Three-dimensional vestibuloocular reflex of the monkey: optimal retinal image stabilization versus listing's law

If the rotational vestibuloocular reflex (VOR) were to achieve optimal retinal image stabilization during head rotations in three-dimensional space, it must turn the eye around the same axis as the head, with equal velocity but in the opposite direction. This optimal VOR strategy implies that the position of the eye in the orbit must not affect the VOR. However, if the VOR were to follow Listing's law, then the slow-phase eye rotation axis should tilt as a function of current eye position. We trained animals to fixate visual targets placed straight ahead or 20 degrees up, down, left or right while being oscillated in yaw, pitch, and roll at 0.5-4 Hz, either with or without a full-field visual background. Our main result was that the visually assisted VOR of normal monkeys invariantly rotated the eye around the same axis as the head during yaw, pitch, and roll (optimal VOR). In the absence of a visual background, eccentric eye positions evoked small axis tilts of slow phases in normal animals. Under the same visual condition, a prominent effect of eye position was found during roll but not during pitch or yaw in animals with low torsional and vertical gains following plugging of the vertical semicircular canals. This result was in accordance with a model incorporating a specific compromise between an optimal VOR and a VOR that perfectly obeys Listing's law. We conclude that the visually assisted VOR of the normal monkey optimally stabilizes foveal as well as peripheral retinal images. The finding of optimal VOR performance challenges a dominant role of plant mechanics and supports the notion of noncommutative operations in the oculomotor control system.     

Noncommutative control in the rotational vestibuloocular reflex

To investigate the role of noncommutative computations in the oculomotor system, three-dimensional (3D) eye movements were measured in seven healthy subjects using a memory-contingent vestibulooculomotor paradigm. Subjects had to fixate a luminous point target that appeared briefly at an eccentricity of 20 degrees in one of four diagonal directions in otherwise complete darkness. After a fixation period of approximately 1 s, the subject was moved through a sequence of two rotations about mutually orthogonal axes in one of two orders (30 degrees yaw followed by 30 degrees pitch and vice versa in upright and 30 degrees yaw followed by 20 degrees roll and vice versa in both upright and supine orientations). We found that the change in ocular torsion induced by consecutive rotations about the yaw and the pitch axis depended on the order of rotations as predicted by 3D rotation kinematics. Similarly, after rotations about the yaw and roll axis, torsion depended on the order of rotations but now due to the change in final head orientation relative to gravity. Quantitative analyses of these ocular responses revealed that the rotational vestibuloocular reflexes (VORs) in far vision closely matched the predictions of 3D rotation kinematics. We conclude that the brain uses an optimal VOR strategy with the restriction of a reduced torsional position gain. This restriction implies a limited oculomotor range in torsion and systematic tilts of the angular eye velocity as a function of gaze direction.     

Axes of eye rotation and Listing's law during rotations of the head

1. The vestibuloocular reflex (VOR) was examined in four alert monkeys during rotations of the head about torsional, vertical, horizontal, and intermediate axes. Eye positions and axes were recorded in three dimensions (3-D). Visual targets were used to optimize gaze stabilization. 2. Axes of eye rotation during slow phases showed small but systematic deviations from collinearity with the axes of head rotation. These noncollinearities apparently resulted from vector summation of torsional, vertical, and horizontal VOR components with different gains. 3. VOR gain was lowest about a head-fixed torsional axis that was correlated with the primary gaze direction, as determined by Listing's law for saccades. As a result, rotation of the head about a partially torsional axis produced noncollinear slow phases, with axes that tilted toward Listing's plane. 4. During slow phases, eye position changed not only in the direction of rotation, but also systematically in other directions. Even axes of eye rotation within Listing's plane caused eye position to move out of the plane to a torsional position that was then held. Thus Listing's law for saccades cannot be a product of plant mechanics. 5. VOR slow phases were simulated with the use of a model that incorporated 3-D rotational kinematics into the indirect path and the oculomotor plant. This demonstrated that the observed pattern of position changes is the expected consequence of rotating the eye about a fixed axis and that to hold these positions the indirect path must employ a 3-D velocity-to-position transformation. 6. Quick phases not only corrected the violations of Listing's law produced by slow phases but anticipated them by directing the eye toward a plane rotated in the direction of head rotation. This was modeled by inputting the vestibular signal to a Listing's law operator that is shared by the quick phase and saccadic systems.     

