The dynamic characteristics of the mouse horizontal vestibulo-ocular and optokinetic response

In the present study the optokinetic reflex, vestibulo-ocular reflex and their interaction were investigated in the mouse, using a modified subconjunctival search coil technique. Gain of the ocular response to sinusoidal optokinetic stimulation was relatively constant for peak velocities lower than 8°/s, ranging from 0.7 to 0.8. Gain decreased proportionally to velocity for faster stimuli. The vestibulo-ocular reflex acted to produce a sinusoidal compensatory eye movement in response to sinusoidal stimuli. The phase of the eye movement with respect to head movement advanced as stimulus frequency decreased, the familiar signature of the torsion pendulum behavior of the semicircular canals. The first-order time constant of the vestibulo-ocular reflex, as measured from the eye velocity decay after a vestibular velocity step, was 660 ms. The response of the vestibulo-ocular reflex changed with stimulus amplitude, having a higher gain and smaller phase lead when stimulus amplitude was increased. As a result of this nonlinear behavior, reflex gain correlated strongly with stimulus acceleration over the 0.1–1.6 Hz frequency range. When whole body rotation was performed in the light the optokinetic and vestibular system combined to generate nearly constant response gain (approximately 0.8) and phase (approximately 0°) over the tested frequency range of 0.1–1.6 Hz. We conclude that the compensatory eye movements of the mouse are similar to those found in other afoveate mammals, but there are also significant differences, namely shorter apparent time constants of the angular VOR and stronger nonlinearities.     

Vestibuloocular reflex, optokinetic response, and their interactions in the alert cat

Ocular movements of alert cats were recorded by classical electronystagmography techniques during (a) vestibular stimulation (sinusoidal rotation of the cat in complete darkness), (b) optokinetic stimulation (sinusoidal rotation of the visual surroundings around the stationary cat), (c) additive visual-vestibular stimulation (sinusoidal rotation of the cat inside the stationary lighted surroundings), and (d) conflicting visual-vestibular stimulation (sinusoidal rotation of the cat together with the visual surroundings in phase and at the same speed). The stimulus amplitudes and frequencies ranged from 3 to 20 degrees and from 0.025 to 1 Hz, respectively. When tested in darkness, the vestibuloocular reflex (VOR) gain was about 0.9 at 1 Hz. At lower frequencies, this gain was a bit lower and a phase lead was observed. The VOR system was nearly linear. The optokinetic response (OKR) gain was about 1 at lower frequencies but strongly decreased at higher frequencies. A phase lag paralleled that decrease in gain. Furthermore, the smaller the amplitude of the visual stimulus, the better the effectiveness of OKR stabilization. When working in the light, the VOR was in phase with the stimulus and its gain was nearly 1, whatever the frequency and the amplitude. The VOR inhibition was more effective at lower frequencies. In these conditions the system was markedly amplitude-dependent for both gain and phase.     

The effect of lesions of the dorsal cap of the inferior olive on the vestibulo-ocular and optikinetic systems of the cat

The gain (eye velocity/head velocity) of the vestibulo-ocular reflex (VOR) of cats was measured in the dark and light for sinusoidal head oscillations at 0.05 and 1.2 Hz with peak velocity of about 30 deg/sec. Animals wore visual reversing prisms chronically and were also subjected to forced oscillation in the light at 0.05 Hz for 2 h per day. Such experience produced adaptive reduction in VOR gain in the dark from 0.85 to 0.10 within about 4 days; qualitatively similar effects were observed at 1.2 Hz. In 4 cats, the dorsal cap of the inferior olive was located electrophysiologically by its responses to visual motion, and bilateral electrolytic lesions were made in or near this structure. The location of lesions was subsequently identified by histology. After lesions, 3 cats were unable to make adaptive changes in VOR gain when confronted with the same reversing prism paradigm; the fourth exhibited appreciable retardation of adaptation. These results imply that the dorsal cap is essential for plastic adaptation of the VOR. However, all cats retained the ability to use reversed vision to reduce VOR gain in the light after lesions.Optokinetic nystagmus (OKN) and optokinetic after nystagmus (OKAN) were measured in a striped optokinetic drum, before and after dorsal cap lesions, at drum velocities of 20 and 40 deg/sec. Lesions of the dorsal cap in 4 cats did not impair either OKN or OKAN. This result indicates that the climbing fiber system reaching the flocculus from the inferior olive is not essential for such optokinetic movements.     

