Effects of mild to moderate sedation on saccadic eye movements.

Sedatives alter the metrics of saccadic eye movements. If these effects are nonspecific consequences of sedation, like drowsiness and loss of attention to the task, or differ between sedatives is still unresolved. A placebo-controlled multi-step infusion of one of three sedatives, propofol or midazolam, both GABA-A agonists, or dexmedetedomidine, an α2-adrenergic agonist, was adopted to compare the effects of these three drugs in exactly the same experimental conditions. 60 healthy human volunteers, randomly divided in 4 groups, participated in the study. Each infusion step, delivered by a computer-controlled infusion pump, lasted 20min. During the last 10min of each step, the subject executed a saccadic task. Target concentration was doubled at each step. This block was repeated until the subject was too sedated to continue or for a maximum of 6 blocks. Subjects were unaware which infusion they were receiving. A video eye tracker was used to record the movements of the right eye. Saccadic parameters were modeled as a function of block number, estimated sedative plasma concentration, and subjective evaluation of sedation. Propofol and midazolam had strong effects on the dynamics and latency of the saccades. Midazolam, and to a less extent, propofol, caused saccades to become increasingly hypometric. Dexmedetedomidine had less impact on saccadic metrics and presented no changes in saccadic gain. Suppression of the sympathetic system associated with dexmedetomidine has different effects on eye movements from the increased activity of the inhibitory GABA-A receptors by propofol and midazolam even when the subjects reported similar sedation level.

Short-term saccadic adaptation in the macaque monkey: a binocular mechanism.

Saccadic eye movements are rapid transfers of gaze between objects of interest. Their duration is too short for the visual system to be able to follow their progress in time. Adaptive mechanisms constantly recalibrate the saccadic responses by detecting how close the landings are to the selected targets. The double-step saccadic paradigm is a common method to simulate alterations in saccadic gain. While the subject is responding to a first target shift, a second shift is introduced in the middle of this movement, which masks it from visual detection. The error in landing introduced by the second shift is interpreted by the brain as an error in the programming of the initial response, with gradual gain changes aimed at compensating the apparent sensorimotor mismatch. A second shift applied dichoptically to only one eye introduces disconjugate landing errors between the two eyes. A monocular adaptive system would independently modify only the gain of the eye exposed to the second shift in order to reestablish binocular alignment. Our results support a binocular mechanism. A version-based saccadic adaptive process detects postsaccadic version errors and generates compensatory conjugate gain alterations. A vergence-based saccadic adaptive process detects postsaccadic disparity errors and generates corrective nonvisual disparity signals that are sent to the vergence system to regain binocularity. This results in striking dynamical similarities between visually driven combined saccade-vergence gaze transfers, where the disparity is given by the visual targets, and the double-step adaptive disconjugate responses, where an adaptive disparity signal is generated internally by the saccadic system.

Macaque pontine omnipause neurons play no direct role in the generation of eye blinks.

We recorded the activity of pontine omnipause neurons (OPNs) in two macaques during saccadic eye movements and blinks. As previously reported, we found that OPNs fire tonically during fixation and pause about 15 ms before a saccadic eye movement. In contrast, for blinks elicited by air puffs, the OPNs paused <2 ms before the onset of the blink. Thus the burst in the agonist orbicularis oculi motoneurons (OOMNs) and the pause in the antagonist levator palpabrae superioris motoneurons (LPSMNs) necessarily precede the OPN pause. For spontaneous blinks there was no correlation between blink and pause onsets. In addition, the OPN pause continued for 40-60 ms after the time of the maximum downward closing of the eyelids, which occurs around the end of the OOMN burst of firing. LPSMN activity is not responsible for terminating the OPN pause because OPN resumption was very rapid, whereas the resumption of LPSMN firing during the reopening phase is gradual. OPN pause onset does not directly control blink onset, nor does pause offset control or encode the transition between the end of the OOMN firing and the resumption of the LPSMNs. The onset of the blink-related eye transients preceded both blink and OPN pause onsets. Therefore they initiated while the saccadic short-lead burst neurons were still fully inhibited by the OPNs and cannot be saccadic in origin. The abrupt dynamic change of the vertical eye transients from an oscillatory behavior to a single time constant exponential drift predicted the resumption of the OPNs.

