Brain connectivity regions of lesions causing focal to bilateral tonic-clonic seizures correlates with gene expression

Focal to bilateral tonic-clonic seizures (FBTCS) is one of the most severe forms of seizures. Why lesions in some brain areas result in FBTCS while lesions in other areas do not? This study aimed to examine whether the locations of lesions causing FBTCS were mapped to specific brain regions and to explore correlation between the specific brain regions and gene expression. A retrospective study was conducted involving 25 patients diagnosed with FBTCS. The lesion network mapping method was employed, utilizing a large database of resting-state fMRI scans to detect brain regions connected to lesions causing FBTCS. Additionally, gene expression profiles related to the specific brain regions of FBTCS were examined using transcriptome neuroimaging association analysis. The lesion locations of FBTCS were found to be heterogeneous, but connected to the specific brain regions. The cerebellum, thalamus, cingulate cortex, and middle frontal gyrus were identified as hubs of the specific brain regions as they were the areas that were both functionally connected to 96 % of lesions, as well as significantly different in connectivity. Moreover, the specific brain regions were colocalized with whole-brain gene expression in the biological processes with synaptic functions, ion channel activity, lysosome and comorbidity pathway. This study suggests that lesions causing FBTCS mapped to the specific brain regions, providing insight into the causal neuroanatomical foundation in FBTCS. Decoding the specific brain regions of FBTCS through transcriptomic may indicate the presence of multiscale interactions in FBTCS, promoting our understanding of the genetic molecular mechanism of FBTCS.