Transcranial direct current stimulation combined with alcohol cue inhibitory control training reduces the risk of early alcohol relapse: A randomized placebo-controlled clinical trial

BackgroundApproximately half of all people with alcohol use disorder (AUD) relapse into alcohol reuse in the next few weeks after a withdrawal treatment. Brain stimulation and cognitive training represent recent forms of complementary interventions in the context of AUD.ObjectiveTo evaluate the clinical efficacy of five sessions of 2 mA bilateral transcranial direct current stimulation (tDCS) for 20 min over the dorsolateral prefrontal cortex (DLPFC) (left cathodal/right anodal) combined with alcohol cue inhibitory control training (ICT) as part of rehabilitation. The secondary outcomes were executive functioning (e.g. response inhibition) and craving intensity, two mechanisms strongly related to abstinence.MethodsA randomized clinical trial with patients (n = 125) with severe AUD at a withdrawal treatment unit. Each patient was randomly assigned to one of four conditions, in a 2 [verum vs. sham tDCS] x 2 [alcohol cue vs. neutral ICT] factorial design. The main outcome of treatment was the abstinence rate after two weeks or more (up to one year).ResultsVerum tDCS improved the abstinence rate at the 2-week follow-up compared to the sham condition, independently of the training condition (79.7% [95% CI = 69.8–89.6] vs. 60.7% [95% CI = 48.3–73.1]; p = .02). A priori contrasts analyses revealed higher abstinence rates for the verum tDCS associated with alcohol cue ICT (86.1% [31/36; 95% CI = 74.6–97.6]) than for the other three conditions (64% [57/89; 95% CI = 54–74]). These positive clinical effects on abstinence did not persist beyond two weeks after the intervention. Neither the reduction of craving nor the improvement in executive control resulted specifically from prefrontal-tDCS and ICT.ConclusionsAUD patients who received tDCS applied to DLPFC showed a significantly higher abstinence rate during the weeks following rehabilitation. When combined with alcohol specific ICT, brain stimulation may provide better clinical outcomes.Trial RegistrationClinicalTrials.gov number NCT03447054 https://clinicaltrials.gov/ct2/show/NCT03447054.     

Transcranial direct current stimulation of prefrontal cortex: An auditory event-related potential study in schizophrenia

Cognitive impairment is one of the most significant factors determining the long-term rehabilitation prospects of schizophrenia patients. Cognitive training has been shown to be beneficial; however, effect sizes of cognitive remediation remain relatively low. Anodal transcranial direct current stimulation (tDCS) increases cortical excitability along with larger N1 auditory event-related potentials (ERPs), thus providing a non-invasive physiological mechanism that is potentially capable of facilitating cognitive training of schizophrenia patients. The current study investigated the effects of left-prefrontal anodal tDCS on auditory discrimination performance and N1, Mismatch Negativity (MMN), and P3b ERPs, which have been linked to cognitive and global function deficits in schizophrenia. We compared 20 min of 2 mA tDCS versus sham stimulation in 14 schizophrenia patients by employing a randomised crossover design. Patients performed equally well in a go/no-go auditory discrimination task when compared to healthy subjects but presented with significantly smaller N1, MMN and P3b amplitudes, which did not change with tDCS. Auditory discrimination performance and reaction times also remained unaffected by tDCS. Our findings suggest that a single application of tDCS has no acute effects on ERPs and associated auditory information processing in schizophrenia patients.     

Transcranial direct current stimulation facilitates category learning

BackgroundAfter two decades of transcranial direct current stimulation (tDCS) research, it is still unclear which applications benefit most from which tDCS protocols. One prospect is the acceleration of learning, where previous work has demonstrated that anodal tDCS applied to the right ventrolateral prefrontal cortex (rVLPFC) is capable of doubling the rate of learning in a visual camouflaged threat detection and category learning task.GoalsQuestions remain as to the specific cognitive mechanisms underlying this learning enhancement, and whether it generalizes to other tasks. The goal of the current project was to expand previous findings by employing a novel category learning task.MethodsParticipants learned to classify pictures of European streets within a discovery learning paradigm. In a double-blind design, 54 participants were randomly assigned to 30 min of tDCS using either 2.0 mA anodal (n = 18), cathodal (n = 18), or 0.1 mA sham (n = 18) tDCS over the rVLPFC.ResultsA linear mixed-model revealed a significant effect of tDCS condition on classification accuracy across training (p = 0.001). Compared to a 4.2% increase in sham participants, anodal tDCS over F10 increased performance by 20.6% (d = 1.71) and cathodal tDCS by 14.4% (d = 1.16).ConclusionsThese results provide further evidence for the capacity of tDCS applied to rVLPFC to enhance learning, showing a greater than quadrupling of test performance after training (491% of sham) in a difficult category learning task. Combined with our previous studies, these results suggest a generalized performance enhancement. Other tasks requiring sustained attention, insight and/or category learning may also benefit from this protocol.     

