The effect of microstimulation of the oculomotor vermis on discharges of fastigial neurons and visually-directed saccades in macaques

The present study confirmed our previous reports that neurons in the fastigial oculomotor region (FOR) of the macaque show presaccadic bursts during contralateral saccades and that the burst duration is closely related to the duration of the accompanying saccade. Furthermore, when the burst duration was reduced by subthreshold electrical stimulation applied to the oculomotor vermis prior to the onset of the burst, the impending visually-directed saccade became hypometric. The reduction in the burst duration was closely related to the degree of the hypometria. Since saccadic burst neurons in the FOR constitute the sole output channel for saccadic signals of the oculomotor vermis, the findings support the hypothesis that the cerebellum can regulate the amplitude of eye movements.     

Saccade-related Purkinje cell activity in the oculomotor vermis during spontaneous eye movements in light and darkness

Saccade-related Purkinje cells (PCs) were recorded in the oculomotor vermis (lobules VI, VII) during spontaneous eye movements and fast phases of optokinetic and vestibular nystagmus in the light and darkness, from two macaque monkeys. All neurons (n=46) were spontaneously active and exhibited a saccade-related change of activity with all saccades and fast phases of nystagmus. Four types of neurons were found: most neurons (n=31) exhibited a saccade-related burst of activity only (VBN); other units (n=7) showed a burst of activity with a subsequent pause (VBPN); some of the units (n=5) paused in relation to the saccadic eye movement (pause units,VPN); a few PCs (n=3) showed a burst of activity in one direction and a pause of activity in the opposite direction. For all neurons, burst activity varied considerably for similar saccades. There were no activity differences between spontaneous saccades and vestibular or optokinetically elicited fast phases of nystagmus. The activity before, during, and after horizontal saccades was quantitatively analyzed. For 24 burst PCs (VBN, VBPN), the burst started before saccade onset in one horizontal direction (preferred direction), on average by 15.3 ms (range 27-5 ms). For all these neurons, burst activity started later in the opposite (non-preferred) direction, on average 4.9 ms (range 20 to -12 ms, P<0.01) before saccade onset. The preferred direction could be either with ipsilateral (42% of neurons) or contralateral (58%) saccades. Nine burst PCs had similar latencies and burst patterns in both horizontal directions. The onset of burst activity of a minority of PCs (n=5) lagged saccade onset in all directions. The pause for VBPN neurons started after the end of the saccade and reached a minimum of activity some 40–50 ms after saccade completion. For all saccades and quick phases of nystagmus, burst duration increased with saccade duration. Peak burst activity was not correlated with saccade amplitude or peak eye velocity. PCs continued to show saccade-related burst activity in the dark. However, in 59% of the PCs (VBN, VBPN), peak burst activity was significantly reduced in the dark (on average 28%, range 15–36%) when saccades with the same amplitude (but longer duration in the dark) were compared. For VBP neurons, the pause component after the saccade disappeared in the dark. The difference in peak burst activity (light vs darkness) is similar to that seen for saccade-related neurons in the fastigial oculomotor region (FOR, the structure receiving direct input from vermal PCs) and suggests that the oculomotor vermis also might affect saccade acceleration and/or deceleration. The findings indicate that in the oculomotor vermis — in contrast to the FOR — several different types of saccade-related neurons (PCs) are found. However, the vast majority of PCs behave qualitatively similar to FOR neurons with regard to the burst activity pattern and a direction-specific burst activity onset starting well before saccade onset. This latency will allow these neurons to influence the initiation of saccades in the saccadic brainstem generator through multisynaptic pathways. At present, it has to be determined how (saccade-related) PC activity determines FOR activity.     

Burst discharges of mossy fibers in the oculomotor vermis of macaque monkeys during saccadic eye movements.

