Diagnostic and mechanistic insights from molecular profiling of explanted stereo-EEG depth electrodes

Epilepsy surgery involving deep brain stereo-electroencephalography (SEEG) offers a unique window into the biology of epilepsy in living humans. Explanted SEEG electrodes retain nucleic acids, enabling identification of somatic variants underlying treatment-resistant epilepsies. Recent studies show SEEG depth electrodes also preserve trace material sufficient for high-quality, region-specific transcriptomic and epigenetic profiling at near-contact resolution, distinguishing seizure onset, propagation and non-involved zones within individuals. We review these advances, focusing on methodologies, how molecular landscapes reflect cellular composition and activity states, and their integration with neurophysiology and clinical data. SEEG-derived molecular profiling captures dynamic brain states with unprecedented spatial and functional resolution, with applications in molecular diagnosis, surgical decision-making and uncovering disease mechanisms to inform future interventions and improve epilepsy management outcomes.