Angular Vestibulo-ocular Reflex Research Articles

Recovery of Bilateral Vestibular Loss in Cogan’s Syndrome—A Case Report

To show that both hearing and vestibular loss can be reversible and quantified in Cogan's syndrome. Immunosuppressive medication was continued for more than 6 years in a young woman with Cogan's syndrome. Standard pure tone audiometry (PTA) and speech discrimination score (SDS) for hearing, motorized head impulse test (MHIT) for horizontal, angular vestibulo-ocular reflex, and erythrocyte sedimentation rate were followed serially. The PTA before medication was 59/74 dB, and it stabilized to 13/46 dB in 2 years. The initial SDS of 92/72% improved later to 100/100%, respectively. The gain of the vestibulo-ocular reflex was asymmetric (32%) and decreased to 0.48/0.25 at the beginning. Two years after the treatment, both the asymmetry (7%) and the gain (0.95/0.82) were recovered within normal limits. Erythrocyte sedimentation rate improved from 40 to 5 mm/h. Our case report of Cogan's syndrome demonstrates objective, simultaneous deterioration of hearing and vestibular function, which improved and stabilized after the introduction of immunosuppressive medication. The efficacy of immunosuppressive medication on vestibular function may be followed repetitively using MHIT in patients with Cogan's syndrome.

Relation of video-head-impulse test and caloric irrigation: a study on the recovery in unilateral vestibular neuritis

The head-impulse test (HIT) is an important test for examining unilateral vestibular hypofunction. The new video-head-impulse test (vHIT) is more sensitive and specific than the clinical bedside-head-impulse test. Alternatively, one can test for vestibular hypofunction with the caloric irrigation test. Various studies have shown that both tests may not always identify vestibular hypofunction; instead, the results of the tests might be contradictory. To further explore the question, of whether vHIT and caloric irrigation test the same part of the angular horizontal vestibulo-ocular reflex (VOR), we examined patients with unilateral vestibular neuritis at different points in time. The tonic vestibular imbalance (e.g., subjective-visual-vertical, ocular torsion and spontaneous nystagmus) and dynamic dysfunction of VOR (vHIT and bithermal caloric irrigation) were measured and quantified. While parameters of the tonic vestibular imbalance were well described by single exponential decay functions, dynamic parameters were less well defined. Therefore, to better compare the time course of pairs of two different parameters, we used a linear regression analysis. No linear correlation was found in the group and individually for the gain asymmetry and the ipsilesional gain of the vHIT with the unilateral weakness of the bithermal caloric irrigation tests. Linear correlation was found for most parameters of tonic vestibular imbalance. These findings are further evidence that vHIT and caloric irrigation test different parts of the angular VOR.

Directional Plasticity Rapidly Improves 3D Vestibulo-Ocular Reflex Alignment in Monkeys Using a Multichannel Vestibular Prosthesis

Bilateral loss of vestibular sensation can be disabling. We have shown that a multichannel vestibular prosthesis (MVP) can partly restore vestibular sensation as evidenced by improvements in the 3-dimensional angular vestibulo-ocular reflex (3D VOR). However, a key challenge is to minimize misalignment between the axes of eye and head rotation, which is apparently caused by current spread beyond each electrode's targeted nerve branch. We recently reported that rodents wearing a MVP markedly improve 3D VOR alignment during the first week after MVP activation, probably through the same central nervous system adaptive mechanisms that mediate cross-axis adaptation over time in normal individuals wearing prisms that cause visual scene movement about an axis different than the axis of head rotation. We hypothesized that rhesus monkeys would exhibit similar improvements with continuous prosthetic stimulation over time. We created bilateral vestibular deficiency in four rhesus monkeys via intratympanic injection of gentamicin. A MVP was mounted to the cranium, and eye movements in response to whole-body passive rotation in darkness were measured repeatedly over 1 week of continuous head motion-modulated prosthetic electrical stimulation. 3D VOR responses to whole-body rotations about each semicircular canal axis were measured on days 1, 3, and 7 of chronic stimulation. Horizontal VOR gain during 1 Hz, 50 °/s peak whole-body rotations before the prosthesis was turned on was <0.1, which is profoundly below normal (0.94 ± 0.12). On stimulation day 1, VOR gain was 0.4-0.8, but the axis of observed eye movements aligned poorly with head rotation (misalignment range ∼30-40 °). Substantial improvement of axis misalignment was observed after 7 days of continuous motion-modulated prosthetic stimulation under normal diurnal lighting. Similar improvements were noted for all animals, all three axes of rotation tested, for all sinusoidal frequencies tested (0.05-5 Hz), and for high-acceleration transient rotations. VOR asymmetry changes did not reach statistical significance, although they did trend toward slight improvement over time. Prior studies had already shown that directional plasticity reduces misalignment when a subject with normal labyrinths views abnormal visual scene movement. Our results show that the converse is also true: individuals receiving misoriented vestibular sensation under normal viewing conditions rapidly adapt to restore a well-aligned 3D VOR. Considering the similarity of VOR physiology across primate species, similar effects are likely to occur in humans using a MVP to treat bilateral vestibular deficiency.

