Parkinson’s disease (PD) chronic L-Dopa treatment often triggers motor complications, such as L-Dopa-induced dyskinesias (LID). LID are reported to be associated with abnormal glutamatergic activity between the striatum and primary motor cortex (M1), resulting in M1 hyperactivation. Beneficial noninvasive brain stimulation (NIBS) paradigms were reported to normalize glutamatergic activity. The objective of the present study was thus to set up a NIBS paradigm in parkinsonian monkeys to investigate motor behavior under basal conditions and with L-Dopa treatment-inducing dyskinesias.

Motor behavior was investigated in five 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) dyskinetic female Macaca fascicularis monkey models of PD, allowing us to monitor the administration of NIBS and drugs. NIBS used were inhibitory protocols, that is, cathodal transcranial direct current stimulation (c-tDCS) and continuous theta-burst stimulation (cTBS). A procedure of three weeks was developed to progressively acclimate animals to the experimental conditions, equipment and noise of c-tDCS and cTBS before stimulating them with either vehicle or L-Dopa.

One session of c-tDCS with L-Dopa yielded no effect, whereas five sessions briefly reduced LID but decreased the duration of L-Dopa anti-PD effects. cTBS alone improved (decreased) parkinsonian scores as compared to sham stimulation or vehicle alone. Two sessions of cTBS with L-Dopa decreased LID without affecting L-Dopa anti-PD effects.

This is the first study testing c-tDCS and cTBS on the motor behavior of MPTP dyskinetic monkeys. As compared to medicated patients, MPTP monkeys offer the opportunity to evaluate NIBS after-effects in drug-free and LID conditions, which are critical in the search for new PD treatment.

Binge eating disorder (BED) is a common and disabling condition, typically presenting with multiple psychiatric and obesity-related comorbidities. Evidence-based treatments are either resource-intensive (psychotherapies) or have side-effects (medications): these achieve remission in around 50% of cases. Novel treatments are needed.

This randomised sham-controlled trial aimed to assess feasibility, acceptability and preliminary efficacy of at-home, self-administered transcranial direct current stimulation (tDCS) and attention bias modification training (ABMT) in adults with binge eating disorder.

Eighty-two participants with binge eating disorder were randomly allocated to real tDCS with ABMT, sham tDCS with ABMT, ABMT only or waitlist control. Intervention groups received ten sessions of their allocated treatment over 2–3 weeks. tDCS (2 mA, 20 min) was self-administered using a bilateral (anode right/cathode left) montage targeting the dorsolateral prefrontal cortex. Outcomes were assessed at baseline, post-treatment and 6-week follow-up.

Prespecified feasibility criteria (recruitment ≥80 participants and retention rate ≥75%) were exceeded, and treatment completion rates were high (98.7%). All interventions reduced binge eating episodes, eating disorder symptoms and related psychopathology between baseline and follow-up, relative to waitlist control (medium-to-large between-group effect sizes for change scores). Small-to-medium effect sizes for change scores favoured real tDCS with ABMT versus comparators, suggesting the verum intervention produces superior outcomes.

At-home, self-administered tDCS with ABMT is feasible and acceptable, and preliminary data on efficacy are promising. This approach could be a useful and scalable alternative or adjunct to established treatments for binge eating disorder. Confirmatory trials can, and should, be pursued.

The DiSCoVeR trial is a multi-site, double-blind, sham controlled, randomized controlled trial (RCT) investigating the feasibility and efficacy of an innovative, self-applied treatment approach for patients suffering from major depressive disorder (MDD). The treatment approach incorporates non-invasive brain stimulation, i.e. prefrontal transcranial direct current stimulation (tDCS), and a videogame designed to enhance emotional cognitive control. This treatment is aimed to be applied at home and monitored remotely.

In this study we are looking at the first 10 single-site patients and comparing expected in person visits (according to the study protocol) versus actual in person visits as well as looking at the patients initial view of the therapy using the therapy evaluation form (CEQ) submitted after the 5th session.

Before continuing to self-administer the treatment at home patients undergo supervised training, during clinic visits, for up to 5 sessions. At the end of the 5th session, they are asked to fill out a therapy evaluation form (CEQ).

