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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.

Inspired by recent technological advances in the gaming industry, we used capture cards to create and LIVE-stream high quality 3D-images. With this novel technique, we developed a real-life stereoscopic 3D full-body illusion paradigm (3D projection). Unlike previous versions of the full-body illusion that rely upon unwieldy head-mounted displays, this paradigm enables the unobstructed investigation of such illusions with neuroscience methods (e.g., transcranial direct current stimulation, transcranial magnetic stimulation, electroencephalography, and near-infrared spectroscopy) and examination of their neural underpinnings. This paper has three aims: (i) to provide a step-by-step guide on how to implement 3D LIVE-streaming, (ii) to explain how this can be used to create a full-body illusion paradigm; and (iii) to present evidence that documents the effectiveness of our methods (de Boer et al., 2020), including suggestions for potential applications. Particularly significant is the fact that 3D LIVE-streaming is not GPU-intensive and can easily be applied to any device or screen that can display 3D images (e.g., TV, tablet, mobile phone). Therefore, these methods also have potential future clinical and commercial benefits. 3D LIVE-streaming could be used to enhance future clinical observations or educational tools, or potentially guide medical interventions with real-time high-quality 3D images. Alternatively, our methods can be used in future rehabilitation programs to aid recovery from nervous system injury (e.g., spinal cord injury, brain damage, limb loss) or in therapies aimed at alleviating psychosis symptoms. Finally, 3D LIVE-streaming could set a new standard for immersive online gaming as well as augmenting online and mobile experiences (e.g., video chat, social sharing/events).

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.

Switching between two or more tasks is a key component in our modern world. Task switching, however, requires time-consuming executive control processes and thus produces performance costs when compared to task repetitions. While executive control during task switching has been associated with activation in the lateral prefrontal cortex (lPFC), only few studies so far have investigated the causal relation between lPFC activation and task-switching performance by modulating lPFC activation. In these studies, the results of lPFC modulation were not conclusive or limited to the left lPFC. In the present study, we aimed to investigate the effect of non-invasive transcranial direct current stimulation [tDCS; anodal tDCS (1 mA, 20 min) vs. cathodal tDCS (1 mA, 20 min) vs. sham tDCS (1 mA, 30 s)] over the right inferior frontal junction on task-switching performance in a well-established task-switching paradigm. In response times, we found a significant effect of tDCS Condition (atDCS, ctDCS vs. sham) on task-switching costs, indicating the modulation of task-switching performance by tDCS. In addition, we found a task-unspecific tDCS Condition effect in the first experimental session, in which participants were least familiar with the task, indicating a general enhancement of task performance in both task repetitions and task-switching trials. Taken together, our study provides evidence that the right lPFC is involved in task switching as well as in general task processing. Further studies are needed to investigate whether these findings can be translated into clinically relevant improvement in older subjects or populations with executive function impairment.

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.

Voluntary actions are accompanied by the experience of controlling one's own movements (sense of agency) and the feeling that the moving body part belongs to one's self (sense of body ownership). So far, agency and body ownership have been investigated separately, leaving the neural underpinnings of the relation between the two largely unexplored. The aim of this study was to explore the causal role of two multisensory brain regions, that is the premotor cortex (PMc) and the cerebellum, in agency and body ownership concurrently on the same behavioral task, i.e., the moving Rubber Hand Illusion (mRHI). Participants watched a rubber hand while moving their hidden hand. The type of movement (active or passive) and posture of the rubber hand (congruent or incongruent) differed in three conditions (active congruent, passive congruent, active incongruent), so that agency and ownership could be elicited either separately or concurrently. Agency and ownership were measured by subjective report and proprioceptive drift. Sham and anodal transcranial direct current stimulation (tDCS) were delivered to the PMc (Experiment 1) or the cerebellum (Experiment 2) prior to the mRHI task. Independent of the site or type of tDCS, subjective reports revealed that both agency and ownership were evoked in the active congruent condition, ownership but not agency in the passive congruent condition, and agency but not ownership in the active incongruent condition. The proprioceptive drift was evoked in the active congruent and the passive congruent condition. Anodal tDCS over the PMc reduced the feeling of agency in the active congruent condition, while it enhanced proprioceptive drift when applied over the cerebellum. These findings suggest a specific causal contribution of the PMc and the cerebellum to bodily self-perception during voluntary movement, with the PMc mainly involved in awareness of action and the cerebellum in proprioceptive adaptation of body position in space.

