Epilepsy is well-recognized as a disorder of brain networks. There is a growing body of research to identify critical nodes within dynamic epileptic networks with the aim to target therapies that halt the onset and propagation of seizures. In parallel, intracranial neuromodulation, including deep brain stimulation and responsive neurostimulation, are well-established and expanding as therapies to reduce seizures in adults with focal epilepsy; and there is emerging evidence for their efficacy in children and generalized seizure disorders. The convergence of these advancing fields is driving an era of ‘network-guided neuromodulation’ for epilepsy. In this review we distil the current literature on network mechanisms underlying neurostimulation for epilepsy. We discuss the modulation of key propagation points in the epileptogenic network, focusing primarily on thalamic nuclei targeted in current clinical practice. These include (a) the anterior nucleus of thalamus, now a clinically approved and targeted site for open loop stimulation, and increasingly targeted for responsive neurostimulation; and (b) the centromedian nucleus of the thalamus, a target for both deep brain stimulation and responsive neurostimulation in generalized-onset epilepsies. We discuss briefly the networks associated with other emerging neuromodulation targets, such as the pulvinar of the thalamus, piriform cortex, septal area, subthalamic nucleus, cerebellum and others. We report synergistic findings garnered from multiple modalities of investigation that revealed structural and functional networks associated with these propagation points – including scalp and invasive electroencephalography, diffusion and functional magnetic resonance imaging. We also report on intracranial recordings from implanted devices which provide us data on the dynamic networks we are aiming to modulate. Finally, we review the continuing evolution of network-guided neurostimulation for epilepsy to accelerate progress towards two major goals: (1) to use pre-surgical network analyses to determine patient candidacy for neurostimulation for epilepsy by providing network biomarkers that predict efficacy; and (2) to deliver precise, personalized and effective antiepileptic stimulation to prevent and arrest seizures, limit seizure propagation through mapping and modulation of each patients’ individual epileptogenic networks.

中文翻译：

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走向网络引导的癫痫神经调节


癫痫被广泛认为是一种大脑网络疾病。越来越多的研究致力于识别动态癫痫网络中的关键节点，旨在找到阻止癫痫发作和蔓延的治疗方法。与此同时，颅内神经调节（包括深部脑刺激和反应性神经刺激）已得到广泛认可，并正在扩大作为减少成人局灶性癫痫发作的治疗方法；越来越多的证据表明它们对儿童和全身性癫痫发作有效。这些先进领域的融合正在推动癫痫“网络引导神经调节”时代的到来。在这篇综述中，我们总结了有关癫痫神经刺激网络机制的最新文献。我们讨论致痫网络中关键传播点的调节，主要关注当前临床实践中针对的丘脑核。这些包括（a）丘脑前核，现在是临床批准的开环刺激的目标部位，并且越来越多地针对响应性神经刺激； (b) 丘脑的中心正中核，是全身性癫痫中深部脑刺激和反应性神经刺激的目标。我们简要讨论与其他新兴神经调节靶点相关的网络，例如丘脑丘脑、梨状皮层、间隔区、丘脑底核、小脑等。我们报告了多种研究方式的协同发现，揭示了与这些传播点相关的结构和功能网络，包括头皮和侵入性脑电图、扩散和功能磁共振成像。 我们还报告了植入设备的颅内记录，这些记录为我们提供了我们想要调节的动态网络的数据。最后，我们回顾了网络引导癫痫神经刺激的持续发展，以加速实现两个主要目标的进展：（1）使用术前网络分析，通过提供预测疗效的网络生物标志物来确定患者是否适合进行癫痫神经刺激； (2) 提供精确、个性化和有效的抗癫痫刺激，以预防和阻止癫痫发作，通过绘制和调节每个患者的个体癫痫网络来限制癫痫发作的蔓延。