Special Issue on tDCSPhysiology of Transcranial Direct Current StimulationStagg, Charlotte J. MD, PhD*†; Antal, Andrea PhD‡; Nitsche, Michael A. MD§∥Author Information From the *Nuffield Department of Clinical Neurosciences, Oxford Centre for Functional MRI of the Brain, and †Department of Psychiatry, Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, United Kingdom; and ‡Department of Clinical Neurophysiology, University Medical Center Göttingen, University of Göttingen, Göttingen; §Department of Psychology and Neurosciences, Leibniz Research Centre for Working Environment and Human Factors, Dortmund; and ∥Department of Neurology, University Medical Hospital Bergmannsheil, Bochum, Germany. Received for publication February 10, 2018; accepted April 24, 2018. Reprints: Michael A. Nitsche, Department of Psychology and Neurosciences, Leibniz Research Centre for Working Environment and Human Factors, Ardeystr. 67, 44139 Dortmund, Germany (e-mail: [email protected]). M.A.N. receives support by the EC Horizon 2020 Program, FET Grant, 686764-LUMINOUS, grants from the German Ministry of Research and Education (GCBS grant 01EE1403C, TRAINSTIM grant 01GQ1424E), and by a grant from the Deutsche Forschungsgemeinschaft, Germany (SFB 1280 Extinction Learning). C.J.S. holds a Sir Henry Dale Fellowship, funded by the Wellcome Trust and the Royal Society (102584/Z/13/Z). The Wellcome Centre for Integrative Neuroimaging is supported by core funding from the Wellcome Trust (203139/Z/16/Z). M.A.N. is in the Advisory Board of Neuroelectrics. C.J.S. and A.A. have no conflicts of interest to report. The Journal of ECT: September 2018 - Volume 34 - Issue 3 - p 144-152 doi: 10.1097/YCT.0000000000000510 Buy Metrics Abstract Direct current stimulation is a neuromodulatory noninvasive brain stimulation tool, which was first introduced in animal and human experiments in the 1950s, and added to the standard arsenal of methods to alter brain physiology as well as psychological, motor, and behavioral processes and clinical symptoms in neurological and psychiatric diseases about 20 years ago. In contrast to other noninvasive brain stimulation tools, such as transcranial magnetic stimulation, it does not directly induce cerebral activity, but rather alters spontaneous brain activity and excitability by subthreshold modulation of neuronal membranes. Beyond acute effects on brain functions, specific protocols are suited to induce long-lasting alterations of cortical excitability and activity, which share features with long-term potentiation and depression. These neuroplastic processes are important foundations for various cognitive functions such as learning and memory formation and are pathologically altered in numerous neurological and psychiatric diseases. This explains the increasing interest to investigate transcranial direct current stimulation (tDCS) as a therapeutic tool. However, for tDCS to be used effectively, it is crucial to be informed about physiological mechanisms of action. These have been increasingly elucidated during the last years. This review gives an overview of the current knowledge available regarding physiological mechanisms of tDCS, spanning from acute regional effects, over neuroplastic effects to its impact on cerebral networks. Although knowledge about the physiological effects of tDCS is still not complete, this might help to guide applications on a scientifically sound foundation. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.