Neural mechanisms underlying improved new-word learning with high-density transcranial direct current stimulation.

Neurobehavioral studies have provided evidence for the effectiveness of anodal tDCS on language production, by stimulation of the left Inferior Frontal Gyrus (IFG) or of left Temporo-Parietal Junction (TPJ). However, tDCS is currently not used in clinical practice outside of trials, because behavioral effects have been inconsistent and underlying neural effects unclear. Here, we propose to elucidate the neural correlates of verb and noun learning and to determine if they can be modulated with anodal high-definition (HD) tDCS stimulation. Thirty-six neurotypical participants were randomly allocated to anodal HD-tDCS over either the left IFG, the left TPJ, or sham stimulation. On day one, participants performed a naming task (pre-test). On day two, participants underwent a new-word learning task with rare nouns and verbs concurrently to HD-tDCS for 20 min. The third day consisted of a post-test of naming performance. EEG was recorded at rest and during naming on each day. Verb learning was significantly facilitated by left IFG stimulation. HD-tDCS over the left IFG enhanced functional connectivity between the left IFG and TPJ and this correlated with improved learning. HD-tDCS over the left TPJ enabled stronger local activation of the stimulated area (as indexed by greater alpha and beta-band power decrease) during naming, but this did not translate into better learning. Thus, tDCS can induce local activation or modulation of network interactions. Only the enhancement of network interactions, but not the increase in local activation, leads to robust improvement of word learning. This emphasizes the need to develop new neuromodulation methods influencing network interactions. Our study suggests that this may be achieved through behavioral activation of one area and concomitant activation of another area with HD-tDCS.

tDCS of right-hemispheric Wernicke's area homologue affects contextual learning of novel lexicon.

Numerous studies have shown robust evidence of the right hemisphere's involvement in the language function, for instance in the processing of intonation, grammar, word meanings, metaphors, etc. However, its role in lexicon acquisition remains obscure. We applied transcranial direct current stimulation (tDCS) over the right-hemispheric homologue of Wernicke's area to assess its putative involvement in the processing of different types of novel semantics. After receiving 15 min of anodal, cathodal, or sham (placebo) tDCS, three groups of healthy participants learnt novel concrete and abstract words in the context of short stories. Learning outcomes were assessed using a battery of tests immediately after this contextual learning session and 24 h later. As a result, an inhibitory effect of cathodal tDCS and a facilitatory effect of anodal tDCS were found for abstract word acquisition only. We also found a significant drop in task performance on the second day of the assessment for both word types in all the stimulation groups, suggesting no significant influence of tDCS on the post-learning consolidation of new memory traces. The results suggest an involvement of Wernicke's right-hemispheric counterpart in initial encoding (but not consolidation) of abstract semantics, which may be explained either by the right hemispheres direct role in processing lexical semantics or by an indirect impact of tDCS on contralateral (left-hemispheric) cortical areas through cross-callosal connections.

The impact of transcranial direct current stimulation on attention bias modification in children with ADHD.

Individuals with attention deficit-hyperactivity disorder (ADHD) struggle with the interaction of attention and emotion. The ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are assumed to be involved in this interaction. In the present study, we aimed to explore the effect of stimulation applied over the dlPFC and vmPFC on attention bias in individuals with ADHD. Twenty-three children with ADHD performed the emotional Stroop and dot probe tasks during transcranial direct current stimulation (tDCS) in 3 conditions: anodal dlPFC (F3)/cathodal vmPFC (Fp2), anodal vmPFC (Fp2)/cathodal dlPFC (F3), and sham stimulation. Findings suggest reduction of attention bias in both real conditions based on emotional Stroop task and not dot probe task. These results were independent of emotional states. The dlPFC and vmPFC are involved in attention bias in ADHD. tDCS can be used for attention bias modification in children with ADHD.

The neural structures of theory of mind are valence-sensitive: evidence from three tDCS studies.

