Despite considerable research, it remains controversial as to whether viral-infections are associated with Meniere's Disease (MD), a clinically heterogeneous set of chronic inner-ear disorders ...strongly associated with endolymphatic hydrops. Here, we investigated whether viral-infections are associated with MD through a systematic review and meta-analysis of observational clinical studies using molecular-diagnostics. Eligible for inclusion were case-controlled studies which ascertained molecular-determinants of past or present viral-infection through either viral nucleic acids or host serological marker in MD cases and non-MD controls. Across online databases and grey literature, we identified 210 potentially relevant articles in the English language, from which a total of 14 articles fully satisfied our eligibility criteria such that meta-groups of 611 MD-cases and 373 controls resulted. The aggregate quality of the modest-sized (14 studies) body of evidence was limited and varied considerably with regards to participant selection, matching, and ascertainment(s) and determinant(s) of viral-infection. Most data identified concerned the human cytomegalovirus (CMV), and meta-analysis of eligible studies revealed that evidence of CMV-infection was associated approximately three-fold with MD compared to controls, however the timing of the infections was indeterminate as the pooled analyses combined antiviral serological markers with viral nucleic acid markers. No association was found for any of HSV-1, -2, VZV, or EBV. Associative analyses of any viral species not aforementioned were precluded by limited data, and thus potential associations between other viral species and MD, especially other than Herpesviridae, are yet to be characterised. Overall, we have found a small association between CMV-infection and MD, however it is to be determined for what sub-groups of MD this finding may be relevant, and ideally the reported association remains would be reproduced by a greater volume of higher quality evidence.
The main objective of this study was to determine whether bone-conducted vibration (BCV) is equally effective in activating both semicircular canal and otolith afferents in the guinea pig or whether ...there is preferential activation of one of these classes of vestibular afferents. To answer this question a large number (346) of single primary vestibular neurons were recorded extracellularly in anesthetized guinea pigs and were identified by their location in the vestibular nerve and classed as regular or irregular on the basis of the variability of their spontaneous discharge. If a neuron responded to angular acceleration it was classed as a semicircular canal neuron, if it responded to maintained roll or pitch tilts it was classified as an otolith neuron. Each neuron was then tested by BCV stimuli-either clicks, continuous pure tones (200-1,500 Hz) or short tone bursts (500 Hz lasting 7 ms)-delivered by a B-71 clinical bone-conduction oscillator cemented to the guinea pig's skull. All stimulus intensities were referred to that animal's own auditory brainstem response (ABR) threshold to BCV clicks, and the maximum intensity used was within the animal's physiological range and was usually around 70 dB above BCV threshold. In addition two sensitive single axis linear accelerometers cemented to the skull gave absolute values of the stimulus acceleration in the rostro-caudal direction. The criterion for a neuron being classed as activated was an audible, stimulus-locked increase in firing rate (a 10% change was easily detectable) in response to the BCV stimulus. At the stimulus levels used in this study, semicircular canal neurons, both regular and irregular, were insensitive to BCV stimuli and very few responded: only nine of 189 semicircular canal neurons tested (4.7%) showed a detectable increase in firing in response to BCV stimuli up to the maximum 2 V peak-to-peak level we delivered to the B-71 oscillator (which produced a peak-to-peak skull acceleration of around 6-8 g and was usually around 60-70 dB above the animal's own ABR threshold for BCV clicks). Regular otolithic afferents likewise had a poor response; only 14 of 99 tested (14.1%) showed any increase in firing rate up to the maximum BCV stimulus level. However, most irregular otolithic afferents (82.8%) showed a clear increase in firing rate in response to BCV stimuli: of the 58 irregular otolith neurons tested, 48 were activated, with some being activated at very low intensities (only about 10 dB above the animal's ABR threshold to BCV clicks). Most of the activated otolith afferents were in the superior division of the vestibular nerve and were probably utricular afferents. That was confirmed by evidence using juxtacellular injection of neurobiotin near BCV activated neurons to trace their site of origin to the utricular macula. We conclude there is a very clear preference for irregular otolith afferents to be activated selectively by BCV stimuli at low stimulus levels and that BCV stimuli activate some utricular irregular afferent neurons. The BCV generates compressional and shear waves, which travel through the skull and constitute head accelerations, which are sufficient to stimulate the most sensitive otolithic receptor cells.
