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ObjectiveNoisy galvanic vestibular stimulation (nGVS) has been shown to partly restore vestibular function and to stabilize stance and gait in patients with incomplete bilateral vestibulopathy (BVP). Here, we examined potential synergistic effects of nGVS when combined with standardized vestibular rehabilitation training (VRT).Methods23 patients with confirmed BVP received a 30-min vestibular rehabilitation training (VRT) program three times a week for 2 weeks. The intervention group (n = 12) was stimulated with nGVS (at individually determined optimal amplitudes) during training, whereas the control group (n = 11) received zero-amplitude nGVS (sham stimulation) during training. Outcome measurements assessed at baseline, after 2 weeks of training, and at 2-week follow-up included quantitative posturography, instrumented gait analysis, Timed Up and Go Test (TUG), Functional Gait Assessment (FGA), and clinical scores related to quality of life and balance confidence.ResultsAfter 2 weeks of VRT, all patients showed moderate improvement in balance. Irrespective of nGVS treatment, performance improved in the TUG (p < 0.013), and in the FGA (p < 0.040). Furthermore, base of support when walking with closed eyes was reduced after 2-week training (p < 0.003). Postural sway did not change. There was no difference between groups and thereby no evidence for an additional influence of nGVS on the VRT treatment effects.ConclusionnGVS does not induce synergistic treatment effects in combination with VRT in patients with BVP when applied during treatment sessions. Hence, rather than being applied in parallel, nGVS and VRT might be complementary therapeutic options with nGVS being used during postural activities in daily life, e.g., walking.

To protect the audiosensory organ from tissue damage from the immune system, the inner ear is separated from the circulating immune system by the blood-labyrinth barrier, which was previously considered an immune-privileged site. Recent studies have shown that macrophages are distributed in the cochlea, especially in the spiral ligament, spiral ganglion, and stria vascularis; however, the direct pathogen defence mechanism used by audiosensory receptor hair cells (HCs) has remained obscure. Here, we show that HCs are protected from pathogens by surrounding accessory supporting cells (SCs) and greater epithelial ridge (GER or Kölliker’s organ) cells (GERCs). In isolated murine cochlear sensory epithelium, we established Theiler’s murine encephalomyelitis virus, which infected the SCs and GERCs, but very few HCs. The virus-infected SCs produced interferon (IFN)-α/β, and the viruses efficiently infected the HCs in the IFN-α/β receptor-null sensory epithelium. Interestingly, the virus-infected SCs and GERCs expressed macrophage marker proteins and were eliminated from the cell layer by cell detachment. Moreover, lipopolysaccharide induced phagocytosis of the SCs without cell detachment, and the SCs phagocytosed the bacteria. These results reveal that SCs function as macrophage-like cells, protect adjacent HCs from pathogens, and provide a novel anti-infection inner ear immune system.

In this paper, the piston clearance leakage model in reciprocating labyrinth compressor is established, and the leakage characteristics of labyrinth piston are analysed. The results show that in the labyrinth entrance section, the gas velocity decreases greatly, and the throttling effect is the most obvious. In the middle section of the labyrinth, the flow velocity descending gradient decreases. In the exit section, the flow rate begins to increase. When the labyrinth clearance is less than or equal to 0.1 mm, the clearance changes has little effect on the leakage. When the clearance is greater than 0.1 mm, the leakage increases rapidly with the clearance increasing. When the piston operates eccentrically, the leakage will increase by 1.5 ∼ 2 times compared with the non-eccentric operation. Therefore, the eccentric operation of the piston should be avoided as much as possible and the clearance should be reduced.

Background Patients with bilateral vestibulopathy (BVP) suffer from impaired vestibular motion perception that is linked to deficits in spatial memory and navigation. Objective To examine the potential therapeutic effect of imperceptible noisy galvanic vestibular stimulation (nGVS) on impaired vestibular perceptual performance in BVP. Methods In 11 patients with BVP (mean age: 54.0 ± 8.3 years, 7 females), we initially determined the nGVS intensity that optimally stabilizes balance during a static posturographic assessment. Subsequently, effects of optimal nGVS vs. sham stimulation on vestibular motion perception were examined in randomized order. Vestibular perceptual performance was determined as direction recognition thresholds for head-centered roll tilt motion on a 6DOF motion platform in the absence of any visual or auditory motion cues. Results For each patient, an nGVS intensity that optimally stabilized static balance compared to sham stimulation could be identified (mean 0.36 ± 0.16 mA). nGVS at optimal intensity resulted in lowered vestibular perceptual thresholds (0.94 ± 0.30 deg/s) compared to sham stimulation (1.67 ± 1.11 deg/s; p  = 0.040). nGVS-induced improvements in vestibular perception were observed in 8 of 11 patients (73%) and were greater in patients with poorer perceptual performance during sham stimulation ( R  = − 0.791; p  = 0.007). Conclusions nGVS is effective in improving impaired vestibular motion perception in patients with BVP, in particular in those patients with poor baseline perceptual performance. Imperceptible vestibular noise stimulation might thus offer a non-invasive approach to target BVP-related impairments in spatial memory, orientation, and navigation.