Saccade-vergence interactions in macaques. I. Test of the omnipause Multiply Model.

Horizontal vergence eye movements are movements in opposite directions used to change fixation between far and near targets. The occurrence of a saccade during vergence causes vergence velocity to be transiently enhanced. The goal of this study was to test in the monkey the previously described Multiply Model (Zee et al. 1992) that holds that, in humans, the speeding of vergence during a saccade may be the result of the disinhibition of a subgroup of vergence-related neurons by the saccadic omnipause neurons (OPNs). In agreement with the Multiply Model: 1) the onset of the enhancement was closely related to saccadic onset, and thus linked to the onset of the OPN pause; 2) the magnitude of the vergence velocity enhancement was strongly dependent on saccade-vergence timing. Contrary to the Multiply Model: 1) the peak of the vergence velocity enhancement was dependent on saccadic peak velocity; 2) the dependency on saccadic peak velocity was not the indirect result of a dependency on saccadic duration and therefore on the duration of the OPN pause; 3) the decline of the vergence enhancement, identified by the time of the peak of the enhancement velocity, occurred too early to be linked to the end of the OPN pause; 4) vergence enhancement had a saccadic-like peak-velocity/size main sequence. Overall, the evidence is incompatible with the OPN Multiply hypothesis of vergence enhancement. Alternative models are described in an accompanying paper.

Saccade-vergence interactions in macaques. II. Vergence enhancement as the product of a local feedback vergence motor error and a weighted saccadic burst.

In the accompanying paper we reported that intrasaccadic vergence enhancement during combined saccade-vergence eye movements reflects saccadic dynamics, which implies the involvement of saccadic burst signals. This involvement was not predicted by the Multiply Model of Zee et al. We propose a model wherein vergence enhancement is the result of a multiplicative interaction between a weighted saccadic burst signal and a nonvisual short-latency estimate of the vergence motor error at the time of the saccade. The enhancement of vergence velocity by saccades causes the vergence goal to be approached more rapidly than if no saccade had occurred. The adjustment of the postsaccadic vergence velocity to this faster reduction in vergence motor error occurred with a time course too fast for visual feedback. This implies the presence of an internal estimate of the progress of the movement and indicates that vergence responses are under the control of a local feedback mechanism. It also implies that the vergence enhancement signal is included in the vergence feedback loop and is an integral part of the vergence velocity command. Our multiplicative model is able to predict the peak velocity of the vergence enhancement as a function of cyclopean saccadic dynamics, smooth vergence dynamics, and saccade-vergence timing with remarkable precision. It performed equally well for both horizontal and vertical saccades with very similar parameters, suggesting a common mechanism for all saccadic directions. A saccade-vergence additive model is also presented, although it would require external switching elements. Possible neural implementations are discussed.

Pontine omnipause activity during conjugate and disconjugate eye movements in macaques.

Previous reports have shown that saccades executed during vergence eye movements are often slower and longer than conjugate saccades. Lesions in the nucleus raphe interpositus, where pontine omnipause neurons (OPNs) are located, were also shown to result in slower and longer saccades. If vergence transiently suppresses the activity of the OPNs just before a saccade, then reduced presaccadic activity might mimic the behavioral effects of a lesion. To test this hypothesis, 64 OPNs were recorded from 7 alert rhesus monkeys during smooth vergence and saccades with and without vergence. The firing rate of many OPNs was modulated by static vergence angle but not by version and showed transient changes during slow vergence without saccades. This modulation was smooth, and not the abrupt pause seen for saccades, indicating that OPNs do not act as gates for vergence commands. We confirmed that saccades made during both convergence and divergence are significantly slower and longer than conjugate saccades. OPNs paused for all saccades, and the pause lead (interval between pause onset and saccadic onset) was significantly longer for saccades with convergence, in agreement with our hypothesis. Contrary to our hypothesis, pause lead was not longer for saccades with divergence, even though these saccades were slowed as much as those occurring during convergence. Furthermore, there was no significant correlation, on a trial-by-trial basis, between pause lead and saccadic slowing. These results suggest that it is unlikely that presaccadic slowing of OPNs is responsible for the slower saccades seen during vergence movements.

