Effect of repeated sessions of transcranial direct current stimulation on subjective and objective measures of recovery and performance in soccer players following a soccer match simulation.

We investigated the effect of repeated sessions of anodal transcranial direct current stimulation (a-tDCS) on subjective and objective measures of recovery, cognitive and sport-specific performance in professional soccer players following a soccer match simulation (SMS). Sixteen soccer players participated in this randomized, crossover, and sham-controlled study. They completed baseline assessments of well-being, total quality recovery (TQR), electromyographic activity (EMG) of the thigh muscles, countermovement jump (CMJ), and cognitive and Loughborough soccer passing test (LSPT) skills. Then, the participants engaged in an SMS routine (2 × 45 min, 15-min intervals). There was no significant difference in rating of perceived exertion (RPE) during the SMS in the anodal (17.25 ± 0.85) and sham (16.93 ± 0.92) conditions (p = 0.19). Following the SMS, the participants were randomized to receive three sessions of a-tDCS (2 mA, 20 min, +F3/-F4) targeting the left dorsolateral prefrontal cortex (DLPFC) or sham immediately after, 24 h, and 48 h after the SMS. Finally, the same outcome measures were evaluated 24 and 48 h following the SMS. A two-way repeated-measures ANOVA showed that a-tDCS stimulation improved passing skills (decreased time to perform the LSPT and number of errors; all ps < 0.01; d = 0.56-2.9) and increased the feeling of well-being (p = 0.02; d = 2.8), with no effect on TQR, cognitive performance, CMJ performance, and EMG. Therefore, the results of the present study indicate, for the first time, that repeated a-tDCS could be used as an adjunct method to accelerate soccer players' well-being and technical performance recovery, particularly after congested matches and/or training sessions. These findings may also be applicable to other team sports with characteristics similar to soccer (e.g., futsal, handball, basketball, etc.).

Application of Transcranial Direct and Alternating Current Stimulation (tDCS and tACS) on Major Depressive Disorder.

The exploration of brain stimulation methods offers a promising avenue to overcome the shortcomings of traditional drug therapies and psychological treatments for major depressive disorder (MDD). Over the past years, there has been an increasing focus on transcranial electrical stimulation (tES), notably for its ease of use and potentially fewer side effects. This chapter delves into the use of transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), which are key components of tES, in managing depression. It begins by introducing tDCS and tACS, summarizing their action mechanisms. Following this introduction, the chapter provides an in-depth analysis of existing meta-analyses, systematic reviews, clinical studies, and case reports that have applied tES in MDD treatment. It also considers the role of tES in personalized medicine by looking at specific patient groups and evaluating research on possible biomarkers that could predict how patients with MDD respond to tES therapy.

Repeated prefrontal tDCS for improving mental health and cognitive deficits in multiple sclerosis: a randomized, double-blind, parallel-group study.

BACKGROUND: Multiple Sclerosis (MS) is an autoimmune disease associated with physical disability, psychological impairment, and cognitive dysfunctions. Consequently, the disease burden is substantial, and treatment choices are limited. In this randomized, double-blind study, we conducted repeated prefrontal electrical stimulation in 40 patients with MS to evaluate mental health variables (quality of life, sleep difficulties, psychological distress) and cognitive dysfunctions (psychomotor speed, working memory, attention/vigilance), marking it as the third largest sample size tDCS research conducted in MS to date. METHODS: The patients were randomly assigned (block randomization method) to two groups of sham (n = 20), or 1.5-mA (n = 20) transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (F3) and right frontopolar cortex (Fp2) with anodal and cathodal stimulation respectively (electrode size: 25 cm2). The treatment included 10 sessions of 20 min of stimulation delivered every other day. Outcome measures were MS quality of life, sleep quality, psychological distress, and performance on a neuropsychological test battery dedicated to cognitive dysfunctions in MS (psychomotor speed, working memory, and attention). All outcome measures were evaluated at the pre-intervention and post-intervention assessments. Both patients and technicians delivering the stimulation were unaware of the type of stimulation being used. RESULTS: Repeated prefrontal real tDCS significantly improved quality of life and reduced sleep difficulties and psychological distress compared to the sham group. It, furthermore, improved psychomotor speed, attention, and vigilance compared to the sham protocol. Improvement in mental health outcome variables and cognitive outperformance were interrelated and could predict each other. CONCLUSIONS: Repeated prefrontal and frontopolar tDCS ameliorates secondary clinical symptoms related to mental health and results in beneficial cognitive effects in patients with MS. These results support applying prefrontal tDCS in larger trials for improving mental health and cognitive dysfunctions in MS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06401928.