Mossy fiber activity was recorded from the oculomotor vermis (lobules VIc and VII) during visually guided saccades. Saccade-related activities of 99 mossy fiber units were observed in two alert macaque monkeys. Ninety-six units were characterized by high-frequency bursts of firing in response to visually guided saccades (burst unit). These units were silent during all periods of fixation in any gaze position. Three units showed eye position-related tonic discharges with saccadic bursts. The lead time of saccadic bursts ranged from 2.6 to 80.5 ms (mean 27.9 ms, SD 16.6 ms). About 75% of the burst units exhibited a long lead burst characterized by a slow buildup, while the remaining units showed short lead bursts with a sharp onset. About 80% of the units showed burst in association with contralaterally directed saccades. The remaining units exhibited bursts in association with ipsilateral saccades. Preferred directions in this population covered the entire field including the vertical and the oblique. About 68% of long lead burst units exhibited the movement field which consists of a whole sector of the entire oculomotor range (directional type). About 32% of long lead burst units showed the movement field which is a closed area within the oculomotor range (vectorial type). On the other hand, peak frequency of short lead burst units increased in proportion to saccade amplitude. The end of the burst in all units always preceded the completion of saccade. The end of burst was time-locked to the completion of saccade, so that the lead time from the end of burst to the end of saccade was consistent among these units and, was constant regardless of saccadic amplitude. The duration between the peak and the offset of burst was correlated with the amplitude of saccade (0.63 < or = r < or = 0.83). Long lead burst of mossy fibers was almost comparable to burst activity in the nucleus reticularis tegmenti pontis (NRTP), while short lead burst of mossy fibers closely resembles activity of excitatory burst neurons in the paramedian pontine reticular formation (PPRF). These findings suggest that the cerebellum receives command signal from the superior colliculus via the NRTP and feedback signal from the PPRF.     

Saccade-related activity in the fastigial oculomotor region of the macaque monkey during spontaneous eye movements in light and darkness

Saccade-related burst neurons were recorded in the caudal part of the fastigial nucleus (fastigial oculomotor region) during spontaneous eye movements and fast phases of optokinetic and vestibular nystagmus in light and darkness from three macaque monkeys. All neurons (n=47) were spontaneously active and exhibited a burst of activity with each saccade and fast phase of nystagmus. Most neurons (n=31) only exhibited a burst of activity, whereas those remaining also exhibited a pause in firing rate before or after the burst. Burst parameters varied considerably for similar saccades. For horizontal saccades all neurons, except for three, had a preferred direction with an earlier onset of burst activity to the contralateral side. For contralateral saccades the burst started on average 17.5 ms before saccade onset, whereas the average lead-time for ipsilateral saccades was only 6.5 ms. Three neurons were classified as isotropic with similar latencies and peak burst activity in all directions. None of the neurons had a preferred direction with an earlier onset of burst activity to the ipsilateral side. Burst duration increased with saccade amplitude, whereas peak burst activity was not correlated with amplitude. There was no relationship between peak burst activity and peak eye velocity. In the dark, neurons generally continued to burst with each saccade and fast phase of nystagmus. Burst for saccades in the dark was compared with burst for saccades of similar amplitude and direction in the light. Saccades in the dark had a longer duration and peak burst activity was reduced on average to 62% (range 36–105%). In three neurons a burst in the dark was no longer clearly distinguishable above the ongoing spontaneous activity. These data suggest that the saccade-related burst neurons in the FOR modify saccadic profiles by directly influencing acceleration and deceleration, respectively, of individual eye movements. This could be achieved by an input to the inhibitory and excitatory burst neurons of the saccadic burst generator in the brainstem. From neuroanatomical studies it is known that FOR neurons project directly to the brainstem regions containing the immediate premotor structures for saccade generation.     

Topography of the oculomotor area of the cerebellar vermis in macaques as determined by microstimulation

1. Oculomotor responses to microstimulation of the cerebellar vermis of macaque monkeys were investigated by using a magnetic search-coil method. 2. The oculomotor responses were conjugate eye movements with an ipsilateral horizontal component. Analyses of amplitude-velocity and amplitude-duration relationships revealed that the peak eye velocities and the durations of the responses were comparable to those of saccadic eye movements. 3. Systematic mapping with microstimulation disclosed that the region in the cerebellar vermis that yielded saccades with weak stimulus currents was confined to lobule VII in five monkeys but included a part of folium VIc in the other four monkeys. This region coincided with the distribution of the saccade-related neural activity observed in the present study and also corresponded to the vermal folia from which we recorded the burst mossy-fiber units and the oculomotor Purkinje cell activity. 4. The oculomotor vermis was defined as that region of the cerebellar vermis that met the following criteria: 1) saccades were evoked with low-intensity microstimulation (with currents less than 10 microA); 2) vigorous saccade-related neural activity was present; and 3) Purkinje cell discharges were modulated with eye movements. The oculomotor vermis was more circumscribed and located more posteriorly than the vermal cortex explored in previous microstimulation experiments on monkeys. 5. Microstimulation of the oculomotor vermis evoked more or less curved saccades in oblique directions. The horizontal and vertical components were not simultaneous in some saccades: the shorter component started later or ended earlier than the other component and their peak velocities were not always synchronous. 6. The amplitude of the saccade depended on stimulus parameters; microstimulation with 10-12 pulses within a period of approximately 20 ms (500-600 Hz) was shown to be optimal. When the pulses were applied to the white matter or to the granular layer, a stimulus current of 10 microA was sufficient to evoke saccades. When the molecular layer was stimulated, evoked saccades were smaller and frequently curved, and an increase in the stimulus current changed either the initial direction or the trajectory of the saccade. 7. When the stimulus current was carefully controlled and maintained near the threshold, the direction of the saccade evoked from the oculomotor vermis was topographically organized.(ABSTRACT TRUNCATED AT 400 WORDS)     

