Active tDCS Research Articles

Effects of cathodal transcranial direct current stimulation on inhibitory and attention control in children and adolescents with attention-deficit hyperactivity disorder: A pilot randomized sham-controlled crossover study

The pathophysiological of attention-deficit hyperactivity disorder (ADHD) includes hypoactivation of the dorso-lateral prefrontal cortex (DLPFC). Most studies have used anodal (excitatory) transcranial direct current stimulation (tDCS) to improve ADHD symptoms, however, a meta-analysis showed limited effect on improving inhibition, and no evidence of attention improvement. We thus present a pilot protocol for investigating the effect of other montage i.e. cathodal (inhibitory) tDCS on neurophysiological and behavioral measures in ADHD. Eleven participants underwent active (1.5 mA, 20 min) and sham cathodal tDCS over the left DLPFC for 5 consecutive days at a 1-month interval. Quantitative electroencephalography was recorded in a resting state with the eyes opened and closed during visual go/no-go and auditory continuous performance tasks at baseline, after five sessions, and at 1-week and 1-month follow-ups. Correct responses and omission errors were recorded. After five active sessions, alpha power increased in the right frontal area when the eyes were opened, and delta power in the left frontal area and omission errors decreased during go/no-go tasks, with no differences at follow-ups. The results revealed improvements in inhibitory control, but not for attention. No aftereffects were observed in either outcomes. However, the changes found in both hemispheres would probably support the hypothesis that cathodal stimulation over the left DLPFC may increase the activity of the right DLPFC via transcallosal inhibition. Results of this pilot trial would help to design and implement a full-scale randomized control trials for further ADHD research. This study was registered on ClinicalTrials.gov (NCT03955692).

Active and sham transcranial direct current stimulation (tDCS) improved quality of life in female patients with fibromyalgia

PurposeFibromyalgia (FM) is a chronic pain syndrome with a strong impact on quality of life (QoL). Treatment of this condition remains a challenge, due to the scarce evidence for the effectiveness of the therapeutic approaches available. Current attention is focused on transcranial direct current stimulation (tDCS), which has yielded promising results for pain treatment. Rather than focusing only on pain relief, in this study, we aimed to determine how active or sham tDCS (over three cortical targets -the primary motor cortex, the dorsolateral prefrontal cortex and the operculo-insular cortex-) affect QoL in patients with FM.MethodsUsing a double-blind, placebo-controlled design, we applied fifteen tDCS sessions of 20’ to initial 130 participants (randomized to any of the four treatment groups). We evaluated the QoL (assessed by SF-36) and the symptoms’ impact (assessed by FIQ-R) in baseline, after treatment and at 6 months follow-up.ResultsAll groups were comparable as regards age, medication pattern and severity of symptoms before the treatment. We found that QoL and symptoms’ impact improved in all treatment groups (including the sham) and this improvement lasted for up to 6 months. However, we did not observe any group effect nor group*treatment interaction.ConclusionsAfter the intervention, we observed a non-specific effect that may be due to placebo, favoured by the expectations of tDCS efficacy and psychosocial variables inherent to the intervention (daily relationship with therapists and other patients in the clinic). Therefore, active tDCS is not superior to sham stimulation in improving QoL in FM.

Effect of Self-administered Transcranial Direct Stimulation in Patients with Major Depressive Disorder: A Randomized, Single-blinded Clinical Trial.

ObjectiveIn numerous studies that have addressed transcranial direct current stimulation (tDCS) devices, participants visit the hospital regularly and undergo stimulation directed by health professionals. This method has the advantage of being able to deliver accurate stimuli in a controlled environment, but it does not adopt the merits of tDCS portability and applicability. Thus, it may be necessary to investigate how self-administered tDCS treatment at home affects depression-related symptoms.MethodsIn this randomized, single-blinded clinical trial, 58 patients with major depressive disorder were assigned to active and sham tDCS stimulation groups, and treatment responses were evaluated biweekly over six weeks. Both active and sham tDCS treatment group were treated with escitalopram. All participants were instructed the protocol and usage of at-home tDCS device, and self-administered tDCS treatment at their home.ResultsThe beck-depression inventory score decreased significantly as treatment progressed, and the degree of symptom improvement was significantly higher in the active group than in the sham tDCS group. There were no significant differences between the two groups in other indices, including the Hamilton Depression Scale.ConclusionThese results suggest that patient-administered tDCS treatment might be effective in improving subjective symptoms of depression.