Meta-analysis of the effects of transcranial direct current stimulation on inhibitory control

BackgroundInhibitory control refers to a central cognitive capacity involved in the interruption and correction of actions. Dysfunctions in these cognitive control processes have been identified as major maintaining mechanisms in a range of mental disorders such as ADHD, binge eating disorder, obesity, and addiction. Improving inhibitory control by transcranial direct current stimulation (tDCS) could ameliorate symptoms in a broad range of mental disorders.ObjectiveThe primary aim of this pre-registered meta-analysis was to investigate whether inhibitory control can be improved by tDCS in healthy and clinical samples. Additionally, several moderator variables were investigated.MethodsA comprehensive literature search was performed on PubMed/MEDLINE database, Web of Science, and Scopus. To achieve a homogenous sample, only studies that assessed inhibitory control in the go-/no-go (GNG) or stop-signal task (SST) were included, yielding a total of 75 effect sizes from 45 studies.ResultsResults of the meta-analysis indicate a small but significant overall effect of tDCS on inhibitory control (g = 0.21) which was moderated by target and return electrode placement as well as by the task. The small effect size was further reduced after correction for publication bias.ConclusionBased on the studies included, our meta-analytic approach substantiates previously observed differences between brain regions, i.e., involvement of the right inferior frontal gyrus (rIFG) vs. the right dorsolateral prefrontal cortex (rDLPFC) in inhibitory control. Results indicate a small moderating effect of tDCS on inhibitory control in single-session studies and highlight the relevance of technical and behavioral parameters.     

Treatment of depression with transcranial direct current stimulation (tDCS): A Review

Major Depression Disorder (MDD) is usually accompanied by alterations of cortical activity and excitability, especially in prefrontal areas. These are reflections of a dysfunction in a distributed cortico-subcortical, bihemispheric network. Therefore it is reasonable to hypothesize that altering this pathological state with techniques of brain stimulation may offer a therapeutic target. Besides repetitive transcranial magnetic stimulation, tonic stimulation with weak direct currents (tDCS) modulates cortical excitability for hours after the end of stimulation, thus, it is a promising non-invasive therapeutic option. Early studies from the 1960s suggested some efficacy of DC stimulation to reduce symptoms in depression, but mixed results and development of psychotropic drugs resulted in an early abandonment of this technique. In the last years tDCS protocols have been optimized. Application of the newly developed stimulation protocols in patients with major depression has shown promise in few pilot studies. Further studies are needed to identify the optimal parameters of stimulation and the clinical and patient characteristics that may condition response to tDCS.     

Transcranial direct current stimulation and the visual cortex

Neuroplastic changes are defined as enduring changes in the organization of the central nervous system, such as the strength of connections, representational patterns, or neuronal properties, either morphological or functional. In recent years, new tools have emerged to induce and manipulate ongoing neuroplastic changes by external stimulation, either by modification of synchronized neuronal activity or modulation of the spontaneous firing rate. The first is performed by transcranial magnetic stimulation (TMS), the latter by direct current stimulation (tDCS). tDCS as a tool aims to induce prolonged neuronal excitability and activity alterations in the human brain via alterations of the neuronal membrane potential and results in prolonged synaptic efficacy changes. Apart from its impressive persistent excitability effects, it is a non-invasive method and can be applied painlessly. Most likely that up- or downregulation of different cortical areas by tDCS will open a new branch in the area of visual psychophysics.     

Transcranial direct current stimulation disrupts tactile perception

The excitability of the cerebral cortex can be modulated by various transcranial stimulation techniques. Transcranial direct current stimulation (tDCS) offers the advantage of portable equipment and could, therefore, be used for ambulatory modulation of brain excitability. However, modulation of cortical excitability by tDCS has so far mostly been shown by indirect measures. Therefore, we examined whether tDCS has a direct behavioral/perceptional effect. We compared tactile discrimination of vibratory stimuli to the left ring finger prior to, during and after tDCS applied for 7 min at 1-mA current intensity in 13 subjects. Stimulation was pseudorandomized into cathodal, anodal and sham conditions in a within-subject design. The active electrode was placed over the corresponding somatosensory cortex at C4 according to the 10-20 EEG system and the reference electrode at the forehead above the contralateral orbita. Cathodal stimulation compared with sham induced a prolonged decrease of tactile discrimination, while anodal and sham stimulation did not. Thus, cortical processing can be modulated in a behaviorally/perceptually meaningful way by weak transcranial current stimulation applied through portable technology. This finding offers a new perspective for the treatment of conditions characterized by alterations of cortical excitability.     

