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

Jonathan C. Ho, Thandar Aung, Arianna Damiani, Lilly Tang, Arka N. Mallela, Donald J. Crammond and Jorge A. González-Martínez ()
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Jonathan C. Ho: University of Pittsburgh
Thandar Aung: University of Pittsburgh
Arianna Damiani: University of Pittsburgh
Lilly Tang: University of Pittsburgh
Arka N. Mallela: University of Pittsburgh
Donald J. Crammond: University of Pittsburgh
Jorge A. González-Martínez: University of Pittsburgh

Nature Communications, 2025, vol. 16, issue 1, 1-8

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-60183-9

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