Structural and Functional Connectivity in Parkinson's Disease Patients With Freezing of Gait and Other Gait Disturbances

ABSTRACT Background Freezing of gait (FoG) is a debilitating motor feature that affects individuals with Parkinson's disease (PD). The mechanism underlying FoG is not entirely understood, which poses a challenge in finding effective treatment. The goal of this study is to advance the understanding of FoG pathophysiology. This study aims to assess the differences in structural connectivity (SC) and functional connectivity (FC) patterns among PD patients with freezing of gait (FoG+), gait disturbances other than freezing (FoG−), and no gait disturbances (NGD). Methods Diffusion‐weighted MRI (dwMRI) and resting‐state functional MRI (rs‐fMRI) were obtained from 9 FoG+, 13 FoG−, and 10 NGD patients. The FC data was processed by a region of interest (ROI)‐to‐ROI analysis using the default preprocessing pipeline from the MATLAB‐based CONN toolbox. SC analysis was performed via diffusion‐based tractography and subsequent connectome reconstructions in MRtrix3. Results Compared to the FoG− and NGD groups, the FoG+ group showed substantial involvement, in both SC and FC, of the limbic system, putamen, parietal lobes, and cerebellum. Furthermore, our results reveal FC alteration between the cerebellum and the median raphe nuclei, which is part of the pontomedullary reticular formation. Conclusions Our results confirmed previous research regarding the alterations in multiple brain areas in those with FoG, particularly the limbic system, putamen, parietal lobe, and cerebellum. We further establish unique FC between the cerebellum and the median raphe nucleus in those with FoG. This finding highlights the role of the cerebellum in regulating posture, gait, and locomotive signals, potentially through serotonergic projections.