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Background: Acute and complete unilateral vestibular deafferentation induces a significant change in ipsilateral vestibuloocular reflex gain, making the patient unable to stabilize gaze during active or passive head movements. This inability creates the illusion that the visual environment is moving, resulting in persistent visual discomfort during rapid angular or linear acceleration of the head. This is known as oscillopsia. Our objective was to understand if the spontaneous sensation of oscillopsias after complete unilateral vestibular deafferentation by vestibular neurotomy at 5 days (D5) and at 3 months (M3) is correlated with the loss of vestibuloocular reflex gain and dynamic visual acuity. Methods: Retrospective cohort study was conducted in an otolaryngology tertiary care center (2019-2022) on patients with complete unilateral vestibular loss by vestibular neurotomy. They were divided into 2 groups according to the presence (group G1) or absence (group G2) of a spontaneous complaint of oscillopsia assessed at M3. Severity of oscillopsias evaluated by Oscillopsia Severity Questionnaire. Vestibuloocular reflex gain based on video head impulse test (vHIT) and the dynamic visual acuity were measured for each group at D5 and M3. Categorical variables were compared using χ2 test and quantitative variables using the nonparametric Wilcoxon-Mann-Whitney test. Results: All patients have a complete vestibular deafferentation at D5 and M3. At D5 (G1 = 8 patients, G2 = 5 patients), there is no significant difference for ipsilateral and contralateral vestibuloocular reflex gains and dynamic visual acuity losses. The Oscillopsia Severity Questionnaire was 2.68 ± 1.03 in G1 and 1.23 ± 1.03 in G2 (P <.05). At M3 (G1 = 9 patients, G2 = 6 patients), there is no significant difference between groups for epidemiologic and clinical data and for vestibuloocular reflex and dynamic visual acuity losses. The Oscillopsia Severity Questionnaire was 2.10 ± 0.63 in G1 and 1.24 ± 0.28 in G2 (P <.05). Conclusions: The spontaneous disabling sensation of oscillopsia after complete unilateral vestibular loss is well assessed by the Oscillopsia Severity Questionnaire but cannot be explained by objective vestibular tests assessing vestibuloocular reflex gain (vHIT) or dynamic visual acuity loss at D5 or M3. Further studies are needed to measure the sensation of oscillopsia under real-life conditions and to identify the factors responsible for its persistence. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

This study utilized cervical vestibular-evoked myogenic potentials tests (cVEMP) and ocular vestibular-evoked myogenic potentials tests (oVEMP) to investigate the vestibulocollic and vestibuloocular reflex arcs and to evaluate cerebellar and brainstem involvement) in essential tremor (ET). Eighteen cases with ET and 16 age- and gender-matched healthy control subjects (HCS) were included in the present study. Otoscopic and neurologic examinations were performed on all participants, and both cervical and ocular VEMP tests were performed. Pathological cVEMP results were increased in the ET group (64.7%) compared to the HCS (41,2%; p > 0.05). The latencies of P1 and N1 waves were shorter in the ET group than in HCS (p = 0.01 and p = 0.001). Pathological oVEMP responses were significantly higher in the ET group (72.2%) compared to the HCS (37.5%; p = 0.01). There was no statistically significant difference in oVEMP N1-P1 latencies between groups (p > 0.05). Because the ET group had high pathological responses to the oVEMP, but not the cVEMP, the upper brainstem pathways may be more affected by ET. [ABSTRACT FROM AUTHOR]

Abstract Background Fragile X syndrome (FXS), the most common inherited intellectual disability, is caused by the loss of expression of the Fragile X Messenger Ribonucleoprotein (FMRP). FMRP is an RNA-binding protein that negatively regulates the expression of many postsynaptic as well as presynaptic proteins involved in action potential properties, calcium homeostasis and neurotransmitter release. FXS patients and mice lacking FMRP suffer from multiple behavioral alterations, including deficits in motor learning for which there is currently no specific treatment. Methods We performed electron microscopy, whole-cell patch-clamp electrophysiology and behavioral experiments to characterise the synaptic mechanisms underlying the motor learning deficits observed in Fmr1KO mice and the therapeutic potential of positive allosteric modulator of mGluR4. Results We found that enhanced synaptic vesicle docking of cerebellar parallel fiber to Purkinje cell Fmr1KO synapses was associated with enhanced asynchronous release, which not only prevents further potentiation, but it also compromises presynaptic parallel fiber long-term potentiation (PF-LTP) mediated by β adrenergic receptors. A reduction in extracellular Ca2+ concentration restored the readily releasable pool (RRP) size, basal synaptic transmission, β adrenergic receptor-mediated potentiation, and PF-LTP. Interestingly, VU 0155041, a selective positive allosteric modulator of mGluR4, also restored both the RRP size and PF-LTP in mice of either sex. Moreover, when injected into Fmr1KO male mice, VU 0155041 improved motor learning in skilled reaching, classical eyeblink conditioning and vestibuloocular reflex (VOR) tests, as well as the social behavior alterations of these mice. Limitations We cannot rule out that the activation of mGluR4s via systemic administration of VU0155041 can also affect other brain regions. Further studies are needed to stablish the effect of a specific activation of mGluR4 in cerebellar granule cells. Conclusions Our study shows that an increase in synaptic vesicles, SV, docking may cause the loss of PF-LTP and motor learning and social deficits of Fmr1KO mice and that the reversal of these changes by pharmacological activation of mGluR4 may offer therapeutic relief for motor learning and social deficits in FXS.

Introduction: The video head impulse test (vHIT) evaluates the vestibulo-ocular reflex (VOR). It's usually recorded from only one eye. Newer vHIT devices allow a binocular quantification of the VOR. Purpose (Aim): To investigate the advantages of simultaneously recorded binocular vHIT (bvHIT) to detect the differences between the VOR gains of the adducting and the abducting eye, to define the most precise VOR measure, and to assess gaze dys/conjugacy. We aimed to establish normative values for bvHIT adducting/abducting eye VOR gains and to introduce the VOR dysconjugacy ratio (vorDR) between adducting and abducting eyes for bvHIT. Methods: We enrolled 44 healthy adult participants in a cross-sectional, prospective study using a repeated-measures design to assess test-retest reliability. A binocular EyeSeeCam Sci 2 device was used to simultaneously record bvHIT from both eyes during impulsive head stimulation in the horizontal plane. Results: Pooled bvHIT retest gains of the adducting eye significantly exceeded those of the abducting eye (mean (SD): 1.08 (SD = 0.06), 0.95 (SD = 0.06), respectively). Both adduction and abduction gains showed similar variability, suggesting comparable precision and therefore equal suitability for VOR asymmetry assessment. The pooled vorDR here introduced to bvHIT was 1.13 (SD = 0.05). The test-retest repeatability coefficient was 0.06. Conclusion: Our study provides normative values reflecting the conjugacy of eye movement responses to horizontal bvHIT in healthy participants. The results were similar to a previous study using the gold-standard scleral search coil, which also reported greater VOR gains in the adducting than in the abducting eye. In analogy to the analysis of saccade conjugacy, we propose the use of a novel bvHIT dysconjugacy ratio to assess dys/conjugacy of VOR-induced eye movements. In addition, to accurately assess VOR asymmetry, and to avoid directional gain preponderance between adduction and abduction VOR-induced eye movements leading to monocular vHIT bias, we recommend using a binocular ductional VOR asymmetry index that compares the VOR gains of only the abduction or only the adduction movements of both eyes. [ABSTRACT FROM AUTHOR]