Saccade-related neurons in the primate fastigial nucleus: what do they encode?

The cerebellar fastigial oculomotor region (FOR) and the overlying oculomotor vermis (OV) are involved in the control of saccadic eye movements, but nature and function of their saccade-related neuronal signals are not fully understood. There is controversy in at least two major aspects: first, lesion studies in OV/FOR reported eye-position-dependent dysmetria-with FOR lesions, centripetal saccades became more hypermetric than centrifugal saccades-suggesting that the cerebellum may compensate for orbital mechanics. However, single-unit studies failed to reveal corresponding eye-position dependencies in FOR saccade-related discharge patterns. Second, some single-unit studies reported precise correlation between burst and saccade duration in the FOR. However, others stated that FOR bursts were only weakly related to saccade properties. In an attempt to resolve these discrepancies, we recorded single FOR units in monkeys that made horizontal saccades (16 degrees ) from different starting positions. Sampling saccades of one fixed amplitude and application of an objective, computer-based burst-detection-routine allowed us to correlate burst parameters (onset latency, peak latency, peak amplitude, number of spikes, duration) and kinematic properties of individual saccades. FOR bursts were found to start and peak earlier and exhibit higher peak burst amplitudes for faster than for slower saccades of the same amplitude. While these correlations between FOR bursts and saccade properties were statistically significant for a minority of approximately 20-25% of individual units, the same effects were also predominant in the remainder of the neuronal sample and statistically significant on the population level. Neuronal activity was not significantly modulated by eye position itself. However, reflecting differences in saccade velocities but not an actual influence of eye position per se, FOR bursts for centripetal and centrifugal saccades exhibited subtle but systematic differences, which closely paralleled, and hence probably explain, the eye-position dependency of deficits observed after FOR inactivation. Our findings indicate that FOR signals reflect much of the kinematic properties of the saccade. Moreover, they are consistent with the idea that the FOR output is purposefully modified according to these kinematic properties to maintain saccadic accuracy.     

A quantitative analysis of the correlations between eye movements and neural activity in the pretectum

The study of the saccadic system has focused mainly on neurons active before the beginning of saccades, in order to determine their contribution in movement planning and execution. However, most oculomotor structures contain also neurons whose activity starts only after the onset of saccades, the maximum of their activity sometimes occurring near saccade end. Their characteristics are still largely unknown. We investigated pretectal neurons with saccade-related activity in the alert cat during eye movements towards a moving target. They emitted a high-frequency burst of action potentials after the onset of saccades, irrespective of their direction, and will be referred to as "pretectal saccade-related neurons". The delay between saccade onset and cell activity varied from 17 to 66 ms on average. We found that burst parameters were correlated with the parameters of saccades; the peak eye velocity was correlated with the peak of the spike density function, the saccade amplitude with the number of spikes in the burst, and burst duration increased with saccade duration. The activity of six pretectal saccade-related neurons was studied during smooth pursuit at different velocities. A correlation was found between smooth pursuit velocity and mean firing rate. A minority of these neurons (2/6) were also visually responsive. Their visual activity was proportional to the difference between eye and target velocity during smooth pursuit (retinal slip). These results indicate that the activity of pretectal saccade-related neurons is correlated with the characteristics of eye movements. This finding is in agreement with the known anatomical projections from premotor regions of the saccadic system to the pretectum.     