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 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

In recent years, there has been a substantial increase in the number of studies investigating the effects that transcranial direct current stimulation (tDCS) can have on exercise performance. Currently, there exists substantial conflict in the literature, with many studies reporting that 10–20 min of tDCS can result in augmented performance, while other studies also report no significant changes. Throughout the literature, there is considerable variance in the tDCS protocols being administered. These differences include electrode placement, stimulation intensity, stimulation duration, and participant’s sex. This variance may account for some of the discrepancies in the results of published studies. Therefore, the goal of this narrative review was to explore the differences in tDCS protocols among these studies to help determine which variations seem to be most effective at producing muscle strength and endurance performance increases. It is suggested that a standardized set of protocols would be beneficial in order to make the comparison of the literature more straightforward. Although, as it currently stands, more research in certain areas surrounding various tDCS variables is needed to determine the most optimal setup for increasing exercise performance.

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.

The first attempts at using electric stimulation to study human brain functions followed the experiments of Luigi Galvani and Giovanni Aldini on animal electricity during the eighteenth century. Since then, the cerebellum has been among the areas that have been studied by invasive and non-invasive forms of electrical and magnetic stimulation. During the nineteenth century, animal experiments were conducted to map the motor-related regions of cerebellar cortex by means of direct electric stimulation. As electric stimulation research on the cerebellum moved into the twentieth century, systematic research of electric cerebellar stimulation led to a better understanding of its effects and mechanism of action. In addition, the clinical potential of cerebellar stimulation in the treatment of motor diseases started to be explored. With the introduction of transcranial electric and magnetic stimulation, cerebellar research moved to non-invasive techniques. During the twenty-first century, following on groundbreaking research that linked the cerebellum to non-motor functions, non-invasive techniques have facilitated research into different aspects of cerebellar functioning. The present review provides a brief historical account of cerebellar neurostimulation and discusses current challenges and future direction in this field of research.

The main goal of this paper is to present a biomarker using Event Related Potentials (ERPs) to assess the impact of Transcranial Direct Current Stimulation (tDCS) on brain activity during an attentional task. 13 participants (6 males, mean age 24.53 ± 4.5), participated in this study. tDCS was used to stimulate Dorso Lateral Prefrontal Cortex (DLPFC) for 5 consecutive days. Immediately before and after the tDCS sessions, the participants performed an Integrated Visual and Auditory-Adult Edition (IVA-AE) task while behavioral and neurophysiological responses were measured. As a result, tDCS led to a significant improvement in reaction time and an increase in visual P600 amplitude (p

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)

Objectives Electric field modeling utilizes structural brain magnetic resonance images (MRI) to model the electric field induced by non-invasive transcranial direct current stimulation (tDCS) in a given individual. Electric field modeling is being integrated with clinical outcomes to improve understanding of inter-individual variability in tDCS effects and to optimize tDCS parameters, thereby enhancing the predictability of clinical effects. The successful integration of modeling in clinical use will primarily be driven by choice of tools and procedures implemented in computational modeling. Thus, the electric field predictions from different modeling pipelines need to be investigated to ensure the validity and reproducibility of tDCS modeling results across clinical or translational studies. Methods We used T1w structural MRI from 32 healthy volunteer subjects and modeled the electric field distribution for a fronto-temporal tDCS montage. For five different computational modeling pipelines, we quantitatively compared brain tissue segmentation and electric field predicted in whole-brain, brain tissues and target brain regions between the modeling pipelines. Results Our comparisons at various levels did not reveal any systematic trend with regards to similarity or dissimilarity of electric field predicted in brain tissues and target brain regions. The inconsistent trends in the predicted electric field indicate variation in the procedures, routines and algorithms used within and across the modeling pipelines. Conclusion Our results suggest that studies integrating electric field modeling and clinical outcomes of tDCS will highly depend upon the choice of the modeling pipelines and procedures. We propose that using these pipelines for further research and clinical applications should be subject to careful consideration, and indicate general recommendations.