Vergence-mediated changes in the axis of eye rotation during the human vestibulo-ocular reflex can occur independent of eye position

The aim of this study was to determine whether vergence-mediated changes in the axis of eye rotation in the human vestibulo-ocular reflex (VOR) would obey Listing's Law (normally associated with saccadic eye movements) independent of the initial eye position. We devised a paradigm for disassociating the saccadic velocity axis from eye position by presenting near and far targets that were centered with respect to one eye. We measured binocular 3-dimensional eye movements using search coils in ten normal subjects and 3-dimensional linear head acceleration using Optotrak in seven normal subjects. The stimuli consisted of passive, unpredictable, pitch head rotations with peak acceleration of ~2,000°/s² and amplitude of ~20°. During the pitch head rotation, each subject fixated straight ahead with one eye, whereas the other eye was adducted 4° during far viewing (94 cm) and 25° during near viewing (15 cm). Our data showed expected compensatory pitch rotations in both eyes, and a vergence-mediated horizontal rotation only in the adducting eye. In addition, during near viewing we observed torsional eye rotations not only in the adducting eye but also in the eye looking straight ahead. In the straight-ahead eye, the change in torsional eye velocity between near and far viewing, which began ~40 ms after the start of head rotation, was 10±6°/s (mean ± SD). This change in torsional eye velocity resulted in a 2.4±1.5° axis tilt toward Listing's plane in that eye. In the adducting eye, the change in torsional eye velocity between near and far viewing was 16±6°/s (mean ± SD) and resulted in a 4.1±1.4° axis tilt. The torsional eye velocities were conjugate and both eyes partially obeyed Listing's Law. The axis of eye rotation tilted in the direction of the line of sight by approximately one-third of the angle between the line of sight and a line orthogonal to Listing's plane. This tilt was higher than predicted by the one-quarter rule. The translational acceleration component of the pitch head rotation measured 0.5 g and may have contributed to the increased torsional component observed during near viewing. Our data show that vergence-mediated eye movements obey a VOR/Listing's Law compromise strategy independent of the initial eye position.     

Context compensation in the vestibuloocular reflex during active head rotations

The vestibuloocular reflex (VOR) needs to modulate its gain depending on target distance to prevent retinal slip during head movements. We investigated gain modulation (context compensation) for binocular gaze stabilization in human subjects during voluntary yaw and pitch head rotations. Movements of each eye were recorded, both when attempting to maintain gaze on a small visual target at straight-ahead in a darkened room and after its disappearance (remembered target). In the analysis, we relied on a binocular coordinate system yielding a version and a vergence component. We examined how frequency and target distance, approached here by using vergence angle, affected the gain and phase of the version component of the VOR and compared the results to the requirements for ideal performance. Linear regression analysis on the version gain-vergence relationship yielded a slope representing the influence of target proximity and an intercept corresponding to the response at zero vergence ("default gain"). The slope of the fitted relationship, divided by the geometrically required slope, provided a measure for the quality of version context compensation ("context gain"). In both yaw and pitch experiments, we found default version gains close to one even for the remembered target condition, indicating that the active VOR for far targets is already close to ideal without visual support. In near target experiments, the presence of visual feedback yielded near unity context gains, indicating close to optimal performance (retinal slip <0.4 degrees /s). For remembered targets, the context gain deteriorated but was still superior to performance in corresponding passive studies reported in the literature. In general, context compensation in the remembered target paradigm was better for vertical than for horizontal head rotations. The phase delay of version eye velocity relative to head velocity was small (approximately 2 degrees) for both horizontal and vertical head movements. Analysis of the vergence data from the near target experiments showed that context compensation took into account that the two eyes require slightly different VORs. In the DISCUSSION, comparison of the present default VOR gains and context gains with data from earlier passive studies has led us to propose a limited role for efference copies during self-generated movements. We also discuss how our analysis can provide a framework for evaluating two different hypotheses for the generation of binocular VOR eye movements.     

The three-dimensional vestibulo-ocular reflex evoked by high-acceleration rotations in the squirrel monkey

The aim of this study was to determine if the angular vestibulo-ocular reflex (VOR) in response to pitch, roll, left anterior–right posterior (LARP), and right anterior–left posterior (RALP) head rotations exhibited the same linear and nonlinear characteristics as those found in the horizontal VOR. Three-dimensional eye movements were recorded with the scleral search coil technique. The VOR in response to rotations in five planes (horizontal, vertical, torsional, LARP, and RALP) was studied in three squirrel monkeys. The latency of the VOR evoked by steps of acceleration in darkness (3,000°/s² reaching a velocity of 150°/s) was 5.8±1.7 ms and was the same in response to head rotations in all five planes of rotation. The gain of the reflex during the acceleration was 36.7±15.4% greater than that measured at the plateau of head velocity. Polynomial fits to the trajectory of the response show that eye velocity is proportional to the cube of head velocity in all five planes of rotation. For sinusoidal rotations of 0.5–15 Hz with a peak velocity of 20°/s, the VOR gain did not change with frequency (0.74±0.06, 0.74±0.07, 0.37±0.05, 0.69±0.06, and 0.64±0.06, for yaw, pitch, roll, LARP, and RALP respectively). The VOR gain increased with head velocity for sinusoidal rotations at frequencies 4 Hz. For rotational frequencies 4 Hz, we show that the vertical, torsional, LARP, and RALP VORs have the same linear and nonlinear characteristics as the horizontal VOR. In addition, we show that the gain, phase and axis of eye rotation during LARP and RALP head rotations can be predicted once the pitch and roll responses are characterized.This work was supported by NIH grant R01 DC02390     

