Skull Vibration-Induced Nystagmus Test (SVINT) in Vestibular Migraine and Menière’s Disease

Background: Vestibular migraine (VM) and Menière’s disease (MD) are the two most frequent episodic vertigo apart from Benign Paroxysmal Positional Vertigo (BPPV) differential diagnosis for them may be troublesome in the early stages. SVINT is a newly proposed vestibular test, which demonstrated to be fast and reliable in diagnoses above all of peripheral vestibular deficits. Methods: We retrieved clinical data from two groups of subjects (200 VM and 605 MD), enrolled between 2010 and 2020. Among others, these subjects were included when performing a SVINT. The purpose of the study is to assess if SVINT can be useful to differentiate the two episodic disorders. Results: 59.2% of MD subjects presented as positive with SVINT while only 6% did so with VM; among other tests, only video HIT demonstrated a different frequency in the two groups (13.1% and 0.5%, respectively), but the low sensitivity in these subjects makes the test unaffordable for diagnostic purposes. Conclusions: Since SVINT demonstrated to be positive in a peripheral vestibular deficit in previous works, we think that our data are consistent with the hypothesis that, in the pathophysiology of VM attacks, the central vestibular pathways are mainly involved.

Cognitive, Systems, and Computational Neurosciences of the Self in Motion

Navigating by path integration requires continuously estimating one's self-motion. This estimate may be derived from visual velocity and/or vestibular acceleration signals. Importantly, these senses in isolation are ill-equipped to provide accurate estimates, and thus visuo-vestibular integration is an imperative. After a summary of the visual and vestibular pathways involved, the crux of this review focuses on the human and theoretical approaches that have outlined a normative account of cue combination in behavior and neurons, as well as on the systems neuroscience efforts that are searching for its neural implementation. We then highlight a contemporary frontier in our state of knowledge: understanding how velocity cues with time-varying reliabilities are integrated into an evolving position estimate over prolonged time periods. Further, we discuss how the brain builds internal models inferring when cues ought to be integrated versus segregated—a process of causal inference. Lastly, we suggest that the study of spatial navigation has not yet addressed its initial condition: self-location. Expected final online publication date for the Annual Review of Psychology, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Truncation of the otoferlin transmembrane domain alters the development of hair cells and reduces membrane docking

Release of neurotransmitter from sensory hair cells is regulated by otoferlin. Despite the importance of otoferlin in the auditory and vestibular pathways, the functional contributions of the domains of the protein have not been fully characterized. Using a zebrafish model, we investigated a mutant otoferlin with a stop codon at the start of the transmembrane domain. We found that both the phenotype severity and the expression level of mutant otoferlin changed with the age of the zebrafish. At the early developmental timepoint of 72 hours post-fertilization (hpf) low expression of the otoferlin mutant coincided with synaptic ribbon deficiencies, reduced endocytosis, and abnormal transcription of several hair cell genes. As development proceeded, expression of the mutant otoferlin increased, and both synaptic ribbons and hair cell transcript levels resembled wild type. However, hair cell endocytosis deficits and abnormalities in the expression of GABA receptors persisted even after upregulation of mutant otoferlin. Analysis of membrane-reconstituted otoferlin measurements suggest a function for the transmembrane domain in liposome docking. We conclude that that deletion of the transmembrane domain reduces membrane docking, attenuates endocytosis, and results in developmental delay of the hair cell.

Absence of a vergence-mediated vestibulo-ocular reflex gain increase does not preclude adaptation

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.

