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.     

Evidence for interacting cortical control of vestibular function and spatial representation in man

The objective of this research was to determine the possible relation between deficits in spatial representation capability and vestibular function following cortical lesions. We thus investigated vestibulo-ocular behaviour in a group of 14 patients with unilateral cortical damage involving the occipito-temporo-parietal junction. Patients were divided in three sub-groups: (1) Group R+: five patients with right sided cortical lesions associated with a left hemi-neglect, (2) Group R−: four patients with right sided cortical lesions with no hemi-neglect and (3) Group L: five patients with left-sided cortical lesions. The patient groups were compared to a group of eight healthy age-matched subjects. The vestibulo-ocular reflex (VOR) was tested in complete darkness by rotating the subject around the vertical axis by sinusoidal rotation at different frequencies, and by steps of acceleration or deceleration. The nystagmus slow phase velocity was measured and plotted as a function of the head velocity and the VOR parameters including gain, bias, time constant and phase were calculated.

The cortical lesions induced a significant VOR asymmetry in terms of: a directional preponderance of the VOR gain to the contralesion side, only during sinusoidal rotation, and, in contrast, a VOR bias and a directional preponderance of the VOR time constant and of the nystagmus frequency to the side of the cortical lesion. These latter VOR deficits were the most significant in the R+ group, i.e. in right cortical lesions with hemi-neglect syndrome. These results demonstrate in man, the existence of a cortical influence on vestibular function related to the mechanisms of spatial representation.     

Vestibular afferent responses to microrotational stimuli

Intracellular microelectrode recording/labelling techniques were used to investigate vestibular afferent responses in the bullfrog, to very small amplitude (less than 0.5 degree p-p) sinusoidal rotations in the vertical plane over the frequency range of 0.063-4 Hz. The axis of rotation was congruent with the axis of the anterior semicircular canal. Robust responses to peak accelerations as low as 0.031 degree/S2 were obtained from units subsequently traced to either the central portion of the anterior canal crista or the striolar region of the utricle. All of these microrotationally sensitive afferent neurons had irregular resting discharge rates and the majority had transfer ratios (relative to rotational velocity) of 1-40 spikes/s per degree/s. Individual utricular afferent velocity transfer ratios were nearly constant over the frequency range of 0.125-4 Hz. Canal units generally displayed decreasing response transfer ratios as stimulus frequencies increased. These findings indicate that although utricular striolar and central crista afferent velocity transfer ratios to microrotations were very similar, utricular striolar afferent neurons were more faithful sensors of very small amplitude rotational velocity in the vertical plane.     

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.     

Testing the vestibular-ocular reflexes: abnormalities of the otolith contribution in patients with neuro-otological disease.

Conventional vestibular rotation testing with the head centered on the axis stimulates the semicircular canals evoking compensatory eye movements. If the head is placed forwards of the axis in an eccentric position the otoliths are also stimulated by a tangential linear acceleration acting laterally to the skull. In normal subjects the additional otolithic stimulus evokes compensatory eye movements with a higher gain than with head centred, particularly for high frequency (greater than 0.1 Hz) stimuli. The responses with head centred and eccentric in various patients with known/suspected neuro-otological abnormalities have been compared. Patients with vestibular neurinectomies who have asymmetrical head centred responses showed greater asymmetry with head eccentric at higher stimulus frequencies. Some patients with cerebellar lesions showed abnormally enhanced or depressed and asymmetrical responses with head eccentric in comparison with head centred responses, which could be normal. The enhancing effects could be specific to low frequency stimuli. All patients who showed abnormal responses with head eccentric also had positional nystagmus provoked by the gravity acceleration vector when the head was tilted laterally. The direction of the positional nystagmus with respect to the gravity vector was not necessarily the same as the direction of the effect on eye movements of lateral acceleration during eccentric oscillation. Patients with benign paroxysmal vertigo or chronic linear vertigo in whom otolithic abnormalities are suspected were not found to have abnormal responses with head eccentric. We conclude that this method of testing may be useful in elucidating pathophysiology but is not a decisive clinical test for the presence of disordered otolith function.     

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.     

