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Introduction: The persistence of post-detoxification problems in drug addiction is one of the disadvantages of the ultra-rapid opioid detoxification (UROD) method. Transcranial direct current stimulation (tDCS) has been introduced in experimental addiction treatment for some years. Results of pilot studies suggest that it might be a promising method for addiction treatment. This study explores the adjunctive application of tDCS during treating opiate addiction with the UROD approach. Methods: This double-blind, sham-controlled clinical trial was carried out on patients with substance abuse admitted to the Bahman Clinic of Yazd City in Iran (from March to September 2014). Forty participants were randomly allocated to treatment and control groups. Two sessions of tDCS (real or sham) over dorsolateral prefrontal cortices (DLPFC) were applied, accompanied by UROD. Withdrawal symptoms and craving were assessed by the drug desire questionnaire and objective opiate withdrawal scale before UROD and for the 24-hour interval after. Results: Transcranial direct current stimulation optimized the opiate addiction treatment through craving and withdrawal syndrome alleviation. Conclusion: The study results indicate that prefrontal tDCS may promote the efficacy of the UROD method in opioid addiction.

Independent gait following stroke is ultimate goal of rehabilitation. Non-invasive neuromodulation achieving it has never been reported. A 74-year-old woman suffered from subarachnoid haemorrhage, followed by hydrocephalus. Both were treated successfully. Even 1 year after the ictus, ambulation was difficult due to truncal instability with lateropulsion mainly to the left side. Transcranial direct current stimulation (tDCS) was applied to the parietal area (2mA for 20 min/day; anode on left side, cathode on right) for 16 days. The intervention improved her truncal instability and she achieved independent gait. tDCS of the parietal area could be a novel treatment option for gait disturbance due to postural instability following stroke.

OBJECTIVE To synthesize and critically appraise literature exploring patient perceptions regarding the therapeutic use of noninvasive brain stimulation. MATERIAL AND METHODS A systematic search of CINHAL, PUBMED, Web of Science, and Medline was performed. Reference lists of relevant articles were also screened. Studies exploring participant perceptions regarding the therapeutic use of noninvasive brain stimulation were eligible for inclusion. Perceptions were divided into three domains: knowledge, experience, and attitudes. Noninvasive brain stimulation was defined as any neuromodulation technique that alters brain activity but does not require invasive methods such as surgery. No restrictions were placed upon study design or participant population. Two reviewers performed data extraction and risk of bias assessment. Data relating to methodological characteristics, participant demographics, type of noninvasive brain stimulation, and nature of perceptions (knowledge, experience, or attitudes) were extracted. RESULTS Four studies comprising data from 163 participants met the inclusion criteria. All studies investigated perceptions of repetitive transcranial magnetic stimulation (rTMS) in psychiatric populations. Most participants perceived rTMS to be safe and beneficial, demonstrated low-levels of fear, and were willing to recommend the intervention to others. No studies were found investigating patient perception of transcranial direct current stimulation (tDCS). CONCLUSION The findings from this review suggest that rTMS is well accepted as a therapeutic treatment among psychiatric populations, providing support for its clinical utility. Future work is needed to determine if similar findings exist for other conditions (e.g., chronic pain) and for other therapeutic forms of brain stimulation (e.g., tDCS).

Transcranial direct current stimulation (tDCS) is a possible neurotherapeutic alternative to psychostimulants in Attention-Deficit/Hyperactivity Disorder (ADHD). However, very little is known regarding the mechanisms of action of tDCS in children and adolescents with ADHD. We conducted the first multi-session, sham-controlled study of anodal tDCS over right inferior frontal cortex (rIFC), a consistently under-functioning region in ADHD, combined with cognitive training (CT) in 50 children/adolescents with ADHD. This study investigated the underlying mechanisms of action on resting and Go/No-Go Task-based QEEG measures in a subgroup of 23 participants with ADHD (n, sham=10; anodal tDCS=13). We found no significant sham versus anodal tDCS group differences in QEEG spectral power during rest and Go/No-Go Task performance, no correlation between the QEEG and Go/No-Go Task performance, and no effect on clinical and cognitive outcome measures. These findings extend the null clinical or cognitive effects in our whole sample of 50 children/adolescents with ADHD. Our findings do not indicate multi-session anodal tDCS with CT over rIFC as a treatment for children/adolescents with ADHD. Larger RCTs should explore different protocols titrated to the individual and using comprehensive measures to assess cognitive, clinical, and neural effects of tDCS and its underlying mechanisms of action in ADHD.

Introduction The observed variability in the effects of transcranial direct current stimulation (tDCS) is influenced by the amount of current reaching the targeted region-of-interest (ROI). Age and sex might affect current density at target ROI due to their impact on cortical anatomy. The present tDCS simulation study investigates the effects of cortical anatomical parameters (volumes, dimension, and torque) on simulated tDCS current density in healthy young, middle-aged, and older males and females. Methodology Individualized head models from 240 subjects (120 males, 18–87 years of age) were used to identify the estimated current density (2 mA current intensity, 25 cm2 electrode) from two simulated tDCS montages (CP5_CZ and F3_FP2) targeting the inferior parietal lobule (IPL) and middle frontal gyrus (MFG), respectively. Cortical parameters including segmented brain volumes (cerebrospinal fluid [CSF], grey and white matter), cerebral-dimensions ( length / width & length / height ) and brain-torque (front and back shift, petalia, and bending) were measured using the magnetic resonance images (MRIs) from each subject. The present study estimated sex differences in current density at these target ROIs mediated by these cortical parameters within each age group. Results For both tDCS montages, females in the older age group received higher current density than their male counterparts at the target ROIs. No sex differences were observed in the middle-aged group. Males in the younger age group had a higher current density than females, only for the parietal montage. Across all age groups, CSF, and grey matter volumes significantly predicted the current intensity estimated at the target sites. In the older age group only, brain-torque was a significant mediator of the sex difference. Conclusions Our findings demonstrate the presence of sex differences in the simulated tDCS current density, however this pattern differed across age groups and stimulation locations. Future studies should consider influence of age and sex on individual cortical anatomy and tailor tDCS stimulation parameters accordingly.

Transcranial direct current stimulation (tDCS) has been widely used to modulate cognition and behavior. However, only a few studies have been probing the brain mechanism underlying the effects of tDCS on cognitive processing, especially throughout electrophysiological markers, such as the P3. This meta-analysis assessed the effects of tDCS in P3 amplitude and latency during an oddball, n-back, and Go/No-Go tasks, as well as during emotional processing. A total of 36 studies were identified, but only 23 were included in the quantitative analysis. The results show that the parietal P3 amplitude increased during oddball and n-back tasks, mostly after anodal stimulation over the left dorsolateral prefrontal cortex (p = 0.018, SMD = 0.4) and right inferior frontal gyrus (p

BACKGROUND: Studies have shown that impairments in the ventromedial prefrontal cortex play a crucial role in violent behavior in forensic patients who also abuse cocaine and alcohol. Moreover, interventions that aimed to reduce violence risk in those patients are found not to be optimal. A promising intervention might be to modulate the ventromedial prefrontal cortex by high-definition (HD) transcranial direct current stimulation (tDCS). The current study aimed to examine HD-tDCS as an intervention to increase empathic abilities and reduce violent behavior in forensic substance dependent offenders. In addition, using electroencephalography, we examined the effects on the P3 and the late positive potential of the event-related potentials in reaction to situations that depict victims of aggression.METHODS: Fifty male forensic patients with a substance dependence were tested in a double-blind, placebo-controlled randomized study. The patients received HD-tDCS 2 times a day for 20 minutes for 5 consecutive days. Before and after the intervention, the patients completed self-reports and performed the Point Subtraction Aggression Paradigm, and electroencephalography was recorded while patients performed an empathy task.RESULTS: Results showed a decrease in aggressive responses on the Point Subtraction Aggression Paradigm and in self-reported reactive aggression in the active tDCS group. Additionally, we found a general increase in late positive potential amplitude after active tDCS. No effects on trait empathy and the P3 were found.CONCLUSIONS: Current findings are the first to find positive effects of HD-tDCS in reducing aggression and modulating electrophysiological responses in forensic patients, showing the potential of using tDCS as an intervention to reduce aggression in forensic mental health care.

