Dynamic Stereoelectroencephalography-Based Phase–Amplitude Coupling in Cingulate Epilepsy

Accurate localization of the theoretical epileptogenic zone in cingulate epilepsy is particularly challenging due to the region's deep anatomical location and complex connectivity. While invasive stereoelectroencephalography (sEEG) methodology offers excellent spatiotemporal sampling of deep intracerebral structures, interpretation of these high-dimensional recordings remains largely qualitative and subject to interpretation by clinician experts. To address this limitation, we propose a quantitative, biomarker-based framework using phase-amplitude coupling (PAC) to investigate 25 seizures recorded from four patients with complex cingulate epilepsy who underwent sEEG followed by surgical treatment (either laser ablation or open resection), achieving ≥ 1 year of sustained seizure freedom. PAC values were computed from sEEG electrode contacts across multiple seizures during pre-ictal and ictal phases, employing wide-frequency and band-specific frequency coupling approaches. Among frequency pairs, theta-beta ([Formula: see text]-[Formula: see text]) coupling consistently demonstrated the most robust differentiation between surgically-treated and untreated contact sites. Our findings highlight frequency-specific PAC-based metrics as a potential tool for mapping dynamic epileptiform activity in brain networks, offering quantitative insight that may refine surgical planning and decision-making in challenging cases of cingulate epilepsy.