Epilepsy is increasingly recognized as a disorder of brain networks rather than a solely focal disease. Beyond the seizure focus, connected brain networks can exert inhibitory control over seizure initiation and propagation resulting in antiseizure effects. Here, we present data from animal and human studies on antiseizure networks and integrate recent results from lesion-, stimulation- and neurophysiological-experiments. Consistent with these results, we present the Interictal Suppression Hypothesis that posits that strong inward connectivity to the seizure focus maintains seizure freedom between events, while collapse of this connectivity accompanies seizure spread and generalization. Workshop discussions highlighted future directions, including mechanistic stimulation studies to interrogate the role of antiseizure networks seizure control and design of therapeutic studies towards network–guided neuromodulation for epilepsy. A deeper mechanistic understanding of antiseizure networks may enable development of precision therapies that target endogenous seizure control rather than simply target the seizure focus.
Schaper et al. (Wed,) studied this question.