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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局部无创深部脑刺激与时间干扰抑制癫痫生物标志物
DOI：
10.1101/2022.03.29.486252
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Acerbo E
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作者：
Acerbo E
脑深部刺激(DBS)电极神经刺激是治疗禁忌症或手术失败的难治性难治性癫痫患者的一种有效的治疗手段。抑制癫痫发作的DBS和相关的致痫生物标志物可以通过高频刺激(HFS)进行，通常在100至165赫兹之间，对各种深层目标，如中颞叶(MTL)，这会导致脑节奏的变化，特别是在海马区。最显著的变化涉及高频振荡(HFO)，即波纹增加，病理性快速涟漪(FR)减少，病理性发作间期癫痫样放电(IED)减少。材料和方法在当前的研究中，我们使用时间干扰(TI)刺激来提供两种癫痫小鼠模型的MTL，特别是海马区的非侵入性DBS(130赫兹)，并使用人类身体来衡量该方法的潜在疗效。对小鼠和人头进行模拟，计算到达海马区的最佳坐标。结果这种无创DBS增加了癫痫小鼠模型的生理波纹，减少了FRS和IED的数量。同样，我们发现130赫兹经颅电流刺激(TCS)无法达到类似的结果。因此，我们通过在人体身体上对TI刺激与TCS的测量，进一步证明了对人类受试者的可译性。结果表明，与TC相比，TI场对人体海马区的穿透性更好。意义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刺激区域的可行性和有效性。这些数据倾向于显示诱导效应的充分局部性特征，并提示在癫痫治疗中有前景的应用。
IntroductionNeurostimulation 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).Materials and methodsIn 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.ResultsThis 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 subjectsviameasurements 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.SignificanceThese 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.