Microstimulation of Interstitial Nucleus of Cajal Evokes Directionally Disconjugate Eye Movements in Monkeys With Pattern Strabismus.

Purpose: Pattern strabismus is characterized by a horizontal misalignment of the eyes that varies with vertical eye position. This disorder has traditionally been described, and treated, as overaction or underaction of the oblique muscles. In recent years, evidence has accumulated that indicate that the disorder is associated with abnormal cross-talk between brainstem pathways that contribute to the horizontal and vertical components of eye movements. The present study was designed to investigate the hypothesis that the key abnormalities are at the level of, or downstream from, the interstitial nucleus of Cajal (INC). Methods: Microstimulation was applied to the INC in two mature rhesus monkeys with "A" pattern strabismus that was experimentally induced in infancy. We asked whether the evoked movements would be vertical and conjugate, as has been previously reported in normal monkeys, or would be directionally disconjugate (i.e. with oblique or horizontal movement observed for at least one eye). Results: Evoked movements were conjugate and vertical for a minority of sites but, for most sites, the evoked movements were directionally disconjugate. Moreover, there was typically a convergent change in horizontal strabismus when the evoked movements were upward and a divergent change when the evoked movements were downward. Conclusions: Microstimulation of INC in monkeys with A-pattern strabismus evokes movements with the expected directional disconjugacies, implying that the key neural abnormalities are within, or downstream from, this structure. High site-to-site variability in the conjugacy/disconjugacy of evoked movements rules out the hypothesis that the abnormalities are solely peripheral.

Reduced activity of vertically acting motoneurons during convergence.

Previous studies have revealed unexpected relationships between the firing rates of horizontally acting motoneurons and vergence. During a vergence task, for example, antidromically identified abducens internuclear neurons show a negative correlation between vergence angle and firing rate, which is the opposite of the modulation displayed by the medial rectus motoneurons to which they project. For a given horizontal eye position, medial rectus motoneurons discharge at a higher rate if the eyes are converged than if the same eye position is reached during a task that requires version; paradoxically, however, the horizontal rectus eye muscles show corelaxation during vergence. These complex and unexpected relationships inspired the present author to investigate whether the tonic firing rates of vertically acting motoneurons in oculomotor nucleus are correlated with vergence angle. Monkeys were trained to fixate a single, randomly selected, visual target among an array of 60 red plus-shaped LEDs, arranged at 12 different distances in three-dimensional space. The targets were arranged to permit dissociation of vertical eye position and vergence angle. Here I report, for the first time, that most vertically acting motoneurons in oculomotor nucleus show a significant negative correlation between tonic firing rate and vergence angle. This suggests the possibility that there may be a general corelaxation of extraocular muscles during vergence.NEW & NOTEWORTHY An array of 60 plus-shaped LEDs, positioned at various locations in three-dimensional space, was used to elicit conjugate and disjunctive saccades while single neurons in oculomotor nucleus were recorded from rhesus monkeys. This study demonstrates that most vertically acting motoneurons in oculomotor nucleus discharge at a lower rate when the eyes are converged.

Abnormal Tuning in Nucleus Prepositus Hypoglossi of Monkeys With "A" Pattern Exotropia.

Purpose: In many individuals with pattern strabismus, the vertical misalignment varies with horizontal eye position. It has been proposed that these cross-axis effects result from abnormal cross-talk between brainstem structures that would normally encode horizontal and vertical eye position and velocity. The nucleus prepositus hypoglossi (NPH) is an ideal structure to test this overarching hypothesis. Neurons in the NPH are believed to mathematically integrate eye velocity signals to generate a tonic signal related to horizontal eye position. We hypothesized that, in monkeys with A-pattern exotropia and vertical inconcomitance, these neurons would show an abnormally large sensitivity to vertical eye position. Methods: Three rhesus monkeys (1 normal and 2 with A-pattern exotropia) were trained to maintain fixation on a visual target as it stepped to various locations on a tangent screen. Extracellular neural activity was recorded from neurons in the NPH. Each neuron's sensitivity to horizontal and vertical eye position was estimated using multiple linear regression and preferred directions computed for each eye. Results: Unexpectedly, the mean preferred directions for the left eye were normal in the monkeys with A-pattern exotropia. For the right eye, there was a clear upward deviation for the right NPH and a downward deviation for the left NPH. In addition, the R2 values were significantly lower for model fits for neurons recorded from the exotropic monkeys. Conclusions: We suggest that vertical inconcomitance results from inappropriate vertical-to-horizontal cross-talk that affects the two eyes differently.