TRanscranial AlterNating current stimulation FOR patients with mild Alzheimer's Disease (TRANSFORM-AD): a randomized controlled clinical trial.

BACKGROUND: The mechanistic effects of gamma transcranial alternating current stimulation (tACS) on hippocampal gamma oscillation activity in Alzheimer's Disease (AD) remains unclear. This study aimed to clarify beneficial effects of gamma tACS on cognitive functioning in AD and to elucidate effects on hippocampal gamma oscillation activity. METHODS: This is a double-blind, randomized controlled single-center trial. Participants with mild AD were randomized to tACS group or sham group, and underwent 30 one-hour sessions of either 40 Hz tACS or sham stimulation over consecutive 15 days. Cognitive functioning, structural magnetic resonance imaging (MRI), and simultaneous electroencephalography-functional MRI (EEG-fMRI) were evaluated at baseline, the end of the intervention and at 3-month follow-up from the randomization. RESULTS: A total of 46 patients were enrolled (23 in the tACS group, 23 in the sham group). There were no group differences in the change of the primary outcome, 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) score after intervention (group*time, p = 0.449). For secondary outcomes, compared to the control group, the intervention group showed significant improvement in MMSE (group*time, p = 0.041) and MoCA scores (non-parametric test, p = 0.025), which were not sustained at 3-month follow-up. We found an enhancement of theta-gamma coupling in the hippocampus, which was positively correlated with improvements of MMSE score and delayed recall. Additionally, fMRI revealed increase of the local neural activity in the hippocampus. CONCLUSION: Effects on the enhancement of theta-gamma coupling and neural activity within the hippocampus suggest mechanistic models for potential therapeutic mechanisms of tACS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03920826; Registration Date: 2019-04-19.

An overview of the effects and mechanisms of transcranial stimulation frequency on motor learning.

Many studies over the recent decades have attempted the modulation of motor learning using brain stimulation. Alternating currents allow for researchers not only to electrically stimulate the brain, but to further investigate the effects of specific frequencies, in and beyond the context of their endogenous associations. Transcranial alternating current stimulation (tACS) has therefore been used during motor learning to modulate aspects of acquisition, consolidation and performance of a learned motor skill. Despite numerous reviews on the effects of tACS, and its role in motor learning, there are few studies which synthesize the numerous frequencies and their respective theoretical mechanisms as they relate to motor and perceptual processes. Here we provide a short overview of the main stimulation frequencies used in motor learning modulation (e.g., alpha, beta, and gamma), and discuss the effect and proposed mechanisms of these studies. We summarize with the current state of the field, the effectiveness and variability in motor learning modulation, and novel mechanistic proposals from other fields.

The effect of computerized cognitive training and transcranial direct current stimulation on working memory among post-stroke individuals: a systematic review with meta-analysis and meta-regression.