Several cortical structures are involved in theory of mind (ToM), including the dorsolateral prefrontal cortex (dlPFC), the ventromedial prefrontal cortex (vmPFC), and the right temporo- parietal junction (rTPJ). We investigated the role of these regions in mind reading with respect to the valence of mental states. Sixty-five healthy adult participants were recruited and received transcranial direct current stimulation (tDCS) (1.5 mA, 20 min) with one week interval in three separate studies. The stimulation conditions were anodal tDCS over the dlPFC coupled with cathodal tDCS over the vmPFC, reversed stimulation conditions, and sham in the first study, and anodal tDCS over the vmPFC, or dlPFC, and sham stimulation, with an extracranial return electrode in the second and third study. During stimulation, participants underwent the reading mind from eyes/voice tests (RMET or RMVT) in each stimulation condition. Anodal left dlPFC/cathodal right vmPFC stimulation increased the accuracy of negative mental state attributions, anodal rTPJ decreased the accuracy of negative and neutral mental state attributions, and decreased the reaction time of positive mental state attributions. Our results imply that the neural correlates of ToM are valence-sensitive.

Effects of transcranial direct current stimulation on motor learning in healthy elderly individuals: a systematic review and meta-analysis.

BACKGROUND: Transcranial direct current stimulation (tDCS) is widely used in motor recovery. Nevertheless, whether tDCS improves motor learning in healthy older adults is still controversial. This review aims to investigate the effectiveness of tDCS on motor learning in healthy elderly individuals. METHODS: The PubMed, Cochrane Library, Web of Science and Embase databases were initially searched from inception to December 5, 2022. The standard mean difference (SMD) with the corresponding 95% confidence intervals (CIs) were analysed via random-effect models. RESULTS: Compared with the sham group, no significant effects were found regarding improvement in motor learning based on the speed or accuracy of the task and reaction time for the tDCS intervention group. After subgroup analysis, a significant effect was found for improved motor learning based on reaction time in the primary motor cortex (M1)-cerebellar group. CONCLUSIONS: This review revealed that tDCS had no significant effect on improving the speed or accuracy of motor learning in healthy elderly adults. However, it has a significant effect on improving the motor learning ability based on the reaction time of the task (mainly referring to the tDCS stimulation position of M1 and cerebellar), although the results have obvious heterogeneity and uncertainty.

The effect of transcranial direct current stimulation (tDCS) on cognitive function recovery in patients with depression following electroconvulsive therapy (ECT): protocol for a randomized controlled trial.

BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective treatment for depressive disorder. However, the use of ECT is limited by its cognitive side effects (CSEs), and no specific intervention has been developed to address this problem. As transcranial direct current stimulation (tDCS) is a safe and useful tool for improving cognitive function, the main objective of this study was to explore the ability to use tDCS after ECT to ameliorate the cognitive side effects. METHODS: 60 eligible participants will be recruited within two days after completing ECT course and randomly assigned to receive either active or sham stimulation in a blinded, parallel-design trial and continue their usual pharmacotherapy. The tDCS protocol consists of 30-min sessions at 2 mA, 5 times per week for 2 consecutive weeks, applied through 15-cm2 electrodes. An anode will be placed over the left dorsolateral prefrontal cortex (DLPFC), and a cathode will be placed over the right supraorbital cortex. Cognitive function and depressive symptoms will be assessed before the first stimulation (T0), after the final stimulation (T1), 2 weeks after the final stimulation (T2), and 4 weeks after the final stimulation (T3) using the Cambridge Neuropsychological Test Automated Battery (CANTAB). DISCUSSION: We describe a novel clinical trial to explore whether the administration of tDCS after completing ECT course can accelerates recovery from the CSEs. We hypothesized that the active group would recover faster from the CSEs and be superior to the sham group. If our hypothesis is supported, the use of tDCS could benefit eligible patients who are reluctant to receive ECT and reduce the risk of self-inflicted or suicide due to delays in treatment. TRIAL REGISTRATION DETAILS: The trial protocol is registered with https://www.chictr.org.cn/ under protocol registration number ChiCTR2300071147 (date of registration: 05.06.2023). Recruitment will start in November 2023.