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.

Context-dependent execution or inhibition of a response is an important aspect of executive control, which is impaired in neuropsychological and addiction disorders. Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) has been considered a remedial approach to address deficits in response control; however, considerable variability has been observed in tDCS effects. These variabilities might be related to contextual differences such as background visual-auditory stimuli or subjects' sex. In this study, we examined the interaction of two contextual factors, participants' sex and background acoustic stimuli, in modulating the effects of tDCS on response inhibition and execution. In a sham-controlled and cross-over (repeated-measure) design, 73 participants (37 females) performed a Stop-Signal Task in different background acoustic conditions before and after tDCS (anodal or sham) was applied over the DLPFC. Participants had to execute a speeded response in Go trials but inhibit their response in Stop trials. Participants' sex was fully counterbalanced across all experimental conditions (acoustic and tDCS). We found significant practice-related learning that appeared as changes in indices of response inhibition (stop-signal reaction time and percentage of successful inhibition) and action execution (response time and percentage correct). The tDCS and acoustic stimuli interactively influenced practice-related changes in response inhibition and these effects were uniformly seen in both males and females. However, the effects of tDCS on response execution (percentage of correct responses) were sex-dependent in that practice-related changes diminished in females but heightened in males. Our findings indicate that participants' sex influenced the effects of tDCS on the execution, but not inhibition, of responses., Highlights In a fully counterbalanced (for sex and all experimental conditions), sham-controlled cross-over study, we examined the effects of tDCS over the left DLPFC in the context of Stop-Signal task.The effects of tDCS on response inhibition was uniform across both males and females.The effects of tDCS on response execution differed in males and females.The tDCS mainly modulated the practice-related (learning-related) changes in participants’ performance, but these effects of tDCS were different between males and females.These findings highlight the need to adequately control for participants' sex and the need to develop sex-specific tDCS protocols in clinical settings.

Effective anticipation skills in sporting cognition have been shown to facilitate expertise in sports. Transcranial direct current stimulation (tDCS) has shown to improve motor and cognitive functioning. Therefore, this study aimed to determine the assistive effects of tDCS on the action observer network in both novice and expert gamers during an occlusion task, as well as the related electroencephalographic spectral power response. Twenty-three novice and 23 expert video gamers received either sham or active tDCS with a right parietal anode and left frontal cathode. Only experts demonstrated a significant improvement in predicting ball direction for the overall and early occlusions after tDCS. Spectral power results revealed significant changes in theta, high-gamma, and delta frequencies. The findings indicate that tDCS was able to modulate anticipatory behavior and cortical activity in experts compared with novice participants, suggesting a facilitatory role for tDCS to improve anticipatory effects and assist as a neurocognitive training technique.

To evaluate the effects of transcranial direct current stimulation on pain and other symptoms of knee osteoarthritis.We performed a single-blind randomized sham-controlled trial with two parallel arms in an outpatient clinic of physical medicine and rehabilitation at a teaching hospital. We randomized 54 patients, 30-70 years of age, with knee osteoarthritis into two groups. They had morning stiffness ≤ 30 min, knee pain ≥ 3 months, joint crepitus, and Kellgren-Lawrence grade 1 or 2 on radiographs. For the active stimulation we administered 2 mA current, 20 min for each session and for the sham group 30 s stimulation and 20 min no current. Using the 10/20 International EEG system, the anode was fixed over the contralateral primary motor cortex (C3 or C4), and the cathode was placed on the ipsilateral supraorbital region (Fp1 or Fp2), with respect to the included knee. The program was repeated once daily over 5 consecutive days. Both groups received acetaminophen. We assessed the patients before and after the interventions, and three months post-intervention. The primary outcome was knee pain on the visual analog scale, and the secondary outcome was the Knee injury and Osteoarthritis Outcome Score.There was a statistically significant reduction in the intensity of pain within sham and active groups (both p 0.001), but no significant difference between the groups (p = 0.226). Analyses of the Knee injury and Osteoarthritis Outcome Scores showed no clinically important changes.Transcranial direct current stimulation does not reduce knee pain, does not abate other symptoms, and does not restore knee function in patients with knee osteoarthritis. The pain reduction in our study could be attributed to either placebo or the acetaminophen effect.