Efferent circuits within the nervous system carry nerve impulses from the central nervous system to sensory end organs. Vestibular efferents originate in the brainstem and terminate on hair cells and ...primary afferent fibers in the semicircular canals and otolith organs within the inner ear. The function of this efferent vestibular system (EVS) in vestibular and motor coordination though, has proven difficult to determine, and remains under debate. We consider current literature that implicate corollary discharge from the spinal cord through the efferent vestibular nucleus (EVN), and hint at a potential role in overall vestibular plasticity and compensation. Hypotheses range from differentiating between passive and active movements at the level of vestibular afferents, to EVS activation under specific behavioral and environmental contexts such as arousal, predation, and locomotion. In this review, we summarize current knowledge of EVS circuitry, its effects on vestibular hair cell and primary afferent activity, and discuss its potential functional roles.
Abstract
Background
Vestibular compensation is a homeostatic process that occurs in the central nervous system in response to peripheral vestibular dysfunction. Experimental studies in rodent models ...have suggested that unilateral peripheral vestibular lesions are correlated with an increase in the intrinsic excitability of central vestibular neurons. This process may be dependent on the intrinsic properties of the neurons themselves. We aimed to conduct a systematic review of the literature to survey the evidence for changes in intrinsic plasticity observed during the acute phase of vestibular compensation.
Methods
We systematically reviewed the literature regarding the electrophysiological effect of experimentally induced unilateral vestibular deafferentation (UVD) on the intrinsic membrane properties of medial vestibular nucleus neurons in animal models. We developed tools to assess the methodological quality (precision, validity and bias) of studies that met pre-determined inclusion and exclusion criteria. We extracted numerical data and performed a meta-analysis of specific quantitative data pooled from these studies.
Results
We identified 17 studies that satisfied the inclusion criteria. There is moderate quality evidence to suggest a statistically significant increase in the intrinsic excitability of medial vestibular nucleus neurons following unilateral vestibular deafferentation. Specifically, the spontaneous discharge rate increases by 4 spikes/s on average and the sensitivity to current stimuli increases.
Conclusion
Using this novel approach, we demonstrate that the methodology of systematic review and meta-analysis is a useful tool in the summation of data across experimental animal studies with similar aims.
Despite the importance of our sense of balance we still know remarkably little about the central control of the peripheral balance system. While previous work has shown that activation of the ...efferent vestibular system results in modulation of afferent vestibular neuron discharge, the intrinsic and synaptic properties of efferent neurons themselves are largely unknown. Here we substantiate the location of the efferent vestibular nucleus (EVN) in the mouse, before characterizing the input and output properties of EVN neurons in vitro. We made transverse serial sections through the brainstem of 4-week-old mice, and performed immunohistochemistry for calcitonin gene-related peptide (CGRP) and choline acetyltransferase (ChAT), both expressed in the EVN of other species. We also injected fluorogold into the posterior canal and retrogradely labelled neurons in the EVN of ChAT:: tdTomato mice expressing tdTomato in all cholinergic neurons. As expected the EVN lies dorsolateral to the genu of the facial nerve (CNVII). We then made whole-cell current-, and voltage-clamp recordings from visually identified EVN neurons. In current-clamp, EVN neurons display a homogeneous discharge pattern. This is characterized by a high frequency burst of action potentials at the onset of a depolarizing stimulus and the offset of a hyperpolarizing stimulus that is mediated by T-type calcium channels. In voltage-clamp, EVN neurons receive either exclusively excitatory or inhibitory inputs, or a combination of both. Despite this heterogeneous mixture of inputs, we show that synaptic inputs onto EVN neurons are predominantly excitatory. Together these findings suggest that the inputs onto EVN neurons, and more specifically the origin of these inputs may underlie EVN neuron function.
•First recording of the vestibular summating potential from mammalian utricular macula, in vivo.•The utricular SP originates from hair cell activity.•The utricular SP is displacement sensitive.•This ...technique provides a novel tool to assess vestibular hair cell function.