Objectives: The neurotropic and neuroinvasive properties of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been described. It remains unknown how SARS-CoV-2 affects the audiovestibular system when it causes mild or severe disease. In this study, the sequelae effect of SARS-CoV-2 on the audiovestibular systems of different patient groups was investigated using objective and subjective test batteries. Methods: In this present study, we evaluated vestibulocochlear functions of patients who previously had Coronavirus Disease-2019 (COVID-19) with pure tone audiometry, ocular vestibular-evoked myogenic potential (o-VEMP), and cervical vestibular-evoked myogenic potential (c-VEMP) tests to identify possible sequelae by comparing them with the control group. Results: We found that the amplitude of p13-n23 was lower in both groups of patients than in the control group (p < 0.001). In the results of the left ear c-VEMP, the amplitude of p13-n23 was statistically different between the outpatient, inpatient, and control groups. The amplitude of p13-n23 was lower in both groups of patients than in the control group (p < 0.001). In the evaluation of the o-VEMP in the left ear, we observed a statistically significant difference in the latency of n10 (p = 0.006) and the amplitude of n10-p15 (p < 0.001) between the groups. The n10 latency was prolonged in both groups of patients compared to the control group and there was no statistically significant difference between groups of patients. Furthermore, the amplitude of n10-p15 was lower in both groups of patients compared to the control group and there were no statistically demonstrable differences between the groups of patients. Conclusions: In conclusion, our results suggest that SARS-CoV-2 may affect the vestibulocochlear system. But we could not find a direct relationship according to the severity of the disease. [ABSTRACT FROM AUTHOR]

Background: Fragile X syndrome (FXS), the most common inherited intellectual disability, is caused by the loss of expression of the Fragile X Messenger Ribonucleoprotein (FMRP). FMRP is an RNA-binding protein that negatively regulates the expression of many postsynaptic as well as presynaptic proteins involved in action potential properties, calcium homeostasis and neurotransmitter release. FXS patients and mice lacking FMRP suffer from multiple behavioral alterations, including deficits in motor learning for which there is currently no specific treatment. Methods: We performed electron microscopy, whole-cell patch-clamp electrophysiology and behavioral experiments to characterise the synaptic mechanisms underlying the motor learning deficits observed in Fmr1KO mice and the therapeutic potential of positive allosteric modulator of mGluR4. Results: We found that enhanced synaptic vesicle docking of cerebellar parallel fiber to Purkinje cell Fmr1KO synapses was associated with enhanced asynchronous release, which not only prevents further potentiation, but it also compromises presynaptic parallel fiber long-term potentiation (PF-LTP) mediated by β adrenergic receptors. A reduction in extracellular Ca2+ concentration restored the readily releasable pool (RRP) size, basal synaptic transmission, β adrenergic receptor-mediated potentiation, and PF-LTP. Interestingly, VU 0155041, a selective positive allosteric modulator of mGluR4, also restored both the RRP size and PF-LTP in mice of either sex. Moreover, when injected into Fmr1KO male mice, VU 0155041 improved motor learning in skilled reaching, classical eyeblink conditioning and vestibuloocular reflex (VOR) tests, as well as the social behavior alterations of these mice. Limitations: We cannot rule out that the activation of mGluR4s via systemic administration of VU0155041 can also affect other brain regions. Further studies are needed to stablish the effect of a specific activation of mGluR4 in cerebellar granule cells. Conclusions: Our study shows that an increase in synaptic vesicles, SV, docking may cause the loss of PF-LTP and motor learning and social deficits of Fmr1KO mice and that the reversal of these changes by pharmacological activation of mGluR4 may offer therapeutic relief for motor learning and social deficits in FXS. [ABSTRACT FROM AUTHOR]

Featured Application: This study protocol will promote efficient sensory reweighting and the integration of postural control, and will modify vestibular and motor responses. The training will be used as a rehabilitation protocol for neurological populations who have sensory integration issues, including those with mild traumatic brain injuries, strokes, and multiple sclerosis. Postural instability is a common symptom of vestibular dysfunction due to an insult to the vestibular system. Vestibular rehabilitation is effective in decreasing dizziness and visual symptoms, and improving postural control through several mechanisms, including sensory reweighting. As part of the sensory reweighting mechanisms, vestibular activation training with headshake activities influences vestibular reflexes. However, combining challenging vestibular and postural tasks to facilitate more effective rehabilitation outcomes is underutilized. Our research goal is to develop a virtual reality vestibular rehabilitation method for vestibular-postural control in neurological populations with vestibular and/or sensorimotor control impairment. The NeuroCom® SMART Balance Master (Natus Medical Inc., Pleasanton, CA, USA), which was used in a prior study, is expensive and bulky. Hence, a novel study protocol is established in this paper with the detailed objectives and pre-/post-intervention data analysis pipeline (ANOVA, t-test, post hoc analysis, etc.) involving modern off-the-shelf sensors and custom instrumentation (electromyography, electrooculography, video head impulse testing, force plates, and virtual reality headsets). It is expected that the training will significantly decrease vestibuloocular reflex gains and eye movement variability, as well as reweight the somatosensory ratio, finetune postural muscle activation, and consequently improve postural flexibility and produce a faster automatic postural response. The findings may have implications for the future development of vestibular rehabilitation protocols. [ABSTRACT FROM AUTHOR]

Spinocerebellar Ataxia Type 6 (SCA6) is a mid-life onset neurodegenerative disease characterized by progressive ataxia, dysarthria, and eye movement impairment. This autosomal dominant disease is caused by the expansion of a CAG repeat tract in the CACNA1A gene that encodes the α1A subunit of the P/Q type voltage-gated Ca2+ channel. Mouse models of SCA6 demonstrate impaired locomotive function and reduced firing precision of cerebellar Purkinje in the anterior vermis. Here, to further assess deficits in other cerebellar-dependent behaviors, we characterized the oculomotor phenotype of a knock-in mouse model with hyper-expanded polyQ repeats (SCA684Q). We found a reduction in the efficacy of the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) in SCA6 mutant mice, without a change in phase, compared to their litter-matched controls. Additionally, VOR motor learning was significantly impaired in SCA684Q mice. Given that the floccular lobe of the cerebellum plays a vital role in the generation of OKR and VOR calibration and motor learning, we investigated the firing behavior and morphology of floccular cerebellar Purkinje cells. Overall, we found a reduction in the firing precision of floccular lobe Purkinje cells but no morphological difference between SCA684Q and wild-type mice. Taken together, our findings establish that gaze stabilization and motor learning are impaired in SCA684Q mice and suggest that altered cerebellar output contributes to these deficits. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate gain and refixation saccades (covert and overt) using a video head impulse test (vHIT) in the horizontal and vertical planes in patients after the onset of unilateral acute vestibular neuritis (AVN). Thirty-five patients were examined in the acute stage of AVN and at follow-up (range, 6–30 months); a control group of 32 healthy subjects also participated. At onset, the mean gain was significantly lower on the affected side in all of the semi-circular canal planes, mainly in the horizontal canal plane, and saccades (covert and overt) were more prevalent in the horizontal compared to the vertical canal planes. Multi-canal affection occurred more frequently (80% for gain, 71% for saccades) than isolated canal affection. At follow-up, which ranged from 6 to 30 months, the gain was recovered in all of the canals (anterior in 50%, horizontal in 42.8%, and posterior canal in 41.1% of cases), while covert and overt saccades were reduced in the horizontal and vertical planes. However, covert saccades were still recorded in a greater proportion (69%) than overt saccades (57%) in the horizontal plane and at a lower rate in the vertical planes. The compensatory mechanisms after AVN mainly involve the horizontal canal, as the refixation saccades—especially covert ones—were more frequently recorded in the horizontal than vertical canals. [ABSTRACT FROM AUTHOR]

