Disrupted topological properties of structural brain networks present a glutamatergic neuropathophysiology in people with narcolepsy

Guoyan Chen; Wen Wang; Haoyang Wu; Xiangchao Zhao; Xiaopeng Kang; Jiafeng Ren; Jun Zhang; Jiaxiu He; Shihui Sun; Zhao Zhong; Danqing Shang; Mengmeng Fan; Jinxiang Cheng; Dan Zhang; Changjun Su; Jiaji Lin

doi:10.1093/sleep/zsae002

Disrupted topological properties of structural brain networks present a glutamatergic neuropathophysiology in people with narcolepsy

Sleep. 2024 Jan 4:zsae002. doi: 10.1093/sleep/zsae002. Online ahead of print.

Authors

Guoyan Chen¹, Wen Wang², Haoyang Wu³, Xiangchao Zhao¹, Xiaopeng Kang⁴, Jiafeng Ren¹, Jun Zhang¹, Jiaxiu He¹, Shihui Sun¹, Zhao Zhong¹, Danqing Shang¹, Mengmeng Fan¹, Jinxiang Cheng¹, Dan Zhang¹, Changjun Su¹, Jiaji Lin^{1

5}

Affiliations

¹ Department of Neurology, The Second Affiliated Hospital of Air Force Medical University, No.569 Xinsi Road, Xi'an, 710038, China.
² Department of Radiology, The Second Affiliated Hospital of Air Force Medical University, No.569 Xinsi Road, Xi'an, 710038, China.
³ Basic Medicine School, Air Force Medical University, No.169 Changle West Road, Xi'an, 710038, China.
⁴ School of Artificial Intelligence, University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100876, China.
⁵ Department of Radiology, Chinese PLA General Hospital/Medical School of Chinese PLA, No.28 Fuxing Road, Beijing, 100853, China.

PMID: 38173348
DOI: 10.1093/sleep/zsae002

Abstract

Study objectives: Growing evidences have documented various abnormalities of the white matter bundles in people with narcolepsy. We sought to evaluate topological properties of brain structural networks, and their association with symptoms and neuropathophysiological features in people with narcolepsy.

Methods: Diffusion tensor imaging (DTI) was conducted for people with narcolepsy (n = 30) and matched healthy controls as well as symptoms assessment. Structural connectivity for each participant was generated to analyze global and regional topological properties and their correlations with narcoleptic features. Further human brain transcriptome was extracted and spatially registered for connectivity vulnerability. Genetic functional enrichment analysis was performed and further clarified using in vivo emission computed tomography data.

Results: A wide and dramatic decrease in structural connectivities was observed in people with narcolepsy, with descending network degree and global efficiency. These metrics were not only correlated with sleep latency and awakening features, but also reflected alterations of sleep macrostructure in people with narcolepsy. Network-based statistics identified a small hyperenhanced subnetwork of cingulate gyrus that was closely related to rapid eye movement sleep behavior disorder (RBD) in narcolepsy. Further imaging genetics analysis suggested glutamatergic signatures were responsible for the preferential vulnerability of connectivity alterations in people with narcolepsy, while additional PET/SPECT data verified that structural alteration was significantly correlated with metabotropic glutamate receptor 5 (mGlutR5) and N-methyl-D-aspartate receptor (NMDA).

Conclusions: People with narcolepsy endured a remarkable decrease in the structural architecture, which was not only be closely related to narcolepsy symptoms but also glutamatergic signatures.

Keywords: Narcolepsy; cingulate gyrus; glutamatergic receptor; structural network; topological property.