A wide body of literature suggests that transcranial direct current stimulation (tDCS) administered over the prefrontal cortex can improve executive function – including decision-making and inhibitory control – in healthy young adults. However, the effects of tDCS in older adults are largely unknown. Here, using a double-blind, sham-controlled approach, changes in a combined perceptual decision-making and inhibitory control task were assessed before and after the application of tDCS (1 mA, 20 minute) targeting the right inferior frontal gyrus (rIFG) or pre-supplementary motor area (preSMA) in 42 young (18–34 years) and 41 older (60–80 years) healthy adults. Compared to sham stimulation, anodal tDCS over the preSMA improved decision-making speed for both age groups. Furthermore, the inhibitory control performance of older and younger adults was improved by preSMA and rIFG stimulation, respectively. This study provides evidence that tDCS can improve both perceptual decision-making and inhibitory control in healthy older adults, with the causal role of the preSMA and rIFG regions in cognitive control appearing to vary as a function of healthy ageing.

Introduction Transcranial direct current stimulation (tDCS) modulates cortical activity and potentiates functional gains achieved during therapeutic protocols. The aim of Integrative Speech Therapy Protocol is to rehabilitate speech in patients with impairments regarding neuropyschomotor development by combining oral motor stimuli, specific articulatory production, and the stimulation of phonological aspects of language. Objective Investigate the effect of transcranial direct current stimulation combined to integrative speech therapy in a child with cerebral palsy. Methods We performed a case study with tDCS and speech therapy in a patient with cerebral palsy and apraxia of speech. To assess the patient's speech, we used a parameterized test for the Brazilian Portuguese speech - ABFW. The CFCS and Vicking Speech Scales presented level IV and III, respectively. The patient underwent two periods with ten stimulation sessions each: first with anodal stimulation over Broca's area; and second over the left dorsolateral prefrontal cortex. Two indices were calculated: the percentage of consonants correct; and percentage of consonants correct-revised. Descriptive statistics were employed for the clinical data. For the outcomes, changes in each score were calculated as the difference in pre-intervention and post-intervention using Wilcoxon-Mann-Whitney test. Results Increases were found in percentage of correct consonants indices as well as to produce two-syllable and three-syllable words after both types of stimulation, characterized mainly by correct vowels that marked the presence of the syllable. Number of phonemes increased 0 to 4 at first the stimulation and 4 to 10 at the second. Conclusion The combined-therapy program contributed to improve the speech rehabilitation results in a patient with cerebral palsy.

BACKGROUND: The ability to manipulate the upper limbs and fingers of stroke patients is very important for independent daily life. Among the latest approaches for upper limb rehabilitation training, transcranial direct current stimulation (tDCS) is a non-invasive stimulation method that stimulates the cranial nerves by attaching electrodes to the scalp. In addition, virtual reality (VR) is an intervention method that provides an environment similar to reality and can help restore function by performing body movements as if playing a game. In addition, VR is an intervention method that provides an environment similar to reality and helps to recover functions by performing body movements as if playing a game. OBJECTIVE: This study was conducted to investigate the effect of anodal tDCS applied to the ipsilateral primary motor cortex (M1) during VR training on the upper limb function, cognition, and executive function of stroke patients. METHODS: After 20 patients were randomly assigned to the experimental group and the control group, the experimental group received tDCS and VR, and the control group received sham tDCS and VR for 20 minutes a day, 5 days a week, for a total of 4 weeks. Participants were evaluated for upper limb function using Box and Block Test (BBT) and Jebsen-Taylor Hand Function Test (JTHFT), and cognitive and executive function using the Stroop Test (ST) and Trail Making Test (TMT). RESULTS: In the experimental group, significant differences were found in the pre- and post-test for the all variance (p< 0.05). Control group is significant differences were found in the pre- and post-test for BBT, ST, TMT (p< 0.05). There were significant differences between the two groups in the post test of BBT and ST (p< 0.05). CONCLUSION: The results of this study suggest that anodal tDCS applied to the ipsilateral M1 during VR training is effective for upper limb function, cognitive function, and executive function in stroke patients.

The aim of this study was to evaluate the effects of transcranial direct current stimulation (tDCS) on anxiety-like behavior and neural parameters in rats with chronic pain exposed to alcohol. Thirty-six adult male Wistar rats were randomly assigned to control (CT), neuropathic pain (NP), NPtDCS, NP + alcohol (NPAL), or NPALtDCS groups, subjected to sciatic nerve chronic constriction injury (CCI) and exposed to alcohol (20% v/v solution, 4 g/kg) or vehicle by gavage for 15 days. Afterward, rats were treated using bimodal tDCS (0.5 mA/20 min/8 days) and tested in the open field. Rats were killed 24 h after the last behavioral assessment, and brain and spinal cord tissue samples were collected and processed for NPY immunohistochemistry, expression of Il1a and Il1b in the spinal cord, cerebellum, and hippocampus, and levels of IL-1α and IL-1β in the same brain structures and the striatum. tDCS reverted the anxiety-like behavior induced by CCI and alcohol, and the increased expression of Il1a in the spinal cord induced by alcohol, which increased the expression of Il1b in the cerebellum. In addition, tDCS modulated the hypothalamic NPY-immunoreactivity, increased the levels of IL-1α in the hippocampus (like NP and AL), and increased the expression of Il1b in the spinal cord (like AL). Thus, this study shows that tDCS changes NP and alcohol-induced anxiety-like behavior, possibly through its central modulatory effect of NPY and spinal cord expression of Il1a and Il1b, being considered a treatment option for alcohol and NP-induced anxiety symptoms.

Purpose of review Chronic pain is debilitating and difficult to treat with pharmacotherapeutics alone. Consequently, exploring alternative treatment methods for chronic pain is essential. Noninvasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are increasingly being investigated for their neuropharmacological effects in the treatment of chronic pain. This review aims to examine and evaluate the present state of evidence regarding the use of tDCS and TMS in the treatment of chronic pain. Recent findings Despite conflicting evidence in the early literature, evidence from recent rigorous research supports the use of tDCS and TMS in treating chronic pain conditions. For both tDCS and TMS, standardized stimulation parameters have been identified with the recommendation for repeated maintenance stimulation to ensure that the analgesic effect is sustained beyond discontinuation of therapy. Summary Due to a lack of defined stimulation protocols, early findings on the efficacy of tDCS and TMS are mixed. Although the application of tDCS and TMS as pain relief approaches is still in its early stages, the introduction of standardized stimulation protocols is paving the way for more robust and informed research.

BACKGROUND: Parkinson’s disease (PD) is a progressive neurodegenerative disorder, characterized by cardinal motor symptoms in addition to cognitive impairment. New insights concerning multisite non-invasive brain stimulation effects have been gained, which can now be used to develop innovative treatment approaches. OBJECTIVE: Map the researchs involving multisite non-invasive brain stimulation in PD, synthesize the available evidence and discuss future directions. METHODS: The databases PubMed, PsycINFO, CINAHL, LILACS and The Cochrane Library were searched from inception until April 2020, without restrictions on the date of publication or the language in which it was published. The reviewers worked in pairs and sequentially evaluated the titles, abstracts and then the full text of all publications identified as potentially relevant. RESULTS: Twelve articles met the inclusion criteria. The target brain regions included mainly the combination of a motor and a frontal area, such as stimulation of the primary motor córtex associated with the dorsolateral prefrontal cortex. Most of the trials showed that this modality was only more effective for the motor component, or for the cognitive and/or non-motor, separately. CONCLUSIONS: Despite the results being encouraging for the use of the multisite aproach, the indication for PD management should be carried out with caution and deserves scientific deepening.