Postural instability is a common symptom of vestibular dysfunction due to an insult to the vestibular system. Vestibular rehabilitation is effective in decreasing dizziness and visual symptoms, and improving postural control through several mechanisms, including sensory reweighting. As part of the sensory reweighting mechanisms, vestibular activation training with headshake activities influences vestibular reflexes. However, combining challenging vestibular and postural tasks to facilitate more effective rehabilitation outcomes is underutilized. Our research goal is to develop a virtual reality vestibular rehabilitation method for vestibular-postural control in neurological populations with vestibular and/or sensorimotor control impairment. The NeuroCom® SMART Balance Master (Natus Medical Inc., Pleasanton, CA, USA), which was used in a prior study, is expensive and bulky. Hence, a novel study protocol is established in this paper with the detailed objectives and pre-/post-intervention data analysis pipeline (ANOVA, t-test, post hoc analysis, etc.) involving modern off-the-shelf sensors and custom instrumentation (electromyography, electrooculography, video head impulse testing, force plates, and virtual reality headsets). It is expected that the training will significantly decrease vestibuloocular reflex gains and eye movement variability, as well as reweight the somatosensory ratio, finetune postural muscle activation, and consequently improve postural flexibility and produce a faster automatic postural response. The findings may have implications for the future development of vestibular rehabilitation protocols.

BACKGROUND: The gain (eye-velocity/head-velocity) of the angular vestibuloocular reflex (aVOR) during head impulses can be increased while viewing near-targets and when exposed to unilateral, incremental retinal image velocity error signals. It is not clear however, whether the tonic or phasic vestibular pathways mediate these gain increases. OBJECTIVE: Determine whether a shared pathway is responsible for gain enhancement between vergence and adaptation of aVOR gain in patients with unilateral vestibular hypofunction (UVH). MATERIAL AND METHODS: 20 patients with UVH were examined for change in aVOR gain during a vergence task and after 15-minutes of ipsilesional incremental VOR adaptation (uIVA) using StableEyes (a device that controls a laser target as a function of head velocity) during horizontal passive head impulses. A 5 % aVOR gain increase was defined as the threshold for significant change. RESULTS: 11/20 patients had >5% vergence-mediated gain increase during ipsi-lesional impulses. For uIVA, 10/20 patients had >5% ipsi-lesional gain increase. There was no correlation between the vergence-mediated gain increase and gain increase after uIVA training. CONCLUSION: Vergence-enhanced and uIVA training gain increases are mediated by separate mechanisms and/or vestibular pathways (tonic/phasic). The ability to increase the aVOR gain during vergence is not prognostic for successful adaptation training. [ABSTRACT FROM AUTHOR]

Throughout Bernard Cohen's active career at Mount Sinai that lasted over a half century, he was involved in research on vestibular control of the oculomotor, body postural, and autonomic systems in animals and humans, contributing to our understanding of such maladies as motion sickness, mal de débarquement syndrome, and orthostatic syncope. This review is an attempt to trace and connect Cohen's varied research interests and his approaches to them. His influence was vast. His scientific contributions will continue to drive research directions for many years to come.

Throughout Bernard Cohen's active career at Mount Sinai that lasted over a half century, he was involved in research on vestibular control of the oculomotor, body postural, and autonomic systems in animals and humans, contributing to our understanding of such maladies as motion sickness, mal de débarquement syndrome, and orthostatic syncope. This review is an attempt to trace and connect Cohen's varied research interests and his approaches to them. His influence was vast. His scientific contributions will continue to drive research directions for many years to come. [ABSTRACT FROM AUTHOR]

The study objective was to understand how the contralesional labyrinth contributes to gaze and gait stability after unilateral vestibular deafferentation (UVD). Head impulse testing (vHIT) was completed in 37 individuals [22 women (59%); age 52.13 ± 11.59 yr, mean ± SD] with UVD from vestibular schwannoma resection. Compensatory saccades (CS) and vestibulo-ocular reflex (VOR) gain were analyzed for both ipsilesional and contralesional impulses. Gait speed (10-m walk test) and endurance (2-min walk test) were collected for 35 individuals. CS were recruited during contralesional head rotation regardless of VOR gain on either the ipsilesional [ρ = 0.21 (-0.14, 0.57); Spearman rank (95% confidence interval)] or contralesional side [ρ = -0.04 (-0.42, 0.35)]. Additionally, the latency of these CS (151.19 ± 52.41 ms) was similar to that of CS generated during ipsilesional rotation (165.65 ± 21.62 ms; P = 0.159). CS recruited during ipsilesional vHIT were of a higher velocity (P < 0.001) and greater frequency (P < 0.001) compared with contralesional CS. VOR gain asymmetry was significantly correlated with gait speed [ρ = -0.37 (-0.73, -0.01)], yet individual VOR gain was not correlated [ipsilesional: ρ = 0.17 (-0.20, 0.55); contralesional: ρ = -0.18 (-0.52, 0.15)]. Our data reveal CS are recruited at similar latencies without correlation to VOR gain or direction of head rotation, and that the central integration of ipsilesional and contralesional vestibular afference correlates with gait. Together, our data suggest the brain considers vestibular afference from both sides when generating related behavioral output after UVD.NEW & NOTEWORTHY After unilateral vestibular deafferentation, compensatory saccades (CS) have similar latencies regardless of the direction of head rotation, and those CS generated during contralesional head rotation are unrelated to extent of vestibular loss. Additionally, the extent of asymmetry in residual vestibular function, not the extent of vestibular loss, correlates with gait speed. Our data suggest a common mechanism is responsible for the generation of CS and restoration of gait speed in vestibular compensation. [ABSTRACT FROM AUTHOR]

Vestibular evoked myogenic potentials (VEMPs) are now widely used for the noninvasive assessment of vestibular function and diagnosis in humans. This review focuses on the origin, properties, and mechanisms of cervical VEMPs and ocular VEMPs; how these reflexes relate to reports of vestibular projections to brain stem and cervical targets; and the physiological role of (otolithic) cervical and ocular reflexes. The evidence suggests that both VEMPs are likely to represent the effects of excitation of irregularly firing otolith afferents. While the air-conducted cervical VEMP appears to mainly arise from excitation of saccular receptors, the ocular VEMP evoked by bone-conducted stimulation, including impulsive bone-conducted stimuli, mainly arises from utricular afferents. The surface responses are generated by brief changes in motor unit firing. The effects that have been demonstrated are likely to represent otolith-dependent vestibulocollic and vestibulo-ocular reflexes, both linear and torsional. These observations add to previous reports of short latency otolith projections to the target muscles in the neck (sternocleidomastoid and splenius) and extraocular muscles (the inferior oblique). New insights have been provided by the investigation and application of these techniques. [ABSTRACT FROM AUTHOR]

Diagnostics of balance disorders has undergone great changes over the last decades. From subjective clinical observation of vestibulospinal and vestibuloocular manifestations, the objective measurement of these manifestations by new methods and devices (stabilometry, videonystagmography, etc.) is used at the present time. The recent tendencies for objectivization of balance disorders, recording the results of individual examinations with subsequent comparison of the results and observation of the development of the disorder in time prevail. The Video Head Impulse Test (VHIT) is the most modern method which complements examination of the balance apparatus. The method enables to examine the complex of all semicircular canals of inner ear, which participate in keeping the balance. The activity of these canals if provided by a phylogenetically old three neuron pathway called vestibuloocular reflex (VOR). The main pathological finding of vHIT examination is the correction saccade of the eye as a compensation mechanism of the functional disorder of VOR. A high-speed camera is capable of recording the most minute and fastest saccade motions of the eye. The paper was intended to summarize available information abiuyt this new and objective method for examination of vestibular apparatus, which has been used in the Czech Republic since 2014. [ABSTRACT FROM AUTHOR]