Neurophysiological and behavioral effects of multisession prefrontal tDCS and concurrent cognitive remediation training in patients with autism spectrum disorder (ASD): A double-blind, randomized controlled fNIRS study

BackgroundThe clinical effects and neurophysiological mechanisms of prefrontal tDCS and concurrent cognitive remediation training in individuals with autism spectrum disorder (ASD) remain unclear. ObjectiveThis two-armed, double-blind, randomized, sham-controlled trial aimed to investigate the beneficial effects of tDCS combined with concurrent cognitive remediation training on adolescents and young adults with ASD. MethodsParticipants were randomly assigned to either active or sham tDCS groups and received 1.5 mA prefrontal tDCS with left dorsolateral prefrontal cortex (dlPFC) cathode placement and right supraorbital region anode placement for 20 minutes over two consecutive weeks. tDCS was delivered concurrently with a computerized cognitive remediation training program. Social functioning and its underlying cognitive processes, as well as prefrontal resting-state functional connectivity (rsFC), were measured. ResultsThe results from 41 participants indicated that multisession prefrontal tDCS, compared to sham tDCS, significantly enhanced the social functioning of ASD individuals [F(1,39) = 4.75, p = .035, ηp2 = 0.11]. This improvement was associated with enhanced emotion recognition [F(1,39) = 8.34, p = .006, ηp2 = 0.18] and cognitive flexibility [F(1,39) = 4.91, p = .033, ηp2 = 0.11]. Specifically, this tDCS protocol optimized information processing efficiency [F(1,39) = 4.43, p = .042, ηp2 = 0.10], and the optimization showed a trend to be associated with enhanced rsFC in the right medial prefrontal cortex (ρ = 0.339, pFDR = .083). ConclusionMultisession tDCS with left dlPFC cathode placement and right supraorbital region anode placement paired with concurrent cognitive remediation training promoted social functioning in individuals with ASD. This appeared to be associated with the enhancement of the functional connectivity of the right medial PFC, a major hub for flexible social information processing, allowing these individuals to process information more efficiently in response to different social situations. Trial registrationClinicalTrials.gov (ID: NCT03814083)

The Effects of a Single Transcranial Direct Current Stimulation Session on Impulsivity and Risk Among a Sample of Adult Recreational Cannabis Users.

Individuals with substance use disorders exhibit risk-taking behaviors, potentially leading to negative consequences and difficulty maintaining recovery. Non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have yielded mixed effects on risk-taking among healthy controls. Given the importance of risk-taking behaviors among substance-using samples, this study aimed to examine the effects of tDCS on risk-taking among a sample of adults using cannabis. Using a double-blind design, 27 cannabis users [M(SD) age = 32.48 (1.99), 41% female] were randomized, receiving one session of active or sham tDCS over the bilateral dorsolateral prefrontal cortex (dlPFC). Stimulation parameters closely followed prior studies with anodal right dlPFC and cathodal left dlPFC stimulation. Risk-taking—assessed via a modified Cambridge Gambling Task—was measured before and during tDCS. Delay and probability discounting tasks were assessed before and after stimulation. No significant effects of stimulation on risk-taking behavior were found. However, participants chose the less risky option ∼86% of the trials before stimulation which potentially contributed to ceiling effects. These results contradict one prior study showing increased risk-taking among cannabis users following tDCS. There was a significant increase in delay discounting of a $1000 delayed reward during stimulation for the sham group only, but no significant effects for probability discounting. The current study adds to conflicting and inconclusive literature on tDCS and cognition among substance-using samples. In conclusion, results suggest the ineffectiveness of single session dlPFC tDCS using an established stimulation protocol on risk-taking, although ceiling effects at baseline may have also prevented behavior change following tDCS.