Patients needed on average 2.3 in person training sessions before continuing the intervention remotely. Nine patients completed CEQ. Results show that on average patients thought that this course will be 4.78 (with probability 95% CI 4.74 to 4.82) points successful at raising their level of functioning and thought that their functioning will have increased on average by 37.8% (CI 37.2% to 38.4%) by the end of the study.

Patients needed less than half of planned in person training visits. Most patients felt like they will gain some improvement from this intervention.

No significant relationships.

Obsessive-compulsive disorder (OCD) is a chronic and impairing condition included in the DSM-5 Obsessive-Compulsive Spectrum Disorders. Despite psychopharmacological and psychotherapeutic measures, there are patients who remain refractory to different therapeutic strategies.

The authors aim to present different alternatives in approach, treatment and management of refractory OCD, based on a review of the existing literature.

Analysis of the data about this subject, considering the review articles and the case reports published at current time and highlighting the most essential topics, concerning the latest developments in the area.

Therapeutic options are presented, including transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS) and ablative neurosurgery.

The treatment of OCD represents a great challenge in clinical practice. Despite the advances accomplished by a more extensive knowledge of the disease and a burden of new techniques in the last decades, more treatment strategies are needed, especially for patients with non-response to conventional treatment.

No significant relationships.

To explore and develop effective treatments is crucial for patients with Alzheimer’s dementia (AD). In pathology, the amyloid deposits of AD result in disruption of the balance between long-term potentiation (LTP) and long-term depression (LTD) of neuronal cells and synaptic plasticity. Transcranial direct current stimulation (tDCS) has been proposed to affect long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. Although an increasing number of studies have been concluded a positive therapeutic effect on cognition in AD, tDCS studies to date are limited on exploring the duration of its efficacy. In this pilot study, we investigate the effects of tDCS in AD and verify its extending beneficial effects for 3 months follow-up period after the end of stimulation.

34 AD participants aged 55-90 years (mean age 75.9 (66-86)) were included in a double-blind, randomized, sham-controlled crossover study. All participants were randomly assigned to receive 10 consecutive daily sessions of active tDCS (or sham) and switched groups 3 months later. The anodal electrode was on the left dorsal lateral prefrontal cortex and the cathodal electrode was on the right supraorbital area. In each active session, we applied a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min in the active group. All subjects received a series of neuropsychological assessments including CDR, MMSE, CASI and WCST at baseline and in 2 weeks, 4 weeks, and 12 weeks post-tDCS (or sham) 10 sessions. Chi-square tests, Wilcoxon signed rank tests and Mann-Whitney U tests were used to assess the differences in participant demographic characteristics and to compare the differences of test scores between groups.

The active tDCS group showed significant improvements on CASI total scores from baseline to 2-weeks, 1-month and 3-months after active stimulations, though the improvement declined over time. There are also different presentations in total correct items, conceptual level responses, failure to maintain sets of WCST between active tDCS and sham groups. There is no difference in MMSE, CASI and WCST scores in the sham groups.

These results suggest a long term-beneficial effects of tDCS in AD.

Dementia with Lewy Bodies (DLB), this second most common form of degenerative dementia, presents more functional disability, more potentially fatal complication, more impaired quality of life than Alzheimer’s dementia. There is no FDA-proved medication can slow, stop or improve the progression of cognitive declines in DLB. Identifying effective treatments is a critical issue for DLB. In neuropathology, extracelluar α-syn oligomers interfere with the expression of long-term potentiation, and influence memory and learning. Transcranial direct current stimulation (tDCS) has been proposed to affect long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. So far, only two researches assess the effect of tDCS in DLB. In this pilot study, we investigate the effects of tDCS in DLB.

Using a double-blind, randomized, sham- controlled and crossover trial design, 11 DLB aged 55-90 years (mean age 77.8) were included in the study. DLB diagnostics is according to DSM-5 criteria. The CDR ratings of DLB participants ranged from 0.5 to 2. The active tDCS (or sham) process includes consecutive daily sessions of active tDCS (or sham) for 10 days. The anodal electrode was over the left dorsal lateral prefrontal cortex (DLPFC) and the cathodal electrode on the right supraorbital area. In each session, we applied a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min in the active group. All subjects received a series of neuropsychological tests, which included CDR, MMSE, CASI, NPI and WCST, before and after these treatment sessions. Chi-square tests, Wilcoxon signed rank tests and Mann-Whitney U tests were used to assess the differences in participant demographic characteristics and to compare the differences among groups.