The role of the otoliths in mammals in the angular vestibuloocular reflex (VOR) has been difficult to determine because there is no surgical technique that can reliably ablate them without damaging the semicircular canals. The Otopetrin1 (Otop1) mouse lacks functioning otoliths because of failure to develop otoconia but seems to have otherwise normal peripheral anatomy and neural circuitry. By using these animals we sought to determine the role of the otoliths in angular VOR baseline function and adaptation. In six Otop1 mice and six control littermates we measured baseline ocular countertilt about the three primary axes in head coordinates; baseline horizontal (rotation about an Earth-vertical axis parallel to the dorsal-ventral axis) and vertical (rotation about an Earth-vertical axis parallel to the interaural axis) sinusoidal (0.2-10 Hz, 20-100°/s) VOR gain (= eye/head velocity); and the horizontal and vertical VOR after gain-increase (1.5×) and gain-decrease (0.5×) adaptation training. Countertilt responses were significantly reduced in Otop1 mice. Baseline horizontal and vertical VOR gains were similar between mouse types, and so was horizontal VOR adaptation. For control mice, vertical VOR adaptation was evident when the testing context, left ear down (LED) or right ear down (RED), was the same as the training context (LED or RED). For Otop1 mice, VOR adaptation was evident regardless of context. Our results suggest that the otolith translational signal does not contribute to the baseline angular VOR, probably because the mouse VOR is highly compensatory, and does not alter the magnitude of adaptation. However, we show that the otoliths are important for gravity context-specific angular VOR adaptation. NEW & NOTEWORTHY This is the first study examining the role of the otoliths (defined here as the utricle and saccule) in adaptation of the angular vestibuloocular reflex (VOR) in an animal model in which the otoliths are reliably inactivated and the semicircular canals preserved. We show that they do not contribute to adaptation of the normal angular VOR. However, the otoliths provide the main cue for gravity context-specific VOR adaptation. [ABSTRACT FROM AUTHOR]

Galvanic vestibular stimulation (GVS) plays an important role in the quest to understand sensory signal processing in the vestibular system under normal and pathological conditions. It has become a highly relevant tool to probe neuronal computations and to assist in the differentiation and treatment of vestibular syndromes. Following its accidental discovery, GVS became a diagnostic tool that generates eye movements in the absence of head/body motion. With the possibility to record extracellular and intracellular spikes, GVS became an indispensable method to activate or block the discharge in vestibular nerve fibers by cathodal and anodal currents, respectively. Bernie Cohen, in his attempt to decipher vestibular signal processing, has used this method in a number of hallmark studies that have added to our present knowledge, such as the link between selective electrical stimulation of semicircular canal nerves and the generation of directionally corresponding eye movements. His achievements paved the way for other major milestones including the differential recruitment order of vestibular fibers for cathodal and anodal currents, pronounced discharge adaptation of irregularly firing afferents, potential activation of hair cells, and fiber type-specific activation of central circuits. Previous disputes about the structural substrate for GVS are resolved by integrating knowledge of ion channel-related response dynamics of afferents, fiber type-specific innervation patterns, and central convergence and integration of semicircular canal and otolith signals. On the basis of solid knowledge of the methodology, specific waveforms of GVS are currently used in clinical diagnosis and patient treatment, such as vestibular implants and noisy galvanic stimulation. [ABSTRACT FROM AUTHOR]

Computational capability and connectivity are key elements for understanding how central vestibular neurons contribute to gaze-stabilizing eye movements during self-motion. In the well-characterized and segmentally distributed hindbrain oculomotor network of goldfish, we determined afferent and efferent connections along with discharge patterns of descending octaval nucleus (DO) neurons during different eye motions. Based on activity correlated with horizontal eye and head movements, DO neurons were categorized into two complementary groups that either increased discharge during both contraversive (type II) eye (e) and ipsiversive (type I) head (h) movements (eIhII) or vice versa (eIhII). Matching time courses of slow-phase eye velocity and corresponding firing rates during prolonged visual and head rotation suggested direct causality in generating extraocular motor commands. The axons of the dominant eIhII subgroup projected either ipsi- or contralaterally and terminated in the abducens nucleus, Area II, and Area I with additional recurrent collaterals of ipsilaterally projecting neurons within the parent nucleus. Distinct feedforward commissural pathways between bilateral DO neurons likely contribute to the generation of eye velocity signals in eIhII cells. The shared contribution of DO and Area II neurons to eye velocity storage likely represents an ancestral condition in goldfish that is clearly at variance with the task separation between mammalian medial vestibular and prepositus hypoglossi neurons. This difference in signal processing between fish and mammals might correlate with a larger repertoire of visuo-vestibular-driven eye movements in the latter species that potentially required a shift in sensitivity and connectivity within the hindbrain-cerebello-oculomotor network. NEW & NOTEWORTHY We describe the structure and function of neurons within the goldfish descending octaval nucleus. Our findings indicate that eye and head velocity signals are processed by vestibular and Area II velocity storage integrator circuitries whereas the velocity-to-position Area I neural integrator generates eye position solely. This ancestral condition differs from that of mammals, in which vestibular neurons generally lack eye position signals that are processed and stored within the nucleus prepositus hypoglossi. [ABSTRACT FROM AUTHOR]

Abstract Introduction Unilateral labyrinthectomy and intra-tympanic gentamycin have been employed in the treatment of Ménière's disease, but the efficacy of these techniques has not been well established. Objective The objective of this study is to measure the time course of recovery from a unilateral labyrinthectomy either after ipsilateral topical treatment with gentamicin to the inner ear or without the previous insult. Methods Twenty-nine adult Mongolian gerbils were randomized into two experimental groups. Group 1 (n = 17) received a right ear gentamicin drug-induced lesion by unilateral labyrinthectomy (UL). Group 2 (n = 12) only received a right unilateral labyrinthectomy lesion. We measured the horizontal vestibulo-ocular responses in gerbils before and after the lesion. The gerbils received an angular acceleration stimulus and their eye movements were recorded. Results The gentamicin lesion resulted in a quicker recovery. Experimental groups underwent a similar time course of recovery. Statistical analysis showed no significant difference between the two groups. Both groups displayed adaptation to the lesion by day 21, but long-term compensation did not completely revert to the original pre-lesion state. Conclusions In a lesion requiring both static and dynamic compensation as in UL, the need for a static compensation may alter pre-existing compensation from a previous dynamic insult and require a new compensation. A previous lesion and adaptation is not preserved for a second lesion and the subject has to re-compensate. Therefore, surgical treatment in Meniere's disease such as UL can be considered without prior gentamicin treatment. Static and dynamic compensations do not appear to be as independent as previous studies have suggested.

