Perfusion Imaging of Fatigue and Time-on-Task Effects in Patients With Parkinson's Disease

Fatigue is a highly prevalent and debilitating non-motor symptom in Parkinson's disease (PD), yet its' neural mechanisms remain poorly understood. Here we combined arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) with a sustained mental workload paradigm to examine the neural correlates of fatigue and time-on-task effects in PD patients. Twenty-one PD patients were scanned at rest and during continuous performance of a 20-min psychomotor vigilance test (PVT). Time-on-task effects were measured by the reaction time changes during the PVT and by self-reported fatigue ratings before and after the PVT. PD subjects demonstrated significant time-on-task effects, including progressively slower reaction time on the PVT and increased post-PVT fatigue ratings compared to pre-PVT. Higher levels of general fatigue were associated with larger increases in mental fatigue ratings after the PVT. ASL imaging data showed increased CBF in the right middle frontal gyrus (MFG), bilateral occipital cortex, and right cerebellum during the PVT compared to rest, and decreased CBF in the right MFG at post-task rest compared to pre-task rest. The magnitude of regional CBF changes in the right MFG and right inferior parietal lobe correlated with subjective fatigue rating increases after the PVT task. These results demonstrate the utility of continuous PVT paradigm for future studies of fatigue and cognitive fatigability in patients, and support the key role of the fronto-parietal attention network in mediating fatigue in PD.