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Transcranial direct current stimulation (tDCS) has been used as treatment for depression, but its effects are heterogeneous. We investigated, in a subsample of the clinical trial Escitalopram versus Electrical Direct Current Therapy for Depression Study (ELECTTDCS), whether white matter areas associated with depression disorder were associated with tDCS response. Baseline diffusion tensor imaging data were analyzed from 49 patients (34 females, mean age 41.9) randomized to escitalopram 20 mg/day, tDCS (2 mA, 30 min, 22 sessions), or placebo. Antidepressant outcomes were assessed by Hamilton Depression Rating Scale-17 (HDRS) after 10-week treatment. We used whole-brain tractography for extracting white matter measures for anterior corpus callosum, and bilaterally for cingulum bundle, striato-frontal, inferior occipito-frontal fasciculus and uncinate. For the rostral body, tDCS group showed higher MD associated with antidepressant effects (estimate = -5.13 ± 1.64, p = 0.002), and tDCS significantly differed from the placebo and the escitalopram group. The left striato-frontal tract showed higher FA associated with antidepressant effects (estimate = -2.14 ± 0.72, p = 0.003), and tDCS differed only from the placebo group. For the right uncinate, the tDCS group lower AD values were associated with higher HDRS decrease (estimate = -1.45 ± 0.67, p = 0.031). Abnormalities in white matter MDD-related areas are associated with tDCS antidepressant effects. Suggested better white matter microstructure of the left prefrontal cortex was associated with tDCS antidepressant effects. Future studies should investigate whether these findings are driven by electric field diffusion and density in these areas.

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Neuropathic pain (NP) is caused by a lesion that triggers pain chronification and central sensitization and it can develop in a different manner, dependent of age. Recent studies have demonstrated the efficacy of transcranial direct current stimulation (tDCS) for treating NP. Then, we aimed to investigate the effects of tDCS and BDNF levels in neuropathic pain rats in development, with 30 days old in the beginning of experiments. Eight-five male Wistar rats were subjected to chronic constriction injury. After establishment of NP, bimodal tDCS was applied to the rats for eight consecutive days, for 20 minutes each session. Subsequently, nociceptive behavior was assessed at baseline, 14 days after surgery, 1 day and 7 days after the end of tDCS. The rats were sacrificed 8 days after the last session of tDCS. An increase in the nociceptive threshold was observed in rats in development 1 day after the end of tDCS (short-term effect), but this effect was not maintained 7 days after the end of tDCS (long-term effect). Furthermore, brain derived neurotrophic factor (BDNF) levels were analyzed in the frontal cortex, spinal cord and serum using ELISA assays. The neuropathic pain model showed an effect of BDNF in the spinal cord of rats in development. There were no effects of BNDF levels of pain or tDCS in the frontal cortex or serum. In conclusion, tDCS is an effective technique to relieve nociceptive behavior at a short-term effect in neuropathic pain rats in development, and BDNF levels were not altered at long-term effect.

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ABSTRACT BACKGROUND AND OBJECTIVES: Fibromyalgia (FM) is a chronic widespread musculoskeletal pain resulting in central sensitization of nociceptive signaling. Transcranial direct current stimulation (tDCS) over the left motor cortex (M1) is a non-invasive neuromodulation technique indicated for a broad range of chronic pain disorders, including FM. Studies suggest that left and right M1 (contralateral and ipsilateral hemisphere of tDCS stimulation) are modulated. But it is necessary to clarify the differences in clinical pain perception comparing the right and left side of the body. This study aimed to evaluate the pain-related difference between right-left side of the body after five sessions of anodal tDCS in women with FM. METHODS: A double-blinded, parallel, randomized, sham-controlled trial with 30 women with FM was performed. Five sessions of anodal C3 and cathodal supraorbital (Fp2) tDCS were conducted (2 mA for 20 min). Pain, impact of FM and anxiety were evaluated. No statistically significant three-way interaction between time, stimulation type and body side were found. RESULTS: Active-tDCS showed significant improvement in pain, but impact of FM and anxiety did not show significant improvement. CONCLUSION: Five sessions of anodal tDCS over the left M1 improves pain in women with FM, however there was no difference between right-left body sides.

