Abstract
BACKGROUND AND PURPOSE: Resting-state functional MRI (rs-fMRI) studies in Parkinson's disease (PD) patients with freezing of gait (FOG) have implicated dysfunctional connectivity over multiple resting-state networks (RSNs). While these findings provided network-specific insights and information related to the aberrant or altered regional functional connectivity (FC), whether these alterations have any effect on topological reorganization in PD-FOG patients is incompletely understood. Understanding the higher order functional organization, which could be derived from the "hub" and the "rich-club" organization of the functional networks, could be crucial to identifying the distinct and unique pattern of the network connectivity associated with PD-FOG. METHODS: In this study, we use rs-fMRI data and graph theoretical approaches to explore the reorganization of RSN topology in PD-FOG when compared to those without FOG. We also compared the higher order functional organization derived using the hub and rich-club measures in the FC networks of these PD-FOG patients to understand whether there is a topological reorganization of these hubs in PD-FOG. RESULTS: We found that the PD-FOG patients showed a noticeable reorganization of hub regions. Regions that are part of the prefrontal cortex, primary somatosensory, motor, and visuomotor coordination areas were some of the regions exhibiting altered hub measures in PD-FOG patients. We also found a significantly altered feeder and local connectivity in PD-FOG. CONCLUSIONS: Overall, our findings demonstrate a widespread topological reorganization and disrupted higher order functional network topology in PD-FOG that may further assist in improving our understanding of functional network disturbances associated with PD-FOG.