The increased use of close range explosives has led to a higher incidence of exposure to blast-related head trauma. Exposure to primary blast waves is a significant cause of morbidity and mortality. Active service members and civilians who have experienced blast waves report high rates of vestibular dysfunction, such as vertigo, oscillopsia, imbalance, and dizziness. Accumulating evidence suggests that exposure to blast-wave trauma produces damage to both the peripheral and central vestibular system; similar to previous findings that blast exposure results in damage to auditory receptors. In this study, mice were exposed to a 63 kPa peak blast-wave over pressure and were examined for vestibular receptor damage as well as behavioral assays to identify vestibular dysfunction. We observed perforations to the tympanic membrane in all blast animals. We also observed significant loss of stereocilia on hair cells in the cristae and macule up to 1 month after blast-wave exposure; damage that is likely permanent. Significant reductions in the ability to perform the righting reflex and balance on a rotating rod that lasted several weeks after blast exposure were prominent behavioral effects. We also observed a significant reduction in horizontal vestibuloocular reflex gain and phase lags in the eye movement responses that lasted many weeks following a single blast exposure event. OKN responses were absent immediately following blast exposure, but began to return after several weeks’ recovery. These results show that blast-wave exposure can lead to peripheral vestibular damage (possibly central deficits as well) and provides some insight into causes of vestibular dysfunction in blast-trauma victims.

Highlights • Brainstem neural circuits for horizontal and vertical saccades. • Reciprocity between upward and its contralateral downward saccade systems. • Similarity of well-known vestibuloocular and saccade generating pathways. • The saccade system and the VOR system share common semicircular canal coordinate. • Commissural inhibition of two superior colliculi supports canal coordinate hypothesis. Abstract Sensory signals for eye movements (visual and vestibular) are initially coded in different frames of reference but finally translated into common coordinates, and share the same final common pathway, namely the same population of extraocular motoneurons. From clinical studies in humans and lesion studies in animals, it is generally accepted that voluntary saccadic eye movements are organized in horizontal and vertical Cartesian coordinates. However, this issue is not settled yet, because neural circuits for vertical saccades remain unidentified. We recently determined brainstem neural circuits from the superior colliculus to ocular motoneurons for horizontal and vertical saccades with combined electrophysiological and neuroanatomical techniques. Comparing well-known vestibuloocular pathways with our findings of commissural excitation and inhibition between both superior colliculi, we proposed that the saccade system uses the same frame of reference as the vestibuloocular system, common semicircular canal coordinate. This proposal is mainly based on marked similarities (1) between output neural circuitry from one superior colliculus to extraocular motoneurons and that from a respective canal to its innervating extraocular motoneurons, (2) of patterns of commissural reciprocal inhibitions between upward saccade system on one side and downward system on the other, and between anterior canal system on one side and posterior canal system on the other, and (3) between the neural circuits of saccade and quick phase of vestibular nystagmus sharing brainstem burst neurons. In support of the proposal, commissural excitation of the superior colliculi may help to maintain Listing's law in saccades in spite of using semicircular canal coordinate. [ABSTRACT FROM AUTHOR]

Cervical vertigo has long been a controversial entity, which is general ly accepted in practice by the medical com munity. We present the sum mary of contemporary knowledge of the scientific bio graphy of cervical vertigo, pos sible etiology, dia gnosis and treatment. This disorder is overdia g - nosed and there is still no laboratory or clinical test to confirm the dia gnosis, while none of the pos sible theories provide fully convinc ing evidence of a cervical mechanism. Appropriate management is difficult and mostly empirical. [ABSTRACT FROM AUTHOR]

The increased use of close range explosives has led to a higher incidence of exposure to blast-related head trauma. Exposure to primary blast waves is a significant cause of morbidity and mortality. Active service members and civilians who have experienced blast waves report high rates of vestibular dysfunction, such as vertigo, oscillopsia, imbalance, and dizziness. Accumulating evidence suggests that exposure to blast-wave trauma produces damage to both the peripheral and central vestibular system; similar to previous findings that blast exposure results in damage to auditory receptors. In this study, mice were exposed to a 63 kPa peak blast-wave over pressure and were examined for vestibular receptor damage as well as behavioral assays to identify vestibular dysfunction. We observed perforations to the tympanic membrane in all blast animals. We also observed significant loss of stereocilia on hair cells in the cristae and macule up to 1 month after blast-wave exposure; damage that is likely permanent. Significant reductions in the ability to perform the righting reflex and balance on a rotating rod that lasted several weeks after blast exposure were prominent behavioral effects. We also observed a significant reduction in horizontal vestibuloocular reflex gain and phase lags in the eye movement responses that lasted many weeks following a single blast exposure event. OKN responses were absent immediately following blast exposure, but began to return after several weeks' recovery. These results show that blast-wave exposure can lead to peripheral vestibular damage (possibly central deficits as well) and provides some insight into causes of vestibular dysfunction in blast-trauma victims. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate whether it is possible to restore the highfrequency angular vestibulo-ocular reflex (aVOR) in patients suffering from a severe bilateral vestibulopathy (BV) and implanted with a vestibular implant prototype. Three patients (S1-3) participated in the study. They received a prototype vestibular implant with one to three electrode branches implanted in the proximity of the ampullary branches of the vestibular nerve. Five electrodes were available for electrical stimulation: one implanted in proximity of the left posterior ampullary nerve in S1, one in the left lateral and another one in the superior ampullary nerves in S2, and one in the right lateral and another one in the superior ampullary nerves in S3. The high-frequency aVOR was assessed using the video head impulse test (EyeSeeCam; EyeSeeTec, Munich, Germany), while motion-modulated electrical stimulation was delivered via one of the implanted vestibular electrodes at a time. aVOR gains were compared to control measurements obtained in the same patients when the device was not activated. In three out of the five tested electrodes the aVOR gain increased monotonically with increased stimulation strength when head impulses were delivered in the plane of the implanted canal. In these cases, gains ranging from 0.4 to values above 1 were measured. A "reversed" aVOR could also be generated when inversed stimulation paradigms were used. In most cases, the gain for excitatory head impulses was superior to that recorded for inhibitory head impulses, consistent with unilateral vestibular stimulation. Improvements of aVOR gain were generally accompanied by a concomitant decrease of corrective saccades, providing additional evidence of an effective aVOR. High inter-electrode and inter-subject variability were observed. These results, together with previous research, demonstrate that it is possible to restore the aVOR in a broad frequency range using motion-modulated electrical stimulation of the vestibular afferents. This provides additional encouraging evidence of the possibility of achieving a useful rehabilitation alternative for patients with BV in the near future. [ABSTRACT FROM AUTHOR]

Zusammenfassung Neurophysiologische Untersuchungen des Hirnstamms stellen auch in Zeiten der hochauflösenden Magnetresonanztomographie weiterhin einen wichtigen Bestandteil in der topographischen Diagnostik von Hirnstammläsionen dar. Während die vestibulär evozierten myogenen Potenziale (VEMP) in der Hals-Nasen-Ohren-Heilkunde einen festen Bestandteil in der neuro-otologischen Diagnostik des Gleichgewichtsorgans eingenommen haben, sind sie in der Neurologie bisher wenig verbreitet. Mit Hilfe der VEMP können unterschiedliche Reflexbögen des Hirnstamms, der vestibulocollische sowie der vestibulookuläre Reflex differenziert neurophysiologisch untersucht werden. Die aktuelle Arbeit soll einen Überblick über die Anatomie und Physiologie sowie die Methodik der VEMP geben. Darüber hinaus sollen die Einsatzmöglichkeiten und Bedeutung der VEMP in der Neurologie dargestellt werden. Summary Even in times of high-resolution magnetic resonance imaging, neurophysiological studies of the brainstem do still play a crucial role in the topographic diagnostic of brainstem pathology. Vestibular evoked myogenic potentials (VEMP) form an integral part of the neurootological examinations in order to establish the functional status of the otolith organs in otorhinolaryngology, whereas they are less established in neurology. By means of VEMP different reflex circuits of the brainstem, the vestibulocollic reflex and the vestibuloocular reflex can be investigated. The recent article gives an overview of the anatomy and physiology of the VEMP and its methodological approach. Furthermore, the characteristics and capabilities of the VEMP in neurological disorders are presented. [ABSTRACT FROM AUTHOR]

