Evidence and Rationale for Centromedian Nucleus versus Internal Medullary Lamina Stimulation for Generalized Epilepsy Through Intra-Operative Multi-Modal Electrophysiology Studies

Abstract Epilepsy's global impact affects 65 million individuals, of which 30% endure drug-resistant epilepsy (DRE). Surgical excision of the epileptogenic zone remains the primary intervention but is often hampered if patients have generalized epilepsy. Neuromodulation, such thalamic centromedian nucleus (CM) neurostimulation, offers a promising alternative. However, the mechanism is unclear by which neurostimulation of the CM modulates cortical neurophysiology to reduce seizures, hampering progress for more effective targeting of the CM. In this study, we introduce a novel multimodal approach that combines intraoperative thalamic and cortical recordings with diffusion tractography to precisely elucidate CM stimulation targets. Our analysis reveals that stimulation of lower cellular activity CM targets produce greater cortical delta activity that is observed during epileptogenic network disruption. We found that this stimulation target lies within the internal medullary lamina, which differs from standard thalamic targets. Our findings show that a personalized implantation method guided by electrophysiological mapping can enhance neurostimulation targets in treating DRE.