Abstracts

Rationale: Understanding the mechanisms of transition from a non-ictal to an ictal state is paramount in identifying the epileptogenic zone (EZ). Phase-amplitude coupling (PAC) between the phase of lower-frequency activity and the amplitude of higher-frequency activity may provide insight. PAC is thought to facilitate information transference between local and macroscale neural networks, where the slower frequencies alter the excitability of local networks. Intracranial electroencephalography (iEEG) studies have reported increased PAC within the EZ during seizures but non-invasive evidence is lacking. Here, we leveraged rarely captured magnetoencephalography (MEG) ictal events to account for the spatiotemporal dynamics of PAC in pediatric drug-resistant epilepsy patients.

Methods: We have collected seizures in 13 participants (9 female, 4-16 years old) during their MEG recordings in anticipation of epilepsy surgery. We derived time-resolved measures of PAC from the MEG source time series in regions of interest defined from the surgically resected zone (RZ) and the contralateral homologous zone (CZ) in patients who achieved long-term ( > 1 year) seizure freedom (N = 8). We analyzed data segments containing inter-ictal and ictal events, deriving PAC between all pairs of lower frequencies in the delta/theta/alpha/beta frequency ranges and the faster gamma/ripple/fast-ripple band ranges.

Results: Our preliminary results indicate that PAC is greater in the RZ compared to the CZ between delta slow activity and the gamma/ripple/fast-ripple band ranges. This overexpression of PAC was observed both in the pre-ictal and ictal stages. Upon ictal onset, we found noticeable increases in PAC in both regions of interest for all delta pairs except for the delta-fast-ripple range pair, which only occurred in the RZ. These observations align with previous iEEG-PAC studies and the concept that events within the fast-ripple frequency range are pathological.

Conclusions: Thus far, our results suggest that non-invasive measures of increased phase-amplitude coupling in both the inter-ictal and ictal states may help delineate the EZ. Our next steps include whole-brain PAC mapping for all participants, which will be related to RZs, surgical outcomes, and pathologies. Furthermore, these measures are accessible to non-invasive whole-brain MEG source mapping recorded over relatively short time periods, with minimal patient preparation, compared to extended exploratory scalp and iEEG monitoring in the clinic. Hence, our findings have the potential to aid presurgical planning and thus improve surgical outcomes, and to advance our understanding of seizure generation dynamics across the brain.

Funding: This work has been supported thanks to the Fonds de recherche du Québec – Santé (FRQS) Formation de doctorat 2024-2025 - BF2 - 347869.