Responsive neurostimulation (RNS) devices, able to detect imminent seizures and to rapidly deliver electrical stimulation to the brain, are effective in reducing seizures in some patients with focal epilepsy. However, therapeutic response to RNS is often slow, is highly variable, and defies prognostication based on clinical factors. A prevailing view holds that RNS efficacy is primarily mediated by acute seizure termination; yet, stimulations greatly outnumber seizures and occur mostly in the interictal state, suggesting chronic modulation of brain networks that generate seizures. Here, using years-long intracranial neural recordings collected during RNS therapy, we found that patients with the greatest therapeutic benefit undergo progressive, frequency-dependent reorganization of interictal functional connectivity. The extent of this reorganization scales directly with seizure reduction and emerges within the first year of RNS treatment, enabling potential early prediction of therapeutic response. Our findings reveal a mechanism for RNS that involves network plasticity and may inform development of next-generation devices for epilepsy.

响应性神经刺激 (RNS) 设备能够检测即将发生的癫痫发作并向大脑快速传递电刺激，可有效减少某些局灶性癫痫患者的癫痫发作。然而，对 RNS 的治疗反应通常很慢，变化很大，并且无法根据临床因素进行预测。一种普遍的观点认为，RNS 的功效主要是由急性发作终止介导的。然而，刺激大大超过癫痫发作，并且主要发生在发作间期，这表明产生癫痫发作的大脑网络的慢性调节。在这里，使用在 RNS 治疗期间收集的长达数年的颅内神经记录，我们发现具有最大治疗益处的患者会经历发作间期功能连接的渐进性、频率依赖性重组。这种重组的程度与癫痫发作的减少直接相关，并在 RNS 治疗的第一年内出现，从而能够对治疗反应进行潜在的早期预测。我们的研究结果揭示了涉及网络可塑性的 RNS 机制，并可能为下一代癫痫设备的开发提供信息。