Long-term repetitive transcranial direct current stimulation in patients with disorders of consciousness: a preliminary study.

OBJECTIVES: To investigate the effects of long-term repetitive transcranial direct current stimulation on patients with DOC in the subacute phase. METHODS: In a randomized, double-blind, controlled study, 33 patients were randomly assigned to the active or sham group, and 28 patients completed the study. Patients in the active group received anodal stimulation over the DLPFC, while patients in the sham group received placebo stimulation (20 min/day, 5 days/week, for 4 weeks). The level of consciousness among patients was assessed with the Coma Recovery Scale-Revised (CRS-R) at baseline and at the end of every week from the first to the fourth week. RESULTS: The CRS-R scores of both the active and sham groups showed a consistent increasing trend over time; however, the treatment effect of the active group was better than that of the sham group. In addition, there was a statistically significant difference in the total CRS-R score between the two groups at weeks 1, 2, 3 and 4. Moreover, 10 patients (71.4%) in the active group and 3 patients (21.4%) in the sham group were regarded as responders. CONCLUSION: Long-term tDCS could improve the level of consciousness of patients with DOC in the subacute stage.

No Frequency-Specific Effect of Transcranial Random Noise Stimulation on Resting EEG.

BACKGROUND: Transcranial random noise stimulation (tRNS) is a form of noninvasive transcranial electrical stimulation that applies alternating current in various randomized frequencies to the cortex, thereby improving cognitive functioning in multiple domains. However, the precise mechanism of tRNS, as well as its impact on human electroencephalography (EEG), remains unclear. This is partly because most studies have used tRNS in conjunction with a cognitive task, making it difficult to tease apart whether the observed changes in EEG are a result of tRNS, the cognitive task, or their interaction. METHODS: Forty-nine healthy individuals participated in this study and were randomly assigned to active tRNS (n = 24) and sham (n = 25) groups. tRNS was delivered for 20 minutes over Fp1/Fp2 and Oz. Resting-state EEG data were collected before and after either tRNS or sham stimulation. RESULTS: Cluster-based permutation tests using FieldTrip revealed no frequency-specific effect of tRNS on resting-state EEG data across four frequency bands (theta, alpha, beta, gamma). CONCLUSIONS: These observations suggest that tRNS itself does not target or alter specific EEG frequencies. Rather, tRNS most likely interacts with the cognitive task/activity at hand to produce an observable difference in post-tRNS EEG. Positive tRNS-EEG findings from previous studies are also likely to have resulted from the interactive and cognitive activity-dependent nature of tRNS.

Effects of Transcranial Direct Current Stimulation on Potential P300-Related Events and Alpha and Beta EEG Band Rhythms in Parkinson's Disease.

BACKGROUND: Parkinson's disease is one of the most common neurodegenerative disorders. While a definitive cure for Parkinson's disease remains elusive, a range of treatments are available to slow its progression and counteract its symptoms. Transcranial direct current stimulation (tDCS) represents a non-invasive method to induce brain plasticity. The aim of this study was to examine the effects of two weeks of tDCS on the left dorsolateral prefrontal cortex (DLPFC) on the neurophysiological functioning of Parkinson's patients. METHODS: Thirty patients aged between 67 and 82 years with Parkinson's disease participated to the experiment. Fifteen underwent tDCS on the left DLPFC, while fifteen underwent sham tDCS. Neurophysiological functions were assessed before and after tDCS using electroencephalogram methods for alpha and beta band rhythms and P300 event-related potential latency. RESULTS: tDCS led to a reduction in the onset latency of the P300 response and an increase in the power spectrum of the alpha and beta band rhythms. CONCLUSIONS: This research enhances our understanding of the potential effects of tDCS in the context of Parkinson's disease treatment, as the reduction in P300 latency and the increase in alpha and beta bands are associated with improvements in cognitive aspects.