During swimming in the amphibian Xenopus laevis, efference copies of rhythmic locomotor commands produced by the spinal central pattern generator (CPG) can drive extraocular motor output appropriate for producing image-stabilizing eye movements to offset the disruptive effects of self-motion. During metamorphosis, X. laevis remodels its locomotor strategy from larval tail-based undulatory movements to bilaterally synchronous hindlimb kicking in the adult. This change in propulsive mode results in head/body motion with entirely different dynamics, necessitating a concomitant switch in compensatory ocular movements from conjugate left-right rotations to non-conjugate convergence during the linear forward acceleration produced during each kick cycle. Here, using semi-intact or isolated brainstem/spinal cord preparations at intermediate metamorphic stages, we monitored bilateral eye motion along with extraocular, spinal axial and limb motor nerve activity during episodes of spontaneous fictive swimming. Our results show a progressive transition in spinal efference copy control of extraocular motor output that remains adapted to offsetting visual disturbances during the combinatorial expression of bimodal propulsion when functional larval and adult locomotor systems co-exist within the same animal. In stages at metamorphic climax, spino-extraocular motor coupling, which previously derived from axial locomotor circuitry alone, can originate from both axial and de novo hindlimb CPGs, although the latter's influence becomes progressively more dominant and eventually exclusive as metamorphosis terminates with tail resorption. Thus, adaptive interactions between locomotor and extraocular motor circuitry allows CPG-driven efference copy signaling to continuously match the changing spatio-temporal requirements for visual image stabilization throughout the transitional period when one propulsive mechanism emerges and replaces another. [ABSTRACT FROM AUTHOR]

Introduction: Unilateral labyrinthectomy and intra-tympanic gentamycin have been employed in the treatment of Ménière's disease, but the efficacy of these techniques has not been well established. Objective: The objective of this study is to measure the time course of recovery from a unilateral labyrinthectomy either after ipsilateral topical treatment with gentamicin to the inner ear or without the previous insult. Methods: Twenty-nine adult Mongolian gerbils were randomized into two experimental groups. Group 1 (n = 17) received a right ear gentamicin drug-induced lesion by unilateral labyrinthectomy (UL). Group 2 (n = 12) only received a right unilateral labyrinthectomy lesion. We measured the horizontal vestibulo-ocular responses in gerbils before and after the lesion. The gerbils received an angular acceleration stimulus and their eye movements were recorded. Results: The gentamicin lesion resulted in a quicker recovery. Experimental groups underwent a similar time course of recovery. Statistical analysis showed no significant difference between the two groups. Both groups displayed adaptation to the lesion by day 21, but long-termcompensation did not completely revert to the original pre-lesion state. Conclusions: In a lesion requiring both static and dynamic compensation as in UL, the need for a static compensation may alter pre-existing compensation from a previous dynamic insult and require a new compensation. A previous lesion and adaptation is not preserved for a second lesion and the subject has to re-compensate. Therefore, surgical treatment in Meniere's disease such as UL can be considered without prior gentamicin treatment. Static and dynamic compensations do not appear to be as independent as previous studies have suggested. [ABSTRACT FROM AUTHOR]

It is still debated to what extent the vestibular deficits in Usher patients are due to either central vestibulocerebellar or peripheral vestibular problems. Here, we determined the origin of the vestibular symptoms in Usher 1B patients by subjecting them to compensatory eye movement tests and by investigating the shaker-1 mouse model, which is known to have the same mutation in the myosin-VIIa gene as Usher 1B patients. We show that myosin-VIIa is not expressed in the human or mouse cerebellum and that the vestibulocerebellum of both Usher 1B patients and shaker-1 mice is functionally intact in that the gain and phase values of their optokinetic reflex are normal. In addition, Usher 1B patients and shaker-1 mice do not show an angular vestibuloocular reflex even though eye movement responses evoked by electrical stimulation of the vestibular nerve appear intact. Finally, we show histological abnormalities in the vestibular hair cells of shaker-1 mice at the ultrastructural level, while the distribution of the primary vestibular afferents and the vestibular brainstem circuitries are unaffected. We conclude that the vestibular dysfunction of Usher 1B patients and shaker-1 mice is peripheral in origin.

Although anatomically well described, the functional role of the mammalian efferent vestibular system (EVS) remains unclear. Unlike in fish and reptiles, the mammalian EVS does not seem to play a role in modulation of primary afferent activity in anticipation of active head movements. However, it could play a role in modulating long-term mechanisms requiring plasticity such as vestibular adaptation. We measured the efficacy of vestibuloocular reflex (VOR) adaptation in α9-knockout mice. These mice carry a missense mutation of the gene encoding the 9 nicotinic acetylcholine receptor (nAChR) subunit. The α9 nAChR subunit is expressed in the vestibular and auditory periphery, and its loss of function could compromise peripheral input from the predominantly cholinergic EVS. We measured the VOR gain (eye velocity/head velocity) in 26 α9-knockout mice and 27 cba129 control mice. Mice were randomly assigned to one of three groups: gain-increase adaptation (1.5x), gain-decrease adaptation (0.5x), or no adaptation (baseline, 1x). After adaptation training (horizontal rotations at 0.5 Hz with peak velocity 20°/s), we measured the sinusoidal (0.2-10 Hz, 20-100°/s) and transient (1,500-6,000°/s²) VOR in complete darkness. 9- Knockout mice had significantly lower baseline gains compared with control mice. This difference increased with stimulus frequency (~5% <1 Hz to ~25% >1 Hz). Moreover, vestibular adaptation (difference in VOR gain of gain-increase and gain-decrease adaptation groups as % of gain increase) was significantly reduced in α9-knockout mice (17%) compared with control mice (53%), a reduction of ~70%. Our results show that the loss of α9 nAChRs moderately affects the VOR but severely affects VOR adaptation, suggesting that the EVS plays a crucial role in vestibular plasticity. [ABSTRACT FROM AUTHOR]

Bilateral vestibulopathy is a relatively widespread and at the same time rarely diagnosed cause of chronic postural instability. Numerous toxic factors, dysmetabolic, autoimmune and neurodegenerative processes can lead to this condition. The main clinical manifestations of bilateral vestibulopathy are balance disorders and visual disturbances (oscillopsia), which can significantly increase the risks of falls in such patients. In addition, cognitive and affective disorders, which also reduce the quality of life in patients with bilateral vestibulopathy, have been described and actively studied in recent years. The diagnosis of bilateral vestibulopathy is based on the results of a clinical neurovestibular study, including a dynamic visual acuity test and a Halmagyi test. A video head impulse test, a bithermal caloric test and a sinusoidal rotation test are used as instrumental methods confirming the dysfunction of the peripheral vestibular system. However, they are still not widespread in neurological practice. Treatment of bilateral vestibulopathy is reduced to vestibular rehabilitation. Encouraging results have been obtained in a number of studies using galvanic vestibular stimulation and the use of vestibular implants. In addition, cognitive rehabilitation methods are currently being developed, which presumably can also improve compensation for bilateral vestibular loss.

