Vestibulo-ocular Reflex Phase Research Articles

Changes in gain of horizontal vestibulo-ocular reflex during spaceflight.

BACKGROUND:The vestibulo-ocular reflex (VOR) is a basic function of the vestibular system that stabilizes gaze during head movement. Investigations on how spaceflight affects VOR gain and phase are few, and the magnitude of observed changes varies considerably and depends on the protocols used.OBJECTIVE:We investigated whether the gain and phase of the VOR in darkness and the visually assisted VOR were affected during and after spaceflight.METHODS:We measured the VOR gain and phase of 4 astronauts during and after a Space Shuttle spaceflight while the subjects voluntary oscillated their head around the yaw axis at 0.33 Hz or 1 Hz and fixed their gaze on a visual target (VVOR) or imagined this target when vision was occluded (DVOR). Eye position was recorded using electrooculography and angular velocity of the head was recorded with angular rate sensors.RESULTS:The VVOR gain at both oscillation frequencies remained near unity for all trials. DVOR gain was more variable inflight and postflight. Early inflight and immediately after the flight, DVOR gain was lower than before the flight. The phase between head and eye position was not altered by spaceflight.CONCLUSION:The decrease in DVOR gain early in the flight and after the flight reflects adaptive changes in central integration of vestibular and proprioceptive sensory inputs during active head movements.

Relationship between motion sickness susceptibility and vestibulo-ocular reflex gain and phase.

It has been proposed that individual susceptibility to motion sickness is related to the vestibulo-ocular reflex (VOR) through the activation of the velocity storage mechanism. We investigated whether motion sickness level was related to the gain and phase of the VOR. VOR gain and phase were measured in 214 subjects while they rotated in yaw at 0.01 Hz, 0.02 Hz, 0.04 Hz, 0.08 Hz, and 0.16 Hz in darkness, and results were compared to the severity of symptoms the subjects experienced during subsequent tests to provoke motion sickness. These tests included cross-coupled angular accelerations, sudden stops in light or in dark, off-vertical axis rotation, and parabolic flight. The subjects were grouped according to the motion sickness level reached during these tests (none, low, medium, or high). No correlation was found between the horizontal VOR gain and motion sickness level. However, for the subjects with high motion sickness level, the VOR phase lead was significantly lower during rotation at frequencies ranging from 0.04 Hz to 0.16 Hz (i.e. the VOR time constant was longer) than the other motion sickness groups. These results support the theory that the longer the time constant for velocity storage, the more severe the motion sickness.

Visual Target Strategies in Infantile Nystagmus Patients With Horizontal Jerk Waveform.

The aim of this study was to propose a new pathophysiological hypothesis for involuntary eye oscillation in infantile nystagmus (IN): patients with IN exhibit impaired gaze fixation, horizontal smooth pursuit and optokinetic nystagmus (OKN) and use saccadic eye movements for these underlying impairments. In order to induce saccades, they make enough angle between gaze and target by precedent exponential slow eye movements. IN consists of the alternate appearance of the saccade and the slow eye movements. Unlike most previous theories, IN is therefore considered a necessary strategy allowing for better vision and not an obstacle to clear vision. In five patients with IN, eye movements were analyzed during the smooth pursuit test, saccadic eye movement test, OKN test and vestibulo-ocular reflex (VOR) test. Their gaze fixation, horizontal smooth pursuit, OKN and the last half of the slow phase of VOR were impaired. The lines obtained by connection of the end eye positions of fast phase of nystagmus coincided with the trajectories of targets. The findings indicate that patients followed the target by the fast but not the slow phase of nystagmus, which supports our hypothesis. By setting the direction of slow phase of nystagmus opposite to the direction of the OKN stimulation, enough angle can be effectively made between the gaze and target for the induction of saccade. This is the mechanism of reversed OKN response. In darkness and when eyes are closed, IN weakens because there is no visual target and neither the saccade for catching up the target or slow phase for induction of the saccade is needed.

Core Body Temperature Effects on the Mouse Vestibulo-ocular Reflex.