Visual contribution to the high-frequency human angular vestibulo-ocular reflex

The vestibulo-ocular reflex (VOR) acts to maintain images stable on the retina by rotating the eyes in exactly the opposite direction, but with equal magnitude, to head velocity. When viewing a near target, this reflex has an increased response to compensate for the translation of the eyes relative to the target that acts to reduce retinal image slip. Previous studies have shown that retinal velocity error provides an important visual feedback signal to increase the low-frequency (<1 Hz) VOR response during near viewing. We sought to determine whether initial eye position and retinal image position error could provide enough information to substantially increase the high-frequency VOR gain (eye velocity/head velocity) during near viewing. Ten human subjects were tested using the scleral search coil technique during horizontal head impulses under different lighting conditions (constant dark, strobe light at 0.5, 1, 2, 4, 10, 15 Hz, constant light) while viewing near (9.5 ± 1.3 cm) and far (104 cm) targets. Our results showed that the VOR gain increased during near viewing compared to far viewing, even during constant dark. For the near target, there was an increase in VOR gain with increasing strobe frequency from 1.17 ± 0.17 in constant dark to 1.36 ± 0.27 in constant light, a 21 ± 9 % increase. For the far target, strobe frequency had no effect. Presentation order of strobe frequency (i.e. 0.5-15 vs. 15-0.5 Hz) did not affect the gain, but it did affect the vergence angle (angle between the two eye's lines of sight). The VOR gain and vergence angles were constant during each trial. Our findings show that a retinal position error signal helps increase the vergence angle and could be invoking vestibular adaptation mechanisms to increase the high-frequency VOR response during near viewing. This is in contrast to the low-frequency VOR that depends more on retinal velocity error and predictive adaptation mechanisms.

The Horizontal Angular Vestibulo-Ocular Reflex: A Nonlinear Mechanism for Context-Dependent Responses

Studies of the vestibulo-ocular reflex (VOR) have revealed that this type of involuntary eye movement is influenced by viewing distance. This paper presents a bilateral model for the horizontal angular VOR in the dark based on realistic physiological mechanisms. It is shown that by assigning proper nonlinear neural computations at the premotor level, the model is capable of replicating target-distance-dependent VOR responses that are in agreement with geometrical requirements. Central premotor responses in the model are also shown to be consistent with experimental observations. Moreover, the model performance after simulated unilateral canal plugging also reproduces experimental observations, an emerging property. Such local nonlinear computations could similarly generate context-dependent behaviors in other more complex motor systems.

Three Dimensional Vestibular Ocular Reflex Testing Using a Six Degrees of Freedom Motion Platform