Mutation of the Cacna1a gene for the P/Q (CaV2.1) calcium channel invariably leads to cerebellar dysfunction. The dysfunction has been attributed to disrupted rhythmicity of cerebellar Purkinje cells, but the hypothesis remains unproven. If irregular firing rates cause cerebellar dysfunction, then the irregularity and behavioral deficits should covary in a series of mutant strains of escalating severity. We compared firing irregularity in floccular and anterior vermis Purkinje cells in the mildly affected rocker and moderately affected tottering Cacna1a mutants and normal C57BL/6 mice. We also measured the amplitude and timing of modulations of floccular Purkinje cell firing rate during the horizontal vestibuloocular reflex (VOR, 0.25-1 Hz) and the horizontal and vertical optokinetic reflex (OKR, 0.125-1 Hz). We recorded Purkinje cells selective for rotational stimulation about the vertical axis (VAPCs) and a horizontal axis (HAPCs). Irregularity scaled with behavioral deficit severity in the flocculus but failed to do so in the vermis, challenging the irregularity hypothesis. Mutant VAPCs exhibited unusually strong modulation during VOR and OKR, the response augmentation scaling with phenotypic severity. HAPCs exhibited increased OKR modulation but in tottering only. The data contradict prior claims that modulation amplitude is unaffected in tottering but support the idea that attenuated compensatory eye movements in Cacna1a mutants arise from defective transfer of Purkinje cell signals to downstream circuitry, rather than attenuated synaptic transmission within the cerebellar cortex. Shifts in the relative sizes of the VAPC and HAPC populations raise the possibility that Cacna1a mutations influence the development of floccular zone architecture. [ABSTRACT FROM AUTHOR]

The neuroactive peptide calcitonin-gene related peptide (CGRP) is known to act at efferent synapses and their targets in hair cell organs, including the cochlea and lateral line. CGRP is also expressed in vestibular efferent neurons as well as a number of central vestibular neurons. Although CGRP-null (-/-) mice demonstrate a significant reduction in cochlear nerve sound-evoked activity compared with wild-type mice, it is unknown whether and how the loss of CGRP influence vestibular system function. Vestibular function was assessed by quantifying the vestibulo-ocular reflex (VOR) in alert mice. The loss of CGRP in (-/-) mice was associated with a reduction of the VOR gain of 50% without a concomitant change in phase. Using immunohistochemistry, we confirmed that, although CGRP staining was absent in the vestibular end-organs of null (-/-) mice, cholinergic staining appeared normal, suggesting that the overall gross development of vestibular efferent innervation was unaltered. We further confirmed that the observed deficit in vestibular function of null (-/-) mice was not the result of nontargeted effects at the level of the extraocular motor neurons and/or their innervation of extraocular muscles. Analysis of the relationship between vestibular quick phase amplitude and peak velocity revealed that extraocular motor function was unchanged, and immunohistochemistry revealed no abnormalities in motor endplates. Together, our findings show that the neurotransmitter CGRP plays a key role in ensuring VOR efficacy. [ABSTRACT FROM AUTHOR]

A sound- and pressure-induced vestibuloocular reflex (VOR) has been described as vertical and torsional in superior canal dehiscence (SCD), and the rotational axes of induced VOR have been assumed to fit with the axis of the affected superior semicircular canal (SC). However, it has been difficult to characterize the pattern of vibration-induced VOR (ViVOR). We aimed to characterize the pattern of ViVOR by comparing the intensity and the axis of ViVOR with several clinical parameters of SCD. Ten symptomatic SCD patients were recruited. SCD size and location were measured on a reformatted image in the plane of the SC. Unilateral vibratory stimulation (100 Hz) was applied to the mastoid surface. ViVOR were recorded using 3D videooculography. The median 3D velocity of ViVOR was measured and the 3D vector trajectory plotted for reference against the axes of the human semicircular canals. A correlation between the magnitude of ViVOR and the size of SCD was evaluated. We also compared the location of SCD with the vertical-to-torsional component ratio of the ViVOR. ViVOR were present in 7 patients; 6 patients showed a substantial horizontal component in the excitatory direction in addition to strong torsional and weak vertical components. The computed rotational axes of ViVOR were located mostly between the axes of the ipsilateral SC and horizontal canal (HC) with a variable deviation to the axis of the ipsilateral posterior canal (PC). The magnitude of ViVOR was not related to the size of the SCD. The vertical-to-torsional component ratio of ViVOR tended to decline as the dehiscence was closer to the common crus. In SCD, mastoid vibration may stimulate the affected-side HC and PC as well as the SC. SCD can be suspected when excitatory horizontal torsional ViVOR direct to the side of the auditory symptoms. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract:The objective of this study was to compare the findings of the bedside head impulse test (HIT), passive head rotation gain, and caloric irrigation in patients with cerebellar ataxia (CA). In 16 patients with CA and bilaterally pathological bedside HIT, VOR gains were measured during HIT and passive head rotation by scleral search coil technique. Eight of the patients had pathologically reduced caloric responsiveness, while the other eight had normal caloric responses. Those with normal calorics showed a slightly reduced HIT gain (mean±SD: 0.73±0.15). In those with pathological calorics, gains 80ms and 100 ms after the HIT as well as the passive rotation VOR gains were significantly lower. The corrective saccade after head turn occurred earlier in patients with pathological calorics (111±62 ms after onset of the HIT) than in those with normal calorics. (191±17 ms, p=0.0064) We indentified two groups of patients with CA: those with an isolated moderate HIT deficit only, probably due to floccular dysfunction, and those with combined HIT, passive rotation and caloric deficit, probably due to a peripheral vestibular deficit. From a clinical point of view, these results show that the bedside HIT alone can be false positive for establishing a diagnosis of a bilateral peripheral vestibular deficit in patients with CA.

The mammalian oculomotor nucleus receives a strong -aminobutyric acid (GABA)ergic synaptic input, whereas such projections have rarely been reported in fish. In order to determine whether this synaptic organization is preserved across vertebrates, we investigated the GABAergic projections to the oculomotor nucleus in the goldfish by combining retrograde transport of biotin dextran amine, injected into the antidromically identified oculomotor nucleus, and GABA immunohistochemistry. The main source of GABAergic afferents to the oculomotor nucleus was the ipsilateral anterior octaval nucleus, with only a few, if any, GABAergic neurons being located in the contralateral tangential and descending nuclei of the octaval column. In mammals there is a nearly exclusive ipsilateral projection from vestibular neurons to the oculomotor nucleus via GABAergic inhibitory inputs; thus, the vestibulooculomotor GABAergic circuitry follows a plan that appears to be shared throughout the vertebrate phylogeny. The second major source of GABAergic projections was the rhombencephalic reticular formation, primarily from the medial area but, to a lesser extent, from the inferior area. A few GABAergic oculomotor projecting neurons were also observed in the ipsilateral nucleus of the medial longitudinal fasciculus. The GABAergic projections from neurons located in both the reticular formation surrounding the abducens nucleus and the nucleus of the medial reticular formation have primarily been related to the control of saccadic eye movements. Finally, all retrogradely labeled internuclear neurons of the abducens nucleus, and neurons in the cerebellum (close to the caudal lobe), were negative for GABA. These data suggest that the vestibuloocular and saccadic inhibitory GABAergic systems appear early in vertebrate phylogeny to modulate the firing properties of the oculomotor nucleus motoneurons.