Changes in gain of the vestibulo-ocular reflex induced by sinusoidal visual stimulation in goldfish

The effects of sustained sinusoidal visual stimulation on the vestibulo-ocular reflex (VOR) and the optokinetic reflex (OKR) were investigated. Goldfish were held stationary inside a striped drum rotating sinusoidally about the vertical axis for 3 h. The VOR gain, the ratio of eye to head rotational velocities, was measured in the dark with passive sinusoidal rotation of the fish and showed modest increases that were greatest at the stimulation frequency. Furthermore, the fish generated spontaneous sinusoidal eye movements at approximately the stimulation frequency, and these movements summated with the response to other frequencies of vestibular stimulation in the dark. It is hypothesized that the pathways of OK and VO stimuli converge and that the animal increases gain in a common part when it attempts to stabilize the visual image by increasing its response to the OK signal. Thus increases in gain of both OKR and VOR are produced.     

The vestibulo ocular reflex (VOR) in otoconia deficient head tilt (het) mutant mice versus wild type C57BL/6 mice

The horizontal and vertical vestibulo ocular reflex (VOR) of head tilted (het) mutant mice was compared to C57BL/6 controls. Eye movements were recorded in darkness using a temporarily attached search coil. Contributions of semicircular canal versus otolith organ signals were investigated by providing a canal only (vertical axis) or canal plus otolith organ (horizontal axis) stimulus. In controls, rotations that stimulated only the canals (upright yaw and on tail roll) produced accurate VOR timing during middle frequency rotations at 0.5 Hz (gain 0.27, phase error 6 degrees), and a phase advanced VOR during low frequency rotations at 0.05 Hz (0.05, 115 degrees). In het mutant mice, these rotations produced a highly attenuated VOR response and phase errors at both 0.5 Hz (0.11, 42 degrees) and 0.05 Hz (0.01, 36 degrees). In controls, rotations that stimulated both the otolith organs and semicircular canals (upright roll and on tail yaw) produced higher VOR gains overall than were elicited during vertical axis rotations, with phase accurate VOR at both 0.5 Hz (0.52, 4 degrees) and 0.05 Hz (0.34, 9 degrees). In het mutant mice, these rotations produced a highly attenuated VOR response and phase errors at both 0.5 Hz (0.14, 51 degrees) and 0.05 Hz (0.01, 43 degrees). During constant velocity rotations about an earth horizontal axis, eye velocity bias and modulation were virtually absent in het mutant mice, while robust in controls. Control mice produced compensatory ocular deviations in response to static head tilt, but responses in het mice were weak and inconsistent. These results show that het mice not only lack all aspects of otolith mediated VOR, but also are deficient in canal mediated VOR. Because semicircular canals are normal in het mice, we conclude that central neurons of the canal VOR are dependent on otolith organ signals for normal performance.     

