Distinct large-scale networks are associated with motor and nonmotor symptoms in Parkinson’s disease

ABSTRACT Parkinson’s disease (PD) is characterized clinically by various motor and nonmotor symptoms. The underlying neuroanatomical correlates of nonmotor symptoms in PD remain poorly understood. We investigated the differences and commonalities in the neuroanatomical correlates 1) between highly prevalent nonmotor features including fatigue, anxiety, depression, and apathy, and 2) between these nonmotor features and motor severity in nondemented subjects with mild PD (Hoehn & Yahr disease stage 2) using structural and functional magnetic resonance imaging. Compared to matched controls, the PD group showed atrophy in the basal ganglia and superior frontal cortex. Motor severity correlated with cortical thinning in frontotemporal regions, as well as with reduced functional connectivity between the frontostriatal and cerebellar networks. The composite nonmotor symptom severity did not show any correlation with the structural brain data, but correlated with reduced functional connectivity in a large-scale network consisting of frontostriatal, parietotemporal, and cerebellar nodes. The individual components of the nonmotor symptoms also mapped onto specific neural networks. Our study shows that motor and nonmotor features in PD are associated with distinct large-scale networks. The basal ganglia and cerebellum are core regions in all of these networks. The abnormal functional connectivity in the nonmotor network seems to be related to cognitive and emotional dysregulation and may have implications for future cognitive decline in PD.