The cholinergic contribution to the resting-state functional network in non-demented Parkinson's disease

The cholinergic system arising from the basal forebrain plays an important role in cognitive performance in Parkinson's disease (PD). Here, we analyzed cholinergic status-dependent cortical and subcortical resting-state functional connectivity in PD. A total of 61 drug-naïve PD patients were divided into tertiles based on normalized substantia innominata (SI) volumes. We compared the resting-state network from seed region of interest in the caudate, posterior cingulate cortex (PCC), and SI between the lowest (PD-L) and highest tertile (PD-H) groups. Correlation analysis of the functional networks was also performed in all subjects. The functional network analysis showed that PD-L subjects displayed decreased striato-cortical functional connectivity compared with PD-H subjects. Selecting the PCC as a seed, the PD-L patients displayed decreased functional connectivity compared to PD-H patients. Meanwhile, PD-L subjects had significantly increased cortical functional connectivity with the SI compared with PD-H subjects. Correlation analysis revealed that SI volume had a positive correlation with functional connectivity from the right caudate and PCC. The present study demonstrated that PD patients exhibited unique functional connectivity from the caudate and the PCC that may be closely associated with cholinergic status, suggesting an important role for the cholinergic system in PD-associated cognition.