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

In focal epilepsy, various seizure features, such as spread and duration, can change from one seizure to the next within the same patient. Importantly, within-patient seizure evolutions do not change randomly over time, but instead appear to fluctuate over circadian and slower timescales. However, the specific timescales of this variability, as well as the specific seizure characteristics that change over time, are unclear. Here we analysed this 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 functional network states. We then compared seizure state occurrence and seizure state duration to (1) time since implantation and (2) patient-specific circadian and multidien cycles in interictal spike rate, which were extracted using empirical mode decomposition. In most patients, the occurrence or duration of at least one state was associated with the time since implantation (8 and 9 patients for state occurrence and state duration, respectively). Additionally, some patients also had one or more states that were associated with phases of circadian and/or multidien spike rate cycles (4 and 7 patients for state occurrence and state duration, respectively). A given state's occurrence and duration were not usually associated with the same timescale. Our results suggest that time-varying factors modulate within-patient seizure evolutions over multiple timescales, with separate processes modulating a seizure state's occurrence and duration. These findings provide new insight into the patterns and mechanisms of intra-patient seizure variability, with potential implications for forecasting and treating seizures.