Transcranial direct current stimulation for the treatment of focal hand dystonia

The treatment of writer's cramp, a task‐specific focal hand dystonia, needs new approaches. A deficiency of inhibition in the motor cortex might cause writer's cramp. Transcranial direct current stimulation modulates cortical excitability and may provide a therapeutic alternative. In this randomized, double‐blind, sham‐controlled study, we investigated the efficacy of cathodal stimulation of the contralateral motor cortex in 3 sessions in 1 week. Assessment over a 2‐week period included clinical scales, subjective ratings, kinematic handwriting analysis, and neurophysiological evaluation. Twelve patients with unilateral dystonic writer's cramp were investigated; 6 received transcranial direct current and 6 sham stimulation. Cathodal transcranial direct current stimulation had no favorable effects on clinical scales and failed to restore normal handwriting kinematics and cortical inhibition. Subjective worsening remained unexplained, leading to premature study termination. Repeated sessions of cathodal transcranial direct current stimulation of the motor cortex yielded no favorable results supporting a therapeutic potential in writer's cramp. © 2011 Movement Disorder Society     

Transcranial direct current stimulation and cognitive training in the rehabilitation of Alzheimer disease: A case study

In the present study we tested the cognitive effects of transcranial direct current stimulation (tDCS) in a case of probable Alzheimer disease (AD). The patient (male, 60?years, mild AD) underwent two cycles of treatments, separated by 2?months. In the first cycle, active stimulation (10 sessions, 2?mA for 20?min; anode over the left dorsolateral prefrontal cortex) was followed by computerised tasks (CTs) specifically chosen to engage the most impaired cognitive processes in the patient (tDCS+CT condition). In the second cycle, which was structured as the first, CTs were administered after placebo stimulation (sham+CT condition). Effects on cognitive performance were evaluated not only by the CTs, but also by neuropsychological tests assessing global cognitive functioning. Statistical analyses revealed that whereas the tDCS+CT condition had few effects on the CTs, it induced a stability of the patient's global cognitive functioning lasting approximately 3?months, which was not achieved when the patient underwent sham+CT condition. Therefore, the synergetic use of tDCS and CTs appeared to slow down the cognitive decline of our patient. This preliminary result, although in need of further confirmation, suggests the potentiality of tDCS as an adjuvant tool for cognitive rehabilitation in AD.     

Enhancing cognitive control training with transcranial direct current stimulation: a systematic parameter study

BackgroundCognitive control (CC) is an important prerequisite for goal-directed behaviour and efficient information processing. Impaired CC is associated with reduced prefrontal cortex activity and various mental disorders, but may be effectively tackled by transcranial direct current stimulation (tDCS)-enhanced training. However, study data are inconsistent as efficacy depends on stimulation parameters whose implementations vary widely between studies.ObjectiveWe systematically tested various tDCS parameter effects (anodal/cathodal polarity, 1/2 mA stimulation intensity, left/right prefrontal cortex hemisphere) on a six-session CC training combined with tDCS.MethodsNine groups of healthy humans (male/female) received either anodal/cathodal tDCS of 1/2 mA over the left/right PFC or sham stimulation, simultaneously with a CC training (modified adaptive Paced Auditory Serial Addition Task [PASAT]). Subjects trained thrice per week (19 min each) for two weeks. We assessed performance progress in the PASAT before, during, and after training. Using a hierarchical approach, we incrementally narrowed down on optimal stimulation parameters supporting CC. Long-term CC effects as well as transfer effects in a flanker task were assessed after the training period as well as three months later.ResultsCompared to sham stimulation, anodal but not cathodal tDCS improved performance gains. This was only valid for 1 mA stimulation intensity and particularly detected when applied to the left PFC.ConclusionsOur results confirm beneficial, non-linear effects of anodal tDCS on cognitive training in a large sample of healthy subjects. The data consolidate the basis for further development of functionally targeted tDCS, supporting cognitive control training in mental disorders and guiding further development of clinical interventions.     

