A meta-analysis of the effects of transcranial direct current stimulation combined with cognitive training on working memory in healthy older adults.

Background: Working memory (WM) loss, which can lead to a loss of independence, and declines in the quality of life of older adults, is becoming an increasingly prominent issue affecting the ageing population. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, is emerging as a potential alternative to pharmacological treatments that shows promise for enhancing WM capacity and May enhance the effects of cognitive training (CT) interventions. Objective: The purpose of this meta-analysis was to explore how different tDCS protocols in combination with CT enhanced WM in healthy older adults. Methods: Randomized controlled trials (RCTs) exploring the effects of tDCS combined with CT on WM in healthy older adults were retrieved from the Web of Science, PubMed, Embase, Scopus and the Cochrane Library databases. The search time period ranged from database inception to January 15, 2024. Methodological quality of the trials was assessed using the risk-of-bias criteria for RCTs from the Cochrane Collaboration Network, and RevMan 5.3 (Cochrane, London, United Kingdom) was used for the meta-analysis of the final literature outcomes. Results: Six RCTs with a total of 323 participants were ultimately included. The results of the meta-analysis show that tDCS combined with CT statistically significantly improves WM performance compared to the control sham stimulation group in healthy older adults [standard mean difference (SMD) = 0.35, 95% CI: 0.11-0.59, I 2 = 0%, Z = 2.86, p = 0.004]. The first subgroup analysis indicated that, when the stimulus intensity was 2 mA, a statistically significant improvement in WM performance in healthy older adults was achieved (SMD = 0.39, 95% CI: 0.08-0.70, I 2 = 6%, Z = 2.46, p = 0.01). The second subgroup analysis showed that long-term intervention (≥ 10 sessions) with tDCS combined with CT statistically significantly improved WM compared to the control group in healthy older adults (SMD = 0.72, 95% CI: 0.22-1.21, I 2 = 0%, Z = 2.85, p = 0.004). Conclusion: tDCS combined with CT statistically significantly improves WM in healthy older adults. For the stimulus parameters, long-term interventions (≥ 10 sessions) with a stimulation intensity of 2 mA are the most effective.

Single session and repeated anodal transcranial direct current stimulation over the right dorsolateral prefrontal cortex increases reflective thinking but not working memory updating performance.

Background: Anodal transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex (DLPFC) has shown to have effects on different domains of cognition yet there is a gap in the literature regarding effects on reflective thinking performance. Objective: The current study investigated if single session and repeated anodal tDCS over the right DLPFC induces effects on judgment and decision-making performance and whether these are linked to working memory (updating) performance or cognitive inhibition. Methods: Participants received anodal tDCS over the right DLPFC once (plus sham tDCS in a second session) or twice (24 h apart). In the third group participants received a single session of sham stimulation only. Cognitive characteristic measures were administered pre-stimulation (thinking disposition, impulsivity, cognitive ability). Experimental tasks included two versions of the Cognitive Reflection Test (numeric vs verbal-CRT), a set of incongruent base-rate vignettes, and two working memory tests (Sternberg task and n-back task). Forty-eight participants (mean age = 26.08 ± 0.54 years; 27 females) were recruited. Results: Single sessions of tDCS were associated with an increase in reflective thinking performance compared to the sham conditions, with stimulation improving scores on incongruent base rate tasks as well as marginally improving numeric CRT scores (compared to sham), but not thinking tasks without a numeric component (verbal-CRT). Repeated anodal stimulation only improved numeric CRT scores. tDCS did not increase working memory (updating) performance. These findings could not be explained by a practice effect or a priori differences in cognitive characteristics or impulsivity across the experimental groups. Conclusion: The current results demonstrate the involvement of the right DLPFC in reflective thinking performance which cannot be explained by working memory (updating) performance or general cognitive characteristics of participants.

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.

Induction and stabilization of delta frequency brain oscillations by phase-synchronized rTMS and tACS.