The vestibular organ is a sensor that measures angular and linear accelerations with six degrees of freedom (6DF). Complete or partial defects in the vestibular organ results in mild to severe equilibrium problems, such as vertigo, dizziness, oscillopsia, gait unsteadiness nausea and/or vomiting. A good and frequently used measure to quantify gaze stabilization is the gain, which is defined as the magnitude of compensatory eye movements with respect to imposed head movements. To test vestibular function more fully one has to realize that 3D VOR ideally generates compensatory ocular rotations not only with a magnitude (gain) equal and opposite to the head rotation but also about an axis that is co-linear with the head rotation axis (alignment). Abnormal vestibular function thus results in changes in gain and changes in alignment of the 3D VOR response. Here we describe a method to measure 3D VOR using whole body rotation on a 6DF motion platform. Although the method also allows testing translation VOR responses (1), we limit ourselves to a discussion of the method to measure 3D angular VOR. In addition, we restrict ourselves here to description of data collected in healthy subjects in response to angular sinusoidal and impulse stimulation. Subjects are sitting upright and receive whole-body small amplitude sinusoidal and constant acceleration impulses. Sinusoidal stimuli (f = 1 Hz, A = 4°) were delivered about the vertical axis and about axes in the horizontal plane varying between roll and pitch at increments of 22.5° in azimuth. Impulses were delivered in yaw, roll and pitch and in the vertical canal planes. Eye movements were measured using the scleral search coil technique (2). Search coil signals were sampled at a frequency of 1 kHz. The input-output ratio (gain) and misalignment (co-linearity) of the 3D VOR were calculated from the eye coil signals (3). Gain and co-linearity of 3D VOR depended on the orientation of the stimulus axis. Systematic deviations were found in particular during horizontal axis stimulation. In the light the eye rotation axis was properly aligned with the stimulus axis at orientations 0° and 90° azimuth, but gradually deviated more and more towards 45° azimuth. The systematic deviations in misalignment for intermediate axes can be explained by a low gain for torsion (X-axis or roll-axis rotation) and a high gain for vertical eye movements (Y-axis or pitch-axis rotation (see Figure 2). Because intermediate axis stimulation leads a compensatory response based on vector summation of the individual eye rotation components, the net response axis will deviate because the gain for X- and Y-axis are different. In darkness the gain of all eye rotation components had lower values. The result was that the misalignment in darkness and for impulses had different peaks and troughs than in the light: its minimum value was reached for pitch axis stimulation and its maximum for roll axis stimulation. Nine subjects participated in the experiment. All subjects gave their informed consent. The experimental procedure was approved by the Medical Ethics Committee of Erasmus University Medical Center and adhered to the Declaration of Helsinki for research involving human subjects. Six subjects served as controls. Three subjects had a unilateral vestibular impairment due to a vestibular schwannoma. The age of control subjects (six males and three females) ranged from 22 to 55 years. None of the controls had visual or vestibular complaints due to neurological, cardio vascular and ophthalmic disorders. The age of the patients with schwannoma varied between 44 and 64 years (two males and one female). All schwannoma subjects were under medical surveillance and/or had received treatment by a multidisciplinary team consisting of an othorhinolaryngologist and a neurosurgeon of the Erasmus University Medical Center. Tested patients all had a right side vestibular schwannoma and underwent a wait and watch policy (Table 1; subjects N1-N3) after being diagnosed with vestibular schwannoma. Their tumors had been stabile for over 8-10 years on magnetic resonance imaging.

Three Dimensional Vestibular Ocular Reflex Testing Using a Six Degrees of Freedom Motion Platform