Short-latency ocular following in humans: sensitivity to binocular disparity.

We show that the initial ocular following responses elicited by motion of a large pattern are modestly attenuated when that pattern is shifted out of the plane of fixation by altering its binocular disparity. If the motion is applied to only restricted regions of the pattern, however, then altering the disparity of those regions severely attenuates their ability to generate ocular following. This sensitivity of the ocular tracking mechanism to local binocular disparity would help the observer who moves through a cluttered 3-D world to stabilize objects in the plane of fixation and ignore all others.

Short-latency disparity vergence in humans.

Eye movement recordings from humans indicated that brief exposures (200 ms) to horizontal disparity steps applied to large random-dot patterns elicit horizontal vergence at short latencies (80.9 +/- 3.9 ms, mean +/- SD; n = 7). Disparity tuning curves, describing the dependence of the initial vergence responses (measured over the period 90-157 ms after the step) on the magnitude of the steps, resembled the derivative of a Gaussian, with nonzero asymptotes and a roughly linear servo region that extended only a degree or two on either side of zero disparity. Responses showed transient postsaccadic enhancement: disparity steps applied in the immediate wake of saccadic eye movements yielded higher vergence accelerations than did the same steps applied some time later (mean time constant of the decay, 200 ms). This enhancement seemed to be dependent, at least in part, on the visual reafference associated with the prior saccade because similar enhancement was observed when the disparity steps were applied in the wake of saccadelike shifts of the textured pattern. Vertical vergence responses to vertical disparity steps were qualitatively similar: latencies were longer (on average, by 3 ms), disparity tuning curves had the same general form but were narrower (by approximately 20%), and their peak-to-peak amplitudes were smaller (by approximately 70%). Initial vergence responses usually had directional errors (orthogonal components) with a very systematic dependence on step size that often approximated an exponential decay to a nonzero asymptote (mean space constant +/- SD, 1.18 +/- 0.66 degrees ). Based on the asymptotes of these orthogonal responses, horizontal errors (with vertical steps) were on average more than three times greater than vertical errors (with horizontal steps). Disparity steps >7 degrees generated "default" responses that were independent of the direction of the step, idiosyncratic, and generally had both horizontal and vertical components. We suggest that the responses depend on detectors that sense local disparity matches, and that orthogonal and "default" responses result from globally "false" matches. Recordings from three monkeys, using identical disparity stimuli, confirmed that monkeys also show short-latency disparity vergence responses (latency approximately 25 ms shorter than that of humans), and further indicated that these responses show all of the major features seen in humans, the differences between the two species being solely quantitative. Based on these data and those of others implying that foveal images normally take precedence, we suggest that the mechanisms under study here ordinarily serve to correct small vergence errors, automatically, especially after saccades.

Radial optic flow induces vergence eye movements with ultra-short latencies.

An observer moving forwards through the environment experiences a radial pattern of image motion on each retina. Such patterns of optic flow are a potential source of information about the observer's rate of progress, direction of heading and time to reach objects that lie ahead. As the viewing distance changes there must be changes in the vergence angle between the two eyes so that both foveas remain aligned on the object of interest in the scene ahead. Here we show that radial optic flow can elicit appropriately directed (horizontal) vergence eye movements with ultra-short latencies (roughly 80 ms) in human subjects. Centrifugal flow, signalling forwards motion, increases the vergence angle, whereas centripetal flow decreases the vergence angle. These vergence eye movements are still evident when the observer's view of the flow pattern is restricted to the temporal hemifield of one eye, indicating that these responses do not result from anisotropies in motion processing but from a mechanism that senses the radial pattern of flow. We hypothesize that flow-induced vergence is but one of a family of rapid ocular reflexes, mediated by the medial superior temporal cortex, compensating for translational disturbance of the observer.

