Mapping Physiological High-Frequency Oscillation Rates of the Cerebral Cortex for Improved Epileptogenic Zone Delineation in Stereoelectroencephalography

Objective: Given the challenges of interpreting preictal- and ictal-phase stereoelectroencephalography (SEEG), a complementary approach of examining interictal activity could be of value. High-frequency oscillations (HFOs), recorded at frequencies greater than 80 Hz in SEEG, are often pronounced in but not unique to the epileptogenic zone (EZ) compared with normal cortex. The aim of this study was to assess a novel HFO-rate-ratio to identify the EZ using region-specific interictal HFO rates, and to estimate the optimal threshold for the HFO rate ratio for both ripples and fast ripples to localize the EZ. Methods: Patients with epilepsy who underwent resective-surgery following SEEG at a single institution (January 2017–December 2022) and had available postoperative magnetic resonance imaging with at least 12 months of follow-up were included. A region-specific normative HFO database was retrospectively constructed using interictal physiological-HFO detected from nonresected brain areas of 37 patients who remained seizure-free after epilepsy surgery. The optimal HFO-rate-ratio was estimated by finding the ratio that best matched the resection volume that defines the EZ in seizure-free patients. Then, an optimal HFO rate ratio was used to detect region-specific pathological-HFOs. Results: Sixty-three patients (32 female, mean age 25 years) with 7,512 bipolar SEEG recordings who underwent surgery for epilepsy were analyzed. The HFO-rate-ratio method accurately localized the EZ in 92% of patients with seizure freedom and identified pathological HFO rates in 80% of patients with persistent seizures, both within (19%) and outside (35%) the resected areas. The optimal threshold for the ripple HFO rate ratio to accurately localize the EZ was 5.8 times the normative value and 2.7 times that of fast ripples, with sensitivity and specificity greater than 85%. Conclusion: These findings provide evidence that differentiating physiological and pathological interictal HFO rates are helpful in localizing the EZ, with potential utility in patient-specific surgical planning. Further prospective validation of this methodology is warranted. Publication History Article published online: 15 July 2026 © 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Medical and Scientific Publishers Private Limited A-13A, Graphix Tower 1, 6th floor, Sector 62, Noida 201309, Uttar Pradesh, India