The vestibular organ is a sensor that measures angular and linear accelerations with six degrees of freedom (6DF). Complete or partial defects in the vestibular organ results in mild to severe equilibrium problems, such as vertigo, dizziness, oscillopsia, gait unsteadiness nausea and/or vomiting. A good and frequently used measure to quantify gaze stabilization is the gain, which is defined as the magnitude of compensatory eye movements with respect to imposed head movements. To test vestibular function more fully one has to realize that 3D VOR ideally generates compensatory ocular rotations not only with a magnitude (gain) equal and opposite to the head rotation but also about an axis that is co-linear with the head rotation axis (alignment). Abnormal vestibular function thus results in changes in gain and changes in alignment of the 3D VOR response. Here we describe a method to measure 3D VOR using whole body rotation on a 6DF motion platform. Although the method also allows testing translation VOR responses 1, we limit ourselves to a discussion of the method to measure 3D angular VOR. In addition, we restrict ourselves here to description of data collected in healthy subjects in response to angular sinusoidal and impulse stimulation. Subjects are sitting upright and receive whole-body small amplitude sinusoidal and constant acceleration impulses. Sinusoidal stimuli (f = 1 Hz, A = 4°) were delivered about the vertical axis and about axes in the horizontal plane varying between roll and pitch at increments of 22.5° in azimuth. Impulses were delivered in yaw, roll and pitch and in the vertical canal planes. Eye movements were measured using the scleral search coil technique 2. Search coil signals were sampled at a frequency of 1 kHz. The input-output ratio (gain) and misalignment (co-linearity) of the 3D VOR were calculated from the eye coil signals 3. Gain and co-linearity of 3D VOR depended on the orientation of the stimulus axis. Systematic deviations were found in particular during horizontal axis stimulation. In the light the eye rotation axis was properly aligned with the stimulus axis at orientations 0° and 90° azimuth, but gradually deviated more and more towards 45° azimuth. The systematic deviations in misalignment for intermediate axes can be explained by a low gain for torsion (X-axis or roll-axis rotation) and a high gain for vertical eye movements (Y-axis or pitch-axis rotation (see Figure 2). Because intermediate axis stimulation leads a compensatory response based on vector summation of the individual eye rotation components, the net response axis will deviate because the gain for X- and Y-axis are different. In darkness the gain of all eye rotation components had lower values. The result was that the misalignment in darkness and for impulses had different peaks and troughs than in the light: its minimum value was reached for pitch axis stimulation and its maximum for roll axis stimulation. Case Presentation Nine subjects participated in the experiment. All subjects gave their informed consent. The experimental procedure was approved by the Medical Ethics Committee of Erasmus University Medical Center and adhered to the Declaration of Helsinki for research involving human subjects. Six subjects served as controls. Three subjects had a unilateral vestibular impairment due to a vestibular schwannoma. The age of control subjects (six males and three females) ranged from 22 to 55 years. None of the controls had visual or vestibular complaints due to neurological, cardio vascular and ophthalmic disorders. The age of the patients with schwannoma varied between 44 and 64 years (two males and one female). All schwannoma subjects were under medical surveillance and/or had received treatment by a multidisciplinary team consisting of an othorhinolaryngologist and a neurosurgeon of the Erasmus University Medical Center. Tested patients all had a right side vestibular schwannoma and underwent a wait and watch policy (Table 1; subjects N1-N3) after being diagnosed with vestibular schwannoma. Their tumors had been stabile for over 8-10 years on magnetic resonance imaging.

Retinoic acid deficiency impairs the vestibular function.

The retinaldehyde dehydrogenase 3 (Raldh3) gene encodes a major retinoic acid synthesizing enzyme and is highly expressed in the inner ear during embryogenesis. We found that mice deficient in Raldh3 bear severe impairment in vestibular functions. These mutant mice exhibited spontaneous circling/tilted behaviors and performed poorly in several vestibular-motor function tests. In addition, video-oculography revealed a complete loss of the maculo-ocular reflex and a significant reduction in the horizontal angular vestibulo-ocular reflex, indicating that detection of both linear acceleration and angular rotation were compromised in the mutants. Consistent with these behavioral and functional deficiencies, morphological anomalies, characterized by a smaller vestibular organ with thinner semicircular canals and a significant reduction in the number of otoconia in the saccule and the utricle, were consistently observed in the Raldh3 mutants. The loss of otoconia in the mutants may be attributed, at least in part, to significantly reduced expression of Otop1, which encodes a protein known to be involved in calcium regulation in the otolithic organs. Our data thus reveal a previously unrecognized role of Raldh3 in structural and functional development of the vestibular end organs.

A New Tool for Investigating the Functional Testing of the VOR

Peripheral vestibular function may be tested quantitatively, by measuring the gain of the angular vestibulo-ocular reflex (aVOR), or functionally, by assessing how well the aVOR performs with respect to its goal of stabilizing gaze in space and thus allow to acquire visual information during the head movement. In recent years, several groups have developed clinical and quantitative approaches to functional testing of the vestibular system based on the ability to identify an optotype briefly displayed on screen during head rotations. Although the proposed techniques differ in terms of the parameters controlling the testing paradigm, no study has thus far dealt with understanding the role of such choices in determining the effectiveness and reliability of the testing approach. Moreover, recent work has shown that peripheral vestibular patients may produce corrective saccades during the head movement (covert saccades), yet the role of these eye movements toward reading ability during head rotations is not yet understood. Finally, no study has thus far dealt with measuring the true performance of their experimental setups, which is nonetheless likely to be crucial information for understanding the effectiveness of functional testing approaches. Thus we propose a new software and hardware research tool allowing the combined measurement of eye and head movements, together with the timing of the optotype on screen, during functional testing of the vestibulo-ocular reflex (VOR) based on the Head Impulse Test. The goal of such tool is therefore that of allowing functional testing of the VOR while collecting the experimental data necessary to understand, for instance, (a) the effectiveness of the covert saccades strategy toward image stabilization, (b) which experimental parameters are crucial for optimizing the diagnostic power of the functional testing approach, and (c) which conditions lead to a successful reading or an error trial.

