Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, 100053, Beijing, China.
Mayo Systems Electrophysiology Laboratory, Departments of Neurology and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
Brain. 2018 Sep 1;141(9):2631-2643. doi: 10.1093/brain/awy187.
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.
癫痫一直被认为是一种源自神经元异常兴奋和同步的脑部疾病。尽管它自古就有记载，但要实现无癫痫发作的治疗目标仍面临重大挑战。丘脑前核深部脑刺激已成为治疗局灶性耐药性癫痫的一种有前途的疗法；然而，其基本作用机制仍不清楚。在这里，我们通过研究 9 例耐药性局灶性癫痫患者在丘脑前核高频刺激（130 Hz）期间皮质的局部场电位记录，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，高频刺激施加于丘脑前核可在广泛的频率范围内使同侧海马背景电活动去同步化，并减少病理性癫痫放电，包括发作间棘波和高频振荡。此外，丘脑前核的高频刺激能够解耦涉及海马和分布式皮质区域的大规模神经活动。我们发现，刺激频率在 15 至 45 Hz 范围内与海马局部场电位的同步化相关，而更高的频率（>45 Hz）则促进同侧海马活动的去同步化。此外，通过海马-丘脑诱发电位和丘脑-海马诱发电位证明了丘脑前核与海马之间的反向有效连通性。总之，研究表明，丘脑前核的高频刺激可使局灶性和大规模癫痫网络去同步化，并提出了减少癫痫发作产生和传播的机制。我们的数据还证明了在颞叶癫痫患者和帕帕兹回路或边缘系统内的起始区中，应用于丘脑前核的深部脑刺激与患者之间存在位置特异性相关性。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。