On CASI, MMSE, NPI and WCST, there were no statistically significant differences between pre- and post the 10-session course for the active and the sham groups. No side effects reported during or immediately after active tDCS stimulation.

These results suggest that left DLPFC anodal, and right deltoid cathodal tDCS, do not improve cognition, behavioral and psychological symptoms in DLB. Larger-scale trials are needed to confirm the effect of tDCS in DLB.

Post-traumatic stress disorder (PTSD), anxiety, and impulsive aggression are linked to transdiagnostic neurocognitive deficits. This includes impaired inhibitory control over inappropriate responses. Prior studies showed that inhibitory control can be improved by modulating the right inferior frontal gyrus (IFG) with transcranial direct current stimulation (tDCS) in combination with inhibitory control training. However, its clinical potential remains unclear. We therefore aimed to replicate a tDCS-enhanced inhibitory control training in a clinical sample and test whether this reduces stress-related mental health symptoms.

In a preregistered double-blind randomized-controlled trial, 100 active-duty military personnel and post-active veterans with PTSD, anxiety, or impulsive aggression symptoms underwent a 5-session intervention where a stop-signal response inhibition training was combined with anodal tDCS over the right IFG for 20 min at 1.25 mA. Inhibitory control was evaluated with the emotional go/no-go task and implicit association test. Stress-related symptoms were assessed by self-report at baseline, post-intervention, and after 3-months and 1-year follow-ups.

Active relative to sham tDCS neither influenced performance during inhibitory control training nor on assessment tasks, and did also not significantly influence self-reported symptoms of PTSD, anxiety, impulsive aggression, or depression at post-assessment or follow-up.

Our results do not support the idea that anodal tDCS over the right IFG at 1.25 mA enhances response inhibition training in a clinical sample, or that this tDCS-training combination can reduce stress-related symptoms. Applying different tDCS parameters or combining tDCS with more challenging tasks might provide better conditions to modulate cognitive functioning and stress-related symptoms.

Infantile hemiplegia due to brain injury is associated with poor attention span, which critically affects the learning and acquisition of new skills, especially among children with left-sided infantile hemiplegia (LSIH). This study aimed to improve the selective visual attention (SVA) of children with LSIH through transcranial direct current stimulation (tDCS).

A total of 15 children participated in this randomized, double-blinded, pilot study; of them, 10 experienced LSIH, and the remaining 5 were healthy age-matched controls. All the children performed the Computerized Stroop Color-Word Test (CSCWT) at baseline, during the 5th and 10th treatment sessions, and at follow-up. The experimental (n = 5) and control groups (n = 5) received tDCS, while the sham group (n = 5) received placebo tDCS. All three groups received cognitive training on alternate days, for 3 weeks, with the aim to improve SVA.

Two-way repeated measures analysis of variance (ANOVA) showed a statistically significant change in the mean scores of CSCWT between time points (baseline, 5th and 10th sessions, and follow-up) within-subject factor, group (experimental, sham) between-subject factor and interaction (time points X group) (p < 0.005). Furthermore, a one-way repeated measures ANOVA showed significant differences between time point (p < 0.005) for the experimental and control group but not the sham group.

These pilot results suggest that future research should be conducted with adequate samples to enable conclusions to be drawn.

Identifying effective treatments is a critical issue for Alzheimer’s dementia (AD). The pathological amyloid deposits of AD result in disruption of the balance between long-term potentiation (LTP) and long-term depression (LTD) of neuronal cells and synaptic plasticity. Brain stimulation in dementia research, especially with relatively safe tDCS, has been taken seriously recently. In theory, tDCS affects long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. Recently, an increasing number of studies have been conducted to evaluate the efficacy of tDCS in AD and concluded a positive therapeutic effect. Currently, there are no studies of tDCS for AD in Taiwan. In this study, we investigate the effects of tDCS in AD.