Unilateral Adaptation of the Human Angular Vestibulo-Ocular Reflex

A recent study showed that the angular vestibulo-ocular reflex (VOR) can be better adaptively increased using an incremental retinal image velocity error signal compared with a conventional constant large velocity-gain demand (×2). This finding has important implications for vestibular rehabilitation that seeks to improve the VOR response after injury. However, a large portion of vestibular patients have unilateral vestibular hypofunction, and training that raises their VOR response during rotations to both the ipsilesional and contralesional side is not usually ideal. We sought to determine if the vestibular response to one side could selectively be increased without affecting the contralateral response. We tested nine subjects with normal vestibular function. Using the scleral search coil and head impulse techniques, we measured the active and passive VOR gain (eye velocity / head velocity) before and after unilateral incremental VOR adaptation training, consisting of self-generated (active) head impulses, which lasted ≈ 15 min. The head impulses consisted of rapid, horizontal head rotations with peak-amplitude 15°, peak-velocity 150°/s and peak-acceleration 3,000°/s(2). The VOR gain towards the adapting side increased after training from 0.92 ± 0.18 to 1.11 ± 0.22 (+22.7 ± 20.2 %) during active head impulses and from 0.91 ± 0.15 to 1.01 ± 0.17 (+11.3 ± 7.5 %) during passive head impulses. During active impulses, the VOR gain towards the non-adapting side also increased by ≈ 8 %, though this increase was ≈ 70 % less than to the adapting side. A similar increase did not occur during passive impulses. This study shows that unilateral vestibular adaptation is possible in humans with a normal VOR; unilateral incremental VOR adaptation may have a role in vestibular rehabilitation. The increase in passive VOR gain after active head impulse adaptation suggests that the training effect is robust.

Sleep Deprivation Has No Effect on Dynamic Visual Acuity in Military Service Members Who Are Healthy

The risk of traumatic brain injury (TBI) and comorbid posttraumatic dizziness is elevated in military operational environments. Sleep deprivation is known to affect a service member's performance while deployed, although little is known about its effects on vestibular function. Recent findings suggest that moderate acceleration step rotational stimuli may elicit a heightened angular vestibulo-ocular reflex (aVOR) response relative to low-frequency sinusoidal stimuli after 26 hours of sleep deprivation. There is concern that a sleep deprivation-mediated elevation in aVOR function could confound detection of comorbid vestibular pathology in service members with TBI. The term "dynamic visual acuity" (DVA) refers to an individual's ability to see clearly during head movement and is a behavioral measure of aVOR function. The Dynamic Visual Acuity Test (DVAT) assesses gaze instability by measuring the difference between head-stationary and head-moving visual acuity. The purpose of this study was to investigate the effects of 26 hours of sleep deprivation on DVA as a surrogate for aVOR function. This observational study utilized a repeated-measures design. Twenty soldiers with no history of vestibular insult or head trauma were assessed by means of the DVAT at angular head velocities of 120 to 180°/s. Active and passive yaw and pitch impulses were obtained before and after sleep deprivation. Yaw DVA remained unchanged as the result of sleep deprivation. Active pitch DVA diminished by -0.005 LogMAR (down) and -0.055 LogMAR (up); passive pitch DVA was degraded by -0.06 LogMAR (down) and -0.045 LogMAR (up). Sample homogeneity largely confounded accurate assessment of test-retest reliability in this study, resulting in intraclass correlation coefficients lower than those previously reported. Dynamic visual acuity testing in soldiers who are healthy revealed no change in gaze stability after rapid yaw impulses and subclinical changes in pitch DVA after sleep deprivation. Findings suggest that DVA is not affected by short-term sleep deprivation under clinical conditions.