Core body temperature has been shown to affect vestibular end-organ and nerve afferents so that their resting discharge rate and sensitivity increase with temperature. Our aim was to determine whether these changes observed in extracellular nerve recordings of anaesthetized C57BL/6 mice corresponded to changes in the behavioural vestibulo-ocular reflex (VOR) of alert mice. The VOR drives eye rotations to keep images stable on the retina during head movements. We measured the VOR gain (eye velocity/head velocity) and phase (delay between vestibular stimulus and response) during whole-body sinusoidal rotations ranging 0.5-12Hz with peak velocity 50 or 100°/s in nine adult C57BL/6 mice. We also measured the VOR during whole-body transient rotations with acceleration 3000 or 6000°/s2 reaching a plateau of 150 or 300°/s. These measures were obtained while the mouse's core body temperature was held at either 32 or 37°C for at least 35min before recording. The temperature presentation order and timing were pseudo-randomized. We found that a temperature increase from 32 to 37°C caused a significant increase in sinusoidal VOR gain of 17% (P<0.001). Temperature had no other effects on the behavioural VOR. Our data suggest that temperature effects on regularly firing afferents best correspond to the changes that we observed in the VOR gain.

High-Speed Video-Oculography for Measuring Three-Dimensional Rotation Vectors of Eye Movements in Mice.

BackgroundThe mouse is the most commonly used animal model in biomedical research because of recent advances in molecular genetic techniques. Studies related to eye movement in mice are common in fields such as ophthalmology relating to vision, neuro-otology relating to the vestibulo-ocular reflex (VOR), neurology relating to the cerebellum’s role in movement, and psychology relating to attention. Recording eye movements in mice, however, is technically difficult.MethodsWe developed a new algorithm for analyzing the three-dimensional (3D) rotation vector of eye movement in mice using high-speed video-oculography (VOG). The algorithm made it possible to analyze the gain and phase of VOR using the eye’s angular velocity around the axis of eye rotation.ResultsWhen mice were rotated at 0.5 Hz and 2.5 Hz around the earth’s vertical axis with their heads in a 30° nose-down position, the vertical components of their left eye movements were in phase with the horizontal components. The VOR gain was 0.42 at 0.5 Hz and 0.74 at 2.5 Hz, and the phase lead of the eye movement against the turntable was 16.1° at 0.5 Hz and 4.88° at 2.5 Hz.ConclusionsTo the best of our knowledge, this is the first report of this algorithm being used to calculate a 3D rotation vector of eye movement in mice using high-speed VOG. We developed a technique for analyzing the 3D rotation vector of eye movements in mice with a high-speed infrared CCD camera. We concluded that the technique is suitable for analyzing eye movements in mice. We also include a C++ source code that can calculate the 3D rotation vectors of the eye position from two-dimensional coordinates of the pupil and the iris freckle in the image to this article.

Rotational chair testing in patients with unilateral peripheral vestibular disorders

Abstract The aim of the study was to evaluate the rotational chair (RC) sinusoidal harmonic acceleration (SHA) test and the rotational velocity step (RVS) test in patients with unilateral peripheral vestibular disorders. This study was retrospective in nature. It was conducted in a clinical tertiary care vestibular function test center. A total of 119 patients (63 men and 56 women) with documented unilateral peripheral vestibular lesions were evaluated with bithermal binaural caloric and sinusoidal and step velocity RC tests. Clinical, caloric, and RC tests were carried out. The study group was selected by including patients with a clinical diagnosis suggestive of peripheral vestibular lesions and with documented unilateral caloric weakness matching the clinical diagnosis, and by excluding patients with a clinical diagnosis suggestive of a peripheral vestibular lesion but not documented by unilateral caloric weakness, as well as patients with incomplete tests or uninterpretable data (due to poor recordings or eye movement artifacts). Caloric testing was performed using an infrared video-oculographic system and a Brookler-Grams closed-loop irrigation unit with standard bithermal irrigations of 30 and 44°C for 45 s each in the following order: L30°C, R30°C, R44°C, and L44°C. The RC testing paradigms used in this study were the rotational SHA test and the RVS test. When patients were classified on the basis of etiology, the most common cause of dizziness in the study group was found to be Mιniθre’s disease (34.9%), followed by vestibular neuritis (31.1%). Seventy-two patients in the study group demonstrated right caloric weakness and 47 patients demonstrated left caloric weakness, whereas only 18 of 119 patients demonstrated directional preponderance. When the RC SHA test parameters (gain, phase, and symmetry) in the study group were compared with the manufacturer’s normal values, statistically significant difference was seen in vestibulo-ocular reflex (VOR) gain at low frequencies (0.01-0.08 Hz), in VOR phase at all frequencies, and in VOR symmetry at low frequencies (0.01-0.04 Hz). In summary, despite the encouraging results of the discriminating power of caloric testing, it should be emphasized that RC testing has its own unique capabilities, such as the following: (i) it is a physiologic stimulus whose frequency and amplitude can be varied precisely; (ii) the stimulus is unrelated to physical features of the external ear or temporal bone; (iii) it is useful in children who may not tolerate caloric testing; and (iv) it is very useful in assessing patients receiving vestibulotoxic drugs. Multiple stimuli of varying intensities can be applied to the vestibular system within a relatively short period of time.

