Antal Andrea, Luber Bruce, Brem Anna-Katharine, Bikson Marom, Brunoni Andre R, Cohen Kadosh Roi, Dubljević Veljko, Fecteau Shirley, Ferreri Florinda, Flöel Agnes, Hallett Mark, Hamilton Roy H, Herrmann Christoph S, Lavidor Michal, Loo Collen, Lustenberger Caroline, Machado Sergio, Miniussi Carlo, Moliadze Vera, Nitsche Michael A, Rossi Simone, Rossini Paolo M, Santarnecchi Emiliano, Seeck Margitta, Thut Gregor, Turi Zsolt, Ugawa Yoshikazu, Venkatasubramanian Ganesan, Wenderoth Nicole, Wexler Anna, Ziemann Ulf, Paulus Walter
Department of Neurology, University Medical Center, Göttingen, Germany.
Noninvasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, USA.
Clin Neurophysiol Pract. 2022 May 25;7:146-165. doi: 10.1016/j.cnp.2022.05.002. eCollection 2022.
Attempts to enhance human memory and learning ability have a long tradition in science. This topic has recently gained substantial attention because of the increasing percentage of older individuals worldwide and the predicted rise of age-associated cognitive decline in brain functions. Transcranial brain stimulation methods, such as transcranial magnetic (TMS) and transcranial electric (tES) stimulation, have been extensively used in an effort to improve cognitive functions in humans. Here we summarize the available data on low-intensity tES for this purpose, in comparison to repetitive TMS and some pharmacological agents, such as caffeine and nicotine. There is no single area in the brain stimulation field in which only positive outcomes have been reported. For self-directed tES devices, how to restrict variability with regard to efficacy is an essential aspect of device design and function. As with any technique, reproducible outcomes depend on the equipment and how well this is matched to the experience and skill of the operator. For self-administered non-invasive brain stimulation, this requires device designs that rigorously incorporate human operator factors. The wide parameter space of non-invasive brain stimulation, including dose (e.g., duration, intensity (current density), number of repetitions), inclusion/exclusion (e.g., subject's age), and homeostatic effects, administration of tasks before and during stimulation, and, most importantly, placebo or nocebo effects, have to be taken into account. The outcomes of stimulation are expected to depend on these parameters and should be strictly controlled. The consensus among experts is that low-intensity tES is safe as long as tested and accepted protocols (including, for example, dose, inclusion/exclusion) are followed and devices are used which follow established engineering risk-management procedures. Devices and protocols that allow stimulation outside these parameters cannot claim to be "safe" where they are applying stimulation beyond that examined in published studies that also investigated potential side effects. Brain stimulation devices marketed for consumer use are distinct from medical devices because they do not make medical claims and are therefore not necessarily subject to the same level of regulation as medical devices (i.e., by government agencies tasked with regulating medical devices). Manufacturers must follow ethical and best practices in marketing tES stimulators, including not misleading users by referencing effects from human trials using devices and protocols not similar to theirs.
在科学领域，增强人类记忆力和学习能力的尝试由来已久。由于全球老年人口比例不断上升以及预计与年龄相关的脑功能认知衰退的增加，这个话题最近受到了广泛关注。经颅脑刺激方法，如经颅磁刺激（TMS）和经颅电刺激（tES），已被广泛用于改善人类认知功能。在此，我们总结了为此目的使用低强度tES的现有数据，并与重复TMS以及一些药物制剂（如咖啡因和尼古丁）进行比较。在脑刺激领域，没有一个领域只报道了积极的结果。对于自我导向的tES设备，如何限制疗效的变异性是设备设计和功能的一个重要方面。与任何技术一样，可重复的结果取决于设备以及设备与操作人员经验和技能的匹配程度。对于自我施用的非侵入性脑刺激，这需要在设备设计中严格纳入人类操作人员因素。非侵入性脑刺激的参数空间很广，包括剂量（如持续时间、强度（电流密度）、重复次数）、纳入/排除标准（如受试者年龄）、稳态效应、刺激前和刺激期间的任务施用，以及最重要的安慰剂或反安慰剂效应，都必须加以考虑。刺激结果预计取决于这些参数，应严格控制。专家们的共识是，只要遵循经过测试和认可的方案（包括例如剂量、纳入/排除标准），并使用遵循既定工程风险管理程序的设备，低强度tES就是安全的。允许在这些参数之外进行刺激的设备和方案，在其应用的刺激超出已发表研究中所研究的范围（这些研究也调查了潜在副作用）时，不能声称是“安全的”。面向消费者销售的脑刺激设备与医疗设备不同，因为它们不提出医疗主张，因此不一定受到与医疗设备相同程度的监管（即由负责监管医疗设备的政府机构监管）。制造商在销售tES刺激器时必须遵循道德和最佳实践，包括不通过引用使用与他们的设备和方案不同的人体试验效果来误导用户。
