Predictive Modeling of Evoked Intracranial EEG Response to Medial Temporal Lobe Stimulation in Patients with Epilepsy

Despite promising advancements, closed-loop neurostimulation for drug-resistant epilepsy (DRE) still relies on manual tuning and produces variable outcomes, while automated predictable algorithms remain an aspiration. As a fundamental step towards addressing this gap, here we study predictive dynamical models of human intracranial EEG (iEEG) response under parametrically rich neurostimulation. Using data from n = 13 DRE patients, we find that stimulation-triggered switched-linear models with ∼300ms of causal historical dependence best explain evoked iEEG dynamics. These models are highly consistent across different stimulation amplitudes and frequencies, allowing for learning a generalizable model from abundant STIM OFF and limited STIM ON data. Further, evoked iEEG in nearly all subjects exhibited a distance-dependent pattern, whereby stimulation directly impacts the actuation site and nearby regions (≲ 20mm), affects medium-distance regions (20 ∼ 100mm) through network interactions, and hardly reaches more distal areas (≳ 100mm). Peak network interaction occurs at 60∼80mm from the stimulation site. Due to their predictive accuracy and mechanistic interpretability, these models hold significant potential for model-based seizure forecasting and closed-loop neurostimulation design.