Influence of long-term optokinetic stimulation on eye movements of the rabbit

Two kinds of optokinetic afternystagmus (OKAN) have been studied in rabbits; positive and negative OKAN. Positive OKAN is the persistence of eye movements evoked by optokinetic stimulation following the termination of the stimulus, with the slow phase of the eye movements in the same direction as the inducing stimulus. Negative OKAN is evoked by long duration optokinetic stimulation, and has a slow phase of opposite direction to the inducing stimulus. The stimulus conditions which are optimal for inducing and maintaining negative OKAN were characterized. Rabbits were placed in an optokinetic drum for periods of 12-96 h (with appropriate intervening periods for food and water). Eye movements were recorded during and after the termination of optokinetic stimulation. The optimum optokinetic stimulus velocity for the induction of negative OKAN was 5 degrees/s. The minimum duration of stimulation for the induction of negative OKAN of maximum velocity was 48 h. Once induced, the slow phase of negative OKAN attained velocities of 50-100 degrees/s. Three conditions of restraint of the rabbits were studied after negative OKAN was induced during the intervening periods when eye movements were not being recorded. These conditions were: (1) unrestrained (full freedom of movement) without visual stimulation (in a dark enclosure); (2) restrained (horizontal head and body movement prevented) without visual stimulation; and (3) restrained with visual stimulation (in the stationary optokinetic drum). Conditions 1 and 2 caused negative OKAN to dissipate within 24 h. Condition 3 caused negative OKAN to be maintained for more than 70 h. The velocity imbalance of the horizontal vestibuloocular reflex (HVOR) was measured at different times following the induction of negative OKAN. It provided a more sensitive index of the central imbalance which caused negative OKAN, than did spontaneous nystagmus. One of the consequences of optokinetic stimulation measured over a 16 h period was a decrease in the gain of the optokinetic reflex. This reduction in gain could represent a central adaptation to maintained stimulation which in the absence of continued optokinetic stimulation is expressed as a nystagmus.     

Vestibulo-ocular dysfunction induced by cortical damage in man: a case report.

We studied the rare case of a patient presenting with vestibulo-ocular dysfunction and clinical vestibular symptoms after right temporo-parietal cortex infarction. The vestibulo-ocular reflex (VOR) was elicited in the dark, by sinusoidal (0.02; 0.05 and 0.1 Hz) and by step velocity rotation (100 degrees/s2) in clockwise and counterclockwise directions. Horizontal and vertical eye movements were recorded by DC electro-oculography (EOG). When compared to a control group of 8 healthy subjects, this patient presented VOR asymmetry with (1) a significant VOR velocity bias toward the lesioned side revealed as a vestibulo-ocular offset that occurred only under dynamic conditions (2) a significant reduction of the VOR time constant when rotation was directed to the lesioned side. VOR gain was normal. We suggest that the parieto-temporal cortex is implicated in the regulation of vestibulo-ocular symmetry in man. This cortical processing of vestibular integration might involve a multidimensional velocity storage integrator that subserves the maintenance of spatial coordinates along the spatial vertical axis.     

Ultralow vestibuloocular reflex time constants

We report detailed oculomotor studies in 3 patients with central nervous system lesions and markedly decreased time constants (less than 2 seconds) of the vestibuloocular reflex (VOR). In 1 patient with Chiari type I malformation, serial measurements over 3 years documented a progressive decrease in the duration of postrotatory nystagmus (100 deg/sec steps, acceleration 140 deg/sec2) until finally there was no sustained nystagmus. At this time, the patient had no response to caloric stimulation or to sinusoidal rotation below 0.2 Hz but normal gain (peak slow-phase eye velocity/peak chair velocity) above 0.4 Hz (phase lead increased). Gaze holding, saccades, smooth pursuit, and optokinetic nystagmus were normal, but optokinetic-after-nystagmus disappeared. The other 2 patients (combined brainstem-cerebellar atrophy) had impaired gaze holding, abnormal smooth pursuit and optokinetic nystagmus, and absent optokinetic-after-nystagmus. VOR gain to step and high-frequency sinusoidal stimuli was increased. The neural mechanism that normally prolongs the VOR time constant may have reduced it in our patients.     

Dynamics of adaptive change in vestibulo-ocular reflex direction. I. Rotations in the horizontal plane

Horizontal and vertical vestibulo-ocular reflex (VOR) eye movements were recorded in alert cats before and after adaptation to vertical optokinetic motion coupled with horizontal rotation at 0.05, 0.25 or 1.0 Hz. Within 15-30 min, the VOR measured in darkness acquired a vertical component; the maximal directional change in the VOR occurred at the frequency of the adapting stimulus. At other frequencies the gain was less and there were phase leads or lags for higher or lower frequencies, respectively. Adaptive VOR was stable for at least 14 h in unrestrained animals with no visual input and decayed within 30 min during rotation in a stationary visual world.     