Presaccadic omnidirectional burst activity in the basal interstitial nucleus in the monkey cerebellum

We recorded saccade-related neurons in the vicinity of the dentate nucleus of the cerebellum in two monkeys trained to perform visually guided saccades and memory-guided saccades. Among 76 saccade-related neurons, 38 showed presaccadic bursts in all directions. More than 80% of such burst neurons were located in the area ventral to, not inside, the dentate nucleus, which corresponded to the basal interstitial nucleus (BIN as previously described). We found that the activity of the BIN neurons was correlated with saccade duration but not with saccade amplitude or velocity. Thus, when tested with visually guided saccades, the burst started about 16 ms before saccade onset and ended about 33 ms before saccade offset, regardless of saccade amplitude. The characteristic timing of the BIN cell activity was maintained for different types of saccades (visually guided, memory-guided and spontaneous saccades), which had different dynamics. Although the number of spikes in a burst for each neuron was linearly correlated with saccade amplitude for a given type of saccade, the slope varied depending on the type of saccade. Peak burst frequency was uncorrelated with saccadic peak velocity. In contrast, burst duration was highly correlated with saccade duration regardless of the type of saccade. These results suggest that BIN neurons may carry information to determine the timing of saccades. Received: 14 August 1997 / Accepted: 17 February 1998     

Cerebellar control of saccadic eye movements: its neural mechanisms and pathways

Microstimulation studies on monkeys have shown that the cerebellar cortex which is related to saccadic function is located in lobules VIc and VII of the vermis. This vermal area is designated as the oculomotor vermis and characterized by low thresholds (less than 10 microA) and by saccade-related neuronal activity. The saccade evoked by the vermal stimulation has been shown to be the result of activation of Purkinje-cell axons. On the other hand, an anterograde WGA-HRP transport study has indicated that the Purkinje-cell axons of the oculomotor vermis terminate almost exclusively in a fatigial region which is designated as the fastigial oculomotor region (FOR). Microstimulation of the oculomotor vermis and the ventromedial aspect of the FOR results in saccades which differ in their horizontal directions, with vermal stimulation resulting in ipsilateral and fastigial stimulation resulting in contralateral saccades. Since the ipsilateral saccades evoked from the caudal part of the FN were suppressed by bicuculline, they were the results of stimulation of the Purkinje axons. It has been also shown that stimulation of the oculomotor vermis causes inhibition of FOR neurons. Furthermore, fastigial neurons bursting with saccades can be recorded only within the anatomical confines of the FOR. These data are consistent with the concept that signals from the vermis are transmitted to the saccadic nuclei of the brainstem via the FOR. Neurons in the FOR have been shown to project to various saccade-related nuclei, including the riMLF and PPRF. Some neurons in the FOR have divergent axon collaterals which terminate in both the vertical and horizontal preoculomotor nuclei. When the initial eye position is changed by stimulating the FN prior to visually-guided saccades, monkeys cannot compensate for the stimulation-induced movement. When the stimulation is delived 75-130 ms after the target presentation, saccades are triggered prematurely. The visuomotor processing for saccades seems to be completed during this period, which is approximately half the latency of normal saccades. When saccades were triggered prematurely at an early stage of information processing, the eyes moved first in the direction of evoked saccade and then changed the direction toward the location of the target without any intervening period. The retinal error information sampled before the stimulation was not disturbed by the cerebellar stimulation. These observations suggest that cerebellar output impulses are projected downstream to saccade-programming circuits where visual information has already been converted into motor-command signals. The cerebellum is a domain for parallel processing of visuomotor information.     

Direction-selective saccadic-burst neurons in the fastigial oculomotor region of the macaque

Summary Discharges of 68 neurons, recorded from the oculomotor region of the fastigial nucleus (FN) of the macaque, were characterized by a burst which started approximately 20 msec prior to the onset of a saccade in a direction contralateral to the recording site. These fastigial neurons also paused before saccades in their nonpreferred direction and then discharged with a subsequent burst. All units were spontaneously active but the tonic level of activity did not reflect eye position. They aggregated within the oculomotor region and the firing of 57 units (83.8%) was suppressed by stimulation of vermal lobule VII. Tonic discharges of six other units were closely related to eye position and located rostral to the burst units. Discharges of 16 units increased during the ipsilateral phase of sinusoidal head rotation and those of 50 units increased during contralateral head rotation. These neurons did not show saccade-related activity. They were widely scattered in the rostral and central portions of the FN. None of these units was inhibited by stimulation of vermal lobule VII.     

