Altered interhemispheric functional cooperation in persistent postural-perceptual dizziness

Background Persistent postural-perceptual dizziness (PPPD) is associated with altered multisensory processing, but its hemispheric functional organization remains poorly understood. We investigated hemispheric functional lateralization and interhemispheric cooperation in PPPD and explored their associations with clinical symptoms and neurotransmitter density maps. Methods A total of 47 patients with PPPD and 52 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Whole-brain maps of the autonomy index (AI) and connectivity between functionally homotopic voxels (CFH) were generated. Between-group differences were assessed using permutation-based analyses adjusted for age, sex, and mean framewise displacement (FD). Associations with clinical measures and spatial correspondence with 13 neurotransmitter density maps were also examined. Results The PPPD and HC groups did not differ significantly in age, sex, or educational level (all p > 0.05). Patients with PPPD had lower MoCA-BJ scores and higher HAMA-14, HAMD-24, PSQI, and DHI scores than HCs, whereas MMSE scores did not differ significantly. No between-group differences in AI survived family-wise error (FWE) correction. By contrast, in the primary analysis, patients with PPPD showed significantly reduced CFH in the right calcarine cortex, right cuneus, left inferior and middle occipital gyri, left inferior parietal lobule, and right middle temporal gyrus. However, no CFH clusters survived cluster-level FWE correction after separately adjusting for HAMA-14, HAMD-24, or PSQI scores. After adjustment for age, sex, and mean FD, CFH in the right calcarine cortex and left inferior parietal lobule showed negative associations with DHI total and DHI-E scores, respectively (Shepherd’s π = −0.363 and −0.452), but neither association remained significant after false discovery rate (FDR) correction. The CFH group-difference map showed nominal positive spatial correlations with the D 2 R and VACh T density maps, but these associations were not significant after FDR correction. Conclusion In primary analysis, PPPD patients exhibited reduced interhemispheric functional cooperation in visual, visuospatial and multisensory regions, while no AI differences survived FWE correction. However, these CFH findings were sensitive to adjustment for affective symptoms and sleep quality; the relative contributions of PPPD, affective symptoms and sleep disturbance remain uncertain. Clinical and neurotransmitter density-map associations did not survive FDR correction and are exploratory.