Linking Vestibular Function and Subcortical Gray Matter Volume Changes in a Longitudinal Study of Aging Adults

Emerging evidence suggests a relationship between impairments of the vestibular (inner ear balance) system and alterations in the function and the structure of the central nervous system (CNS) in older adults. However, it is unclear whether age-related vestibular loss is associated with volume loss in brain regions known to receive vestibular input. To address this gap, we investigated the association between vestibular function and the volumes of four structures that process vestibular information (the hippocampus, entorhinal cortex, thalamus, and basal ganglia) in a longitudinal study of 97 healthy, older participants from the Baltimore Longitudinal Study of Aging. Vestibular testing included cervical vestibular-evoked myogenic potentials (cVEMP) to measure saccular function, ocular VEMP (oVEMP) to measure utricular function, and video head impulse tests to measure the horizontal semicircular canal vestibulo-ocular reflex (VOR). Participants in the sample had vestibular and brain MRI data for a total of one (18.6%), two (49.5%), and three (32.0%) visits. Linear mixed-effects regression was used to model regional volume over time as a function of vestibular physiological function, correcting for age, sex, intracranial volume, and intersubject random variation in the baseline levels and rates of change of volume over time. We found that poorer saccular function, characterized by lower cVEMP amplitude, is associated with reduced bilateral volumes of the basal ganglia and thalamus at each time point, demonstrated by a 0.0714 cm3 ± 0.0344 (unadjusted p = 0.038; 95% CI: 0.00397–0.139) lower bilateral-mean volume of the basal ganglia and a 0.0440 cm3 ± 0.0221 (unadjusted p = 0.046; 95% CI: 0.000727–0.0873) lower bilateral-mean volume of the thalamus for each 1-unit lower cVEMP amplitude. We also found a relationship between a lower mean VOR gain and lower left hippocampal volume (β = 0.121, unadjusted p = 0.018, 95% CI: 0.0212–0.222). There were no significant associations between volume and oVEMP. These findings provide insight into the specific brain structures that undergo atrophy in the context of age-related loss of peripheral vestibular function.

Structural and Functional Neuroplasticity Following Bilateral Vestibular Loss: A Longitudinal [18F]-UCB-H/[18F]-FDG Dual Tracer Rat Study

Neuronal lesions trigger mechanisms of structural and functional neuroplasticity, which can support recovery. However, the temporal and spatial appearance of structure-function changes and their interrelation remain unclear. The current study aimed to directly compare serial whole-brain in vivo measurements of functional plasticity (by [18F]-FDG-PET) and structural synaptic plasticity (by [18F]-UCB-H-PET) before and after bilateral labyrinthectomy in rats and investigate the effect of locomotor training. Complex structure-function changes were found after bilateral labyrinthectomy: in brainstem-cerebellar circuits, regional cerebral glucose metabolism (rCGM) decreased early, followed by reduced synaptic density. In the thalamus, increased [18F]-UCB-H binding preceded a higher rCGM uptake. In frontal-basal ganglia loops, an increase in synaptic density was paralleled by a decrease in rCGM. In the group with locomotor training, thalamic rCGM and [18F]-UCB-H binding increased following bilateral labyrinthectomy compared to the no training group. Rats with training had relatively fewer body rotations. In conclusion, combined [18F]-FDG/[18F]-UCB-H dual tracer imaging reveals that adaptive neuroplasticity after bilateral vestibular loss is not a uniform process but is composed of complex spatial and temporal patterns of structure-function coupling in networks for vestibular, multisensory, and motor control, which can be modulated by early physical training.

