Regional brain dysfunction patterns associated with rapid eye movement sleep behavior disorder and visual hallucinations in Parkinson’s disease: a resting-state fMRI study with exploratory ROI-based factorial analysis

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Background Rapid eye movement sleep behavior disorder (RBD) and visual hallucinations (VH) are prognostically relevant non-motor symptoms in Parkinson’s disease (PD), but their combined effects on local brain dysfunction remain unclear. Objective To characterize regional brain dysfunction patterns associated with RBD and VH in PD and to explore candidate-region symptom-related effects within regions showing overall between-group differences. Methods In this cross-sectional study, 96 patients with PD were divided into four groups according to the presence or absence of RBD and VH (24 per group). Resting-state functional MRI was analyzed using amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). Whole-brain four-group analyses were first used to identify regions with overall between-group differences, followed by exploratory ROI-based 2 × 2 factorial analyses within candidate regions. Additional whole-brain voxel-wise 2 × 2 factorial analyses were performed as supplementary analyses. Correlations between imaging indices and clinical scales were also examined. Results Patients with both RBD and VH showed the greatest clinical burden and worse cognitive performance. Whole-brain analyses revealed abnormalities in frontal, temporal, cerebellar, supplementary motor, and precuneus regions. Exploratory candidate-region analyses with Benjamini–Hochberg FDR correction showed RBD-related patterns in precuneus ReHo, cerebellar lobule VIII ReHo, and SMA ALFF; VH-related patterns in OFC ReHo, precuneus ReHo, cerebellar Crus I ReHo, SMA ALFF, and temporal pole ALFF; and interaction-like patterns in OFC ReHo and temporal pole ALFF. These ROI-based findings were interpreted as post hoc exploratory results rather than independent confirmatory evidence. Imaging abnormalities were correlated with RBD severity, freezing of gait, hallucination burden, and cognition. Conclusion Coexisting RBD and VH may identify a clinically more severe PD subtype associated with regional abnormalities involving cerebellar, motor, default mode, and association-related regions. Symptom-related main and interaction patterns should be interpreted as candidate-region exploratory findings requiring further confirmation in larger studies.