Asymmetric adaptive gain changes of the vertical vestibulo-ocular reflex in cats

The present study was conducted to examine adaptive gain changes of vertical vestibulo-ocular reflex (VOR) after exposure to a vertical visual-vestibular mismatch in cats. The visual-vestibular mismatch was induced by oscillating the animals for an hour about an inter-aural axis at frequencies of 0.16 and 0.32 Hz with the peak velocity of 20 degrees/s, coupled with either in-phase ("gain decrease" conditioning) or out-of-phase ("gain increase" conditioning) sinusoidal rotation of a random-dot pattern. Eye movements were measured with a magnetic search coil system. Before conditioning, vertical VOR showed up-down asymmetric responses. That is, upward slow phase eye velocity (SPV) in response to downward head rotation was significantly larger than downward SPV in response to upward head rotation. After adaptation to "gain increase" conditioning, VOR gain increased in both stimulus directions. The increase in VOR gain was significantly larger for upward SPV than for downward SPV. After adaptation to "gain decrease" conditioning, VOR gain decreased in both stimulus directions. The decrease in VOR gain was, however, significantly larger for downward SPV than for upward SPV. Our results indicate that VOR in the vertical plane adaptively changes but that the gain change shows a directional asymmetry. This asymmetry was dependent on the direction of the slip of visual image rather than the direction of head rotation, and the gain change was smaller when the retinal slip was generated downward. Possible explanations for the asymmetry are discussed on a physiological and anatomical basis.     

Dependence of cat vestibulo-ocular reflex direction adaptation on animal orientation during adaptation and rotation in darkness

Four series of experiments investigated how adaptive changes in direction of the cat's vestibulo-ocular reflex (VOR) vary with position of the animal during adaptive training and postadaptive testing. In all experiments VOR was measured electrooculographically during rotations about earth-horizontal and vertical axes in the dark before and after 2 h of adaptation in which 0.25 Hz sinusoidal whole body rotation about a horizontal/vertical axis was paired with synchronous 0.25 Hz rotation of a visual pattern about a vertical/horizontal axis, respectively. In upright sagittal (US) experiments, coupling of pitch rotation with visual pattern rotation about an earth vertical axis yielded an adaptive horizontal VOR response to pitch rotation whose gain had a local maximum at 0.25-0.5 Hz plus a sustained rise for frequencies below 0.1 Hz. When post-tests were done with the animal rolled 90 degrees onto its side and rotated about the earth vertical axis (pitch relative to the cat), the low frequency rise was eliminated and the 0.25 Hz peak was reduced. In on side sagittal (SS) experiments, where training was done in the latter (on side) position, training produced only the 0.25 Hz peak without the low frequency rise, indicating that the rise is due to coupling of otolith input to horizontal VOR. Again the 0.25 Hz peak was reduced when testing was done with the cat oriented 90 degrees from the training position (in the US position). This indicates that the cross-coupled canal-ocular reflex response is modulated or gated by the position of the animal with respect to gravity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Eye movements in patients with absent voluntary horizontal gaze

Despite the complete absence of horizontal saccades, two patients with pontine gliomas had horizontal reflex eye movements within a range of +/- 20 degrees. The gain (peak eye velocity/peak stimulus velocity) and phase of the vestibulo-ocular reflex were normal, but the optokinetic gain was decreased. The latency, accuracy, and peak velocity of vertical saccades were normal. Apparently the voluntary gaze centers in the pontine reticular formation are not crucial for generating horizontal vestibular or vertical saccadic eye movements.     

Changes in gain of the vestibulo-ocular reflex induced by combined visual and vestibular stimulation in goldfish

Adaptive changes in the vestibulo-ocular reflex (VOR) of goldfish were produced in a few hours by sinusoidally rotating restrained fish in the horizontal plane inside a vertically striped drum. The drum could also be sinusoidally rotated so that the gain of the VOR (the ratio of eye to head angular velocity) would have to increase to two or decrease to zero in order to maintain a stable retinal image. During 'training' towards two VOR gain measured at the stimulation frequency of 0.125 Hz increased rapidly over 6 h of stimulation to about 1.5 from an initial gain of 0.7. Half of that change occurred in the first 30 min. During training towards zero VOR gain measured at the stimulation frequency decreased to 0.15. About one-third of that change occurred in the first 30 min. Testing at different sinusoidal frequencies after 6 h stimulation showed that increases in VOR gain were generated across a 6-octave range; however, reductions in gain were produced over a narrow frequency range close to the training frequency. Gain reductions occurred more rapidly on a second day of stimulation. In a paradigm simulating reversing prisms, partial reversal of the VOR was observed in some fish. However, these fish also demonstrated spontaneous slow sinusoidal eye movements that may have represented a different means of adjusting eye movements to stabilize the retinal image. Goldfish provide a useful preparation for the study of adaptive gain changes in vertebrate oculomotor systems.     

Eye oscillations in strobe reared cats

Cats reared from birth in stroboscopic illumination develop abnormal spontaneous eye oscillations of low amplitude. The present experiments were undertaken to define these eye movements as recorded in the dark, in stroboscopic light of various frequencies, after exposure to normal light and after attenuation of the vestibulo-ocular reflex (VOR) gain by optical reversal of vision. The interaction of spontaneous eye oscillations with voluntary saccadic eye movements, and optokinetic tracking (OKN), were also studied. Two cats, reared from birth to 18 months Hz strobe light, and one normally reared control animal, were used. Horizontal movement of the right eye was measured by the scleral eye coil method. The frequency content of eye movement records was determined by power spectral analysis. VOR gain was estimated in the dark, by rotating the animals sinusoidally at1/8 Hz and 5°/sec velocity amplitude. In the dark, both strobe reared cats had abnormal spontaneous eye oscillations at a frequency close to 8 Hz, with peak-to-peak amplitudes of 0.5–1.0°. These abnormal eye movements did not interfere with, nor were they abolished by, normal oculomotor activity. The introduction of strobe light modified the spontaneous eye movements by entraining the oscillations at a given ‘forcing’ frequency, and by producing a number of harmonics or sub-harmonics. In one of the strobe reared animals, the effect of normal light was to reduce the characteristic ‘dark’ value of 9 Hz, to a new maintained ‘light’ value of 2.7 Hz. Adaptive attenuation of the VOR gain caused the abolition of regular spontaneous eye oscillations in the dark; nevertheless, oscillations to single strobe flashes could still be elicited in the VOR adapted condition. The results are interpreted as representing an organised attempt by the developing oculomotor system to attain the goal of stable visual perception in a new visual environment.     

Adaptability of the vestibulo-ocular reflex to vision reversal in strobe reared cats

Optical reversal of vision brings about adaptive changes in the vestibulo-ocular reflex (VOR) tending to reduce retinal image slip during head movement. The present experiments investigated this form of adaptation in cats whose complement of direction sensitive central visual cells had been substantially reduced by rearing in 8 Hz stroboscopic light. Horizontal vision reversal was produced by dove prisms carried in a skull-mounted mask. A scleral eye coil was used to measure horizontal eye movements. VOR gain and phase were measured in the dark during sinusoidal rotation using test stimuli of1/8 Hz and 5- of 20°/sec velocity amplitude. Initially, strobe reared cats produced virtually normal VOR in the dark, except for slight but significant exaggeration of the normal phase advancement to be expected at1/8 Hz. Addition of their familiar strobe illumination produced almost perfect oculomotor compensation. Maintained vision reversal in both strobe and normal illumination produced similar patterns of adaptive change in normal and strobe reared subjects, i.e. all animals exhibited an initial fast, and subsequent much slower, stage of gain attenuation, with similar changes in phase. Thus, strobe rearing did not prevent the development of an essentially normal VOR, nor did it interfere significantly with the ability to adapt in response to vision reversal. Since strobe rearing depletes direction selective visual movement detectors in the cortex and superior colliculi, it is inferred that signals responsible for activating the adaptive process are probably carried mainly in the accessory optic, rather than cortical and collicular, visual system.     