Symmetry of oculomotor burst neuron coordinates about Listing's plane.

1. The purpose of this investigation was to determine the axes of eye rotation generated by oculomotor burst neuron populations and the coordinate system that they collectively define. In particular, we asked if such coordinates might be related to constraints in the emergent behavior, i.e., Listing's law for saccades. 2. The mesencephalic rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) was identified in four monkeys with the use of single-unit recording, and then explored with the use of electrical microstimulation and pharmacological inactivation with the inhibitory gamma-aminobutyric acid (GABA) agonist muscimol. Three-dimensional (3-D) eye positions and velocities were recorded in one or both eyes while alert animals made eye movements in response to visual stimuli and head rotation. 3. Unilateral stimulation of the riMLF (20 microA, 200 Hz, 300-600 ms) produced conjugate, constant velocity eye rotations, which then stopped abruptly and held their final positions. This is expected if the riMLF produces phasic signals upstream from the oculomotor integrator. 4. Units that burst before upward or downward saccades were recorded intermingled in each side of the riMLF. Unilateral stimulation of the same riMLF sites produced eye rotations about primarily torsional axes, clockwise (CW) during right riMLF stimulation and counterclockwise (CCW) during left stimulation. Only small and inconsistent vertical components were observed, supporting the view that the riMLF carries intermingled up and down signals. 5. The torsional axes of eye rotation produced by riMLF stimulation did not correlate to external anatomic landmarks. Instead, stimulation axes from both riMLF sides aligned with the primary gaze direction orthogonal to Listing's plane of eye positions recorded during saccades. 6. Injection of muscimol into one side of the riMLF produced a conjugate deficit in saccades and quick phases, including a 50% reduction in all vertical velocities and complete loss of one torsional direction. CW was lost after right riMLF inactivation, and CCW was lost after left inactivation. 7. The plane that separated the intact torsional axes from the missing axes correlated with the orientation of Listing's plane. Thus, during left or right riMLF inactivation, the vertical axes of intact horizontal saccades were abnormally aligned with Listing's plane. The orientation of these axes was not correlated with external anatomic landmarks. 8. As suggested by their alignment with Listing's plane, the intact vertical axes of horizontal saccades following riMLF inactivation were orthogonal to torsional riMLF stimulation axes.(ABSTRACT TRUNCATED AT 400 WORDS)     

The three-dimensional vestibulo-ocular reflex during prolonged microgravity

Single-case, longitudinal studies of the three-dimensional vestibulo-ocular response (VOR) were conducted with two spaceflight subjects over a 180-day mission. For reference, a control study was performed in the laboratory with 13 healthy volunteers. Horizontal, vertical and torsional VOR was measured during active yaw, pitch and roll oscillations of the head, performed during visual fixation of real and imaginary targets. The control group was tested in the head-upright position, and in the gravity-neutral, onside and supine positions. Binocular eye movements were recorded throughout using videooculography, yielding eye position in Fick co-ordinates. Eye velocity was calculated using quaternion algebra. Head angular velocities were measured by a head-mounted rate sensor. Eye/head velocity gain and phase were evaluated for the horizontal, vertical and torsional VOR. The inclination of Listing's plane was also calculated for each test session. Control group gain for horizontal and vertical VOR was distributed closely around unity during real-target fixation, and reduced by 30-50% during imaginary-target trials. Phase was near zero throughout. During head pitch in the onside position, vertical VOR gain did not change significantly. Analysis of up/down asymmetry indicated that vertical VOR gain for downward head movement was significantly higher than for upward head movement. Average torsional VOR gain with real-target fixation was significantly higher than with imaginary-target fixation. No difference in phase was found. In contrast to vertical VOR gain, torsional VOR gain was significantly lower in the gravity-neutral supine position. Spaceflight subjects showed no notable modification of horizontal or vertical VOR gain or phase during real-target fixation over the course of the mission. However, the up/down asymmetry of vertical VOR gain was inverted in microgravity. Torsional VOR gain was clearly reduced in microgravity, with some recovery in the later phase. After landing, there was a dip in gain during the first 24 h, with subsequent recovery to near baseline over the 13-day period tested. Listing's plane appeared to remain stable throughout the mission. The findings reflect various functions of the otolith responses. The reduced torsional VOR gain in microgravity is attributed to the absence of the gravity-dependent, dynamic stimulation to the otoliths (primarily utricles). On the other hand, the reversal of vertical VOR up/down gain asymmetry in microgravity is attributed to the off-loading of the constant 1-g bias (primarily to the saccules) on Earth. The observed increase in torsional VOR gain from the 1st to the 6th month in microgravity demonstrates the existence of longer-term adaptive processes than have previously been considered. Likely factors are the adaptive reweighting of neck-proprioceptive afferents and/or enhancement of efference copy.     

