A technical guide to tDCS, and related non-invasive brain stimulation tools.

Transcranial electrical stimulation (tES), including transcranial direct and alternating current stimulation (tDCS, tACS) are non-invasive brain stimulation techniques increasingly used for modulation of central nervous system excitability in humans. Here we address methodological issues required for tES application. This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches. It aims to help the reader to appropriately design and conduct studies involving these brain stimulation techniques, understand limitations and avoid shortcomings, which might hamper the scientific rigor and potential applications in the clinical domain.

Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel.

The field of transcranial electrical stimulation (tES) has experienced significant growth in the past 15 years. One of the tES techniques leading this increased interest is transcranial direct current stimulation (tDCS). Significant research efforts have been devoted to determining the clinical potential of tDCS in humans. Despite the promising results obtained with tDCS in basic and clinical neuroscience, further progress has been impeded by a lack of clarity on international regulatory pathways. We therefore convened a group of research and clinician experts on tDCS to review the research and clinical use of tDCS. In this report, we review the regulatory status of tDCS, and we summarize the results according to research, off-label and compassionate use of tDCS in the following countries: Australia, Brazil, France, Germany, India, Iran, Italy, Portugal, South Korea, Taiwan and United States. Research use, off label treatment and compassionate use of tDCS are employed in most of the countries reviewed in this study. It is critical that a global or local effort is organized to pursue definite evidence to either approve and regulate or restrict the use of tDCS in clinical practice on the basis of adequate randomized controlled treatment trials.

Cognitive control therapy and transcranial direct current stimulation for depression: a randomized, double-blinded, controlled trial.

BACKGROUND: Based on findings that major depressive disorder (MDD) is associated to decreased dorsolateral prefrontal cortical (DLPFC) activity; interventions that increase DLPFC activity might theoretically present antidepressant effects. Two of them are cognitive control therapy (CCT), a neurocognitive intervention that uses computer-based working memory exercises, and transcranial direct current stimulation (tDCS), which delivers weak, electric direct currents over the scalp. METHODS: We investigated whether tDCS enhanced the effects of CCT in a double-blind trial, in which participants were randomized to sham tDCS and CCT (n=17) vs. active tDCS and CCT (n=20). CCT and tDCS were applied for 10 consecutive workdays. Clinicaltrials.gov identifier: NCT01434836. RESULTS: Both CCT alone and combined with tDCS ameliorated depressive symptoms after the acute treatment period and at follow-up, with a response rate of approximately 25%. Older patients and those who presented better performance in the task throughout the trial (possibly indicating greater engagement and activation of the DLPFC) had greater depression improvement in the combined treatment group. LIMITATIONS: Our exploratory findings should be further confirmed in prospective controlled trials. DISCUSSION: CCT and tDCS combined might be beneficial for older depressed patients, particularly for those who have cognitive resources to adequately learn and improve task performance over time. This combined therapy might be specifically relevant in this subgroup that is more prone to present cognitive decline and prefrontal cortical atrophy.

Interactions between transcranial direct current stimulation (tDCS) and pharmacological interventions in the Major Depressive Episode: findings from a naturalistic study.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive, neuromodulatory technique with an emerging role for treating major depression. OBJECTIVE: To investigate the interactions between tDCS and drug therapy in unipolar and bipolar depressed patients who were refractory for at least one pharmacological treatment. METHODS: This was a naturalistic study using data from 54 female and 28 male patients (mean age of 54 years) that consecutively visited our psychiatric unit. They received active tDCS (five consecutive days, 2mA, anodal stimulation over the left and cathodal over the right dorsolateral prefrontal cortex, twice a day, 20minutes). The outcome variable (mood) was evaluated using the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS). Predictor variables were age, gender, disorder and pharmacological treatment (seven dummy variables). We performed univariate and multivariate analyses as to identify predictors associated to the outcome. RESULTS: After 5 days of treatment, BDI and HDRS scores decreased significantly (29%±36%, 18%±9%, respectively, P<0.01 for both). Benzodiazepine use was independently associated with a worse outcome in both univariate (ß=4.92, P<0.01) and multivariate (ß=5.8, P<0.01) analyses; whereas use of dual-reuptake inhibitors positively changed tDCS effects in the multivariate model (ß=-4.7, P=0.02). A similar trend was observed for tricyclics (ß=-4, P=0.06) but not for antipsychotics, non-benzodiazepine anticonvulsants and other drugs. CONCLUSION: tDCS over the DLPFC acutely improved depressive symptoms. Besides the inherent limitations of our naturalistic design, our results suggest that tDCS effects might vary according to prior pharmacological treatment, notably benzodiazepines and some antidepressant classes. This issue should be further explored in controlled studies.

Transcranial direct current stimulation (tDCS) in unipolar vs. bipolar depressive disorder.

Transcranial direct current stimulation (tDCS) is a non-invasive method for brain stimulation. Although pilot trials have shown that tDCS yields promising results for major depressive disorder (MDD), its efficacy for bipolar depressive disorder (BDD), a condition with high prevalence and poor treatment outcomes, is unknown. In a previous study we explored the effectiveness of tDCS for MDD. Here, we expanded our research, recruiting patients with MDD and BDD. We enrolled 31 hospitalized patients (24 women) aged 30-70 years 17 with MDD and 14 with BDD (n = 14). All patients received stable drug regimens for at least two weeks before enrollment and drug dosages remained unchanged throughout the study. We applied tDCS over the dorsolateral prefrontal cortex (anodal electrode on the left and cathodal on the right) using a 2 mA-current for 20 min, twice-daily, for 5 consecutive days. Depression was measured at baseline, after 5 tDCS sessions, one week later, and one month after treatment onset. We used the scales of Beck (BDI) and Hamilton-21 items (HDRS). All patients tolerated treatment well without adverse effects. After the fifth tDCS session, depressive symptoms in both study groups diminished, and the beneficial effect persisted at one week and one month. In conclusion, our preliminary study suggests that tDCS is a promising treatment for patients with MDD and BDD.2.