Effectiveness of Conventional Dysphagia Therapy (CDT), Neuromuscular Electrical Stimulation (NMES), and Transcranial Direct Current Stimulation (tDCS) in Acute Post-Stroke Dysphagia: A Comparative Evaluation.

This study aims to compare the effectiveness of conventional dysphagia therapy (CDT), neuromuscular electrical stimulation (NMES), and transcranial direct current stimulation (tDCS) in the treatment of post-stroke dysphagia. A single-blind randomized controlled trial was conducted with 40 acute stroke patients - 18 females and 22 males with a mean age of 65.8 ± 11.9. The subjects were grouped into 4, with 10 individuals in each. The procedures administered to groups were as follows: the first group, sham tDCS and sham NMES; the second group, tDCS and sham NMES; the third group, NMES and sham tDCS; and the fourth group, all therapy procedures. CDT was applied to all groups either as a standalone procedure or combined with one or two of the instrumental techniques. Gugging Swallowing Screen (GUSS) and Videofluoroscopic Swallowing Study (VFSS) were employed to determine the severity of dysphagia and the effectiveness of treatment modalities. Additionally, the Penetration Aspiration Scale (PAS), Functional Oral Intake Scale (FOIS), and Dysphagia Severity Rating Scale (DSRS) were administered to interpret VFSS data. Pre- and post-treatment comparisons of all groups have revealed a statistically significant difference for all parameters except for the PAS scores at International Dysphagia Diet Standardization Initiative (IDDSI)-Level 4 consistencies. However, the differences between pre- and post-treatment scores of the fourth group across all parameters were significant - GUSS (p = 0.005), FOIS (p = 0.004), DSRS (p = 0.005), PAS IDDSI-4 (p = 0.027), PAS IDDSI-0 (p = 0.004). Inter-group comparisons, on the other hand, pointed out that the difference between pre- and post-treatment GUSS, FOIS, DSRS, and PAS scores at IDDSI Level-0 consistencies was statistically significant for all groups - GUSS (p = 0,009), FOIS (p = 0,004), DSRS (p = 0,002), PAS IDDSI-0 (p = 0,049). Closer examination of treatment groups indicated that the tDCS + CDT group, the NMES + CDT group, and the group that underwent the combination of three modalities made better progress than the one that was treated with only CDT. Though not statistically significant, the NMES + CDT group achieved better improvement than the tDCS + CDT group. This study has yielded that the group in which NMES, tDCS, and CDT were applied in combination has achieved better results than all the other groups. All treatment modalities applied to accelerate the general recovery process in acute stroke patients with dysphagia were found to be effective for the treatment of post-stroke swallowing disorders. The use of instrumental treatments such as NMES and tDCS enhanced the effectiveness of the treatment and provided more significant progress. Furthermore, combining treatment modalities such as NMES and tDCS was more effective when compared to using only conventional therapy. As a result, the most effective treatment outcomes were obtained by the group receiving CDT, NMES, and tDCS in combination. Therefore, the use of combined approaches has been recommended in appropriate patients; yet the provisional results should be tested in randomized trials with more participants.

Somatosensory evoked potentials amplitude is enhanced after non-invasive brain stimulation in chronic ischemic stroke: Preliminary results from a randomised control trial.