Effects of optokinetic velocity and medial vestibulo-cerebellum lesions on vestibulo-ocular reflex direction adaptation in the cat

Adaptive horizontal vestibulo-ocular reflex eye movements in response to vertical (pitch) rotations were produced by exposing three cats to synchronized horizontal optokinetic and vertical vestibular oscillations at 0.25 Hz. The effects of optokinetic stimulus velocity (6–80°/s peak) and nodulo-uvular cerebellum lesions were studied. All optokinetic velocities elicited vestibulo-ocular reflex direction adaptation, though 6°/s stimuli were somewhat less effective. Restricted aspirations of cerebellar vermis lobules IX and X in two cats resulted in reduced but still clearly evident adaptation.     

Frequency dependence of cat vestibulo-ocular reflex direction adaptation: single frequency and multifrequency rotations

Vertical and horizontal vestibulo-ocular reflex (VOR) eye movements were recorded in alert cats during horizontal rotation in total darkness before and after a 2 h vestibulo-ocular reflex direction adaptation procedure. Adaptation stimuli were whole body horizontal vestibular rotation coupled to synchronous vertical optokinetic motion. The waveform of the adaptation stimuli was either a sinusoid at 0.05, 0.1, 0.25, 0.5, or 1 Hz, or a sum of sinusoids containing 0.2, 0.3, 0.5, 0.7, 1.1, and 1.7 Hz. Exposure to single frequency stimuli produced adaptive vertical VOR with a gain that was greatest near the training frequency; adaptive VOR phases were advanced below, accurate at, and lagged above the training frequency. Exposure to the multifrequency waveform produced a uniform modest increase in gain across frequencies, with accurate adaptive VOR phase.     

Horizontal and vertical vestibulo-ocular and cervico-ocular reflexes in the monkey during high frequency rotation

In the alert monkey the horizontal vestibulo-ocular reflex (VOR) is basically compensatory over the range of 0.5 to 6 Hz with a gain near unity, and with the phase of the compensatory eye position having a minimal lag with respect to head position. Typical frequency-dependent eye movement patterns were observed. Vertical VOR is also compensatory having the same phase relations but with a reduced gain (-2.5 to -3.7 dB). In this range, vestibular input appears to be the predominant sensory influence on reflex eye movements. Additional optokinetic reflexes do not improve the VOR above 0.5 Hz. The horizontal cervico-ocular reflex (COR) is minimal or absent in normal monkeys.     

Vestibulo-ocular responses during the states of sleep in the cat.

The vestibulo-ocular response (VOR) was recorded during natural sleep in cats with chronically implanted electrodes. By using a small amplitude sinusoidal head rotation (11 degrees) peak-to-peak at 0.4 Hz) which elicited only slow compensatory eye movements, the VOR amplitude was found to decrease steeply (down to 40% or less) during slow-wave sleep. The phase of the VOR with respect to head position remained approximately constant. With a larger amplitude of sinusoidal rotation (320 degrees peak-to-peak at 0.05 Hz) the VOR response included nystagmus. During slow-wave sleep, nystagmus disappeared and the overall amplitude of the response decreased. Simultaneously, the phase of the eye response with respect to head position shifted by up to 90 degrees in advance. During paradoxical sleep, VOR disappeared in all cases and was replaced by randomly occurring bursts of rapid eye movements. These results are discussed in terms of a parametric control model of VOR.     

Dynamics of adaptive change in vestibulo-ocular reflex direction. II. Sagittal plane rotations

Alert cats were rotated sinusoidally (0.25 Hz) in their sagittal plane while viewing optokinetic motion in their horizontal plane. Vertical and horizontal vestibulo-ocular reflex (VOR) was measured in the dark before and after 2 h of these adaptation stimuli in upright or onside orientation of the cat. Onside exposure produced maximal adaptive horizontal VOR at the training frequency. Upright exposure produced highest gain at lower frequencies. A cat with inoperative vertical canals adapted only to upright exposure. We conclude that in the presence of horizontal image rotation either vertical canal or otolith stimulation can produce adaptation in VOR direction and stimulation of both produces complex adaptation dynamics.