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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.

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.