Altered large-scale functional brain networks in neurological Wilson's disease

Wilson's disease patients with neurological symptoms have motor symptoms and cognitive deficits, including frontal executive, visuospatial processing, and memory impairments. Although the brain structural abnormalities associated with Wilson's disease have been documented, it remains largely unknown how Wilson's disease affects large-scale functional brain networks. In this study, we investigated functional brain networks in Wilson's disease. Particularly, we analyzed resting state functional magnetic resonance images of 30 Wilson's disease patients and 26 healthy controls. First, functional brain networks for each participant were extracted using an independent component analysis method. Then, a computationally efficient pattern classification method was developed to identify discriminative brain functional networks associated with Wilson's disease. Experimental results indicated that Wilson's disease patients, compared with healthy controls, had altered large-scale functional brain networks, including the dorsal anterior cingulate cortex and basal ganglia network, the middle frontal gyrus, the dorsal striatum, the inferior parietal lobule, the precuneus, the temporal pole, and the posterior lobe of cerebellum. Classification models built upon these networks distinguished between neurological WD patients and HCs with accuracy up to 86.9% (specificity: 86.7%, sensitivity: 89.7%). The classification scores were correlated with the United Wilson's Disease Rating Scale measures and durations of disease of the patients. These results suggest that Wilson's disease patients have multiple aberrant brain functional networks, and classification scores derived from these networks are associated with severity of clinical symptoms.