Frequency band coupling with high-frequency activities during seizures shifts from θ band in tonic phase to δ band in clonic phase

Objective: To clarify variations in the relationship between high-frequency activities (HFAs) and low frequency bands from the tonic to the clonic phase in focal to bilateral tonic-clonic seizures (FBTCS), using phase-amplitude coupling. Methods: This retrospective study enrolled six patients with drug-resistant focal epilepsy who underwent intracranial electrode placement for presurgical invasive electroencephalography at Osaka University Hospital (July 2018-July 2019). We used intracranial electrodes to record seizures in focal epilepsy (11 FBTCS). The magnitude of synchronization index (SIm) and receiver operating characteristic (ROC) analysis were used to analyze the coupling between HFA amplitude (80-250 Hz) and lower frequencies phase. Results: The {theta} (4-8 Hz)-HFA SIm peaked in the tonic phase, whereas the {delta} (2-4 Hz)-HFA SIm peaked in the clonic phase. ROC analysis indicated that the {delta}-HFA SIm discriminated well the clonic from the tonic phase. Conclusions: The main low-frequency band modulating the HFA shifted from the {theta} band in the tonic phase to the {delta} band in the clonic phase. Significance: In FBTCS, low-frequency band coupling with HFA amplitude varies temporally. Especially, the {delta} band is specific to the clonic phase. These results suggest dynamically neurophysiological changes in the thalamus or basal ganglia throughout FBTCS.