ORIGINAL RESEARCH article
Front. Neurol.
Sec. Epilepsy
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1632484
Ictal phase-amplitude coupling as a biomarker for seizure onset zone in neocortical epilepsy
Provisionally accepted
Kazuki Nishioka1,2
Yasushi Iimura1,2*
Takumi Mitsuhashi1,2
Hiroharu Suzuki1,2
Tetsuya Ueda1,2
Kazuki Nomura1,2Yao Miao3
Toshihisa Tanaka4
Hiroshi Otsubo1,5
Hidenori Sugano1,2,6Akihide Kondo1,2- 1Department of neurosurgery, Juntendo university, Tokyo, Japan
- 2Epilepsy Center, Juntendo University Hospital, Tokyo, Japan
- 3Shenzhen Technology University, Shenzhen, Guangdong, China
- 4Department of Electrical Engineering and Computer Science, Tokyo University of Agriculture and Technology, Tokyo, Japan
- 5Division of Neurology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
- 6Sugano Neurosurgery Clinic, Tokyo, Japan
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Objective: To assess ictal phase-amplitude coupling (PAC) dynamics during seizure generation and explore whether ictal PAC analysis can help identify the seizure onset zone (SOZ) in neocortical epilepsy.We analyzed ictal intracranial electroencephalography recordings from 22 seizures in six patients with drug-resistant neocortical epilepsy who achieved International League Against Epilepsy Class I outcomes following resection surgery. PAC strength was quantified using the modulation index (MI), computed by coupling the amplitude of high-frequency bands (ripples: 80-200 Hz; fast ripples: 200-300 Hz) with the phase of slow-wave bands (1-2 Hz, 2-3 Hz, 3-4 Hz and 4-8 Hz). MI values were compared across SOZ, peri-SOZ (adjacent electrodes), and non-SOZ regions.Localization accuracy was evaluated using the area under the curve (AUC) from receiver operating characteristic curve analysis.Results: Across all PAC between ripples and slow wave bands, MI values were significantly higher in the SOZ compared to the peri-SOZ and non-SOZ regions (p < 0.001). During the late phase of seizure onset, MIRipples/4-8 Hz was also significantly higher in the peri-SOZ region than in the non-SOZ region (p < 0.001). MIRipples/4-8 Hz (AUC: 0.853) and MIRipples/3-4 Hz (AUC: 0.846) demonstrated strong SOZ localization performance. MIRipples/3-4 Hz distinguished SOZ from peri-SOZ (AUC: 0.800).Elevated MI during seizure onset accurately localized the SOZ in neocortical epilepsy.Ictal PAC may be a useful biomarker for identifying SOZ in neocortical epilepsy.
Keywords: high-frequency oscillations, modulation index, phase-amplitude coupling, Neocortical epilepsy, ictal EEG analysis
Received: 21 May 2025; Accepted: 01 Aug 2025.
Copyright: © 2025 Nishioka, Iimura, Mitsuhashi, Suzuki, Ueda, Nomura, Miao, Tanaka, Otsubo, Sugano and Kondo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yasushi Iimura, Department of neurosurgery, Juntendo university, Tokyo, Japan
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.