Resting-state fMRI study on drug-naïve early-stage patients with Parkinson's disease and with fatigue

Fatigue is one of the most common and debilitating non-motor symptoms in patients with Parkinson's disease (PD), which could manifest during the early stage of the disease and persist through the disease course. However, the treatment options for fatigue remain limited for patients with PD.Using seed-based resting-state functional magnetic resonance imaging, we explored the fatigue-related functional deficiencies in the anterior caudate nucleus, anterior putamen, and posterior putamen in a cohort of early-stage drug-naïve patients with PD. Thirty-eight patients with PD, 19 with and 19 without fatigue, and 31 matched healthy controls were selected. The fatigue status was defined based on the score obtained from the fatigue severity scale (FSS).Patients with PD with fatigue exhibited a decreased connectivity in the cerebellar-striatal, cortico-striatal, and mesolimbic-striatal loops. No increased functional connectivity was observed. The abnormal connections of the dorsal striatum subdivisions overlapped to extensive brain regions, including the cerebellum, inferior frontal gyrus, inferior temporal gyrus, lingual gyrus, rolandic operculum, insular, and hippocampus.Our findings revealed that the widespread functional deficiency in the striatal-cerebellar-cerebral cortical network may be critical to the pathology underlying fatigue in the early-stage PD. The key feature of fatigue-related connectivity was observed between the caudate nucleus and the cerebellum, which could serve as a potential biomarker or treatment target for fatigue in early-stage patients with PD in future studies.