The Summating Potential (SP) was first recorded in the cochlea in the 1950s and represents an objective measure of cochlear hair cell function, in vivo. Despite being a regular tool in hearing research, a similar response has not yet been recorded from the vestibular system. This is mainly due to the lack of experimental techniques available to record electrical vestibular hair cell responses in isolation from the much larger cochlear potentials. Here we demonstrate the first recordings of the vestibular SP, evoked by Bone-Conducted Vibration (BCV) and Air-Conducted Sound (ACS) stimuli, in anaesthetized guinea pigs. Field potential measurements were taken from the basal surface of the utricular macula, and from the facial nerve canal following surgical or chemical ablation of the cochlea. SPs were evoked by stimuli with frequencies above ~200 Hz, and only with moderate to high intensity (~0.005–0.05 g) BCV and ACS (~120–140 dB SPL). Neural blockade abolished the Vestibular short-latency Evoked Potential (VsEP) and Vestibular Nerve Neurophonic (VNN) from the facial nerve canal recordings but did not abolish the vestibular SP nor the vestibular microphonic. Importantly, the vestibular SP was irreversibly abolished from the utricle and facial nerve canal recordings following local gentamicin application, highlighting its hair cell origin. This is the first study to record the Summating Potential from the mammalian vestibular system, in vivo, providing a novel research tool to assess vestibular hair cell function during experimental manipulations and animal models of disease.
The COVID-19 pandemic has created substantial and profound barriers to several forms of health care engagement. For Black sexual minority men, this may include engagement with pre-exposure ...prophylaxis (PrEP) to prevent HIV infection, with significant implications for HIV disparities. Our study explored how the COVID-19 pandemic affected Black sexual minority men, with a focus on relationships between COVID-19 and PrEP engagement.
We sampled 24 Black sexual minority men attending HIV prevention-related events in the greater D.C. Metropolitan area (D.C., Maryland, Virginia).
We conducted qualitative phone interviews among our sample. Questions were primarily focused on the COVID-19 pandemic and how it affected engagement and considerations of PrEP use. Interviews were transcribed and qualitatively analyzed using the 6 stages of thematic analysis.
We identified 3 major themes from our thematic analysis: Changes in the health care system, changes in sexual and relationship contexts, and COVID-19 vaccine hesitancy and misinformation. Relationships between COVID-19 vaccine hesitancy and PrEP hesitancy were especially prevalent, with participants describing that COVID-19 hesitancy can directly deter PrEP use through eroding medical trust further.
We identified changes in the health care system, sexual and relationship contexts, and COVID-19 vaccine hesitancy as important issues driven by COVID-19 with significant implications for PrEP use. The COVID-19 pandemic has changed the health care and social landscape in profound ways that affect PrEP access, sexual networks, and associated HIV vulnerability. Future research further exploring relationships between specific pandemic stressors and HIV prevention among Black sexual minority men is recommended .
Vestibular-evoked myogenic potentials (VEMPs) provide a simple and cost-effective means to assess the patency of vestibular reflexes. VEMP testing constitutes a core screening method in a clinical ...battery that probes vestibular function. The confidence one has in interpreting the results arising from VEMP testing is linked to a fundamental understanding of the underlying functional anatomy and physiology. In this review, we will summarize the key role that studies across a range of animal models have fulfilled in contributing to this understanding, covering key findings regarding the mechanisms of excitation in the sensory periphery, the processing of sensory information in central networks, and the distribution of reflexive output to the motor periphery. Although VEMPs are often touted for their simplicity, work in animals models have emphasized how vestibular reflexes operate within a broader behavioral and functional context, and as such vestibular reflexes are influenced by multisensory integration, governed by task demands, and follow principles of muscle recruitment. We will conclude with considerations of future questions, and the ways in which studies in current and emerging animal models can contribute to further use and refinement of this test for both basic and clinical research purposes.
It has long been known that the vast majority of all information en route to the cerebral cortex must first pass through the thalamus. The long held view that the thalamus serves as a simple hi ...fidelity relay station for sensory information to the cortex, however, has over recent years been dispelled. Indeed, multiple projections from the vestibular nuclei to thalamic nuclei (including the ventrobasal nuclei, and the geniculate bodies)- regions typically associated with other modalities- have been described. Further, some thalamic neurons have been shown to respond to stimuli presented from across sensory modalities. For example, neurons in the rat anterodorsal and laterodorsal nuclei of the thalamus respond to visual, vestibular, proprioceptive and somatosensory stimuli and integrate this information to compute heading within the environment. Together, these findings imply that the thalamus serves crucial integrative functions, at least in regard to vestibular processing, beyond that imparted by a "simple" relay. In this mini review we outline the vestibular inputs to the thalamus and provide some clinical context for vestibular interactions in the thalamus. We then focus on how vestibular inputs interact with other sensory systems and discuss the multisensory integration properties of the thalamus.
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