Velocity-selective adaptation of the horizontal and cross-axis vestibulo-ocular reflex in the mouse.

One commonly observed phenomenon of vestibulo-ocular reflex (VOR) adaptation is a frequency-selective change in gain (eye velocity/head velocity) and phase (relative timing between the vestibular stimulus and response) based on the frequency content of the adaptation training stimulus. The neural mechanism behind this type of adaptation is not clear. Our aim was to determine whether there were other parameter-selective effects on VOR adaptation, specifically velocity-selective and acceleration-selective changes in the horizontal VOR gain and phase. We also wanted to determine whether parameter selectivity was also in place for cross-axis adaptation training (a visual-vestibular training stimulus that elicits a vestibular-evoked torsional eye movement during horizontal head rotations). We measured VOR gain and phase in 17 C57BL/6 mice during baseline (no adaptation training) and after gain-increase, gain-decrease and cross-axis adaptation training using a sinusoidal visual-vestibular (mismatch) stimulus with whole-body rotations (vestibular stimulus) with peak velocity 20 and 50°/s both with a fixed frequency of 0.5Hz. Our results show pronounced velocity selectivity of VOR adaptation. The difference in horizontal VOR gain after gain-increase versus gain-decrease adaptation was maximal when the sinusoidal testing stimulus matched the adaptation training stimulus peak velocity. We also observed similar velocity selectivity after cross-axis adaptation training. Our data suggest that frequency selectivity could be a manifestation of both velocity and acceleration selectivity because when one of these is absent, e.g. acceleration selectivity in the mouse, frequency selectivity is also reduced.

Computer-aided vestibular autorotational testing of the vestibulo-ocular reflex in senile vestibular dysfunction

Background and objective Studies have already investigated vestibulo-ocular reflex (VOR) responses in elderly subjects, mostly at low frequencies (<1 Hz) during passive head turns, or continuous active head turns in a rotational chair. However, natural head movements usually occur at frequencies above 1 Hz and at varying rates, rather than at continuously increasing rates as tested in most studies to date. The aim of this study was to compare VOR responses within or between normal and bilateral peripheral vestibular hypofunction (BPVH) elderly subjects with a computer base program incorporating random active high-frequency head movements. Subjects Seventeen senior patients with bilateral peripheral vestibular hypofunction and 13 age-matched paid healthy subjects participated in this study. Design All the subjects performed 8 s of active, side-to-side head motions at 1 Hz, 2 Hz and 3 Hz in response to four experimental conditions: (A) a stationary visual target; (B) a stationary visual target and a moving target with a horizontal trajectory; (C) a stationary visual target and a moving target with a spiral trajectory; and (D) a stationary visual target with combined horizontal- and vertical-spiral moving targets. Results Repeated-measures ANOVA showed that across the different frequencies of headshaking, a significant increase took place in the phase lag of the BPVH subjects ( p < 0.001) compared with the normal controls. Post hoc analysis showed significant within-group differences in BPVH subjects (1 Hz vs 2 Hz, 2 Hz vs 3 Hz) and normal controls (1 Hz vs 2 Hz, 1 Hz vs 3 Hz). A significant VOR gain took place among the BPVH subjects at 3 Hz VAT ( p < 0.001) as compared with 1 Hz VAT and no significant differences in VOR gain could be detected among the controls at either of these frequencies. Repeated-measures ANOVA revealed that under our test conditions, significant main effect was noted for VOR asymmetry ( F = 4.45, p < 0.05). Post hoc analysis showed significant within-group differences in the BPVH subjects (test A vs test B, test A vs test C, and test A vs test D). Conclusions Our results showed that the VAT paradigm can be improved by using concurrent horizontal and vertical moving targets. The VOR phase may be useful for differentiating VAT responses between BPVH and healthy elderly subjects. Moreover, the results of this study demonstrate that gains in VOR at different frequencies of headshaking and asymmetry during different test conditions can be useful parameters for within-group assessment.