This is the second chapter of the series on the use of clinical neurophysiology for the study of movement disorders. It focusses on methods that can be used to probe neural circuits in brain and spinal cord. These include use of spinal and supraspinal reflexes to probe the integrity of transmission in specific pathways; transcranial methods of brain stimulation such as transcranial magnetic stimulation and transcranial direct current stimulation, which activate or modulate (respectively) the activity of populations of central neurones; EEG methods, both in conjunction with brain stimulation or with behavioural measures that record the activity of populations of central neurones; and pure behavioural measures that allow us to build conceptual models of motor control. The methods are discussed mainly in relation to work on healthy individuals. Later chapters will focus specifically on changes caused by pathology.

BackgroundAmblyopia is the interocular visual acuity difference of two lines or more with the best correction in both eyes. It is treated with ocular occlusion therapy, but its success depends on neuroplasticity, and thus is effective in children but not adults. Transcranial Direct Current Stimulation (tDCS) is suggested to increase neuroplasticity.ObjectiveTo determine if combined intervention of bilateral tDCS and ocular occlusion improves visual function in adults with amblyopia.MethodsA double-blind randomized, controlled pilot trial was conducted in 10 volunteers with amblyopia. While applying ocular occlusion and performing a reading task, participants received bilateral tDCS (n= 5) or sham stimulation (n= 5), with the anodal tDCS electrode in the contralateral visual cortex and the cathodal in the ipsilateral visual cortex in relation to the amblyopic eye. Visual function (through visual acuity, stereopsis, and contrast sensitivity tests) and visual evoked potential (with checkerboard pattern stimuli presentation) were evaluated immediately after.ResultsA total of 30 min after treatment with bilateral tDCS, visual acuity improved by 0.16 (± 0.025) LogMAR in the treatment group compared with no improvement (–0.02 ± 0.02) in five controls (p= 0.0079), along with a significant increase in the amplitude of visual evoked potentials of the amblyopic eye response (p= 0.0286). No significant changes were observed in stereopsis and contrast sensitivity. No volunteer reported any harm derived from the intervention.ConclusionOur study is the first to combine anodal and cathodal tDCS for the treatment of amblyopia, showing transient improved visual acuity in amblyopic adults.

Background: Unihemispheric concurrent dual-site anodal transcranial direct current stimulation (a-tDCSUHCDS) of the primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) are introduced as effective techniques on M1 corticospinal excitability enhancement and its after-effects. Objectives: The current study aimed at investigating the potential effects of multiple sessions of a-tDCSUHCDS of M1-DLPFC on motor skills learning in healthy individuals. Methods: The randomized, clinical trial was conducted on a total of 37 volunteers completed all sessions of the study and were randomly divided into two groups of a-tDCSUHCDS and sham stimulation by the block randomization method. The current study was performed from January to May 2017 in Iran. Participants attended daily 20-minute motor training sessions for three consecutive days, while they concurrently received a-tDCS. Motor skills were assessed before the intervention (day 1), immediately after the intervention (day 3), and one week after the completion of the intervention. Results: A total of 37 participants were included in the data analysis. Immediately after the completion of the intervention on day 3, mean skills in the experimental and control groups were 0.33 and 0.30, respectively. One week after the completion of the intervention, mean skills in the experimental and control groups were 0.36 and 0.29, respectively. The trend of motor learning considerably increased in the experimental (0.17; P < 0.001) and control (0.11; P < 0.001) groups. No significant difference was observed in motor learning immediately after the intervention between the groups (P = 0.23), while there was a significant difference in long-term offline learning between the groups (P = 0.04). Conclusions: Greater motor skills in the a-tDCSUHCDS group compared with the sham tDCS group at one-week retention indicated the robustness of the a-tDCSUHCDS effect.

Objective: Transcranial direct current stimulation (tDCS) and mindfulness practices have been proposed as a potential approach to improve executive functions (EFs) and reduce craving in persons with substance use disorders. Based on the neural mechanisms of action of each of these interventions, the combination of both non-pharmacological interventions might have additive effects. In the current study, the effects of tDCS combined with mindfulness-based substance abuse treatment (MBSAT) to improve EFs and reduce craving were investigated in early abstinent methamphetamine abuse. Methods: Eighty (youths aged between 18 and 21) early-abstinent methamphetamine users were randomly assigned to the research groups (tDCS group [n = 20], mindfulness group [n = 20], combined mindfulness-tDCS group [n = 20], and sham group [n = 20]). Active tDCS (1.5 mA,20 min, 12 sessions) or sham tDCS was appliedover the left dorsolateral prefrontal cortex and the MBSAT protocol was used over twelve 50-min sessions. Results: Both in the post-test phase (immediately after the intervention) and follow-up phase (one month after the intervention), performance in most EFs tasks significantly improved in the combination group which received real tDCS ＋ MBSAT, as compared to baseline values and sham stimulation group. Similarly, a significant reduction in craving was observed after intervention inall treatment groups, but not the sham stimulation group. Interestingly, the increase in EFs and the reduction in craving post versus pre tDCS ＋ MBSAT intervention were correlated. Conclusion: Findings from the current study provide initial support for the clinical effectiveness of combination tDCS ＋ MBSAT, possibly influencing cognitive/affective processes.

Background and purpose Multiple sclerosis (MS) is a chronic inflammatory disease causing a wide range of symptoms including motor and cognitive impairment, fatigue and pain. Over the last two decades, non-invasive brain stimulation, especially transcranial direct current stimulation (tDCS), has increasingly been used to modulate brain function in various physiological and pathological conditions. However, its experimental applications for people with MS were noted only as recently as 2010 and have been growing since then. The efficacy for use in people with MS remains questionable with the results of existing studies being largely conflicting. Hence, the aim of this review is to paint a picture of the current state of tDCS in MS research grounded on studies applying tDCS that have been done to date. Methods A keyword search was performed to retrieve articles from the earliest article identified until 14 February 2021 using a combination of the groups (1) ‘multiple sclerosis’, ‘MS’ and ‘encephalomyelitis’ and (2) ‘tDCS’ and ‘transcranial direct current stimulation’. Results The analysis of the 30 articles included in this review underlined inconsistent effects of tDCS on the motor symptoms of MS based on small sample sizes. However, tDCS showed promising benefits in ameliorating fatigue, pain and cognitive symptoms. Conclusion Transcranial direct current stimulation is attractive as a non-drug approach in ameliorating MS symptoms, where other treatment options remain limited. The development of protocols tailored to the individual's own neuroanatomy using high definition tDCS and the introduction of network mapping in the experimental designs might help to overcome the variability between studies.

Background: Alcohol dependence is a significant public health problem, contributing to the global health burden. Due to its immense socio-economic burden, various psychosocial, psychological, and pharmacological approaches have attempted to alter the behaviour of the patient misusing or abusing alcohol, but their efficacy is modest at best. Therefore, there is a search for newer treatment approaches, including non-invasive brain stimulation in the management of alcohol dependence. We plan to study the efficacy of Prefrontal Cortex Transcranial direct current stimulation Treatment in Alcohol dependence syndrome (PreCoTTA). Methods: Two hundred twenty-five male patients with alcohol dependence syndrome will be randomized into the three study arms (2 active, left dorsolateral prefrontal cortex and left orbitofrontal cortex, and 1 sham) to receive a total of 14 tDCS sessions (10 continuous and 4 booster sessions). Data will be collected from these sessions at five different time points on clinical, neuropsychological and biochemical parameters. In addition, 225 healthy age and education matched controls will be administered the neuropsychological test battery at baseline for comparison with the patient group. Discussion: The proposed study aims to explore the use of non-invasive brain stimulation; tDCS as a treatment alternative. We also aim to overcome the methodological gaps of limited sample sizes, fewer tDCS intervention sessions, lack of long-term follow-ups to measure the sustainability of gains, and lack of comprehensive measures to track changes in functioning and abstinence after tDCS intervention. The main outcomes include clinical (reduction in cue-induced craving, time to first drink, and QFI); neuropsychological (risk-taking, impulsivity, and other neuropsychological domains), and biochemical markers (BDNF, leptin and adiponectin). The findings of the study will have translational value as they may help to improve the clinician’s ability to effectively manage craving in patients with alcohol dependence syndrome. Furthermore, we will have a better understanding of the neuropsychological and biochemical effects of non-invasive brain stimulation techniques which are of interest in the comprehensive treatment of addiction disorders. Trial registration: The study has been registered with the Clinical Trials Registry-India (CTRI/ 2020/09/027582) on September 03rd 2020.

Transcranial direct current stimulation (tDCS) is a form of novel brain stimulating method that has attracted interest owing to its relative inexpensiveness and ease of administration. It has been evaluated in many studies for its effectiveness in improving cognitive symptoms in Alzheimer's disease (AD). However, our understanding regarding its efficacy and the most effective way of administering tDCS (in terms of lead placement to achieve response and prevent harmful consequences) is still evolving. The current meta-analysis was conducted to resolve the above issues. A search using appropriate keywords and medical subject headings was conducted on PubMed, Scopus and DOAJ database. Studies were analysed on pre-defined inclusion and exclusion criteria. Finally 11 studies were included for quantitative analysis from 1,021 obtained from initial search. All the studies included were methodologically of high quality, though an asymmetrical funnel plot raised the possibility of publication bias. tDCS was found to significantly improve the scores on cognition as compared to sham. Anodal tDCS was found to be significantly beneficial in this regards, whereas cathodal and dual stimulation were not. There were no significant difference in the number of drop-outs and adverse reaction in tDCS and sham group. The quality of evidence that we have reviewed in this study is robust. tDCS, particularly anodal tDCS is an effective treatment modality in AD. It is well tolerated in patients with AD. However, further studies are warranted to probe the role of tDCS in other domains of AD.

Background Dorsal root ganglion (DRG) stimulation, an invasive method of neuromodulation, and transcranial direct current stimulation (tDCS), a non-invasive method of altering cortical excitability, have both proven effective in relieving chronic pain. Objective We employed a randomized, sham-controlled crossover study design to investigate whether single-session tDCS would have an additive therapeutic effect alongside DRG stimulation (DRGS) in the treatment of chronic pain. Methods Sixteen neuropathic pain patients who were previously implanted with DRG stimulators were recruited. Baseline pain scores were established with DRGS-OFF. Pain scores were then recorded with DRGS-ON, after paired sham tDCS stimulation, and after paired active anodal tDCS (a-tDCS) stimulation. For active tDCS, patients were randomized to ‘MEG (magnetoencephalography) localized’ tDCS or contralateral motor cortex (M1) tDCS for 30 min. EEG recordings and evaluations of tDCS adverse effects were also collected. Results All participants reported the interventions to be tolerable with no significant adverse effects during the session. Paired DRGS/active tDCS resulted in a significant reduction in pain scores compared to paired DRGS-ON/sham tDCS or DRGS alone. There was no difference in the additive effect of M1 vs. MEG-localized tDCS. Significant augmentation of beta activity was observed between DRGS-OFF and DRGS-ON conditions, as well as between paired DRGS-ON/sham tDCS and paired DRGS-ON/active tDCS. Conclusion Our results indicate that a single session of tDCS alongside DRGS is safe and can significantly reduce pain acutely in neuropathic pain patients. Paired invasive/non-invasive neuromodulation is a promising new treatment strategy for pain management and should be evaluated further to assess long-term benefits.

BACKGROUND Functional movement disorder (FMD), a conversion disorder characterized by involuntary movements, is difficult to treat. METHODS We aimed to assess the effects of anodal transcranial direct current stimulation (tDCS) and yoga in FMD patients (n=5). TDCS of the right temporoparietal junction, a brain region relevant in the sense of self-agency, was conducted. Subjects underwent both sham and anodal tDCS with a washout period of 3 weeks. Yoga was used as a mode of exercise, as well as in conjunction with stimulation to sustain potential changes in neural plasticity. RESULTS A total of 5 subjects completed the study [mean age: 52 (SE: 4) y, disease duration: 5 (SE: 1.6) y], undergoing both sham and anodal tDCS. Anodal tDCS does not appear to be superior to sham tDCS in alleviating symptoms and disability, but combining tDCS and yoga appears to lead to mild improvement noted on clinical observation, based on the change in the efficacy index of Clinical Global Impression found in 4 subjects. CONCLUSION Our study results suggest that anodal tDCS is not superior to sham tDCS in alleviating subjective symptoms and disability in FMD. However, interpretation of these results is limited due to the small number of stimulation sessions and number of subjects. Future studies using more frequent stimulation sessions are needed to further determine whether anodal tDCS may have a therapeutic effect in this patient group compared with sham tDCS.

Introduction: Transcranial direct current stimulation (tDCS) has been studied as an adjunctive treatment option for substance use disorders (SUDs). Alterations in brain structure following SUD may change tDCS-induced electric field (EF) and subsequent responses. However, group-level differences between healthy controls (HC) and participants with SUDs in terms of EF and its association with cortical architecture have not yet been modeled quantitatively. Objective: We provided a methodology for group-level analysis of computational head models (CHMs) to investigate the influence of cortical morphology metrics on EFs. Method: Whole-brain surface-based morphology was conducted and cortical thickness, volume, and surface area were compared between participants with CUD (n=20) and age-matched HC (n=22). We also simulated EFs for bilateral tDCS over DLPFC. Effects of structural alterations on EF distribution were investigated based on individualized CHMs. Results: In terms of EF, no significant difference was found within the prefrontal cortex. However, EFs were significantly different in left-postcentral and right-superior temporal gyrus (P < 0.05) with higher level of variance in CUD compared to HC (F39,43=5.31,P

Although Charcot characterized classic cerebellar symptoms in people with multiple sclerosis (PwMS) in 1877, the impact of cerebellar dysfunction on MS symptoms has predominately been evaluated in the last two decades. Recent studies have clearly demonstrated the association between cerebellar pathology, including atrophy and reduced fractional anisotropy in the peduncles, and motor impairments, such as reduced gait velocity and time to complete walking tasks. However, future studies using novel imaging techniques are needed to elucidate all potential pathophysiology that is associated with disability in PwMS. Additionally, future studies are required to determine the most effective treatments for motor impairments in PwMS, including the specific type and duration of exercise interventions, and potential means to amplify their effects, such as transcranial direct current stimulation (tDCS). This mini-review critically discusses the distinct role of cerebellar dysfunction in motor impairments in PwMS, potential treatments, and directions for future studies.

Background After a stroke, 80% of the chronic patients have difficulties to use their paretic upper limb (UL) in activities of daily life (ADL) even after rehabilitation. Virtual reality therapy (VRT) and anodal transcranial direct current stimulation (tDCS) are two innovative methods that have shown independently to positively impact functional recovery of the paretic UL when combined with conventional therapy. The objective of the project will be to evaluate the impact of adding anodal high-definition (HD)-tDCS during an intensive 3-week UL VRT and conventional therapy program on paretic UL function in chronic stroke. Methods The ReArm project is a quadruple-blinded, randomized, sham-controlled, bi-centre, two-arm parallel, and interventional study design. Fifty-eight chronic (> 3 months) stroke patients will be recruited from the Montpellier and Nimes University Hospitals. Patients will follow a standard 3-week in-patient rehabilitation program, which includes 13 days of VRT (Armeo Spring, 1 × 30 min session/day) and conventional therapy (3 × 30 min sessions/day). Twenty-nine patients will receive real stimulation (4x1 anodal HD-tDCS montage, 2 mA, 20 min) to the ipsilesional primary motor cortex during the VRT session and the other 29 patients will receive active sham stimulation (2 mA, 30 s). All outcome measures will be assessed at baseline, at the end of rehabilitation and again 3 months later. The primary outcome measure will be the wolf motor function test. Secondary outcomes will include measures of UL function (Box and Block Test), impairment (Fugl Meyer Upper Extremity), compensation (Proximal Arm Non-Use), ADL (Actimetry, Barthel Index). Other/exploratory outcomes will include pain, fatigue, effort and performance, kinematics, and motor cortical region activation during functional motor tasks. Discussion This will be the first trial to determine the impact of adding HD-tDCS during UL VRT and conventional therapy in chronic stroke patients. We hypothesize that improvements in UL function will be greater and longer-lasting with real stimulation than in those receiving sham. Trial registration The ReArm project was approved by The French Research Ethics Committee, (Comité de Protection des Personnes-CPP SUD-EST II, N°ID-RCB: 2019-A00506-51, http://www.cppsudest2.fr/). The ReArm project was registered on ClinicalTrials.gov (NCT04291573, 2nd March 2020.