Congenital cytomegalovirus (CMV) infection is the leading cause of non-hereditary congenital sensorineural hearing loss (SNHL). The natural course and the pathophysiology of inner ear lesions during human fetal CMV infection have not yet been reported. Inner ear lesions were investigated in six CMV-infected fetuses aged 19–35 postconceptional weeks and correlated with central nervous system (CNS) lesions. All the fetuses had high viral loads in the amniotic fluid and severe visceral and CNS lesions visible by ultrasound. Diffuse lesions consisting of both cytomegalic cells containing inclusion bodies and inflammation were found within all studied structures including the inner ear, brain, other organs, and placenta, suggesting hematogenous dissemination. Cochlear infection was consistently present and predominated in the stria vascularis (5/6), whereas the supporting cells in the organ of Corti were less often involved (2/6). Vestibular infection, found in 4/6 cases, was florid; the non-sensory epithelia, including the dark cells, were extensively infected. The endolymphatic sac was infected in 1 of 3 cases. The severity of inner ear infection was correlated with the CNS lesions, confirming the neurotropism of CMV. This study documenting infection of the structures involved in endolymph secretion and potassium homeostasis in fetuses with high amniotic fluid viral loads suggests that potassium dysregulation in the endolymphatic compartment of the inner ear may lead to secondary degeneration of the sensory structures. In addition, the occurrence of SNHL depends on the intensity and duration of the viral infection and inflammation.

Postural instability is a common symptom of vestibular dysfunction that impacts a person’s day-to-day activities. Vestibular rehabilitation is effective in decreasing dizziness, visual symptoms and improving postural control through several mechanisms including sensory reweighting of the vestibular, visual and somatosensory systems. As part of the sensory reweighting mechanisms, vestibular activation exercises with headshaking influence vestibular-ocular reflex (VOR). However, combining challenging vestibular and postural tasks to facilitate more effective rehabilitation outcomes is under-utilized. Understanding how and why this may work is unknown. The aim of the study was to assess sensory reweighting of postural control processing and VOR after concurrent vestibular activation and weight shift training (WST) in healthy young adults. Forty-two participants (18–35years) were randomly assigned into four groups: No training/control (CTL), a novel visual feedback WST coupled with a concurrent, rhythmic active horizontal or vertical headshake activity (HHS and VHS), or the same WST with no headshake (NHS). Training was performed for five days. All groups performed baseline- and post-assessments using the video head impulse test, sensory organization test, force platform rotations and electro-oculography. Significantly decreased horizontal eye movement variability in the HHS group compared to the other groups suggests improved gaze stabilization ( p = .024). Significantly decreased horizontal VOR gain ( p = .040) and somatosensory downweighting ( p = .050) were found in the combined headshake groups (HHS and VHS) compared to the other two groups (NHS and CTL). The training also showed a significantly faster automatic postural response ( p = .003) with improved flexibility ( p = .010) in the headshake groups. The concurrent training influences oculomotor function and suggests improved gaze stabilization through vestibular recalibration due to adaptation and possibly habituation. The novel protocol could be modified into progressive functional activities that would incorporate gaze stabilization exercises. The findings may have implications for future development of vestibular rehabilitation protocols.

Noisy galvanic vestibular stimulation (nGVS) has been shown to enhance postural stability during stimulation, and the enhancing effect has been observed to persist for several hours post-stimulation. However, these effects were observed without proper control (sham condition) and the possibility of experimental bias has not been ruled out. The lasting effect of nGVS on postural stability therefore remains in doubt. We investigated the lasting effect of nGVS on postural stability using a control (sham) condition to confirm or infirm the possibility of experimental bias. 28 participants received either nGVS or a sham stimulation. Static postural control was examined before stimulation, immediately after 30 minutes of nGVS and one-hour post-stimulation. Results showed a significant improvement of sway velocity (p<0.05) and path length (p<0.05) was observed following nGVS, as previously shown. A similar improvement of sway velocity (p<0.05) and path length (p<0.05) was observed in sham group and no significant difference was found between nGVS group and sham group (p>0.05), suggesting that the observed postural improvement in nGVS could be due to a learning effect. This finding suggests the presence of experimental bias in the nGVS effect on postural stability, and highlights the need to use a sham condition in the exploration of the nGVS effect so as to disentangle the direct effect of the electrical stimulation from a learning effect. Furthermore, numerous parameters and populations need to be tested in order to confirm or infirm the presence of a real long-lasting effect of nGVS on postural stability.

