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      Transcranial Direct Current Stimulation: Challenges, Opportunities, and Impact on Psychiatry and Neurorehabilitation

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          Abstract

          The simplicity of the technique of transcranial direct current stimulation (tDCS) can be observed as it consists of a current generator and two electrodes that are placed over the scalp and can deliver weak direct currents. Despite its simplicity, the field of non-invasive brain stimulation has had a rapid and exponential increase in the past 10 years. It is in fact an “old, new” technique – as external brain electric stimulation with electric currents has been recurrently described in medical literature since ancient times (Brunoni et al., 2011b), although the technique was reappraised only recently after the seminal studies of Priori et al. (1998) and Nitsche and Paulus (2000), which showed that it could modify cortical excitability in a polarity-dependent manner, i.e., while anode induces neuronal depolarization and thus activation of neural networks beneath the electrode, the cathode induces the opposite effects (i.e., hyperpolarization and consequent inhibition). From 1998 onward, several studies showed that tDCS modulates a plethora of behavioral, sensorial, or motor effects according to parameters of stimulation and subjects’ characteristics. Two important characteristics of tDCS – the duration of its effects and its safety – have attracted the attention of a large number of scientists and clinicians. Indeed tDCS effects can last for several hours beyond the period of stimulation in some cases (Fregni and Pascual-Leone, 2007) and induce changes in brain biochemistry (Rango et al., 2008). In addition, studies in experimental animals show that tDCS is safe (Liebetanz et al., 2009), and a systematic review found that adverse effects are mild and transient (Brunoni et al., 2011a). Another important characteristic of tDCS is that it can potentially be adapted for home-use, which would bring about an important advance to the therapeutic field of brain stimulation (Priori et al., 2009). From a methodological perspective, it has a reliable sham method as compared with, for instance, rTMS. Such characteristics (ease of use, low cost, portability, safe, potent effects) render tDCS a sound device for further clinical research, either as a substitutive therapy or a complementary treatment for other interventions (drug therapy, physical therapy, psychotherapy, and so forth) (Brunoni et al., 2011c), especially considering patients that are unable or unwilling to receive standard treatments. Nonetheless, tDCS clinical trials are still in their infancy. One possible reason is that tDCS use requires basic knowledge on a neural basis of electrical current fields and neuroscience. In fact, an incorrect electrode montage or stimulation of the “wrong” area might generate non-specific or even negative effects (Datta et al., 2010; Mahmoudi et al., 2010; Mendonca et al., 2011). Therefore, it is more difficult to observe positive clinical effects by serendipity – also because tDCS has presently no standard clinical use, all effects can only be observed through research. Further, tDCS trials are methodologically complicated due to attrition, since the protocols demand daily stimulation for 1–4 weeks. A possible solution would be to use portable devices – specific tailored caps could be assembled in for targeting only the desired scalp areas. Furthermore, tDCS may be a device with little commercial interest compared to other medicines or even rTMS – in fact, by being too affordable and with a limited possibility of patenting, more robust business ventures are easily discouraged to develop tDCS commercially. Not surprisingly, at the present time tDCS research is mainly conducted in academic settings, usually with public grants. Nevertheless, this scenario could rapidly change depending on whether effective parameters of stimulation and findings are shown in clinical research. Finally, a simple reason to explain the current stage of development of tDCS is timing. Clinical trials, as well as the reporting and dissemination of results, usually has a significant time span. Considering such challenges, we proposed a Research Topic in Frontiers in Psychiatry, named The frontiers of clinical research on tDCS in neuropsychiatry. The results were surprisingly positive, with 22 articles from new and experienced research groups that, considered together, represent a robust contribution to the advancement of the field. We are also grateful to all the reviewers – many of them productive researchers in the field – for their invaluable help in making suggestions that ultimately improved the manuscripts significantly. The articles hereby presented are divided in five main sections – in the first one, the neurobiological effects of tDCS are reviewed (Medeiros et al., 2012) and original articles on the electrophysiological effects of tDCS on visuo-spatial working memory (Heimrath et al., 2012), human color discrimination (Costa et al., 2012), and motor cortical excitability (Chaieb et al., 2012) are presented. The second section contains original articles exploring the behavioral effects of tDCS such as on the saccade task (Kanai et al., 2012), automatic verbal processes (Vannorsdall et al., 2012), working memory (Jones and Berryhill, 2012), emotional processing (Nitsche et al., 2012) and production of untruthful responses (Fecteau et al., 2012), and one review by Brasil-Neto (2012) on tDCS’ effects in learning and memory. The third section shows original articles on the clinical effects of tDCS on tinnitus (De Ridder and Vanneste, 2012), major depressive disorder (Blumberger et al., 2012; Knotkova et al., 2012) and pain (DosSantos et al., 2012), and reviews its effects on Alzheimer's disease (Hansen, 2012), stroke (Adeyemo et al., 2012; Madhavan and Shah, 2012), and smoking addiction (Fraser and Rosen, 2012). The fourth section presents computational theoretical models of tDCS for further application in clinical practice (Datta et al., 2012; Neuling et al., 2012; Sadleir et al., 2012). The last section reviews the application of spinal tDCS (Cogiamanian et al., 2012). Moving tDCS research from bench to bedside has significant challenges. Nevertheless, there are opportunities for tDCS development as pharmacotherapy is reaching an efficacy and safety plateau and there are still unmet demands for the treatment of several disorders. tDCS therefore represents an interesting alternative that can offer additional therapeutic gains with a minimum of or no side effects. Whether the obstacles of clinical trials are solved or not, this collection of articles presented in this Research Topic provides promising evidence that tDCS could rise in the near future as a novel therapeutic tool and have a significant impact n psychiatry and neurorehabilitation.