Decreased activity of piriform cortex and orbitofrontal hyperactivation in Usher Syndrome, a human disorder of ciliary dysfunction

Usher syndrome (USH) is a condition characterized by ciliary dysfunction leading to retinal degeneration and hearing/vestibular loss. Putative olfactory deficits in humans have been documented at the psychophysical level and remain to be proven at the neurophysiological level. Thus, we aimed to study USH olfactory impairment using functional magnetic resonance imaging. We analyzed differences in whole-brain responses between 27 USH patients and 26 healthy participants during an olfactory detection task with a bimodal odorant (n-butanol). The main research question was whether between-group differences could be identified using a conservative whole-brain approach and in a ROI-based approach in key olfactory brain regions. Results indicated higher olfactory thresholds in USH patients, thereby confirming the hypothesis of reduced olfactory acuity. Importantly, we found decreased BOLD activity for USH patients in response to odorant stimulation in the right piriform cortex, while right orbitofrontal cortex showed increased activity. We also found decreased activity in other higher-level regions in a whole brain approach. We suggest that the hyper activation in the orbitofrontal cortex possibly occurs as a compensatory mechanism after the under-recruitment of the piriform cortex. This study suggests that olfactory deficits in USH can be objectively assessed using functional neuroimaging which reveals differential patterns of activity both in low- and high-level regions of the olfactory network.

Prevalence of Pediatric and Adolescent Balance Disorders: Analysis of a Mono-Institutional Series of 472 Patients

(1) Background: To assess the prevalence and frequency distribution of balance disorders in children and adolescents to delineate the planning of a targeted clinical and instrumental diagnostic work-up; (2) Methods: Retrospective analysis of the clinical documentation of patients under 18 years suffering from balance disorders from 2010 to 2019. Detailed collection of clinical history, accurate clinical examination, including both nystagmus and vestibulospinal signs examinations, and specific instrumental testing were the basis of the diagnostic process. (3) Results: A total of 472 participants were included in the study. Vestibular loss (26.1%) was the most frequent cause of vertigo in children, followed by vestibular migraine (21.2%) and benign paroxysmal positional vertigo (10.2%). In 1.1% of patients, the cause of vertigo remained undefined; (4) Conclusions: The diagnostic process applied was effective in understanding the cause of balance disorders in most cases and prevents more complex and expensive investigations reserved for only a few selected cases.

Representation of Body Orientation in Vestibular-Defective Patients Before and After Unilateral Vestibular Loss

Introduction: The unilateral vestibular syndrome results in postural, oculomotor, perceptive, and cognitive symptoms. This study was designed to investigate the role of vestibular signals in body orientation representation, which remains poorly considered in vestibular patients.Methods: The subjective straight ahead (SSA) was investigated using a method disentangling translation and rotation components of error. Participants were required to align a rod with their body midline in the horizontal plane. Patients with right vestibular neurotomy (RVN; n =8) or left vestibular neurotomy (LVN; n = 13) or vestibular schwannoma resection were compared with 12 healthy controls. Patients were tested the day before surgery and during the recovery period, 7 days and 2 months after the surgery.Results: Before and after unilateral vestibular neurotomy, i.e., in the chronic phases, patients showed a rightward translation bias of their SSA, without rotation bias, whatever the side of the vestibular loss. However, the data show that the lower the translation error before neurotomy, the greater its increase 2 months after a total unilateral vestibular loss, therefore leading to a rightward translation of similar amplitude in the two groups of patients. In the early phase after surgery, SSA moved toward the operated side both in translation and in rotation, as typically found for biases occurring after unilateral vestibular loss, such as the subjective visual vertical (SVV) bias.Discussion and Conclusion: This study gives the first description of the immediate consequences and of the recovery time course of body orientation representation after a complete unilateral vestibular loss. The overall evolution differed according to the side of the lesion with more extensive changes over time before and after left vestibular loss. It is noteworthy that representational disturbances of self-orientation were highly unusual in the chronic stage after vestibular loss and similar to those reported after hemispheric lesions causing spatial neglect, while classical ipsilesional biases were reported in the acute stage. This study strongly supports the notion that the vestibular system plays a major role in body representation processes and more broadly in spatial cognition. From a clinical point of view, SSA appeared to be a reliable indicator for the presence of a vestibular disorder.

