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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月6日

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  • Jonathan C. Ho,
  • Thandar Aung,
  • Arianna Damiani,
  • Lilly Tang,
  • Arka N. Mallela,
  • Donald J. Crammond,
  • Jorge A. González-Martínez

摘要

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.