Non-invasive brain stimulation for the management of arterial hypertension.

The neural control of the cardiovascular system is a complex process that involves many structures at different levels of nervous system. Several cortical areas are involved in the control of systemic blood pressure, such as the sensorimotor cortex, the medial prefrontal cortex and the insular cortex. Non-invasive brain stimulation techniques - repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) - induce sustained and prolonged functional changes of the human cerebral cortex. rTMS and tDCS has led to positive results in the treatment of some neurological and psychiatric disorders. Because experiments in animals show that cortical modulation can be an effective method to regulate the cardiovascular system, non-invasive brain stimulation might be a novel tool in the therapeutics of human arterial hypertension. We here review the experimental evidence that non-invasive brain stimulation can influence the autonomic nervous system and discuss the hypothesis that focal modulation of cortical excitability by rTMS or tDCS can influence sympathetic outflow and, eventually, blood pressure, thus providing a novel therapeutic tool for human arterial hypertension.

Temporal cortex direct current stimulation enhances performance on a visual recognition memory task in Alzheimer disease.

Several studies have reported that transcranial direct current stimulation (tDCS), a non-invasive method of neuromodulation, enhances some aspects of working memory in healthy and Parkinson disease subjects. The aim of this study was to investigate the impact of anodal tDCS on recognition memory, working memory and selective attention in Alzheimer disease (AD). Ten patients with diagnosis of AD received three sessions of anodal tDCS (left dorsolateral prefrontal cortex, left temporal cortex and sham stimulation) with an intensity of 2 mA for 30 min. Sessions were performed in different days in a randomised order. The following tests were assessed during stimulation: Stroop, Digit Span and a Visual Recognition Memory task (VRM). The results showed a significant effect of stimulation condition on VRM (p = 0.0085), and post hoc analysis showed an improvement after temporal (p = 0.01) and prefrontal (p = 0.01) tDCS as compared with sham stimulation. There were no significant changes in attention as indexed by Stroop task performance. As far as is known, this is the first trial showing that tDCS can enhance a component of recognition memory. The potential mechanisms of action and the implications of these results are discussed.

Modulatory effects of anodal transcranial direct current stimulation on perception and pain thresholds in healthy volunteers.

BACKGROUND AND PURPOSE: We aimed to evaluate whether transcranial direct current stimulation (tDCS) is effective in modulating sensory and pain perception thresholds in healthy subjects as to further explore mechanisms of tDCS in pain relief. METHODS: Twenty healthy subjects received stimulation with tDCS under four different conditions of stimulation: anodal tDCS of the primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), occipital cortex (V1), and sham tDCS. The order of conditions was randomized and counterbalanced across subjects. Perception threshold and pain threshold to peripheral electrical stimulation of the right index finger were evaluated by a blinded rater. RESULTS: The results showed a significant effect of the interaction time versus stimulation condition for perception (P = 0.046) and pain threshold (P = 0.015). Post hoc comparisons revealed that anodal stimulation of M1 increased both perception (P < 0.001, threshold increase of 6.5%) and pain (P = 0.001, threshold increase of 8.3%) thresholds significantly, whilst stimulation of the DLPFC increased pain threshold only (P = 0.046, threshold increase of 10.0%). There were no significant effects for occipital or sham stimulation. CONCLUSIONS: These results show that both M1 and DLFPC anodal tDCS can be used to modulate pain thresholds in healthy subjects; thus, the mechanism of tDCS in modulating pain involves pathways that are independent of abnormal pain-related neural activity.

Transient tinnitus suppression induced by repetitive transcranial magnetic stimulation and transcranial direct current stimulation.

Modulation of activity in the left temporoparietal area (LTA) by 10 Hz repetitive transcranial magnetic stimulation (rTMS) results in a transient reduction of tinnitus. We aimed to replicate these results and test whether transcranial direct current stimulation (tDCS) of LTA could yield similar effect. Patients with tinnitus underwent six different types of stimulation in a random order: 10-Hz rTMS of LTA, 10-Hz rTMS of mesial parietal cortex, sham rTMS, anodal tDCS of LTA, cathodal tDCS of LTA and sham tDCS. A non-parametric analysis of variance showed a significant main effect of type of stimulation (P = 0.002) and post hoc tests showed that 10-Hz rTMS and anodal tDCS of LTA resulted in a significant reduction of tinnitus. These effects were short lasting. These results replicate the findings of the previous study and, in addition, show preliminary evidence that anodal tDCS of LTA induces a similar transient tinnitus reduction as high-frequency rTMS.

A sham stimulation-controlled trial of rTMS of the unaffected hemisphere in stroke patients.

The authors investigated the use of slow-frequency repetitive transcranial magnetic stimulation (rTMS) to the unaffected hemisphere to decrease interhemispheric inhibition of the lesioned hemisphere and improve motor function in patients within 12 months of a stroke. Patients showed a significant decrease in simple and choice reaction time and improved performance of the Purdue Pegboard test with their affected hand after rTMS of the motor cortex in the intact hemisphere as compared with sham rTMS.