INTRODUCTION: A sense of proper sensory processing of head motion and the coordination of visual and postural movements to maintain equilibrium is critical to everyday function. The vestibular system is an intricate organization that involves multiple levels of sensory processing to achieve this goal. PURPOSE: This chapter provides an overview of the anatomical structures and pathways of the vestibular system. SUMMARY: The five major vestibular structures are located in the inner ear and include: the utricle, the saccule, and the lateral, superior, and posterior semicircular canals. Hair cells on the neuroepithelium of the peripheral vestibular organs carry sensory impulses to primary processing centers in the brainstem and the cerebellum. These areas send input via ascending and descending projections to coordinate vital reflexes, such as the vestibuloocular reflex and the vestibulospinal reflex, which allow for the proper orientation of the eyes and body in response to head motion. Specific connections regarding higher level cortical vestibular structures are poorly understood. CONCLUSION: Vestibular centers in the brainstem, cerebellum, and cerebral cortex function to integrate sensory information from the peripheral vestibular organs, visual system, and proprioceptive system to allow for proper balance and orientation of the body in its environment. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare the findings of the bedside head-impulse test (HIT), passive head rotation gain, and caloric irrigation in patients with cerebellar ataxia (CA). In 16 patients with CA and bilaterally pathological bedside HIT, vestibuloocular reflex (VOR) gains were measured during HIT and passive head rotation by scleral search coil technique. Eight of the patients had pathologically reduced caloric responsiveness, while the other eight had normal caloric responses.Those with normal calorics showed a slightly reduced HIT gain (mean±SD: 0.73±0.15). In those with pathological calorics, gains 80 and 100ms after the HIT as well as the passive rotation VOR gains were significantly lower. The corrective saccade after head turn occurred earlier in patients with pathological calorics (111±62ms after onset of the HIT) than in those with normal calorics (191±17 ms, p =0.0064).We identified two groups of patients with CA: those with an isolated moderate HIT deficit only, probably due to floccular dysfunction, and those with combined HIT, passive rotation, and caloric deficit, probably due to a peripheral vestibular deficit. From a clinical point of view, these results show that the bedside HIT alone can be false-positive for establishing a diagnosis of a bilateral peripheral vestibular deficit in patients with CA. [ABSTRACT FROM AUTHOR]

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The aim of the experiments was to use virtual reality stimulation to reweight visuovestibular sensory inputs in order to improve balance performances in ice dancers. In five athletes (three women and two men, mean age 22.5 years) from the Italian National Team rotational ocular reflexes were studied, both in the dark (rotational vestibuloocular reflex r-VOR) and in the light (rotational visuovestibuloocular reflex, r-VVOR). The athletes were rotated on a motorized chair and ocular reflexes were recorded by electrooculography. Skaters trained once a day for 20 days to maintain a one-leg stance on an oscillating platform during semi-immersion in a projected video acquired by a digital photocamera fixed to their head when they were skating. r-VOR gain increased significantly ( p<0.001) in the three athletes with the lowest pretraining values. The virtual reality technique adopted is also as easy to perform in the usual training context, can be proposed as a low-cost well-tolerated approach also for specific training of patients with poor balance at least when oculomotor performance has to be optimized. [ABSTRACT FROM AUTHOR]

A proprioceptive representation of eye position exists in area 3a of primate somatosensory cortex (Wang X, Zhang M, Cohen IS, Goldberg ME. Nat Neurosci 10: 640-646, 2007). This eye position signal is consistent with a fusimotor response (Taylor A, Durbaba R, Ellaway PH, Rawlinson S. J Physiol 571: 711-723, 2006) and has two components during a visually guided saccade task: a short-latency phasic response followed by a tonic response. While the early phasic response can be excitatory or inhibitory, it does not accurately reflect the eye's orbital position. The late tonic response appears to carry the proprioceptive eye position signal, but it is not clear when this component emerges and whether the onset of this signal is reliable. To test the temporal dynamics of the tonic proprioceptive signal, we used an oculomotor smooth pursuit task in which saccadic eye movements and phasic proprioceptive responses are suppressed. Our results show that the tonic proprioceptive eye position signal consistently lags the actual eye position in the orbit by 60 ms under a variety of eye movement conditions. To confirm the proprioceptive nature of this signal, we also studied the responses of neurons in a vestibuloocular reflex (VOR) task in which the direction of gaze was held constant; response profiles and delay times were similar in this task, suggesting that this signal does not represent angle of gaze and does not receive visual or vestibular inputs. The length of the delay suggests that the proprioceptive eye position signal is unlikely to be used for online visual processing for action, although it could be used to calibrate an efference copy signal. [ABSTRACT FROM AUTHOR]

Experimental animal models have suggested that the modulation of the amplitude and direction of vestibular reflexes are important functions of the vestibulocerebellum and contribute to the control of gaze and balance. These critical vestibular functions have been infrequently quantified in human cerebellar disease. In 13 subjects with ataxia telangiectasia (A-T), a disease associated with profound cerebellar cortical degeneration, we found abnormalities of several key vestibular reflexes. The vestibuloocular reflex (VOR) was measured by eye movement responses to changes in head rotation. The vestibulocollic reflex (VCR) was assessed with cervical vestibular-evoked myogenic potentials (cVEMPs), in which auditory clicks led to electromyographic activity of the sternocleidomastoid muscle. The VOR gain (eye velocity/head velocity) was increased in all subjects with A-T. An increase of the VCR, paralleling that of the VOR, was indirectly suggested by an increase in cVEMP amplitude. In A-T subjects, alignment of the axis of eye rotation was not with that of head rotation. Subjects with A-T thus manifested VOR cross-coupling, abnormal eye movements directed along axes orthogonal to that of head rotation. Degeneration of the Purkinje neurons in the vestibulocerebellum probably underlie these deficits. This study offers insights into how the vestibulocerebellum functions in healthy humans. It may also be of value to the design of treatment trials as a surrogate biomarker of cerebellar function that does not require controlling for motivation or occult changes in motor strategy on the part of experimental subjects. [ABSTRACT FROM AUTHOR]

The gaze stabilization test (GST) is a computerized test of the vestibulo-ocular reflex that reports maximum head velocity while maintaining fixed visual acuity. The GST thus assesses the vestibulo-ocular reflex differently from the dynamic visual acuity test (DVAT). The purpose of this study was to assess the reliability, stability, and validity of the GST in a healthy young and older population. Forty subjects (20 older adults with mean (SD) age of 76.3 (5.3) and 20 young controls with mean (SD) age of 25.2 (3.2)) performed the GST and DVAT assessments. The version of the GST used in this study has a tunneled mirror system to ensure a consistent participant distance of 4 m from the computer screen. All subjects repeated trials within 30 minutes of initial testing. Twenty subjects (10 from each age group) returned 7–10 days later to repeat the GST and DVAT assessments. Vestibular symptoms were assessed before and after GST and DVAT assessments. The mean (SD) GST scores for the older group were 123 (33) deg/s in the yaw plane and 108 (27) deg/s in the pitch plane. For the young group, mean (SD) GST scores were 157 (34) deg/s in the yaw plane and 141(25) deg/s in the pitch plane. There was a significant between-group difference for GST scores in both yaw and pitch planes (p< 0.01). The intraclass correlation coefficient (ICC) for GST scores performed on the same day was 0.75 in the yaw plane and 0.69 in the pitch plane. The ICC including the 20 subjects who repeated the GST within 7–10 days was 0.59 in the yaw plane and 0.54 in the pitch plane. In general, GST was more stable than DVAT. GST was more stable in younger vs. older subjects whereas DVAT was more stable in older vs. younger subjects. Concurrent validity, determined by Spearman correlation coefficients between GST and DVAT loss results were -0.62 in the yaw plane and -0.38 in the pitch plane (p< 0.02). These results suggest that the gaze stabilization test (GST) has good same-day test-retest reliability and stability in healthy young and older adults. The moderate correlation between same-day GST and DVAT loss scores suggest the two tests may be measuring similar, but different constructs. [ABSTRACT FROM AUTHOR]