Supplementary eye field: representation of saccades and relationship between neural response fields and elicited eye movements

The functional organization of the low-threshold supplementary eye field (SEF) was studied by analyzing presaccadic activity, electrically elicited saccades, and the relationship between them. Response-field optimal vectors, defined as the visual field coordinates or saccadic eye-movement dimensions evoking the highest neural discharge, were quantitatively estimated for 160 SEF neurons by systematically varying peripheral target location relative to a central fixation point and then fitting the responses to Gaussian functions. Saccades were electrically elicited at 109 SEF sites by microstimulation (70 ms, 10-100 microA) during central fixation. The distribution of response fields and elicited saccades indicated a complete representation of all contralateral saccades in SEF. Elicited saccade polar directions ranged between 97 and 262 degrees (data from left hemispheres were transformed to a right-hemisphere convention), and amplitudes ranged between 1.8 and 26.9 degrees. Response-field optimal vectors (right hemisphere transformed) were nearly all contralateral as well; the directions of 115/119 visual response fields and 80/84 movement response fields ranged between 90 and 279 degrees, and response-field eccentricities ranged between 5 and 50 degrees. Response-field directions for the visual and movement activity of visuomovement neurons were strongly correlated (r = 0.95). When neural activity and elicited saccades obtained at exactly the same sites were compared, response fields were highly predictive of elicited saccade dimensions. Response-field direction was highly correlated with the direction of saccades elicited at the recording site (r = 0.92, n = 77). Similarly, response-field eccentricity predicted the size of subsequent electrically elicited saccades (r = 0.49, n = 60). However, elicited saccades were generally smaller than response-field eccentricities and consistently more horizontal when response fields were nearly vertical. The polar direction of response fields and elicited saccades remained constant perpendicular to the cortical surface, indicating a columnar organization of saccade direction. Saccade direction progressively shifted across SEF; however, these orderly shifts were more indicative of a hypercolumnar organization rather than a single global topography. No systematic organization for saccade amplitude was evident. We conclude that saccades are represented in SEF by congruent visual receptive fields, presaccadic movement fields, and efferent mappings. Thus SEF specifies saccade vectors as bursts of activity by local groups of neurons with appropriate projections to downstream oculomotor structures. In this respect, SEF is organized like the superior colliculus and the frontal eye field even though SEF lacks an overall global saccade topography. We contend that all specialized oculomotor functions of SEF must operate within the context of this fundamental organization.     

Relationship of presaccadic activity in frontal eye field and supplementary eye field to saccade initiation in macaque: Poisson spike train analysis

The purpose of this study was to investigate the temporal relationship between presaccadic neuronal discharges in the frontal eye fields (FEF) and supplementary eye fields (SEF) and the initiation of saccadic eye movements in macaque. We utilized an analytical technique that could reliably identify periods of neuronal modulation in individual spike trains. By comparing the observed activity of neurons with the random Poisson distribution generated from the mean discharge rate during the trial period, the period during which neural activity was significantly elevated with a predetermined confidence level was identified in each spike train. In certain neurons, bursts of action potentials were identified by determining the period in each spike train in which the activation deviated most from the expected Poisson distribution. Using this method, we related these defined periods of modulation to saccade initiation in specific cell types recorded in FEF and SEF. Cells were recorded in SEF while monkeys made saccades to targets presented alone. Cells were recorded in FEF while monkeys made saccades to targets presented alone or with surrounding distractors. There were no significant differences in the time-course of activity of the population of FEF presaccadic movement cells prior to saccades generated to singly presented or distractor-embedded targets. The discharge of presaccadic movement cells in FEF and SEF could be subdivided quantitatively into an early prelude followed by a high-rate burst of activity that occurred at a consistent interval before saccade initiation. The time of burst onset relative to saccade onset in SEF presaccadic movement cells was earlier and more variable than in FEF presaccadic movement cells. The termination of activity of another population of SEF neurons, known as preparatory set cells, was time-locked to saccade initiation. In addition, the cessation of SEF preparatory set cell activity coincided precisely with the beginning of the burst of SEF presaccadic movement cells. This finding raises the possibility that SEF preparatory set cells may be involved in saccade initiation by regulating the activation of SEF presaccadic movement cells. These results demonstrate the utility of the Poisson spike train analysis to relate periods of neuronal modulation to behavior.     