Vestibuloocular Reflex Adaptation Investigated With Chronic Motion-Modulated Electrical Stimulation of Semicircular Canal Afferents

To investigate vestibuloocular reflex (VOR) adaptation produced by changes in peripheral vestibular afference, we developed and tested a vestibular "prosthesis" that senses yaw-axis angular head velocity and uses this information to modulate the rate of electrical pulses applied to the lateral canal ampullary nerve. The ability of the brain to adapt the different components of the VOR (gain, phase, axis, and symmetry) during chronic prosthetic electrical stimulation was studied in two squirrel monkeys. After characterizing the normal yaw-axis VOR, electrodes were implanted in both lateral canals and the canals were plugged. The VOR in the canal-plugged/instrumented state was measured and then unilateral stimulation was applied by the prosthesis. The VOR was repeatedly measured over several months while the prosthetic stimulation was cycled between off, low-sensitivity, and high-sensitivity stimulation states. The VOR response initially demonstrated a low gain, abnormal rotational axis, and substantial asymmetry. During chronic stimulation the gain increased, the rotational axis improved, and the VOR became more symmetric. Gain changes were augmented by cycling the stimulation between the off and both low- and high-sensitivity states every few weeks. The VOR time constant remained low throughout the period of chronic stimulation. These results demonstrate that the brain can adaptively modify the gain, axis, and symmetry of the VOR when provided with chronic motion-modulated electrical stimulation by a canal prosthesis.

Retention of habituation of vestibulo-ocular reflex and sensation of rotation in humans

In humans, habituation of vestibulo-ocular reflex (VOR) by repeated caloric or rotational stimulation has been well documented. However, less attention has been directed to the effect of habituation on the sensation of self-rotation and little is known about the retention duration of vestibular habituation. To investigate these characteristics, subjects were exposed to ten sessions of angular velocity steps in yaw, with a chair rotating either alternatively in both CW and CCW directions (bidirectional protocol) or always in the same direction (unidirectional protocol), i.e., CW or CCW. The retention of habituation of VOR and sensation of rotation induced by both protocols was studied for a period up to 8 months following the end of the habituation protocols. There was a progressive decline in the VOR peak slow phase velocity and time constant throughout the sessions during both protocols. These parameters then followed an exponential recovery with a time constant of about 1 month. The duration of the sensation of rotation also habituated during repeated angular velocity steps, but it was shorter for both directions of stimulation, including after the unidirectional protocol. Sinusoidal VOR gain was not affected by vestibular habituation to velocity steps, but sinusoidal VOR phase showed an increase in phase lead at 0.02 and 0.04 Hz, which also returned to baseline values within about 1 month. We conclude that vestibular habituation is a long-lasting phenomenon. These results may be helpful for designing and scheduling the protocols for drug studies using crossover design, rehabilitation of balance disorder patients, and for the application of intermittent artificial gravity during space missions.

System identification of the human vestibulo-ocular reflex during head-free tracking

A method was developed to identify the linear, system level dynamics of the horizontal, angular vestibulo-ocular reflex (VOR) as it stabilized vision during head-free tracking of a visual target. Small amplitude, broad spectrum, stochastic torque perturbations were applied to the head while the subject tracked an unpredictable, moving target with active head and eye motions. Stochastic system identification techniques were used to design the torque and target inputs and to conduct the analysis such that the linear dynamics of the VOR, independently of the visual system's influence on eye motions, were determined. The linear analysis was limited to evaluating VOR dynamics from approximately 0.5 to 4.5 Hz. Nonlinearities in the head-neck system affected the low frequency response of the head to the torque perturbations, and the eye velocity sequence was affected by nonlinearities and degraded by noise at high frequencies. The VOR's gain was near 1.0 between about 0.5 and 2.5 Hz, and then decreased steadily to 0.85 as the frequency increased towards 4.0 Hz. The VOR phase angle was also frequency dependent and corresponded to VOR eye motions lagging the head's disturbance motion by less than 10 ms at frequencies greater than 1.0 Hz.

