Department of Biomedical Engineering, The City College of New York of CUNY, New York, NY 10031, USA; Biomedical Engineering Department, Amirkabir University of Technology, Tehran, Iran.
Dipartimento di Studi Umanistici, University Federico II, Naples and IRCCS Fondazione Santa Lucia, Rome Italy.
Brain Stimul. 2018 Mar-Apr;11(2):310-321. doi: 10.1016/j.brs.2017.12.002. Epub 2017 Dec 13.
Transcranial direct current stimulation (tDCS) is investigated to modulate neuronal function by applying a fixed low-intensity direct current to scalp.
We critically discuss evidence for a monotonic response in effect size with increasing current intensity, with a specific focus on a question if increasing applied current enhance the efficacy of tDCS.
We analyzed tDCS intensity does-response from different perspectives including biophysical modeling, animal modeling, human neurophysiology, neuroimaging and behavioral/clinical measures. Further, we discuss approaches to design dose-response trials.
Physical models predict electric field in the brain increases with applied tDCS intensity. Data from animal studies are lacking since a range of relevant low-intensities is rarely tested. Results from imaging studies are ambiguous while human neurophysiology, including using transcranial magnetic stimulation (TMS) as a probe, suggests a complex state-dependent non-monotonic dose response. The diffusivity of brain current flow produced by conventional tDCS montages complicates this analysis, with relatively few studies on focal High Definition (HD)-tDCS. In behavioral and clinical trials, only a limited range of intensities (1-2 mA), and typically just one intensity, are conventionally tested; moreover, outcomes are subject brain-state dependent. Measurements and models of current flow show that for the same applied current, substantial differences in brain current occur across individuals. Trials are thus subject to inter-individual differences that complicate consideration of population-level dose response.
The presence or absence of simple dose response does not impact how efficacious a given tDCS dose is for a given indication. Understanding dose-response in human applications of tDCS is needed for protocol optimization including individualized dose to reduce outcome variability, which requires intelligent design of dose-response studies.
经颅直流电刺激（tDCS）通过在头皮上施加固定的低强度直流电来调节神经元功能。
我们批判性地讨论了效应大小随电流强度增加呈单调响应的证据，特别关注一个问题，即增加施加的电流是否会增强 tDCS 的疗效。
我们从不同角度分析了 tDCS 强度与反应的关系，包括生物物理建模、动物模型、人类神经生理学、神经影像学和行为/临床测量。此外，我们还讨论了设计剂量反应试验的方法。
物理模型预测大脑中的电场随施加的 tDCS 强度增加而增加。由于很少测试相关的低强度范围，因此缺乏动物研究数据。成像研究的结果模棱两可，而人类神经生理学，包括使用经颅磁刺激（TMS）作为探针，表明存在复杂的状态依赖非单调剂量反应。常规 tDCS 组合产生的脑电流弥散性使这种分析变得复杂，而针对聚焦的高清晰度（HD）-tDCS 的研究相对较少。在行为和临床试验中，通常只测试 1-2 mA 的有限强度范围，而且通常只测试一个强度；此外，结果还受大脑状态的影响。电流流动的测量和模型表明，对于相同的施加电流，个体之间的大脑电流存在显著差异。因此，试验受到个体间差异的影响，这使得考虑人群水平的剂量反应变得复杂。
简单剂量反应的存在与否并不影响特定 tDCS 剂量对特定适应症的疗效。了解 tDCS 在人类应用中的剂量反应对于协议优化是必要的，包括个体化剂量以减少结果变异性，这需要智能设计剂量反应研究。
