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.     

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 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.     

Transcranial direct current stimulation: A novel approach in the treatment of vascular depression

BackgroundDespite the impact of depression in terms of personal suffering and socioeconomic burden, most currently available treatment options are often ineffective. A particularly difficult-to-treat depressive disorder characteristic of the elderly is vascular depression, a late-life depressive syndrome related to a variety of potential vascular mechanisms. Transcranial Direct Current Stimulation (tDCS), a non-invasive and effective somatic approach to depression, also showed positive effects on cognitive deficits.AimWe performed a double-blind randomized study to investigate the efficacy of tDCS as augmentation strategy to sertraline in the treatment of vascular depression, hypothesizing a positive effect in both depressive symptoms and cognitive functions.MethodsWe enrolled 93 inpatients over 60 years of age with a diagnosis of vascular depression. Depressive symptoms were weekly assessed (T0, T1, T2) with the 21-items Hamilton depression rating scale (HDRS). Cognitive functioning was evaluated with the Milan Overall Dementia Assessment (MODA) at baseline and after the treatment protocol. All patients were randomly assigned into three groups, Group I: one tDCS stimulation per day, Group II: two tDCS stimulations per day, Sham group: one sham tDCS stimulation per day. Stimulation was performed for 10 consecutive working days.ResultsA significant interaction time1treatment was observed on HDRS scores (F = 14, p < 0.001). All groups improved at T1 but whereas Group II significantly differed from the Sham group (p < 0.001) we observed no difference between Sham and Group I. At T2 all groups improved but Group II showed the greater improvement (vs. Sham p < 0.001; vs. Group I p < 0.001) and the Sham group the smallest (vs. Group I p = 0.005). A significant interaction time1treatment was also observed on MODA scores (F = 3.31, p = 0.04). Only subjects treated with tDCS improved at T2 (Group I: p < 0.001; Group II: p = 0.007). However, no difference between Group I and II was shown.ConclusiontDCS as augmentation treatment of an adequate pharmacotherapy is a potential strategy in the management of vascular depression, a disease known to be often unresponsive to antidepressants only. Non-invasiveness, the absence of severe side effects and the possibility of administering it to outpatients at an affordable price make tDCS an important tool in clinical practice.     

Supervised transcranial direct current stimulation (tDCS) at home: A guide for clinical research and practice

BackgroundTranscranial direct current stimulation (tDCS) is a method of noninvasive neuromodulation and potential therapeutic tool to improve functioning and relieve symptoms across a range of central and peripheral nervous system conditions. Evidence suggests that the effects of tDCS are cumulative with consecutive daily applications needed to achieve clinically meaningful effects. Therefore, there is growing interest in delivering tDCS away from the clinic or research facility, usually at home.ObjectiveTo provide a comprehensive guide to operationalize safe and responsible use of tDCS in home settings for both investigative and clinical use.MethodsProviding treatment at home can improve access and compliance by decreasing the burden of time and travel for patients and their caregivers, as well as to reach those in remote locations and/or living with more advanced disabilities.ResultsTo date, methodological approaches for at-home tDCS delivery have varied. After implementing the first basic guidelines for at-home tDCS in clinical trials, this work describes a comprehensive guide for facilitating safe and responsible use of tDCS in home settings enabling access for repeated administration over time.ConclusionThese guidelines provide a reference and standard for practice when employing the use of tDCS outside of the clinic setting.     

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.     

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.     

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 stimulation for the treatment of major depressive disorder: a summary of preclinical, clinical and translational findings

Major depressive disorder (MDD) is a common psychiatric illness, with 6-12% lifetime prevalence. It is also among the five most disabling diseases worldwide. Current pharmacological treatments, although relatively effective, present important side effects that lead to treatment discontinuation. Therefore, novel treatment options for MDD are needed. Here, we discuss the recent advancements of one new neuromodulatory technique--transcranial direct current stimulation (tDCS)--that has undergone intensive research over the past decade with promising results. tDCS is based on the application of weak, direct electric current over the scalp, leading to cortical hypo- or hyper-polarization according to the specified parameters. Recent studies have shown that tDCS is able to induce potent changes in cortical excitability as well as to elicit long-lasting changes in brain activity. Moreover, tDCS is a technique with a low rate of reported side effects, relatively easy to apply and less expensive than other neuromodulatory techniques--appealing characteristics for clinical use. In the past years, 4 of 6 phase II clinical trials and one recent meta-analysis have shown positive results in ameliorating depression symptoms. tDCS has some interesting, unique aspects such as noninvasiveness and low rate of adverse effects, being a putative substitutive/augmentative agent for antidepressant drugs, and low-cost and portability, making it suitable for use in clinical practice. Still, further phase II and phase III trials are needed as to better clarify tDCS role in the therapeutic arsenal of MDD.     