Abnormal Eye Position Signals in Interstitial Nucleus of Cajal in Monkeys With "A" Pattern Strabismus.

Purpose: Pattern strabismus is characterized by a cross-axis pattern of horizontal and vertical misalignments. In A-pattern strabismus, for example, a divergent change in the horizontal misalignment occurs on downgaze. Work with nonhuman primate models has provided evidence that this disorder is associated with abnormal cross-talk between brainstem pathways that normally encode horizontal and vertical eye position and velocity. Neurons in the interstitial nucleus of Cajal (INC) are normally sensitive to vertical eye position; in the present study, we test the hypothesis that, in monkeys with pattern strabismus, some INC neurons will show an abnormal sensitivity to horizontal eye position. Methods: Monkeys were rewarded for fixating a visual target that stepped to various locations on a tangent screen. Single neurons were recorded from INC in one normal monkey, and two with A-pattern strabismus. Multiple linear regression analysis was used to estimate the preferred direction for each neuron. Results: In the normal monkey, all INC neurons had preferred directions within 20° of pure vertical (either up or down). The preferred directions were significantly more variable in the monkeys with pattern strabismus, with a minority being more sensitive to horizontal eye position than vertical eye position. In addition, the vertical eye position sensitivity was significantly less in the monkeys with strabismus. Conclusions: In pattern strabismus, neurons in INC show neurophysiological abnormalities consistent with a failure to develop normal tuning properties. Results were consistent with the hypothesis that, in pattern strabismus, INC receives an abnormally strong signal related to horizontal eye position.

A Rhesus Monkey With a Naturally Occurring Impairment of Disparity Vergence. I. Behavioral Comparisons to Vergence in a Normal Animal.

Purpose: Human children with disorders affecting vergence eye movements have difficulty during close work, such as reading. Patients with convergence insufficiency show a receded near point and an exophoria that is greater at near than at far. Neurologic abnormalities may underlie these symptoms, but it is difficult to test this idea directly because there is no animal model for this disorder. In the present case report, we describe behavioral testing in a rhesus monkey with a naturally occurring impairment of vergence eye movements (monkey CI). Methods: Three monkeys were trained to perform a variety of oculomotor tasks that required saccades, vergence, and/or smooth tracking of a visual target moving in depth. Results: Two of the monkeys (N1 and N2) were able to perform these tasks correctly. The third, monkey CI, was able to correctly perform these tasks when the required vergence angle was ≤5° but had difficulty when the task required larger convergence. This animal showed a consistent exodeviation that worsened as the target drew closer. When a variable prism was used to test disparity vergence in monkey CI, the animal showed an unstable convergence response (maximum 6°) that increased with prism correction, up to 12 prism diopters. By comparison, monkey N1 was able to achieve stable, appropriate convergence up to 26 prism diopters. Monkey CI's performance on vergence tasks improved when a large-field random checkerboard pattern was used to provide additional depth cues. Conclusions: Monkey CI appears to have a naturally occurring disorder of vergence eye movements.

A Rhesus Monkey With a Naturally Occurring Impairment of Disparity Vergence. II. Abnormal Near Response Cell Activity in the Supraoculomotor Area.

Purpose: Convergence insufficiency is a very common disorder that can have significant adverse effects on school performance. When reading, children with this disorder often experience diplopia and headaches. We have recently obtained a rhesus monkey with a naturally occurring impairment of vergence eye movements. In the companion paper, we report behavioral testing that shows a pattern of impairments similar to what clinicians observe in human children with convergence insufficiency, including a receded near point, an exophoria that increases as target distance decreases, and difficulty maintaining an appropriate vergence angle when presented with a large field stimulus at near. For the present case report, we wondered whether these behavioral deficits would be associated with abnormal discharge patterns in brainstem neurons related to vergence eye movements. Methods: Single unit activity was recorded from near and far response cells in the supraoculomotor area in the vergence-impaired monkey, while he performed a smooth vergence tracking task or fixated visual targets at different distances. Results: We found an abnormally weak sensitivity to both vergence angle and vergence velocity. Nonetheless, these neurons modulated in association with contextually inappropriate slow vergence movements that occurred in the absence of saccades but not for slow divergence drifts that immediately followed converging saccades. Modulation of activity was more robust when additional depth cues were available. Conclusions: These data suggest that disorders affecting vergence eye movements may be associated with impoverished sensory input to the near and far response cells and, perhaps, aberrant tuning in vergence-related neurons.