Transmastoid galvanic stimulation does not affect the vergence-mediated gain increase of the human angular vestibulo-ocular reflex

Vergence is one of several viewing contexts that require an increase in the angular vestibular-ocular reflex (aVOR) response. A previous monkey study found that the vergence-mediated gain (eye/head velocity) increase of the aVOR was attenuated by 64% when anodic currents, which preferentially lower the activity of irregularly firing vestibular afferents, were delivered to both labyrinths. We sought to determine whether there was similar evidence implicating a role for irregular afferents in the vergence-mediated gain increase of the human aVOR. Our study is based upon analysis of the aVOR evoked by head rotations, delivered passively while subjects viewed a near (15cm) or far (124cm) target and applying galvanic vestibular stimulation (GVS) via surface electrodes. We tested 12 subjects during 2-3 sessions each. Vestibular stimuli consisted of passive whole-body rotations (sinusoids from 0.05-3Hz and 12-25°/s, and transients with peak ~15°, 50°/s, 500°/s(2)) and head-on-body impulses (peak ~30°, 150°/s, 3,000°/s(2)). GVS was on for 10s every 20s. All polarity combinations were tested, with emphasis on uni- and bi-lateral anodic inhibition. The average stimulus current was 5.9±1.6mA (range: 3-9.5mA), vergence angle (during near viewing) was 22.6±2.8° and slow-phase eye velocity caused by left anodic current stimulation with head stationary was -3.4±1.1°/s, -0.2±0.6°/s and 2.5±1.4°/s (torsion, vertical, horizontal). No statistically significant GVS effects were observed, suggesting that surface electrode GVS has no effect on the vergence-mediated gain increase of the aVOR at the current levels (~6mA) tolerated by most humans. We conclude that clinically practical transmastoid GVS does not effectively silence irregular afferents and hypothesize that currents >10mA are needed to reproduce the monkey results.

Pre-flight sensorimotor adaptation protocols for suborbital flight1

Commercial suborbital flights, which include 3-5 minutes of 0 g between hyper-g launch and landing phases, will present suborbital passengers with a challenging sensorimotor experience. Based on the results of neurovestibular research in parabolic and orbital flight, and the anticipated wide range of fitness and experience levels of suborbital passengers, neurovestibular disturbances are likely to be problematic in this environment. Pre-flight adaptation protocols might alleviate some of these issues. Therefore, we describe a set of sensorimotor tests to evaluate passengers before suborbital flight, including assessment of the angular vestibulo-ocular reflex (VOR), ocular skew and disconjugate torsion, subjective visual vertical, and roll vection. Performance on these tests can be examined for correlations with in-flight experience, such as motion sickness, disorientation, and visual disturbances, based on questionnaires and cabin video recordings. Through an understanding of sensorimotor adaptation to parabolic and orbital flight, obtained from many previous studies, we can then suggest appropriate pre-flight adaptation procedures.

Role of Cerebellum in Motion Perception and Vestibulo-ocular Reflex—Similarities and Disparities

Vestibular velocity storage enhances the efficacy of the angular vestibulo-ocular reflex (VOR) during relatively low-frequency head rotations. This function is modulated by GABA-mediated inhibitory cerebellar projections. Velocity storage also exists in perceptual pathway and has similar functional principles as VOR. However, it is not known whether the neural substrate for perception and VOR overlap. We propose two possibilities. First, there is the same velocity storage for both VOR and perception; second, there are nonoverlapping neural networks: one might be involved in perception and the other for the VOR. We investigated these possibilities by measuring VOR and perceptual responses in healthy human subjects during whole-body, constant-velocity rotation steps about all three dimensions (yaw, pitch, and roll) before and after 10 mg of 4-aminopyridine (4-AP). 4-AP, a selective blocker of inward rectifier potassium conductance, can lead to increased synchronization and precision of Purkinje neuron discharge and possibly enhance the GABAergic action. Hence 4-AP could reduce the decay time constant of the perceived angular velocity and VOR. We found that 4-AP reduced the decay time constant, but the amount of reduction in the two processes, perception and VOR, was not the same, suggesting the possibility of nonoverlapping or partially overlapping neural substrates for VOR and perception. We also noted that, unlike the VOR, the perceived angular velocity gradually built up and plateau prior to decay. Hence, the perception pathway may have additional mechanism that changes the dynamics of perceived angular velocity beyond the velocity storage. 4-AP had no effects on the duration of build-up of perceived angular velocity, suggesting that the higher order processing of perception, beyond the velocity storage, might not occur under the influence of mechanism that could be influenced by 4-AP.

