Functional connectivity underpinnings of fatigue in "Drug-Naive" patients with Parkinson's disease

Introduction Fatigue is a common problem in PD either in the early or later stage of the disease. Using resting-state functional MRI, we investigated the functional correlates of fatigue in a cohort of drug-naive patients with PD. MethodsMRI at 3Tesla was collected in 40 patients with PD, 20 with and 20 without fatigue, and 20 matched healthy controls. Presence and the severity of fatigue were defined based on the 16-item Parkinson fatigue scale. Single-subject and group-level independent component analysis was used to investigate functional connectivity differences within the major resting state networks between patients subgroups and healthy controls. In addition, we used voxel-based morphometry to test whether between-group functional changes were related to structural differences. ResultsDistressing fatigue was associated with a decreased connectivity in the supplementary motor area within the sensorimotor network and an increased connectivity in the prefrontal and posterior cingulate cortices within the default mode network (P <0.05 corrected). Fatigue severity was correlated with both sensorimotor and default mode networks connectivity changes. Voxel-based morphometry analysis did not reveal any significant volume differences between all patients with PD and healthy controls and between patients with PD with and without fatigue (P <0.05; family-wise error). ConclusionsOur findings revealed that primary PD-related fatigue is associated with an altered default mode network and sensorimotor network connectivity in drug-naive patients. We hypothesize that these divergent motor and cognitive networks connectivity changes and their adaptive or maladaptive functional outcome may play a prominent role in the pathophysiology of fatigue in PD.