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.

Recent theories suggest that self-consciousness, in its most elementary form, is functionally disconnected from the phenomenal body. Patients with psychosis frequently misattribute their thoughts and actions to external sources; and in certain out-of-body experiences, lucid states, and dreams body-ownership is absent but self-identification is preserved. To explain these unusual experiences, we hypothesized that self-identification depends on inferring self-location at the right angular gyrus (i.e. perspective-taking). This process relates to the discrimination of self-produced signals (endogenous attention) from environmental stimulation (exogenous attention). Therefore, when this mechanism fails, this causes altered sensations and perceptions. We combined a Full-body Illusion paradigm with brain stimulation (HD-tDCS) and found a clear causal association between right angular gyrus activation and alterations in self-location (perspective-taking). Anodal versus sham HD-tDCS resulted in: a more profound out-of-body shift (with reduced sense of agency); and a weakened ability to discriminate self from other perspectives. We conclude that self-identification is mediated in the brain by inferring self-location (i.e. perspective-taking). Self-identification can be decoupled from the bodily self, explaining phenomena associated with disembodiment. These findings present novel insights into the relationship between mind and body, and may offer important future directions for treating psychosis symptoms and rehabilitation programs to aid in the recovery from a nervous system injury. The brain’s ability to locate itself might be the key mechanism for self-identification and distinguishing self from other signals (i.e. perspective-taking)., SCOPUS: ar.j, info:eu-repo/semantics/published

During the past decade, it became clear that the electric field elicited by non-invasive brain stimulation (NIBS) techniques such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are substantially influenced by variations in individual head and brain anatomy. In addition to structural variations in the healthy, several psychiatric disorders are characterized by anatomical alterations that are likely to further constrain the intracerebral effects of NIBS. Here, we present high-resolution realistic head models derived from structural magnetic resonance imaging data of 19 healthy adults and 19 patients diagnosed with major depressive disorder (MDD). By using a freely available software package for modelling the electric fields induced by different NIBS protocols, we show that our head models are well-suited for assessing inter-individual and between-group variability in the magnitude and focality of tDCS-induced electric fields for two protocols targeting the left dorsolateral prefrontal cortex.

BackgroundOscillatory rhythms during sleep such as slow oscillations (SO) and spindles, and most importantly their coupling, are thought to underlie processes of memory consolidation. External slow oscillatory transcranial direct current stimulation (so-tDCS) with a frequency of 0.75 Hz has been shown to improve this coupling and memory consolidation, however, effects varied quite markedly between individuals, studies, and species. Here, we aimed to determine how precisely the frequency of stimulation has to match the naturally occurring SO frequency in individuals to optimally improve SO-spindle coupling. Moreover, we systematically tested stimulation durations necessary to induce changes.MethodsWe addressed these questions by comparing so-tDCS with individualized frequency to standardized frequency of 0.75 Hz in a within-subject design with 28 older participants during napping while systematically varying stimulation train durations between 30 s, 2 min, and 5 min.ResultsStimulation trains as short as 30 s were sufficient to modulate the coupling between SOs and spindle activity. Contrary to our expectations, so-tDCS with standardized frequency indicated stronger aftereffects with regard to SO-spindle coupling compared to individualized frequency. Angle and variance of spindle maxima occurrence during the SO cycle were similarly modulated.ConclusionIn sum, short stimulation trains were sufficient to induce significant changes in sleep physiology allowing for more trains of stimulation, which provides methodological advantages and possibly even larger behavioral effects in future studies. With regard to individualized stimulation frequency, further options of optimization need to be investigated, such as closed-loop stimulation to calibrate stimulation frequency to the SO frequency at time of stimulation onset.Significance statementApplication of slow oscillatory transcranial direct current stimulation during sleep has been shown to enhance specific memory-relevant sleep parameters and memory performance after sleep, albeit with a high degree of variability. Here, we systematically explored two major stimulation parameters possibly accounting for this variability in humans: frequency and duration of stimulation. We found, contrary to our expectations, standardized frequency stimulation with 0.75 Hz being superior to individualized frequency stimulation in enhancing specific sleep parameters. Moreover short stimulation trains of 30 seconds were as effective as 5 min in modulating aftereffects. These are encouraging findings, implying methodological advantages as larger quantity of aftereffects data can be obtained within the same time window, which may also lead to enhanced behavioral stimulation effects.