Ontogeny of Mouse Vestibulo-Ocular Reflex Following Genetic or Environmental Alteration of Gravity Sensing

The vestibular organs consist of complementary sensors: the semicircular canals detect rotations while the otoliths detect linear accelerations, including the constant pull of gravity. Several fundamental questions remain on how the vestibular system would develop and/or adapt to prolonged changes in gravity such as during long-term space journey. How do vestibular reflexes develop if the appropriate assembly of otoliths and semi-circular canals is perturbed? The aim of present work was to evaluate the role of gravity sensing during ontogeny of the vestibular system. In otoconia-deficient mice (ied), gravity cannot be sensed and therefore maculo-ocular reflexes (MOR) were absent. While canals-related reflexes were present, the ied deficit also led to the abnormal spatial tuning of the horizontal angular canal-related VOR. To identify putative otolith-related critical periods, normal C57Bl/6J mice were subjected to 2G hypergravity by chronic centrifugation during different periods of development or adulthood (Adult-HG) and compared to non-centrifuged (control) C57Bl/6J mice. Mice exposed to hypergravity during development had completely normal vestibulo-ocular reflexes 6 months after end of centrifugation. Adult-HG mice all displayed major abnormalities in maculo-ocular reflexe one month after return to normal gravity. During the next 5 months, adaptation to normal gravity occurred in half of the individuals. In summary, genetic suppression of gravity sensing indicated that otolith-related signals might be necessary to ensure proper functioning of canal-related vestibular reflexes. On the other hand, exposure to hypergravity during development was not sufficient to modify durably motor behaviour. Hence, 2G centrifugation during development revealed no otolith-specific critical period.

Modeling spatial tuning of adaptation of the angular vestibulo-ocular reflex

Gain adaptation of the yaw angular vestibular ocular reflex (aVOR) induced in side-down positions has gravity-independent (global) and -dependent (localized) components. When the head oscillation angles are small during adaptation, localized gain changes are maximal in the approximate position of adaptation. Concurrently, polarization vectors of canal-otolith vestibular neurons adapt their orientations during these small-angle adaptation paradigms. Whether there is orientation adaptation with large amplitude head oscillations, when the head is not localized to a specific position, is unknown. Yaw aVOR gains were decreased by oscillating monkeys about a yaw axis in a side-down position in a subject-stationary visual surround for 2 h. Amplitudes of head oscillation ranged from 15° to 180°. The yaw aVOR gain was tested in darkness at 0.5 Hz, with small angles of oscillation (±15°) while upright and in tilted positions. The peak value of the gain change was highly tuned for small angular oscillations during adaptation and significantly broadened with larger oscillation angles during adaptation. When the orientation of the polarization vectors associated with the gravity-dependent component of the neural network model was adapted toward the direction of gravity, it predicted the localized learning for small angles and the broadening when the orientation adaptation was diminished. The model-based analysis suggests that the otolith orientation adaptation plays an important role in the localized behavior of aVOR as a function of gravity and in regulating the relationship between global and localized adaptation.

The Under-compensatory Roll aVOR Does Not Affect Dynamic Visual Acuity

Rotations of the head evoke compensatory reflexive eye rotations in the orbit to stabilize images onto the fovea. In normal humans, the angular vestibulo-ocular reflex (aVOR) gain (eye/head velocity) changes depending on the head rotation plane. For pitch and yaw head rotations, the gain is near unity, but during roll head rotations, the aVOR gain is ∼ 0.7. The purpose of this study was to determine whether this physiological discrepancy affects dynamic visual acuity (DVA)--a functional measure of the aVOR that requires subjects to identify letters of varying acuities during head rotation. We used the scleral search coil technique to measure eye and head velocity during passive DVA testing in yaw, roll, and pitch head impulses in healthy controls and patients with unilateral vestibular hypofunction (UVH). For control subjects, the mean aVOR gain during roll impulses was significantly lower than the mean aVOR gain during yaw and pitch impulses; however, there was no difference in DVA between yaw, roll, or pitch. For subjects with UVH, only aVOR gain during head rotations toward the affected side (yaw) were asymmetric (ipsilesional, 0.32 ± 0.17, vs. contralesional, 0.95 ± 0.05), with no asymmetry during roll or pitch. Similarly, there was a large asymmetry for DVA only during yaw head rotations, with no asymmetry in roll or pitch. Interestingly, DVA during roll toward the affected ear was better than DVA during yaw toward the affected ear--even though the ipsilesional roll aVOR gain was 60 % lower. During roll, the axis of eye rotation remains nearly perpendicular to the fovea, resulting in minimal displacement between the fovea and fixation target image projected onto the back of the eye. For subjects with UVH, the DVA score during passive horizontal impulses is a better indicator of poor gaze stability than during passive roll or pitch.