Using a double-blind, randomized and sham- controlled trial design, Sixteen AD aged 55-90 years (8 active, mean age 73.88 and 8 sham, mean age 74.75) were included in the study. AD diagnostics is according to DSM-5 criteria. The CDR ratings of AD participants ranged from 0.5 to 2. All subjects completed ten consecutive daily sessions in which they received either an active or a sham tDCS over the left dorsal lateral prefrontal cortex (anodal) and a cathodal electrode on the right supraorbital area. In each session, we applied a current intensity of 2 mA and an electrode size of 35 cm2 for 30 min in the active group. All subjects received a series of neuropsychological tests, which included CDR, MMSE, CASI and WCST, before and after these treatment sessions on the first day and 4 weeks later. Chi- square test, Wilcoxon signed ranks test and Mann-Whitney U test were used to assess the differences in participant demographic characteristics and to compare the differences among groups.

The active group showed significant improvement in total correct item, Conceptual level Responses (reflecting insight into the correct sorting principles), Categories Completed (reflecting overall success), and Trials to complete first categories (reflecting initial conceptual ability) of WCST 4 weeks later after the final stimulation. There were no statistically significant differences between before and after the 10-session course for the sham group.

tDCS stimulation improves cognitive operation and Conceptual Ability of AD.

Cognition is commonly affected in brain disorders. Non-invasive brain stimulation (NIBS) may have procognitive effects, with high tolerability. This meta-analysis evaluates the efficacy of transcranial magnetic stimulation (TMS) and transcranial Direct Current Stimulation (tDCS) in improving cognition, in schizophrenia, depression, dementia, Parkinson's disease, stroke, traumatic brain injury, and multiple sclerosis.

A PRISMA systematic search was conducted for randomized controlled trials. Hedges' g was used to quantify effect sizes (ES) for changes in cognition after TMS/tDCS v. sham. As different cognitive functions may have unequal susceptibility to TMS/tDCS, we separately evaluated the effects on: attention/vigilance, working memory, executive functioning, processing speed, verbal fluency, verbal learning, and social cognition.

We included 82 studies (n = 2784). For working memory, both TMS (ES = 0.17, p = 0.015) and tDCS (ES = 0.17, p = 0.021) showed small but significant effects. Age positively moderated the effect of TMS. TDCS was superior to sham for attention/vigilance (ES = 0.20, p = 0.020). These significant effects did not differ across the type of brain disorder. Results were not significant for the other five cognitive domains.

Our results revealed that both TMS and tDCS elicit a small trans-diagnostic effect on working memory, tDCS also improved attention/vigilance across diagnoses. Effects on the other domains were not significant. Observed ES were small, yet even slight cognitive improvements may facilitate daily functioning. While NIBS can be a well-tolerated treatment, its effects appear domain specific and should be applied only for realistic indications (i.e. to induce a small improvement in working memory or attention).

Transcranial direct current stimulation (tDCS) is a non-invasive, neuromodulatory technique with an emerging role for treating major depression.

To investigate the interactions between tDCS and drug therapy in unipolar and bipolar depressed patients who were refractory for at least one pharmacological treatment.

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, 2 mA, anodal stimulation over the left and cathodal over the right dorsolateral prefrontal cortex, twice a day, 20 minutes). 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.

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 (β = 4.92, P < 0.01) and multivariate (β = 5.8, P < 0.01) analyses; whereas use of dual-reuptake inhibitors positively changed tDCS effects in the multivariate model (β = –4.7, P = 0.02). A similar trend was observed for tricyclics (β = –4, P = 0.06) but not for antipsychotics, non-benzodiazepine anticonvulsants and other drugs.

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.

Impaired illness awareness or insight into illness (IIA) is a common feature of schizophrenia that contributes to medication nonadherence and poor clinical outcomes. Neuroimaging studies suggest IIA may arise from interhemispheric imbalance in frontoparietal regions, particularly in the posterior parietal area (PPA) and the dorsolateral prefrontal cortex (dlPFC). In this pilot study, we examined the effects of transcranial direct current stimulation (tDCS) on brain regions implicated in IIA.

Eleven patients with schizophrenia with IIA (≥3 PANSS G12) and 10 healthy controls were included. A crossover design was employed where all participants received single-session bi-frontal, bi-parietal, and sham stimulation in random order. For each condition, we measured (i) blood oxygen level-dependent (BOLD) response to an illness awareness task pre- and post-stimulation, (ii) regional cerebral blood-flow (rCBF) prior to and during stimulation, and (iii) changes in illness awareness.