Primate frontal eye fields. II. Physiological and anatomical correlates of electrically evoked eye movements

We studied single neurons in the frontal eye fields of awake macaque monkeys and compared their activity with the saccadic eye movements elicited by microstimulation at the sites of these neurons. Saccades could be elicited from electrical stimulation in the cortical gray matter of the frontal eye fields with currents as small as 10 microA. Low thresholds for eliciting saccades were found at the sites of cells with presaccadic activity. Presaccadic neurons classified as visuomovement or movement were most associated with low (less than 50 microA) thresholds. High thresholds (greater than 100 microA) or no elicited saccades were associated with other classes of frontal eye field neurons, including neurons responding only after saccades and presaccadic neurons, classified as purely visual. Throughout the frontal eye fields, the optimal saccade for eliciting presaccadic neural activity at a given recording site predicted both the direction and amplitude of the saccades that were evoked by microstimulation at that site. In contrast, the movement fields of postsaccadic cells were usually different from the saccades evoked by stimulation at the sites of such cells. We defined the low-threshold frontal eye fields as cortex yielding saccades with stimulation currents less than or equal to 50 microA. It lies along the posterior portion of the arcuate sulcus and is largely contained in the anterior bank of that sulcus. It is smaller than Brodmann's area 8 but corresponds with the union of Walker's cytoarchitectonic areas 8A and 45. Saccade amplitude was topographically organized across the frontal eye fields. Amplitudes of elicited saccades ranged from less than 1 degree to greater than 30 degrees. Smaller saccades were evoked from the ventrolateral portion, and larger saccades were evoked from the dorsomedial portion. Within the arcuate sulcus, evoked saccades were usually larger near the lip and smaller near the fundus. Saccade direction had no global organization across the frontal eye fields; however, saccade direction changed in systematic progressions with small advances of the microelectrode, and all contralateral saccadic directions were often represented in a single electrode penetration down the bank of the arcuate sulcus. Furthermore, the direction of change in these progressions periodically reversed, allowing particular saccade directions to be multiply represented in nearby regions of cortex.(ABSTRACT TRUNCATED AT 400 WORDS)     

Burst discharges of fastigial neurons in macaque monkeys are driven by vision- and memory-guided saccades but not by spontaneous saccades.

Discharges from 61 saccadic burst neurons in the fastigial oculomotor region were recorded for two trained macaque monkeys during vision-guided or memory-guided saccades or spontaneous saccades in the dark. Although these neurons exhibited vigorous, burst discharges during both vision-guided and memory-guided saccades, only weak bursts were observed during spontaneous saccades in the dark. Especially in 10 of the 61 neurons, saccadic burst discharge was almost completely absent during spontaneous saccades in the dark. These findings suggest that the cerebellum plays an important role in the control of vision-guided saccades as well as memory-guided saccades, but not of spontaneous saccades in the dark.     

Gaze shift duration, independent of amplitude, influences the number of spikes in the burst for medium-lead burst neurons in pontine reticular formation

Changes in the direction of the line of sight (gaze) allow successive sampling of the visual environment. Saccadic eye movements accomplish this goal when the head does not move. Medium-lead burst neurons (MLBs) in the paramedian pontine reticular formation (PPRF) discharge a high frequency burst of action potentials starting ~12 ms before the saccade begins. A subgroup of MLBs rostral of abducens nucleus monosynaptically excites oculomotor neurons. The number of spikes in the presaccadic burst is correlated with the amplitude of the horizontal component of the saccade, and the peak discharge rate is correlated with peak eye velocity. During head-unrestrained gaze shifts, a linear relationship between the number of action potentials in MLB bursts and gaze (but not eye) amplitude has been reported. The anatomical connection of MLBs to motor neurons and the similarity between the phasic motor neuron burst and MLB discharge have raised questions about the usefulness of counting spikes in MLBs to determine their role in eye-head coordination. We investigated this issue using a behavioral technique that permits a dissociation of eye movement amplitude and duration during constant vector gaze shifts. Surprisingly, during gaze shifts of constant amplitude and direction, we observe a nearly linear, positive correlation between saccade duration and spike number associated with a negative correlation between spike number and saccade amplitude. These data constrain models of the oculomotor controller and may further define the time-dependence of hypothesized neural integration in this system.     

