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.

Cerebellar influences on saccade plasticity.

Inaccurate saccades adapt to become more accurate. In this experiment the role of cerebellar output to the oculomotor system in adapting saccade size was investigated. We measured saccade adaptation after temporary inactivation of saccade-related neurons in the caudal part of the fastigial nucleus which projects to the oculomotor brain stem. We located caudal fastigial nucleus neurons with single unit recording and injected 0.1% muscimol among them. Two monkeys received bilateral injections and two monkeys unilateral injections. Unilateral injections made ipsiversive saccades hypermetric (gains >1.5) and contraversive saccades hypometric (gains approximately 0.6). Bilateral injections made both leftward and rightward saccades hypermetric (gains >1.5). During unilateral inactivation neither ipsiversive nor contraversive saccade size adapted after approximately 1,000 saccades. During bilateral inactivation, adaptation was either small or very slow. Most intact monkeys completely adapt after approximately 1,000 saccades to similar dysmetrias produced by intrasaccadic target displacement. After the monkeys receiving bilateral injections made >1,000 saccades in each horizontal direction, we placed them in the dark so that the muscimol dissipated without the monkeys receiving visual feedback about its saccade gain. After the dark period, 20-degree saccades were adapted to be 12% smaller, and 4-degree saccades to be 7% smaller. We expect this difference in adaptation because during caudal fastigial nucleus inactivation, monkeys made many large overshooting saccades and few small overshooting saccades. We conclude from these results that: (1) caudal fastigial nucleus activity is important in adapting dysmetric saccades; and (2) bilateral caudal fastigial nucleus inactivation impairs the relay of adapted signals to the oculomotor system, but it does not stop all adaptation from occurring.

Gaze-stabilizing deficits and latent nystagmus in monkeys with brief, early-onset visual deprivation: eye movement recordings.

The normal development and the capacity to calibrate gaze-stabilizing systems may depend on normal vision during infancy. At the end of 1 yr of dark rearing, cats have gaze-stabilizing deficits similar to that of the newborn human infant including decreased monocular optokinetic nystagmus (OKN) in the nasal to temporal (N-T) direction and decreased velocity storage in the vestibuloocular reflex (VOR). The purpose of this study is to determine to what extent restricted vision during the first 2 mo of life in monkeys affects the development of gaze-stabilizing systems. The eyelids of both eyes were sutured closed in three rhesus monkeys (Macaca mulatta) at birth. Eyelids were opened at 25 days in one monkey and 40 and 55 days in the other two animals. Eye movements were recorded from each eye using scleral search coils. The VOR, OKN, and fixation were examined at 6 and 12 mo of age. We also examined ocular alignment, refraction, and visual acuity in these animals. At 1 yr of age, visual acuity ranged from 0.3 to 0.6 LogMAR (20/40-20/80). All animals showed a defect in monocular OKN in the N-T direction. The velocity-storage component of OKN (i.e., OKAN) was the most impaired. All animals had a mild reduction in VOR gain but had a normal time constant. The animals deprived for 40 and 55 days had a persistent strabismus. All animals showed a nystagmus similar to latent nystagmus (LN) in human subjects. The amount of LN and OKN defect correlated positively with the duration of deprivation. In addition, the animal deprived for 55 days demonstrated a pattern of nystagmus similar to congenital nystagmus in human subjects. We found that restricted visual input during the first 2 mo of life impairs certain gaze-stabilizing systems and causes LN in primates.

Gaze-stabilizing deficits and latent nystagmus in monkeys with early-onset visual deprivation: role of the pretectal not.

