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Increased Gray Matter Density and Functional Connectivity of the Pons in Restless Legs Syndrome

Authors Xu Z, Han T, Li T, Zhang X, Huang Z, Zhan S, Liu C, Xu J, Wang Y

Received 24 November 2019

Accepted for publication 7 March 2020

Published 24 March 2020 Volume 2020:12 Pages 221—230

DOI https://doi.org/10.2147/NSS.S239852

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Professor Steven A Shea


Zhexue Xu,1,2,* Tao Han,1,2,* Tian Li,3 Xiaodong Zhang,3 Zhaoyang Huang,1,2 Shuqin Zhan,1,2 Chunyan Liu,1,2 Jinping Xu,3 Yuping Wang1,2

1Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, People’s Republic of China; 2Beijing Key Laboratory of Neuromodulation, Beijing 100053, People’s Republic of China; 3Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Chunyan Liu
Department of Neurology, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing 100053, People’s Republic of China
Email lcy_e_mail@163.com

Jinping Xu
Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People’s Republic of China
Email jp.xu@siat.ac.cn

Background: Neurophysiological and radiological studies provide accumulating evidence for the involvement of the brainstem in the pathogenesis of restless legs syndrome (RLS). The analysis of the various subregions of the brainstem may help us better understand the pathophysiological mechanisms underlying the disorder. In this study, we investigated the structural and functional changes in the various subregions of the brainstem in RLS patients.
Methods: The subregional changes in gray matter density and functional connectivity in the brainstem were analyzed in 20 drug-naive idiopathic RLS patients, as well as 18 normal control (NC) subjects for comparison. Correlation analyses and multivariate pattern analyses using linear support vector machine (SVM) were conducted.
Results: We found significantly increased gray matter density in two clusters in the pons (designated pons_1 and pons_2) and in one cluster in the midbrain in RLS patients compared with NC subjects. Further functional connectivity analyses revealed significantly decreased functional connectivity between the midbrain and the right middle occipital gyrus, between pons_1 and the right orbital part of the superior frontal gyrus, and between pons_2 and the right parahippocampus in RLS compared with NC. Moreover, the functional connectivity between pons_2 and the right supplementary motor area (SMA) was significantly increased in RLS compared with NC. This change in RLS was marginally correlated with RS_RLS scores in the RLS patients. SVM-based classification showed an AUC of 0.955 using gray matter density of pons_2, and functional connectivity between pons_2 and SMA as features.
Conclusion: Collectively, our findings suggest that changes in gray matter density and functional connectivity in the pons may play a pathologic role in RLS. Furthermore, these abnormal changes in the pons might help to discriminate RLS from healthy subjects.

Keywords: restless legs syndrome, gray matter density, brainstem, multivariate pattern analysis

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