Visualization of Phase-Amplitude Coupling Using Rhythmic High-Frequency Activity

High-frequency activities (HFAs) and phase-amplitude coupling (PAC) are gaining attention as 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. We used intracranial electrodes to record seizures of symptomatic focal epilepsy (15 seizures in seven patients). Ripples (80-250 Hz), as representative of HFAs, were evaluated along with PAC. The synchronization index (SI), representing PAC, was used to analyze the coupling between the amplitude of ripples and the phase of lower frequencies. 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. We created a video in which the intracranial electrode contacts were represented by circles that were scaled linearly to the power changes of ripple. The video showed that fluctuation of the diameter of these circles indicated the rhythmic changes during significant high values of θ-ripple PAC. Moreover, clonic seizures were observed when values of δ-ripple PAC were significantly high. We inferred that ripple activities occurring during seizure evolution were modulated by θ rhythm, and ripple activities involved in clonic seizures were modulated by δ rhythm. In addition, we concluded that rhythmic circles′ fluctuation presented in the video represents the PAC phenomenon. Our video is thus a useful tool for understanding how ripple activity is modulated by the low-frequency phase in relation with PAC.