparation and execution were dysfunctional. A minority of PD patients had abnormal cue-information memory or difficulty in understanding the task. Some PD patients with normal cue-information memory changed strategy to initiate smooth tracking. Strategy changes were also observed to compensate for impaired pursuit during whole body rotation while the target moved with the head. We discuss PD pathophysiology by comparing eye movement task results with neuropsychological and motor symptom evaluations of individual patients and further with monkey results, and suggest possible neural circuits for these functions/dysfunctions.

Relationship between improvements in motor performance and changes in anticipatory postural adjustments during whole-body reaching training.

Anticipatory postural adjustments (APAs) provide postural stability and play an important role in ensuring appropriate motor performance. APAs also change in various situations. However, it is unknown whether changes in APAs during repetitive movement training contribute to improvement in motor performance. This study aimed to investigate the relationship between improvement in motor performance and changes in APAs during repeated reaching training, as well as the learning effects on APA changes. Sixteen healthy subjects (23 ± 2 years of age) stood barefoot on a force platform and reached as quickly and accurately as possible to a target placed at their maximum reach distance immediately following a beep signal in a reaction time condition. Whole-body reaching training with the right arm was repeated 100 times for three consecutive days. Motor performance and APAs were evaluated on the first day, after discontinuation of training for one day, and again at three months. In addition, reaching with the left arm (untrained limb) was tested on the first and the fifth training day. Body position segments were measured using three-dimensional motion analysis. Surface electromyography of eight postural muscles in both lower limbs was recorded. Kinetics data were recorded using the force platform. Whole-body reaching training induced not only improvements in motor performance (e.g., increased peak hand velocity), but also changes in APAs (e.g., earlier APA onset and increased amplitude). These changes were strongly correlated with and occurred earlier than improvements in motor performance. The learning effects on APAs were retained after the discontinuation of training and were generalized to the untrained limb. These results suggest that change in APAs contributes to improvement in motor performance; that is, the central nervous system may be able to adapt APAs for improvement in motor performance.

No-go neurons in the cerebellar oculomotor vermis and caudal fastigial nuclei: planning tracking eye movements.

The cerebellar dorsal vermis lobules VI-VII (oculomotor vermis) and its output region (caudal fastigial nuclei, cFN) are involved in tracking eye movements consisting of both smooth-pursuit and saccades, yet, the exact role of these regions in the control of tracking eye movements is still unclear. We compared the neuronal discharge of these cerebellar regions using a memory-based, smooth-pursuit task that distinguishes discharge related to movement preparation and execution from the discharge related to the processing of visual motion signals or their memory. Monkeys were required to pursue (i.e., go), or not pursue (i.e., no-go) in a cued direction, based on the memory of visual motion direction and go/no-go instructions. Most (>60 %) of task-related vermal Purkinje cells (P-cells) and cFN neurons discharged specifically during the memory period following no-go instructions; their discharge was correlated with memory of no-go instructions but was unrelated to eye movements per se during the action period of go trials. The latencies of no-go discharge of vermal P-cells and cFN neurons were similar, but were significantly longer than those of supplementary eye field (SEF) no-go neurons during an identical task. Movement-preparation signals were found in ~30 % of smooth-pursuit-related neurons in these cerebellar regions and some of them also carried visual memory signals. Our results suggest that no-go neurons are a newly revealed class of neurons, detected using the memory-based pursuit task, in the oculomotor vermis-cFN pathway and that this pathway contributes specifically to planning requiring the working memory of no-go instructions and preparation of tracking eye movements.

Cue-dependent memory-based smooth-pursuit in normal human subjects: importance of extra-retinal mechanisms for initial pursuit.

Using a cue-dependent memory-based smooth-pursuit task previously applied to monkeys, we examined the effects of visual motion-memory on smooth-pursuit eye movements in normal human subjects and compared the results with those of the trained monkeys. These results were also compared with those during simple ramp-pursuit that did not require visual motion-memory. During memory-based pursuit, all subjects exhibited virtually no errors in either pursuit-direction or go/no-go selection. Tracking eye movements of humans and monkeys were similar in the two tasks, but tracking eye movements were different between the two tasks; latencies of the pursuit and corrective saccades were prolonged, initial pursuit eye velocity and acceleration were lower, peak velocities were lower, and time to reach peak velocities lengthened during memory-based pursuit. These characteristics were similar to anticipatory pursuit initiated by extra-retinal components during the initial extinction task of Barnes and Collins (J Neurophysiol 100:1135-1146, 2008b). We suggest that the differences between the two tasks reflect differences between the contribution of extra-retinal and retinal components. This interpretation is supported by two further studies: (1) during popping out of the correct spot to enhance retinal image-motion inputs during memory-based pursuit, pursuit eye velocities approached those during simple ramp-pursuit, and (2) during initial blanking of spot motion during memory-based pursuit, pursuit components appeared in the correct direction. Our results showed the importance of extra-retinal mechanisms for initial pursuit during memory-based pursuit, which include priming effects and extra-retinal drive components. Comparison with monkey studies on neuronal responses and model analysis suggested possible pathways for the extra-retinal mechanisms.

