Search

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]

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

Abstract: Vestibular information is essential for the control of posture, balance, and eye movements. The vestibular nerve projects to the four nuclei of the vestibular nuclear complex (VNC), as well as to several additional brainstem nuclei and the cerebellum. We have found that expression of the calcium-binding proteins calretinin (CR) and calbindin (CB), and the synthetic enzyme for nitric oxide synthase (nNOS) define subdivisions of the medial vestibular nucleus (MVe) and the nucleus prepositus (PrH), in cat, monkey, and human. We have asked if the pattern of expression of nonphosphorylated neurofilament protein (NPNFP) might define additional subdivisions of these or other nuclei that participate in vestibular function. We studied the distribution of cells immunoreactive to NPNFP in the brainstems of 5 cats and one squirrel monkey. Labeled cells were scattered throughout the four nuclei of the VNC, as well as in PrH, the reticular formation (RF) and the external cuneate nucleus. We used double-label immunofluorescence to visualize the distribution of these cells relative to other neurochemically defined subdivisions. NPNFP cells were excluded from the CR and CB regions of the MVe. In PrH, NPNFP and nNOS were not colocalized. Cells in the lateral vestibular nucleus and RF colocalized NPNFP and a marker for glutamatergic neurons. We also found that the cholinergic cells and axons of cranial nerve nuclei 3, 4, 6, 7,10 and 12 colocalize NPNFP. The data suggest that NPNFP is expressed by a subset of glutamatergic projection neurons of the vestibular brainstem. NPNFP may be a marker for those cells that are especially vulnerable to the effects of normal aging, neurological disease or disruption of sensory input. [Copyright &y& Elsevier]

Abstract: In Xenopus laevis tadpoles, effects of asymmetrical light conditions on the roll-induced vestibuloocular reflex (rVOR) were tested for the developmental period between stage 47 and 49. For comparison, the rVOR was tested in dim- and high-symmetrical light environments. Test parameters were the rVOR gain and rVOR amplitude. Under all light conditions, the rVOR increased from tadpole stage 47 to 49. For all stages, the asymmetrical light field induced the strongest response, the dim light field the weakest one. The response for the left and right eye was identical, even if the tadpoles were tested under asymmetrical light conditions. The experiments can be considered as hints (1) for an age-dependent light sensitivity of vestibular neurons, and (2) for the existence of control systems for coordinated eye movements that has its origin in the proprioceptors of the extraocular eye muscles. [Copyright &y& Elsevier]

Semicircular canals have been sensors of angular acceleration for 450 million years. This vertebrate adaptation enhances survival by implementing postural and visual stabilization during motion in a three-dimensional environment. We used an integrated neuroethological approach in larval Xenopus to demonstrate that semicircular canal dimensions, and not the function of other elements, determines the onset of angular acceleration detection. Before angular vestibuloocular function in either the vertical or horizontal planes, at stages 47 and 48, respectively, each individual component of the vestibuloocular system was shown to be operational: extraocular muscles could be activated, central neural pathways were complete, and canal hair cells were capable of evoking graded responses. For Xenopus, a minimum semicircular canal lumen radius of 60μm was necessary to permit endolymph displacement sufficient for sensor function at peak accelerations of 400°/s2. An intra-animal comparison demonstrated that this size is reached in the vertical canals earlier in development than in the horizontal canals, corresponding to the earlier onset of vertical canal-activated ocular motor behavior. Because size constitutes a biophysical threshold for canal-evoked behavior in other vertebrates, such as zebrafish, we suggest that the semicircular canal lumen and canal circuit radius are limiting the onset of vestibular function in all small vertebrates. Given that the onset of gravitoinertial acceleration detection precedes angular acceleration detection by up to 10 d in Xenopus, these results question how the known precise spatial patterning of utricular and canal afferents in adults is achieved during development. [ABSTRACT FROM AUTHOR]