Objective: Evaluate the effect of transcranial direct current stimulation (tDCS) combined with reading therapy on the performance of reading tasks in a serie of cases of children and adolescents with developmental dyslexia (DD). Method: (IRB/UNIFESP number:1281/2017). Four dyslexic students (two children and two adolescents) were evaluated with regards to rate and accuracy of reading fluency on three occasions: pre-intervention as well as one and six months after intervention. The intervention consisted of five consecutive sessions of active tDCS (1 mA for 20 minutes), followed by a two-day interval and another five sessions of tDCS combined with cognitive skills stimulation of phonological processing and decoding of words. Anodal tDCS was administered over the left parieto-occipital cortex, with the cathode placed over contralateral deltoid muscle. Each session was preceded by execution of semantic-lexical and phonological evocation tasks. Data were analyzed using Friedman test and JT method for analysis of clinical significance and the reliable change index. Results: Improvements were found in text reading rate and accuracy and word accuracy at the one-month and six-month evaluation. A significant increase was found in correct reading of words and pseudowords six months after intervention. Most of the improvements were reliable, with clinical significance in some cases. Conclusion: Transcranial direct current stimulation combined with a reading stimulation program proved effective at improving reading skills in these participants.

Objectives Previous work has shown effects of transcranial direct current stimulation (tDCS) on clinical pain measures, qualitative sensory testing measures, and peripheral inflammation. The present report extends this research to investigate the effect of tDCS on brain-derived neurotrophic factor (BDNF) levels. Materials and methods This secondary analysis examined a sample of 40 older adults (50 to 70 y old) with symptomatic knee osteoarthritis randomly assigned in a 1:1 fashion to active (n=20) or sham (n=20) tDCS for 20 minutes on 5 consecutive days. BDNF was measured before the first session and after the final treatment session. Generalized linear modeling evaluated BDNF plasma levels as a function of tDCS group, adjusted for baseline. Bayesian statistical inference was used to quantify the probability that effects of the treatment exist. Results Generalized linear modeling indicated a 90.4% posterior probability that the sham condition had 49.9% higher BDNF at the end of treatment, controlling for baseline. Follow-up analyses within the active TDCS group supported an association between change in BDNF and change in clinical pain, and exploratory analyses found an effect of tDCS on irisin. Discussion Results indicated that tDCS could be a potential nonpharmacological treatment to decrease BDNF levels, which may in turn decrease pain. This study adds to a growing literature suggesting that tDCS affects cortical excitability, and consequentially, the neural circuits implicated in pain modulation. In addition to a direct connection to analgesia, BDNF changes may reflect tDCS-induced changes in different cortical areas and/or neural circuits.

Neuromodulation has gained attention as a potential non-pharmacological intervention for mild cognitive impairment (MCI). However, no studies have directly compared the effects of transcranial alternating current stimulation (tACS) with transcranial direct current stimulation (tDCS) on MCI patients. We aimed to identify the more promising and efficient therapeutic option between tACS and tDCS for cognitive enhancement in MCI patients. We compared the effects of gamma-tACS with tDCS on cognitive function and electroencephalography (EEG) in MCI patients. In this sham-controlled, double-blinded, repeated-measures study with the order of the stimulation counterbalanced across patients (n = 20), both gamma-tACS (40 H z) and tDCS were administered at the same intensity (2 mA) in the dorsolateral prefrontal cortex for 30 min. Cognitive tests (Stroop and Trail-Making-Test [TMT]) and EEG were performed before and after single-session stimulation. Gamma-tACS improved the Stroop-color in comparison with tDCS (p = .044) and sham (p = .010) and enhanced the TMT-B in comparison with sham (p = .021). However, tDCS was not significantly different from sham in changes of any cognitive test scores. In EEG analysis, gamma-tACS increased beta activity in comparison with sham and tDCS, whereas tDCS decreased delta and theta activity in comparison with sham. Gamma-tACS also increased beta 2 source activity in the anterior cingulate, compared to sham. The cognitive benefits of tACS in MCI patients appeared superior to those of tDCS. tACS facilitated cognitive function by increasing beta activity, while tDCS delayed the progression of MCI symptoms by decreasing slow-frequency activity. Thus, tACS could be used as a new therapeutic option for MCI.

Cognitive deficits and negative symptoms in schizophrenia are associated with poor functional outcomes and limited in terms of treatment. The Schizophrenia Treatment With Electric Transcranial Stimulation (STARTS) trial has shown efficacy of transcranial direct current stimulation (tDCS) for improving negative symptoms. In this secondary analysis, we investigate its effects on cognitive performance. In STARTS, a double-blinded, sham-controlled, randomized clinical trial, patients were treated with twice-daily, 20-min, 2-mA fronto-temporal tDCS over 5 days or sham-tDCS. In 90 patients, we evaluated the cognitive performance up to 12 weeks post-treatment. We found that active-tDCS showed no beneficial effects over sham-tDCS in any of the tests. Based on a 5-factor cognitive model, improvements of executive functions and delayed memory were observed in favor of sham-tDCS. Overall, the applied active-tDCS protocol, primarily designed to improve negative symptoms, did not promote cognitive improvement. We discuss possible protocol modification potentially required to increase tDCS effects on cognition. ClinicalTrials.gov identifier: NCT02535676

Background Transcranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation whose potential as a cognitive therapy is hindered by our limited understanding of how participant and experimental factors influence its effects. Using functional MRI to study brain networks, we have previously shown in healthy controls that the physiological effects of tDCS are strongly influenced by brain state. We have additionally shown, in both healthy and traumatic brain injury (TBI) populations, that the behavioral effects of tDCS are positively correlated with white matter (WM) structure. Objectives In this study we investigate how these two factors, WM structure and brain state, interact to shape the effect of tDCS on brain network activity. Methods We applied anodal, cathodal and sham tDCS to the right inferior frontal gyrus (rIFG) of healthy (n = 22) and TBI participants (n = 34). We used the Choice Reaction Task (CRT) performance to manipulate brain state during tDCS. We acquired simultaneous fMRI to assess activity of cognitive brain networks and used Fractional Anisotropy (FA) as a measure of WM structure. Results We find that the effects of tDCS on brain network activity in TBI participants are highly dependent on brain state, replicating findings from our previous healthy control study in a separate, patient cohort. We then show that WM structure further modulates the brain-state dependent effects of tDCS on brain network activity. These effects are not unidirectional - in the absence of task with anodal and cathodal tDCS, FA is positively correlated with brain activity in several regions of the default mode network. Conversely, with cathodal tDCS during CRT performance, FA is negatively correlated with brain activity in a salience network region. Conclusions Our results show that experimental and participant factors interact to have unexpected effects on brain network activity, and that these effects are not fully predictable by studying the factors in isolation., Highlights • We replicated the brain state and polarity dependent effects of tDCS. • White matter structure influences tDCS's state-dependent changes in neural activity • The parameters of tDCS may operate under a hierarchy of influence.

