Chronic iEEG recordings and interictal spike rate reveal multiscale temporal modulations in seizure states

Background and Objectives: Many biological processes are modulated by rhythms on circadian and multidien timescales. In focal epilepsy, various seizure features, such as spread and duration, can change from one seizure to the next within the same patient. However, the specific timescales of this variability, as well as the specific seizure characteristics that change over time, are unclear. Methods: Here, in a cross-sectional observational study, we analysed within-patient seizure variability in 10 patients with chronic intracranial EEG recordings (185-767 days of recording time, 57-452 analysed seizures/patient). We characterised the seizure evolutions as sequences of a finite number of patient-specific functional seizure network states (SNSs). We then compared SNS occurrence and duration to (1) time since implantation and (2) patient-specific circadian and multidien cycles in interictal spike rate. Results: In most patients, the occurrence or duration of at least one SNS was associated with the time since implantation. Some patients had one or more SNSs that were associated with phases of circadian and/or multidien spike rate cycles. A given SNS's occurrence and duration were usually not associated with the same timescale. Discussion: Our results suggest that different time-varying factors modulate within-patient seizure evolutions over multiple timescales, with separate processes modulating a SNS's occurrence and duration. These findings imply that the development of time-adaptive treatments in epilepsy must account for several separate properties of epileptic seizures, and similar principles likely apply to other neurological conditions.