A neural integrator (NI) is presumed to exist in the oculomotor system to assist in numerous tasks such as maintaining gaze on imaginary targets in the dark. It is shared by all ocular reflexes including the vestibuloocular reflex (VOR). It has been widely accepted that the NI acts as a ldquoperfectrdquo integrator even in the dark with time constants as large as 1950s. However, the NI time constant is often less than ideal and its value can also be dependent on context [W. W. P. Chan and H. L. Galiana, ldquoIntegrator function in the oculomotor system is dependent on sensory context,rdquo J. Neurophysiol., vol. 93, pp. 3709--3717, Feb. 2005.]. In this paper, a nonlinear feedback model is postulated to model the context-dependent properties of the NI. Algorithms are first developed and validated to fit both linear and nonlinear NI models to experimental data in the presence of ocular nystagmus. Preliminary results indicate that even normal subjects can have a nonlinear VOR and NI. [ABSTRACT FROM PUBLISHER]

Abstract: Objective: Recent work has demonstrated the existence of ocular vestibular evoked myogenic potentials (OVEMPs), which likely reflect projections underlying the translational vestibular ocular reflex (TVOR). We examined extraocular muscle activity associated with impulsive acceleration of the head in the transmastoid plane. Methods: Accelerometry was measured in 4 subjects in response to acceleration impulses produced by a gamma function delivered with a Minishaker (4810, Bruel & Kjaer). This stimulus produced peak head accelerations of 0.13–0.14g occurring at between 3.1 and 4.0ms at the mastoids for both right and left head movement. OVEMPs were recorded in 10 normal subjects with 5 directions of gaze, using electrode pairs placed lateral to, above and below the eyes. Results: OVEMPs occurred at short latency, with initial peaks between 10.3ms (p10) and 15.3ms (n15). For a given recording site and gaze direction, the responses were determined solely by the direction of imposed acceleration. Conclusions: We propose that, given the transtemporal nature of the stimuli, utricular afferents are likely to be powerfully activated. The OVEMPs evoked may be generated by the lateral recti and oblique muscles. Significance: Sudden lateral accelerations of the head evoke the translational VOR and ocular counter rolling reflex and the pattern of muscle activations indicated by the OVEMPs appear to be a manifestation of these reflexes. [Copyright &y& Elsevier]

Out-of-plane head movements performed during fast rotation produce non-compensatory nystagmus, sensations of illusory motion, and often motion sickness. Adaptation to this cross-coupled Coriolis stimulus has previously been demonstrated for head turns made in the yaw (transverse) plane of motion, during supine head-on-axis rotation. An open question, however, is if adaptation to head movements in one plane of motion transfers to head movements performed in a new, unpracticed plane of motion. Evidence of transfer would imply the brain builds up a generalized model of the vestibular sensory-motor system, instead of learning a variety of individual input/output relations separately. To investigate, over two days 9 subjects performed pitch head turns (sagittal plane) while rotating, before and after a series of yaw head turns while rotating. A Control Group of 10 subjects performed only the pitch movements. The vestibulo-ocular reflex (VOR) and sensations of illusory motion were recorded in the dark for all movements. Upon comparing the two groups we failed to find any evidence of transfer from the yaw plane to the pitch plane, suggesting that adaptation to cross-coupled stimuli is specific to the particular plane of head movement. The findings have applications for the use of centrifugation as a possible countermeasure for long duration spaceflight. Adapting astronauts to unconstrained head movements while rotating will likely require exposure to head movements in all planes and directions. [ABSTRACT FROM AUTHOR]

Abstract: Using collision tests of orthodromically and antidromically generated spikes, we studied the axonal pathways, axonal projection levels, and soma location of anterior semicircular canal (AC) nerve-activated vestibulospinal neurons in decerebrate cats. AC nerve-activated vestibulospinal neurons (n =74) were mainly located in the ventral portion of the lateral vestibular nuclei and the rostral portion of the descending vestibular nucleus, which is consistent with previous studies. Of these neurons, 15% projected through the ipsilateral (i-) lateral vestibulospinal tract (LVST), 74% projected through the medial vestibulospinal tract (MVST), and 11% projected through the contralateral (c-) LVST. The vast majority (78%) of AC nerve-activated vestibulospinal neurons were activated antidromically only from the cervical segment of the spinal cord; 15% of neurons were activated from the T1 segment and only one neuron was activated from the L3 segment. AC nerve-activated vestibulospinal neurons may primarily target the neck muscles and thus contribute to the vestibulocollic reflex. Most of the c-LVST neurons were also activated antidromically from the oculomotor nucleus, suggesting that they are closely related to the control of combined eye-head movements. [Copyright &y& Elsevier]

