Reduced task-related functional connectivity during a set-shifting task in unmedicated Parkinson’s disease patients

Patients with Parkinson's disease (PD) often suffer from cognitive impairments, including set-shifting deficits, in addition to the characteristic motor symptoms. It is hypothesized that the striatal dopamine depletion leads to a sub-optimal functional connectivity between task-related brain areas and consequently results in impaired task-performance. In this study, we aimed to examine this hypothesis by investigating the task-related functional connectivity of brain areas that are believed to be involved in set-shifting, such as the dorsolateral prefrontal cortex (DLPFC), posterior parietal cortex (PPC) and the superior frontal gyrus (SFG), during a set-shifting task. The neural activity of 18 unmedicated patients with PD, and 35 age-, gender-, and education-matched healthy controls was recorded while performing a set-shifting task in an MRI scanner. We found that PD patients, compared with controls, showed i) a decrease in positive coupling between the left DLPFC and the right insular cortex, and the right SFG and anterior cingulate cortex, ii) an increase in positive coupling between the left SFG and the perirhinal cortex, and iii) an increase in negative coupling between the right SFG and the anterior cingulate cortex, primary motor cortex, precuneus, and PPC, and an increase in negative coupling between the left DLPFC and the left and right SFG. These results indicate that important task-related areas of PD patients have decreased functional connectivity with task-related regions and increased connectivity with task-unrelated areas. We hypothesize that the hyperactivation we found in PD patients in our previous study compensates for this sub-optimal functional connectivity, thereby forestalling behavioural deficits.