Tuning of gravity-dependent and gravity-independent vertical angular VOR gain changes by frequency of adaptation

The gain of the vertical angular vestibulo-ocular reflex (aVOR) was adaptively increased and decreased in a side-down head orientation for 4 h in two cynomolgus monkeys. Adaptation was performed at 0.25, 1, 2, or 4 Hz. The gravity-dependent and -independent gain changes were determined over a range of head orientations from left-side-down to right-side-down at frequencies from 0.25 to 10 Hz, before and after adaptation. Gain changes vs. frequency data were fit with a Gaussian to determine the frequency at which the peak gain change occurred, as well as the tuning width. The frequency at which the peak gravity-dependent gain change occurred was approximately equal to the frequency of adaptation, and the width increased monotonically with increases in the frequency of adaptation. The gravity-independent component was tuned to the adaptive frequency of 0.25 Hz but was uniformly distributed over all frequencies when the adaptation frequency was 1-4 Hz. The amplitude of the gravity-independent gain changes was larger after the aVOR gain decrease than after the gain increase across all tested frequencies. For the aVOR gain decrease, the phase lagged about 4° for frequencies below the adaptation frequency and led for frequencies above the adaptation frequency. For gain increases, the phase relationship as a function of frequency was inverted. This study demonstrates that the previously described dependence of aVOR gain adaptation on frequency is a property of the gravity-dependent component of the aVOR only. The gravity-independent component of the aVOR had a substantial tuning curve only at an adaptation frequency of 0.25 Hz.

Rezeptorfunktion der Bogengänge

Perturbation of semicircular canal function may result in a pathological angular vestibulo-ocular reflex (aVOR). The resulting impairment in gaze stabilization is perceived as "vertigo" or "dizziness" and may occur following receptor function impairment of all three semicircular canals. The head impulse test reveals hidden (covert-catchup) or visible (overt-catchup) saccades in disturbances of semicircular function. Most peripheral vestibular disorders can be treated conservatively. There are surgical treatment options for some diseases, such as intractable benign paroxysmal positional vertigo and superior semicircular canal dehiscence. Vestibular training promotes central reorganization of the VOR. Impaired semicircular receptor function, in particular bilateral vestibulopathy, may affect spatial orientation and cognitive processes. Balance prostheses could serve as a replacement for receptors in the future.

Patterns of spontaneous and head-shaking nystagmus in cerebellar infarction: imaging correlations

Horizontal head-shaking may induce nystagmus in peripheral as well as central vestibular lesions. While the patterns and mechanism of head-shaking nystagmus are well established in peripheral vestibulopathy, they require further exploration in central vestibular disorders. To define the characteristics and mechanism of head-shaking nystagmus in central vestibulopathies, we investigated spontaneous nystagmus and head-shaking nystagmus in 72 patients with isolated cerebellar infarction. Spontaneous nystagmus was observed in 28 (39%) patients, and was mostly ipsilesional when observed in unilateral infarction (15/18, 83%). Head-shaking nystagmus developed in 37 (51%) patients, and the horizontal component of head-shaking nystagmus was uniformly ipsilesional when induced in patients with unilateral infarction. Perverted head-shaking nystagmus occurred in 23 (23/37, 62%) patients and was mostly downbeat (22/23, 96%). Lesion subtraction analyses revealed that damage to the uvula, nodulus and inferior tonsil was mostly responsible for generation of head-shaking nystagmus in patients with unilateral posterior inferior cerebellar artery infarction. Ipsilesional head-shaking nystagmus in patients with unilateral cerebellar infarction may be explained by unilateral disruption of uvulonodular inhibition over the velocity storage. Perverted (downbeat) head-shaking nystagmus may be ascribed to impaired control over the spatial orientation of the angular vestibulo-ocular reflex due to uvulonodular lesions or a build-up of vertical vestibular asymmetry favouring upward bias due to lesions involving the inferior tonsil.