Interstitial nucleus of cajal encodes three-dimensional head orientations in Fick-like coordinates

Two central, related questions in motor control are 1) how the brain represents movement directions of various effectors like the eyes and head and 2) how it constrains their redundant degrees of freedom. The interstitial nucleus of Cajal (INC) integrates velocity commands from the gaze control system into position signals for three-dimensional eye and head posture. It has been shown that the right INC encodes clockwise (CW)-up and CW-down eye and head components, whereas the left INC encodes counterclockwise (CCW)-up and CCW-down components, similar to the sensitivity directions of the vertical semicircular canals. For the eyes, these canal-like coordinates align with Listing's plane (a behavioral strategy limiting torsion about the gaze axis). By analogy, we predicted that the INC also encodes head orientation in canal-like coordinates, but instead, aligned with the coordinate axes for the Fick strategy (which constrains head torsion). Unilateral stimulation (50 microA, 300 Hz, 200 ms) evoked CW head rotations from the right INC and CCW rotations from the left INC, with variable vertical components. The observed axes of head rotation were consistent with a canal-like coordinate system. Moreover, as predicted, these axes remained fixed in the head, rotating with initial head orientation like the horizontal and torsional axes of a Fick coordinate system. This suggests that the head is ordinarily constrained to zero torsion in Fick coordinates by equally activating CW/CCW populations of neurons in the right/left INC. These data support a simple mechanism for controlling head orientation through the alignment of brain stem neural coordinates with natural behavioral constraints.     

Implications of rotational kinematics for the oculomotor system in three dimensions

1. This paper develops three-dimensional models for the vestibuloocular reflex (VOR) and the internal feedback loop of the saccadic system. The models differ qualitatively from previous, one-dimensional versions, because the commutative algebra used in previous models does not apply to the three-dimensional rotations of the eye. 2. The hypothesis that eye position signals are generated by an eye velocity integrator in the indirect path of the VOR must be rejected because in three dimensions the integral of angular velocity does not specify angular position. Computer simulations using eye velocity integrators show large, cumulative gaze errors and post-VOR drift. We describe a simple velocity to position transformation that works in three dimensions. 3. In the feedback control of saccades, eye position error is not the vector difference between actual and desired eye positions. Subtractive feedback models must continuously adjust the axis of rotation throughout a saccade, and they generate meandering, dysmetric gaze saccades. We describe a multiplicative feedback system that solves these problems and generates fixed-axis saccades that accord with Listing's law. 4. We show that Listing's law requires that most saccades have their axes out of Listing's plane. A corollary is that if three pools of short-lead burst neurons code the eye velocity command during saccades, the three pools are not yoked, but function independently during visually triggered saccades. 5. In our three-dimensional models, we represent eye position using four-component rotational operators called quaternions. This is not the only algebraic system for describing rotations, but it is the one that best fits the needs of the oculomotor system, and it yields much simpler models than do rotation matrix or other representations. 6. Quaternion models predict that eye position is represented on four channels in the oculomotor system: three for the vector components of eye position and one inversely related to gaze eccentricity and torsion. 7. Many testable predictions made by quaternion models also turn up in models based on other mathematics. These predictions are therefore more fundamental than the specific models that generate them. Among these predictions are 1) to compute eye position in the indirect path of the VOR, eye or head velocity signals are multiplied by eye position feedback and then integrated; consequently 2) eye position signals and eye or head velocity signals converge on vestibular neurons, and their interaction is multiplicative.(ABSTRACT TRUNCATED AT 400 WORDS)     

The human vertical vestibulo-ocular reflex during combined linear and angular acceleration with near-target fixation

