Foundation Models for Epileptogenic Zone Identification in Drug-Resistant Epilepsy

Accurate identification of the epileptogenic zone (EZ) is essential for seizure freedom after resective surgery in drug-resistant epilepsy, yet seizure freedom rates remain below 50%. We developed EpiiSLM, a dual foundation model system for EZ identification with stereo-electroencephalography (sEEG), by training a signal foundation model on 104,990 minutes of sEEG recordings from the Montreal Neurological Institute & Hospital, while leveraging all recordings regardless of surgical outcome and anchoring EZ biomarker extraction on non-epileptic signals. A language foundation model then integrates sEEG-derived outputs with multimodal clinical information to produce interpretable predictions. Under leave-one-patient-out evaluation, EpiiSLM achieved 0.978 contact-level positive predictive value (PPV), outperforming the seizure onset zone(SOZ)-as-EZ baseline by 15.1% (p < 0.05), and 100% region-level accuracy; on an external dataset, EpiiSLM achieved 0.857 contact-level PPV. EpiiSLM requires only one night of interictal sleep data, suggesting potential to reduce invasive sEEG monitoring duration and improve surgical outcomes.