Evaluation of betahistine for the prevention of seasickness: Effect on vestibular function, psychomotor performance and efficacy at sea

Betahistine was evaluated for the prevention of seasickness in a laboratory and sea study. The effect of 48 mg betahistine on the vestibulo-ocular reflex (VOR) and on psychomotor performance was evaluated in twelve young healthy subjects in a double-blind, placebo controlled, randomized, crossover design. The vestibulo-ocular reflex was evaluated by the Sinusoidal Harmonic Acceleration (SHA) test at frequencies of 0.01, 0.02, 0.04, 0.08 and 0.16 Hz. Psychomotor performance was assessed by both computerized and paper and pencil test batteries. No significant differences in VOR gain or phase were found between betahistine and placebo treatment for any of the frequencies tested. No significant differences were found between treatments for any of the psychomotor performance tests or other possible side effects. The effect of 48 mg betahistine on seasickness severity was evaluated in 83 subjects during a voyage in rough seas. Betahistine had a borderline non-statistically significant effect on the prevention of seasickness in comparison with placebo (p = 0.053), with no notable side effects. Although our results are insufficient to recommend betahistine as an anti-seasickness drug, further studies are required to determine its possible effectiveness in less provocative motion sickness situations.

Flexibility of vestibulo-ocular reflex adaptation to modified visual input in human

The vestibulo-ocular reflex (VOR) serves to keep images relatively stable on the retina. To maintain appropriate performance and minimize image slip throughout life, VOR is subjected to long-term adaptive regulation by visual input. It has been reported that adaptive changes in VOR gain (eye velocity/head velocity) are evoked either by fitting subjects with magnifying, miniaturizing, or reversing spectacles during normal behavior, or by moving a large visual field in or out of phase relative to the subject's head movement. The changes in VOR gain are frequency selective. Here, we examine the extent of VOR gain flexibility by causing VORs of similar direction to undergo different behavioral gain changes. Nine healthy adults participated in the study, ranging in age from 24 to 38 years (mean: 26 years) and with no history of neurotological symptoms. All subjects were clinically normal according to a screening battery that included combined neurologic and otologic physical examinations. Horizontal and vertical eye positions were recorded by bitemporal DC-coupled electro-oculography (EOG). The subject sat in a rotating chair. The axis of rotation of the body was always earth-vertical, with the interaural axis crossing the axis of rotation of the chair. The head was pointed 20° downwards in all experiments and stabilized in this position using a chin rest. The chair was surrounded by a half-cylindrical optokinetic screen (78 cm in diameter) placed in front of the subject, onto which random dot patterns were projected. Goggles were used to ensure that the subject was in complete darkness during both pre- and postadaptation periods. The chair was rotated sinusoidally at maximum amplitude of 30° or 60°: for 30° the stimulation was at 0.1, 0.2, 0.3, and 0.4 Hz; for 60° it was at 0.1, 0.2, and 0.3 Hz. VOR adaptation was obtained by inducing a retinal slip velocity by short-term alteration of the visual input of the large field; this change was produced by a combination of sinusoidal head rotation and the random dot patterns. In each adaptation session, the sinusoidal head rotation was either at 0.1 or 0.3 Hz and the amplitude was 30°. The random dot pattern was synchronized with sinusoidal head rotation in the same direction (x0 experiment) to make the retinal slip zero, and in the opposite direction to make the retinal slip twofold (x2 experiment). Therefore, a total of four adaptation protocols were tested. The subjects were asked to fixate on a single dot with the eyes straight-ahead in the x0 experiment, and follow it within random dot patterns in the x2 experiment. Each adaptation session lasted for 30 min. Two adaptation experiments were performed on each subject once per day. The averages of VOR gain and phase lag were calculated using Fourier analysis. Seven of the subjects who participated in the x2 adaptation experiment at 0.3 Hz and 30° amplitude showed a steady increase of VOR gain within a couple of trials. One of the remaining two subjects showed a decrease in VOR gain in all the three trials, and the other subject showed a VOR gain increase in three trials and decrease in two trials. In the x2 adaptation experiment at 0.3 Hz and 30° amplitude (peak velocity: 28°/s), the percentage gain change ((post−pre)/pre) was 133% at the same stimulation and 100% at 0.4 Hz (peak velocity: 37°/s). The gain change was 65% at 0.1 Hz and 60° amplitude (peak velocity: 18°/s), and 64% at 0.2 Hz and 60° amplitude (peak velocity: 37°/s). In the x1 adaptation experiment (30° at 0.3 Hz), the percentage gain change was −62% under the same conditions, −50% at 0.1 Hz and 60° amplitude, and −30% at 0.2 Hz and 60° amplitude. No change of VOR gain was observed at other frequencies, and the subject was not adapted at 0.1 Hz and 30° amplitude. The larger VOR gain increase in the x2 adaptation experiment for the faster head angular acceleration leads to the conclusion that the VOR gain mechanism can set very different gain states for the VOR that are quite similar in terms of the head acceleration.