Vergence eye movements in response to binocular disparity without depth perception.

Primates use vergence eye movements to align their two eyes on the same object and can correct misalignments by sensing the difference in the positions of the two retinal images of the object (binocular disparity). When large random-dot patterns are viewed dichoptically and small binocular misalignments are suddenly imposed (disparity steps), corrective vergence eye movements are elicited at ultrashort latencies. Here we show that the same steps applied to dense anticorrelated patterns, in which each black dot in one eye is matched to a white dot in the other eye, initiate vergence responses that are very similar, except that they are in the opposite direction. This sensitivity to the disparity of anticorrelated patterns is shared by many disparity-selective neurons in cortical area V1, despite the fact that human subjects fail to perceive depth in such stimuli. These data indicate that the vergence eye movements initiated at ultrashort latencies result solely from locally matched binocular features, and derive their visual input from an early stage of cortical processing before the level at which depth percepts are elaborated.

Short-latency disparity vergence responses and their dependence on a prior saccadic eye movement.

1. A dichoptic viewing arrangement was used to study the initial vergence eye movements elicited by brief horizontal disparity steps applied to large textured patterns in three rhesus monkeys. Disconjugate steps (range, 0.2-10.9 degrees) were applied to the patterns at selected times (range, 13-303 ms) after 10 degrees leftward saccades into the center of the pattern. The horizontal and vertical positions of both eyes were recorded with the electromagnetic search coil technique. 2. Without training or reinforcement, disparity steps of suitable amplitude consistently elicited vergence responses at short latencies. For example, with 1.8 degrees crossed-disparity steps applied 26 ms after the centering saccade, the mean latency of onset of convergence for each of the three monkeys was 52.2 +/- 3.8 (SD) ms, 52.3 +/- 5.2 ms, and 53.4 +/- 4.1 ms. 3. Experiments in which the disparity step was confined to only one eye indicated that each eye was not simply tracking the apparent motion that is saw. For example, when crossed-disparity steps were confined to the right eye (which saw leftward steps), the result was (binocular) convergence in which the left eye moved to the right even though that eye had seen only a stationary scene. This movement of the left eye cannot have resulted from independent monocular tracking and indicates that the vergences here derived from the binocular misalignment of the two retinal images. 4. The initial vergence responses to crossed-disparity steps had the following main features. 1) They were always in the correct (i.e., convergent) direction over the full range of stimuli tested, the initial vergence acceleration increasing progressively with increases in disparity until reaching a peak with steps of 1.4-2.4 degrees and declining thereafter to a nonzero asymptote as steps exceeded 5-7 degrees. 2) They showed transient postsaccadic enhancement whereby steps applied in the immediate wake of a saccadic eye movement resulted in much higher initial vergence accelerations than the same steps applied some time later. The response decline in the wake of a saccade was roughly exponential with time constants of 67 +/- 5 (SD) ms, 35 +/- 2 ms, and 54 +/- 4 ms for the three animals. 3) That the postsaccadic enhancement might have resulted in part from the visual stimulation associated with the prior saccade was suggested by the finding that enhancement could also be observed when the disparity steps were applied in the wake of (conjugate) saccadelike shifts of the textured pattern. However, this visual enhancement did not reach a peak unit 17-37 ms after the end of the "simulated" saccade, and the peak enhancement averaged only 45% of that after a "real" saccade. 4) Qualitatively similar transient enhancements in the wake of real and simulated saccades have also been reported for initial ocular following responses elicited by conjugate drifts of the visual scene. We replicated the enhancement effects on ocular following to allow a direct comparison with the enhancement effects on disparity vergence using the same animals and visual stimulus patterns and, despite some clear quantitative differences, we suggest that the enhancement effects share a similar etiology. 5. Initial vergence responses to uncrossed-disparity steps had the following main features. 1) They were in the correct (i.e., divergent) direction only for very small steps (< 1.5-2.5 degrees), and then only when postsaccadic delays were small; when the magnitude of the steps was increased beyond these levels, responses declined to zero and thereafter reversed direction, eventually reaching a nonzero (convergent) asymptote similar to that seen with large crossed-disparity steps; convergent responses were also seen with larger vertical disparity steps, suggesting that they represent default responses to any disparity exceeding a few degrees. 2) As the postsaccadic delay was increased, responses to small steps (1.8 degrees) declined to zero and thereafter re

A role for stereoscopic depth cues in the rapid visual stabilization of the eyes.

