Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions.
BACKGROUND
Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past 10 years, tDCS physiologic mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodologic, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them.


METHODS
We convened a workgroup of researchers in the field to review, discuss, and provide updates and key challenges of tDCS use in clinical research.
We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (1) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (2) methodologic aspects related to the clinical research of tDCS as divided according to study phase (ie, preclinical, phase I, phase II, and phase III studies); (3) ethical and regulatory concerns; and (4) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS.
Department of Neurosciences and Behavior, Institute of Psychology, University of São Paulo, São Paulo, Brazil.
Andre Russowsky
AR
Brunoni
Department of Clinical Neurophysiology, Georg-August University, Goettingen, Germany.
Michael A
MA
Nitsche
Department of Psychology, University of Milano-Bicocca, Milan, Italy; Neuropsychological Laboratory, IRCCS Instituto Auxologico Italiano, Milan, Italy.
Nadia
N
Bolognini
The City College of City University of New York, New York, New York.
Marom
M
Bikson
Massachusetts Institute of Technology, Boston, Massachusetts.
Tim
T
Wagner
Massachusets Eye and Ear Infirmary, Harvard University, Boston, Massachusetts.
Lotfi
L
Merabet
Burke Medical Research Institute, White Plains, New York.
Dylan J
DJ
Edwards
Boston University School of Medicine, Boston, Massachusetts.
Antoni
A
Valero-Cabre
Department of Neurology, Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Alexander
A
Rotenberg
Berenson-Allen Center for Non-invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Alvaro
A
Pascual-Leone
Centro Clinico per la Neurostimolazione, le Neurotecnologie ed i Disordini del Movimento, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano Dipartimento di Scienze Neurologiche, Milan, Italy.
Roberta
R
Ferrucci
Centro Clinico per la Neurostimolazione, le Neurotecnologie ed i Disordini del Movimento, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano Dipartimento di Scienze Neurologiche, Milan, Italy.
Alberto
A
Priori
Social and Cognitive Neuroscience Laboratory and Developmental Disorders Program, Center for Health and Biological Sciences, Mackenzie Prebyterian University, Sao Paulo, Brazil.
Paulo Sergio
PS
Boggio
Laboratory of Neuromodulation, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: fregni.felipe@mgh.harvard.edu.
Felipe
F
Fregni
D000818:Animals; D035843:Biomedical Research / Q000639:trends*; D001921:Brain / Q000503:physiopathology*; D001927:Brain Diseases / Q000503:physiopathology* / Q000628:therapy*; D005544:Forecasting; D006801:Humans; D050781:Transcranial Magnetic Stimulation / Q000639:trends*