The Effect of High-frequency Cortical Stimulation on SEEG-recorded Interictal Epileptiform Discharges

More than 15 million patients worldwide suffer from drug-resistant epilepsy (DRE). Surgical removal of the seizure onset zone (SOZ), the brain region(s) responsible for epileptogenic discharge initiation, is the best available treatment for these patients. The post-surgical outcome depends on the successful identification and resection of the SOZ. Therefore, finding robust biomarkers of epileptogenicity that allow clinicians to accurately localize the SOZ is of paramount importance. Most commonly, SOZ mapping localizes ictal activity occurring spontaneously or evoked by cortical stimulation (CS) during presurgical evaluation of patients with epilepsy using stereoelectroncephalography (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 investigation. We recorded intracranial signals from thirty DRE patients (seizure-free post-surgery). Bipolar and high frequency (50 Hz) CS was performed with a pulse width of 300 µs and current spanning 1–6 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 IED rates significantly increased post-stimulation compared to pre-stimulation within the SOZ, while no significant change was observed outside the SOZ (Mann-Whitney U test, p-value <0.001, 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.