The purpose of this study was to examine the effect of fixation target distance on the human vestibuloocular reflex (VOR) during eccentric rotation in pitch. Such rotation induces both angular and linear acceleration. Eight normal subjects viewed earth-fixed targets that were either remote or near to the eyes during wholebody rotation about an earth-horizontal axis that was either oculocentric or 15 cm posterior (eccentric) to the eyes. Eye and head movements were recorded using magnetic search coils. Using a servomotor-driven chair, passive whole-body rotations were delivered as trains of single-frequency sinusoids at frequencies from 0.8 to 2.0 Hz and as pseudorandom impulses of acceleration. In the light, the visually enhanced VOR (VVOR) was recorded while subjects were asked to fixate targets at one of several distances. In darkness, subjects were asked to remember targets that had been viewed immediately prior to the rotation. In order to eliminate slip of the retinal image of a near target when the axis of rotation of the head is posterior to the eyes, the ideal gain (compensatory eye velocity divided by head velocity) of the VVOR and VOR must exceed 1.0. Both the VOR and VVOR were found to have significantly enhanced gains during sinusoidal and pseudorandom impulses of rotation (P<0.05). Enhancement of VVOR gain was greatest at low frequencies of head rotation and decreased with increasing frequency. However, enhanced VOR gain only slightly exceeded 1.0, and VVOR gain enhancement was significantly lower than the expected ideal values for the stimulus conditions employed (P<0.05). During oculocentric rotations with near targets, both the VOR and VVOR tended to exhibit small phase leads that increased with rotational frequency. In contrast, during eccentric rotations with near targets, there were small phase lags that increased with frequency. Visual tracking contributes during ocular compensatory responses to sustained head rotation, although the latency of visual tracking reflexes exceeds 100 ms. In order to study initial vestibular responses prior to modification by visual tracking, we presented impulses of head acceleration in pseudorandom sequence of initial positions and directions, and evaluated the ocular response in the epoch from 25 to 80 ms after movement onset. As with sinusoidal rotations, pseudorandom eccentric head rotation in the presence of a near, earth-fixed target was associated with enhancement of VVOR and VOR gains in the interval from 25 to 80 ms from movement onset. Despite the inability of visual tracking to contribute to these responses, VVOR gain significantly exceeded VOR gain for pseudorandom accelerations. This gain enhancement indicates that target distance and linear motion of the head are considered by the human ocular motor system in adjustment of performance of the early VOR, prior to a contribution by visual following reflexes. Vergence was appropriate to target distance during all VVOR rotations, but varied during VOR rotations with remembered targets. For the 3-m target distance, vergence during the VOR was stable over each entire trial but slightly exceeded the ideal value. For the 0.1-m near target, instantaneous vergence during the VOR typically declined gradually in a manner not corresponding to the time course of instantaneous VOR gain change; mean vergence over entire trials ranged from 60 to 90% of ideal, corresponding to target distances for which ideal gain would be much higher than actually observed. These findings suggest a dissociation between vergence and VOR gain during eccentric rotation with near targets in the frequency range from 0.8 to 2.0 Hz.     

Vertical eye position-dependence of the human vestibuloocular reflex during passive and active yaw head rotations.

Vertical eye position-dependence of the human vestibuloocular reflex during passive and active yaw head rotations. The effect of vertical eye-in-head position on the compensatory eye rotation response to passive and active high acceleration yaw head rotations was examined in eight normal human subjects. The stimuli consisted of brief, low amplitude (15-25 degrees ), high acceleration (4,000-6,000 degrees /s2) yaw head rotations with respect to the trunk (peak velocity was 150-350 degrees /s). Eye and head rotations were recorded in three-dimensional space using the magnetic search coil technique. The input-output kinematics of the three-dimensional vestibuloocular reflex (VOR) were assessed by finding the difference between the inverted eye velocity vector and the head velocity vector (both referenced to a head-fixed coordinate system) as a time series. During passive head impulses, the head and eye velocity axes aligned well with each other for the first 47 ms after the onset of the stimulus, regardless of vertical eye-in-head position. After the initial 47-ms period, the degree of alignment of the eye and head velocity axes was modulated by vertical eye-in-head position. When fixation was on a target 20 degrees up, the eye and head velocity axes remained well aligned with each other. However, when fixation was on targets at 0 and 20 degrees down, the eye velocity axis tilted forward relative to the head velocity axis. During active head impulses, the axis tilt became apparent within 5 ms of the onset of the stimulus. When fixation was on a target at 0 degrees, the velocity axes remained well aligned with each other. When fixation was on a target 20 degrees up, the eye velocity axis tilted backward, when fixation was on a target 20 degrees down, the eye velocity axis tilted forward. The findings show that the VOR compensates very well for head motion in the early part of the response to unpredictable high acceleration stimuli-the eye position- dependence of the VOR does not become apparent until 47 ms after the onset of the stimulus. In contrast, the response to active high acceleration stimuli shows eye position-dependence from within 5 ms of the onset of the stimulus. A model using a VOR-Listing's law compromise strategy did not accurately predict the patterns observed in the data, raising questions about how the eye position-dependence of the VOR is generated. We suggest, in view of recent findings, that the phenomenon could arise due to the effects of fibromuscular pulleys on the functional pulling directions of the rectus muscles.     

