Persistent aberrant cortical phase–amplitude coupling following seizure treatment in absence epilepsy models

Key points In two monogenic models of absence epilepsy, interictal beta/gamma power is augmented in homozygous stargazer (stg/stg) but not homozygous tottering (tg/tg) mice. There are distinct gene‐linked patterns of aberrant phase–amplitude coupling in the interictal EEG of both stg/stg and tg/tg mice, compared to +/+ and stg/+ mice. Treatment with ethosuximide significantly blocks seizures in both genotypes, but the abnormal phase–amplitude coupling remains. Seizure‐free stg/+ mice have normal power and phase–amplitude coupling, but beta/gamma power is significantly reduced with NMDA receptor blockade, revealing a latent cortical network phenotype that is separable from, and therefore not a result of, seizures. Altogether, these findings reveal gene‐linked quantitative electrographic biomarkers free from epileptiform activity, and provide a potential network correlate for persistent cognitive deficits in absence epilepsy despite effective treatment.