Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions. Brain Stimul

Department of Neurosciences and Behavior, Institute of Psychology, University of São Paulo, São Paulo, Brazil.
Brain Stimulation (Impact Factor: 4.4). 04/2011; 5(3):175-95. DOI: 10.1016/j.brs.2011.03.002
Source: PubMed


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. MAIN FINDINGS/DISCUSSION: 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.

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    • "Although we found that tDCS-dependent SCF modulations were localized in task-related areas characterized in absence of stimulation (Fig.3, Supplementary Table S2), source localization at higher spatial resolution than applied here might provide further evidence for the involvement of such mechanisms. As the return electrode placed over the contralateral supraorbital region is neither inert nor inactive, direct contribution of this electrode to the observed physiological effects cannot be excluded (Brunoni et al., 2012). Provided same polarity, the supraorbital return electrode may have influenced brain activity similar to the contralateral more posterior placement. "
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    ABSTRACT: Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0-4Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior.
    NeuroImage 10/2015; DOI:10.1016/j.neuroimage.2015.09.068 · 6.36 Impact Factor
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    • "Thus, a more likely possibility is that the interactions reflect physiological carry-over effects between stimulation types. So far, prolonged effects of tDCS have typically been reported after administration of multiple stimulation sessions (Brunoni et al., 2012; Olma et al., 2013). However, it is possible that multiple sessions are only necessary in order for behavioral effects to last without further stimulation, whereas if a different type of stimulation is administered as a follow-up, its effects may be modified even by a single previous administration of stimulation. "
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    ABSTRACT: High-definition transcranial direct current stimulation (HD-tDCS) is a novel brain stimulation method that has high potential for use in language therapy for speakers with aphasia, due to its safety and focality. This study aimed to obtain foundational data on using HD-tDCS to modulate language processing in healthy speakers. Participants received stimulation either of Broca's area or of the left angular gyrus (20 min of anodal, cathodal, and sham stimulation on separate days), followed by naming and lexical decision tasks with single-word verb and noun stimuli. We found that cathodal stimulation over both Broca's area and the left angular gyrus increased naming speed for both verbs and nouns, challenging the traditional view of cathodal stimulation as suppressive or leading to decreased performance. The effect did not extend to the lexical decision task. Additionally, effects of specific stimulation types depended on the order of their administration, suggesting possible physiological carry-over and/or task novelty effects. These results are relevant to the application of HD-tDCS to enhance and direct neural plasticity in patients with neurogenic language disorders.
    NeuroRegulation 10/2015; 2(3):111-125. DOI:10.15540/nr.2.3.111
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    • "Stimulation of constant current is widely used in the field of non-invasive brain stimulation, with particular interest directed towards research related to the recovery of motor function after stroke, treatment of depression, chronic pain, and several neurological and psychiatric condition, as well as modulation of various cognitive function (e.g. attention, working memory) [1]. A special problem during electrical stimulation is the current regulation. "
    Dataset: ELS-3

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