Drug-resistant focal epilepsy (DRE) remains a major cause of morbidity in children, with up to one-third of patients continuing to seize despite surgical intervention. Emerging evidence implicates somatic mosaic variants and epigenetic dysregulation in epileptogenesis, yet spatially resolved molecular studies have been limited. Building on advances demonstrating that tissue adherent to stereo-EEG (sEEG) electrodes contains viable neural cells, this project will perform integrated genomic, transcriptomic, and epigenetic profiling of sEEG-adherent and resected brain tissue to characterize seizure onset, propagation, and non-involved regions. Using long- and short-read sequencing, we aim to identify region-specific molecular signatures underlying epileptogenic circuits. These findings will establish a minimally invasive framework for linking molecular mechanisms with electrophysiology in human epilepsy.
Principal Investigator(s)