BACKGROUND: Working memory (WM) impairment is a common phenomenon after stroke; however, its management in rehabilitation is less researched. This systematic review and meta-analysis aimed to provide a quantitative synthesis of the impact of computerised cognitive training (CCT) and transcranial direct current stimulation (tDCS) on WM span in post-stroke individuals. METHODS: The literature search in PubMed, Embase, Scopus, and Cochrane Library focused on randomized controlled trials testing the effect of CCT and tDCS on treated stroke patients as compared to untreated controls. Neuropsychological instruments such as Digit Span Forward/Backward and Visual Span Forward Tests defined the outcome of WM span. After extracting study characteristics and quality assessment using the Cochrane Risk of Bias Tool, we conducted a meta-analysis and meta-regression using standardised mean differences. RESULTS: The search yielded 4142 articles, nine of which (N = 461) fulfilled the inclusion criteria. In the case of CCT, we found significant improvement in Digit Span Backward Test (Z = 2.65, P = 0.008; 95% CI [0.10, 0.67]) and Visual Span Forward Test performance (Z = 3.05, P = 0.002; 95% CI [0.15, 0.69]), while for tDCS, we could not find a sufficient number of studies for the analysis. Furthermore, no significant moderating factor was found in the meta-regression. CONCLUSIONS: In conclusion, CCT appears to be a suitable choice to enhance WM span performance after stroke. However, further research is needed to investigate the effect of tDCS due to the limited number of studies. TRIAL REGISTRATION: The meta-analysis was conducted according to PRISMA (Preferred Reporting of Systematic Reviews and Meta-Analyses) standards with a PROSPERO registration protocol (ID: CRD42023387182).

Effects of transcranial direct current stimulation on pain and physical function in patients with knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Keen Osteoarthritis (KOA) is a common chronic disabling disease characterized by joint pain and dysfunction, which seriously affects patients' quality of life. Recent studies have shown that transcranial direct current stimulation (tDCS) was a promising treatment for KOA. PURPOSE: Investigate the effects of tDCS on pain and physical function in patients with KOA. METHODS: Randomized controlled trials related to tDCS and KOA were systematically searched in the PubMed, Embase, Medline, Cochrane Library, CINHL, and Web of Science databases from inception to July 23, 2024. The pain intensity was evaluated using the visual analog scale or the numeric rating scale, and the pain sensitivity was assessed using conditioned pain modulation, pressure pain threshold, heat pain threshold, or heat pain tolerance. The physical function outcome was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index or the Knee injury and Osteoarthritis Outcome Score. Statistical analysis was performed using Review Manager 5.4. RESULTS: Seven studies with a total of 503 participants were included. Compared to sham tDCS, tDCS was effective in reducing the short-term pain intensity (SMD: -0.58; 95% CI: -1.02, -0.14; p = 0.01) and pain sensitivity (SMD: -0.43; 95% CI: -0.70, -0.16; p = 0.002) but failed to significantly improve the long-term pain intensity (SMD: -0.26; 95% CI: -0.59, 0.08; p = 0.13) in KOA patients. In addition, tDCS did not significantly improve the short-term (SMD: -0.13; 95% CI: -0.35, 0.08; p = 0.22) and long-term (SMD: 0.02; 95% CI: -0.22, 0.25; p = 0.90) physical function in patients with KOA. CONCLUSIONS: The tDCS can reduce short-term pain intensity and sensitivity but fails to significantly relieve long-term pain intensity and improve the physical function in patients with KOA. Thus, tDCS may be a potential therapeutic tool to reduce short-term pain intensity and pain sensitivity in patients with KOA.

[An efficient and practical electrode optimization method for transcranial electrical stimulation].

Transcranial electrical stimulation (TES) is a non-invasive neuromodulation technique with great potential. Electrode optimization methods based on simulation models of individual TES field could provide personalized stimulation parameters according to individual variations in head tissue structure, significantly enhancing the stimulation accuracy of TES. However, the existing electrode optimization methods suffer from prolonged computation times (typically exceeding 1 d) and limitations such as disregarding the restricted number of output channels from the stimulator, further impeding their clinical applicability. Hence, this paper proposes an efficient and practical electrode optimization method. The proposed method simultaneously optimizes both the intensity and focality of TES within the target brain area while constraining the number of electrodes used, and it achieves faster computational speed. Compared to commonly used electrode optimization methods, the proposed method significantly reduces computation time by 85.9% while maintaining optimization effectiveness. Moreover, our method considered the number of available channels for the stimulator to distribute the current across multiple electrodes, further improving the tolerability of TES. The electrode optimization method proposed in this paper has the characteristics of high efficiency and easy operation, potentially providing valuable supporting data and references for the implementation of individualized TES.

