Integrative genomic and spatial transcriptomic analysis elucidates the oligodendrocyte‐mediated etiology of epileptic cortical thinning

Focal epilepsy is often accompanied by a progressive thinning of the brain's cortex, which has traditionally been viewed purely as cumulative damage from repeated seizures. In this study, we investigated whether an underlying genetic predisposition also plays a role. By analyzing large-scale genetic and brain imaging datasets, we discovered a shared genetic link between focal epilepsy and cortical thinning. Furthermore, we traced this genetic vulnerability specifically to oligodendrocytes-the cells responsible for supporting and insulating nerve fibers. Our findings suggest that cortical thinning is not merely a "scar" from seizures, but partly a preexisting structural vulnerability driven by reduced protective functions of specific genes (such as DPYSL5 and SLC16A8) in these support cells. This offers a new perspective on preventing brain structural changes in epilepsy.