Abnormal visual-vestibular cerebro-cerebellar connectivity in persistent postural-perceptual dizziness

Objective: Patients with persistent postural-perceptual dizziness (PPPD) perceive unsteadiness associated with abnormal ego- or visual motion perception. Maladaptive multisensory integration and visual dependency have been proposed implicating abnormal functional connectivity (FC). Based on the crucial impact of the cerebellum for prediction errors of sensory perception, we specifically investigated group-related differences in FC between visual cortex, multisensory vestibular cortical areas and the cerebellum. Methods: Resting-state activity (seed-based functional connectivity using a priori regions of interest and fractional amplitude of low-frequency fluctuations, fALFF) was compared between a large cohort of 53 PPPD patients and 54 age- and sex-matched HC and related to various disease parameters and baseline postural sway speed. Results: FC between the patients' posterior insula and the visual (lingual) cortex, as well as the supramarginal gyrus was lower. In contrast, it was markedly larger between the patients' (i) visual motion-related area MT/V5 and cerebellar Crus I, (ii) multisensory operculum and caudal vermis, (iii) OP3 and Crus II, and (iv) inferior parietal lobe and vermis. fALFF was larger in the patients' right hippocampus. Interpretation: The abnormally low cortical visual-vestibular FC may provide a neural substrate for the patients' maladaptive multisensory integration with aberrant inter-sensory reweighting. The larger cerebro-cerebellar FC with cerebellar areas involved in sensory and postural prediction errors control (required for updating internal models of motion) might account for the abnormally high sensory precision weighting leading to the patients' altered egomotion perception. Longitudinal studies are required to investigate whether the larger cerebrocerebellar connectivity is compensatory or dysfunctional in nature.