Evidence-based therapeutic options for children with developmental coordination disorder (DCD) are scarce. This work explored the effects of cerebellar anodal transcranial direct current stimulation (atDCS) on three 48 h-apart motor sequence learning and upper limb coordination sessions in children with DCD. The results revealed that, as compared to a Sham intervention (n = 10), cerebellar atDCS (n = 10) did not meaningfully improve execution speed but tended to reduce the number of execution errors during motor sequence learning. However, cerebellar atDCS did neither meaningfully influence offline learning nor upper limb coordination, suggesting that atDCS’ effects are circumscribed to its application duration. These results suggest that cerebellar atDCS could have beneficial effects as a complementary therapeutic tool for children with DCD.

Many cognitive functions, including working memory, are processed within large-scale brain networks. We targeted the right frontoparietal network (FPN) with one session of transcranial direct current stimulation (tDCS) in an attempt to modulate the cognitive speed of a visual working memory task (WMT) in 27 young healthy subjects using a double-blind crossover design. We further explored the neural underpinnings of induced changes by performing resting-state fMRI prior to and immediately after each stimulation session with the main focus on the interaction between a task-positive FPN and a task-negative default mode network (DMN). Twenty minutes of 2 mA anodal tDCS was superior to sham stimulation in terms of cognitive speed manipulation of a subtask with processing of objects and tools in unconventional views (i.e., the higher cognitive load subtask of the offline WMT). This result was linked to the magnitude of resting-state functional connectivity decreases between the stimulated FPN seed and DMN seeds. We provide the first evidence for the action reappraisal mechanism of object and tool processing. Modulation of cognitive speed of the task by tDCS was reflected by FPN-DMN cross-talk changes.

There is evidence for dissociable, causal roles for two key social brain regions in young adults. Specifically, the right temporoparietal junction (rTPJ) is associated with embodied perspective taking, whereas the dorsomedial prefrontal cortex (dmPFC) is associated with the integration of social information. However, it is unknown whether these causal brain-behaviour associations are evident in older adults. Fifty-two healthy older adults were stratified to receive either rTPJ or dmPFC anodal high-definition transcranial direct current stimulation in a sham-controlled, double-blinded, repeated-measures design. Self-other processing was assessed across implicit and explicit level one (line-of-sight) and level two (embodied rotation) visual perspective taking (VPT) tasks, and self-other encoding effects on episodic memory. Both rTPJ and dmPFC stimulation reduced the influence of the alternate perspective during level one VPT, indexed by a reduced congruency effect (difference between congruent and incongruent perspectives). There were no stimulation effects on level two perspective taking nor self-other encoding effects on episodic memory. Stimulation to the rTPJ and dmPFC improved perspective selection during level one perspective taking. However, dissociable effects on self-other processing, previously observed in young adults, were not identified in older adults. The results provide causal evidence for age-related changes in social brain function that requires further scrutinization. Supplementary Information The online version contains supplementary material available at 10.3758/s13415-021-00929-2.

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.