Evidence-based modeling of network discharge dynamics during periodic pacing to control epileptiform activity

Abstract

Deep brain stimulation (DBS) is a promising therapeutic approach for epilepsy treatment. Recently, research has focused on the implementation of stimulation protocols that would adapt to the patients need (adaptive stimulation) and deliver electrical stimuli only when it is most useful. A formal mathematical description of the effects of electrical stimulation on neuronal networks is a prerequisite for the development of adaptive DBS algorithms. Using tools from non-linear dynamic analysis, we describe an evidence-based, mathematical modeling approach that (1) accurately simulates epileptiform activity at time-scales of single and multiple ictal discharges, (2) simulates modulation of neural dynamics during epileptiform activity in response to fixed, low-frequency electrical stimulation, (3) defines a mapping from real-world observations to model state, and (4) defines a mapping from model state to real-world observations. We validate the real-world utility of the model's properties by statistical comparison between the number, duration, and interval of ictal-like discharges observed in vitro and those simulated in silica under conditions of repeated stimuli at fixed-frequency. These validation results confirm that the evidence-based modeling approach captures robust, informative features of neural network dynamics of in vitro epileptiform activity under periodic pacing and support its use for further implementation of adaptive DBS protocols for epilepsy treatment.