Impaired structural and reserved functional topological organizations of brain networks in Parkinson's disease with freezing of gait

Lina Wang; Caiting Gan; Huimin Sun; Min Ji; Heng Zhang; Xingyue Cao; Min Wang; Yongsheng Yuan; Kezhong Zhang

doi:10.21037/qims-22-351

Impaired structural and reserved functional topological organizations of brain networks in Parkinson's disease with freezing of gait

Quant Imaging Med Surg. 2023 Jan 1;13(1):66-79. doi: 10.21037/qims-22-351. Epub 2022 Sep 28.

Authors

Lina Wang^#¹, Caiting Gan^#¹, Huimin Sun^#¹, Min Ji¹, Heng Zhang¹, Xingyue Cao¹, Min Wang², Yongsheng Yuan¹, Kezhong Zhang¹

Affiliations

¹ Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
² Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

^# Contributed equally.

Abstract

Background: Freezing of gait (FOG) is a common disabling motor disturbance in Parkinson's disease (PD). Our study aimed to probe the topological organizations of structural and functional brain networks and their coupling in FOG.

Methods: In this cross-sectional retrospective study, a total of 30 PD patients with FOG (PD-FOG), 40 patients without FOG, and 25 healthy controls (HCs) underwent clinical assessments and magnetic resonance imaging (MRI) scanning. Large-scale structural and functional brain networks were constructed. Subsequently, global and nodal graph theoretical properties and functional-structural coupling were investigated. Finally, correlations between the altered brain topological properties and freezing severity were analyzed in PD-FOG.

Results: For structural networks, at the global level, PD-FOG exhibited increased normalized characteristic path length (P=0.040, Bonferroni-corrected) and decreased global efficiency (P=0.005, Bonferroni-corrected) compared with controls, and showed reduced global (P=0.001, Bonferroni-corrected) and local (P=0.032, Bonferroni-corrected) efficiency relative to patients without FOG. At the nodal level, nodal efficiency of structural networks was reduced in PD-FOG compared with PD patients without FOG, located in the left supplementary motor area (SMA), gyrus rectus, and middle cingulate cortex (MCC) (all P<0.05, Bonferroni-corrected). Notably, altered global and nodal properties of structural networks were significantly correlated with Freezing of Gait Questionnaire scores [all P<0.05, false discovery rate (FDR)-corrected]. However, only an increase in local efficiency (P=0.003, Bonferroni-corrected) of functional networks was identified in PD-FOG compared with those without FOG. No significant structural-functional coupling was detected among the 3 groups.

Conclusions: This study demonstrates the extensively impaired structural and relatively reserved functional network topological organizations in PD-FOG. Our results also provide evidence that the pathogenesis of PD-FOG is primarily attributable to network vulnerability established by crucial structural damage, especially in the left SMA, gyrus rectus, and MCC.

Keywords: Freezing of gait (FOG); Parkinson’s disease (PD); structural-functional coupling; supplementary motor area (SMA); topology.