Peripheral Vestibular Dysfunction Is a Common Occurrence in Children With Non-syndromic and Syndromic Genetic Hearing Loss

Hearing loss (HL) is the most common sensory deficit in humans and is frequently accompanied by peripheral vestibular loss (PVL). While often overlooked, PVL is an important sensory dysfunction that may impair development of motor milestones in children and can have a significant negative impact on quality of life. In addition, many animal and in vitro models of deafness use vestibular hair cells as a proxy to study cochlear hair cells. The extent of vestibular end organ dysfunction associated with genetic pediatric hearing loss is not well-understood. We studied children with a known genetic cause of hearing loss who underwent routine preoperative vestibular testing prior to cochlear implantation between June 2014 and July 2020. Vestibular testing included videonystagmography, rotary chair, video head impulse testing, and/or vestibular evoked myogenic potentials. Etiology of HL was determined through history, physical examination, imaging, laboratory testing, and/or genetic testing. Forty-four children (21 female/23 male) met inclusion criteria; 24 had genetic non-syndromic and 20 had genetic syndromic forms of HL. Mean age at the time of testing was 2.8 ± 3.8 years (range 7 months−17 years). The most common cause of non-syndromic HL was due to mutations in GJB2 (n = 13) followed by MYO15A (3), MYO6 (2), POU3F4 (2), TMPRSS3 (1), CDH23 (1), TMC1 (1), and ESRRB (1). The most common forms of syndromic HL were Usher syndrome (4) and Waardenburg (4), followed by SCID/reticular dysgenesis (3), CHARGE (2), CAPOS (1), Coffin-Siris (1), Jervell and Lange-Nielsen (1), Noonan (1), peroxisome biogenesis disorder (1), Perrault (1), and Trisomy 21 (1). Overall, 23 patients (52%) had PVL. A larger proportion of children with syndromic forms of HL had PVL (12/20, 60%) compared with children with genetic non-syndromic HL (11/24, 46%), though without statistical significant (p = 0.3). The occurrence of PVL varied by affected gene. In conclusion, PVL is a common finding in children with syndromic and non-syndromic genetic HL undergoing vestibular evaluation prior to cochlear implantation. Improved understanding of the molecular physiology of vestibular hair cell dysfunction is important for clinical care as well as research involving vestibular hair cells in model organisms and in vitro models.

The Neural Basis of Skull Vibration Induced Nystagmus (SVIN)

I list a summary of the major clinical observations of SVIN in patients with total unilateral vestibular loss (TUVL) and show how basic results from neurophysiology can explain these clinical observations. The account integrates results from single neuron recordings of identified semicircular canal and otolith afferent neurons in guinea pigs in response to low frequency skull vibration with evidence of the eye movement response in cats to selective semicircular canal stimulation (both individual and combined) and a simple model of nystagmus generation to show how these results explain most of the major characteristics of SVIN.

The Cognitive-Vestibular Compensation Hypothesis: How Cognitive Impairments Might Be the Cost of Coping With Compensation

Previous research in vestibular cognition has clearly demonstrated a link between the vestibular system and several cognitive and emotional functions. However, the most coherent results supporting this link come from rodent models and healthy human participants artificial stimulation models. Human research with vestibular-damaged patients shows much more variability in the observed results, mostly because of the heterogeneity of vestibular loss (VL), and the interindividual differences in the natural vestibular compensation process. The link between the physiological consequences of VL (such as postural difficulties), and specific cognitive or emotional dysfunction is not clear yet. We suggest that a neuropsychological model, based on Kahneman’s Capacity Model of Attention, could contribute to the understanding of the vestibular compensation process, and partially explain the variability of results observed in vestibular-damaged patients. Several findings in the literature support the idea of a limited quantity of cognitive resources that can be allocated to cognitive tasks during the compensation stages. This basic mechanism of attentional limitations may lead to different compensation profiles in patients, with or without cognitive dysfunction, depending on the compensation stage. We suggest several objective and subjective measures to evaluate this cognitive-vestibular compensation hypothesis.