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          Most cited references32

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          Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation.

          In this paper we demonstrate in the intact human the possibility of a non-invasive modulation of motor cortex excitability by the application of weak direct current through the scalp. Excitability changes of up to 40 %, revealed by transcranial magnetic stimulation, were accomplished and lasted for several minutes after the end of current stimulation. Excitation could be achieved selectively by anodal stimulation, and inhibition by cathodal stimulation. By varying the current intensity and duration, the strength and duration of the after-effects could be controlled. The effects were probably induced by modification of membrane polarisation. Functional alterations related to post-tetanic potentiation, short-term potentiation and processes similar to postexcitatory central inhibition are the likely candidates for the excitability changes after the end of stimulation. Transcranial electrical stimulation using weak current may thus be a promising tool to modulate cerebral excitability in a non-invasive, painless, reversible, selective and focal way.
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            Polarization of the human motor cortex through the scalp.

            Direct currents (DC) applied directly to central nervous system structures produce substantial and long-lasting effects in animal experiments. We tested the functional effects of very weak scalp DC (< 0.5 mA, 7 s) on the human motor cortex by assessing the changes in motor potentials evoked by transcranial magnetic brain stimulation. We performed four different experiments in 15 healthy volunteers. Our findings led to the conclusion that such weak (< 0.5 mA) anodal scalp DC, alternated with a cathodal DC, significantly depresses the excitability of the human motor cortex, providing evidence that a small electric field crosses the skull and influences the brain. A possible mechanism of action of scalp DC is the hyperpolarization of the superficial excitatory interneurones in the human motor cortex.
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              Inter-Individual Variation during Transcranial Direct Current Stimulation and Normalization of Dose Using MRI-Derived Computational Models

              Background: Transcranial Direct Current Stimulation (tDCS) is a non-invasive, versatile, and safe neuromodulation technology under investigation for the treatment of neuropsychiatric disorders, adjunct to rehabilitation, and cognitive enhancement in healthy adults. Despite promising results, there is variability in responsiveness. One potential source of variability is the intensity of current delivered to the brain which is a function of both the operator controlled tDCS dose (electrode montage and total applied current) and subject specific anatomy. We are interested in both the scale of this variability across anatomical typical adults and methods to normalize inter-individual variation by customizing tDCS dose. Computational FEM simulations are a standard technique to predict brain current flow during tDCS and can be based on subject specific anatomical MRI. Objective: To investigate this variability, we modeled multiple tDCS montages across three adults (ages 34–41, one female). Results: Conventional pad stimulation led to diffuse modulation with maximum current flow between the pads across all subjects. There was high current flow directly under the pad for one subject while the location of peak induced cortical current flow was variable. The High-Definition tDCS montage led to current flow restricted to within the ring perimeter across all subjects. The current flow profile across all subjects and montages was influenced by details in cortical gyri/sulci. Conclusion: This data suggests that subject specific modeling can facilitate consistent and more efficacious tDCS.
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                Author and article information

                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                27 March 2013
                2013
                : 4
                : 19
                Affiliations
                [1] 1Clinical Research Center, University Hospital, University of Sao Paulo Sao Paulo, Brazil
                [2] 2Cognitive Neuroscience Laboratory and Developmental Disorders Program, Center for Health and Biological Sciences, Mackenzie Presbyterian University Sao Paulo, Brazil
                [3] 3Clinical Center for Neurotechnology, Neurostimulation and Movement Disorders, Fondazione IRCCS “Ca’ Granda” Ospedale Maggiore di Milano Milano, Italy
                [4] 4Department of Medical-Surgical Pathophysiology and Transplants Section of Neurosciences, University of Milan Milano, Italy
                [5] 5Laboratory of Neuromodulation, Spaulding Rehabilitation Hospital, Harvard Medical School Boston, MA, USA
                Author notes

                Edited by: Ziad Nahas, Medical University of South Carolina, USA

                Reviewed by: Ziad Nahas, Medical University of South Carolina, USA

                This article was submitted to Frontiers in Neuropsychiatric Imaging and Stimulation, a specialty of Frontiers in Psychiatry.

                Article
                10.3389/fpsyt.2013.00019
                3608899
                23544030
                2dbdc25c-f856-4ef1-9ece-9559e09ca116
                Copyright © 2013 Brunoni, Boggio, Ferrucci, Priori and Fregni.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 21 January 2013
                : 14 March 2013
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 34, Pages: 3, Words: 2261
                Categories
                Psychiatry
                Editorial

                Clinical Psychology & Psychiatry
                Clinical Psychology & Psychiatry

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