Transcranial direct current stimulation enhances the protective effect of isoflurane preconditioning on cerebral ischemia/reperfusion injury: A new mechanism associated with the nuclear protein Akirin2.

AIMS: Ischemic stroke is a major cause of disability and mortality worldwide. Transcranial direct current stimulation (tDCS) and isoflurane (ISO) preconditioning exhibit neuroprotective properties. However, it remains unclear whether tDCS enhances the protective effect of ISO preconditioning on ischemic stroke, and the underlying mechanisms are yet to be clarified. METHOD: A model of middle cerebral artery occlusion (MCAO), a rat ischemia-reperfusion (I/R) injury model, and an in vitro oxygen-glucose deprivation/re-oxygenation (O/R) model of ischemic injury were developed. ISO preconditioning and tDCS were administered daily for 7 days before MCAO modeling. Triphenyltetrazolium chloride staining, modified neurological severity score, and hanging-wire test were conducted to assess infarct volume and neurological outcomes. Untargeted metabolomic experiments, adeno-associated virus, lentiviral vectors, and small interfering RNA techniques were used to explore the underlying mechanisms. RESULTS: tDCS/DCS enhanced the protective effects of ISO pretreatment on I/R injury-induced brain damage. This was evidenced by reduced infarct volume and improved neurological outcomes in rats with MCAO, as well as decreased cortical neuronal death after O/R injury. Untargeted metabolomic experiments identified oxidative phosphorylation (OXPHOS) as a critical pathological process for ISO-mediated neuroprotection from I/R injury. The combination of tDCS/DCS with ISO preconditioning significantly inhibited I/R injury-induced OXPHOS. Mechanistically, Akirin2, a small nuclear protein that regulates cell proliferation and differentiation, was found to decrease in the cortex of rats with MCAO and in cortical primary neurons subjected to O/R injury. Akirin2 functions upstream of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). tDCS/DCS was able to further upregulate Akirin2 levels and activate the Akirin2/PTEN signaling pathway in vivo and in vitro, compared with ISO pretreatment alone, thereby contributing to the improvement of cerebral I/R injury. CONCLUSION: tDCS treatment enhances the neuroprotective effects of ISO preconditioning on ischemic stroke by inhibiting oxidative stress and activating Akirin2-PTEN signaling pathway, highlighting potential of combination therapy in ischemic stroke.

Glaucoma Rehabilitation Using ElectricAI Transcranial Stimulation (GREAT)-Optimizing Stimulation Protocol for Vision Enhancement Using an RCT.

Purpose: We compared the effect of three different transcranial electrical stimulation (tES) protocols delivered to the occipital lobe on peripheral vision in patients with glaucoma. Methods: A double-masked, placebo-controlled study was conducted with 35 patients with glaucoma. We compared three different tES protocols: anodal transcranial direct current stimulation (a-tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS) against sham stimulation. Each patient attended four stimulation sessions (a-tDCS, tACS, tRNS, and sham) in a random order with at least 48 hours between visits. Stimulation involved placing an anodal electrode over the occipital lobe (Oz) and cathodal electrode on the cheek for 20 minutes. High-resolution perimetry (HRP) and multifocal visual evoked potential (mfVEP) measurements were made before and immediately after stimulation. Changes in HRP detection accuracy/reaction time and mfVEP signal-to-noise ratio (SNR)/latency were analyzed using linear mixed models. Results: Compared to sham, HRP detection accuracy was significantly improved after a-tDCS in both the central 20-degree (b = 0.032, P = 0.018) and peripheral analysis (b = 0.051, P = 0.002). Additionally, mfVEP SNR was significantly increased (b = 0.016, P = 0.017) and the latency was shortened (b = -1.405, P = 0.04) by the a-tDCS in the central 20-degree analysis. In the peripheral analysis, there was a trend toward an enhancement of SNR after a-tDCS stimulation (b = 0.014, P = 0.052), but it did not reach statistical significance; latency was increased after tACS (b = 1.623, P = 0.041). No significant effects were found in comparison to other active tES protocols. Conclusions: A single session of a-tDCS enhances perceptual and electrophysiologic measures of vision in patients with glaucoma. However, the small magnitude of changes observed in HRP (3.2% for accuracy in central and 5.1% in peripheral) did not exceed previous test variability and may not be clinically meaningful. Translational Relevance: a-tDCS holds promise as a potential treatment for enhancing visual function. However, future studies are needed to evaluate the long-term effects and clinical relevance of this intervention using validated measures of perimetric changes in the visual field.

