The bed nucleus of the stria terminalis as a neuromodulatory target for refractory epilepsy

Refractory epilepsy remains a significant clinical challenge, affecting over a third of patients with epilepsy and drastically increasing their risk of sudden unexpected death in epilepsy (SUDEP). Furthermore, psychiatric comorbidities - such as depression and anxiety disorders - are highly prevalent among patients with epilepsy. As neuromodulatory therapeutic approaches evolve, it is paramount that novel targets for stimulation are explored that may concomitantly reduce seizure burden, ameliorate psychiatric comorbidities, and/or reduce SUDEP risk. Here, we review physiological factors that are thought to contribute to SUDEP and which may reduce risk of SUDEP if addressed therapeutically, then we describe how the bed nucleus of the stria terminalis (BNST) represents a forebrain limbic region that concurrently influences many of these physiological processes. We conclude by synthesizing recent findings regarding the BNST in patients and preclinical models of epilepsy and propose that this evidence positions the BNST as a promising extra-thalamic target for therapeutic neurostimulation in patients with refractory epilepsy.