Activity of near-response cells during disconjugate saccades in strabismic monkeys.

Infantile strabismus is a common disorder characterized by a chronic misalignment of the eyes, impairment of binocular vision, and oculomotor abnormalities. Nonhuman primates with strabismus, induced in infancy, show a pattern of abnormalities similar to those of strabismic children. This allows strabismic nonhuman primates to serve as an ideal animal model to examine neural mechanisms associated with aberrant oculomotor behavior. Here, we test the hypothesis that impairment of disparity vergence and horizontal saccade disconjugacy in exotropia and esotropia are associated with disrupted tuning of near- and far-response neurons in the supraoculomotor area (SOA). In normal animals, these neurons carry signals related to vergence position and/or velocity. We hypothesized that, in strabismus, these neurons modulate inappropriately in association with saccades between equidistant targets. We recorded from 62 SOA neurons from 4 strabismic animals (2 esotropes and 2 exotropes) during visually guided saccades to a target that stepped to different locations on a tangent screen. Under these same conditions, SOA neurons in normal animals show no detectable modulation. In our strabismic subjects, we found that a subset of SOA neurons carry weak vergence velocity signals during saccades. In addition, a subset of SOA neurons showed clear modulation associated with slow fluctuations of horizontal strabismus angle in the absence of a saccade. We suggest that abnormal SOA activity contributes to fixation instability but plays only a minor role in the horizontal disconjugacy of saccades that do not switch fixation from one eye to the other. NEW & NOTEWORTHY The present study is the first to investigate the activity of neurons in the supraoculomotor area (SOA) during horizontally disconjugate saccades in a nonhuman primate model of infantile strabismus. We report that fluctuations of horizontal strabismus angle, during fixation of static targets on a tangent screen, are associated with contextually inappropriate modulation of SOA activity. However, firing rate modulation during saccades is too weak to make a major contribution to horizontal disconjugacy.

Response of supraoculomotor area neurons during combined saccade-vergence movements.

Combined saccade-vergence movements allow humans and other primates to align their eyes with objects of interest in three-dimensions. In the absence of saccades, vergence movements are typically slow, symmetrical movements of the two eyes in opposite directions. However, combined saccade-vergence movements produce vergence velocities that exceed values observed during vergence alone. This phenomenon is often called "vergence enhancement", or "saccade-facilitated vergence," though it is important to consider that rapid vergence changes, known as "vergence transients," are also observed during conjugate saccades. We developed a visual target array that allows monkeys to make saccades in all directions between targets spaced at distances that correspond to ~1° intervals of vergence angle relative to the monkey. We recorded the activity of vergence-sensitive neurons in the supra-oculomotor area (SOA), located dorsal and lateral to the oculomotor nucleus while monkeys made saccades with vergence amplitudes ranging from 0 to 10°. The primary focus of this study was to test the hypothesis that neurons in the SOA fire a high frequency burst of spikes during saccades that could generate the enhanced vergence. We found that individual neurons encode vergence velocity during both saccadic and non-saccadic vergence, yet firing rates were insufficient to produce the observed enhancement of vergence velocity. Our results are consistent with the hypothesis that slow vergence changes are encoded by the SOA while fast vergence movements require an additional contribution from the saccadic system. NEW & NOTEWORTHY Research into combined saccade-vergence movements has so far focused on exploring the saccadic neural circuitry, leading to diverging hypotheses regarding the role of the vergence system in this behavior. In this study, we report the first quantitative analysis of the discharge of individual neurons that encode vergence velocity in the monkey brain stem during combined saccade-vergence movements.

Comparison of three models of saccade disconjugacy in strabismus.

In pattern strabismus the horizontal and vertical misalignments vary with eye position along the orthogonal axis. The disorder is typically described in terms of overaction or underaction of oblique muscles. Recent behavioral studies in humans and monkeys, however, have reported that such actions are insufficient to fully explain the patterns of directional and amplitude disconjugacy of saccades. There is mounting evidence that the oculomotor abnormalities associated with strabismus are at least partially attributable to neurophysiological abnormalities. A number of control systems models have been developed to simulate the kinematic characteristics of saccades in normal primates. In the present study we sought to determine whether these models could simulate the abnormalities of saccades in strabismus by making two assumptions: 1) in strabismus the burst generator gains differ for the two eyes and 2) abnormal crosstalk exists between the horizontal and vertical saccadic circuits in the brain stem. We tested three models, distinguished by the location of the horizontal-vertical crosstalk. All three models were able to simulate amplitude and directional saccade disconjugacy, postsaccadic drift, and a pattern strabismus for static fixation, but they made different predictions about the dynamics of saccades. By assuming that crosstalk occurs at multiple nodes, the Distributed Crosstalk Model correctly predicted the dynamics of saccades. These new models make additional predictions that can be tested with future neurophysiological experiments.NEW & NOTEWORTHY Over the past several decades, numerous control systems models have been devised to simulate the known kinematic features of saccades in normal primates. These models have proven valuable to neurophysiology, as a means of generating testable predictions. The present manuscript, as far as we are aware, is the first to present control systems models to simulate the known abnormalities of saccades in strabismus.