Effects of high-definition tDCS targeting individual motor hotspot with EMG-driven robotic hand training on upper extremity motor function: a pilot randomized controlled trial.

BACKGROUND: Delivering HD-tDCS on individual motor hotspot with optimal electric fields could overcome challenges of stroke heterogeneity, potentially facilitating neural activation and improving motor function for stroke survivors. However, the intervention effect of this personalized HD-tDCS has not been explored on post-stroke motor recovery. In this study, we aim to evaluate whether targeting individual motor hotspot with HD-tDCS followed by EMG-driven robotic hand training could further facilitate the upper extremity motor function for chronic stroke survivors. METHODS: In this pilot randomized controlled trial, eighteen chronic stroke survivors were randomly allocated into two groups. The HDtDCS-group (n = 8) received personalized HD-tDCS using task-based fMRI to guide the stimulation on individual motor hotspot. The Sham-group (n = 10) received only sham stimulation. Both groups underwent 20 sessions of training, each session began with 20 min of HD-tDCS and was then followed by 60 min of robotic hand training. Clinical scales (Fugl-meyer Upper Extremity scale, FMAUE; Modified Ashworth Scale, MAS), and neuroimaging modalities (fMRI and EEG-EMG) were conducted before, after intervention, and at 6-month follow-up. Two-way repeated measures analysis of variance was used to compare the training effect between HDtDCS- and Sham-group. RESULTS: HDtDCS-group demonstrated significantly better motor improvement than the Sham-group in terms of greater changes of FMAUE scores (F = 6.5, P = 0.004) and MASf (F = 3.6, P = 0.038) immediately and 6 months after the 20-session intervention. The task-based fMRI activation significantly shifted to the ipsilesional motor area in the HDtDCS-group, and this activation pattern increasingly concentrated on the motor hotspot being stimulated 6 months after training within the HDtDCS-group, whereas the increased activation is not sustainable in the Sham-group. The neuroimaging results indicate that neural plastic changes of the HDtDCS-group were guided specifically and sustained as an add-on effect of the stimulation. CONCLUSIONS: Stimulating the individual motor hotspot before robotic hand training could further enhance brain activation in motor-related regions that promote better motor recovery for chronic stroke. TRIAL REGISTRATION: This study was retrospectively registered in ClinicalTrials.gov (ID NCT05638464).

Impact of Electric Field Magnitude in the Left Dorsolateral Prefrontal Cortex on Changes in Intrinsic Functional Connectivity Using Transcranial Direct Current Stimulation: A Randomized Crossover Study.

This study investigated whether the electric field magnitude (E-field) delivered to the left dorsolateral prefrontal cortex (L-DLPFC) changes resting-state brain activity and the L-DLPFC resting-state functional connectivity (rsFC), given the variability in tDCS response and lack of understanding of how rsFC changes. Twenty-one healthy participants received either 2 mA anodal or sham tDCS targeting the L-DLPFC for 10 min. Brain imaging was conducted before and after stimulation. The fractional amplitude of low-frequency fluctuation (fALFF), reflecting resting brain activity, and the L-DLPFC rsFC were analyzed to investigate the main effect of tDCS, main effect of time, and interaction effects. The E-field was estimated by modeling tDCS-induced individual electric fields and correlated with fALFF and L-DLPFC rsFC. Anodal tDCS increased fALFF in the left rostral middle frontal area and decreased fALFF in the midline frontal area (FWE p < 0.050), whereas sham induced no changes. Overall rsFC decreased after sham (positive and negative connectivity, p = 0.001 and 0.020, respectively), with modest and nonsignificant changes after anodal tDCS (p = 0.063 and 0.069, respectively). No significant differences in local rsFC were observed among the conditions. Correlations were observed between the E-field and rsFC changes in the L-DLPFC (r = 0.385, p = 0.115), left inferior parietal area (r = 0.495, p = 0.037), and right lateral visual area (r = 0.683, p = 0.002). Single-session tDCS induced resting brain activity changes and may help maintain overall rsFC. The E-field in the L-DLPFC is associated with rsFC changes in both proximal and distally connected brain regions to the L-DLPFC.

