The alteration of cortical microstructure similarity in drug-resistant epilepsy correlated with mTOR pathway genesResearch in context
Hang Cao,
Penghu Wei,
Yuda Huang,
Ningrui Wang,
Lin-Ai Guo,
Xiaotong Fan,
Zhenming Wang,
Liankun Ren,
Yueshan Piao,
Jie Lu,
Yongzhi Shan,
Xiaosong He,
Guoguang Zhao
Affiliations
Hang Cao
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China
Penghu Wei
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China; Clinical Research Center for Epilepsy, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China; Beijing Municipal Geriatric Medical Research Center, 45 Changchun St, Beijing, 100053, China
Yuda Huang
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China
Ningrui Wang
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China
Lin-Ai Guo
Department of Pathology, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China
Xiaotong Fan
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China
Zhenming Wang
Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China
Liankun Ren
Department of Neurology, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China
Yueshan Piao
Department of Pathology, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China; Clinical Research Center for Epilepsy, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China; National Medical Center for Neurological Diseases, 45 Changchun St, Beijing, 100053, China
Jie Lu
Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China; Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, 45 Changchun St, Beijing, 100053, China
Yongzhi Shan
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China; Corresponding author.
Xiaosong He
Department of Psychology, University of Science and Technology of China, No 96 Jinzhai Rd, Hefei, 230026, China; Corresponding author.
Guoguang Zhao
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China; Clinical Research Center for Epilepsy, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China; Beijing Municipal Geriatric Medical Research Center, 45 Changchun St, Beijing, 100053, China; Corresponding author. Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China.
Summary: Background: Drug-resistant epilepsy (DRE) is associated with distributed laminar disruptions due to cytoarchitectonic pathologies, which may be characterized by multimodal MRI approaches such as morphometric similarity networks (MSNs). However, the genetic and histological underpinning of MSN alterations in DRE remains poorly understood, hampering its clinical application. Methods: We enrolled 60 patients with DRE and 23 controls, acquiring T1 and diffusion spectrum imaging data with a 3.0T GE SIGNA Premier scanner. Morphometric similarity networks (MSNs) were constructed and analyzed to identify microstructure similarity differences between patients and controls. Subsequently, patient-specific MSN alteration patterns were associated with gene expression using the GAMBA tool, and layer-specific neuronal signature mapping were also applied. During these analyses, sex and age were adjusted as covariates and multiple comparisons corrections were applied when appropriate. Findings: We observed widespread MSN changes in patients with DRE and identified five distinct MSN alteration patterns. Major patterns presented pattern-specific associations with expressions of epilepsy-related genes, particularly involving the mTOR pathway. Histological analysis confirmed the presence of cortical microstructure changes in areas with MSN alterations and revealed cellular abnormalities matching the aforementioned genetic risks. Interpretation: Our findings highlight the potential of quantifying laminar-related microstructure integrity using MSN to uncover the cytoarchitectonic changes in the pathophysiology of DRE. This approach may facilitate the identification of genetic and histological underpinnings of MSN alterations in DRE, ultimately aiding in the development of targeted therapeutic strategies. Fundings: The National Natural Science Foundation of China, the Ministry of Science and Technology of the People's Republic of China, and the Beijing Municipal Health Commission.