Neural mechanisms of oculomotor abnormalities in the infantile strabismus syndrome.

Infantile strabismus is characterized by numerous visual and oculomotor abnormalities. Recently nonhuman primate models of infantile strabismus have been established, with characteristics that closely match those observed in human patients. This has made it possible to study the neural basis for visual and oculomotor symptoms in infantile strabismus. In this review, we consider the available evidence for neural abnormalities in structures related to oculomotor pathways ranging from visual cortex to oculomotor nuclei. These studies provide compelling evidence that a disturbance of binocular vision during a sensitive period early in life, whatever the cause, results in a cascade of abnormalities through numerous brain areas involved in visual functions and eye movements.

Electrical Microstimulation of the Superior Colliculus in Strabismic Monkeys.

PURPOSE: Visually guided saccades are disconjugate in human and nonhuman strabismic primates. The superior colliculus (SC) is a region of the brain topographically organized in visual and motor maps where the saccade goal is spatially coded. The present study was designed to investigate if a site of stimulation on the topographic motor map was evoking similar or different saccade vectors for each eye. METHODS: We used microelectrical stimulation (MS) of the SC in two strabismic (one esotrope and one exotrope) and two control macaques under binocular and monocular viewing conditions. We compared the saccade amplitudes and directions for each SC site and each condition independently of the fixating eye and then between each fixating eye. A comparison with disconjugacies of visually guided saccades was also performed. RESULTS: We observed different saccade vectors for the two eyes in strabismic monkeys, but conjugate saccades in normal monkeys. Evoked saccade vectors for the left eye when that eye was fixating the target were different from those of the right eye when it was fixating. The disconjugacies evoked by the MS were not identical but similar to those observed for visually guided saccades especially for the dominant eye. CONCLUSIONS: Our results suggest that, in strabismus, the saccade generator does not interpret activation of a single location of the SC as the same desired displacement for each eye. This finding is important for advancing understanding of the development of neural circuits in strabismus. French Abstract.

Abnormal tuning of saccade-related cells in pontine reticular formation of strabismic monkeys.

Strabismus is a common disorder, characterized by a chronic misalignment of the eyes and numerous visual and oculomotor abnormalities. For example, saccades are often highly disconjugate. For humans with pattern strabismus, the horizontal and vertical disconjugacies vary with eye position. In monkeys, manipulations that disturb binocular vision during the first several weeks of life result in a chronic strabismus with characteristics that closely match those in human patients. Early onset strabismus is associated with altered binocular sensitivity of neurons in visual cortex. Here we test the hypothesis that brain stem circuits specific to saccadic eye movements are abnormal. We targeted the pontine paramedian reticular formation, a structure that directly projects to the ipsilateral abducens nucleus. In normal animals, neurons in this structure are characterized by a high-frequency burst of spikes associated with ipsiversive saccades. We recorded single-unit activity from 84 neurons from four monkeys (two normal, one exotrope, and one esotrope), while they made saccades to a visual target on a tangent screen. All 24 neurons recorded from the normal animals had preferred directions within 30° of pure horizontal. For the strabismic animals, the distribution of preferred directions was normal on one side of the brain, but highly variable on the other. In fact, 12/60 neurons recorded from the strabismic animals preferred vertical saccades. Many also had unusually weak or strong bursts. These data suggest that the loss of corresponding binocular vision during infancy impairs the development of normal tuning characteristics for saccade-related neurons in brain stem.

Abnormal activity of neurons in abducens nucleus of strabismic monkeys.