RESUMO JUSTIFICATIVA E OBJETIVOS: A fibromialgia (FM) é uma dor musculoesquelética crônica generalizada que resulta na sensibilização central da sinalização nociceptiva. A estimulação transcraniana de corrente contínua (eTCC) sobre o córtex motor esquerdo (M1) é uma técnica de neuromodulação não invasiva indicada para uma ampla gama de distúrbios de dor crônica, incluindo a FM. Estudos sugerem a modulação do M1 esquerdo e direito (hemisfério contralateral e ipsilateral da eTCC). Mas é necessário esclarecer as diferenças na percepção clínica da dor comparando os lados direito e esquerdo do corpo. Este estudo teve como objetivo avaliar a diferença relacionada à dor entre o lado direito e esquerdo do corpo após cinco sessões de eTCC anodal em mulheres com FM. MÉTODOS: Foi realizado um estudo duplo-cego, paralelo, randomizado e controlado por sham com 30 mulheres com FM. Foram realizadas cinco sessões de eTCC anodais C3 e supraorbitais catodais (Fp2) (2 mA por 20 min). Foram avaliados a dor, o impacto da FM e a ansiedade. Não foi encontrada nenhuma interação de três vias estatisticamente significativa entre tempo, tipo de estimulação e lado do corpo. RESULTADOS: A eTCC-Ativa mostrou uma melhora significativa na dor, mas o impacto da FM e da ansiedade não mostrou uma melhora significativa. CONCLUSÃO: Cinco sessões de eTCC anodal sobre o M1 esquerdo melhoram a dor nas mulheres com FM, entretanto não houve diferença entre os lados direito e esquerdo do corpo.

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CONTEXT: Chronic pain in end-stage renal disease (ESRD) is an increasingly neglected clinical problem affecting more than 60% of patients. Long-term chronic pain could be associated with brain imbalance in circuits of pain matrix and is associated with poor quality of life (QoL) and mood disturbance. OBJECTIVES: The aim of this study was evaluating the effects of transcranial direct current stimulation (tDCS) on pain, QoL, depression, anxiety and affectivity in ESRD patients undergoing hemodialysis (HD). METHODS: This double-blind, randomized, sham-controlled trial included 30 patients with chronic pain undergoing HD. Participants were allocated to Active tDCS and Sham tDCS and received ten non-consecutive sessions of anodal motor cortex stimulation (M1/Sp2 montage) at 2 mA intensity for 20 min. The primary outcome was pain assessed using numeric rating scale (NRS) and collected at baseline, immediately after the 10th day of intervention, one week, two weeks, and four weeks after the last stimulation. Secondary outcomes included QoL, depression, anxiety and affectivity collected before and after intervention. RESULTS: A mixed ANOVA model showed significant interaction between group and time on pain F(4.112) = 3.106, P = 0.01 with main effects of group (P = 0.03). Before and after intervention, a significant improvement was observed in QoL (P = 0.009), general health (P = 0.03), fatigue (P = 0.05), symptoms (P = 0.05) depression (P = 0.01) and anxiety (P = 0.01). No difference was found for affectivity. CONCLUSION: Anodal tDCS over the motor cortex emerges as a potential therapeutic approach for improving pain, QoL, and mood in patients with ESRD.

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Transcranial direct current stimulation (tDCS) has been showing promising effects for the treatment of obsessive-compulsive disorder (OCD), but there is still no conclusion on its efficacy for this disorder. We performed a systematic review and meta-analysis of trials using tDCS for OCD and a computer modeling analysis to evaluate the electric field (EF) strengths of different electrode assemblies in brain regions of interest (ROIs) (PROSPERO-42021262465). PubMed/MEDLINE, Embase, Cochrane Library and Web of Science databases were searched from inception to 25 September 2022. Randomized controlled trials (RCTs) and open-label studies were included. The primary aim was the effect size (Hedges' g) of continuous outcomes and potential moderators of response. For EF modeling, SimNIBS software was used. Four RCTs and four open-label trials were included (n = 241). Results revealed a large effect of tDCS in the endpoint, but no significant effect between active and sham protocols. No predictor of response was found. EF analysis revealed that montages using the main electrode over the (pre)supplementary motor area with an extracephalic reference electrode might lead to stronger EFs in the predefined ROIs. Our results revealed that tDCS might be a promising intervention to treat OCD; however, larger studies are warranted.