We studied the role of the pretectal nucleus of the optic tract (NOT) in the development of monocular optokinetic nystagmus (OKN) asymmetries and latent nystagmus (LN) in two monkeys reared with binocular deprivation (BD) caused by binocular eyelid suture for either the first 25 or 55 days of life. Single-unit recordings were performed in the right and left NOT of both monkeys at 2-3 yr of age and compared with similar unit recordings in normally reared monkeys. We also examined ocular motor behavior during electrical stimulation of the NOT and during pharmacological inactivation and activation using GABA(A) agonists and antagonists. In BD animals a large proportion of NOT units was dominated by the contralateral eye, in striking contrast to normal animals where 100% of NOT units were sensitive to stimuli delivered to either eye. In the 55-day BD animal no binocularly sensitive neurons were found, while in the 25-day BD animal 60% of NOT units retained at least some binocular sensitivity. Differences in direction sensitivity were also observed in BD animals. We found that 56% of units in the 55-day BD monkey and 10% of units in the 25-day BD monkey responded preferentially to contraversive visual motion. In contrast, only 5% of the NOT units encountered in normally reared monkeys respond preferentially during contraversive visual motion, the rest were most sensitive to ipsiversive visual motion. NOT neurons of BD monkeys showed a wide range of speed sensitivities similar to that of normal monkeys. Unilateral electrical stimulation of the NOT in BD animals induced a conjugate nystagmus with slow phases directed toward the side of stimulation. When we blocked the activity of NOT units with muscimol, a potent GABA(A) agonist, LN was abolished. In contrast, LN was increased when spontaneous activity of the NOT was enhanced with bicuculline, a GABA(A) antagonist. Our results indicate that the NOT in BD monkeys plays an important role in the OKN deficits and LN generation during monocular viewing. We hypothesize that the large proportion of units dominated by the contralateral eye contribute to the development of monocular OKN asymmetries and LN.

The role of the cerebellum in voluntary eye movements.

In general the cerebellum is crucial for the control but not the initiation of movement. Voluntary eye movements are particularly useful for investigating the specific mechanisms underlying cerebellar control because they are precise and their brain-stem circuitry is already well understood. Here we describe single-unit and inactivation data showing that the posterior vermis and the caudal fastigial nucleus, to which it projects, provide a signal during horizontal saccades to make them fast, accurate, and consistent. The caudal fastigial nucleus also is necessary for the recovery of saccadic accuracy after actual or simulated neural or muscular damage causes horizontal saccades to be dysmetric. Saccade-related activity in the interpositus nucleus is related to vertical saccades. Both the caudal fastigial nucleus and the flocculus/paraflocculus are necessary for the normal smooth eye movements that pursue a small moving spot. By using eye movements, we have begun to uncover basic principles that give us insight into how the cerebellum may control movement in general.

Visual influences on the development and recovery of the vestibuloocular reflex in the chicken.

Whenever the head turns, the vestibuloocular reflex (VOR) produces compensatory eye movements to help stabilize the image of the visual world on the retina. Uncompensated slip of the visual world across the retina results in a gradual change in VOR gain to minimize the image motion. VOR gain changes naturally during normal development and during recovery from neuronal damage. We ask here whether visual slip is necessary for the development of the chicken VOR (as in other species) and whether it is required for the recovery of the VOR after hair cell loss and regeneration. In the first experiment, chickens were reared under stroboscopic illumination, which eliminated visual slip. The horizontal and vertical VORs (h- and vVORs) were measured at different ages and compared with those of chickens reared in normal light. Strobe-rearing prevented the normal development of both h- and vVORs. After 8 wk of strobe-rearing, 3 days of exposure to normal light caused the VORs to recover partially but not to normal values. In the second experiment, 1-wk-old chicks were treated with streptomycin, which destroys most vestibular hair cells and reduces hVOR gain to zero. In birds, vestibular hair cells regenerate so that after 8 wk in normal illumination they appear normal and hVOR gain returns to values that are normal for birds of that age. The treated birds in this study recovered in either normal or stroboscopic illumination. Their hVOR and vVOR and vestibulocollic reflexes (VCR) were measured and compared with those of untreated, age-matched controls at 8 wk posthatch, when hair cell regeneration is known to be complete. As in previous studies, the gain of the VOR decreased immediately to zero after streptomycin treatment. After 8 wk of recovery under normal light, the hVOR was normal, but vVOR gain was less than normal. After 8 wk of recovery under stroboscopic illumination, hVOR gain was less than normal at all frequencies. VCR recovery was not affected by the strobe environment. When streptomycin-treated, strobe-recovered birds were then placed in normal light for 2 days, hVOR gain returned to normal. Taken together, the results of these experiments suggest that continuous visual feedback can adjust VOR gain. In the absence of appropriate visual stimuli, however, there is a default VOR gain and phase to which birds recover or revert, regardless of age. Thus an 8-wk-old chicken raised in a strobe environment from hatch would have the same gain as a streptomycin-treated chicken that recovers in a strobe environment.

