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

AbstractPatients 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

Postural Control in Bilateral Vestibular Failure: Its Relation to Visual, Proprioceptive, Vestibular, and Cognitive Input

Patients with bilateral vestibular failure (BVF) suffer from postural and gait unsteadiness with an increased risk of falls. The aim of this study was to elucidate the differential role of otolith, semicircular canal (SSC), visual, proprioceptive, and cognitive influences on the postural stability of BVF patients. Center-of-pressure displacements were recorded by posturography under six conditions: target visibility; tonic head positions in the pitch plane; horizontal head shaking; sensory deprivation; dual task; and tandem stance. Between-group analysis revealed larger postural sway in BVF patients on eye closure; but with the eyes open, BVF did not differ from healthy controls (HCs). Head tilts and horizontal head shaking increased sway but did not differ between groups. In the dual task condition, BVF patients maintained posture indistinguishable from controls. On foam and tandem stance, postural sway was larger in BVF, even with the eyes open. The best predictor for the severity of bilateral vestibulopathy was standing on foam with eyes closed. Postural control of our BVF was indistinguishable from HCs once visual and proprioceptive feedback is provided. This distinguishes them from patients with vestibulo-cerebellar disorders or functional dizziness. It confirms previous reports and explains that postural unsteadiness of BVF patients can be missed easily if not examined by conditions of visual and/or proprioceptive deprivation. In fact, the best predictor for vestibular hypofunction (VOR gain) was examining patients standing on foam with the eyes closed. Postural sway in that condition increased with the severity of vestibular impairment but not with disease duration. In the absence of visual control, impaired otolith input destabilizes BVF with head retroflexion. Stimulating deficient SSC does not distinguish patients from controls possibly reflecting a shift of intersensory weighing toward proprioceptive-guided postural control. Accordingly, proprioceptive deprivation heavily destabilizes BVF, even when visual control is provided