Identifying a whole-brain connectome-based model in drug-naïve Parkinson's disease for predicting motor impairment

Abstract

Identifying a whole-brain connectome-based predictive model in drug-naïve patients with Parkinson's disease and verifying its predictions on drug-managed patients would be useful in determining the intrinsic functional underpinnings of motor impairment and establishing general brain-behavior associations. In this study, we constructed a predictive model from the resting-state functional data of 47 drug-naïve patients by using a connectome-based approach. This model was subsequently validated in 115 drug-managed patients. The severity of motor impairment was assessed by calculating Unified Parkinson's Disease Rating Scale Part III scores. The predictive performance of model was evaluated using the correlation coefficient (r_true ) between predicted and observed scores. As a result, a connectome-based model for predicting individual motor impairment in drug-naïve patients was identified with significant performance (r_true = .845, p < .001, p_permu = .002). Two patterns of connection were identified according to correlations between connection strength and the severity of motor impairment. The negative motor-impairment-related network contained more within-network connections in the motor, visual-related, and default mode networks, whereas the positive motor-impairment-related network was constructed mostly with between-network connections coupling the motor-visual, motor-limbic, and motor-basal ganglia networks. Finally, this predictive model constructed around drug-naïve patients was confirmed with significant predictive efficacy on drug-managed patients (r = .209, p = .025), suggesting a generalizability in Parkinson's disease patients under long-term drug influence. In conclusion, this study identified a whole-brain connectome-based model that could predict the severity of motor impairment in Parkinson's patients and furthers our understanding of the functional underpinnings of the disease.

Keywords: Parkinson's disease; brain connectome; motor impairment; predictions; resting-state fMRI.