Transcranial direct current stimulation (tDCS) for depression in pregnancy: A pilot randomized controlled trial

BackgroundDepression in pregnancy negatively affects maternal-child health. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation treatment for depression, has not been evaluated in pregnancy.ObjectiveTo conduct a pilot randomized controlled trial (RCT) to evaluate tDCS for antenatal depression.MethodsIn this pilot RCT in Toronto, Ontario (October 2014 to December 2016), adult pregnant women 14–32 weeks gestation with major depressive disorder who had declined antidepressant medication were considered for inclusion. Participants were randomly assigned 1:1 to tDCS or sham-control. Active tDCS comprised 30-min sessions of 2 mAmp direct current delivered over the dorsolateral prefrontal cortex, 5 days per week, for 3 weeks. Sham was administered similarly, but with current turned off after 30 s. Main outcomes were feasibility, acceptability, and protocol adherence. Maternal Montgomery Asperg Depression Rating Scale (MADRS) was measured post-treatment and at 4 and 12 weeks postpartum.ResultsOf 20 women randomized, 16 completed treatment and provided data (124 tDCS, 122 sham sessions). Views of treatment were positive with no serious adverse events. Post-treatment estimated marginal mean MADRS scores were 11.8 (standard error, SE 2.66) for tDCS and 15.4 (SE 2.51) for sham (p = 0.34). At 4 weeks postpartum, 75.0% of tDCS women were remitted versus 12.5% sham-control (p = 0.04).ConclusionsResults support proceeding to a definitive RCT to evaluate tDCS for antenatal depression. The preliminary efficacy estimates immediately post-treatment and in the postpartum, are encouraging with respect to the potential use of tDCS to improve treatment rates in this population. The trial was registered at: clinical trials.gov (NCT02116127).     

Transcranial direct current brain stimulation decreases impulsivity in ADHD

Background

Impulsivity is a core deficit in attention deficit hyperactivity disorder (ADHD). Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) has been shown to modulate cognitive control circuits and could enhance DLPFC activity, leading to improved impulse control in ADHD.

Transcranial direct current stimulation (tDCS) in the treatment of depression: Systematic review and meta-analysis of efficacy and tolerability

BackgroundTranscranial direct current stimulation (tDCS) is a potential alternative treatment option for major depressive episodes (MDE).ObjectivesWe address the efficacy and safety of tDCS in MDE.MethodsThe outcome measures were Hedges’ g for continuous depression ratings, and categorical response and remission rates.ResultsA random effects model indicated that tDCS was superior to sham tDCS (k = 11, N = 393, g = 0.30, 95% CI = [0.04, 0.57], p = 0.027). Adjunctive antidepressant medication and cognitive control training negatively impacted on the treatment effect. The pooled log odds ratios (LOR) for response and remission were positive, but statistically non-significant (response: k = 9, LOR = 0.36, 95% CI[−0.16, 0.88], p = 0.176, remission: k = 9, LOR = 0.25, 95% CI [−0.42, 0.91], p = 0.468). We estimated that for a study to detect the pooled continuous effect (g = 0.30) at 80% power (alpha = 0.05), a total N of at least 346 would be required (with the total N required to detect the upper and lower bound being 49 and 12,693, respectively).ConclusionstDCS may be efficacious for treatment of MDE. The data do not support the use of tDCS in treatment-resistant depression, or as an add-on augmentation treatment. Larger studies over longer treatment periods are needed.     

Testing assumptions on prefrontal transcranial direct current stimulation: Comparison of electrode montages using multimodal fMRI

Background

Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) has been widely applied in cognitive neurosciences and advocated as a therapeutic intervention, e.g. in major depressive disorder. Although several targets and protocols have been suggested, comparative studies of tDCS parameters, particularly electrode montages and their cortical targets, are still lacking.

Transcranial direct current stimulation for the treatment of post-stroke depression in aphasic patients: a case series

ABSTRACT

Aphasia is a common consequence of stroke; it is estimated that about two-thirds of aphasic patients will develop depression in the first year after the stroke. Treatment of post-stroke depression (PSD) is challenging due to the adverse effects of pharmacotherapy and difficulties in evaluating clinical outcomes, including aphasia. Transcranial direct current stimulation (tDCS) is a novel treatment that may improve clinical outcomes in the traditionally pharmacotherapy-refractory PSD. Our aim was to evaluate the safety and efficacy of tDCS for patients with PSD and with aphasia. The Stroke Aphasic Depression Questionnaire (SADQ) and the Aphasic Depression Rating Scale (ADRS) were used to evaluate the severity of PSD. The diagnoses of PSD and aphasia were confirmed by a psychiatrist and a speech-language pathologist, respectively. In this open case series, patients (n = 4) received 10 sessions (once a day) of bilateral tDCS to the dorsolateral prefrontal cortex (DLPFC) and two additional sessions after two and four weeks, for a total of 12 sessions. All patients exhibited improvement in depression after tDCS, as indicated by a decrease in SADQ (47.5%) and in ADRS (65.7%). This improvement was maintained four weeks after the treatment. In this preliminary, open-label study conducted in four PSD patients with aphasia, bilateral tDCS over the DLPFC was shown to induce a substantial mood improvement; tDCS was safe and well tolerated by every patient. Stroke patients with aphasia can be safely treated for PSD with tDCS. Sham-controlled studies are necessary to evaluate this technique further.     

