Nallammai Muthiah, Jon T. Willie
BACKGROUND: Drug-resistant epilepsy (DRE) remains a major therapeutic challenge, and neuromodulation has emerged as an essential palliative option for patients who are not candidates for resective or ablative surgery. Deep brain stimulation (DBS) and responsive neurostimulation are now widely used in clinical practice. SUMMARY: Randomized trials and long-term studies demonstrate durable seizure reductions and improvements in quality of life, although patient and target selection, device programming, and adverse effects remain key considerations. Traditional DBS targets such as the anterior and centromedian thalamic nuclei and hippocampus are those supported by robust evidence, while emerging targets including the pulvinar, subthalamic nucleus, globus pallidus internus, cerebellum, and white-matter tracts require further investigation. Multitarget and multidevice approaches are increasingly reported for highly refractory cases, reflecting the complexity of epileptogenic networks and a drive to improve results. Advances in neuroimaging, biomarkers, adaptive stimulation, and preoperative invasive recording of thalamocortical circuits ("thalamic stereoelectroencephalography") promise to refine target selection and optimize outcomes; but controversies and challenges remain. KEY MESSAGE: Neuromodulation as a rapidly evolving field that offers meaningful seizure control and quality-of-life improvements for patients with otherwise intractable epilepsy. Network principles, advanced imaging, invasive thalamic recording, biomarkers, and multimodal approaches promise a more personalized approach to selecting traditional and emerging DBS targets for epilepsy.