Default-mode network connectivity in cognitively unimpaired drug-naive patients with rigidity-dominant Parkinson's disease

Parkinson's disease (PD) with akinetic rigidity (PDAR) is more likely to develop cognitive deficits compared to PD with tremor-dominant symptoms (PDTD). The default mode network (DMN) is highly relevant for cognitive processes, so this study tested the functional connectivity (FC) of DMN in cognitively unimpaired PDAR patients. Resting-state fMRI data were collected in 21 cognitively unimpaired early stage drug-naive patients with PDAR and 21 healthy controls (HC). PD patients were matched closely to HCs for demographic and cognitive variables. FC of DMN was evaluated by seed-based correlation approach. Compared to HCs, despite comparable cognitive performance and no statistically discernible GM volume differences, a disruption in the DMN of PDAR subjects was detected. A decreased FC of DMN was found, specifically prominent in the posterior DMN. We also found a significantly increased FC of the anterior DMN. Three parts of left medial prefrontal regions (anterior, ventral, and dorsal) had significantly increased FC with the cerebellum. In addition, increased FC values of the anterior and ventral parts were negatively correlated with cognitive scores. An evident decline of FC of posterior DMN and enhanced compensatory FC of anterior DMN suggested an early functional disruption of DMN in PDAR prior to clinical evidence of cognitive impairment. It could be hypothesized that the dysfunction of DMN connectivity may have a role in the development of cognitive decline in PD. However, further longitudinal studies are warranted to understand the underlying neural mechanisms and their relevance to clinical and cognitive outcomes in PDAR subtype.