Reduced functional connectivity in early-stage drug-naive Parkinson's disease: a resting-state fMRI study

Although cardinal motor symptoms in Parkinson's disease (PD) are attributed to dysfunction of corticostriatal loops, early clinical nonmotor features are more likely to be associated with other pathologic mechanisms. We enrolled 52 early-stage drug-naive PD patients and 52 age- and sex-matched healthy controls and used resting-state functional connectivity magnetic resonance imaging to evaluate alteration of the functional brain network in PD, focusing in particular on the functional connectivity of the striatum subregions. Relative to healthy controls, the PD patient group showed reduced functional connectivity in mesolimbic-striatal and corticostriatal loops. Although the deceased functional connectivity within cortical sensorimotor areas was only evident in the most affected putamen subregion, reduced functional connectivity with mesolimbic regions was prevalent throughout the striatum. No increased functional connectivity was found in this cohort. By studying a cohort of early-stage drug-naive PD patients, we ruled out the potential confounding effect of prolonged antiparkinson medication use on the functional integration of neural networks. We demonstrate decreased functional integration across neural networks involving striatum, mesolimbic cortex, and sensorimotor regions in these patients and postulate that the prevalent disconnection in mesolimbic-striatal loops is associated with some early clinical nonmotor features in PD. This study offers additional insight into the early functional integration of neural networks in PD.