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

Abstract

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.

Pre‐synaptic and post‐synaptic A‐type K+ channels regulate glutamatergic transmission and switching of the network into epileptiform oscillations

“…The regular paces (e.g. the less variable inter‐burst intervals, Figures 3 and 7) of network oscillations unlocked by concurrent inhibition of pre‐synaptic and post‐synaptic A‐channels are consistent with the stereotyped pathological oscillations found in epilepsy patients (Hashimoto et al, 2021; Liu et al, 2018; Matsumoto et al, 2013). More uniform paces of discharges presumably may lead to hypersynchronous network activities, which would be simpler coding and carry less information, compared with more variable normal oscillations.…”

“…Our present results demonstrate that the A-channels-tuned glutamatergic input serves as an extrinsic drive for rhythmic activity in the BLA network. Disinhibition of glutamatergic transmission by Achannel (K v 1.4 and K v 4.3) inhibition would switch the network activities from apparent random firings to synchronous pacemaking reverberations, with the same frequencies in the low delta-like range as those in a seizure network (Chou et al, 2020;Hashimoto et al, 2021).…”

“…Our present results demonstrate that the A‐channels‐tuned glutamatergic input serves as an extrinsic drive for rhythmic activity in the BLA network. Disinhibition of glutamatergic transmission by A‐channel (K v 1.4 and K v 4.3) inhibition would switch the network activities from apparent random firings to synchronous pacemaking reverberations, with the same frequencies in the low delta‐like range as those in a seizure network (Chou et al, 2020; Hashimoto et al, 2021). Accordingly, the A‐channel activator NS‐5806 (Calloe et al, 2010), a drug primarily targeting K v 4.3 channels without apparent lethal arrhythmic effect in living animals (Cheng et al, 2017; Gurabi et al, 2014; Sakai et al, 2017), abolished ictogenic burst discharges as well as behavioural seizures induced by selective excitation of glutamatergic neurons in the BLA.…”

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

“…In this retrospective study, we enrolled six patients with drug-resistant focal epilepsy who underwent intracranial electrode placement for presurgical invasive electroencephalography (EEG) and who were admitted to Osaka University Hospital between July 2018 and July 2019 (Table 1). Some patients (P1 to P5) in this study were the same patients as those included in our previous study (Hashimoto et al, 2021a(Hashimoto et al, , 2021b.…”

“…Studies related to pathological PAC have demonstrated that ictal HFA amplitude is coupled with δ (Nariai et al, 2011) or θ (Ibrahim et al, 2014) bands. Our previous studies investigating FBTCS have shown that PAC between infra-slow activities and HFAs precede ictal HFAs (Hashimoto et al, 2020b(Hashimoto et al, , 2021a. Moreover, previous studies have mainly focused on ictal PAC or PAC of the seizure onset zone (SOZ), and it remains unclear how PAC dynamically changes throughout FBTCS.…”