Altered resting-state functional connectivity in patients with chronic bilateral vestibular failure

Abstract

Patients with bilateral vestibular failure (BVF) suffer from gait unsteadiness, oscillopsia and impaired spatial orientation. Brain imaging studies applying caloric irrigation to patients with BVF have shown altered neural activity of cortical visual–vestibular interaction: decreased bilateral neural activity in the posterior insula and parietal operculum and decreased deactivations in the visual cortex. It is unknown how this affects functional connectivity in the resting brain and how changes in connectivity are related to vestibular impairment.We applied a novel data driven approach based on graph theory to investigate altered whole-brain resting-state functional connectivity in BVF patients (n= 22) compared to age- and gender-matched healthy controls (n= 25) using resting-state fMRI. Changes in functional connectivity were related to subjective (vestibular scores) and objective functional parameters of vestibular impairment, specifically, the adaptive changes during active (self-guided) and passive (investigator driven) head impulse test (HIT) which reflects the integrity of the vestibulo-ocular reflex (VOR).BVF patients showed lower bilateral connectivity in the posterior insula and parietal operculum but higher connectivity in the posterior cerebellum compared to controls. Seed-based analysis revealed stronger connectivity from the right posterior insula to the precuneus, anterior insula, anterior cingulate cortex and the middle frontal gyrus. Excitingly, functional connectivity in the supramarginal gyrus (SMG) of the inferior parietal lobe and posterior cerebellum correlated with the increase of VOR gain during active as compared to passive HIT, i.e., the larger the adaptive VOR changes the larger was the increase in regional functional connectivity.Using whole brain resting-state connectivity analysis in BVF patients we show that enduring bilateral deficient or missing vestibular input leads to changes in resting-state connectivity of the brain. These changes in the resting brain are robust and task-independent as they were found in the absence of sensory stimulation and without a region-related a priori hypothesis. Therefore they may indicate a fundamental disease-related change in the resting brain. They may account for the patients' persistent deficits in visuo-spatial attention, spatial orientation and unsteadiness. The relation of increasing connectivity in the inferior parietal lobe, specifically SMG, to improvement of VOR during active head movements reflects cortical plasticity in BVF and may play a clinical role in vestibular rehabilitation.

Association Between Visuospatial Ability and Vestibular Function in the Baltimore Longitudinal Study of Aging

“…A study of 10 individuals with bilateral vestibular failure found that they developed significant hippocampal atrophy and associated impairments in visuospatial tasks such as navigation in a virtual maze . Another study in 22 individuals with bilateral vestibular loss found decreases in functional connectivity of temporoparietal junction structures critical for visuospatial processing and the rest of the brain …”

“…10 Another study in 22 individuals with bilateral vestibular loss found decreases in functional connectivity of temporoparietal junction structures critical for visuospatial processing and the rest of the brain. 37 The association between vestibular and cognitive dysfunction may also relate to the influence of the vestibular system on working memory and attentional processes. A significant association was found in factor analyses between vestibular function and the working memory and attention factor, which chiefly included the Forward and Backward Digit Span tasks, which are tests of short-term memory.…”

Bilateral Vestibular Hypofunction: Challenges in Establishing the Diagnosis in Adults

“…BVH patients rely more on other sensory inputs such as vision [62,63,64]. However, an increased visual dependence can result in symptoms of vertigo that are provoked or aggravated by specific visual contexts (e.g.…”

“…Therefore, the hippocampus could be one of the main structures in which the cognitive and emotional effects of vestibular loss interact [73,74]. Other parts of the brain show changes in resting-state connectivity due to BVH, which may also account for the persistent deficits in visuospatial attention and spatial orientation as well as unsteadiness [63]. In other words, cognitive deficits can be related to vestibulopathy and should not be disregarded while taking the history of a patient.…”

Hippocampal gray matter volume in bilateral vestibular failure

“…However, it may be promising that deafferentation from bilateral peripheral vestibular signals leads to even more fundamental changes: resting‐state activity in the brain, irrespective of any vestibular task, shows profound changes of functional connectivity in BVF patients [Göttlich et al, ]. There was lower bilateral connectivity in the posterior insula and parietal operculum but higher connectivity in the posterior cerebellum.…”