Abstract
INTRODUCTION: This study aims to identify early brain network changes in de novo Parkinson's disease (PD) using resting state-functional Magnetic Resonance Imaging (rs-fMRI), graph-theoretical analysis, and a functional brain network disruption index (k), applied here for the first time to de novo PD. MATERIALS AND METHODS: The study enrolled untreated de novo PD patients and age- and sex-matched healthy controls. PD patients underwent comprehensive clinical assessments (MDS-UPDRS III, H&Y, MMSE, MoCA, NMSS). MRI data were acquired on a 3T system, including 3D T1-weighted MPRAGE and rs-fMRI. rs-fMRI data were pre-processed and analysed using graph theory. RESULTS: The study included 30 de novo PD patients and 30 healthy controls. While global network metrics did not differ significantly, local metrics revealed a reduced disruption index k in de novo PD patients. The disruption index k was negatively correlated with MMSE scores and demonstrated strong discriminatory power between PD patients and healthy controls based on clustering coefficient metrics. Significant differences in hub regions were found, as some disappeared in PD patients while others emerged compared to healthy controls. CONCLUSIONS: This study provides evidence of widespread functional alterations in the local brain networks of de novo Parkinson's disease (PD) patients, suggesting early reorganization of brain connectivity. The disruption index (k) demonstrated the ability to detect early and subtle changes in functional brain networks in de novo Parkinson patients. SIGNIFICANCE: rs-fMRI can provide valuable insights into the early stages of PD pathophysiology helping to understand the complexity of PD.