Abstract: The clawed toad Xenopus laevis is a common experimental animal used in many disciplines of life sciences, such as integrative, developmental and molecular biology or experimental medicine. Since 30 years, Xenopus is used in biological research in space. Important milestones were the years 1975, when Xenopus embryos flew for the first time on the Russian space station Salut-4 and 1994, when Xenopus eggs were successfully fertilized for the first time in space during the Japanese Spacelab mission STS-47 and developed in microgravity to vital tadpoles. Most Xenopus studies were related to embryogenesis and development. Observations during and after altered gravity revealed changes such as the thickening of the blastocoel roof, the dorsalization of the tail, and modifications of vestibular reflexes, fictive and freely swimming. Many changes were reversible even during microgravity exposure. Studies about the vestibuloocular reflex or synapse formation revealed an age-related sensitivity to altered gravity. Xenopus offers useful tools for studies about microgravity effects on living systems. Its oocyte is a suitable model to study ion channel function in space; the dorsalization model can be used to analyse growth factor sensibilities. Hardware for life support of adults, tadpoles and embryos (cf. SUPPLY unit in combination with miniaquaria) as well as for controlled experiments in space are prerequisites for an extension of research with Xenopus. The application aspect is based on the fact that fundamental research per se brings benefit to man. [Copyright &y& Elsevier]

Abstract: Diazepam is a popular medicine used in the treatment of acute vertigo. In the past, many studies investigating the effect of diazepam in peripheral vestibular destruction have been reported. However, no previous study has yet investigated the effect of diazepam on a model with a transient and reversible vestibular function similar to recurrent vertigo as seen in Meniere''s disease. We thus made a peripheral vestibular re-input model by the unilateral intracochlear administration of tetrodotoxin (TTX) using an osmotic pump and then examined the influence of diazepam on the vestibular system in this model. Hartley white guinea pigs were intracochlearly administered with TTX on the right side for 3 days by an osmotic pump. Animals were divided into three groups, TTX alone (control group (n = 7)), TTX and an intraperitoneal diazepam injection once a day for 3 days (diazepam group (n = 6)) and vehicle injection (vehicle group (n = 6)). A caloric response and vestibuloocular reflex (VOR) were observed at 7 and 14 days after completing 3 days of TTX administration. Seven days after vestibular re-input, a directional preponderance of the nystagmus (DP) to the TTX-treated side was observed in the control and vehicle groups on VOR examination. DP was not observed in the diazepam group on any examined day. The R/L time ratio of caloric response showed no statistical difference between three groups on any examined day. These results suggest that diazepam may thus be useful for patients in an acute stage of peripheral vestibular vertigo by decreasing their vertiginous symptoms. [Copyright &y& Elsevier]

Vestibuloocular reflex (VOR) performance and adaptation have been investigated during antagonism of cerebellar AMPA/quisqualate and kainate receptors (AMPA/KA) by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Injection of CNQX into the vestibulo-cerebellum of the goldfish before adaptation significantly inhibited and, at the highest dosage, completely prevented acquisition of adaptive reflex gain increases and decreases during a 3-h training period. Injection of CNQX before initiation of VOR adaptive training did not affect pre-adapted baseline performance of the reflex. Injection of CNQX, 1 to 2 h after the initiation of training did not alter the performance of adaptive gain increases that occurred before the injection. If injection of CNQX occurred at the end of adaptive training, there was an accelerated loss of the previously adapted gain changes during the retention period when the animal remained stationary in the dark. CNQX injection did not produce any permanent or long-term deficits, because goldfish could be retrained 48 h later to produce adaptive VOR gain changes similar to control animals. Thus, this work demonstrates that the AMPA/KA receptors located in the vestibulo-cerebellum of the goldfish are necessary for acquisition of short-term adaptive VOR gain increases and decreases. The deficit in adaptive capability was not the result of a deficit in performance, because CNQX did not inhibit an adaptive change that had already occurred as long as the adapting vestibular and visual stimulation continued. This adaptive performance could possibly be maintained by other glutamatergic (metabotropic) receptors located on the Purkinje cells. The retention of adapted gain increases and decreases after CNQX application was inhibited because AMPA/KA antagonism accelerated VOR gain loss after the completion of training when no vestibular or visual stimulation was present. Because the AMPA/KA receptors are located only in the molecular layer of the goldfish cerebellum, these results are, presumably, the result of AMPA/KA receptor antagonism at synapses located on the Purkinje cell dendrite tree. [ABSTRACT FROM AUTHOR]

