Functional Brain Dysconnectivity in Parkinson's Disease: A 5‐Year Longitudinal Study

Abstract Background Tracking longitudinal functional brain dysconnectivity in Parkinson's disease (PD) is a key element to decoding the underlying physiopathology and understanding PD progression. Objectives The objectives of this follow‐up study were to explore, for the first time, the longitudinal changes in the functional brain networks of PD patients over 5 years and to associate them with their cognitive performance and the lateralization of motor symptoms. Methods We used a 5‐year longitudinal cohort of PD patients (n = 35) who completed motor and non‐motor assessments and sequent resting state (RS) high‐density electroencephalography (HD‐EEG) recordings at three timepoints: baseline (BL), 3 years follow‐up (3YFU) and 5 years follow‐up (5YFU). We assessed disruptions in frequency‐dependent functional networks over the course of the disease and explored their relation to clinical symptomatology. Results In contrast with HC (n = 32), PD patients showed a gradual connectivity impairment in α2 (10‐13 Hz) and β (13–30 Hz) frequency bands. The deterioration in the global cognitive assessment was strongly correlated with the disconnected networks. These disconnected networks were also associated with the lateralization of motor symptoms, revealing a dominance of the right hemisphere in terms of impaired connections in the left‐affected PD patients in contrast to dominance of the left hemisphere in the right‐affected PD patients. Conclusions Taken together, our findings suggest that with disease progression, dysconnectivity in the brain networks in PD can reflect the deterioration of global cognitive deficits and the lateralization of motor symptoms. RS HD‐EEG may be an early biomarker of PD motor and non‐motor progression. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society