The ventromedial prefrontal cortex plays an important role in implicit emotion regulation: A focality-optimized multichannel tDCS study in anxiety individuals.

The regulation of emotions is a crucial facet of well-being and social adaptability, with explicit strategies receiving primary attention in prior research. Recent studies, however, emphasize the role of implicit emotion regulation, particularly implicating the ventromedial prefrontal cortex (VMPFC) in association with its implementation. This study delves into the nuanced role of the VMPFC through focality-optimized multichannel transcranial direct current stimulation (tDCS), shedding light on its causal involvement in implicit reappraisal. The primary goal was to evaluate the effectiveness of VMFPC-targeted tDCS and elucidate its role in individuals with high trait anxiety. Participants engaged in implicit and explicit emotion regulation tasks during multichannel tDCS targeting the VMPFC. The outcome measures encompassed negative emotion ratings, pupillary diameter, and saccade count, providing a comprehensive evaluation of emotion regulation efficiency. The intervention exhibited a notable impact, resulting in significant reductions in negative emotion ratings and pupillary reactions during implicit reappraisal, highlighting the indispensable role of the VMPFC in modulating emotional responses. Notably, these effects demonstrated sustained efficacy up to 1 day postintervention. This study underscores the potency of VMPFC-targeted multichannel tDCS in augmenting implicit emotion regulation. This not only contributes insights into the neural mechanisms of emotion regulation but also suggests innovative therapeutic avenues for anxiety disorders. The findings present a promising trajectory for future mood disorder interventions, bridging the gap between implicit emotion regulation and neural stimulation techniques.

Investigating combined acupuncture and transcranial direct current stimulation in patients with poststroke shoulder pain from China: protocol for a randomised controlled trial.

INTRODUCTION: Poststroke shoulder pain is a common complication that severely affects the recovery of upper limb motor function. Acupuncture has positive analgesic effects in treating poststroke shoulder pain, and studies have demonstrated the efficacy of transcranial direct current stimulation (tDCS) in treating patients with this pain. However, whether acupuncture combined with tDCS has a superior rehabilitation effect on poststroke shoulder pain is currently unknown. We aimed to observe the effect of the combined intervention on poststroke shoulder pain and explore its possible central analgesic mechanism. METHODS AND ANALYSIS: This study describes a randomised controlled trial using assessor blinding. A total of 135 poststroke patients with shoulder pain will be randomly assigned in a 1:1:1 ratio to the tDCS group, acupuncture group and combined group (acupuncture plus tDCS). All three groups will undergo conventional rehabilitation treatment. Participants in the tDCS group will receive tDCS stimulation on the M1 area for 20 min, while the acupuncture group will receive 20 min of acupuncture. The combined treatment group will receive both. All treatments will be performed five times per week for 4 weeks. The primary outcome indicator in this study is the Visual Analogue Scale pain score. Secondary outcome indicators include shoulder mobility, Shoulder Pain and Disability Index, Fugl-Meyer Motor Function Scale, Modified Barthel Index Scale, Self-Rating Anxiety and Depression Scale and functional MRI. All scale results will be assessed at baseline and at 2 weeks and 4 weeks, and during follow-up at 1 month, 3 months and 6 months postdischarge. A repeated analysis of variance will be conducted to observe the group×time interaction effects of the combined intervention. Moreover, functional MRI will be applied to explore the central analgesic mechanism. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of the Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine (2023KY-039-001). The results of the study will be published in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300078270.

Lasting effects of transcranial direct current stimulation on the inducibility of synaptic plasticity by paired-associative stimulation in humans.