空間識・シリーズ教育講座 ５． 半規管の座標学

To study the sense of spatial orientation, understanding the coordinate system of the labyrinth is indispensable. The 100-year-old stereoscopic photograph of the labyrinth shows the three semicircular canals arranged as if a three-coordinate axis. Behavioral observation of canal nerve stimulation 40 years ago disclosed that electrical stimulation of the canal nerve moved the eyes along the canal when the head was fixed. When the head was free to move, it moved the head in the same direction, and it moved the animal in space when the animal was free to move.Stereo-measurements of the labyrinth determined that the semicircular canals are not orthogonal to each other, and the synergistic pairs of canals in the right and left ears are not on one plane. The semicircular canal nerves sent information regarding head rotation velocity on the non-orthogonal canal coordinate axis. A three-dimension analysis of the vestibulo-ocular reflex (VOR) before and after canal plugging enabled precise measurements of semicircular canal contribution to VOR. The summed gain and phases of plugged VOR were comparable to the VOR of normal; LC (four vertical canals plugged) +VC (bilateral lateral canals plugged) =Normal, and RALP+LARP (sum of one pair of vertical canals intact) =VC, however, rotation in light did not change after plugging. These findings indicate that a semicircular canal coordinate system is firm and does not adapt after inactivation, although, sufficiently compensated by vision while moving in light.

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

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

Short-term vestibular responses to repeated rotations

To investigate the short-term vestibular habituation, we performed the 4 successive velocity step tests on 28 volunteers, the peak velocity of which was 100 deg/sec with acceleration and deceleration of 100 deg/sec2. As the repeated rotations might alter the vestibulo-ocular reflex (VOR), sinusoidal rotations at a frequency of 0.16 Hz were also given before and after the 4 successive velocity step tests to investigate the changes of gain and phase of VOR. The 28 volunteers were divided into two groups, group I and II, according to their responses to repeated rotations. In group I (25 subjects, mean age 23.7 year), the mean values of the slow cumulative eye position (SCEP), the time integral of eye velocity during nystagmus, was reduced after each trial of the 4-successive velocity step tests as follows; 403.4 +/- 29 degree (1st trial), 346.2 +/- 37 degree (2nd trial), 278.3 +/- 33 degree (3rd trial) and 256.6 +/- 36 degree (4th trial). The time constant of the nystagmus was also reduced as follows; 12.9 +/- 0.78 second (1st trial), 12 +/- 0.63 second (2nd trial), 9.7 +/- 0.78 second (3rd trial) and 9.9 +/- 0.54 second (4th trial). In group II (3 subjects, mean age 28.3 year), the mean values of SCEP gradually increased; 774.3 +/- 135 degree (1st trial), 1127 +/- 178 degree (2nd trial), 1096.3 +/- 123.4 degree (3rd trial) and 1225.7 +/- 199.7 degree (4th trial). The time constant of the nystagmus increased; 15.7 +/- 2.7 second (1st trial), 22 +/- 4.5 second (2nd trial), 22.3 +/- 3.3 second (3rd trial) and 23.3 +/- 5.7 second (4th trial). The gain of vestibulo-ocular reflex (VOR) induced by sinusoidal rotations at a frequency 0.16 Hz increased in both groups: 0.59 +/- 0.03 to 0.78 +/- 0.06 (group I) and 0.65 +/- 0.07 to 1.15 +/- 0.06 (group II). Phase changes were also observed. In group I, the phase was shifted from 0.6 +/- 0.6 degree to -0.40 +/- 0.6 degree. In group II, the phase was shifted from 3.67 +/- 1.86 degree to -0.33 +/- 0.33 degree. The repeated rotation did not induce a common nystagmic response in all subjects. Thus, person to person variations should be considered in short term vestibular habituation.

