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Functional and structural MRI of prefrontal cortex (PFC) may provide putative biomarkers for predicting the treatment response to transcranial direct current stimulation (tDCS) in depression. A recent MRI study from ELECT-TDCS (Escitalopram versus Electrical Direct-Current Theror Depression Study) showed that depression improvement after tDCS was associated with gray matter volumes of PFC subregions. Based thereon, we investigated whether antidepressant effects of tDCS are similarly associated with baseline resting-state functional connectivity (rsFC). A subgroup of 51 patients underwent baseline rsFC-MRI. All patients of ELECT-TDCS were randomized to three treatment arms for 10 weeks (anodal-left, cathodal-right PFC tDCS plus placebo medication; escitalopram 10 mg/day for 3 weeks and 20 mg/day thereafter plus sham tDCS; and placebo medication plus sham tDCS). RsFC was calculated for various PFC regions and analyzed in relation to the individual antidepressant response. There was no significant association between baseline PFC connectivity of essential structural regions, nor any other PFC regions (after correction for multiple comparisons) and patients’ individual antidepressant response. This study did not reveal an association between antidepressants effects of tDCS and baseline rsFC, unlike the gray matter volume findings. Thus, the antidepressant effects of tDCS may be differentially related to structural and functional MRI measurements.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation intervention investigated for the treatment of depression. Clinical results have been heterogeneous, partly due to the variability of electric field (EF) strength in the brain owing to interindividual differences in head anatomy. Therefore, we investigated whether EF strength was correlated with behavioral changes in 16 depressed patients using simulated electric fields in real patient data from a controlled clinical trial. We hypothesized that EF strength in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), brain regions implicated in depression pathophysiology, would be associated with changes in depression, mood and anxiety scores. SimNIBS were used to simulate individual electric fields based on the MRI structural T1-weighted brain scans of depressed subjects. Linear regression models showed, at the end of the acute treatment phase, that simulated EF strength was inversely associated with negative affect in the bilateral ACC (left: β = − 160.463, CI [− 291.541, − 29.385], p = 0.021; right: β = − 189.194, CI [− 289.479, − 88.910], p = 0.001) and DLPFC (left: β = − 93.210, CI [− 154.960, − 31.461], p = 0.006; right: β = − 82.564, CI [− 142.867, − 22.262], p = 0.011) and with depression scores in the left ACC (β = − 156.91, CI [− 298.51, − 15.30], p = 0.033). No association between positive affect or anxiety scores, and simulated EF strength in the investigated brain regions was found. To conclude, our findings show preliminary evidence that EF strength simulations might be associated with further behavioral changes in depressed patients, unveiling a potential mechanism of action for tDCS. Further studies should investigate whether individualization of EF strength in key brain regions impact clinical response.

Introduction: Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation intervention that has been investigated for several psychiatric disorders, including Obsessive-Compulsive Disorder (OCD). As there are several candidate brain regions for targeting OCD relevant networks, clinical studies using tDCS have considerably varied in terms of the electrode montages used. Computer modeling of electric field currents induced by tDCS can help guiding the research of relevant targets for OCD. In this review, the authors used this tool to investigate targeted brain areas from previous studies of tDCS in OCD. Areas covered: A literature search for articles with the keywords 'tDCS', 'Transcranial Direct Current Stimulation' and 'Obsessive Compulsive Disorder' was conducted to identify relevant publications. For comparing different electrode montages, electric field (EF) models were performed using high-resolution brain scan templates. Authors found 13 studies mostly showing an improvement in OCD symptoms. The electrode montages varied considerably between studies. Nonetheless, two main patterns of EFs could be identified: 'focal montages', with EFs concentrated in the prefrontal cortex, and 'diffuse montages', with widespread EFs over cortical areas. Expert opinion: Electric field simulation can guide future clinical trials in psychiatry, using personalized tDCS montages with distinct electrode positioning according to clusters of symptoms.

Introduction: Prefrontal cortex (PFC) regions are promising targets for therapeutic applications of non-invasive brain stimulation, e.g. transcranial direct current stimulation (tDCS), which has been proposed as a novel intervention for major depressive disorder (MDD) and negative symptoms of schizophrenia (SCZ). However, the effects of tDCS vary inter-individually, and dose–response relationships have not been established. Stimulation parameters are often tested in healthy subjects and transferred to clinical populations. The current study investigates the variability of individual MRI-based electric fields (e-fields) of standard bifrontal tDCS across individual subjects and diagnoses. Method: The study included 74 subjects, i.e. 25 patients with MDD, 24 patients with SCZ, and 25 healthy controls (HC). Individual e-fields of a common tDCS protocol (i.e. 2 mA stimulation intensity, bifrontal anode-F3/cathode-F4 montage) were modeled by two investigators using SimNIBS (2.0.1) based on structural MRI scans. Result: On a whole-brain level, the average e-field strength was significantly reduced in MDD and SCZ compared to HC, but MDD and SCZ did not differ significantly. Regions of interest (ROI) analysis for PFC subregions showed reduced e-fields in Sallet areas 8B and 9 for MDD and SCZ compared to HC, whereas there was again no difference between MDD and SCZ. Within groups, we generally observed high inter-individual variability of e-field intensities at a higher percentile of voxels. Conclusion: MRI-based e-field modeling revealed significant differences in e-field strengths between clinical and non-clinical populations in addition to a general inter-individual variability. These findings support the notion that dose–response relationships for tDCS cannot be simply transferred from healthy to clinical cohorts and need to be individually established for clinical groups. In this respect, MRI-based e-field modeling may serve as a proxy for individualized dosing.

