Unstable slow oscillations couple with epileptogenic fast‐rhythm bistability in sleep‐related epilepsy: A stereoelectroencephalographic study

Objective: Although slow waves in δ (.5–4 Hz) characterize non-rapid eye movement (NREM) sleep, in patients with sleep-related epilepsy, seizures most frequently emerge during NREM stage 2, known to be promoted by δ-band instability. Meanwhile, the epileptogenic zone (EZ) shows localized bistability in β–γ-band (15–200 Hz) neuronal oscillations, indicating a catastrophic shift toward seizure. We aim to clarify the mechanistic link between δ-band synchrony and β–γ-band bistability in epilepsy. Methods: We studied a cohort of 14 patients with sleep hypermotor epilepsy (22.3 ± 10.8 years old, seven males). Seven- to 9-h stereoelectroencephalographic sleep recordings were segmented into 10-min uninterrupted, interictal N2 and N3 epochs, and phase synchrony, phase–amplitude coupling (PAC), and bistability were assessed. Canonical correlation was examined to answer whether PAC links δ phase to β–γ bistability. Results: Compared to non-EZ, the EZ exhibited larger 15–200-Hz bistability along with stronger 2–8-Hz and 15–100-Hz synchrony throughout N2 and N3. Compared to N3, N2 showed stronger PAC between 2–30-Hz phases in the non-EZ and 5–150-Hz amplitudes in the EZ. Canonical correlations between δ phase modulated PAC, and both bistability and synchrony were identified during N2 (r =.86 and.82) and N3 (r =.84 and.80), with the strongest contributors being 2–4-Hz synchrony and bistability in 2–4-Hz and 15–200-Hz bands. Correlations between interictal spikes and canonical covariates of bistability and PAC (r2 =.62 for N2 and.56 for N3) validated their relevance to epileptogenicity. Significance: δ-Band synchrony and β–γ-band bistability are not isolated epileptogenic mechanisms but likely act synergistically, playing a pivotal role in seizure generation through the coupling of δ phases and β–γ amplitudes across large networks, with significant contributions from nonepileptogenic tissues.