Evidence of Anti-Inflammatory Effect of Transcranial Direct Current Stimulation in a CFA-Induced Chronic Inflammatory Pain Model in Wistar Rats

Introduction: Given that chronic inflammatory pain is highly prevalent worldwide, it is important to study new techniques to treat or relieve this type of pain. The present study evaluated the effect of transcranial direct current stimulation (tDCS) in rats submitted to a chronic inflammatory model by nociceptive response, biomarker levels (brain-derived neurotrophic factor [BDNF] and interleukin [IL]-6 and IL-10), and by histological parameters. Methods: Sixty-day-old male Wistar rats were used in this study and randomized by weight into 6 major groups: total control, control + sham-tDCS, control + active tDCS, total CFA, CFA + sham-tDCS, and CFA + active tDCS. After inflammatory pain was established, the animals were submitted to the treatment protocol for 8 consecutive days, according to the experimental group. The nociceptive tests (von Frey and hot plate) were assessed, and euthanasia by decapitation occurred at day 8 after the end of tDCS treatment, and the blood serum and central nervous structures were collected for BDNF and IL measurements. All experiments and procedures were approved by the Institutional Committee for Animal Care and Use (UFPel #4538). Results: The tDCS treatment showed a complete reversal of the mechanical allodynia induced by the pain model 24 h and 8 days after the last tDCS session, and there was partial reversal of the thermal hyperalgesia at all time points. Serum BDNF levels were decreased in CFA + sham-tDCS and CFA + tDCS groups compared to the control + tDCS group. The control group submitted to tDCS exhibited an increase in serum IL-6 levels in relation to the other groups. In addition, there was a significant decrease in IL-10 striatum levels in control + tDCS, CFA, and CFA + sham-tDCS groups in relation to the control group, with a partial tDCS effect on the CFA pain model. Local histology demonstrated tDCS effects in decreasing lymphocytic infiltration and neovascularization and tissue regeneration in animals exposed to CFA. Conclusion: tDCS was able to reverse the mechanical allodynia and decrease thermal hyperalgesia and local inflammation in a chronic inflammatory pain model, with a modest effect on striatum IL-10 levels. As such, we suggest that analgesic tDCS mechanisms may be related to tissue repair by modulating the local inflammatory process.

The efficacy of non-invasive, non-convulsive electrical neuromodulation on depression, anxiety and sleep disturbance: a systematic review and meta-analysis.

The effects of non-invasive, non-convulsive electrical neuromodulation (NINCEN) on depression, anxiety and sleep disturbance are inconsistent in different studies. Previous meta-analyses on transcranial direct current stimulation (tDCS) and cerebral electrotherapy stimulation (CES) suggested that these methods are effective on depression. However, not all types of NINECN were included; results on anxiety and sleep disturbance were lacking and the influence of different populations and treatment parameters was not completely analyzed. We searched PubMed, Embase, PsycInfo, PsycArticles and CINAHL before March 2021 and included published randomized clinical trials of all types of NINCEN for symptoms of depression, anxiety and sleep in clinical and non-clinical populations. Data were pooled using a random-effects model. The main outcome was change in the severity of depressive symptoms after NINCEN treatment. A total of 58 studies on NINCEN were included in the meta-analysis. Active tDCS showed a significant effect on depressive symptoms (Hedges' g = 0.544), anxiety (Hedges' g = 0.667) and response rate (odds ratio = 1.9594) compared to sham control. CES also had a significant effect on depression (Hedges' g = 0.654) and anxiety (Hedges' g = 0.711). For all types of NINCEN, active stimulation was significantly effective on depression, anxiety, sleep efficiency, sleep latency, total sleep time, etc. Our results showed that tDCS has significant effects on both depression and anxiety and that these effects are robust for different populations and treatment parameters. The rational expectation of the tDCS effect is 'response' rather than 'remission'. CES also is effective for depression and anxiety, especially in patients with disorders of low severity.

Modulating Cognitive-Motor Multitasking with Commercial-off-the-Shelf Non-Invasive Brain Stimulation.