PURPOSE: Infantile strabismus is characterized by persistent misalignment of the eyes. Mounting evidence suggests that the disorder is associated with abnormalities at the neural level, but few details are known. This study investigated the signals carried by abducens neurons in monkeys with experimentally induced strabismus. We wanted to know whether the firing rates of individual neurons are exclusively related to the position and velocity of one eye and whether the overall level of activity of the abducens nucleus was in the normal range. METHODS: We recorded 58 neurons in right and left abducens nuclei while strabismic monkeys (one esotrope and one exotrope) performed a saccade task. We analyzed the firing rates associated with static horizontal eye position and saccades by fitting the data with a dynamic equation that included position and velocity terms for each eye. Results were compared to previously published data in normal monkeys. RESULTS: For both strabismic monkeys the overall tonic activity was 50 to 100 spikes/s lower, for every suprathreshold eye position, than what has previously been reported for normal monkeys. This was mostly the result of lower baseline activity; the slopes of rate-position curves were similar to those in previous reports in normal monkeys. The saccade velocity sensitivities were similar to those of normal monkeys, 0.35 for the esotrope and 0.40 for the exotrope. For most neurons the firing rate was more closely related to the position and velocity of the ipsilateral eye. CONCLUSIONS: These data suggest that strabismus can be associated with reduced neural activity in the abducens nucleus.

Vertical and oblique saccade disconjugacy in strabismus.

PURPOSE: Previous studies have shown that horizontal saccades are disconjugate in humans and monkeys with strabismus. The present study was designed to extend these results to vertical and oblique saccades. A major goal was to assess the conjugacy in terms of both amplitude and direction. METHODS: Saccadic eye movements were recorded binocularly in three adult monkeys. One had normal eye alignment, one had exotropia resulting from a bilateral medial rectus tenotomy in the first week of life, and one had esotropia resulting from prism rearing during the first 3 months of life. We assessed the conjugacy of saccades in various directions by comparing both amplitude and direction. RESULTS: Saccades in the strabismic monkeys were disconjugate in terms of both amplitude and direction. These effects were as large for vertical and oblique saccades as for horizontal ones. However, the pattern of disconjugacy often varied as a function of saccade direction. In some cases, saccades that appeared to be conjugate in terms of amplitude differed substantially when direction was taken into account. CONCLUSIONS: These data indicate that the assessment of saccade disconjugacy in strabismus may yield misleading results if direction is not considered. The complex pattern of disconjugacy suggests that strabismus is associated with substantial abnormalities within the circuitry controlling saccades. Neurophysiological studies are needed to identify the specific neural substrates for these behavioral effects.

Activity of long-lead burst neurons in pontine reticular formation during head-unrestrained gaze shifts.

Primates explore a visual scene through a succession of saccades. Much of what is known about the neural circuitry that generates these movements has come from neurophysiological studies using subjects with their heads restrained. Horizontal saccades and the horizontal components of oblique saccades are associated with high-frequency bursts of spikes in medium-lead burst neurons (MLBs) and long-lead burst neurons (LLBNs) in the paramedian pontine reticular formation. For LLBNs, the high-frequency burst is preceded by a low-frequency prelude that begins 12-150 ms before saccade onset. In terms of the lead time between the onset of prelude activity and saccade onset, the anatomical projections, and the movement field characteristics, LLBNs are a heterogeneous group of neurons. Whether this heterogeneity is endemic of multiple functional subclasses is an open question. One possibility is that some may carry signals related to head movement. We recorded from LLBNs while monkeys performed head-unrestrained gaze shifts, during which the kinematics of the eye and head components were dissociable. Many cells had peak firing rates that never exceeded 200 spikes/s for gaze shifts of any vector. The activity of these low-frequency cells often persisted beyond the end of the gaze shift and was usually related to head-movement kinematics. A subset was tested during head-unrestrained pursuit and showed clear modulation in the absence of saccades. These "low-frequency" cells were intermingled with MLBs and traditional LLBNs and may represent a separate functional class carrying signals related to head movement.

Stimulation of pontine reticular formation in monkeys with strabismus.

PURPOSE: Saccade disconjugacy in strabismus could result from any of a number of factors, including abnormalities of eye muscles, the plant, motoneurons, near response cells, or atypical tuning of neurons in saccade-related areas of the brain. This study was designed to investigate the possibility that saccade disconjugacy in strabismus is associated with abnormalities in paramedian pontine reticular formation (PPRF). METHODS: We applied microstimulation to 22 sites in PPRF and 20 sites in abducens nucleus in three rhesus macaque monkeys (one normal, one esotrope, and one exotrope). RESULTS: When mean velocity was compared between the two eyes, a slight difference was found for 1/5 sites in the normal animal. Significant differences were found for 5/6 sites in an esotrope and 10/11 sites in an exotrope. For five sites in the strabismic monkeys, the directions of evoked movements differed by more than 40° between the two eyes. When stimulation was applied to abducens nucleus (20 sites), the ipsilateral eye moved faster for 4/6 sites in the normal animal and all nine sites in the esotrope. For the exotrope, however, the left eye always moved faster, even for three sites on the right side. For the strabismic animals, stimulation of abducens nucleus often caused a different eye to move faster than stimulation of PPRF. CONCLUSIONS: These data suggest that PPRF is organized at least partly monocularly in strabismus and that disconjugate saccades are at least partly a consequence of unbalanced saccadic commands being sent to the two eyes.