OBJECTIVE: To investigate the effects of transcranial electrical and magnetic non-invasive brain stimulation (NIBS) protocols on somatosensory evoked potential (SEP) in chronic ischemic stroke. METHODS: 33 patients were randomly assigned to one of the four treatment groups of the transcranial direct current stimulation (tDCS) and/or repetitive transcranial magnetic stimulation (rTMS) protocol. SEP parameters were recorded before and after ten days of the treatment session. All the statistical analyses were carried out using SPSS version 19. RESULTS: It was found that there is a statistically significant improvement in the N20-P22 mean amplitude after treatment sessions in all groups except the group where tDCS and rTMS groups were sham. On paired t-tests, the difference betweeen post and pre-stimulation SEP amplitudes for the real tDCS and real rTMS coupled group was 1.045 ± 0.732 (p value = 0.005). For sham tDCS+real rTMS group, 1.05 ± 0.96 (P = 0.04); for real tDCS+sham rTMS 0.543 ± 0.332 (P = 0.01) and for double sham stimulation, 0.204 ± 0.648 (P =  0.4) respectively CONCLUSION: In ischemic stroke patients, either or coupled true transcranial tDCS and rTMS was found to be safe and significantly enhanced the amplitude of cortical somatosensory potentials when combined with standard physiotherapy, in the interim analysis of an ongoing randomised controlled trial. CLINICAL TRIAL REGISTRY OF INDIA: CTRI/2019/11/022009 SIGNIFICANCE: The results of this research indicates the importance of RCTs in developing robust improved NIBS protocols coupled to physiotherapy to enhance the sensory-motor functional recovery following ischemic stroke.

Systematic review and meta-analysis of transcranial direct current stimulation (tDCS) for global cognition in mild cognitive impairment and Alzheimer's disease.

OBJECTIVE: To systematically assess the effectiveness of transcranial direct current stimulation (tDCS) on global cognition in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). DATA SOURCES: Ten databases were retrieved for pertinent Chinese and English studies published up until February 2023. DATA EXTRACTION: Two researchers independently selected the literature, extracted the data, evaluated using the Cochrane Collaboration's quality criteria, and then cross-checked. Meta-analysis was performed using RevMan 5.4. RESULTS: 22 studies involving 1074 patients were included. Compared with the control group received the interventions such as pharmacotherapy, cognitive stimulation, et al., with/without sham-tDCS, while the experiment group received tDCS added to the interventions of the control group. The meta-analysis found that tDCS increased MMSE, MoCA, MODA scores and reduced the P300 latency scores (all P < 0.05). CONCLUSION: The tDCS can ameliorate the global cognition of patients with MCI and AD, and it has a better rehabilitation effect than non-tDCS or sham-tDCS.

Outcome measures for electric field modeling in tES and TMS: A systematic review and large-scale modeling study.

BACKGROUND: Electric field (E-field) modeling is a potent tool to estimate the amount of transcranial magnetic and electrical stimulation (TMS and tES, respectively) that reaches the cortex and to address the variable behavioral effects observed in the field. However, outcome measures used to quantify E-fields vary considerably and a thorough comparison is missing. OBJECTIVES: This two-part study aimed to examine the different outcome measures used to report on tES and TMS induced E-fields, including volume- and surface-level gray matter, region of interest (ROI), whole brain, geometrical, structural, and percentile-based approaches. The study aimed to guide future research in informed selection of appropriate outcome measures. METHODS: Three electronic databases were searched for tES and/or TMS studies quantifying E-fields. The identified outcome measures were compared across volume- and surface-level E-field data in ten tES and TMS modalities targeting two common targets in 100 healthy individuals. RESULTS: In the systematic review, we extracted 308 outcome measures from 202 studies that adopted either a gray matter volume-level (n = 197) or surface-level (n = 111) approach. Volume-level results focused on E-field magnitude, while surface-level data encompassed E-field magnitude (n = 64) and normal/tangential E-field components (n = 47). E-fields were extracted in ROIs, such as brain structures and shapes (spheres, hexahedra and cylinders), or the whole brain. Percentiles or mean values were mostly used to quantify E-fields. Our modeling study, which involved 1,000 E-field models and > 1,000,000 extracted E-field values, revealed that different outcome measures yielded distinct E-field values, analyzed different brain regions, and did not always exhibit strong correlations in the same within-subject E-field model. CONCLUSIONS: Outcome measure selection significantly impacts the locations and intensities of extracted E-field data in both tES and TMS E-field models. The suitability of different outcome measures depends on the target region, TMS/tES modality, individual anatomy, the analyzed E-field component and the research question. To enhance the quality, rigor, and reproducibility in the E-field modeling domain, we suggest standard reporting practices across studies and provide four recommendations.

