Ictal phase-amplitude coupling as a biomarker for seizure onset zone in neocortical epilepsy

Front Neurol. 2025 Sep 3;16:1632484. doi: 10.3389/fneur.2025.1632484. eCollection 2025.

ABSTRACT

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.

METHODS: 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, MI_{Ripples/4-8 Hz} was also significantly higher in the peri-SOZ region than in the non-SOZ region (p < 0.001). MI_{Ripples/4-8 Hz} (AUC: 0.853) and MI_{Ripples/3-4 Hz} (AUC: 0.846) demonstrated strong SOZ localization performance. MI_{Ripples/3-4 Hz} distinguished SOZ from peri-SOZ (AUC: 0.800).

CONCLUSION: 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.

PMID:40969212 | PMC:PMC12440772 | DOI:10.3389/fneur.2025.1632484