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Recent trials of chronic EEG in humans showed that epilepsy is a cyclical disorder of the brain with rhythms at multiple time-scales: circadian, multi-day (multidien) or even seasonal. Here, we analyzed chronic EEG data (>30 days) in male epileptic rats and unraveled not only circadian but also, slower, multidien rhythms of interictal epileptiform activity with periodicity of about 2–3 and 5–7 days. Importantly, seizures were not uniformly distributed over time, but rather clustered at preferential phases of these underlying rhythms, delineating critical circadian times and multidien phase of heightened seizure risk. Multidien rhythms were not synchronous across animals or with human intervention suggesting an endogenous generator. In epilepsy, across species, unknown factors modulate seizure timing in cyclical patterns over multiple days.
•Epilepsy cycles at multidien timescales are unraveled in animal models.•The relationship between seizures and IEA takes place at multiple timescales.•Seizures tend to cluster in a given phase of multidien rhythms spanning a few days.•Multidien rhythms are asynchronous across rats and with environmental cues, suggesting an endogenous modulation.