A three-dimensional analysis of vergence movements at various levels of elevation

Earlier studies have shown that eye positions, recorded in subjects scanning a distant visual scene with the head in a stable position, have only two degrees of freedom (Listing's law). Due to cyclovergence, this law is modified in near-vision. Two previous quantitative studies have documented that the sign of the torsional vergence component depends systematically on elevation: when fixating a nearby target, the eyes show intorsion in up gaze, extorsion in down gaze and no cyclotorsion at some intermediate elevation level (to be denoted as the null elevation). Both studies found a linear cyclovergence/elevation relation, but disagreed on the amount of cyclotorsion. A further uncertainty is how this phenomenon develops dynamically when the binocular fixation point shifts from a far to a near position. Therefore, we have investigated the dynamic coupling between the horizontal and torsional components of vergence in human subjects who were instructed to refixate a light target after it stepped in depth. The target steps were presented at various vertical and horizontal directions relative to the straight-ahead axis of the cyclopean eye. We found that the quantitative relations among horizontal vergence, torsional vergence and elevation were intermediate between those found in the two earlier near-vision studies and that they correspond reasonably to the predictions of a model by Mok and co-workers. The cyclotorsion vergence component had about the same latency and dynamics as the horizontal component. When refixations were studied at different elevations, the torsional vergence component changed from incyclotorsion in up gaze to excyclotorsion in down gaze. In agreement with expectations derived from two quantiative models, the null elevation of cyclovergence was near the binocular primary position. Furthermore, we found no consistent additional dependence on the horizontal direction of the refixation trajectory relative to the midsaggital plane. Other experiments showed that the cyclotorsional changes accompanying convergence were not critically dependent upon the visual conditions. Quantitatively similar cyclotorsional components were found even in convergent refixations executed in full darkness towards the location of a remembered (flashed) near target. We conclude that visual feedback is unlikely to be very important in controlling cyclovergence in these various conditions.     

Dynamics and directionality of the vestibulo-collic reflex (VCR) in mice

The vestibulo-collic reflex (VCR) stabilizes the head in space by excitation of neck muscles that oppose head rotation. Recently, the mouse vestibulo-ocular reflex (VOR) has been characterized so that genetic manipulations of the vestibular system can be examined. We have characterized the dynamics and directionality of the VCR in mice restrained at the neck so that studies of vestibular system genetics may include comparisons to normal VCR in addition to VOR. Head rotations were measured in darkness with a three-dimensional search coil system during whole body rotations. The VCR in four C57BL/6 mice was present in pitch, roll, and yaw directions with an overall average gain of 0.28. Phase was accurately compensatory to oppose head rotation across a wide range of frequencies from 0.02 Hz to 2.0 Hz. Compensatory head rotations were greatest in the direction opposing the applied stimulus and weak or absent in other directions. Constant velocity rotations about horizontal axes elicited head velocity modulation and bias similar to that observed in the VOR. We conclude that the VCR of mice is similar to that in other mammals.     

Vestibular catch-up saccades in labyrinthine deficiency

During rapid head rotations, saccades ipsiversive with compensatory vestibulo-ocular reflex (VOR) slow phases may augment the deficient VOR and assist gaze stabilization in space. The present experiments compared these vestibular catch-up saccades (VCUSs) with visually and memory-guided saccades. To characterize VCUSs and their relationship to deficiency of the initial VOR, we delivered random, whole-body transients of 1000 and 2800 degrees/s2 peak yaw acceleration around four different eccentric vertical axes in eight unilaterally and one bilaterally vestibulopathic subjects, as well as nine age-matched normal subjects. Eye and head movements were sampled at 1200 Hz using magnetic search coils. Subjects fixed targets at either 500 or 15 cm distance immediately before unpredictable onset of rotation in darkness. Under all testing conditions, normal subjects exhibited only compensatory vestibular slow phases and occasional anticompensatory quick phases. This behavior was also typical of unilaterally vestibulopathic subjects rotated contralesionally. When rotated ipsilesionally, however, vestibulopathic subjects had deficient slow-phase VOR gain with prolonged latency, and six of the nine exhibited saccadic movements in the compensatory direction (VCUSs). Higher head accelerations preferentially evoked VCUSs, but there were no preferred combinations of target distances and eccentric rotation axes. Peak velocities and durations of VCUSs increased with saccade amplitude. The latency distribution for VCUSs peaked around 70 ms, substantially shorter than reported for either visually guided express saccades or vestibular memory contingent saccades. The latency of each VCUS was highly correlated with the gaze error prior to that VCUS. The amplitude of VCUSs was calibrated to gaze position error, such that VCUSs reduced gaze error by an average of 37%. Thus when VOR slow-phase responses cannot compensate fully for head rotation, vestibular gaze position error can nevertheless calibrate the programming of VCUSs to augment the deficient VOR, much like catch-up saccades substitute for deficient visual pursuit.     