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BACKGROUND: Generalized anxiety disorder (GAD) is a common condition with current treatments being only moderately effective. Non-invasive brain stimulation techniques might provide a novel approach for treating GAD. Transcranial direct current stimulation (tDCS) has shown promising efficacy and tolerability for major depression but has not been investigated for GAD yet. Thus, we investigated the effects of tDCS on patients with GAD. METHODS: We conducted a pilot, double-blind, randomized, sham-controlled trial on 30 GAD patients. Five sessions of tDCS (2 mA, 20 min, anode over the left dorsolateral prefrontal cortex and cathode over the right supraorbital cortex) were performed. Anxiety was the primary outcome and it was measured by the Hamilton Anxiety Rating Scale and the Beck Anxiety Inventory. Secondary outcomes were accessed by the Lipp Inventory of Stress Symptoms for Adults, Positive and Negative Affect Schedule, and the Beck Depression Inventory (BDI). Data were examined at baseline, after the 5th day of intervention, and at 1-week follow-up. RESULTS: Thirty patients finished the study. There were no significant improvements in anxiety, mood symptoms of stress, affectivity or depression. Anodal stimulation of the left DLPFC showed significant improvements in physical symptoms of stress in GAD patients. LIMITATIONS: Additional tDCS sessions could have resulted in larger tDCS effects. CONCLUSION: Five sessions of anodal tDCS over the DLPFC did not improve the main outcomes for GAD patients, although physical symptoms of stress were improved. The role of tDCS in GAD should be explored in larger patient samples using different parameters.

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OBJECTIVE: To assess the impact of tDCS on posture, gait and coordination of movements in subjects with cerebellar ataxia. PATIENTS AND METHODS: This is a two-phase, double blind, auto matched, pilot study. Seven people were selected to participate in the study aged from 14 to 57. tDCS and sham-tDCS were applied at different times to all participants for 40 min over five consecutive days so that they were blind to which of the two techniques was applied at any one time. The area stimulated was the bilateral motor cortex. Subjects were evaluated before and after the interventions using the Scale for Assessment and Rating of Ataxia (SARA) and specific tests to measure posture and balance were carried out using the Wii Fit platform and CvMob software. RESULTS: The study indicates a statistically significant improvement in respect of gait parameters and the total score of the SARA scale and Wii Fit platform after tDCS when compared with data obtained from sham-tDCS trials (p: 0,03). The adverse events relating to tDCS were all self-limiting and from mild to moderate intensity. CONCLUSION: Despite the small sample size, tDCS showed positive results in some motor parameters and could be considered a valuable new option for the treatment of cerebellar ataxias.

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Introduction: Rehabilitation techniques have been used to facilitate reading acquisition in dyslexia. However, many individuals continue to present academic impairment throughout life. New intervention strategies are necessary to further help this population. Objectives: Assess the impact of transcranial direct current stimulation on reading skills in children and adolescents with dyslexia. Methods: The study was conducted with one-group pretest-posttest. Participants received 2 mA transcranial direct current stimulation during 30 minutes for 5 consecutive days. Reading performance was measured by a group of tasks (identification and reading of letters, syllables, words, nonwords, and text). Results: A significant increase in the number of correct answers for nonwords and text tasks was observed after transcranial direct current stimulation (P = .035 and P = .012, respectively). Conclusion: The transcranial direct current stimulation seems to be a promising tool for the treatment of reading problems in dyslexia. Future studies are necessary to confirm the effects of transcranial direct current stimulation and to establish optimal intervention protocol in this population.