Prior neuroimaging and neurophysiological studies have found that the right posterior parietal cortex (PPC) plays an important role in mental rotation ability. Transcranial direct-current stimulation (tDCS) has been shown the potential to enhance cognitive ability by delivering a low current to the brain cortex of interest, via electrodes on the scalp. Here, we tested whether stimulating the PPC with tDCS can improve three-dimensional mental rotation performance and narrow gender difference. The classic three-dimensional Shepard-Metzler task was measured after three stimulation conditions (right PPC, left PPC, sham stimulation). The results indicated that stimulating the right PPC induced an improvement in accuracy and response time of mental rotation relative to sham stimulation. Stimulating the left PPC caused an enhancement in the accuracy but not in the response time. Gender difference during mental rotation was diminished after stimulation. These findings indicated that the PPC regions played a causal role in mental rotation ability. tDCS could be used as a promising non-invasive method to improve mental rotation skills in individuals with lower ability and to provide an effective therapeutic tool for neurological disorder rehabilitation.

Background Many studies have shown effects of anodal transcranial direct current stimulation (a-tDCS) and high-frequency transcranial random noise stimulation (tRNS) on elevating cortical excitability. Moreover, tRNS with a direct current (DC)-offset is more likely to lead to increases in cortical excitability than solely tRNS. While a-tDCS over primary motor cortex (M1) has been shown to attenuate pain perception, tRNS + DC-offset may prove as an effective means for pain relief. Objective This study aimed to examine effects of a-tDCS and high-frequency tRNS + DC-offset over M1 on pain expectation and perception, and assess whether these effects could be influenced by the certainty of pain expectation. Methods Using a double-blinded and sham-controlled design, 150 healthy participants were recruited to receive a single-session a-tDCS, high-frequency tRNS + DC-offset, or sham stimulation over M1. The expectation and perception of electrical stimulation in certain and uncertain contexts were assessed at baseline, immediately after, and 30 min after stimulation. Results Compared with sham stimulation, a-tDCS induced immediate analgesic effects that were greater when the stimulation outcome was expected with uncertainty; tRNS induced immediate and sustained analgesic effects that were mediated by decreasing pain expectation. Nevertheless, we found no strong evidence for tRNS being more effective for attenuating pain than a-tDCS. Conclusions The analgesic effects of a-tDCS and tRNS showed different temporal courses, which could be related to the more sustained effectiveness of high-frequency tRNS + DC-offset in elevating cortical excitability. Moreover, expectations of pain intensity should be taken into consideration to maximize the benefits of neuromodulation.

Objective Many studies have examined the effectiveness of transcranial direct current stimulation (tDCS) on human pain perception in both healthy populations and pain patients. Nevertheless, studies have yielded conflicting results, likely due to differences in stimulation parameters, experimental paradigms, and outcome measures. Human experimental pain models that utilize indices of pain in response to well-controlled noxious stimuli can avoid many confounds present in clinical data. This study aimed to assess the robustness of tDCS effects on experimental pain perception among healthy populations. Methods We conducted three meta-analyses that analyzed tDCS effects on ratings of perceived pain intensity to suprathreshold noxious stimuli, pain threshold and tolerance. Results The meta-analyses showed a statically significant tDCS effect on attenuating pain-intensity ratings to suprathreshold noxious stimuli. In contrast, tDCS effects on pain threshold and pain tolerance were statistically non-significant. Moderator analysis further suggested that stimulation parameters (active electrode size and current density) and experimental pain modality moderated the effectiveness of tDCS in attenuating pain-intensity ratings. Conclusion The effectiveness of tDCS on attenuating experimental pain perception depends on both stimulation parameters of tDCS and the modality of experimental pain. Significance This study provides some theoretical basis for the application of tDCS in pain management.

Background: In recent years, it is reported that non-invasive brain stimulation [including transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS)] could improve lower limb function in patients after stroke. However, some studies showed no effect. In the present study, we aimed to make a meta-analysis to assess effect of non-invasive brain stimulation on lower limb function in patients after stroke. Methods: Studies exploring the effect of tDCS or rTMS on lower limb function in patients after stroke were searched on the PubMed, Web of Science, EMBASE, Medline, Google Scholar before March 2021. Meta-analysis was made to summarize results of these studies. Results: The present study showed significantly better walking speed, mobility and muscle strength increase effect in tDCS group compared to sham tDCS group [walking speed: standard mean difference (SMD) = 1.14, 95% CI = 0.48 to 1.80, I2 = 74.0%, p value for Q test < 0.001; mobility: SMD = 0.79, 95% CI = 0.21 to 1.36, I2 = 53.8%, p value for Q test = 0.043; muscle strength: SMD = 2.79, 95% CI = 0.61 to 4.98, I2 = 93.9%, p value for Q test < 0.001]. In addition, meta-analysis showed significantly better walking speed, balance and motor function increase effect in rTMS group compared to sham rTMS group [walking speed: SMD = 3.31, 95% CI = 1.38 to 5.24, I2 = 92.1%, p value for Q test < 0.001; balance: SMD = 3.54, 95% CI = 1.45 to 5.63, I2 = 95.4%, p value for Q test < 0.001; motor function: SMD = 1.65, 95% CI = 0.53 to 2.76, I2 = 90.3%, p value for Q test < 0.001]. Conclusions: This meta-analysis suggested that non-invasive brain stimulation improved lower limb function in patients after stroke. More large scale, blinded RCTs were necessary to confirm the effect of rTMS and tDCS on lower limb function in patients after stroke.

Background\ud \ud Although non-invasive central and peripheral stimulations are accruing support as promising treatments in different neurological conditions, their effects on dysarthria have not been systematically investigated.\ud \ud \ud \ud Objective\ud \ud The purpose of this review was to examine the evidence base of non-invasive stimulation for treating dysarthria, identify which stimulation parameters have the most potential for treatment and determine safety risks.\ud \ud \ud \ud Methods\ud \ud A systematic review with meta-analysis, when possible, involving publications indexed in MEDLINE, PsychINFO, EMBASE CINHAL the Linguistics and Language Behavioral Abstracts, Web of Science, Cochrane Register of Control Trials and 2 trial registries was completed. Articles were searched in December 2018 and updated in June 2021 using keywords related to brain and electrical stimulation, dysarthria and research design. We included trials with randomised, cross-over or quasi-experimental designs; involving a control group; and investigating treatment of neurogenic dysarthria with non-invasive stimulation. Methodological quality was determined with the Cochrane's Risk of Bias-2 tool.\ud \ud \ud \ud Results\ud \ud In total, 6186 studies were identified; 10 studies (6 randomised controlled trials and 4 cross-over studies) fulfilled the inclusion criteria. All 10 trials (268 adults with Parkinson's disease, stroke and neurodegenerative cerebellar ataxia) focused on brain stimulation (6 repetitive transcranial magnetic stimulation; 3 transcranial direct current stimulation; and 1 repetitive transorbital alternating current stimulation). Adjunct speech-language therapy was delivered in 2 trials. Most trials reported one or more positive effects of stimulation on dysarthria-related features; however, given the overall high risk of bias and heterogeneity in participant, trial and outcome measurement characteristics, no conclusions can be drawn. Post-treatment size effects for 2 stroke trials demonstrated no statistically significant differences between active and sham stimulation across 3 dysarthria outcomes.\ud \ud \ud \ud Conclusions\ud \ud Evidence for use of non-invasive brain stimulation in treating dysarthria remains inconclusive. Research trials that provide reliable and replicable findings are required.