At baseline, patients with schizophrenia showed higher BOLD-response to an illness awareness task in the left-PPA compared to healthy controls. Bi-parietal stimulation reduced the interhemispheric imbalance in the PPA compared to sham stimulation. Relatedly, bi-parietal stimulation increased rCBF beneath the anode (21% increase in the right-PPA), but not beneath the cathode (5.6% increase in the left-PPA). Bi-frontal stimulation did not induce changes in rCBF. We found no changes in illness awareness.

Although single-session tDCS did not improve illness awareness, this pilot study provides mechanistic justification for future investigations to determine if multi-session bi-parietal tDCS can induce sustained changes in brain activity in the PPA in association with improved illness awareness.

Growing evidence has indicated that right ventrolateral prefrontal cortex (RVLPFC) is critical in down-regulating emotional responses to social exclusion, and that depression is accompanied by social emotional dysregulation associated with reduced lateral prefrontal engagement. This study used anodal transcranial direct current stimulation (tDCS) to examine whether stimulating RVLPFC could improve emotional down-regulation of social exclusion in individuals with high depressive mood (DM).

A total of 96 high and 94 low DM individuals received active or sham tDCS while viewing social exclusion or individual negative pictures under no-reappraisal (passive viewing) and reappraisal conditions. Participants rate their negative emotional experience following the presentation of each image. Pupil diameter and visual fixation duration were also recorded during the task.

It was found that tDCS-activated RVLPFC induced a stronger regulation effect on social exclusion than individual negative emotions. The effect of tDCS on regulation of social exclusion was more pronounced in low v. high DM individuals.

These findings demonstrate the specific role of RVLPFC on social emotion regulation, which has implications for refining target areas for the treatment of social emotion dysregulation in depression. However the findings do not suggest that high DM individuals benefit from a single-tDCS session on the emotion regulation of social exclusion. Thus we suggest to use multiple tDCS sessions or transcranial magnetic stimulation to further explore the therapeutic proposal in the future.

Noninvasive brain stimulation can modulate neural processing within the motor cortex and thereby might be beneficial in the rehabilitation of hemispatial neglect after stroke.

We review the pertinent literature regarding the use of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation in order to facilitate recovery of hemispatial neglect after stroke.

Twenty controlled trials (including 443 stroke patients) matched our inclusion criteria. Methodology and results of each study are presented in a comparative approach. Current data seem to indicate a better efficiency of repetitive transcranial magnetic stimulation, compared to tDCS to ameliorate hemispatial neglect after stroke.

Noninvasive brain stimulation has the potential to facilitate recovery of hemispatial neglect after stroke, but until today, there are not enough data to claim its routine use.

Individuals with Lewy body dementia (LBD) typically exhibit impairments in attentional and executive function. Current pharmacological treatments have limited efficacy, with associated side effects. Transcranial direct current stimulation (tDCS) may represent an alternative treatment, as cognitive improvements have been demonstrated in healthy individuals. However, no studies to date have assessed the feasibility of tDCS in an LBD population. The aim of this preliminary study, therefore, was to assess the tolerability of tDCS, as well as its effects upon attentional and visuoperceptual performance, in LBD patients.

Thirteen participants completed attentional (simple reaction time, choice reaction time, and digit vigilance) and forced-choice visuoperceptual (angle and motion perception) tasks before and after one 20-min session of active tDCS (0.08 mA/cm2). The anodal electrode was applied to the left dorsolateral prefrontal cortex and the cathodal electrode was applied to the right deltoid. Attentional (task accuracy and reaction time to correct answers) and visuoperceptual (task accuracy and difficulty) outcome measures were compared using paired t-tests.

All participants tolerated stimulation and did not report any side effects during or immediately after stimulation. Post-stimulation improvements were observed in the choice reaction time (increased percentage of correct answers; p = 0.01) and digit vigilance (reduced mean reaction time to correct answers; p = 0.02) attention tasks. Visuoperceptual task performance did not improve (all p-values > 0.05).

Attentional, but not visuoperceptual, improvements were observed following stimulation in LBD patients. Larger-scale, placebo-controlled trials are needed to confirm whether tDCS is a useful treatment option for attentional deficits in LBD.