Amrit Kashyap Paul M. Mueller Gadi Miron Christian Meisel ^*

• Charité University Medicine Berlin, Berlin, Germany

Epilepsy is characterized by recurrent, unprovoked seizures. Accurate prediction of seizure occurrence has long been a clinical goal since this would allow to optimize patient treatment, prevent injuries due to seizures, and alleviate the patient burden of unpredictability. Advances in implantable electroencephalographic (EEG) devices, allowing for long-term interictal EEG recordings, have facilitated major progress in this field. Recently, it has been discovered that interictal brain activity demonstrates circadian and multi-dien cycles that are strongly aligned, or phase locked, with seizure risk. Thus, cyclical brain activity patterns have been used to forecast seizures. However, in the effort to develop a clinically useful EEG based seizure forecasting system, challenges remain. Firstly, multiple EEG features demonstrate cyclical patterns, but it remains unclear which feature is best suited for predicting seizures. Secondly, the technology for long-term EEG recording is currently limited in both spatial and temporal sampling resolution. In this study, we compare five established EEG metrics: synchrony, spatial correlation, temporal correlation, signal variance which have been motivated from critical dynamics theory, and interictal epileptiform discharges (IED) which are a traditional marker of seizure propensity. We assess their effectiveness in detecting 24-hour and seizure cycles as well as their robustness under spatial and temporal subsampling. Analyzing intracranial EEG data from 23 patients, we report that all examined features exhibit 24-hour cycles. Spatial correlation, signal variance, and synchrony showed the highest phase locking with seizures, while IED rates were the lowest. Notably, spatial and temporal correlation were also found to be highly correlated to each other, as were signal variance and IED – suggesting some features may reflect similar aspects of cortical dynamics, whereas others provide complementary information. All features proved robust under subsampling, indicating that the dynamic properties of interictal activity evolve slowly and are not confined to specific brain regions. Our results may aid future translational research by assisting in design and testing of EEG based seizure forecasting systems.