Discharge of monkey nucleus reticularis tegmenti pontis neurons changes during saccade adaptation

Saccade accuracy is maintained by adaptive mechanisms that continually modify saccade amplitude to reduce dysmetria. Previous studies suggest that adaptation occurs upstream of the caudal fastigial nucleus (CFN), the output of the oculomotor cerebellar vermis but downstream from the superior colliculus (SC). The nucleus reticularis tegmenti pontis (NRTP) is a major source of afferents to both the oculomotor vermis and the CFN and in turn receives direct input from the SC. Here we examine the activity of NRTP neurons in four rhesus monkeys during behaviorally induced changes in saccade amplitude to assess whether their discharge might reveal adaptation mechanisms that mediate changes in saccade amplitude. During amplitude decrease adaptation (average, 22%), the gradual reduction of saccade amplitude was accompanied by an increase in the number of spikes in the burst of 19/34 neurons (56%) and no change for 15 neurons (44%). For the neurons that increased their discharge, the additional spikes were added at the beginning of the saccadic burst and adaptation also delayed the peak-firing rate in some neurons. Moreover, after amplitude reduction, the movement fields changed shape in all 15 open field neurons tested. Our data show that saccadic amplitude reduction affects the number of spikes in the burst of more than half of NRTP neurons tested, primarily by increasing burst duration not frequency. Therefore adaptive changes in saccade amplitude are reflected already at a major input to the oculomotor cerebellum.     

Activity of mesencephalic vertical burst neurons during saccades and smooth pursuit

The activity of vertical burst neurons (BNs) was recorded in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF-BNs) and in the interstitial nucleus of Cajal (NIC-BNs) in head-restrained cats while performing saccades or smooth pursuit. BNs emitted a high-frequency burst of action potentials before and during vertical saccades. On average, these bursts led saccade onset by 14 +/- 4 ms (mean +/- SD, n = 23), and this value was in the range of latencies ( approximately 5-15 ms) of medium-lead burst neurons (MLBNs). All NIC-BNs (n = 15) had a downward preferred direction, whereas riMLF-BNs showed either a downward (n = 3) or an upward (n = 5) preferred direction. We found significant correlations between saccade and burst parameters in all BNs: vertical amplitude was correlated with the number of spikes, maximum vertical velocity with maximum of the spike density, and saccade duration with burst duration. A correlation was also found between instantaneous vertical velocity and neuronal activity during saccades. During fixation, all riMLF-BNs and approximately 50% of NIC-BNs (7/15) were silent. Among NIC-BNs active during fixation (8/15), only two cells had an activity correlated with the eye position in the orbit. During smooth pursuit, most riMLF-BNs were silent (7/8), but all NIC-BNs showed an activity that was significantly correlated with the eye velocity. This activity was unaltered during temporary disappearance of the visual target, demonstrating that it was not visual in origin. For a given neuron, its ON-direction during smooth pursuit and saccades remained identical. The activity of NIC-BNs during both saccades and smooth pursuit can be described by a nonlinear exponential function using the velocity of the eye as independent variable. We suggest that riMLF-BNs, which were not active during smooth pursuit, are vertical MLBNs responsible for the generation of vertical saccades. Because NIC-BNs discharged during both saccades and pursuit, they cannot be regarded as MLBNs as usually defined. NIC-BNs could, however, be the site of convergence of both the saccadic and smooth pursuit signals at the premotoneuronal level. Alternatively, NIC-BNs could participate in the integration of eye velocity to eye position signals and represent input neurons to a common integrator.     

Adaptive modification of saccade size produces correlated changes in the discharges of fastigial nucleus neurons

Saccade accuracy is known to be maintained by adaptive mechanisms that progressively reduce any visual error that consistently exists when the saccade ends. We used an experimental paradigm known to induce adaptation of saccade size while monitoring the neural correlates of this adaptation. In rhesus monkeys where the medial and lateral recti of one eye were surgically weakened, patching the unoperated eye and forcing the monkey to use the weakened eye induced a gradual increase in saccade size in both eyes until the viewing, weak eye almost acquired the target in one step. Subsequent patching of the weakened eye gradually reversed the situation, so that the saccades in the viewing, normal eye decreased from an initial overshooting to normal. In the caudal fastigial nuclei of unadapted monkeys, neurons typically exhibit an early burst of spikes that is correlated with the onset of contraversive saccades and a later burst of spikes that is correlated with the termination of ipsiversive saccades. Comparing the discharges of the same fastigial neurons recorded before and during adaptation, this basic pattern did not change, but some parameters of the discharges did. The most consistent changes were in the latency of the burst for ipsiversive saccades, which was positively correlated with saccade size (1.28 ms/deg), and in the number of spikes associated with contraversive saccades, which was also positively correlated (0.55 spikes/deg). The former was more important when saccade size was decreasing, and the latter was more important when saccade size was increasing. Based on current knowledge of the anatomical connections of fastigial neurons, as well as on the effects of cerebellar lesions and on recordings in other structures, we argue that these changes are appropriate for causing the associated changes in saccade size.     

