Brain stimulation has, for many decades, been considered as a potential solution for the unmet needs of the many people living with drug-resistant epilepsy. Clinically, there are several different approaches in use, including vagus nerve stimulation (VNS), deep brain stimulation of the thalamus, and responsive neurostimulation (RNS). Across populations of patients, all deliver reductions in seizure load and SUDEP risk, yet do so variably, and the improvements seem incremental rather than transformative. In contrast, within the field of experimental neuroscience, the transformational impact of optogenetic stimulation is evident; by providing a means to control subsets of neurons in isolation, it has revolutionized our ability to dissect out the functional relations within neuronal microcircuits. It is worth asking, therefore, how pre-clinical optogenetics research could advance clinical practice in epilepsy? Here, we review the state of the clinical field, and the recent progress in pre-clinical animal research. We report various breakthrough results, including the development of new models of seizure initiation, its use for seizure prediction, and for fast, closed-loop control of pathological brain rhythms, and what these experiments tell us about epileptic pathophysiology. Finally, we consider how these pre-clinical research advances may be translated into clinical practice.
Keywords: brain-machine interface; epilepsy; feedback control; neuromodulation; optogenetics; seizure.
© The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain.