High-frequency stimulation of anterior nucleus of thalamus desynchronizes epileptic network in humans
High-frequency stimulation of anterior nucleus of thalamus desynchronizes epileptic network in humans
复制标题
丘脑前核的高频刺激使人类癫痫网络不同步
DOI：
10.1093/brain/awy187
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发表时间：
2018-09-01
期刊：
影响因子：
14.5
通讯作者：
Wang, Yuping
中科院分区：
文献类型：
--
作者：
Yu, Tao;Wang, Xueyuan;Wang, Yuping
癫痫被经典地视为一种大脑疾病，由神经元兴奋性和同步性异常增强引起。尽管它自古以来就被描述，但实现癫痫自由发作的治疗目标仍然面临着巨大的挑战。丘脑前核深部脑刺激已成为治疗局部抗药性癫痫的一种很有前途的疗法；然而，其基本作用机制尚不清楚。在这里，我们通过研究9例耐药局灶性癫痫患者在高频刺激(130赫兹)丘脑前核时皮层的局部场电位记录，表明去同步化是丘脑前核深部脑刺激的潜在机制。我们证明，对丘脑前核施加高频刺激可以在较宽的频率范围内使同侧海马区的背景电活动失去同步性，并减少病理性癫痫放电，包括发作间期棘波和高频振荡。此外，高频刺激丘脑前核能够分离涉及海马区和分布皮质区域的大规模神经活动。我们发现，从15到45赫兹的刺激频率与海马局域场电位的同步化有关，而更高的频率(>；45赫兹)则促进同侧海马区活动的去同步。此外，丘脑-丘脑诱发电位和丘脑-海马诱发电位显示丘脑前核和海马区之间存在相互的有效连接。综上所述，高频刺激丘脑前核可以使局灶性和大规模癫痫网络失去同步性，并被认为是减少癫痫发作产生和传播的机制。我们的数据还表明，丘脑前核和颞叶癫痫患者的深部脑刺激与Papaz环路或边缘系统内的癫痫起始区之间存在特定的位置相关性。我们的观察结果可能有助于指导电极植入以提高临床疗效。
Epilepsy has been classically seen as a brain disorder resulting from abnormally enhanced neuronal excitability and synchronization. Although it has been described since antiquity, there are still significant challenges achieving the therapeutic goal of seizure freedom. Deep brain stimulation of the anterior nucleus of the thalamus has emerged as a promising therapy for focal drug-resistant epilepsy; the basic mechanism of action, however, remains unclear. Here, we show that desynchronization is a potential mechanism of deep brain stimulation of the anterior nucleus of the thalamus by studying local field potentials recordings from the cortex during high-frequency stimulation (130 Hz) of the anterior nucleus of the thalamus in nine patients with drug-resistant focal epilepsy. We demonstrate that high-frequency stimulation applied to the anterior nucleus of the thalamus desynchronizes ipsilateral hippocampal background electrical activity over a broad frequency range, and reduces pathological epileptic discharges including interictal spikes and high-frequency oscillations. Furthermore, high-frequency stimulation of the anterior nucleus of the thalamus is capable of decoupling large-scale neural activity involving the hippocampus and distributed cortical areas. We found that stimulation frequencies ranging from 15 to 45 Hz were associated with synchronization of hippocampal local field potentials, whereas higher frequencies (>45 Hz) promoted desynchronization of ipsilateral hippocampal activity. Moreover, reciprocal effective connectivity between the anterior nucleus of the thalamus and the hippocampus was demonstrated by hippocampal-thalamic evoked potentials and thalamic-hippocampal evoked potentials. In summary, high-frequency stimulation of the anterior nucleus of the thalamus is shown to desynchronize focal and large-scale epileptic networks, and here is proposed as the mechanism for reducing seizure generation and propagation. Our data also demonstrate position-specific correlation between deep brain stimulation applied to the anterior nucleus of the thalamus and patients with temporal lobe epilepsy and seizure onset zone within the Papaz circuit or limbic system. Our observation may prove useful for guiding electrode implantation to increase clinical efficacy.