Simultaneous activation of multiple vestibular pathways upon electrical stimulation of semicircular canal afferents

Background and purpose Vestibular implants seem to be a promising treatment for patients suffering from severe bilateral vestibulopathy. To optimize outcomes, we need to investigate how, and to which extent, the different vestibular pathways are activated. Here we characterized the simultaneous responses to electrical stimuli of three different vestibular pathways. Methods Three vestibular implant recipients were included. First, activation thresholds and amplitude growth functions of electrically evoked vestibulo-ocular reflexes (eVOR), cervical myogenic potentials (ecVEMPs) and vestibular percepts (vestibulo-thalamo-cortical, VTC) were recorded upon stimulation with single, biphasic current pulses (200 µs/phase) delivered through five different vestibular electrodes. Latencies of eVOR and ecVEMPs were also characterized. Then we compared the amplitude growth functions of the three pathways using different stimulation profiles (1-pulse, 200 µs/phase; 1-pulse, 50 µs/phase; 4-pulses, 50 µs/phase, 1600 pulses-per-second) in one patient (two electrodes). Results The median latencies of the eVOR and ecVEMPs were 8 ms (8–9 ms) and 10.2 ms (9.6–11.8 ms), respectively. While the amplitude of eVOR and ecVEMP responses increased with increasing stimulation current, the VTC pathway showed a different, step-like behavior. In this study, the 200 µs/phase paradigm appeared to give the best balance to enhance responses at lower stimulation currents. Conclusions This study is a first attempt to evaluate the simultaneous activation of different vestibular pathways. However, this issue deserves further and more detailed investigation to determine the actual possibility of selective stimulation of a given pathway, as well as the functional impact of the contribution of each pathway to the overall rehabilitation process.

Optogenetic fMRI interrogation of brain-wide central vestibular pathways

Blood oxygen level-dependent functional MRI (fMRI) constitutes a powerful neuroimaging technology to map brain-wide functions in response to specific sensory or cognitive tasks. However, fMRI mapping of the vestibular system, which is pivotal for our sense of balance, poses significant challenges. Physical constraints limit a subject’s ability to perform motion- and balance-related tasks inside the scanner, and current stimulation techniques within the scanner are nonspecific to delineate complex vestibular nucleus (VN) pathways. Using fMRI, we examined brain-wide neural activity patterns elicited by optogenetically stimulating excitatory neurons of a major vestibular nucleus, the ipsilateral medial VN (MVN). We demonstrated robust optogenetically evoked fMRI activations bilaterally at sensorimotor cortices and their associated thalamic nuclei (auditory, visual, somatosensory, and motor), high-order cortices (cingulate, retrosplenial, temporal association, and parietal), and hippocampal formations (dentate gyrus, entorhinal cortex, and subiculum). We then examined the modulatory effects of the vestibular system on sensory processing using auditory and visual stimulation in combination with optogenetic excitation of the MVN. We found enhanced responses to sound in the auditory cortex, thalamus, and inferior colliculus ipsilateral to the stimulated MVN. In the visual pathway, we observed enhanced responses to visual stimuli in the ipsilateral visual cortex, thalamus, and contralateral superior colliculus. Taken together, our imaging findings reveal multiple brain-wide central vestibular pathways. We demonstrate large-scale modulatory effects of the vestibular system on sensory processing.

Neuronal variability and tuning are balanced to optimize naturalistic self-motion coding in primate vestibular pathways

It is commonly assumed that the brain’s neural coding strategies are adapted to the statistics of natural stimuli. Specifically, to maximize information transmission, a sensory neuron’s tuning function should effectively oppose the decaying stimulus spectral power, such that the neural response is temporally decorrelated (i.e. ‘whitened’). However, theory predicts that the structure of neuronal variability also plays an essential role in determining how coding is optimized. Here, we provide experimental evidence supporting this view by recording from neurons in early vestibular pathways during naturalistic self-motion. We found that central vestibular neurons displayed temporally whitened responses that could not be explained by their tuning alone. Rather, computational modeling and analysis revealed that neuronal variability and tuning were matched to effectively complement natural stimulus statistics, thereby achieving temporal decorrelation and optimizing information transmission. Taken together, our findings reveal a novel strategy by which neural variability contributes to optimized processing of naturalistic stimuli.