Cognitive processes involved in smooth pursuit eye movements: behavioral evidence, neural substrate and clinical correlation.

Smooth-pursuit eye movements allow primates to track moving objects. Efficient pursuit requires appropriate target selection and predictive compensation for inherent processing delays. Prediction depends on expectation of future object motion, storage of motion information and use of extra-retinal mechanisms in addition to visual feedback. We present behavioral evidence of how cognitive processes are involved in predictive pursuit in normal humans and then describe neuronal responses in monkeys and behavioral responses in patients using a new technique to test these cognitive controls. The new technique examines the neural substrate of working memory and movement preparation for predictive pursuit by using a memory-based task in macaque monkeys trained to pursue (go) or not pursue (no-go) according to a go/no-go cue, in a direction based on memory of a previously presented visual motion display. Single-unit task-related neuronal activity was examined in medial superior temporal cortex (MST), supplementary eye fields (SEF), caudal frontal eye fields (FEF), cerebellar dorsal vermis lobules VI-VII, caudal fastigial nuclei (cFN), and floccular region. Neuronal activity reflecting working memory of visual motion direction and go/no-go selection was found predominantly in SEF, cerebellar dorsal vermis and cFN, whereas movement preparation related signals were found predominantly in caudal FEF and the same cerebellar areas. Chemical inactivation produced effects consistent with differences in signals represented in each area. When applied to patients with Parkinson's disease (PD), the task revealed deficits in movement preparation but not working memory. In contrast, patients with frontal cortical or cerebellar dysfunction had high error rates, suggesting impaired working memory. We show how neuronal activity may be explained by models of retinal and extra-retinal interaction in target selection and predictive control and thus aid understanding of underlying pathophysiology.

[Cerebellum and eye movement control -- neuronal mechanisms of memory-based smooth-pursuit and their early clinical application].

Recent studies implicate the cerebellum in cognitive functions in addition to its well-established roles in motor control and learning. Using a memory-based smooth-pursuit task that separates visual working memory from motor preparation and execution, monkeys were trained to pursue (i.e., go) or not pursue (i.e., no-go), a cued direction, based on the working memory of visual motion-direction and a go/no-go instruction. Task-related neuronal activity was examined in cerebral and cerebellar major smooth-pursuit pathways. Different cerebral and cerebellar areas carried distinctly different signals during memory-based smooth-pursuit. In the cerebellum, prediction-related signals (visual working memory, pursuit selection and movement preparation) were represented in the vermal lobules VI-VII and caudal fastigial nucleus, whereas the floccular region (flocculus and ventral paraflocculus) contained predominantly execution-related signals. This task was applied to patients with cerebellar degeneration and idiopathic Parkinson's disease (PD). None of the PD patients tested exhibited impaired working memory of motion-direction and/or go/no-go selection, but they did show task-specific difficulty in generating an initial smooth-pursuit component, suggesting difficulty in smooth-pursuit preparation. In contrast, most cerebellar patients exhibited impaired visual working memory in addition to difficulty in preparing for and executing smooth-pursuit. These results suggest different roles for the basal ganglia and cerebellum in smooth-pursuit planning.

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.

[Disturbance in voluntary control of saccadic eye movements in disorders of social brain].

