Temporal interference stimulation targets deep brain regions by modulating neural oscillations.
Temporal interference stimulation targets deep brain regions by modulating neural oscillations.
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DOI：
10.1016/j.brs.2020.11.007
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发表时间：
2021-01
影响因子：
7.7
通讯作者：
Bikson, Marom
中科院分区：
文献类型：
--
作者：
Esmaeilpour, Zeinab;Kronberg, Greg;Reato, Davide;Parra, Lucas C.;Bikson, Marom
关键词：
大脑的时间干扰（TI）刺激产生在kHz范围内振荡的调幅电场，目的是实现非侵入性靶向脑深部刺激。然而，人类调节深部脑活动所需的电流强度（敏感性）以及在这些强度下浅表脑区域是否幸免（选择性）仍然不清楚。我们开发了一个实验约束的理论TI灵敏度kHz电场给定膜低通滤波特性的衰减，和TI的选择性深层结构的调制和未调制的电场在大脑中的分布。对于未调制的0.05-2 kHz正弦波形和具有0.1-2 kHz载波频率的5 Hz调幅波形，确定调制卡巴胆碱诱导的大鼠海马切片中的γ振荡的电场阈值。神经元的影响复制与计算网络模型，探索潜在的机制，然后耦合到一个验证的电流模型的人的头部。调幅电场在大脑深部区域较强，而未调制电场在皮层区域最大。实验和模型均证实了时间干扰刺激的空间选择性仅取决于脑深部神经元振荡的相位调制。与未调制kHz相比，适应机制（例如GABAb）增强了对振幅调制波形的敏感性，并在调制伽马振荡中产生选择性（即振幅调制与未调制kHz刺激中的更高伽马调制）。载波频率的选择强烈影响对调幅刺激的敏感性。使用100 Hz载波频率的调幅刺激需要~5 V/m（对应于头皮表面的~13 mA），而1 kHz载波频率~60 V/m（~160 mA）和2 kHz载波频率~80 V/m（~220 mA）才能显著调制伽马振荡。灵敏度增加（头皮电流需要降低）的理论神经元膜更快的时间常数。TI灵敏度（头皮所需的电流）取决于接近kHz载波频率的神经元膜时间常数（例如轴突）。TI选择性由比幅度调制频率更快的网络自适应（例如GABAb）控制。因此，我们显示神经元和网络振荡时间常数确定所需的头皮电流和可实现的选择性与TI在人类。
Temporal interference (TI) stimulation of the brain generates amplitude-modulated electric fields oscillating in the kHz range with the goal of non-invasive targeted deep brain stimulation. Yet, the current intensities required in human (sensitivity) to modulate deep brain activity and if superficial brain region are spared (selectivity) at these intensities remains unclear. We developed an experimentally constrained theory for TI sensitivity to kHz electric field given the attenuation by membrane low-pass filtering property, and for TI selectivity to deep structures given the distribution of modulated and unmodulated electric fields in brain. The electric field threshold to modulate carbachol-induced gamma oscillations in rat hippocampal slices was determined for unmodulated 0.05–2 kHz sine waveforms, and 5 Hz amplitude-modulated waveforms with 0.1–2 kHz carrier frequencies. The neuronal effects are replicated with a computational network model to explore the underlying mechanisms, and then coupled to a validated current-flow model of the human head. Amplitude-modulated electric fields are stronger in deep brain regions, while unmodulated electric fields are maximal at the cortical regions. Both experiment and model confirmed the hypothesis that spatial selectivity of temporal interference stimulation depends on the phasic modulation of neural oscillations only in deep brain regions. Adaptation mechanism (e.g. GABAb) enhanced sensitivity to amplitude modulated waveform in contrast to unmodulated kHz and produced selectivity in modulating gamma oscillation (i.e. Higher gamma modulation in amplitude modulated vs unmodulated kHz stimulation). Selection of carrier frequency strongly affected sensitivity to amplitude modulation stimulation. Amplitude modulated stimulation with 100 Hz carrier frequency required ~5 V/m (corresponding to ~13 mA at the scalp surface), whereas, 1 kHz carrier frequency ~60 V/m (~160 mA) and 2 kHz carrier frequency ~80 V/m (~220 mA) to significantly modulate gamma oscillation. Sensitivity is increased (scalp current required decreased) for theoretical neuronal membranes with faster time constants. The TI sensitivity (current required at the scalp) depends on the neuronal membrane time-constant (e.g. axons) approaching the kHz carrier frequency. TI selectivity is governed by network adaption (e.g. GABAb) that is faster than the amplitude-modulation frequency. Thus, we show neuronal and network oscillations time-constants determine the scalp current required and the selectivity achievable with TI in humans.
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