One growing area of multitasking research involves a focus on performing cognitive and motor tasks in tandem. In these situations, increasing either cognitive or motor demands has implications for performance in both tasks, an effect which is thought to be due to competing neural resources. Separate research suggests that non-invasive brain stimulation may offer a means to mitigate performance decrements experienced during multitasking. In the present study, we investigated the degree to which a commercially available non-invasive brain stimulation device (Halo Sport) alters balance performance in the presence of different types of cognitive demands. Specifically, we tested if performing a secondary cognitive task impacts postural sway in healthy young adults and if we could mitigate this impact using transcranial direct current stimulation (tDCS) applied over the primary motor cortex. Furthermore, we included conditions of unstable and stable surfaces and found that lower surface stability increased postural sway. In addition, we found that cognitive load impacted postural sway but in the opposite pattern we had anticipated, with higher sway found in the single-task control condition compared to executive function conditions. Finally, we found a small but significant effect of tDCS on balance with decreased sway for active (compared to sham) tDCS.

Combined Yoga and Transcranial Direct Current Stimulation Increase Functional Connectivity and Synchronization in the Frontal Areas.

Transcranial direct current stimulation (tDCS) is a non-invasive neuro-stimulation technique that can modulate cortical excitability. Similarly, yoga is shown to affect the brain's neural activity and networks. Here, we aimed to investigate the effect of combined yoga and tDCS on brain oscillations and networks using resting-state electroencephalography recordings. In a randomized, cross-over, double-blind design, twenty-two healthy subjects participated in a yoga/active tDCS session (2mA; 20min; anode-F3, cathode F4) or yoga/sham tDCS on 2 separate days. Resting-state EEG data were collected before and after each intervention. Power spectral density (PSD) and functional connectivity, measured by a synchronization measure, phase-locking value, were computed for each condition. There were no significant differences in PSD values among the two interventions. The network-based statistic method was employed for detecting functional connectivity differences between yoga/active and yoga/sham tDCS interventions. Results show that the addition of active tDCS to yoga is associated with increased functional connectivity of the scalp and source EEG data in the frontal area. The changes were widespread, intra-hemispheric, and inter-hemispheric connections, which were mainly between the frontal area to other regions. At the source level, most of the connectivity changes were found in the fronto-parietal network. These findings suggest that combining yoga with tDCS might lead to brain network changes related to the executive and attentional functions.

Brain activity and upper limb movement analysis in children with Down syndrome undergoing transcranial direct current stimulation combined with virtual reality training: study protocol for a randomized controlled trial

BackgroundChildren with Down syndrome have poorer functional and sensory skills compared to children with typical development. Virtual reality (VR) training could help improve these skills. Moreover, transcranial direct current stimulation (tDCS) has achieved promising results in terms of enhancing the effects of physical and sensory therapy by modulating cortical excitability.Methods/designTwo investigations are proposed: (1) an observational study with a convenience sample consisting of children with Down syndrome (group 1—cognitive age of 6 to 12 years according to the Wechsler Abbreviated Scale of Intelligence) and children with typical development 6 to 12 years of age (group 2). Both groups will undergo evaluations on a single day involving a three-dimensional analysis of upper limb movements, an analysis of muscle activity of the biceps and brachial triceps muscles and an analysis of visuospatial and cognitive-motor variables. (2) Analysis of clinical intervention: a pilot study and clinical trial will be conducted involving individuals with Down syndrome (cognitive age of 6 to 12 years according to the Wechsler Abbreviated Scale of Intelligence). The sample will be defined after conducting a pilot study with the same methodology as that to be used in the main study. The participants will be randomly allocated to two groups: An experimental group submitted to anodal tDCS combined with a VR game and a manual motor task and a control group submitted to sham tDCS combined with a VR game and a manual motor task. The training protocol will involve 10 sessions of active or sham tDCS during memory and motor task games. Three 20-min sessions will be held per week for a total of 10 sessions. Evaluations will be performed on three different occasions: pre-intervention, post-intervention (after 10 sessions) and follow-up (1 month after the intervention). Evaluations will consist of analyses of electroencephalographic signals, electromyographic signals of the biceps and triceps brachii, and the three-dimensional reconstruction of the reaching movement. The results will be analyzed statistically with the significance level set at 5% (p ≤ 0.05).DiscussionThe optimization of the results obtained with virtual reality training is believed to be related to the interactive experience with a wide range of activities and scenarios involving multiple sensory channels and the creation of exercises, the intensity of which can be adjusted to the needs of children. Therefore, the proposed study aims to complement the literature with further information on tDCS and VR training considering different variables to provide the scientific community with clinical data on this combination of interventions.Trial registrationBrazilian Clinical Trials Registry (REBEC) protocol number RBR-43pk59 registered on 2019 March 27 https://ensaiosclinicos.gov.br/rg/RBR-43pk59 and Human Research Ethics Committee number 3.608.521 approved on 2019 September 30. Protocol version 2021 October 20. Any changes to the protocol will be reported to the committees and approved. Informed consent will be obtained from all participants by the clinical research coordinator and principal investigator.

