Phase-amplitude coupling between infraslow and high-frequency activities well discriminates between the preictal and interictal states

Infraslow activity (ISA) and high-frequency activity (HFA) are key biomarkers for studying epileptic seizures. We aimed to elucidate the relationship between ISA and HFA around seizure onset. We enrolled seven patients with drug-resistant focal epilepsy who underwent intracranial electrode placement. We comparatively analyzed the ISA, HFA, and ISA-HFA phase-amplitude coupling (PAC) in the seizure onset zone (SOZ) or non-SOZ (nSOZ) in the interictal, preictal, and ictal states. We recorded 15 seizures. HFA and ISA were larger in the ictal states than in the interictal or preictal state. During seizures, the HFA and ISA of the SOZ were larger and occurred earlier than those of nSOZ. In the preictal state, the ISA-HFA PAC of the SOZ was larger than that of the interictal state, and it began increasing at approximately 87 s before the seizure onset. The receiver-operating characteristic curve revealed that the ISA-HFA PAC of the SOZ showed the highest discrimination performance in the preictal and interictal states, with an area under the curve of 0.926. This study demonstrated the novel insight that ISA-HFA PAC increases before the onset of seizures. Our findings indicate that ISA-HFA PAC could be a useful biomarker for discriminating between the preictal and interictal states.