Synopsis

Keywords: Epilepsy, fMRI (resting state)

Combining structural and functional neuroimaging analyses with brain transcriptional data, the present study investigated GMV and fALFF changes in children with RE as well as their underlying gene transcriptional profiles. VBM and fALFF analyses showed altered GMV and fALFF in brain regions associated with behavioral and cognitive regulation. Transcription-neuroimaging spatial correlation analyses further identified genes correlated with GMV and fALFF changes in RE, respectively. Moreover, functional enrichment analysis demonstrated that RE-related genes were enriched for the regulation of biological process. These findings may provide us with important knowledge for understanding the pathophysiological basis of this disease.

Background

Rolandic epilepsy (RE) is a common pediatric epilepsy syndrome that has been widely reported to show abnormal brain structure and function. However, the genetic mechanisms underlying structural and functional changes remain largely unknown.

Methods

Based on the structural and resting-state functional MRI data of 22 drug-naïve children with RE and 33 healthy controls, we conducted voxel-based morphology (VBM) and fractional amplitude of low-frequency fluctuation (fALFF) analyses to compared cortical morphology and spontaneous brain activity between the two groups. In combination with the Allen Human Brain Atlas, transcriptome-neuroimaging spatial correlation analyses were applied to exploring gene expression profiles associated with GMV and fALFF changes in RE.

Results

VBM analysis demonstrated significantly increased GMV in the right brainstem and right middle cingulate gyrus in RE. Moreover, children with RE exhibited significantly increased fALFF in left temporal pole, while decreased fALFF in right thalamus and left precuneus. These brain structural and functional alterations were closely related to behavioral and cognitive deficits and the fALFF-linked gene expression profiles were enriched for cellular, metabolic as well as positive and negative regulations of biological process.

Conclusion

Our findings suggest that brain morphological and functional abnormalities in children with RE involve complex polygenic genetic mechanisms.

Acknowledgements

We thank the Allen Institute for Brain Science founders and staff who supplied the brain expression data. We also thank the subjects who contributed to this study. Address correspondence to Dr. Heng Liu, Department of Radiology, Affiliated Hospital of Zunyi Medical University, Medical Imaging Center of Guizhou Province, Zunyi 563003, China. Email: zmcliuh@163.com and Dr Jiaojian Wang, State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China. Email: jiaojianwang@uestc.edu.cn.

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