Department of Neurosurgery, Great Ormond Street Hospital, London, UK.
Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Brain. 2022 Oct 21;145(10):3347-3362. doi: 10.1093/brain/awac234.
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-onset epilepsy; and there is emerging evidence for their efficacy in children and generalized-onset 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 (i) the anterior nucleus of thalamus, now a clinically approved and targeted site for open loop stimulation, and increasingly targeted for responsive neurostimulation; and (ii) 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 have revealed structural and functional networks associated with these propagation points - including scalp and invasive EEG, and diffusion and functional MRI. 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 neuromodulation for epilepsy to accelerate progress towards two translational goals: (i) to use pre-surgical network analyses to determine patient candidacy for neurostimulation for epilepsy by providing network biomarkers that predict efficacy; and (ii) to deliver precise, personalized and effective antiepileptic stimulation to prevent and arrest seizure propagation through mapping and modulation of each patients' individual epileptogenic networks.
癫痫被公认为是一种大脑网络紊乱。越来越多的研究旨在确定动态癫痫网络中的关键节点,目的是针对阻止癫痫发作和传播的疗法。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,作为治疗局灶性癫痫成人癫痫发作的方法已得到广泛应用和扩展;并且有证据表明,它们在儿童和全面性癫痫发作障碍中的疗效也在不断涌现。这些不断发展的领域的融合正在推动癫痫的“网络指导神经调节”时代。在这篇综述中,我们总结了目前关于癫痫神经调节的网络机制的文献。我们讨论了在癫痫网络中关键“传播点”的调节,主要集中在当前临床实践中靶向的丘脑核。这些包括(i)丘脑前核,现在是临床批准和靶向的开环刺激部位,并且越来越多地作为反应性神经刺激的靶点;以及(ii)丘脑中央核,是全面性癫痫发作中深部脑刺激和反应性神经刺激的靶点。我们简要讨论了与其他新兴神经调节靶点相关的网络,例如丘脑的丘脑枕、梨状皮层、隔区、丘脑底核、小脑和其他区域。我们报告了从多种研究模式中获得的协同发现,这些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 EEG 以及扩散和功能 MRI。我们还报告了来自植入设备的颅内记录,这些记录为我们提供了有关我们旨在调节的动态网络的数据。最后,我们回顾了癫痫网络指导神经调节的不断发展,以加速向两个转化目标的进展:(i) 使用术前网络分析来确定神经刺激治疗癫痫的患者候选资格,提供预测疗效的网络生物标志物;以及(ii) 通过对每位患者的个体化致痫网络进行映射和调节,提供精确、个性化和有效的抗癫痫刺激来预防和阻止癫痫发作的传播。
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