Transcranial direct current stimulation associated with physical-therapy in acute stroke patients - A randomized,triple blind,sham-controlled study

BackgroundTranscranial Direct Current Stimulation has been increasing in popularity in the last few years. Despite vast amounts of articles on the use of tDCS on stroke patients, very little has been done during the acute phase.ObjectivesMeasure the effects of tDCS on functional and sensory outcomes throughout the first year post onset of stroke.Methods50 acute stroke patients were randomized and placed into either the treatment or sham group. Anodal tDCS was applied (2 mA, 20 min) 5 times a week during the first month post stroke. Patients were evaluated with the Wolf Motor Function Test, the Semmes Weinstein Monofilament Test, the Upper Extremity section (UEFM), the Lower Extremity section (LEFM) and the Somatosensory section of the Fugl Meyer Test, the Tardieu Spasticity Scale, the Stroke Impact Scale (SIS), the Hospital Anxiety and Depression Scale (HADS) and the Barthel Index. Evaluations were held at 48 h post stroke, week 1, 2, 3, 4, 3 months, 6 months and 1 year.ResultsThere were statistically and clinically significant improvements after tDCS in all functional motor outcomes, and somatosensory functions. Differences between both groups for the main outcome (WMFT time) were 51% (p = 0.04) at one month, and 57% (p = 0.02) at one year.ConclusiontDCS seems to be an effective adjuvant to conventional rehabilitation techniques. If applied in the acute stages of stroke, functional recovery is not only accelerated, but improved, and results are maintained up to one-year post stroke.     

Transcranial direct current stimulation reduces seizure frequency in patients with refractory focal epilepsy: A randomized,double-blind,sham-controlled,and three-arm parallel multicenter study

BackgroundTranscranial direct current stimulation (tDCS) has been explored in epilepsy with limited samples, varied parameters, and inconclusive results. We aimed to study the efficacy of tDCS for patients with refractory focal epilepsy.MethodWe conducted a randomized, double-blind, sham-controlled, and three-arm (Group 1 (sham), Group 2 (20-min), and Group 3 (2 × 20-min)) tDCS parallel multicenter study. The primary outcome measurement was seizure frequencies (SFs). The study consisted of 28-days baseline, 14-days treatment, and 56-days follow-up. The cathode was placed over the epileptogenic focus, and the current intensity was 2 mA. The generalized estimating equations model, one-way analysis of variance, chi-square and Kruskal-Wallis test were used for analysis.ResultsOf the 82 enrolled patients, 70 patients were included for final analysis (Group 1, n = 21; Group 2, n = 24; and Group 3, n = 25). There was a significant reduction in SFs for both active tDCS groups compared with the sham group. Patients in Group 2 showed a significantly 50.73–21.91% greater reduction in SFs that lasted for 4 weeks (p = 0.008–0.060). Patients in Group 3 showed a significantly 63.19–49.79% greater reduction in SFs compared with the sham group that lasted for 5 weeks (p = 0.011–0.045). Patients in Group 3 had a 64.98–66.32% greater reduction in SFs at W9–W10, when compared with Group 2 (p = 0.021–0.022).ConclusionFourteen consecutive days tDCS significantly decreased SFs in patients with refractory focal epilepsy, with 2 × 20-min daily stimulation protocol being superior to 20-min daily stimulation protocol.     

Repetitive transcranial magnetic stimulation (rTMS) versus transcranial direct current stimulation (tDCS) in the management of patients with fibromyalgia: A randomized controlled trial

ObjectivesThe aim of this study was to compare the effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on pain and quality of life in patients with fibromyalgia.MethodsThirty participants were randomized into two groups of 15 patients, to receive 3 sessions of either high-frequency (10 Hz) rTMS or 2 mA, 20 min anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex (DLPFC) over 1 week. Pain was assessed using a Visual Analog Scale (VAS) before treatment, immediately after treatment, 6 and 12 weeks later. Quality of life was evaluated using the Revised Fibromyalgia Impact Questionnaire (FIQR) and psychiatric symptoms were measured using the Depression Anxiety Stress Scale-21 Item (DASS-21) before treatment, and 6 and 12 weeks after treatment.ResultsFor the VAS there was a significant time-group interaction, showing that the behavior of two groups differed regarding changes of VAS in favor of the RTMS group (df = 1.73, F = 4.80, p = <0.016). Time-group interaction effect on DASS-21 and FIQR was not significant. 66.6% of patients in rTMS group and 26.6% of patients in tDCS group experienced at least a 30% reduction of VAS from baseline to last follow-up (p = 0.028).DiscussionWith the methodology used in this study, both rTMS and tDCS were safe modalities and three sessions of rTMS over DLPFC had greater and longer lasting analgesic effects compared to tDCS in patients with FM. However, considering the limitations of this study, further studies are needed to explore the most effective modality.     

Transcranial direct current stimulation for migraine: a systematic review and meta‐analysis of randomized controlled trials

BackgroundTranscranial direct current stimulation (tDCS) is a promising method for migraine treatment. In this study, we investigated the efficacy and safety of tDCS for migraine by conducting a systematic review and meta‐analysis of randomized controlled trials (RCTs).MethodsWe searched PubMed, EMBASE, Cochrane Library, and Web of Science up to December 02, 2021 for RCTs reporting tDCS for migraine treatment. Two authors independently evaluated the eligibility of the retrieved trials and extracted relevant data. Outcomes for the quantitative synthesis were reduction in migraine days per month and adverse events.ResultsEleven RCTs that included 425 patients with migraine were evaluated in the meta‐analysis. The efficacy and safety of anodal or cathodal stimulation targeting different brain areas, including primary motor cortex (M1), primary sensory cortex (S1), dorsolateral prefrontal cortex (DLPFC), and visual cortex (VC), were assessed in the RCTs enrolled. We found that tDCS with M1 and VC activation could reduce No. of migraine days per month in patients with migraine. Meanwhile, tDCS with VC inhibition could also reduce No. of migraine days per month in patients with migraine. However, there were no differences in the incidence of adverse events between the two groups.ConclusiontDCS activates M1 or activates/inhibits VC which could improve migraine symptoms. tDCS is an effective, preventive, and safe treatment for migraine.