Disorders of the social brain include Autism Spectrum Disorders (ASD), schizophrenia (SZ) and schizoid- and schizotypal-personality disorders. ASD is one of the developmental disorders with brain dysfunction, but the pathophysiology has not been clarified. In contrast, recent studies suggest that schizophrenia patients have pathologic findings mainly in the frontal and temporal cortices. The frontal eye movement related areas are involved in voluntary control of saccadic eye movements such as anti-saccades. We examined voluntary control of saccadic eye movements in 13 adult subjects aged 20-35 with ASD and compared the results with the performances of 13 controls. In the anti-saccade task, ASD subjects showed error rates of 37.3 +/- 27.6 (mean +/- SD)%, significantly higher than controls (13.8 +/- 14.1%), although only 5 ASD subjects showed error rates higher than mean + 2SD of the controls. It has been shown that schizophrenia patients showed abnormalities in the antisaccade task including higher error rate and longer latencies. In our study about 70% of 99 schizophrenia patients showed abnormalities in the anti-saccade task. Difficulties in inhibiting reflexive saccades and initiating saccades without target based on working memory suggest dysfunction of the frontal eye movement areas such as the frontal eye field, supplementary eye field and prefrontal cortex. Although the number of ASD subjects examined was relatively small, the percentage of subjects who showed significantly higher error rates (mean 37.3%) was less compared to those of schizophrenics (mean 70%), suggesting less involvement of the frontal eye movement related areas in the ASD.

[Neurophysiological studies in autism spectrum disorders--comparison with those in schizophrenia].

There have been reports that autism spectrum disorders (ASD) share common symptoms with schizophrenia. Several imaging studies showed the overlap of the impaired brain circuit in ASD and schizophrenia. Accordingly, differential diagnoses between adult ASD and schizophrenia without positive symptoms are sometimes difficult. We examined whether they show common results in functional MRI studies involving viewing photos of different facial expressions, such as angry, happy, sad, and neutral faces. We also examined oculomotor tasks that consist of saccadic and smooth pursuit eye movements in the two groups of patients. In fMRI studies, 15 schizophrenia patients (8 females) and 15 ASD patients (9 females) who met the criteria for DSM-IV participated. For the typically developed (TD) control group, 15 subjects (6 females) with no history of neurological or psychiatric disorders were recruited from the community. There was no significant difference in ages and sex ratios among these three groups. ANOVA comparison indicated that the ASD group showed significantly reduced activity in the right fusiform gyrus (FG) on viewing sad, happy, and neutral expressions but higher activity in the right mirror neuron system in the frontal cortex during viewing an angry expression. These results suggest a disturbance of the FG for face recognition and an excessive reaction to angry faces in ASD subjects. On the other hand, schizophrenics showed significantly reduced activation in widespread cortical areas, including the frontal, parietal, temporal, and occipital cortex, in comparison with TD and ASD individuals. We also examined voluntary control of saccadic and smooth pursuit eye movements in 13 adult subjects aged 20-35 with ASD (5 females) and compared the results with the performance of 13 TDs. Saccadic and smooth pursuit eye movements were recorded using an infrared system. Compared with TDs, 38% of the ASD subjects showed higher error rates in the anti-saccade task. However, in horizontal sinusoidal smooth pursuit, they showed normal gains. On the other hand, about 70% of 99 schizophrenics showed abnormalities in the antisaccade tasks. In the smooth pursuit task, 60-70% of schizophrenics showed a lower gain than controls. In this study, although all of the ASD subjects were adults and the number examined was relatively small, their abnormalities in fMRI and eye movement tasks were milder than those of schizophrenics.

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.

Memory-based smooth pursuit: neuronal mechanisms and preliminary results of clinical application.

Using a memory-based smooth-pursuit task, macaque monkeys were trained to pursue (i.e., go) or not pursue (i.e., no-go), a cued direction, based on the memory of visual motion-direction and a go/no-go instruction. Task-related neuronal activity was examined in the supplementary eye fields, caudal frontal eye fields, cerebellar floccular region, dorsal vermis lobules VI-VII, and caudal fastigial nuclei. Different cerebral and cerebellar areas carried distinctly different signals during memory-based smooth pursuit. Chemical inactivation of these areas produced effects consistent with the differences in signals represented in each area. This task was applied to patients with idiopathic Parkinson's disease (PD), because impaired visual working memory has been reported during cognitive tasks in PD. None of the PD patients tested exhibited impaired working memory of motion-direction and/or go/no-go selection, but they had difficulty in preparing for and executing smooth-pursuit eye movements, suggesting a selective motor-related disturbance in Parkinson's disease.

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.

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.

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.

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.

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 have not distinguished activity associated with the preparation for pursuit from discharge related to processing or memory of the target motion signals. Using a memory-based task 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 to pursue, and the preparation for pursuit eye movements. Bilateral muscimol injection into SEF resulted in directional errors in smooth pursuit, errors of whether 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.

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.