The Effects of Transcranial Direct Current Stimulation (tDCS) on the Cognitive Functions: A Systematic Review and Meta-analysis.

Previous studies have investigated the effect of transcranial direct current stimulation (tDCS) on cognitive functions. However, these studies reported inconsistent results due to differences in experiment design, measurements, and stimulation parameters. Nonetheless, there is a lack of meta-analyses and review studies on tDCS and its impact on cognitive functions, including working memory, inhibition, flexibility, and theory of mind. We performed a systematic review and meta-analysis of tDCS studies published from the earliest available data up to October 2021, including studies reporting the effects of tDCS on cognitive functions in human populations. Therefore, these systematic review and meta-analysis aim to comprehensively analyze the effects of anodal and cathodal tDCS on cognitive functions by investigating 69 articles with a total of 5545 participants. Our study reveals significant anodal tDCS effects on various cognitive functions. Specifically, we observed improvements in working memory reaction time (RT), inhibition RT, flexibility RT, theory of mind RT, working memory accuracy, theory of mind accuracy and flexibility accuracy. Furthermore, our findings demonstrate noteworthy cathodal tDCS effects, enhancing working memory accuracy, inhibition accuracy, flexibility RT, flexibility accuracy, theory of mind RT, and theory of mind accuracy. Notably, regarding the influence of stimulation parameters of tDCS on cognitive functions, the results indicated significant differences across various aspects, including the timing of stimulation (online vs. offline studies), population type (clinical vs. healthy studies), stimulation duration (< 15 min vs. > 15 min), electrical current intensities (1-1.5 m.A vs. > 1.5 m.A), stimulation sites (right frontal vs. left frontal studies), age groups (young vs. older studies), and different cognitive tasks in each cognitive functioning aspect. In conclusion, our results demonstrate that tDCS can effectively enhance cognitive task performance, offering valuable insights into the potential benefits of this method for cognitive improvement.

Comparison of Two Therapeutic Approaches of Cerebellar Transcranial Direct Current Stimulation in a Sardinian Family Affected by Spinocerebellar Ataxia 38: a Clinical and Computerized 3D Gait Analysis Study.

Spinocerebellar ataxia 38 (SCA 38) is a very rare autosomal dominant inherited disorder caused by a mutation in ELOV5 gene, specifically expressed in cerebellar Purkinje cells, encoding an enzyme involved in the synthesis of fatty acids. Seven symptomatic SCA 38 patients of a Sardinian family were administered 15 sessions of cerebellar anodal transcranial direct current stimulation (tDCS) in a cross-over study, employing deltoid cerebellar-only (C-tDCS) and cerebello-spinal (CS-tDCS) cathodal montage. Clinical evaluation was performed at baseline (T0), after 15 sessions of tDCS (T1) and after 1 month of follow-up (T2). Modified International Cooperative Ataxia Rating Scale (MICARS) and the Robertson dysarthria profile were used to rate ataxic and dysarthric symptoms, respectively. Alertness and split attention tests from Zimmermann test battery for attentional performance were employed to rate attentive functions. Moreover, 3D computerized gait analysis was employed to obtain a quantitative measure of efficacy of tDCS on motor symptoms. While clinical data showed that both CS and C-tDCS improved motor, dysarthric, and cognitive scores, the quantitative analysis of gait revealed significant improvement in spatio-temporal parameters only for C-tDCS treatment. Present findings, yet preliminary and limited by the small size of the tested sample, confirm the therapeutic potential of cerebellar tDCS in improving motor and cognitive symptoms in spinocerebellar ataxias and underline the need to obtain quantitative and objective measures to monitor the efficacy of a therapeutic treatment and to design tailored rehabilitative interventions. ClinicalTrials.gov identifier: NCT05951010.

Effects of transcranial direct current stimulation and transcranial random noise stimulation on working memory and task-related EEG in major depressive disorder.

