Abstracts

Rationale: Changes in spectral content within defined frequency bands have been commonly used in the last few decades as an indicator of abnormal neuronal network activity in recordings from epileptic patients and animal models of epilepsy. The rate of occurrence of high-frequency oscillations (HFOs, ~80-500 Hz) as well as changes in the spectral content of infraslow activity (ISA, 0.01-0.1 Hz), have been associated with the onset of different seizures originating from different regions and have been considered as markers for seizure generation. Recent studies have begun to investigate the cross-frequency coupling (CFC) phenomenon in healthy individuals as well as in epileptic patients, in which synchronized, low-frequency activity in large neuronal populations influences higher-frequency neuronal activity. Since epilepsy is a disease arising from an excessive interaction between neurons and/or networks, evaluating the changes in CFC between different spectral components may reveal more information on the seizure generation. The precise role of CFC (both phase-amplitude coupling (PAC) and amplitude-amplitude coupling (AAC)) in the generation of seizures is poorly studied and requires further investigation. In this study we evaluate the changes in PAC and AAC between low (0.01-1 Hz) and high (ripples: 80-250 Hz, and fast ripples: 250-500 Hz) frequency bands at seizure onset, and explore their potential role in seizure generation. Methods: Seizures recorded from patients with medical refractory epilepsy who underwent presurgical evaluation with intracranial electrodes were analyzed. Cross-frequency coupling (CFC: PAC and AAC) between low (0.01-1 Hz) and high (80-250 Hz, and 250-500 Hz) frequency bands at seizure onset were measured using generalized linear modeling (GLM) framework. The CFC was measured in the seizure onset channel between 5 s before seizure onset and 5 s after seizure onset. The changes in PAC and AAC between ISA and ripple frequency band as well as ISA and fast ripple frequency band were analyzed to identify their possible variabilities. Results: Seizures (n=256) recorded from 27 patients diagnosed with medical refractory epilepsy were investigated. The analysis of changes in CFC around the seizure onset showed that in 79% of seizures there is an interaction between ISA and ripple, or ISA and fast ripple frequency band. Among all the measures, the increase in the PAC between ISA and ripple frequency band was seen most commonly (62%) either alone or in the presence of other interactions. The AAC between ISA and fast ripple frequency band was observed the least and only in 21% of seizures. Conclusions: These findings suggest that the interactions between different frequency bands may account for mechanisms involved at seizure generation and identifying their differences may provide additional information about how seizures might differ in initiation and propagation. This difference can be investigated by identifying the changes in the interactions between different frequency bands and eventually may be able to pinpoint the involvement of different neuronal elements and networks in the generation of seizures. Funding: Fonds de recherche du Québec – Santé (FRQS)National Institutes of Health (NIH)