Phase-amplitude coupling of ripple activities during seizure evolution with theta phase

Abstract Objective High-frequency activities (HFAs) and phase-amplitude coupling (PAC) are key neurophysiological biomarkers for studying human epilepsy. We aimed to clarify and visualize how HFAs are modulated by the phase of low-frequency bands during seizures. Methods We used intracranial electrodes to record seizures of focal epilepsy (12 focal-to-bilateral tonic-clonic seizures and three focal-aware seizures in seven patients). The synchronization index, representing PAC, was used to analyze the coupling between the amplitude of ripples (80–250 Hz) and the phase of lower frequencies. We created a video in which the intracranial electrode contacts were scaled linearly to the power changes of ripple. Results The main low frequency band modulating ictal-ripple activities was the θ band (4–8 Hz), and after completion of ictal-ripple burst, δ (1–4 Hz)-ripple PAC occurred. The ripple power increased simultaneously with rhythmic fluctuations from the seizure onset zone, and spread to other regions. Conclusions Ripple activities during seizure evolution were modulated by the θ phase. The PAC phenomenon was visualized as rhythmic fluctuations. Significance Ripple power associated with seizure evolution increased and spread with fluctuations. The θ oscillations related to the fluctuations might represent the common neurophysiological processing involved in seizure generation.