Characteristics of the pupillary light reflex in the macaque monkey: discharge patterns of pretectal neurons.

Anatomical and physiological data have implicated the pretectal olivary nucleus (PON) as the midbrain relay for the pupillary light reflex in a variety of species. To determine the nature of the discharge of pretectal light reflex relay neurons, we recorded their activity in monkeys that were fixating a stationary spot while a full-field random-dot stimulus was flashed on for 1 s. Based on their discharge patterns, neurons in or near the PON came in two varieties. The most prevalent neuron discharged a burst of spikes 56 ms (on average) after the light came on followed by a sustained rate for the duration of the stimulus (burst-sustained neurons). When the light went off, nearly all neurons (33/34) ceased firing, and then all the neurons with a resting response in the dark (n = 15) resumed firing. Both the firing rate within the burst and the sustained discharge rate increased with log light intensity and the latency of the burst decreased. The burst and cessation of firing were better aligned with the stimulus occurrence than with the onset of pupillary constriction or dilation. Taken together, these data suggest that burst-sustained neurons respond to the visual stimulus eliciting the pupillary change rather than dictating the metrics of the subsequent pupillary response. Electrical stimulation at the site of four of five burst-sustained neurons elicited pupillary constriction at low stimulus strengths after a latency of approximately 100 ms. When the electrode was moved 250 microm away from the burst-sustained neuron, the elicited response disappeared. Reconstructions of the locations of burst-sustained luminance neurons place them in the PON or its immediate vicinity. We suggest that PON burst-sustained neurons constitute the pretectal relay for the pupillary light reflex. A minority of our recorded pretectal neurons discharged a burst of spikes at both light onset and light offset. For most of these transient neurons, neither the burst rate nor the interburst rate was significantly related to light intensity. We conclude that these neurons are not involved in the light reflex but subserve some other pretectal function.

Characteristics of the pupillary light reflex in the macaque monkey: metrics.

To investigate whether the simian light reflex is a reasonable model for the human light reflex, we elicited pupillary responses in three behaving rhesus macaques. We measured the change in pupillary area in response to brief (100 ms), intermediate (1 s), and long (3-5 s) light flashes delivered by light-emitting diodes while the monkey fixated a stationary target. Individual responses in the same monkey to either 100-ms or 1-s stimuli of the same light intensity were quite variable. Nevertheless, in response to the 100-ms stimulus, average pupillary constriction and peak constriction velocity increased and latency decreased linearly with the log of stimulus luminance. The minimum average constriction latency across monkeys for the brightest flash was 136 ms. A linear decrease of constriction latency with stimulus luminance also occurs in humans, but their latencies are approximately 70 ms longer. In addition, peak constriction velocity was highly correlated with the decrease in pupillary area. Dilation metrics were not as well related to stimulus luminance as were constriction metrics. The latency from flash offset to the onset of dilation was relatively constant, averaging approximately 480 ms. Peak dilation velocity was also correlated, but less well, with the increase in pupillary area. Constriction generally was greater and of longer duration for 1-s light pulses than for 100-ms pulses of equal luminance. The initial time courses of the responses to the two stimuli of different durations were identical until approximately 150 ms after response onset. Human pupillary responses for long and short flashes also have identical initial time courses. For very long (3-5 s) and very bright constant-luminance stimuli, the simian pupil underwent oscillations at frequencies of 0.9-1.6 Hz. Similar oscillations, called hippus, occur in the human pupillary light reflex. Like humans, the monkeys also exhibited consensual and binocular pupillary responses. Except for response latency, the pupillary responses in the two primate species are otherwise quite similar. Therefore any knowledge we gain about the neuronal substrate of the simian light reflex can be expected to have considerable relevance when extrapolated to humans.