Effects of rTMS and tDCS on neuropathic pain after brachial plexus injury: a randomized placebo-controlled pilot study

Neuropathic pain after brachial plexus injury (NPBPI) is a highly disabling clinical condition and is increasingly prevalent due to increased motorcycle accidents. Currently, no randomized controlled trials have evaluated the effectiveness of non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS) in patients suffering from NPBPI. In this study, we directly compare the efficacy of 10-Hz rTMS and anodal 2 mA tDCS techniques applied over the motor cortex (5 daily consecutive sessions) in 20 patients with NPBPI, allocated into 2 parallel groups (active or sham). The order of the sessions was randomised for each of these treatment groups according to a crossover design and separated by a 30-day interval. Scores for “continuous” and “paroxysmal” pain (primary outcome) were tabulated after the last stimulation day and 30 days after. Secondary outcomes included the improvement in multidimensional aspects of pain, anxiety state and quality of life from a qualitative and quantitative approach. Active rTMS and tDCS were both superior to sham in reducing continuous (p < 0.001) and paroxysmal (p = 0.002; p = 0.02) pain as well as in multidimensional aspects of pain (p = 0.001; p = 0.002) and anxiety state (p = < 0.001; p = 0.005). Our results suggest rTMS and tDCS are able to treat NPBPI with little distinction in pain and anxiety state, which may promote the use of tDCS in brachial plexus injury pain management, as it constitutes an easier and more available technique.Clinical Trial Registration: http://www.ensaiosclinicos.gov.br/, RBR-5xnjbc – Sep 3, 2018.

Modulation of brain networks during MR-compatible transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) can influence performance on behavioral tasks and improve symptoms of brain conditions. Yet, it remains unclear precisely how tDCS affects brain function and connectivity. Here, we measured changes in functional connectivity (FC) metrics in blood-oxygenation-level-dependent (BOLD) fMRI data acquired during MR-compatible tDCS in a whole-brain analysis with corrections for false discovery rate. Volunteers (n = 64) received active tDCS, sham tDCS, and rest (no stimulation), using one of three previously established electrode tDCS montages targeting left dorsolateral prefrontal cortex (DLPFC, n = 37), lateral temporoparietal area (LTA, n = 16), or superior temporal cortex (STC, n = 11). In brain networks where simulated E field was highest in each montage, connectivity with remote nodes decreased during active tDCS. During active DLPFC-tDCS, connectivity decreased between a fronto-parietal network and subgenual ACC, while during LTA-tDCS connectivity decreased between an auditory-somatomotor network and frontal operculum. Active DLPFC-tDCS was also associated with increased connectivity within an orbitofrontal network overlapping subgenual ACC. Irrespective of montage, FC metrics increased in sensorimotor and attention regions during both active and sham tDCS, which may reflect the cognitive-perceptual demands of tDCS. Taken together, these results indicate that tDCS may have both intended and unintended effects on ongoing brain activity, stressing the importance of including sham, stimulation-absent, and active comparators in basic science and clinical trials of tDCS.

