Altered Intra- and Inter-Network Connectivity in Drug-Naive Patients With Early Parkinson's Disease

The aim of our study was to investigate differences in whole brain connectivity at different levels between drug-naive individuals with early Parkinson's disease (PD) and healthy controls (HCs). Resting-state functional magnetic resonance imaging data were collected from 47 patients with early-stage, drug-naive PD and 50 HCs. Functional brain connectivity was analyzed at the integrity, network, and edge levels; UPDRS-III, MMSE, MOCA, HAMA, and HAMD scores, reflecting the symptoms of PD, were collected for further regression analysis. Compared with age-matched HCs, reduced functional connectivity were mainly observed in the visual (VSN), somatomotor (SMN), limbic (LBN), and deep gray matter networks (DGN) at integrity level [p < 0.05, false discovery rate (FDR) corrected]. Intra-network analysis indicated decreased functional connectivity in DGN, SMN, LBN, and ventral attention networks (VAN). Inter-network analysis indicated reduced functional connectivity in nine pairs of resting-state networks. At the edge level, the LBN was the center of abnormal functional connectivity (p < 0.05, FDR corrected). MOCA score was associated with the intra-network functional connectivity strength (FC) of the DGN, and inter-network FC of the DGN-VAN. HAMA and HAMD scores were associated with the FC of the SMN and DGN, and either the LBN or VAN, respectively. We demonstrated variations in whole brain connections of drug-naive patients with early PD. Major changes involved the SMN, DGN, LBN, and VSN, which may be relevant to symptoms of early PD. Additionally, our results support PD as a disconnection syndrome.

Automated summary

This study investigated differences in whole brain connectivity between drug-naive individuals with early Parkinson's disease and healthy controls. The findings suggest that there are reduced functional connectivity in multiple brain networks in PD patients, and these connectivity changes are associated with symptoms and cognitive function.