The human horizontal vestibulo-ocular reflex during combined linear and angular acceleration

 We employed binocular magnetic search coils to study the vestibulo-ocular reflex (VOR) and visually enhanced vestibulo-ocular reflex (VVOR) of 15 human subjects undergoing passive, whole-body rotations about a vertical (yaw) axis delivered as a series of pseudorandom transients and sinusoidal oscillations at frequencies from 0.8 to 2.0 Hz. Rotations were about a series of five axes ranging from 20 cm posterior to the eyes to 10 cm anterior to the eyes. Subjects were asked to regard visible or remembered targets 10 cm, 25 cm, and 600 cm distant from the right eye. During sinusoidal rotations, the gain and phase of the VOR and VVOR were found to be highly dependent on target distance and eccentricity of the rotational axis. For axes midway between or anterior to the eyes, sinusoidal gain decreased progressively with increasing target proximity, while, for axes posterior to the otolith organs, gain increased progressively with target proximity. These effects were large and highly significant. When targets were remote, rotational axis eccentricity nevertheless had a small but significant effect on sinusoidal gain. For sinusoidal rotational axes midway between or anterior to the eyes, a phase lead was present that increased with rotational frequency, while for axes posterior to the otolith organs phase lag increased with rotational frequency. Transient trials were analyzed during the first 25 ms and from 25 to 80 ms after the onset of the head rotation. During the initial 25 ms of transient head rotations, VOR and VVOR gains were not significantly influenced by rotational eccentricity or target distance. Later in the transient responses, 25–80 ms from movement onset, both target distance and eccentricity significantly influenced gain in a manner similar to the behavior during sinusoidal rotation. Vergence angle generally remained near the theoretically ideal value during illuminated test conditions (VVOR), while in darkness vergence often varied modestly from the ideal value. Regression analysis of instantaneous VOR gain as a function of vergence demonstrated only a weak correlation, indicating that instantaneous gain is not likely to be directly dependent on vergence. A model was proposed in which linear acceleration as sensed by the otoliths is scaled by target distance and summed with angular acceleration as sensed by the semicircular canals to control eye movements. The model was fit to the sinusoidal VOR data collected in darkness and was found to describe the major trends observed in the data. The results of the model suggest that a linear interaction exists between the canal and otolithic inputs to the VOR. Received: 1 April 1996 / Accepted: 15 October 1996     

The effect of gravity on the horizontal and vertical vestibulo-ocular reflex in the rat

Horizontal and vertical eye movements were recorded in alert pigmented rats using chronically implanted scleral search coils or temporary glue-on coils to test the dependence of the vestibulo-ocular reflex (VOR) upon rotation axis and body orientation. The contributions of semicircular-canal versus otolith-organ signals to the VOR were investigated by providing canal-only (vertical axis) and canal plus otolith (horizontal axis) stimulation conditions. Rotations that stimulated canals only (upright yaw and nose-up roll) produced an accurate VOR during middle- and high-frequency rotations (0.2-2 Hz). However, at frequencies below 0.2 Hz, the canal-only rotations elicited a phase-advanced VOR. The addition of a changing gravity stimulus, and thus dynamic otolith stimulation, to the canal signal (nose-up yaw, on-side yaw, and upright roll) produced a VOR response with accurate phase down to the lowest frequency tested (0.02 Hz). In order to further test the dependence of the VOR on gravitational signals, we tested vertical VOR with the head in an inverted posture (inverted roll). The VOR in this condition was advanced in phase across all frequencies tested. At low frequencies, the VOR during inverted roll was anticompensatory, characterized by slow-phase eye movement in the same direction as head movement. The substantial differences between canalonly VOR and canal plus otolith VOR suggest an important role of otolith organs in rat VOR. Anticompensatory VOR during inverted roll suggests that part of the otolith contribution arises from static tilt signals that are inverted when the head is inverted.     