Asymmetrical perception of body rotation after unilateral injury to human vestibular cortex

Vestibular information plays a key role in many perceptual and cognitive functions, but surprisingly little is known about how vestibular signals are processed at the cortical level in humans. To address this issue, we tested the ability of two patients, with damage to key components of the vestibular network in either the left or right hemisphere, to perceive passive whole-body rotations (25-125 degrees) about the yaw axis. In both patients, the posterior insula, hippocampus, putamen, and thalamus were extensively damaged. The patients' responses were compared with those of nine age- and sex-matched neurologically intact participants. The body rotations were conducted without vision and the peak angular velocities ranged from 40 degrees to 90 degrees per second. Perceived rotation was assessed by open-loop manual pointing. The right hemisphere patient exhibited poor sensitivity for body rotations toward the contralesional (left) hemispace and generally underestimated the rotations. By contrast, his judgments of rotations toward the ipsilesional (right) hemispace greatly overestimated the physical rotation by 50-70 degrees for all tested magnitudes. The left hemisphere patient's responses were more appropriately scaled for both rotation directions, falling in the low-normal range. These findings suggest that there is some degree of hemispheric specialization in the cortical processing of dynamic head rotations in the yaw plane. In this view, right hemisphere structures play a dominant role, processing rotations in both directions, while left hemisphere structures process rotations only toward the contralesional hemispace.     

Central processing of human ocular torsion analyzed by galvanic vestibular stimulation

We examined the dynamics of human ocular torsion (OT) responses to sinusoidal galvanic vestibular stimulation (GVS) (0.005-1.67 Hz). The tonic OT showed a lowpass characteristic with a time constant of 1.74 s and a gain of 0.93 deg/mA. In two subjects, nystagmus dominated the observable OT pattern at frequencies <0.1 Hz. The nystagmus slow phases showed an exponential trajectory with a time constant of 1.49 s. The dynamics of both tonic OT and torsional nystagmus in our study were similar to the dynamics of OT induced by rotation and linear acceleration found in the literature. We propose a model for the central processing of torsional eye movements that is based on a common neural integration of semicircular canal (SC) and utricular inputs as well as nystagmus bursts. The sensitivity of all vestibular afferents to GVS was derived to be 0.76 spikes/s/mA. SC effects on OT are at least 3.5 times higher than utricular effects.     

Dyslexic children have normal vestibular responses to rotation

We examined the rotational vestibular responses of carefully screened dyslexic and control populations (34 dyslexics and 33 controls). The subject groups had equivalent performance IQs but differed significantly on verbal IQ and on silent and oral reading. Children with significant neurologic, visual, or hearing deficits were excluded. We measured eye movements provoked by sinusoidal rotation of the subjects (in total darkness) at low frequencies (0.01 to 0.16 Hz). Gain, phase, and preponderance (asymmetry) of the responses were calculated from the eye velocity and stimulus velocity waveforms. There were no differences between the groups in any of these measures. We conclude that there are no clinically measurable differences in this aspect of vestibular function in our carefully selected populations of dyslexic and control children.     

Violation of homogeneity by the vestibulo-ocular reflex of the goldfish

The vestibulo-ocular reflex (VOR) allows animals to maintain stable gaze during head rotations by generating compensatory eye rotations. The VOR is typically tested using sinusoidal head rotation, and VOR gain is calculated as the ratio of the amplitude of eye to head rotational velocity. Through habituation, prolonged exposure to lower frequency sinusoidal head rotation in the dark decreases VOR gain. The VOR has been treated and modeled as a linear system. If it is linear, then the VOR must obey the principle of homogeneity: VOR gain at a particular frequency should be the same regardless of head velocity. We examined the habituated goldfish VOR for homogeneity. We found that it violated this basic principle of linear systems and is therefore non-linear.     

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.     

Visual-vestibular interaction and cerebellar atrophy.

The vestibular and optokinetic ocular control systems were studied in 10 patients with cerebellar atrophy and in 10 normal subjects using (1) constant velocity optokinetic stimulation, (2) sinusoidal rotation in the dark, and (3) sinusoidal rotation in the light with a surrounding fixed optokinetic drum. The gain (maximum slow component velocity/maximum head or drum velocity) of induced nystagmus was calculated from electro-oculographic recordings. Optokinetic nystagmus was abnormal in seven patients and the average optokinetic gain in the patients was significantly (p less than 0.01) less than that of the normal group. Three patients with "clinically pure" cerebellar atrophy had increased vestibular responses, and one patient with clinical signs of peripheral neuropathy had decreased responses, probably due to associated vestibular nerve disease. The average vestibulo-ocular reflex gain in patients did not differ significantly from controls (p greater than 0.05). Three patients had normal vestibular and optokinetic responses when tested independently, but had abnormal visual-vestibular interaction. These patients probably had selective disorders of the midline cerebellar pathways that mediate visual-vestibular interaction. By studying each system, both independently and during interaction, all patients were identified as abnormal, and a more precise anatomic localization of the atrophy was obtained.     