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Objective: Theta-burst stimulation (TBS) modulates synaptic plasticity more efficiently than standard repetitive transcranial magnetic stimulation delivery and may be a promising modality for neuropsychiatric disorders such as autism spectrum disorder (ASD). At present there are few effective interventions for prefrontal cortex dysfunction in ASD. We report on an open-label, pilot study of intermittent TBS (iTBS) to target executive function deficits and restricted, repetitive behaviors in male children and adolescents with ASD. Methods: Ten right-handed, male participants, aged 9-17 years with ASD were enrolled in an open-label trial of iTBS treatment. Fifteen sessions of neuronavigated iTBS at 100% motor threshold targeting the right dorsolateral prefrontal cortex were delivered over 3 weeks. Results: Parent report scores on the Repetitive Behavior Scale Revised and the Yale-Brown Obsessive Compulsive Scale demonstrated improvements with iTBS treatment. Participants demonstrated improvements in perseverative errors on the Wisconsin Card Sorting Test and total time for the Stroop test. The iTBS treatments were well tolerated with no serious adverse effects. Conclusion: These preliminary results suggest that further controlled interventional studies of iTBS for ASD are warranted.

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OBJECTIVE: To evaluate the efficacy of noninvasive brain stimulation (NIBS) on pain control in migraine patients. BACKGROUND: Recent studies have used NIBS as an abortive and prophylactic treatment for migraine; however, its efficacy regarding meaningful clinical effects remains to be critically analyzed. DESIGN: Systematic review of controlled clinical trials. METHODS: Searches were conducted in six databases: MEDLINE (via PubMed), LILACS (via BIREME), CINAHL (via EBSCO), Scopus (via EBSCO), Web of Science, and CENTRAL. Two independent authors searched for randomized controlled clinical trials published through until January 2016 that involved the use of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) in migraineurs. Studies which met the eligibility criteria were assessed and methodological quality was examined using the Cochrane tool for assessing risk of bias. Information about pain intensity (primary outcome), migraine attacks, painkiller intake, and adverse effects were extracted. RESULTS: Eight studies were included in the quantitative analysis with 153 migraine patients that received NIBS and 143 sham NIBS. In overall meta-analysis, we did not find significant results for pain intensity (SMD: -0.61; CI: -1.35 to 0.13; P = .11), for migraine attacks (SMD: -0.44; 95%; CI: -1.15 to 0.26; P = .22), and for painkiller intake (SMD: -0.57; 95% CI: -1.21 to 0.07; P = .08). However, subgroup analysis considering only tDCS effects have demonstrated a decrease for pain intensity (SMD: -0.91; 95% CI: -1.79 to -0.03; P = .04), migraine attacks (SMD: -0.75; 95% CI: -1.25 to -0.24; P = .004), and painkiller intake (SMD: -0.64; 95% CI: -1.21 to -0.07; P = .03). Subgroup analysis for TMS did not reveal significant effects for any outcome. CONCLUSION: Low or very low quality of evidence suggests that our primary outcome evaluation failed to find support for the superiority of NIBS over sham treatment. Although, subgroup analysis reveals that tDCS have moderate to high effects and could be a promising nonpharmacological alternative to pain control, mainly for painkiller intake reduction. However, there is a need for larger controlled trials with methodological rigor, which could increase the power of result inference.

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Studies investigating the possible benefits of transcranial direct current stimulation on left dorsolateral prefrontal cortex in children and adolescents with attention-deficit hyperactivity disorder (ADHD) have not been performed. This study assesses the effect of transcranial direct current stimulation in children and adolescents with ADHD on neuropsychological tests of visual attention, visual and verbal working memory, and inhibitory control. An auto-matched clinical trial was performed involving transcranial direct current stimulation in children and adolescents with ADHD, using SNAP-IV and subtests Vocabulary and Cubes of the Wechsler Intelligence Scale for Children III (WISC-III). Subjects were assessed before and after transcranial direct current stimulation sessions with the Digit Span subtest of the WISC-III, inhibitory control subtest of the NEPSY-II, Corsi cubes, and the Visual Attention Test (TAVIS-3). There were 9 individuals with ADHD according to Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria. There was statistically significant difference in some aspects of TAVIS-3 tests and the inhibitory control subtest of NEPSY-II. Transcranial direct current stimulation can be related to a more efficient processing speed, improved detection of stimuli, and improved ability to switch between an ongoing activity and a new one.

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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.

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