Fifty percent of inner ear disorders are caused by genetic mutations. To develop treatments for genetic inner ear disorders, we designed gene replacement therapies using synthetic adeno-associated viral vectors to deliver the coding sequence for Transmembrane Channel-Like ( Tmc ) 1 or 2 into sensory hair cells of mice with hearing and balance deficits due to mutations in Tmc1 and closely related Tmc2 . Here we report restoration of function in inner and outer hair cells, enhanced hair cell survival, restoration of cochlear and vestibular function, restoration of neural responses in auditory cortex and recovery of behavioral responses to auditory and vestibular stimulation. Secondarily, we find that inner ear Tmc gene therapy restores breeding efficiency, litter survival and normal growth rates in mouse models of genetic inner ear dysfunction. Although challenges remain, the data suggest that Tmc gene therapy may be well suited for further development and perhaps translation to clinical application. Mutations in the mechanotransduction channel component TMC1/2 cause deafness. Here, the authors use a synthetic AAV to replace TMC1 and 2 in the inner ear and show restoration of cochlear and vestibular function, of neuronal reponses in the auditory cortex and of hearing and balance in mice.

Intravenous contrast agent-enhanced magnetic resonance imaging of the endolymphatic space (ELS) of the inner ear permits direct, in-vivo, non-invasive visualization of labyrinthine structures and thus verification of endolymphatic hydrops (ELH). However, current volumetric assessment approaches lack normalization. The aim of this study was to develop a probabilistic atlas of the inner ear’s bony labyrinth as a first step towards an automated and reproducible volume-based quantification of the ELS. The study included three different datasets: a source dataset (D1) to build the probabilistic atlas and two testing sets (D2, D3). D1 included 24 right-handed patients (12 females; mean age 51.5 ± 3.9 years) and D2 5 patients (3 female; mean age 48.8 ± 5.01 years) with vestibular migraine without ELH or any measurable vestibular deficits. D3 consisted of five patients (one female; mean age 46 ± 5.2 years) suffering from unilateral Menière’s disease and ELH. Data processing comprised three steps: preprocessing using an affine and deformable fusion registration pipeline, computation of an atlas for the left and right inner ear using a label-assisted approach, and validation of the atlas based on localizing and segmenting previously unseen ears. The three-dimensional probabilistic atlas of the inner ear’s bony labyrinth consisted of the internal acoustic meatus and inner ears (including cochlea, otoliths, and semicircular canals) for both sides separately. The analyses showed a high level of agreement between the atlas-based segmentation and the manual gold standard with an overlap of 89% for the right ear and 86% for the left ear (measured by dice scores). This probabilistic in vivo atlas of the human inner ear’s bony labyrinth and thus of the inner ear’s total fluid space for both ears represents a necessary step towards a normalized, easily reproducible and reliable volumetric quantification of the perilymphatic and endolymphatic space in view of MR volumetric assessment of ELH. The proposed atlas lays the groundwork for state-of-the-art approaches (e.g., deep learning) and will be provided to the scientific community.

Motion sickness is the cause of major physical discomfort and impaired performance in many susceptible individuals. Some habituate to sea conditions, whereas others remain chronically susceptible, requiring lifelong pharmaceutical treatment. The present study sets out to investigate whether galvanic vestibular stimulation (GVS) coupled with rotatory chair stimulation could mimic sea conditions and alleviate motion sickness symptoms in individuals deemed chronically susceptible. Thirty seasickness susceptible subjects, after at least six months of regular sailing, were enrolled in a prospective, single-blind, randomised controlled study. The treatment group underwent GVS coupled with inverse phase rotatory chair impulse in sinusoidal harmonic acceleration protocol. The control group underwent a sham procedure. All subjects performed repeated velocity step tests to determine the vestibular time constant (Tc) and completed a seasickness questionnaire. The GVS rotatory chair procedure decreased the prevalence of severe seasickness. The number of motion sickness clinic visits and anti-motion sickness drug consumption were reduced in the treatment group three-month post intervention as compared to control. In addition, there was significant reduction of Tc in the treatment group. GVS coupled with rotatory chair impulse could decrease motion sickness severity, induce neurophysiological learning processes and promote habituation to seasickness in chronic susceptible subjects. This is a novel and promising non-pharmacological method to treat motion sickness susceptible individuals. Furthermore, the investigation demonstrated that adaptation to sea conditions may take place even after years of susceptibility to seasickness. This study was retrospectively registered on August 10th 2021 and assigned the identifier number NCT05004818.