Deficits of gaze stability in multiple axes following unilateral vestibular lesions

 Abnormalities in the vestibulo-ocular reflex (VOR) after unilateral vestibular injury may cause symptomatic gaze instability. We compared five subjects who had unilateral vestibular lesions with normal control subjects. Gaze stability and VOR gain were measured in three axes using scleral magnetic search coils, in light and darkness, testing different planes of rotation (yaw and pitch), types of stimulus (sinusoids from 0.8 to 2.4 Hz, and transient accelerations) and methods of rotation (active and passive). Eye velocity during horizontal tests reached saturation during high-velocity/acceleration ipsilesional rotation. Rapid vertical head movements triggered anomalous torsional rotation of the eyes. Gaze instability was present even during active rotation in the light, resulting in oscillopsia. These abnormal VOR responses are a consequence of saturating nonlinearities, which limit the usefulness of frequency-domain analysis of rotational test data in describing these lesions. Received: 22 April 1996 / Accepted: 18 February 1997     

Horizontal ocular vergence and the three-dimensional response to whole-body roll motion

We evaluated the human binocular response to roll motion in the dark and during visual fixation with horizontal convergence. Six normal human subjects were exposed to manually driven, whole-body rotation about an earth-vertical, naso-occipital axis, under two conditions: (I) oscillation at 0.4 Hz (peak velocity 69+/-3.8 degree/s) in the dark, and whilst fixating an axial light-emitting diode at 48 cm ('near') and at 206 cm ('far'); (II) constant velocity rotation (56.5+/-3.1 degree/s) for 40 s, clockwise and counter-clockwise, in the dark, and sudden stops. Eye and head movements were monitored using scleral search coils. In head-fixed, angular velocity coordinates roll motion always evoked conjugate ocular torsion, with small conjugate horizontal and disconjugate vertical components. The resultant binocular eye responses were rotations about convergent axes. During oscillation with target fixation the convergence of the rotation axes was larger than that predicted by target geometry, producing disconjugate oscillations of vertical gaze about the target ('skewing'). Fast-phase eye movements were primarily resetting rotations about the same convergent rotation axes as the slow phases, but the small vertical velocity components had oscillatory, asymmetrical profiles. In response to velocity steps the slow-phase eye velocity decayed exponentially with time constants of 4.5+/-1.5 s for the torsional component and 5.8+/-1.9 s for the 'vertical vergence' component (right eye-left eye recordings). We conclude that in normal human subjects dynamic vertical canal stimulation with horizontal gaze convergence evokes rotation of the eyes about convergent axes and a small skewing of the eyes.     

Effect of viewing distance and location of the axis of head rotation on the monkey's vestibuloocular reflex. I. Eye movement responses.

1. The vestibuloocular reflex (VOR) stabilizes images on the retina against movements of the head in space. Viewing distance, target eccentricity, and location of the axis of rotation may influence VOR responses because rotation of the head about most axes in space rotates and translates the eyes relative to visual targets. To study the VOR response to combined rotation and translation, monkeys were placed on a rate table and rotated briefly in the dark about a vertical axis that was located in front of or behind the eyes. The monkeys fixated a near or far visual target that was extinguished before the rotation. Eye movements were recorded from both eyes by the use of the search coil technique. 2. Peak eye velocity evoked by the VOR was linearly related to vergence angle for any axis of rotation. The percent change in the VOR with near target viewing relative to far target viewing at a vergence angle of 20 degrees was linearly related to the location of the axis of rotation. Axes located behind the eyes produced positive changes in VOR amplitude, and axes located in front of the eyes produced negative changes in VOR amplitude. An axis of rotation located in the coronal plane containing the centers of rotation of the eyes produced no modification of VOR amplitude. For any axis, the VOR compensated for approximately 90% of the translation of the eye relative to near targets. 3. The initial VOR response was not correct in magnitude but was refined by a series of three temporally delayed corrections of increasing complexity. The earliest VOR-evoked eye movement (10-20 ms after rotation onset) was independent of viewing distance and rotational axis location. In the next 100 ms, eye speed appeared to be sequentially modified three times: within 20 ms by viewing distance; within 30 ms by otolith translation; and within 100 ms by eye translation relative to the visual target. 4. These data suggest a formal model of the VOR consisting of four channels. Channel 1 conveys an unmodified head rotation signal with a pure delay of 10 ms. Channel 2 conveys an angular head velocity signal, modified by viewing distance with a pure delay of 20 ms, but invariant with respect to the location of the axis of rotation. Channel 3 conveys a linear head velocity signal, dependent on the location of the axis of rotation, that is modified by viewing distance with a pure delay of 30 ms.(ABSTRACT TRUNCATED AT 400 WORDS)