Incomplete evidence that increasing current intensity of tDCS boosts outcomes

Zeinab Esmaeilpour; Paola Marangolo; Benjamin M Hampstead; Sven Bestmann; Elisabeth Galletta; Helena Knotkova; Marom Bikson

doi:10.1016/j.brs.2017.12.002

Incomplete evidence that increasing current intensity of tDCS boosts outcomes

Brain Stimul. 2018 Mar-Apr;11(2):310-321. doi: 10.1016/j.brs.2017.12.002. Epub 2017 Dec 13.

Authors

Zeinab Esmaeilpour¹, Paola Marangolo², Benjamin M Hampstead³, Sven Bestmann⁴, Elisabeth Galletta⁵, Helena Knotkova⁶, Marom Bikson⁷

Affiliations

¹ 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. Electronic address: zesmaeilpour@ccny.cuny.edu.
² Dipartimento di Studi Umanistici, University Federico II, Naples and IRCCS Fondazione Santa Lucia, Rome Italy.
³ VA Ann Arbor Healthcare System, Ann Arbor, MI 48105, USA; Department of Psychiatry, University of Michigan, Ann Arbor, MI 48105, USA.
⁴ Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, UK.
⁵ Rusk Rehabilitation Medicine, New York University Langone Medical Center, USA.
⁶ MJHS Institute for Innovation in Palliative Care, New York, NY, USA; Department of Family and Social Medicine, Albert Einstein College of Medicine, The Bronx, NY, USA.
⁷ Department of Biomedical Engineering, The City College of New York of CUNY, New York, NY 10031, USA.

Abstract

Background: Transcranial direct current stimulation (tDCS) is investigated to modulate neuronal function by applying a fixed low-intensity direct current to scalp.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Dose-control; Dose-response; Neuromodulation; Transcranial direct current stimulation (tDCS).

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Animals
Brain / diagnostic imaging
Brain / physiology*
Humans
Individuality
Neuroimaging / methods
Transcranial Direct Current Stimulation / methods*
Transcranial Magnetic Stimulation / methods
Treatment Outcome

Abstract

Publication types

MeSH terms

Grants and funding