Flexibility in the adaptation of the vestibulo-ocular reflex to modified visual inputs in humans

The vestibulo-ocular reflex (VOR) serves to stabilize images on the retina. To maintain appropriate performance and minimize image slippage throughout life, the VOR is subject to long-term adaptive regulation in response to visual input. Adaptive changes in VOR gain (eye velocity/head velocity) can be evoked either by fitting subjects with magnifying, miniaturizing, or reversing spectacles during normal behavior or by moving a large visual field in or out of phase relative to the subject's head movement. These changes exhibit frequency-selectivity. Here, we examine the flexibility of VOR gains by causing VOR in similar directions to undergo different behavioral gain changes. Nine healthy adults, ranging in age from 24 to 38 (mean 28.5) with no history of neurotological symptoms participated in the study. All subjects demonstrated clinically normal functioning on a screening battery of tests that included combined neurologic and otologic physical examinations. Horizontal and vertical eye positions were recorded by bitemporal DC coupled electrooculography (EOG). The subject sat in a rotating chair. The axis of rotation of the body was always earth-vertical, the interaural axis crossing the axis of rotation of the chair. The head was positioned at 20 degrees down in all experiments and was stabilized in this position using a chin rest. The chair was 78 cm in diameter and was shielded by a half-cylindrical optokinetic screen positioned in front of the subjects. Random dot patterns were projected onto this screen. During per- and post-adaptation periods, goggles were fitted to ensure that the subject was in complete darkness and the chair was rotated sinusoidally. The amplitude of the rotating chair was 30 degrees and 60 degrees. Frequencies of rotation were 0.1 Hz, 0.2 Hz, 0.3 Hz and 0.4 Hz for amplitudes of 30 degrees and 0.1 Hz, 0.2 Hz, and 0.3 Hz for amplitudes of 60 degrees. To induce VOR adaptation, the retinal slippage velocity caused by the visual input of a large field was changed for short-term; the change was produced by a combination of sinusoidal head rotation and random dot patterns. During each adaptation session, the frequencies of sinusoidal head rotation were either 0.1 Hz or 0.3 Hz and the amplitude was 30 degrees. The random dot patterns were synchronized with the sinusoidal head rotation in the same direction to make the retinal slippage zero (x0 experiment) and in the opposite direction to double the retinal slippage (x2 experiment). Therefore, a total of four adaptation protocols were tested. The subjects were asked to fix their eyes on a single dot by looking straight ahead in the x0 experiment and to follow the dot in the random dot pattern in the x2 experiment. Each adaptation session lasted for 30 minutes. Each subject participated in couple of adaptation experiments everyday. The average VOR gain and phase lag were calculated using a Fourier transformation. Out of all the subjects who participated in the x2 adaptation experiment at 0.3 Hz with an amplitude of 30 degrees, seven subjects showed a steady increase in VOR gain during a couple of the trials. One out of the remaining two subjects showed a decrease in VOR gain in all three trials. Another subject showed an increase in VOR gain during three trials and a decrease in two trials. In the x2 adaptation experiment with a range of 30 degrees at 0.3 Hz (peak velocity: 28 degrees/s), the percent change in gain (post-pre/pre) was 133% at the same stimulation and 100% at 0.4 Hz (peak velocity: 37 degrees/s). The percent change in gain was 65% for amplitudes of 60 degrees at 0.1 Hz (peak velocity: 18 degrees/s) and 64% for amplitudes 60 degrees at 0.2 Hz (peak velocity: 37 degrees/s). In the x1 adaptation experiment (30 degrees at 0.3 Hz), the percent change in gain was -62% for the same conditions and -50% for amplitude of 60 degrees at 0.1 Hz and -30% for amplitudes of 60 degrees at 0.2 Hz. No change, in VOR gain was observed at the other frequencies. The

Eye movement deficits following ibotenic acid lesions of the nucleus prepositus hypoglossi in monkeys II. Pursuit, vestibular, and optokinetic responses.