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.

Effect of reversible inactivation of superior colliculus on head movements.

Because of limitations in the oculomotor range, many gaze shifts must be accomplished using coordinated movements of the eyes and head. Stimulation and recording data have implicated the primate superior colliculus (SC) in the control of these gaze shifts. The precise role of this structure in head movement control, however, is not known. The present study uses reversible inactivation to gain insight into the role of this structure in the control of head movements, including those that accompany gaze shifts and those that occur in the absence of a change in gaze. Forty-five lidocaine injections were made in two monkeys that had been trained on a series of behavioral tasks that dissociate movements of the eyes and head. Reversible inactivation resulted in clear impairments in the animals' ability to perform gaze shifts, manifested by increased reaction times, lower peak velocities, and increased durations. In contrast, comparable effects were not found for head movements (with or without gaze shifts) with the exception of a very small increase in reaction times of head movements associated with gaze shifts. Eye-head coordination was clearly affected by the injections with gaze onset occurring relatively later with respect to head onset. Following the injections, the head contributed slightly more to the gaze shift. These results suggest that head movements (with and without gaze shifts) can be controlled by pathways that do not involve SC.

Role of the primate superior colliculus in the control of head movements.

One important behavioral role for head movements is to assist in the redirection of gaze. However, primates also frequently make head movements that do not involve changes in the line of sight. Virtually nothing is known about the neural basis of these head-only movements. In the present study, single-unit extracellular activity was recorded from the superior colliculus while monkeys performed behavioral tasks that permit the temporal dissociation of gaze shifts and head movements. We sought to determine whether superior colliculus contains neurons that modulate their activity in association with head movements in the absence of gaze shifts and whether classic gaze-related burst neurons also discharge for head-only movements. For 26% of the neurons in our sample, significant changes in average firing rate could be attributed to head-only movements. Most of these increased their firing rate immediately prior to the onset of a head movement and continued to discharge at elevated frequency until the offset of the movement. Others discharged at a tonic rate when the head was stable and decreased their activity, or paused, during head movements. For many putative head cells, average firing rate was found to be predictive of head displacement. Some neurons exhibited significant changes in activity associated with gaze, eye-only, and head-only movements, although none of the gaze-related burst neurons significantly modulated its activity in association with head-only movements. These results suggest the possibility that the superior colliculus plays a role in the control of head movements independent of gaze shifts.

Behavioral evaluation of movement cancellation.

The countermanding saccade task has been used in many studies to investigate the neural mechanisms that underlie the decision to execute or restrain rapid eye movements. In this task, the presentation of a saccade target is sometimes followed by the appearance of a stop cue that indicates that the subject should cancel the planned movement. Performance has been modeled as a race between motor preparation and cancellation processes. The signal that reaches its activation threshold first determines whether a saccade is generated or cancelled. In these studies, an important parameter is the time required to process the stop cue, referred to as the stop signal reaction time (SSRT). The SSRT is estimated using statistical approaches, the validity of which has not been unequivocally established. A more direct measure of this parameter might be obtainable if a method was available to "unmask" the developing motor command. This can be accomplished by air-puff-evoked blinks, which inhibit pontine omnipause neurons that serve as an inhibitory gate for the saccadic system. In the present study, brief puffs of air were used to elicit blinks at various times while rhesus monkeys performed a countermanding saccade task. If the developing motor command has not yet been cancelled, this should trigger a saccade. When blinks occurred between approximately 50 and 200 ms after target onset, saccades were often evoked. Saccades were rarely evoked more than approximately 70 ms after stop cue onset; this value represents a behavioral evaluation of SSRT and was comparable to the estimates obtained using standard statistical approaches. When saccades occurred near the SSRT on blink trials, they were often hypometric. Furthermore, Monte Carlo simulations were performed to model the effects of blink time on the race model. Overall, the study supports the validity of the statistical methods currently in use.