Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers.
Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers.
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DOI：
10.3389/fnins.2022.945221
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发表时间：
2022
影响因子：
4.3
通讯作者：
Williamson, Adam
中科院分区：
文献类型：
--
作者：
Acerbo, Emma;Jegou, Aude;Luff, Charlotte;Dzialecka, Patrycja;Botzanowski, Boris;Missey, Florian;Ngom, Ibrahima;Lagarde, Stanislas;Bartolomei, Fabrice;Cassara, Antonino;Neufeld, Esra;Jirsa, Viktor;Carron, Romain;Grossman, Nir;Williamson, Adam
脑深部电刺激（DBS）电极对顽固性耐药癫痫患者的神经刺激是一种有效的治疗干预，当切除手术禁忌或失败时。抑制性DBS可以通过高频刺激（HFS）来抑制癫痫发作和相关的癫痫生物标志物，通常在100到165赫兹之间，刺激各种深层目标，如中颞叶（MTL），这导致大脑节律的变化，特别是在海马体中。最显著的变化与高频振荡（hfo）有关，即波纹增加，病理性快速波纹（FRs）减少，病理性癫痫样间期放电（ied）减少。在目前的研究中，我们使用时间干扰（TI）刺激在两种癫痫小鼠模型中提供MTL（特别是海马）的非侵入性DBS (130 Hz)，并使用人类尸体来验证该方法在人类患者中的潜在疗效。对小鼠和人类头部进行了模拟，以计算到达海马体的最佳坐标。这种非侵入性DBS增加了小鼠癫痫模型的生理波纹，并减少了FRs和ied的数量。同样，我们发现130hz经颅电流刺激（TCS）无法达到类似的结果。因此，我们通过在人体尸体中测量TI刺激与TCS进一步证明了对人类受试者的可翻译性。结果表明，与TCS相比，TI场对人海马的穿透性更好。这些结果首次证明了TI在不影响周围组织的情况下对深度区域进行刺激的可行性和效率。这些数据倾向于显示诱导效应的充分局灶性，并表明在癫痫治疗中有前景的应用。
Neurostimulation applied from deep brain stimulation (DBS) electrodes is an effective therapeutic intervention in patients suffering from intractable drug-resistant epilepsy when resective surgery is contraindicated or failed. Inhibitory DBS to suppress seizures and associated epileptogenic biomarkers could be performed with high-frequency stimulation (HFS), typically between 100 and 165 Hz, to various deep-seated targets, such as the Mesio-temporal lobe (MTL), which leads to changes in brain rhythms, specifically in the hippocampus. The most prominent alterations concern high-frequency oscillations (HFOs), namely an increase in ripples, a reduction in pathological Fast Ripples (FRs), and a decrease in pathological interictal epileptiform discharges (IEDs). In the current study, we use Temporal Interference (TI) stimulation to provide a non-invasive DBS (130 Hz) of the MTL, specifically the hippocampus, in both mouse models of epilepsy, and scale the method using human cadavers to demonstrate the potential efficacy in human patients. Simulations for both mice and human heads were performed to calculate the best coordinates to reach the hippocampus. This non-invasive DBS increases physiological ripples, and decreases the number of FRs and IEDs in a mouse model of epilepsy. Similarly, we show the inability of 130 Hz transcranial current stimulation (TCS) to achieve similar results. We therefore further demonstrate the translatability to human subjects via measurements of the TI stimulation vs. TCS in human cadavers. Results show a better penetration of TI fields into the human hippocampus as compared with TCS. These results constitute the first proof of the feasibility and efficiency of TI to stimulate at depth an area without impacting the surrounding tissue. The data tend to show the sufficiently focal character of the induced effects and suggest promising therapeutic applications in epilepsy.
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