Primates have visual tracking systems that help stabilize the eyes on the surroundings by responding to retinal image motion at ultra-short latencies. However, as the observer moves through the environment, the image motion on the retina depends on the three-dimensional structure of the scene. We report here that the very earliest of these tracking responses is elicited only by objects moving in the immediate vicinity of the plane of fixation: objects nearer or farther are ignored. This selectivity is achieved by means of a stereoscopic depth mechanism which uses the fact that the two eyes have differing viewpoints, so only objects in the plane of fixation have images that occupy corresponding positions on the two retinae. Such behaviour is readily explained by the known binocular properties of some motion-selective neurons in the visual cortex. Some (stereoanomalous) subjects showed highly specific tracking deficits as though lacking one subtype of these neurons.

Human ocular responses to translation of the observer and of the scene: dependence on viewing distance.

Recent experiments on monkeys have indicated that the eye movements induced by brief translation of either the observer or the visual scene are a linear function of the inverse of the viewing distance. For the movements of the observer, the room was dark and responses were attributed to a translational vestibulo-ocular reflex (TVOR) that senses the motion through the otolith organs; for the movements of the scene, which elicit ocular following, the scene was projected and adjusted in size and speed so that the retinal stimulation was the same at all distances. The shared dependence on viewing distance was consistent with the hypothesis that the TVOR and ocular following are synergistic and share central pathways. The present experiments looked for such dependencies on viewing distance in human subjects. When briefly accelerated along the interaural axis in the dark, human subjects generated compensatory eye movements that were also a linear function of the inverse of the viewing distance to a previously fixated target. These responses, which were attributed to the TVOR, were somewhat weaker than those previously recorded from monkeys using similar methods. When human subjects faced a tangent screen onto which patterned images were projected, brief motion of those images evoked ocular following responses that showed statistically significant dependence on viewing distance only with low-speed stimuli (10 degrees/s). This dependence was at best weak and in the reverse direction of that seen with the TVOR, i.e., responses increased as viewing distance increased. We suggest that in generating an internal estimate of viewing distance subjects may have used a confounding cue in the ocular-following paradigm--the size of the projected scene--which was varied directly with the viewing distance in these experiments (in order to preserve the size of the retinal image). When movements of the subject were randomly interleaved with the movements of the scene--to encourage the expectation of ego-motion--the dependence of ocular following on viewing distance altered significantly: with higher speed stimuli (40 degrees/s) many responses (63%) now increased significantly as viewing distance decreased, though less vigorously than the TVOR. We suggest that the expectation of motion results in the subject placing greater weight on cues such as vergence and accommodation that provide veridical distance information in our experimental situation: cue selection is context specific.

Ocular compensation for self-motion. Visual mechanisms.