Changes in the human vestibulo-ocular reflex after loss of peripheral sensitivity

Quantitative rotational testing was used to study changes in the vestibulo-ocular reflex of patients with unilateral and bilateral peripheral vestibular lesions. Compared with normal subjects, the patients exhibited a characteristic pattern of decreased gain and increased phase lead at low frequencies of sinusoidal stimulation and decreased time constants on impulsive stimulation. By contrast, gain and phase measurements on high-frequency-low-amplitude sinusoidal stimulation were often normal. In the patients with bilateral lesions, the results of caloric testing correlated with the results of low-frequency rotational testing but not with the results of high-frequency testing. There are two main clinical implications of these findings. First, patients with absent response to caloric stimulation (unilateral or bilateral) may have a normal response to high-frequency sinusoidal rotation (i.e., the frequencies that constitute most natural head movements). This probably explains why such patients do not report oscillopsia. Second, low-frequency sinusoidal rotational testing and caloric testing are more sensitive than high-frequency sinusoidal or impulsive rotational testing for detecting early loss of vestibular sensitivity due, for example, to ototoxic drugs.     

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)     

Visual afference mediates head and trunk stability in vestibular hypofunction

Humans must maintain head and trunk stability while walking. The purpose of this study was to compare the kinematics of healthy controls and patients with vestibular hypofunction (VH) when walking and making head rotations of different frequencies in both light and dark conditions. We recruited eight individuals with VH and nine healthy control subjects to perform four tasks at their preferred gait speed, being normal walk, walking and making yaw head rotations at 1.5 Hz and 2 Hz, and walking in the dark and making yaw head rotations at 1.5 Hz. Linear kinematics as well as head, trunk, and pelvis angular velocities were captured using the Vicon motion analysis system (Vicon Motion Systems, Oxford, UK). We found no difference in walking velocities for any of the four walking conditions across groups. The lateral displacement of the center of mass was increased in VH patients. In the dark, patients had more head instability in pitch (larger amplitudes and velocities) even though they were walking and making active yaw head rotations. Patients also had a smaller relative phase angle (mean 3.50 ± standard deviation 2.13°) than controls (mean 10.31 ± standard deviation 2.70°) (p < 0.01). Our data suggest that patients with VH have difficulty walking with a straight trajectory when turning their head. Additionally, patients with VH have an abnormal excursion of spontaneous pitch head rotation while walking and making active yaw head turns, which is dependent on vision. Rehabilitation for these patients should consider applying unique head rotation frequencies when training gait with head turns as well as alternating their exposure to light.     

Assessment of vestibulo-ocular reflexes in congenital nystagmus

The vestibulo-ocular reflex and its suppression by fixation of a target rotating with the subject were tested in 18 subjects with congenital nystagmus using steps of constant velocity rotation and sinusoidal stimuli swept in frequency between 0.01 and 1.0 Hz. Responses to stopping stimuli were abnormal in waveform and of short duration in most subjects tested. This pattern was attributed to masking of the response by spontaneous eye movements and to adaptation. In contrast, during both oscillation in the dark and attempted suppression of the vestibulo-ocular reflex, all subjects had nystagmus that was modulated with the stimulus during all frequencies of stimulation. The phase relationship of the nystagmus to the motion stimulus was the same as in normal subjects. Estimates of the gain of the vestibulo-ocular reflex response were not meaningful because of contamination of the vestibular response by the congenital nystagmus waveforms. Modulation of amplitude and reversal of nystagmus in phase with the vestibular stimulus at all frequencies of oscillation were shown most clearly during attempted suppression of the vestibulo-ocular reflex. This finding is clinically useful because it establishes suppression as a test of the presence of vestibular function in congenital nystagmus.     

Proprioceptive input overrides vestibulo-spinal drive during human locomotion

The aim of this study was to evaluate the influence of vestibulo-spinal drive on the performance of various locomotor-like movements. The extent of body rotation was assessed during walking (1 Hz and 2 Hz), running and hopping in place after vestibular stimulation (10 body rotations; 0.5 Hz). Compared to the controls, body rotations with eyes closed were larger during hopping than while running and smallest during walking independent of stepping frequency. A close correlation existed between the absolute duration of stance phase of the two legs and the rotation of the body. It is suggested that the amount of proprioceptive feedback from the legs determines the influence of vestibulo-spinal input on body movement.     

Instability of gaze during locomotion in patients with deficient vestibular function

We measured the stability of gaze in the horizontal and vertical planes, in 2 patients with bilaterally deficient vestibular function while they sat, stood still, walked in place, and made active horizontal and vertical head rotations. During sitting and standing, gaze was equally as stable as that in normal subjects. During walking in place, however, gaze velocity was double that of normal subjects. Thus, our patients' complaints of impaired vision and oscillopsia during walking could be ascribed to excessive motion of images on their retinas. Eye movements compensated for head rotations more effectively (higher gain) during active head rotations than during locomotion; this difference may be due to the predictable nature of active head movements. We conclude that testing of patients with vestibular symptoms should include stimuli corresponding to the rotational head perturbations that occur during locomotion; such head rotations have nonpredictable characteristics and a frequency range of 0.5 to 5.0 Hz.     

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.