Temporal characteristics of error signals driving saccadic gain adaptation in the macaque monkey.

Saccadic gain (saccade amplitude/target amplitude) can be reduced gradually by repeatedly stepping the target backward during the saccade. The gain reduction produced by this paradigm is thought to be driven by an error signal created by the backstep. We investigated the effects of varying the timing of this error signal relative to the end of the saccade by using two different paradigms in macaques. In the brief backstep paradigm, the target was stepped backward 30% during the saccade but extinguished after different durations. For very short backstep durations (32 ms), little gain reduction occurred. As backstep duration increased, the amount of gain reduction also increased. When backstep duration reached 80 ms, the amount of gain reduction was just under that achieved during the conventional adaptation paradigm in which the backstep remained visible for 1000-1200 ms. In the delayed backstep paradigm, as the saccade occurred, we extinguished the target and then, after a delay, illuminated it for 1 s at the backstep location. In most experiments with short delay times of 16-64 ms, the saccadic gain reduction reached that achieved during conventional adaptation. At delays of 112-208 ms, the amount of gain reduction decreased to approximately 75% of that reached during conventional adaptation. With still longer delays, the amount of gain reduction decreased more gradually. At delays of 750 ms, average gain reduction was 10%. By delays of 1.5 s, gain reduction had fallen essentially to zero. Taken together, these data suggest that the error signal must be present for a limited time ( approximately 80-100 ms) after the saccade to produce the most robust saccadic gain adaptation. However, errors present as long as 750 ms after the saccade still can produce a significant gain reduction.

Flexibility of saccade adaptation in the monkey: different gain states for saccades in the same direction.

Saccadic accuracy, measured as the ratio of the size of a saccade to the size of the target step that elicits it, i.e., saccade gain, can be altered by jumping the target surreptitiously during the targeting saccade. The gain change produced by this paradigm does not generalize or transfer to saccades of all sizes. Instead, the amount of transfer decreases the more the tested saccade differs in amplitude and direction from that adapted. Here, we tested the limits of this saccade-size specificity by attempting to impose quite different gain states on saccades in the same direction. We altered the saccadic gain by intrasaccadic target jumps of 30% of the initial target step, either forward to produce a gain increase or backward to produce a gain decrease. Three different conditions were studied: (1) saccades to target steps of 20 degrees or 7 degrees were adapted in individual sessions with backward and forward jumps, respectively; (2) saccades to target steps of 20 degrees caused backward target jumps during the same session in which saccades to 7 degrees target steps caused forward steps; (3) the target jumps accompanying 20 and 7 degrees saccades were the same as in (2), but in addition, there were intermediate-sized saccades to 13.5 degrees target steps with no intrasaccadic target jumps. Saccadic gain adaptation was quite flexible. In condition 2, we could simultaneously increase the gain of saccades to 7 degrees target steps while decreasing the gain of saccades to 20 degrees steps in the same direction. Intermediate horizontal saccades to 13.5 degrees target steps experienced gain reductions (average: 6.9%), which were not the sum of gain changes expected from separate 20 degrees gain decreases and 7 degrees gain increases alone, as predicted from condition 1. If adaptation at 20 degrees and 7 degrees occurred while an animal also tracked a non-adapting 13.5 degrees target step (paradigm 3), the gain reduction of saccades to the 13.5 degrees step was reduced considerably (3.4%). Thus, the mechanism that adapts saccade size can support a robust gain increase for saccades of one size while simultaneously supporting a robust gain decrease for saccades only 13 degrees larger. Furthermore, the presence during adaptation of a non-adapted target step with a size intermediate to the two adapting steps reestablishes a nearly normal gain within only 6.5 degrees of a robust gain increase and decrease. These data indicate that saccadic gain adaptation can set very different gain states for saccades with rather similar vectors.

Apparent dissociation between saccadic eye movements and the firing patterns of premotor neurons and motoneurons.