Transcranial Direct Current Stimulation on Parkinson's Disease: Systematic Review and Meta-Analysis

Background: Clinical impact of transcranial direct current stimulation (tDCS) alone for Parkinson's disease (PD) is still a challenge. Thus, there is a need to synthesize available results, analyze methodologically and statistically, and provide evidence to guide tDCS in PD.Objective: Investigate isolated tDCS effect in different brain areas and number of stimulated targets on PD motor symptoms.Methods: A systematic review was carried out up to February 2021, in databases: Cochrane Library, EMBASE, PubMed/MEDLINE, Scopus, and Web of science. Full text articles evaluating effect of active tDCS (anodic or cathodic) vs. sham or control on motor symptoms of PD were included.Results: Ten studies (n = 236) were included in meta-analysis and 25 studies (n = 405) in qualitative synthesis. The most frequently stimulated targets were dorsolateral prefrontal cortex and primary motor cortex. No significant effect was found among single targets on motor outcomes: Unified Parkinson's Disease Rating Scale (UPDRS) III – motor aspects (MD = −0.98%, 95% CI = −10.03 to 8.07, p = 0.83, I2 = 0%), UPDRS IV – dyskinesias (MD = −0.89%, CI 95% = −3.82 to 2.03, p = 0.55, I2 = 0%) and motor fluctuations (MD = −0.67%, CI 95% = −2.45 to 1.11, p = 0.46, I2 = 0%), timed up and go – gait (MD = 0.14%, CI 95% = −0.72 to 0.99, p = 0.75, I2 = 0%), Berg Balance Scale – balance (MD = 0.73%, CI 95% = −1.01 to 2.47, p = 0.41, I2 = 0%). There was no significant effect of single vs. multiple targets in: UPDRS III – motor aspects (MD = 2.05%, CI 95% = −1.96 to 6.06, p = 0.32, I2 = 0%) and gait (SMD = −0.05%, 95% CI = −0.28 to 0.17, p = 0.64, I2 = 0%). Simple univariate meta-regression analysis between treatment dosage and effect size revealed that number of sessions (estimate = −1.7, SE = 1.51, z-score = −1.18, p = 0.2, IC = −4.75 to 1.17) and cumulative time (estimate = −0.07, SE = 0.07, z-score = −0.99, p = 0.31, IC = −0.21 to 0.07) had no significant association.Conclusion: There was no significant tDCS alone short-term effect on motor function, balance, gait, dyskinesias or motor fluctuations in Parkinson's disease, regardless of brain area or targets stimulated.

The effect of transcranial direct current stimulation on cognitive performance in youth with persistent cognitive symptoms following concussion: a controlled pilot study

ABSTRACT Objective Explore the feasibility, tolerability, and early efficacy of transcranial direct current stimulation (tDCS) as a therapeutic intervention for youth with cognitive persistent post-concussion symptoms (PPCS). Hypothesis tDCS improves performance on a dual task working memory (WM) paradigm in youth with cognitive PPCS. Participants Twelve youth experiencing cognitive PPCS. Design A quasi-randomized pilot trial was used to explore the tolerability of, and performance differences on, a dual N-Back WM task paired with active or sham tDCS over 3 sessions. Measures Accuracy and reaction time on WM task and self-report of tDCS tolerability. Results Trends toward increases in accuracy from Day 1 to 3 seen in both groups. Active tDCS group performed better than sham on Day 2 in N-Back level N2 (p = .019), and marginally better than the sham group on Day 3 in level N3 (p = .26). Participants reported tDCS as tolerable; compared to the active tDCS group, the sham group reported more “considerable” (p = .078) and “strong” symptoms (p = .097). Conclusion tDCS is a promising tool for enhancing WM performance and is a feasible and tolerable adjunct to behavioral interventions in youth with cognitive PPCS. A clinical trial to demonstrate efficacy is warranted.

Effects of transcranial direct current stimulation on physical and mental health in older adults with chronic musculoskeletal pain: a randomized controlled trial.

We investigated the effects of transcranial direct current stimulation (tDCS) combined with physical therapy (PT) on pain levels, physical activity levels, quality of life, and depression in older adults with chronic musculoskeletal pain. Twenty-five older adults (9 males and 16 females), aged between 66 and 86years (active group 77.2 ± 3.9; sham group 76.6 ± 6.2), volunteers were randomly allocated in the active (active tDCS + PT) and sham groups (sham tDCS + PT), and received the intervention three times per week for 8weeks. Pain level, physical activity level, depression state, and quality of life were assessed based on the Visual Analog Scale (VAS), Physical Activity Scale for the Elderly (PASE), Beck Depression Inventory (BDI) scale, and Short-Form 36 Health Survey Questionnaire (SF-36), respectively. Measurements were conducted four times: at baseline, mid-intervention, post-intervention, and 1-month follow-up. As a result, at 8weeks, the active group yielded greater improvements in VAS, BDI, and SF-36 scores than the sham tDCS group. At follow-up, the tDCS group led to a greater improvement in VAS, PASE, and SF-36 scores compared to sham tDCS group (p < 0.05). Our results suggest a beneficial effect of tDCS combined with PT in older adults with chronic musculoskeletal pain in the reduction of pain sensation, increment of physical activity level, increment of the quality of life, and reduction of depression incidents. This opens the possibility the possibility of using tDCS as a regular treatment for this population's physical and mental health.

