Fatigue brain network functional connectivity in Parkinson's disease

Fatigue is a nonmotor symptom that negatively affects Parkinson's disease (PD) patients' quality of life. The study of fatigue is complex and the brain functional neural underpinnings of fatigue in PD are yet to be clarified. The aim of this study was to investigate the functional connectivity (FC) of the fatigue brain network in PD-related fatigue symptomatology. Forty-nine PD patients, divided into PD patients with fatigue (PD-f) and PD patients with no fatigue (PD-nf), and 33 healthy controls participated in the study. Participants completed the Fatigue Severity Scale for the assessment of fatigue and underwent an extensive neuropsychological battery. Functional magnetic resonance imaging was also obtained during resting-state. FC differences were studied using a whole-brain analysis with CONN Functional Connectivity Toolbox. The PD-f group showed lower FC between left dorsolateral prefrontal cortex and right accumbens (reward network), and higher FC between the left insula and left posterior parahippocampal gyrus (interoceptive paralimbic area) compared to the PD-nf group. Fatigue was positively correlated with the FC between the left insula and the left posterior parahippocampal gyrus in PD. Hypoactivation in the reward network and hyperactivation in the interoceptive-paralimbic areas may be underlying factors in fatigue symptomatology in PD. In fact, fatigue was found to be correlated with FC in interoceptive-paralimbic areas. These results contribute to a better understanding of the underlying neural mechanisms of the fatigue brain network in PD patients.