Saccadic eye movements result from high-frequency bursts of activity in ocular motoneurons. This phasic activity originates in premotor burst neurons. When the head is restrained, the number of action potentials in the bursts of burst neurons and motoneurons increases linearly with eye movement amplitude. However, when the head is unrestrained, the number of action potentials now increase as a function of the change in the direction of the line of sight during eye movements of relatively similar amplitudes. These data suggest an apparent uncoupling of premotor neuron and motoneuron activity from the resultant eye movement.

Vertical Purkinje cells of the monkey floccular lobe: simple-spike activity during pursuit and passive whole body rotation.

To understand how the simian floccular lobe is involved in vertical smooth pursuit eye movements and the vertical vestibuloocular reflex (VOR), we examined simple-spike activity of 70 Purkinje (P) cells during pursuit eye movements and passive whole body rotation. Fifty-eight cells responded during vertical and 12 during horizontal pursuit. We classified P cells as vertical gaze velocity (VG) if their modulation occurred for movements of both the eye (during vertical pursuit) and head (during pitch VOR suppression) with the modulation during one less than twice that of the other and was less during the target-fixed-in-space condition (pitch VOR X1) than during pitch VOR suppression. VG P cells constituted only a minority of vertical P cells (19%). Other vertical P cells that responded during pitch VOR suppression were classified as vertical eye and head velocity (V/) P cells (48%), regardless of the synergy of their response direction during smooth pursuit and VOR suppression. Vertical P cells that did not respond during pitch VOR suppression but did respond during rotation in vertical planes other than pitch were classified as off-pitch V/ P cells (33%). The mean eye-velocity and eye-position sensitivities of the three types of vertical P cells were similar. One-third (2/7 VG, 2/11 V/, 6/13 off-pitch V/), in addition, showed eye position sensitivity during saccade-free fixations. Maximal vestibular activation directions (MADs) were examined during VOR suppression by applying vertical whole body rotation with the monkeys oriented in different vertical planes. The MADs for VG P cells and V/ P cells with eye and vestibular sensitivity in the same direction were distributed near the pitch plane, suggesting convergence of bilateral anterior canal inputs. In contrast, MADs of off-pitch V/ P cells and V/ P cells with oppositely directed eye and vestibular sensitivity were shifted toward the roll plane, suggesting convergence of anterior and posterior canal inputs of the same side. Unlike horizontal G P cells, the modulation of many VG and V/ P cells when the target was fixed in space (pitch VOR X1) was not well predicted by the linear addition of their modulations during vertical pursuit and pitch VOR suppression. These results indicate that the populations of vertical and horizontal eye-movement P cells in the floccular lobe have markedly different discharge properties and therefore may be involved in different kinds of processing of vestibular-oculomotor interactions.

Characteristics of simian adaptation fields produced by behavioral changes in saccade size and direction.

The gain of saccadic eye movements can be altered gradually by moving targets either forward or backward during targeting saccades. If the gain of saccades to targets of only one size is adapted, the gain change generalizes or transfers only to saccades with similar vectors. In this study, we examined the spatial extent of such saccadic size adaptation, i.e., the gain adaptation field. We also attempted to adapt saccade direction by moving the target orthogonally during the targeting saccade to document the extent of a direction or cross-axis adaptation field. After adaptive gain decreases of horizontal saccades to 15 degrees target steps, >82% of the gain reduction transferred to saccades to 25 degrees horizontal target steps but only approximately 30% transferred to saccades to 5 degrees steps. For the horizontal component of oblique saccades to target steps with 15 degrees horizontal components and 10 degrees upward or downward vertical components, the transfer was similar at 51 and 60%, respectively. Thus the gain decrease adaptation field was quite asymmetric in the horizontal dimension but symmetric in the vertical dimension. Although gain increase adaptation produced a smaller gain change (13% increase for a 30% forward adapting target step) than did gain decrease adaptation (20% decrease for a 30% backward adapting target step), the spatial extent of gain transfer was quite similar. In particular, the gain increase adaptation field displayed asymmetry in the horizontal dimension (58% transfer to 25 degrees saccades but only 32% transfer to 5 degrees saccades) and symmetry in the vertical direction (50% transfer to the horizontal component of 10 degrees upward and 40% transfer to 10 degrees downward oblique saccades). When a 5 degrees vertical target movement was made to occur during a saccade to a horizontal 10 degrees target step, a vertical component gradually appeared in saccades to horizontal targets. More than 88% of the cross-axis change in the vertical component produced in 10 degrees saccades transferred to 20 degrees saccades but only 12% transferred to 4 degrees saccades. The transfer was similar to the vertical component of oblique saccades to target steps with either 10 degrees upward (46%) or 10 degrees downward (46%) vertical components. Therefore both gain and cross-axis adaptation fields have similar spatial profiles. These profiles resemble those of movement fields of neurons in the frontal eye fields and superior colliculus. How those structures might participate in the adaptation process is considered in the DISCUSSION.