Effects of non-invasive brain stimulation in multiple sclerosis: systematic review and meta-analysis.

Objective:The objective of this meta-analysis was to summarize evidence on the therapeutic effects of non-invasive brain stimulation (NIBS) on core symptoms of multiple sclerosis (MS). Specifically, findings from studies deploying transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) protocols were summarized in this review.Methods:We systematically searched articles published in four databases, until 31 May 2021, which compared the effects of active tDCS or rTMS with sham intervention in MS patients. We used a random-effects model for this meta-analysis. Meta-regression and subgroup meta-analysis were used to examine the effects of stimulation dose and different stimulation protocols, respectively.Results:Twenty-five randomized controlled trials (RCTs) were included in this review, consisting of 19 tDCS and 6 rTMS studies. tDCS led to a significant and immediate reduction of fatigue with a large effect size (Hedges’s g = −0.870, 95% confidence intervals (CI) = [−1.225 to −0.458], number needed to treat (NNT) = 2). Particularly, a subgroup analysis showed that applying tDCS over the left DLPFC and bilateral S1 led to fatigue reductions compared to sham stimulation. Furthermore, tDCS had favorable effects on fatigue in MS patients with low physical disability but not those with high physical disability, and additionally improved cognitive function. Finally, whereas rTMS was observed to reduce muscle spasticity, these NIBS protocols showed no further effect on MS-associated pain and mood symptoms.Conclusion:tDCS in MS alleviates fatigue and improves cognitive function whereas rTMS reduces muscle spasticity. More high-quality studies are needed to substantiate the therapeutic effects of different NIBS protocols in MS.

Home-based transcranial direct current stimulation (tDCS) and motor imagery for phantom limb pain using statistical learning to predict treatment response: an open-label study protocol.

Phantom limb pain (PLP) management has been a challenge due to its response heterogeneity and lack of treatment access. This study will evaluate the feasibility of a remotely home-based M1 anodal tDCS combined with motor imagery in phantom limb patients and assess the preliminary efficacy, safety, and predictors of response of this therapy. This is a pilot, single-arm, open-label trial in which we will recruit 10 subjects with phantom limb pain. The study will include 20 sessions. All participants will receive active anodal M1 tDCS combined with phantom limb motor imagery training. Our primary outcome will be the acceptability and feasibility of this combined intervention. Moreover, we will assess preliminary clinical (pain intensity) and physiological (motor inhibition tasks and heart rate variability) changes after treatment. Finally, we will implement a supervised statistical learning (SL) model to identify predictors of treatment response (to tDCS and phantom limb motor imagery) in PLP patients. We will also use data from our previous clinical trial (total observations=224 [n=112 x timepoints = 2)) for our statistical learning algorithms. The new prospective data from this open-label study will be used as an independent test dataset. This protocol proposes to assess the feasibility of a novel, neuromodulatory combined intervention that will allow the design of larger remote clinical trials, thus increasing access to safe and effective treatments for PLP patients. Moreover, this study will allow us to identify possible predictors of pain response and PLP clinical endotypes.