Effects of repeated anodal transcranial direct current stimulation on auditory fear extinction in C57BL/6J mice

BackgroundTrauma-based psychotherapy is a first line treatment for post-traumatic stress disorder (PTSD) but not all patients achieve long-term remission. Transcranial direct current stimulation (tDCS) received considerable attention as a neuromodulation method that may improve trauma-based psychotherapy.ObjectiveWe explored the effects of repeated anodal tDCS over the prefrontal cortex (PFC) on fear extinction in mice as a preclinical model for trauma-based psychotherapy.MethodsWe performed auditory fear conditioning with moderate or high shock intensity on C57BL6/J mice. Next, mice received anodal tDCS (0.2 mA, 20 min) or sham stimulation over the PFC twice daily for five consecutive days. Extinction training was performed by repeatedly exposing mice to the auditory cue the day after the last stimulation session. Early and late retention of extinction were evaluated one day and three weeks after extinction training respectively.ResultsWe observed no significant effect of tDCS on the acquisition or retention of fear extinction in mice subjected to fear conditioning with moderate intensity. However, when the intensity of fear conditioning was high, tDCS significantly lowered freezing during the acquisition of extinction, regardless of the extinction protocol. Moreover, when tDCS was combined with a strong extinction protocol, we also observed a significant improvement of early extinction recall. Finally, we found that tDCS reduced generalized fear induced by contextual cues when the intensity of conditioning is high and extinction training limited.ConclusionsOur data provide a rationale to further explore anodal tDCS over the PFC as potential support for trauma-based psychotherapy for PTSD.     

Noninvasive remote activation of the ventral midbrain by transcranial direct current stimulation of prefrontal cortex

The midbrain lies deep within the brain and has an important role in reward, motivation, movement and the pathophysiology of various neuropsychiatric disorders such as Parkinson''s disease, schizophrenia, depression and addiction. To date, the primary means of acting on this region has been with pharmacological interventions or implanted electrodes. Here we introduce a new noninvasive brain stimulation technique that exploits the highly interconnected nature of the midbrain and prefrontal cortex to stimulate deep brain regions. Using transcranial direct current stimulation (tDCS) of the prefrontal cortex, we were able to remotely activate the interconnected midbrain and cause increases in participants'' appraisals of facial attractiveness. Participants with more enhanced prefrontal/midbrain connectivity following stimulation exhibited greater increases in attractiveness ratings. These results illustrate that noninvasive direct stimulation of prefrontal cortex can induce neural activity in the distally connected midbrain, which directly effects behavior. Furthermore, these results suggest that this tDCS protocol could provide a promising approach to modulate midbrain functions that are disrupted in neuropsychiatric disorders.     

Effects of transcranial direct current stimulation on working memory in patients with Parkinson's disease

OBJECTIVES: Cognitive impairment is a common feature in Parkinson's disease (PD) and is an important predictor of quality of life. Past studies showed that some aspects of cognition, such as working memory, can be enhanced following dopaminergic therapy and transcranial magnetic stimulation. The aim of our study was to investigate whether another form of noninvasive brain stimulation, anodal transcranial direct current stimulation (tDCS), which increases cortical excitability, is associated with a change in a working memory task performance in PD patients. METHODS: We studied 18 patients (12 men and 6 women) with idiopathic PD. The patients performed a three-back working memory task during active anodal tDCS of the left dorsolateral prefrontal cortex (LDLPFC), anodal tDCS of the primary motor cortex (M1) or sham tDCS. In addition, patients underwent two different types of stimulation with different intensities: 1 and 2 mA. RESULTS: The results of this study show a significant improvement in working memory as indexed by task accuracy, after active anodal tDCS of the LDLPFC with 2 mA. The other conditions of stimulation: sham tDCS, anodal tDCS of LDLPFC with 1 mA or anodal tDCS of M1 did not result in a significant task performance change. CONCLUSION: tDCS may exert a beneficial effect on working memory in PD patients that depends on the intensity and site of stimulation. This effect might be explained by the local increase in the excitability of the dorsolateral prefrontal cortex.