50 Hz Cortical stimulation increases interictal epileptiform discharges at the seizure onset zone

More than 15 million patients worldwide suffer from drug-resistant epilepsy (DRE). Surgical removal of the seizure onset zone (SOZ)-the brain region(s) from where seizures arise-is the best available treatment for these patients, with post-surgical outcomes depending on the successful identification and resection of the SOZ. Most commonly, SOZ mapping localizes ictal activity occurring spontaneously or evoked by cortical stimulation (CS) during pre-surgical evaluation of patients with epilepsy using stereoelectroencephalography (SEEG). Mapping events such as interictal epileptiform discharges (IEDs), paroxysmal hypersynchronic electrical discharges that often occur outside ictal discharges or during CS, have been less used for SOZ localization. We test the hypothesis that IEDs triggered by CS via SEEG investigation can contribute to the mapping of the SOZ. We evaluated the impact of CS on IEDs in patients investigated with SEEG on epilepsy surgery. We recorded intracranial signals from 30 DRE patients (seizure-free post-surgery). Bipolar and high-frequency (50 Hz) CS were performed with a pulse width of 300 µs and current spanning of 1-8 mA. IEDs were automatically detected pre- and post-stimulation, and their normalized absolute changes were quantified within and outside the SOZ (identified by ictal discharges). We found that the IED rates significantly increased post-stimulation compared with pre-stimulation within the SOZ, while no significant change was observed outside the SOZ (linear mixed-effect model, P-value < 0.001, and AUC = 98% for SOZ and 71% for non-SOZ). This effect was present regardless of whether the stimulation was applied to the SOZ or non-SOZ regions, indicating a broader effect of stimulation on the SOZ. Our results offer a quantitative tool for identifying epileptogenic areas in patients with DRE, enhancing the mapping and localization of the SOZ and potentially improving surgical outcomes.