OBJECTIVE: To compare effects of transcranial direct current stimulation (tDCS) and transcranial random noise stimulation with a direct-current offset (tRNS + DC-offset) on working memory (WM) performance and task-related electroencephalography (EEG) in individuals with Major Depressive Disorder (MDD). METHODS: Using a sham-controlled, parallel-groups design, 49 participants with MDD received either anodal tDCS (N = 16), high-frequency tRNS + DC-offset (N = 16), or sham stimulation (N = 17) to the left dorsolateral prefrontal cortex (DLPFC) for 20-minutes. The Sternberg WM task was completed with concurrent EEG recording before and at 5- and 25-minutes post-stimulation. Event-related synchronisation/desynchronisation (ERS/ERD) was calculated for theta, upper alpha, and gamma oscillations during WM encoding and maintenance. RESULTS: tDCS significantly increased parieto-occipital upper alpha ERS/ERD during WM maintenance, observed on EEG recorded 5- and 25-minutes post-stimulation. tRNS + DC-offset did not significantly alter WM-related oscillatory activity when compared to sham stimulation. Neither tDCS nor tRNS + DC-offset improved WM performance to a significantly greater degree than sham stimulation. CONCLUSIONS: Although tDCS induced persistent effects on WM-related oscillatory activity, neither tDCS nor tRNS + DC-offset enhanced WM performance in MDD. SIGNIFICANCE: This reflects the first sham-controlled comparison of tDCS and tRNS + DC-offset in MDD. These findings directly contrast with evidence of tRNS-induced enhancements in WM in healthy individuals.

Examining the synergistic effects of a cognitive control video game and a home-based, self-administered non-invasive brain stimulation on alleviating depression: the DiSCoVeR trial protocol.

Enhanced behavioral interventions are gaining increasing interest as innovative treatment strategies for major depressive disorder (MDD). In this study protocol, we propose to examine the synergistic effects of a self-administered home-treatment, encompassing transcranial direct current stimulation (tDCS) along with a video game based training of attentional control. The study is designed as a two-arm, double-blind, randomized and placebo-controlled multi-center trial (ClinicalTrials.gov: NCT04953208). At three study sites (Israel, Latvia, and Germany), 114 patients with a primary diagnosis of MDD undergo 6 weeks of intervention (30 × 30 min sessions). Patients assigned to the intervention group receive active tDCS (anode F3 and cathode F4; 2 mA intensity) and an action-like video game, while those assigned to the control group receive sham tDCS along with a control video game. An electrode-positioning algorithm is used to standardize tDCS electrode positioning. Participants perform their designated treatment at the clinical center (sessions 1-5) and continue treatment at home under remote supervision (sessions 6-30). The endpoints are feasibility (primary) and safety, treatment efficacy (secondary, i.e., change of Montgomery-Åsberg Depression Rating Scale (MADRS) scores at week six from baseline, clinical response and remission, measures of social, occupational, and psychological functioning, quality of life, and cognitive control (tertiary). Demonstrating the feasibility, safety, and efficacy of this novel combined intervention could expand the range of available treatments for MDD to neuromodulation enhanced interventions providing cost-effective, easily accessible, and low-risk treatment options.ClinicalTrials.gov: NCT04953208.

Causal Relationship between the Right Auditory Cortex and Speech-Evoked Envelope-Following Response: Evidence from Combined Transcranial Stimulation and Electroencephalography.

Speech-evoked envelope-following response (EFR) reflects brain encoding of speech periodicity that serves as a biomarker for pitch and speech perception and various auditory and language disorders. Although EFR is thought to originate from the subcortex, recent research illustrated a right-hemispheric cortical contribution to EFR. However, it is unclear whether this contribution is causal. This study aimed to establish this causality by combining transcranial direct current stimulation (tDCS) and measurement of EFR (pre- and post-tDCS) via scalp-recorded electroencephalography. We applied tDCS over the left and right auditory cortices in right-handed normal-hearing participants and examined whether altering cortical excitability via tDCS causes changes in EFR during monaural listening to speech syllables. We showed significant changes in EFR magnitude when tDCS was applied over the right auditory cortex compared with sham stimulation for the listening ear contralateral to the stimulation site. No such effect was found when tDCS was applied over the left auditory cortex. Crucially, we further observed a hemispheric laterality where aftereffect was significantly greater for tDCS applied over the right than the left auditory cortex in the contralateral ear condition. Our finding thus provides the first evidence that validates the causal relationship between the right auditory cortex and EFR.

