Abstract
BACKGROUND: After vestibular impairment, the body undergoes static and dynamic compensation. Static compensation is characterized by the resolution of spontaneous nystagmus, indicating rebalanced bilateral vestibular nuclei activity. It remains unclear whether ascending vestibular projections remain abnormal thereafter. This study investigated abnormal functional activity along vestibular nucleus-thalamus-cortex projection pathways in chronic unilateral vestibulopathy (CUVP) after static compensation using degree centrality (DC) and functional connectivity (FC) analyses. METHODS: In total, 25 CUVP patients and 25 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI). The DC analysis identified abnormal functional activity in vestibular nucleus-thalamus-cortex pathways, particularly in the subcortical structures. The seed-based FC analyses used eight seeds (the bilateral vestibular nuclei, and the bilateral pulvinar, mediodorsal, and ventrolateral ventral thalamic regions) with 10,000 non-parametric permutations and a cluster-level family-wise error rate (FWER)-corrected threshold of P<0.05. The region-of-interest (ROI)-based FC analyses examined connections among the vestibular nucleus, thalamic subregions (the pulvinar and ventrolateral ventral thalamus), and multisensory vestibular/sensorimotor/visual cortices with a false discovery rate (FDR)-corrected threshold of P<0.05 to confirm the pathway abnormalities. A regression analysis assessed the relationships between the altered brain metrics and Dizziness Handicap Inventory (DHI) scores. RESULTS: Compared with the healthy controls, the CUVP patients showed reduced DC in the bilateral thalamus (ventrolateral ventral thalamus, and pulvinar), cerebellum, precuneus, postcentral gyrus, and premotor areas (all FDR-corrected P<0.05). Using the vestibular nucleus, pulvinar, and ventrolateral ventral thalamus as the seed regions, similar bilateral patterns of FC change were observed, with notably reduced FC between the pulvinar and visual cortex, as well as between the ventrolateral ventral thalamus and sensorimotor cortex (all FWER-corrected P<0.05). The ROI-based FC analyses confirmed abnormalities along the vestibular nucleus-ventrolateral ventral thalamus/pulvinar-multisensory vestibular/sensorimotor/visual cortices pathways (all FDR-corrected P<0.05). The regression analysis revealed negative associations between thalamic DC/FC changes and DHI scores (all FDR-corrected P<0.05). CONCLUSIONS: Patients with CUVP exhibit persistent abnormalities in the vestibular nucleus-thalamus-cortex pathways even after the establishment of static compensation. The ventrolateral ventral thalamus and pulvinar may serve as key nodes in these abnormalities.