Department of Neurosurgery, University of Utah, Salt Lake City, UT 84132, USA.
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, USA.
Brain. 2024 Feb 1;147(2):521-531. doi: 10.1093/brain/awad343.
In patients with drug-resistant epilepsy, electrical stimulation of the brain in response to epileptiform activity can make seizures less frequent and debilitating. This therapy, known as closed-loop responsive neurostimulation (RNS), aims to directly halt seizure activity via targeted stimulation of a burgeoning seizure. Rather than immediately stopping seizures as they start, many RNS implants produce slower, long-lasting changes in brain dynamics that better predict clinical outcomes. Here we hypothesize that stimulation during brain states with less epileptiform activity drives long-term changes that restore healthy brain networks. To test this, we quantified stimulation episodes during low- and high-risk brain states-that is, stimulation during periods with a lower or higher risk of generating epileptiform activity-in a cohort of 40 patients treated with RNS. More frequent stimulation in tonic low-risk states and out of rhythmic high-risk states predicted seizure reduction. Additionally, stimulation events were more likely to be phase-locked to prolonged episodes of abnormal activity for intermediate and poor responders when compared to super-responders, consistent with the hypothesis that improved outcomes are driven by stimulation during low-risk states. These results support the hypothesis that stimulation during low-risk periods might underlie the mechanisms of RNS, suggesting a relationship between temporal patterns of neuromodulation and plasticity that facilitates long-term seizure reduction.
在耐药性癫痫患者中，针对癫痫样活动的大脑电刺激可以使发作频率降低，症状减轻。这种治疗方法被称为闭环反应性神经刺激（RNS），旨在通过对正在发展的癫痫发作进行靶向刺激，直接阻止癫痫发作。许多 RNS 植入物不会立即阻止发作，而是产生较慢、持续时间较长的大脑动力学变化，从而更好地预测临床结果。在这里，我们假设在癫痫样活动较少的脑状态下进行刺激会产生长期变化，从而恢复健康的大脑网络。为了验证这一点，我们在接受 RNS 治疗的 40 名患者的队列中，对低风险和高风险脑状态下的刺激进行了定量分析——即，在产生癫痫样活动的风险较低或较高的时期进行刺激。与超级应答者相比，在紧张低风险状态下更频繁地进行刺激，以及在节律高风险状态外进行刺激，可预测癫痫发作减少。此外，与超级应答者相比，中间和差反应者的刺激事件更有可能与异常活动的延长发作相位锁定，这与刺激在低风险状态下可改善预后的假设一致。这些结果支持了在低风险期进行刺激可能是 RNS 机制的基础这一假设，表明神经调节和可塑性的时间模式之间存在关系，这有助于长期减少癫痫发作。