Home-based transcranial direct current stimulation (tDCS) and motor imagery for phantom limb pain using statistical learning to predict treatment response: an open-label study protocol

Background: Phantom limb pain (PLP) management has been a challenge due to its response heterogeneity and lack of treatment access. This study will evaluate the feasibility of a remotely home-based M1 anodal tDCS combined with motor imagery in phantom limb patients and assess the preliminary efficacy, safety, and predictors of response of this therapy. Methods: This is a pilot, single-arm, open-label trial in which we will recruit 10 subjects with phantom limb pain. The study will include 20 sessions. All participants will receive active anodal M1 tDCS combined with phantom limb motor imagery training. Our primary outcome will be the acceptability and feasibility of this combined intervention. Moreover, we will assess preliminary clinical (pain intensity) and physiological (motor inhibition tasks and heart rate variability) changes after treatment. Finally, we will implement a supervised statistical learning (SL) model to identify predictors of treatment response (to tDCS and phantom limb motor imagery) in PLP patients. We will also use data from our previous clinical trial (total observations=224 [n=112 x timepoints = 2)) for our statistical learning algorithms. The new prospective data from this open-label study will be used as an independent test dataset. Discussion: This protocol proposes to assess the feasibility of a novel, neuromodulatory combined intervention that will allow the design of larger remote clinical trials, thus increasing access to safe and effective treatments for PLP patients. Moreover, this study will allow us to identify possible predictors of pain response and PLP clinical endotypes. Keywords: phantom limb pain, home-based tDCS, motor imagery, statistical learning, remote trial.

Home-Based Transcranial Direct Current Stimulation for the Treatment of Symptoms of Depression and Anxiety in Temporal Lobe Epilepsy: A Randomized, Double-Blind, Sham-Controlled Clinical Trial.

We conducted a double-blind randomized clinical trial in order to examine the effects and the safety of home-based transcranial direct current stimulation (tDCS) on depressive and anxious symptoms of patients with temporal lobe epilepsy (TLE). We evaluated 26 adults with TLE and depressive symptoms randomized into two different groups: active tDCS (tDCSa) and Sham (tDCSs). The patients were first submitted to 20 sessions of tDCS for 20 min daily, 5 days a week for 4 weeks and then received a maintenance tDCS application in the research laboratory once a week for 3 weeks. The intensity of the current was 2 mA, applied bilaterally over the dorsolateral prefrontal cortex, with the anode positioned on the left side and the cathode on the right side. Participants were evaluated on days 1, 15, 30, and 60 of the study using the Beck Depression Inventory II (BDI). A follow-up evaluation was performed 1 year after the end of treatment. They were also evaluated for quality of life and for anxious symptoms as secondary outcomes. The groups did not differ in clinical, socioeconomic or psychometric characteristics at the initial assessment. There was no statistically significant difference between groups regarding reported adverse effects, seizure frequency or dropouts. On average, between the 1st and 60th day, the BDI score decreased by 43.93% in the active group and by 44.67% in the Sham group (ΔBDIfinal – initial = −12.54 vs. −12.20, p = 0.68). The similar improvement in depressive symptoms observed in both groups was attributed to placebo effect and interaction between participants and research group and not to tDCS intervention per se. In our study, tDCS was safe and well tolerated, but it was not effective in reducing depressive or anxiety symptoms in patients with temporal lobe epilepsy.Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT03871842].

Neuroinflammatory effects of tDCS in ovariectomized rats with chronic inflammation

Introduction: Postmenopausal women are more susceptible to chronic condition such as osteoporosis, arthritis and other inflammatory diseases. Then, we investigated the effects of transcranial direct current stimulation (tDCS) upon biomarkers levels in ovariectomized rats subjected to inflammatory model. Methods: 20 females adult Wistar rats were subjected to ovariectomy and complete Freund’s adjuvant (CFA)-induced inflammation model and divided into two groups: OAS and OAT (active tDCS). Fifteen days after, rats were submitted to bimodal tDCS treatment (20min, 0.5mA, 8 days). Rats were killed 24 h after the last session of tDCS, tissue samples (hypothalamus, cerebral cortex and brainstem) were collected, for biomarkers analysis by ELISA. And paws were extracted for histological analysis. Results: tDCS increased hypothalamus TNF-α; IL-1β; IL-10 and NGF levels. Also, tDCS group increased cortical cerebral TNF-α and NGF levels; as well as IL-1β levels in the brainstem. Inflammatory profile was observed in the histology of hindpaws, however, no tDCS effect was observed. Conclusion: bimodal tDCS showed an effect in the inflammatory central axis, with a small effect in the peripheral site evaluated in this current study through the histology.