Ocular oscillations generated by coupling of brainstem excitatory and inhibitory saccadic burst neurons

The human saccadic system is potentially unstable and may oscillate if the burst neurons, which generate saccades, are not inhibited by omnipause neurons. A previous study showed that combined saccade vergence movements can evoke oscillations in normal subjects. We set out to determine: 1) whether similar oscillations can be recorded during other paradigms associated with inhibition of omnipause neurons; 2) whether lesions of the fastigial nuclei disrupt such oscillations; and 3) whether such oscillations can be reproduced using a model based on the coupling of excitatory and inhibitory burst neurons. We recorded saccadic oscillations during vergence movements, combined saccade-vergence movements, vertical saccades, pure vergence and blinks in three normal subjects, and in a patient with saccadic hypermetria due to a surgical lesion affecting both fastigial nuclei. During combined saccade-vergence, normal subjects and the cerebellar patient developed small-amplitude (0.1–0.5°), high-frequency (27–35 Hz), conjugate horizontal saccadic oscillations. Oscillations of a similar amplitude and frequency occurred during blinks, pure vergence and vertical saccades. One normal subject could generate saccadic oscillations voluntarily (~0.7° amplitude, 25 Hz) during sustained convergence. Previous models proposed that high-frequency eye oscillations produced by the saccadic system (saccadic oscillations), occur because of a delay in a negative feedback loop around high-gain, excitatory burst neurons in the brainstem. The feedback included the cerebellar fastigial nuclei. We propose another model that accounts for saccadic oscillations based on 1) coupling of excitatory and inhibitory burst neurons in the brainstem and 2) the hypothesis that burst neurons show post-inhibitory rebound discharge. When omnipause neurons are inhibited (as during saccades, saccade-vergence movements and blinks), this new model simulates oscillations with amplitudes and frequencies comparable to those in normal human subjects. The finding of saccadic oscillations in the cerebellar patient is compatible with the new model but not with the recent models including the fastigial nuclei in the classic negative-feedback loop model. Our model proposes a novel mechanism for generating oscillations in the oculomotor system and perhaps in other motor systems too.     

Competition between saccade goals in the superior colliculus produces saccade curvature

When saccadic eye movements are made in a search task that requires selecting a target from distractors, the movements show greater curvature in their trajectories than similar saccades made to single stimuli. To test the hypothesis that this increase in curvature arises from competitive interactions between saccade goals occurring near the time of movement onset, we performed single-unit recording and microstimulation experiments in the superior colliculus (SC). We found that saccades that ended near the target but curved toward a distractor were accompanied by increased presaccadic activity of SC neurons coding the distractor site. This increased activity occurred approximately 30 ms before saccade onset and was abruptly quenched on saccade initiation. The magnitude of increased activity at the distractor site was correlated with the amount of curvature toward the distractor. In contrast, neurons coding the target location did not show any significant difference in discharge for curved versus straight saccades. To determine whether this pattern of SC discharge is causally related to saccade curvature, we performed a second series of experiments using electrical microstimulation. Monkeys made saccades to single visual stimuli presented without distractors, and we stimulated sites in the SC that would have corresponded to distractor sites in the search task. The stimulation was subthreshold for evoking saccades, but when its temporal structure mimicked the activity recorded for curved saccades in search, the subsequent saccades to the visual target showed curvature toward the location coded by the stimulation site. The effect was larger for higher stimulation frequencies and when the stimulation site was in the same colliculus as the representation of the visual target. These results support the hypothesis that the increased saccade curvature observed in search arises from rivalry between target and distractor goals and are consistent with the idea that the SC is involved in the competitive neural interactions underlying saccade target selection.