Non-invasive brain stimulation and neuroenhancement

Andrea Antal, Bruce Luber, Anna Katharine Brem, Marom Bikson, Andre R. Brunoni, Roi Cohen Kadosh, Veljko Dubljević, Shirley Fecteau, Florinda Ferreri, Agnes Flöel, Mark Hallett, Roy H. Hamilton, Christoph S. Herrmann, Michal Lavidor, Collen Loo, Caroline Lustenberger, Sergio Machado, Carlo Miniussi, Vera Moliadze, Michael A. NitscheSimone Rossi, Paolo M. Rossini, Emiliano Santarnecchi, Margitta Seeck, Gregor Thut, Zsolt Turi, Yoshikazu Ugawa, Ganesan Venkatasubramanian, Nicole Wenderoth, Anna Wexler, Ulf Ziemann, Walter Paulus

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations


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.

Original languageEnglish
Pages (from-to)146-165
Number of pages20
JournalClinical Neurophysiology Practice
StatePublished - Jan 2022

Bibliographical note

Funding Information:
RH is currently supported by research grants from the NIH (R01AG059763) and U.S. Department of Defense (PR191513). He has received fees as a speaker by Starfish Neuroscience and Alexion Pharmaceuticals. None of these sources of support are related to this work.

Funding Information:
FF and her research program are partially supported by the Italian National Institute of Health, Grant number GR-2016-02361802.

Funding Information:
BL is supported by the NIMH Intramural Research Program (ZIAMH002955).

Funding Information:
GV acknowledges the support of Department of Biotechnology (DBT) – Wellcome Trust India Alliance (IA/CRC/19/1/610005) and Department of Biotechnology, Government of India (BT/HRD-NBA-NWB/38/2019-20(6)).

Funding Information:
MAN is supported by Deutsche Forschungsgemeinschaft (DFG) – Projektnummer 316803389 – SFB 1280 “Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Projektnummer 316803389 – SFB 1280, the German Federal Ministry of Education and Research (BMBF, GCBS grant 01EE1501), and the EU (Neurotwin, H2020, grant 101017716).

Funding Information:
UZ received grants from the German Ministry of Education and Research (BMBF), European Research Council (ERC), German Research Foundation (DFG), Janssen Pharmaceuticals NV and Takeda Pharmaceutical Company Ltd., and consulting fees from Bayer Vital GmbH, Pfizer GmbH and CorTec GmbH, all not related to this work.

Funding Information:
C Loo and her research program receive competitive grant funding from the Australian National Health and Medical Research Council.

Funding Information:
WP is currently supported by a research grant of the EU Joint Programme – Neurodegenerative Disease Research (JPND).

Funding Information:
YU is supported by research grants from the Research Project Grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (grants number: 18K10821, 10H01091, 20K07866).

Funding Information:
CL is supported by the Swiss National Science Foundation (PZ00P3_179795). She is a member of the Scientific Advisory Board of Emma Sleep GmbH.

Funding Information:
VM acknowledges the financial support by STIPED funding from the European Union’s Horizon 2020 research and innovation programme (no. 731827).

Funding Information:
ML and AA are supported by the Volkswagen Foundation German 2018 – Israeli Cooperation in Biological and Life Sciences, Medicine [number A128416]. AA is additionally supported by the BMBF (Stimcode, 01FP2124B).

Funding Information:
MH is supported by the NINDS Intramural Research Program. He is an inventor of patents held by NIH for an immunotoxin for the treatment of focal movement disorders and the H-coil for magnetic stimulation; in relation to the latter, he has received license fee payments from the NIH (from Brainsway). He is on the Medical Advisory Boards of CALA Health and Brainsway (both unpaid positions). He is on the Editorial Board of approximately 15 journals and receives royalties and/or honoraria from publishing from Cambridge University Press, Oxford University Press, Springer, Wiley, Wolters Kluwer, and Elsevier. He has research grants from Medtronic, Inc. for a study of DBS for dystonia and CALA Health for studies of a device to suppress tremor.

Funding Information:
AF is supported by the Deutsche Forschungsgemeinschaft (327654276 – SFB 1315 to AF).

Funding Information:
ARB receives scholarships and support from FAPESP (18/21722-8, 19/06009-6), the Brazilian National Council of Scientific Development (CNPq-1B), University of São Paulo Medical School (PIPA-FMUSP), and the UK Academy of Medical Sciences (Newton Advanced Fellowship), and the International Health Cohort Consortium (IHCC). ARB has equity in Flow Neuroscience, and receives in-kind support from Soterix Medical, MagVenture, Flow Neuroscience, Neurosoft, and NeuroConn.

Funding Information:
NW is supported by the Swiss National Science Foundation (320030_175616) and the National Research Foundation, Prime Minister’s Office, Singapore under its Campus for Research Excellence and Technological Enterprise (CREATE) programme (FHT).

Funding Information:
CSH holds a patent on brain stimulation and was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2177/1 – Project ID 390895286.

Publisher Copyright:
© 2022 International Federation of Clinical Neurophysiology


  • Cognitive enhancement
  • DIY stimulation
  • Home-stimulation
  • Neuroenhancement
  • Transcranial brain stimulation
  • tACS
  • tDCS


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