Short- and long-term consequences of canal plugging on gaze shifts in the rhesus monkey. I. Effects on gaze stabilization.

Short- and long-term consequences of canal plugging on gaze shifts in the rhesus monkey. I. Effects on gaze stabilization. To study the contribution of the vestibular system to the coordinated eye and head movements of a gaze shift, we plugged the lumens of just the horizontal (n = 2) or all six semicircular canals (n = 1) in monkeys trained to make horizontal head-unrestrained gaze shifts to visual targets. After the initial eye saccade of a gaze shift, normal monkeys exhibit a compensatory eye counterrotation that stabilizes gaze as the head movement continues. This counterrotation, which has a gain (eye velocity/head velocity) near one has been attributed to the vestibuloocular reflex (VOR). One day after horizontal canal plugging, the gain of the passive horizontal VOR at frequencies between 0.1 and 1.0 Hz was <0.10 in the horizontal-canal-plugged animals and zero in the all-canal-plugged animal. One day after surgery, counterrotation gain was approximately 0.3 in the animals with horizontal canals plugged and absent in the animal with all canals plugged. As the time after plugging increased, so too did counterrotation gain. In all three animals, counterrotation gain recovered to between 0.56 and 0.75 within 80-100 days. The initial loss of compensatory counterrotation after plugging resulted in a gaze shift that ended long after the eye saccade and just before the end of the head movement. With recovery, the length of time between the end of the eye saccade and the end of the gaze movement decreased. This shortening of the duration of reduced gain counterrotation occurred both because head movements ended sooner and counterrotation gain returned to 1.0 more rapidly relative to the end of the eye saccade. Eye counterrotation was not due to activation of pursuit eye movements as it persisted when gaze shifts were executed to extinguished targets. Also counterrotation was not due simply to activation of neck receptors because counterrotation persisted after head movements were arrested in midflight. We suggest that the neural signal that is used to cause counterrotation in the absence of vestibular input is an internal copy of the intended head movement.

Recovery of the vestibulocolic reflex after aminoglycoside ototoxicity in domestic chickens.

Avian auditory and vestibular hair cells regenerate after damage by ototoxic drugs, but until recently there was little evidence that regenerated vestibular hair cells function normally. In an earlier study we showed that the vestibuloocular reflex (VOR) is eliminated with aminoglycoside antibiotic treatment and recovers as hair cells regenerate. The VOR, which stabilizes the eye in the head, is an open-loop system that is thought to depend largely on regularly firing afferents. Recovery of the VOR is highly correlated with the regeneration of type I hair cells. In contrast, the vestibulocolic reflex (VCR), which stabilizes the head in space, is a closed-loop, negative-feedback system that seems to depend more on irregularly firing afferent input and is thought to be subserved by different circuitry than the VOR. We examined whether this different reflex also of vestibular origin would show similar recovery after hair cell regeneration. Lesions of the vestibular hair cells of 10-day-old chicks were created by a 5-day course of streptomycin sulfate. One day after completion of streptomycin treatment there was no measurable VCR gain, and total hair cell density was approximately 35% of that in untreated, age-matched controls. At 2 wk postlesion there was significant recovery of the VCR; at this time two subjects showed VCR gains within the range of control chicks. At 3 wk postlesion all subjects showed VCR gains and phase shifts within the normal range. These data show that the VCR recovers before the VOR. Unlike VOR gain, recovering VCR gain correlates equally well with the density of regenerating type I and type II vestibular hair cells, except at high frequencies. Several factors other than hair cell regeneration, such as length of stereocilia, reafferentation of hair cells, and compensation involving central neural pathways, may be involved in behavioral recovery. Our data suggest that one or more of these factors differentially affect the recovery of these two vestibular reflexes.