Our understanding of how the brain controls eye movements has benefited enormously from the comparison of neuronal activity with eye movements and the quantification of these relationships with mathematical models. Although these early studies focused on horizontal and vertical eye movements, recent behavioural and modelling studies have illustrated the importance, but also the complexity, of extending previous conclusions to the problems of controlling eye and head orientation in three dimensions (3-D). An important facet in understanding 3-D eye orientation and movement has been the discovery of mobile, soft-tissue sheaths or ‘pulleys’ in the orbit which might influence the pulling direction of extraocular muscles. Appropriately placed pulleys could generate the eye-position-dependent tilt of the ocular rotation axes which are characteristic for eye movements which follow Listing's law. Based on such pulley models of the oculomotor plant it has recently been proposed that a simple two-dimensional (2-D) neural controller would be sufficient to generate correct 3-D eye orientation and movement. In contrast to this apparent simplification in oculomotor control, multiple behavioural observations suggest that the visuo-motor transformations, as well as the premotor circuitry for saccades, pursuit eye movements and the vestibulo-ocular reflexes, must include a neural controller which operates in 3-D, even when considering an eye plant with pulleys. This review summarizes the most recent work and ideas on this controversy. In addition, by proposing directly testable hypotheses, we point out that, in analogy to the previously successful steps towards elucidating the neural control of horizontal eye movements, we need a quantitative characterization first of motoneuron and next of premotor neuron properties in 3-D before we can succeed in gaining further insight into the neural control of 3-D motor behaviours. [ABSTRACT FROM AUTHOR]

Vestibular implants are implantable devices that attempt to partially restore vestibular function in patients with severe bilateral vestibulopathy of peripheral origin, using electrical currents. There have been substantial research efforts, first in animals and more recently in humans, towards the development of vestibular implants. Our group, the Geneva- Maastricht team, developed an original concept based on a modified cochlear implant. This device, developed in close collaboration with MED-EL (Innsbruck, Austria), provides 1 to 3 extra-cochlear electrodes which are implanted in the vicinity of vestibular afferents in addition to the cochlear implant array. We started implantations in humans in 2007 and, to date, 13 patients with severe bilateral vestibulopathy were implanted with these prototype devices, without surgical or medical complications. Special surgical techniques have been developed for safe implantation of these devices and their feasibility has been demonstrated in human subjects. Humans have demonstrated surprising adaptation capabilities to the artificial vestibular signal. Successful restoration of the vestibulo-ocular reflex in the mid- to high-frequency range has been demonstrated using standard clinical tests (rotatory chair and video-head impulse test). We also showed that it is possible to activate the vestibulo-collic reflex using measures of cervical myogenic vestibular evoked potentials. Controlled postural responses could also be obtained with our prototype vestibular implant device. Finally, visual abilities in dynamic settings were restored with the vestibular implant. The latter is a major step forward, providing the first ever demonstration of useful rehabilitation of this patient population. The results obtained so far in humans are very encouraging. We hope that the increasing interest in this field and the substantial research efforts allocated will lead to a clinical application in the near future. It should also be mentioned that the vestibular implant opens new possibilities for exploring several fundamental issues: balance function, the adaptive capacities of the brain, the processes of temporal integration of sensory information necessary for equilibrium, and probably for better understanding vestibular physiology and vestibular disorders. Therefore, the vestibular implant opens new perspectives, not only as an effective therapeutic tool, but also pushes us to go beyond current knowledge and well established clinical concepts. [ABSTRACT FROM AUTHOR]