Transcranial direct current stimulation (tDCS) over prefrontal cortex (PFC) regions is currently proposed as therapeutic intervention for major depression and other psychiatric disorders. The in-depth mechanistic understanding of this bipolar and non-focal stimulation technique is still incomplete. In a pilot study, we investigated the effects of bifrontal stimulation on brain metabolite levels and resting state connectivity under the cathode using multiparametric MRI techniques and computational tDCS modeling. Within a double-blind cross-over design, 20 subjects (12 women, 23.7 ± 2 years) were randomized to active tDCS with standard bifrontal montage with the anode over the left dorsolateral prefrontal cortex (DLPFC) and the cathode over the right DLPFC. Magnetic resonance spectroscopy (MRS) was acquired before, during, and after prefrontal tDCS to quantify glutamate (Glu), Glu + glutamine (Glx) and gamma aminobutyric acid (GABA) concentration in these areas. Resting-state functional connectivity MRI (rsfcMRI) was acquired before and after the stimulation. The individual distribution of tDCS induced electric fields (efields) within the MRS voxel was computationally modelled using SimNIBS 2.0. There were no significant changes of Glu, Glx and GABA levels across conditions but marked differences in the course of Glu levels between female and male participants were observed. Further investigation yielded a significantly stronger Glu reduction after active compared to sham stimulation in female participants, but not in male participants. For rsfcMRI neither significant changes nor correlations with MRS data were observed. Exploratory analyses of the effect of efield intensity distribution on Glu changes showed distinct effects in different efield groups. Our findings are limited by the small sample size, but correspond to previously published results of cathodal tDCS. Future studies should address gender and efield intensity as moderators of tDCS induced effects. Electronic supplementary material The online version of this article (10.1007/s00406-020-01177-0) contains supplementary material, which is available to authorized users.

Functional and structural MRI of prefrontal cortex (PFC) may provide putative biomarkers for predicting the treatment response to transcranial direct current stimulation (tDCS) in depression. A recent MRI study from ELECT-TDCS (Escitalopram versus Electrical Direct-Current Theror Depression Study) showed that depression improvement after tDCS was associated with gray matter volumes of PFC subregions. Based thereon, we investigated whether antidepressant effects of tDCS are similarly associated with baseline resting-state functional connectivity (rsFC). A subgroup of 51 patients underwent baseline rsFC-MRI. All patients of ELECT-TDCS were randomized to three treatment arms for 10 weeks (anodal-left, cathodal-right PFC tDCS plus placebo medication; escitalopram 10 mg/day for 3 weeks and 20 mg/day thereafter plus sham tDCS; and placebo medication plus sham tDCS). RsFC was calculated for various PFC regions and analyzed in relation to the individual antidepressant response. There was no significant association between baseline PFC connectivity of essential structural regions, nor any other PFC regions (after correction for multiple comparisons) and patients' individual antidepressant response. This study did not reveal an association between antidepressants effects of tDCS and baseline rsFC, unlike the gray matter volume findings. Thus, the antidepressant effects of tDCS may be differentially related to structural and functional MRI measurements.

Transcranial direct current stimulation (tDCS) has been explored for treatment of several neuropsychiatric disorders. For tDCS use in structural brain lesions there is some evidence from motor stroke rehabilitation and post-stroke depression. Here we report the application of tDCS in a woman previously diagnosed with schizophrenia presenting refractory auditory verbal hallucinations and left prefrontal tissue lesion. Treatment with 20 left fronto-temporal tDCS had no effect on psychiatric symptoms and neuropsychological evaluation. An ex-post electric field simulation and calculation of dorsolateral prefrontal cortex activation showed lower activation in this patient compared to a matched non-lesioned schizophrenia, and healthy control brain.

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Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique used to modulate neural tissue. Neuromodulation apparently improves cognitive functions in several neurologic diseases treatment and sports performance. In this study, we present a comprehensive, integrative review of tDCS for motor rehabilitation and motor learning in healthy individuals, athletes and multiple neurologic and neuropsychiatric conditions. We also report on neuromodulation mechanisms, main applications, current knowledge including areas such as language, embodied cognition, functional and social aspects, and future directions. We present the use and perspectives of new developments in tDCS technology, namely high-definition tDCS (HD-tDCS) which promises to overcome one of the main tDCS limitation (i.e., low focality) and its application for neurological disease, pain relief, and motor learning/rehabilitation. Finally, we provided information regarding the Transcutaneous Spinal Direct Current Stimulation (tsDCS) in clinical applications, Cerebellar tDCS (ctDCS) and its influence on motor learning, and TMS combined with electroencephalography (EEG) as a tool to evaluate tDCS effects on brain function.