Action of the brain stem saccade generator during horizontal gaze shifts. I. Discharge patterns of omnidirectional pause neurons.

Omnidirectional pause neurons (OPNs) pause for the duration of a saccade in all directions because they are part of the neural mechanism that controls saccade duration. In the natural situation, however, large saccades are accompanied by head movements to produce rapid gaze shifts. To determine whether OPNs are part of the mechanism that controls the whole gaze shift rather than the eye saccade alone, we monitored the activity of 44 OPNs that paused for rightward and leftward gaze shifts but otherwise discharged at relatively constant average rates. Pause duration was well correlated with the duration of either eye or gaze movement but poorly correlated with the duration of head movement. The time of pause onset was aligned tightly with the onset of either eye or gaze movement but only loosely aligned with the onset of head movement. These data suggest that the OPN pause does not encode the duration of head movement. Further, the end of the OPN pause was often better aligned with the end of the eye movement than with the end of the gaze movement for individual gaze shifts. For most gaze shifts, the eye component ended with an immediate counterrotation owing to the vestibuloocular reflex (VOR), and gaze ended at variable times thereafter. In those gaze shifts where eye counterrotation was delayed, the end of the pause also was delayed. Taken together, these data suggest that the end of the pause influences the onset of eye counterrotation, not the end of the gaze shift. We suggest that OPN neurons act to control only that portion of the gaze movement that is commanded by the eye burst generator. This command is expressed by driving the saccadic eye movement directly and also by suppressing VOR eye counterrotation. Because gaze end is less well correlated with pause end and often occurs well after counterrotation onset, we conclude that elements of the burst generator typically are not active till gaze end, and that gaze end is determined by another mechanism independent of the OPNs.

Saccadic gain modification: visual error drives motor adaptation.

The brain maintains the accuracy of saccadic eye movements by adjusting saccadic amplitude relative to the target distance (i.e., saccade gain) on the basis of the performance of recent saccades. If an experimenter surreptitiously moves the target backward during each saccade, thereby causing the eyes to land beyond their targets, saccades undergo a gradual gain reduction. The error signal driving this conventional saccadic gain adaptation could be either visual (the postsaccadic distance of the target from the fovea) or motoric (the direction and size of the corrective saccade that brings the eye onto the back-stepped target). Similarly, the adaptation itself might be a motor adjustment (change in the size of saccade for a given perceived target distance) or a visual remapping (change in the perceived target distance). We studied these possibilities in experiments both with rhesus macaques and with humans. To test whether the error signal is motoric, we used a paradigm devised by Heiner Deubel. The Deubel paradigm differed from the conventional adaptation paradigm in that the backward step that occurred during the saccade was brief, and the target then returned to its original displaced location. This ploy replaced most of the usual backward corrective saccades with forward ones. Nevertheless, saccadic gain gradually decreased over hundreds of trials. Therefore, we conclude that the direction of saccadic gain adaptation is not determined by the direction of corrective saccades. To test whether gain adaptation is a manifestation of a static visual remapping, we decreased the gain of 10 degrees horizontal saccades by conventional adaptation and then tested the gain to targets appearing at retinal locations unused during adaptation. To make the target appear in such "virgin territory," we had it jump first vertically and then 10 degrees horizontally; both jumps were completed and the target spot extinguished before saccades were made sequentially to the remembered target locations. Conventional adaptation decreased the gain of the second, horizontal saccade even though the target was in a nonadapted retinal location. In contrast, the horizontal component of oblique saccades made directly to the same virgin location showed much less gain decrease, suggesting that the adaptation is specific to saccade direction rather than to target location. Thus visual remapping cannot account for the entire reduction of saccadic gain. We conclude that saccadic gain adaptation involves an error signal that is primarily visual, not motor, but that the adaptation itself is primarily motor, not visual.

