Functional connectivity between resting-state networks reflects decline in executive function in Parkinson's disease: A longitudinal fMRI study

Deficits in cognitive functioning are a common yet poorly understood symptom in Parkinson's disease (PD). Recent studies have highlighted the importance of (dynamic) interactions between resting-state networks for cognition, which remains understudied in PD. We investigated how altered (dynamic) functional interactions between brain networks relate to cognitive dysfunction in PD patients. In this fMRI study, 50 PD patients (mean age 65.5 years ± 6.27) on dopaminergic medication were studied cross-sectionally, and of this cohort 31 PD patients were studied longitudinally. MRI imaging and neuropsychological testing was performed at two time points, with a follow-up duration of approximately three years. Functional connectivity within and between seven resting-state networks was calculated (both statically and dynamically) and correlated with four neuropsychological test scores; a combined score of (four) executive tasks, a motor perseveration, memory, and category fluency task. Cognitive dysfunction was determined based on a longitudinal sample of age-matched healthy controls (n = 13). PD patients showed dysfunction on six out of seven cognitive tasks when compared to healthy controls. Severity of executive dysfunction was correlated with higher static and lower dynamic functional connectivity between deep gray matter regions and the frontoparietal network (DGM-FPN). Over time, declining executive function was related to increasing static DGM-FPN connectivity, together with changes of connectivity involving the dorsal attention network (amongst others with the ventral attention network). Static functional connectivity between the ventral and dorsal attention network correlated with motor perseveration. Our findings demonstrate that in PD patients, dysfunctional communication between (i) subcortical, fronto-parietal and attention networks mostly underlies worsening of executive functioning, (ii) attention networks are involved in motor perseveration