NR4A1 Methylation Associated Multimodal Neuroimaging Patterns Impaired in Temporal Lobe Epilepsy

Frontiers in Neuroscience

Jian Yang¹  Jing Sui³  Xingdong Yang⁴  Wenyue Wu⁵  Bo Xiao⁶  Wenbiao Xiao⁶  Lili Long⁶  Chaorong Liu⁶  Hongyu Long⁶  Vince D. Calhoun⁷  Shile Qi⁷  Rongtao Jiang⁸  Dongmei Zhi⁸ 

[1] Beijing Engineering Research Center of Mixed Reality and Advanced Display, School of Optics and Electronics, Beijing Institute of Technology, Beijing, China;Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China;CAS Centre for Excellence in Brain Science and Intelligence Technology, Institute of Automation, Chinese Academy of Sciences, Beijing, China;Department of Neurology, Beijing Haidian Hospital, Beijing, China;Department of Neurology, The Second Affiliated Hospital, Nanchang University, Nanchang, China;Department of Neurology, Xiangya Hospital, Central South University, Changsha, China;Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia Institute of Technology, Georgia State University − Emory University, Atlanta, GA, United States;University of Chinese Academy of Sciences, Beijing, China;

关键词: temporal lobe epilepsy;    multimodal fusion;    methylation levels of NR4A1;    functional connectivity;    fractional anisotropy;    gray matter volume;   

DOI  :  10.3389/fnins.2020.00727

来源: DOAJ

【 摘 要 】

DNA hypermethylation has been widely observed in temporal lobe epilepsy (TLE), in which NR4A1 knockdown has been reported to be able to alleviate seizure severity in mouse model, while the underlying methylation-imaging pathway modulated by aberrant methylation levels of NR4A1 remains to be clarified in patients with TLE. Here, using multi-site canonical correlation analysis with reference, methylation levels of NR4A1 in blood were used as priori to guide fusion of three MRI features: functional connectivity (FC), fractional anisotropy (FA), and gray matter volume (GMV) for 56 TLE patients and 65 healthy controls. Post-hoc correlations were further evaluated between the identified NR4A1-associated brain components and disease onset. Results suggested that higher NR4A1 methylation levels in TLE were related with impaired temporal-cerebellar and occipital-cerebellar FC strength, lower FA in cingulum (hippocampus), and reduced GMV in putamen, temporal pole, and cerebellum. Moreover, findings were also replicated well in both patient subsets with either right TLE or left TLE only. Particularly, right TLE patients showed poorer cognitive abilities and more severe brain impairment than left TLE patients, especially more reduced GMV in thalamus. In summary, this work revealed a potential imaging-methylation pathway modulated by higher NR4A1 methylation in TLE via data mining, which may impact the above-mentioned multimodal brain circuits and was also associated with earlier disease onset and more cognitive deficits.

【 授权许可】

Unknown