In monkeys, there are several reflexes that generate eye movements to compensate for the observer's own movements. Two vestibuloocular reflexes compensate selectively for rotational (RVOR) and translational (TVOR) disturbances of the head, receiving their inputs from the semicircular canals and otolith organs, respectively. Two independent visual tracking systems that deal with residual disturbances of gaze are manifest in the two components of the optokinetic response: the indirect or delayed component (OKNd) and the direct or early component (OKNe). We hypothesize that OKNd--like the RVOR--is phylogenetically old, being found in all animals with mobile eyes, and that it evolved as a backup to the RVOR to compensate for rotational disturbances of gaze. Indeed, optically induced changes in the gain of the RVOR result in parallel changes in the gain of OKNd, consistent with the idea of shared pathways as well as shared functions. In contrast, OKNe--like the TVOR--seems to have evolved much more recently in frontal-eyed animals and, we suggest, acts as a backup to the TVOR to deal primarily with translational disturbances of gaze. Frontal-eyed animals with good binocular vision must be able to keep both eyes directed at the object of regard irrespective of proximity, and in order to achieve this during translational disturbances, the output of the TVOR is modulated inversely with the viewing distance. OKNe shares this sensitivity to absolute depth, consistent with the idea that it is synergistic with the TVOR and shares some of its central pathways. There is evidence that OKNe is also sensitive to relative depth cues such as motion parallax, which we suggest helps the system to segregate the object of regard from other elements in the scene. However, there are occasions when the global optic flow cannot be resolved into a single vector useful to the oculomotor system (e.g., when the moving observer looks towards the direction of heading). We suggest that on such occasions a third independent tracking mechanism, the smooth pursuit system, is deployed to stabilize gaze on the local feature of interest. In this scheme, the pursuit system has an attentional focusing mechanism that spatially filters the visual motion inputs driving the oculomotor system. The major distinguishing features of the 3 visual tracking mechanisms are summarized in Table 1.

Ocular responses to translation and their dependence on viewing distance. II. Motion of the scene.

1. The ocular following responses induced by brief (100-ms) movements of the visual scene were examined for their dependence on viewing distance in 5 monkeys (Macaca mulatta). The horizontal positions of both eyes and the vertical position of one eye were recorded using the electromagnetic search-coil technique. Accommodation was monitored in selected experiments by use of an infrared optometer. Test patterns (random dots) were back-projected onto a translucent tangent screen facing the animal. Six viewing distances were used (range, 20-150 cm), the size and speed of the image on the screen being adjusted for each so as to preserve a constant retinal image. 2. Response measures based on the amplitude of the first peak in the eye acceleration profile or the eye velocity achieved at specific times all indicated that ocular following responses were inversely related to viewing distance, the relationship being linear for the earliest measures. On average, the sensitivity to viewing distance was comparable with that reported for the translational vestibuloocular reflex (TVOR) in the preceding paper: as viewing distance increased from 20 cm, ocular following decremented at a mean rate (+/- SD) of 17 +/- 3% per m-1, while the TVOR decremented at a mean rate (+/- SD) of 18 +/- 1% per m-1. 3. Ocular following responses showed the postsaccadic enhancement described by Kawano and Miles regardless of viewing distance. To a first approximation, the effects of postsaccadic enhancement and viewing distance summed linearly. 4. The dependence of ocular following on speed showed the progressive saturation previously described by Miles et al. at all viewing distances, the peak eye velocity achieved being inversely related to the viewing distance, indicating that the saturation must originate upstream of the dependence on viewing distance. Under normal viewing conditions, this speed saturation will tend to offset the dependence on viewing distance because the retinal slip speeds experienced by the moving observer will tend to vary inversely with viewing distance, resulting in greater saturation with nearer viewing. 5. Wedge prisms were used to dissociate vergence and accommodation and indicated that ocular following responses were sensitive to selective increases in either vergence (base-out prism with the screen at 100 cm) or accommodation (base-in prism with the screen at 20 cm). However, as with the TVOR, the magnitude of the effects showed considerable variability from one animal to another and, in some particular animals, from one direction to another.(ABSTRACT TRUNCATED AT 400 WORDS)

Ocular responses to linear motion are inversely proportional to viewing distance.

Eye movements exist to improve vision, in part by preventing excessive retinal image slip. A major threat to the stability of the retinal image comes from the observer's own movement, and there are visual and vestibular reflexes that operate to meet this challenge by generating compensatory eye movements. The ocular responses to translational disturbances of the observer and of the scene were recorded from monkeys. The associated vestibular and visual responses were both linearly dependent on the inverse of the viewing distance. Such dependence on proximity is appropriate for the vestibular reflex, which must transform signals from Cartesian to polar coordinates, but not for the visual reflex, which operates entirely in polar coordinates. However, such shared proximity effects in the visual reflex could compensate for known intrinsic limitations that would otherwise compromise performance at near viewing.