Gain adaptation of eye and head movement components of simian gaze shifts.

Gain adaptation of eye and head movement components of simian gaze shifts. J. Neurophysiol. 78: 2817-2821, 1997. To investigate the site of gaze adaptation in primates, we reduced the gain of large head-restrained gaze shifts made to 50 degrees target steps by jumping the target 40% backwards during a targeting saccade and then tested gain transfer to the eye- and head-movement components of head-unrestrained gaze shifts. After several hundred backstep trials, saccadic gain decreased by at least 10% in 8 of 13 experiments, which were then selected for further study. The minimum saccadic gain decrease in these eight experiments was 12.8% (mean = 18.4%). Head-unrestrained gaze shifts to ordinary 50 degrees target steps experienced a gain reduction of at least 9.3% (mean = 14.9%), a mean gain transfer of 81%. Both the eye and head components of the gaze shift also decreased. However, average head movement gain decreased much more (22.1%) than eye movement gain (9.2%). Also, peak head velocity generally decreased significantly (20%), but peak eye velocity either increased or remained constant (average increase of 5.6%). However, the adapted peak eye and head velocities were appropriate for the adapted, smaller gaze amplitudes. Similar dissociations in eye and head metrics occurred when head-unrestrained gaze shifts were adapted directly (n = 2). These results indicated that head-restrained saccadic gain adaptation did not produce adaptation of eye movement alone. Nor did it produce a proportional gain change in both eye and head movement. Rather, normal eye and head amplitude and velocity relations for a given gaze amplitude were preserved. Such a result could be explained most easily if head-restrained adaptation were realized before the eye and head commands had been individualized. Therefore, gaze adaptation is most likely to occur upstream of the creation of separate eye and head movement commands.

Participation of caudal fastigial nucleus in smooth pursuit eye movements. II. Effects of muscimol inactivation.

We studied the effect of temporarily inactivating the caudal fastigial nucleus (CFN) in three rhesus macaques trained to make smooth pursuit eye movements. We injected the gamma-aminobutyric acid A agonist muscimol into one or both CFNs where we had recorded pursuit-related neurons a few minutes earlier. Inactivating the CFN on one side impaired pursuit in one monkey so severely that it could not follow step-ramp targets moving at 20 degrees/s, the target velocity that we used to test the other two monkeys. We tested this monkey with targets moving at 10 degrees/s. In all three monkeys, unilateral CFN inactivation either increased the acceleration of ipsilateral step-ramp pursuit (in 2 monkeys, to 144 and 220% of normal) or decreased the acceleration of contralateral pursuit (in 1 monkey, to 71% of normal). Muscimol injected into both CFNs in two of the monkeys left both ipsilateral and contralateral acceleration nearly normal in both monkeys (101% of normal). Unilateral CFN inactivation also impaired the velocity of maintained pursuit as the monkeys tracked a target moving at a constant velocity or oscillating sinusoidally. Averaged across both types of movements in all three monkeys, gains for ipsilateral, contralateral, upward, and downward pursuit were 94, 67, 84, and 73% of normal, respectively. Unilateral CFN inactivation also impaired the monkeys' ability to suppress their vestibuloocular reflex (VOR). Averaged across the two monkeys VOR gain during suppression increased from 0.06 to 0.25 during yaw rotation and from 0.21 to 0.59 during pitch rotation. Bilateral CFN inactivation reduced pursuit gains in all directions more than unilateral injection did. In the two monkeys tested, ipsilateral, contralateral, upward, and downward gains went from 94, 86, 85, and 74% of normal, respectively, after we inactivated one CFN to 88, 73, 80, and 64% of normal after we also inactivated the second CFN. We can explain many, but not all, of the effects of CFN activation on smooth pursuit with the behavior of CFN neurons, and the assumption that the activity of each CFN neuron helps drive pursuit movements in the direction that best activates that neuron. We conclude that the CFN, like the flocculus-ventral paraflocculus, is a cerebellar region involved in control of smooth pursuit.