Altered static and dynamic regional homogeneity in basal ganglia–thalamocortical circuits and their association with neuropsychiatric manifestations in Wilson’s disease

Purpose: Wilson's disease (WD) is an autosomal recessive disorder caused by ATP7B mutations, resulting in impaired copper metabolism and progressive neuropsychiatric manifestations. This study investigated spatiotemporal alterations in regional brain activity using static and dynamic resting-state fMRI with regional homogeneity (ReHo), and their relationships with clinical features. Methods: Resting-state fMRI data were acquired from WD patients and healthy controls (HCs). Static and dynamic ReHo analyses were performed to characterize local synchronization strength and temporal variability of spontaneous neural activity. Group differences were assessed across the basal ganglia, thalamus, cerebellum, and cortical regions. Associations between altered ReHo metrics and clinical measures were evaluated with FDR correction for multiple comparisons. Results: Compared with HCs, WD patients exhibited widespread ReHo abnormalities involving the basal ganglia (putamen and globus pallidus), thalamus, cerebellum, and cortical regions. Static ReHo in the left putamen and globus pallidus was positively associated with anxiety severity, while right putaminal ReHo was negatively associated with neurological severity and positively associated with disease duration. Dynamic ReHo in the left middle frontal gyrus showed negative associations with depression severity and disease duration. All brain-behavior correlations survived FDR correction, indicating robust effects. Conclusion: WD is characterized by disrupted spatiotemporal organization of local functional synchronization within cerebellar and basal ganglia-thalamo-cortical circuits. These findings support a network-level dysfunction model involving subcortical synchronization deficits and cortical temporal instability, which together underpin neuropsychiatric manifestations and disease progression.