BACKGROUND: Transcranial direct current stimulation (tDCS) is capable of eliciting changes in cortical neuroplasticity. Increasing duration or repetition of tDCS during the after-effects of a first stimulation has been hypothesized to enhance efficacy. Computational models suggest sequential stimulation patterns with changing polarities to further enhance effects. Lasting tDCS effects on neural plasticity are of great importance for clinical applications. OBJECTIVE: The study systematically examined the influence of different tDCS paradigms on long term potentiation (LTP)-like plasticity in humans, focusing on stimulation duration, repetition frequency and sequential combinations of changing polarities as the underlying characteristics. METHODS: Amplitude changes of motor evoked potentials (MEP) were measured in response to paired associative stimulation (PAS) 6 h after application of different tDCS protocols. In total, 36 healthy participants completed the study, randomised into three groups with different stimulation protocols (N = 12 each). RESULTS: tDCS was able to display lasting modulatory effects on the inducibility of LTP-like plasticity in the human motor cortex 6 h after stimulation. TDCS with the anode on primary motor cortex significantly increased MEP amplitudes following PAS induction. Further analyses highlighted single stimulation block duration to be of higher importance than repetitive protocols for efficacy of effects. CONCLUSIONS: tDCS is capable of inducing lasting changes in the brain's capability to interact with future stimuli. Especially, effects on the inducibility of LTP-like plasticity might only be detectable with specific tests such as PAS and might otherwise be overlooked. Refined tDCS protocols should focus on higher current and duration of single stimulations instead of implementing complex repetitive schedules.

Neuromodulation of Executive Dysfunction in Patients with Acute Stroke Using Transcranial Direct Current Stimulation: Study Protocol for a Triple-Blind, Randomized Sham-Controlled Trial.

Research on the benefits of non-invasive brain stimulation in stroke patients to improve executive functions is scarce. The objective of this study was to investigate the effectiveness of transcranial direct current stimulation (tDCS) in combination with cognitive training for the rehabilitation of executive functions in acute and subacute stroke patients as well as to explore the underlying physiological mechanisms. A triple-blinded, randomized-controlled clinical trial will be conducted involving 60 stroke patients with frontal or basal ganglia lesions and a Montreal Cognitive Assessment (MoCA) score less than 26. Participants will be randomly assigned to receive active tDCS (anode over the left dorsolateral prefrontal cortex, cathode at the right supraorbital region, 20 min at 2 mA) or sham tDCS in a 1:1 ratio for 10 sessions, followed by targeted executive function training. The primary efficacy outcome will be the MoCA score, while secondary outcomes will include the five-digit test (inhibitory control), the Digit Span Task (working memory), the abbreviated version of the Wisconsin Card Sorting test (cognitive flexibility), modified Rankin scale (functional state), Beck-II depression inventory, apathy evaluation scale, and the WHOQOL-BREF (quality of life), assessed immediately after the intervention and at 1, 3, 6, and 12 months post-intervention. Additionally, resting-state functional connectivity and blood biomarkers, such as neurotrophins, growth factors, and inflammatory molecules, will be evaluated before and after the intervention. This study will contribute to the investigation of the efficacy of tDCS in rehabilitating executive functions in acute and subacute stroke patients. The multidimensional approach utilized in this study, which includes analysis of resting-state connectivity and neuroplasticity-related blood biomarkers, is expected to provide insights into the underlying brain mechanisms involved in the rehabilitation of dysexecutive syndrome.

tDCS for the treatment of negative symptoms in youth at clinical-high-risk for psychosis: A feasibility study.

Negative symptoms are often found in youth at clinical high risk (CHR) for psychosis. The present study explored the feasibility of using tDCS in conjunction with CBT in the treatment of negative symptoms in 5 youths at CHR. We sought to determine whether the protocol was feasible given the requirement for repeated visits over a three-week period, and to determine if measures of neurobiological change could be included, both acutely and following three weeks of stimulation. The results from this study suggest that the protocol is feasible for these youth, and the inclusion of MRI scanning sessions yielded good quality data.