Refining centromedian nucleus stimulation for generalized epilepsy with targeting and mechanistic insights from intraoperative electrophysiology

Abstract Epilepsy affects 65 million people worldwide, with 30% suffering from drug-resistant epilepsy. While surgical resection is the primary treatment, its application is limited in generalized epilepsy. Centromedian nucleus neurostimulation offers a promising alternative, yet its mechanisms rema...

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Bibliographic Details
Main Authors: Jonathan C. Ho, Thandar Aung, Arianna Damiani, Lilly Tang, Arka N. Mallela, Donald J. Crammond, Jorge A. González-Martínez
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60183-9
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Summary:Abstract Epilepsy affects 65 million people worldwide, with 30% suffering from drug-resistant epilepsy. While surgical resection is the primary treatment, its application is limited in generalized epilepsy. Centromedian nucleus neurostimulation offers a promising alternative, yet its mechanisms remain unclear, limiting target optimization. We present a multimodal approach integrating intraoperative thalamic and sub-scalp electroencephalogram recordings with post-implant reconstructions to define neural targets affected by centromedian nucleus stimulation. We find that stimulating low-activity regions near the centromedian nucleus, particularly the white matter of internal medullary lamina, induces significant cortical delta power increases greater than stimulation within high-activity areas inside the nucleus. Implantation in these low-activity targets results in greater than 50% seizure reduction in all three subjects. These findings suggest that seizure control primarily involves stimulating white matter regions such as the internal medullary lamina rather than the centromedian nucleus itself. A personalized, electrophysiology-guided implantation approach may enhance neurostimulation efficacy in drug-resistant epilepsy.
ISSN:2041-1723