Effects of Multisession Transcranial Direct Current Stimulation on Stress Regulation and Emotional Working Memory: A Randomized Controlled Trial in Healthy Military Personnel.

OBJECTIVES: Top-down stress regulation, important for military operational performance and mental health, involves emotional working memory and the dorsolateral prefrontal cortex (DLPFC). Multisession transcranial direct current stimulation (tDCS) applied over the DLPFC during working memory training has been shown to improve working memory performance. This study tested the hypothesis that combined tDCS with working memory training also improves top-down stress regulation. However, tDCS response differs between individuals. Resting-state electrophysiological brain activity was post hoc explored as a possible predictor of tDCS response. The predictive value of the ratio between slow-wave theta oscillations and fast-wave beta oscillations (theta/beta ratio) was examined, together with the previously identified tDCS response predictors age, education, and baseline working memory performance. MATERIALS AND METHODS: Healthy military service members (n = 79) underwent three sessions of real or sham tDCS over the right DLPFC (anode: F4, cathode: behind C2) at 2 mA for 20 minutes during emotional working memory training (N-back task). At baseline and within a week after the tDCS training sessions, stress regulation was assessed by fear-potentiated startle responses and subjective fear in a threat-of-shock paradigm with instructed emotional downregulation. Results were analyzed in generalized linear mixed-effects models. RESULTS: Threat-of-shock responses and emotional working memory performance showed no significant group-level effects of the real vs sham tDCS training intervention (p > 0.07). In contrast, when considering baseline theta/beta ratios or the other tDCS response predictors, exploratory results showed a trait-dependent beneficial effect of tDCS on emotional working memory training performance during the first session (p < 0.01). CONCLUSIONS: No evidence was found for effectivity of the tDCS training intervention to improve stress regulation in healthy military personnel. The emotional working memory training results emphasize the importance of studying the effects of tDCS in relation to individual differences. CLINICAL TRIAL REGISTRATION: This study was preregistered on September 16, 2019, at the Netherlands Trial Register (www.trialregister.nl) with ID: NL8028.

[Effects of non-invasive neuromodulation on the cognitive profile of people with anorexia nervosa: A scoping review]. / Effets de la neuromodulation cérébrale non invasive sur le profil cognitif des personnes atteintes d'anorexie mentale : étude de la portée.

BACKGROUND: The use of non-invasive neuromodulation is emerging in the treatment of anorexia nervosa. Despite promising results, further research is needed to improve our understanding of these techniques and to adapt interventions to this population. As anorexia nervosa is associated with several cognitive difficulties and cerebral anomalies, the aim of the present study was to summarize the available data on the effects of non-invasive neuromodulation on the neuropsychological profile of people with anorexia nervosa. METHOD: A scoping review was conducted by searching in PsycINFO, PubMed and CINAHL databases to systematically identify relevant studies published between 1994 and 2023 on the treatment of anorexia nervosa with repetitive transcranial magnetic stimulation, transcranial direct current stimulation or neurofeedback electroencephalogram. RESULTS: Seventeen articles were included, including 12 on repetitive transcranial magnetic stimulation, four on transcranial direct current stimulation and one on neurofeedback electroencephalogram. Of these, only three studies included a neuropsychological measure to assess the impact of neuromodulation on participants' cognitive functions. CONCLUSIONS: Including detailed neuropsychological measures in clinical trials of non-invasive neuromodulation is highly recommended and appears essential to improve our understanding of these techniques and optimize their efficacy in the treatment of anorexia nervosa.