The eyes are moved by a combination of neural commands that code eye velocity and eye position. The eye position signal is supposed to be derived from velocity-coded command signals by mathematical integration via a single oculomotor neural integrator. For horizontal eye movements, the neural integrator is thought to reside in the rostral nucleus prepositus hypoglossi (nph) and project directly to the abducens nuclei. In a previous study, permanent, serial ibotenic acid lesions of the nph in three rhesus macaques compromised the neural integrator for fixation but saccades were not affected. In the present study, to determine further whether the nph is the neural substrate for a single oculomotor neural integrator, the effects of those lesions on smooth pursuit, the vestibulo-ocular reflex (VOR), vestibular nystagmus (VN), and optokinetic nystagmus (OKN) are documented. The lesions were correlated with long-lasting deficits in eye movements, indicated most clearly by the animals' inability to maintain steady gaze in the dark. However, smooth pursuit and sinusoidal VOR in the dark, like the saccades in the previous study, were affected minimally. The gain of horizontal smooth pursuit (eye movement/target movement) decreased slightly (<25%) and phase lead increased slightly for all frequencies (0.3-1.0 Hz, +/-10 degrees target tracking), most noticeably for higher frequencies (0.8-0.7 and approximately 20 degrees for 1.0-Hz tracking). Vertical smooth pursuit was not affected significantly. Surprisingly, horizontal sinusoidal VOR gain and phase also were not affected significantly. Lesions had complex effects on both VN and OKN. The plateau of per- and postrotatory VN was shortened substantially ( approximately 50%), whereas the initial response and the time constant of decay decreased slightly. The initial OKN response also decreased slightly, and the charging phase was prolonged transiently then recovered to below normal levels like the VN time constant. Maximum steady-state, slow eye velocity of OKN decreased progressively by approximately 30% over the course of the lesions. These results support the previous conclusion that the oculomotor neural integrator is not a single neural entity and that the mathematical integrative function for different oculomotor subsystems is most likely distributed among a number of nuclei. They also show that the nph apparently is not involved in integrating smooth pursuit signals and that lesions of the nph can fractionate the VOR and nystagmic responses to adequate stimuli.

Rotation Vector Analysis of Eye Movement in Three Dimensions with an Infrared CCD Camera

We have developed a new technique for analyzing the rotation vector of eye movement in three dimensions with an infrared CCD camera based on the following four assumptions: i) the eye rotates on a point; ii) the pupil edge is a circle; iii) the distance from the center of eye rotation to pupil circle remains unchanged despite the rotation; iv) the image of the eye by the CCD camera is projected onto a plane which is perpendicular to the camera axis. After taking digital images of voluntary circular eye movements, we first constructed a three-dimensional frame of reference fixed on the orbita of the subject wearing a goggle equipped with an infrared CCD camera, and determined the space coordinates of the center of eye rotation, the center of the pupil, and an iris freckle. We then took digital images of the eye movements during a saccade or vestibulo-ocular reflex (VOR) and analyzed the axis and angle of the eye movements by the trajectories of the center of the pupil and the iris freckle. Finally, Listing's plane of saccade and the gain and the phase of VOR were obtained. The suitability of this technique is examined.

Comparison of Manual Whole-Body and Passive and Active Head-On-Body Rotational Testing with Conventional Rotary Chair Testing

New methods of rotational testing of the vestibulo-ocular reflex (VOR) using manually generated or patient-generated sinusoidal head movements have recently been advocated for clinical use in circumstances where conventional rotary chair testing methods are not feasible. However, studies seeking to provide evidence for the validity of these methods by comparing their results with an accepted "gold-standard" have been conspicuously absent in the literature. In this study, we compared results for VOR gain, phase, and asymmetry obtained using whole-body and head-on-body rotational stimuli with those obtained by conventional rotary chair testing in 35 subjects with either unilateral or bilateral vestibular deficits over the range of frequencies from 0.025 Hz to 1 Hz. Our results provide evidence for the validity of manual whole-body and active and passive head-on-body rotational testing methods by demonstrating excellent agreement between each of these and conventional rotational chair testing for VOR gain, phase, and asymmetry within the frequency range studied. Small differences at specific-paradigm datapoints are likely secondary to subtle limitations of our experimental design. With further refinement, we expect the new methods will be useful adjuncts for evaluating patients with vestibular complaints in selected clinical situations.