BACKGROUND Exposed-based psychotherapy is a mainstay of treatment for obsessive-compulsive disorder (OCD) and anxious psychopathology. The medial prefrontal cortex (mPFC) and the default mode network (DMN), which is anchored by the mPFC, promote safety learning. Neuromodulation targeting the mPFC might augment therapeutic safety learning and enhance response to exposure-based therapies. METHODS To characterize the effects of mPFC neuromodulation on functional connectivity, 17 community volunteers completed resting-state functional magnetic resonance imaging scans before and after 20 min of frontopolar anodal multifocal transcranial direct current stimulation (tDCS). To examine the effects of tDCS on therapeutic safety learning, 24 patients with OCD completed a pilot randomized clinical trial; they were randomly assigned (double-blind, 50:50) to receive active or sham frontopolar tDCS before completing an in vivo exposure and response prevention (ERP) challenge. Changes in subjective emotional distress during the ERP challenge were used to index therapeutic safety learning. RESULTS In community volunteers, frontal pole functional connectivity with the middle and superior frontal gyri increased, while connectivity with the anterior insula and basal ganglia decreased (ps

Background Treatments of freezing of gait (FOG) in Parkinson's disease are suboptimal. Objective The aim of this study was to evaluate the effects of multiple sessions of transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex and primary motor cortex (M1) on FOG. Methods Seventy-seven individuals with Parkinson's disease and FOG were enrolled in a double-blinded randomized trial. tDCS and sham interventions comprised 10 sessions over 2 weeks followed by five once-weekly sessions. FOG-provoking test performance (primary outcome), functional outcomes, and self-reported FOG severity were assessed. Results Primary analyses demonstrated no advantage for tDCS in the FOG-provoking test. In secondary analyses, tDCS, compared with sham, decreased self-reported FOG severity and increased daily living step counts. Among individuals with mild-to-moderate FOG severity, tDCS improved FOG-provoking test time and self-report of FOG. Conclusions Multisession tDCS targeting the left dorsolateral prefrontal cortex and M1 did not improve laboratory-based FOG-provoking test performance. Improvements observed in participants with mild-to-moderate FOG severity warrant further investigation. © 2021 International Parkinson and Movement Disorder Society.

Background and aims- Nicotine is a highly addictive substance in tobacco products that dysregulates several neurotransmitters in the brain and impairs executive function. Non-invasive brain stimulation (NIBS) methods such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are promising treatments for nicotine dependence. We investigated the efficacy and acceptability of NIBS in managing smoking cessation through a systematic review and network meta-analysis (NMA). Methods- We conducted a systematic review to identify randomized controlled trials (RCTs) that investigated the efficacy of NIBS for smoking cessation. All pairwise meta-analyses and NMA procedures were conducted using random-effects and frequentist models. The co-primary outcomes were (1) the change in number of cigarettes smoked per day (change in frequency of smoking) in patients with nicotine dependence after NIBS and (2) acceptability (the dropout rate). The effect sizes for co-primary outcomes of change in frequency of smoking and acceptability were assessed according to standardized mean difference (SMD) and odds ratio, respectively. Results- Twelve RCTs with 710 participants (mean age: 44.2 years, 31.2% female) were included. Compared with the sham control, 10-Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) was associated with the largest changes in smoking frequency [SMD = −1.22, 95% confidence interval (95% CI) = −1.77 to −0.66]. The 2-mA bifrontal tDCS (SMD = −0.97, 95% CI = −1.32 to −0.62) and 10-Hz deep rTMS over the bilateral DLPFC with cue provocation (SMD = −0.77, 95% CI = −1.20 to −0.34) were associated with a significantly larger decrease in smoking frequency versus the sham. None of the investigated NIBSs was associated with dropout rates significantly different from those of the sham control groups. Conclusion- Prefrontal non-invasive brain stimulation interventions appear to reduce the number of cigarettes smoked with good acceptability.

Background: Occipital strokes often cause permanent homonymous hemianopia leading to significant disability. In previous studies, non-invasive electrical brain stimulation (NIBS) has improved vision after optic nerve damage and in combination with training after stroke. Objective: We explored different NIBS modalities for rehabilitation of hemianopia after chronic stroke. Methods: In a randomized, double-blinded, sham-controlled, three-armed trial, altogether 56 patients with homonymous hemianopia were recruited. The three experiments were: i) repetitive transorbital alternating current stimulation (rtACS, n = 8) vs. rtACS with prior cathodal transcranial direct current stimulation over the intact visual cortex (tDCS/rtACS, n = 8) vs. sham (n = 8); ii) rtACS (n = 9) vs. sham (n = 9); and iii) tDCS of the visual cortex (n = 7) vs. sham (n = 7). Visual functions were evaluated before and after the intervention, and after eight weeks follow-up. The primary outcome was change in visual field assessed by high-resolution and standard perimetries. The individual modalities were compared within each experimental arm. Results: Primary outcomes in Experiments 1 and 2 were negative. Only significant between-group change was observed in Experiment 3, where tDCS increased visual field of the contralesional eye compared to sham. tDCS/rtACS improved dynamic vision, reading, and visual field of the contralesional eye, but was not superior to other groups. rtACS alone increased foveal sensitivity, but was otherwise ineffective. All trial-related procedures were tolerated well. Conclusions: This exploratory trial showed safety but no main effect of NIBS on vision restoration after stroke. However, tDCS and combined tDCS/rtACS induced improvements in visually guided performance that need to be confirmed in larger-sample trials. NCT01418820 (clinicaltrials.gov)

Objective To systematically review how patient characteristics and/or transcranial direct current stimulation (tDCS) parameters influence tDCS effectiveness in respect to upper limb function post-stroke. Methods Three electronic databases were searched for sham-controlled randomised trials using the Fugl-Meyer Assessment for upper extremity as outcome measure. A meta-analysis and nine subgroup-analyses were performed to identify which tDCS parameters yielded the greatest impact on upper limb function recovery in stroke patients. Results Eighteen high-quality studies (507 patients) were included. tDCS applied in a chronic stage yields greater results than tDCS applied in a (sub)acute stage. Additionally, patients with low baseline upper limb impairments seem to benefit more from tDCS than those with high baseline impairments. Regarding tDCS configuration, all stimulation types led to a significant improvement, but only tDCS applied during therapy, and not before therapy, yielded significant results. A positive dose–response relationship was identified for current/charge density and stimulation duration, but not for number of sessions. Conclusion Our results demonstrate that tDCS improves upper limb function post-stroke. However, its effectiveness depends on numerous factors. Especially chronic stroke patients improved, which is promising as they are typically least amenable to recovery. Significance The current work highlights the importance of several patient-related and protocol-related factors regarding tDCS effectiveness.

Chronic low back pain (CLBP) is highly disabling, but often without identifiable source. Focus has been on impaired anti-nociceptive mechanisms contributing to pain maintenance, though methods of targeting this impairment remain limited. This randomised-controlled cross-over pilot trial used active versus sham medial prefrontal cortex (mPFC) high-definition transcranial direct current stimulation (HD-tDCS) for 3-consecutive days to improve descending pain inhibitory function. Twelve CLBP patients were included with an average visual analogue scale (VAS) pain intensity of 3.0 ± 1.5 and pain duration of 5.3 ± 2.6 years. Pressure pain thresholds (PPTs), conditioned pain modulation (CPM), and temporal summation of pain (TSP) assessed by cuff algometry, as well as pain symptomatology (intensity, unpleasantness, quality, disability) and related psychological features (pain catastrophizing, anxiety, affect), were assessed on Day1 before 3 consecutive days of HD-tDCS sessions (each 20 minutes), at 24-hours (Day 4) and 2-weeks (Day 21) following final HD-tDCS. Blinding was successful. No significant differences in psychophysical (PPT, CPM, TSP), symptomatology or psychological outcomes were observed between active and sham HD-tDCS on Day4 and Day21. CPM-effects at Day 1 negatively correlated with change in CPM-effect at Day4 following active HD-tDCS (P = .002). Lack of efficacy was attributed to several factors, not least that patients did not display impaired CPM at baseline. Trial registration: : ClinicalTrials.gov (NCT03864822). Perspective: Medial prefrontal HD-tDCS did not alter pain, psychological nor psychophysical outcomes, though correlational analysis suggested response may depend on baseline pain inhibitory efficacy, with best potential effects in patients with severe impairments in descending pain inhibitory mechanisms. Future work should focus on appropriate patient selection and optimising stimulation targeting.