Noninvasive brain stimulation (NIBS) has exceedingly become a major area of research in the last decade. Methods such as repetitive transcranial magnetic stimulation (rTMS), or transcranial direct current stimulation (tDCS), have been investigated as new paradigms in treatment in a variety of psychiatric and neurological disorders. In psychiatry, focus has been laid on NIBS treatment for major depression and other affective disorders. Several neurobiological mechanisms may explain the effects of NIBS. They all seem to mediate neuroplasticity which accounts for the long-lasting poststimulation effects of NIBS. Involved pathways consist of neurotransmitters such as dopamine, gamma aminobutyric acid and n-methyl- d -aspartic acid receptors, the brain-derived neurotrophic factor, or coding genes. Studies combining NIBS and electrophysiological or neuroimaging methods contributed to the better understanding of some basic mechanisms that may increase treatment response in the future, with promising results observed considering the functional connectivity of specific brain areas. Still, response to NIBS remains variable, which limits its clinical application to date. There is a great need to further increase the understanding of the underlying neurobiological mechanisms, clinical feasibility, and the efficacy of these techniques.

Introduction The physiological effects of transcranial direct current stimulation (tDCS) in non-motor cortex areas are not well understood. The dorsolateral prefrontal cortex (DLPFC) is a key tDCS target in several psychiatric disorders, and mechanisms of tDCS action are of particular interest. We therefore investigated the effects of tDCS over the DLPFC evaluating GABA, glutamate/glutamine (Glx) and glutamate (Glu) concentrations in healthy subjects. Methods Nineteen healthy subjects (11 women, mean age 23) were randomly assigned to active (20 min, 2 mA, 5 × 7 cm electrodes) and sham tDCS using a double-blind, cross-over design. The anode was positioned over F3 (left DLPFC), the cathode over F4 (right DLPFC). A MRS MEGA-PRESS sequence (TE = 68 ms, TR = 2000 ms) was acquired before, during, and after stimulation. Gannet 3.0 and LcModel were used to quantify GABA, Glx and Glu concentrations. Repeated-measures mixed effects models were conducted comparing pre, during and post measurements of active and sham tDCS. Mistakenly, the right and not the left DLPFC was targeted using MRS, therefore evaluating changes induced by cathodal tDCS in the right DLPFC. Results We found a significant reduction of right DLPFC glutamate concentrations during active stimulation (df = 133; P = .023; effect size d = 0.398) as well as a significant reduction of Glx concentration during active stimulation (df = 133; P = .007; effect size d = 0.477). No changes of GABA concentration in cortical regions in proximity to the cathode was observed during or after anodal tDCS stimulation. Conclusions Despite the methodological mistake on prefrontal data collection, the results are biologically plausible and contribute to unveil cathodal tDCS mechanisms of action over the right DLPFC. Confirming results of other trials by Stagg et al. (2009) [1] and Kim et al. (2014) [2] , cathodal stimulation exerts inhibitory effects on the brain. However, several methodological factors (e.g electrical field strengths and distribution, tDCS parameters and individual differences) may limit conclusive interpretation.

Introduction Transcranial direct current stimulation (tDCS) has been proposed as novel treatment for major depressive disorder (MDD), based on clinical pilot studies as well as randomized controlled monocentric trials. Methods The DepressionDC study investigates efficacy and tolerability of prefrontal tDCS used as an additive therapy to an antidepressant medication (SSRI) as treatment for major depression in a double-blinded, randomized, placebo-controlled multicenter trial [1] . There is a consensus on parameters like electrical current (1–2 mA) and the critical impedance values are known from safety-studies, but the in vivo stability of these technical parameters over the stimulation period has not been investigated yet. For the DepressionDC study a novel system for recording and monitoring of technical data has been established in order to continuously control tDCS quality and allow posthoc analysis of technical data in conjunction with clinical outcome criteria. Here, we present a blind analysis of the technical data of 280 active tDCS sessions from multiple centers in order to monitor tDCS quality at this stage of the study. The descriptive analysis showed high homogeneity and stability of the technical parameters over the time of the tDCS session in 120 active stimulations from a single center, as well as in 160 active stimulations across different study sites. To determine tDCS-affected brain areas we leveraged the freely available Simnibs 2.0.1. software to develop subject-specific head model based on MRI data and calculate electric fields (and current density) induced by tDCS. Calculating the electric field, the peak electric field strength as well as activation graduation by percentiles in every single subject, revealed stable and homogenous activation patterns in all participants. Online recording of technical parameters across centers and individual e-field modelling for defining tDCS dosage at target sites are promising deliverables from the DepressionDC trial for further clinical applications.