Topological reorganization of functional hubs in patients with Parkinson's disease with freezing of gait

Author:

Sreenivasan Karthik1,Bayram Ece2,Zhuang Xiaowei1,Longhurst Jason3,Yang Zhengshi1,Cordes Dietmar14,Ritter Aaron1,Caldwell Jessica1,Cummings Jeffrey L.5,Mari Zoltan1,Litvan Irene2,Bluett Brent6,Mishra Virendra R.17ORCID

Affiliation:

1. Cleveland Clinic Lou Ruvo Center for Brain Health Las Vegas Nevada USA

2. Department of Neurosciences University of California San Diego La Jolla California USA

3. Department of Physical Therapy and Athletic Training Saint Louis University St. Louis Missouri USA

4. Department of Radiology University of Colorado Boulder Boulder Colorado USA

5. Chambers‐Grundy Center for Transformative Neuroscience Department of Brain Health School of Integrated Health Sciences University of Nevada Las Vegas Nevada USA

6. Central California Movement Disorders Pismo Beach California USA

7. Department of Radiology, Heersink School of Medicine The University of Alabama at Birmingham Birmingham Alabama USA

Abstract

AbstractBackground and PurposeResting‐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.MethodsIn 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.ResultsWe 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.ConclusionsOverall, 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.

Funder

National Institutes of Health

Publisher

Wiley

Subject

Neurology (clinical),Radiology, Nuclear Medicine and imaging

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