Freezing of gait (FOG) is a common motor symptom in Parkinson's disease (PD). Although FOG reduces quality of life, affects mobility and increases the risk of falls, there are little to no effective treatments to alleviate FOG. Non-invasive brain stimulation (NIBS) has recently yielded attention as a potential treatment to reduce FOG symptoms however, stimulation parameters and protocols remain inconsistent and require further research. Specifically, targets for stimulation require careful review. Thus, with current neuroimaging and neuro-electrophysiological evidence, we consider potential cortical targets thought to be involved in the pathophysiology of FOG according to the Interference model, and within reach of NIBS. We note that the primary motor cortex, the supplementary motor area and the dorsolateral prefrontal cortex have already drawn attention as NIBS targets for FOG, but based on neuroimaging evidence the premotor cortex, the medial prefrontal cortex, the cerebellum, and more particularly, the posterior parietal cortex should be considered as potential regions for stimulation. We also discuss different methodological considerations, such as stimulation type, medication state, and hemisphere to target, and future perspectives for NIBS protocols in FOG.

The purpose of this study was to investigate the therapeutic effects of transcranial direct current stimulation on swallowing function in poststroke patients.We searched for potentially eligible randomized controlled trials from electronic databases, including the PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Periodical (VIP) databases, from their inception to January 15, 2021. All statistical analyses were performed using RevMan 5.4, and the standardized mean difference with 95% confidence intervals was estimated for the swallowing function outcomes and to understand the mean effect size.Ten studies involving 343 participants were included in this meta-analysis. The overall analyses demonstrated a significant effect size for swallowing function. Subgroup analyses suggested that both acute and chronic stroke patients showed significant effects on swallowing function after transcranial direct current stimulation. Furthermore, compared with sham stimulation, transcranial direct current stimulation anodal to the affected, unaffected, and bilateral hemispheres can produce a significant effect size for swallowing function in stroke patients.This meta-analysis showed that transcranial direct current stimulation is likely to be effective for the recovery of dysphagia in poststroke patients, in the acute or chronic phase, and that the effect of anodal transcranial direct current stimulation to unaffected hemispheres is larger.

The brain has the innate ability to undergo neuronal plasticity, which refers to changes in its structure and functions in response to continued changes in the environment. Although these concepts are well established in animal slice preparation models, their application to a large number of human subjects could only be achieved using noninvasive brain stimulation (NIBS) techniques. In this review, we discuss the mechanisms of plasticity induction using NIBS techniques including transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), random noise stimulation (RNS), transcranial ultrasound stimulation (TUS), vagus nerve stimulation (VNS), and galvanic vestibular stimulation (GVS). We briefly introduce these techniques, explain the stimulation parameters and potential clinical implications. Although their mechanisms are different, all these NIBS techniques can be used to induce plasticity at the systems level, to examine the neurophysiology of brain circuits and have potential therapeutic use in psychiatric and neurological disorders. TMS is the most established technique for the treatment of brain disorders, and repetitive TMS is an approved treatment for medication-resistant depression. Although the data on the clinical utility of the other modes of stimulation are more limited, the electrical stimulation techniques (tDCS, tACS, RNS, VNS, GVS) have the advantage of lower cost, portability, applicability at home, and can readily be combined with training or rehabilitation. Further research is needed to expand the clinical utility of NIBS and test the combination of different modes of NIBS to optimize neuromodulation induced clinical benefits.

The causal mechanisms and treatment for the negative symptoms and cognitive dysfunction in schizophrenia are the main issues attracting the attention of psychiatrists over the last decade. The first part of this review summarizes the pathogenesis of schizophrenia, especially the negative symptoms and cognitive dysfunction from the perspectives of genetics and epigenetics. The second part describes the novel medications and several advanced physical therapies (e.g., transcranial magnetic stimulation and transcranial direct current stimulation) for the negative symptoms and cognitive dysfunction that will optimize the therapeutic strategy for patients with schizophrenia in future.

Background The ubiquitous vascular response to transcranial electrical stimulation (tES) has been attributed to the secondary effect of neuronal activity forming the classic neurovascular coupling. However, the current density delivered transcranially concentrates in: A) the cerebrospinal fluid of subarachnoid space where cerebral vasculature resides after reaching the dural and pial surfaces and B) across the blood-brain-barrier after reaching the brain parenchyma. Therefore, it is anticipated that tES has a primary vascular influence. Objectives Focused review of studies that demonstrated the direct vascular response to electrical stimulation and studies demonstrating evidence for tES-induced vascular effect in coupled neurovascular systems. Results tES induces both primary and secondary vascular phenomena originating from four cellular elements; the first two mediating a primary vascular phenomenon mainly in the form of an immediate vasodilatory response and the latter two leading to secondary vascular effects and as parts of classic neurovascular coupling: 1) The perivascular nerves of more superficially located dural and pial arteries and medium-sized arterioles with multilayered smooth muscle cells; and 2) The endothelial lining of all vessels including microvasculature of blood-brain barrier; 3) Astrocytes; and 4) Neurons of neurovascular units. Conclusion A primary vascular effect of tES is highly suggested based on various preclinical and clinical studies. We explain how the nature of vascular response can depend on vessel anatomy (size) and physiology and be controlled by stimulation waveform. Further studies are warranted to investigate the mechanisms underlying the vascular response and its contribution to neural activity in both healthy brain and pathological conditions – recognizing many brain diseases are associated with alteration of cerebral hemodynamics and decoupling of neurovascular units.

Background Transcranial direct current stimulation (tDCS) is a promising nonpharmacological intervention for treating depression. We aimed to provide an updated meta-analysis assessing the anti-depressant efficacy of tDCS. Methods We searched the literature from the first available date to 30 December 2020 to identify relevant randomized controlled trials (RCTs). Results 27 RCTs (N = 1204 patients, 653 in active tDCS and 551 in sham tDCS) were included. Active tDCS was superior to sham tDCS (g = 0.46, 95 % CI 0.15−0.76) in modulating depressive symptoms measured by depression rating scales. Active tDCS was also superior to sham tDCS in reducing response and remission rates, but these differences did not reach statistically significant levels (ORresponse = 1.75, 95 % CI 0.85–3.58; ORremission = 1.29, 95 % CI 0.59–2.83). The two groups had comparable dropout rates (OR = 1.28, 95 % CI 0.62–1.64). Conclusion For treatments of depressive episodes, tDCS may be efficacious. Specific tDCS parameters (e.g., a 2-mA stimulation current and 30-min sessions) and clinical characteristics (e.g., antidepressant-free) may augment the treatment efficacy of tDCS.

Background Transcranial direct current stimulation (tDCS) provides a noninvasive polarity-specific constant current to treat epilepsy, through a mechanism possibly involving excitability modulation and neural oscillation. Objective To determine whether EEG oscillations underlie the interictal spike changes after tDCS in rats with chronic spontaneous seizures. Methods Rats with kainic acid-induced spontaneous seizures were subjected to cathodal tDCS or sham stimulation for 5 consecutive days. Video-EEG recordings were collected immediately pre- and post-stimulation and for the subsequent 2 weeks following stimulation. The acute pre-post stimulation and subacute follow-up changes of interictal spikes and EEG oscillations in tDCS-treated rats were compared with sham. Ictal EEG with seizure behaviors, hippocampal brain-derived neurotrophic factor (BDNF) protein expression, and mossy fiber sprouting were compared between tDCS and sham rats. Results Interictal spike counts were reduced immediately following tDCS with augmented delta and diminished beta and gamma oscillations compared with sham. Cathodal tDCS also enhanced delta oscillations in normal rats. However, increased numbers of interictal spikes with a decrease of delta and theta oscillations were observed in tDCS-treated rats compared with sham during the following 2 weeks after stimulation. Resuming tDCS suppressed the increase of interictal spike activity. In tDCS rats, hippocampal BDNF protein expression was decreased while mossy fiber sprouting did not change compared with sham. Conclusions The inverse relationship between the changes of delta oscillation and interictal spikes during tDCS on and off stimulation periods indicates that an enhanced endogenous delta oscillation underlies the tDCS inhibitory effect on epileptic excitability.