BACKGROUND: Brain oscillations in the delta frequency band have been linked with deep sleep and consolidation of declarative memory during sleep. However, the causal relationship of these associations remains not competely clarified, primarily due to constraints by technical limitations of brain stimulation approaches suited to induce and stabilize respective oscillatory activity in the human brain. The objective of this study was to establish a non-invasive brain stimulation protocol capable of reliably inducing, and stabilizing respective oscillatory activity in the delta frequency range. HYPOTHESIS: We aimed to develop an efficient non-invasive brain stimulation (NIBS) protocol for delta frequency induction and stabilization via concurrent, phase-locked repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS). We hypothesized that rTMS induces oscillatory resting-state activity in the delta frequency and that tACS stabilizes this effect, as has been shown before for alpha and theta frequencies. METHODS: 19 healthy participants took part in a repeated-measures experimental protocol. We applied rTMS pulses synchronized with the peak or trough phase of 0.75Hz tACS over the bilateral prefrontal cortex. Resting state EEG in eyes-open (EO) and eyes-closed (EC) conditions was recorded before, immediately after and every 10 min for up to 1 h after intervention. RESULTS: rTMS phase-synchronized to the trough of the tACS waveform significantly increased delta frequency activity for up to 60 min in both EO and EC conditions after stimulation. The effects extended from frontal to temporal regions and this enhancement of oscillatory activity was shown to be specific for the delta frequency range. CONCLUSION: Concurrent, trough-synchronized 0.75 Hz rTMS combined with tACS may be a reliable protocol to induce long-lasting oscillatory activity in the delta frequency range. The results of the current study might perspectively be relevant for clinical treatment of sleep disturbances which are accompanied by pathologically altered brain oscillations, and enhancement of memory consolidation.

The effects of repetitive transcranial magnetic and transcranial direct current stimulation on memory functions in older adults with mild cognitive impairment: a systematic review and meta-analysis.

Mild cognitive impairment (MCI) is a condition that impairs activities of daily living, and often transforms to dementia. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) show promise in improving cognitive functions in MCI patients. In this meta-analysis, we aimed to compare the effects of rTMS and tDCS on memory functions in MCI patients. We explored eight databases from their inception to March 16, 2024. We obtained 11 studies with 406 patients with MCI. We used the standardized mean difference (SMD) with a 95% confidence interval (CI) to synthesize the effect size. rTMS and tDCS significantly improved memory functions in MCI patients (SMD = 0.61; 95% CI: 0.41-0.82; p < 0.00001; I2 = 22%). In subgroup analysis of number of stimulation sessions, both rTMS and tDCS over 10 sessions (SMD = 0.84; 95% CI: 0.50-1.17, p < 0.00001, I2 = 0%) significantly improved the memory function in MCI patients. The subgroup analyses on different stimulation types (SMD = 0.78; 95% CI: 0.51-1.06; p < 0.00001; I2 = 0%) and treatment persistent effects (SMD = 0.93; 95% CI: 0.51-1.35, p < 0.0001, I2 = 0%) showed that rTMS was more effective than tDCS. rTMS with a stimulation frequency of 10 Hz (SMD = 0.86; 95% CI: 0.51-1.21; p < 0.00001; I2 = 0%) and over 10 sessions (SMD = 0.98; 95% CI: 0.58-1.38; p < 0.00001; I2 = 0%) at multiple sites (SMD = 0.97; 95% CI: 0.44-1.49; p = 0.0003; I2 = 0%) showed a great improvement in the memory performance of patients with MCI. rTMS was more likely to appear temporary side effects (risk ratio (RR) = 3.18, 95% CI: 1.29-7.83, p = 0.01). This meta-analysis suggests that rTMS and tDCS are safe and efficient tools to improve memory functions in patients with MCI, while rTMS had a larger effect than tDCS. rTMS with a stimulation frequency of 10 Hz targeted on multiple sites over 10 sessions showed the greatest effect. We could not conclude parameters of tDCS because of insufficient data. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024558991.

Acute aerobic exercise modulates cognition and cortical excitability in adults with attention-deficit hyperactivity disorder (ADHD) and healthy controls.

Evidence suggests aerobic exercise has beneficial effects on cognitive performance in adults with attention-deficit hyperactivity disorder (ADHD). The underlying mechanisms might depend on mechanisms of exercise-mediated brain physiology. The study aims to investigate the effects of acute aerobic exercise on cortical excitability and cognitive performance, and the correlation between these phenomena in adults with ADHD. Twenty-six drug-naïve ADHD adults, and twenty-six age-, and gender-matched healthy controls were assessed with respect to cortical excitability and cognitive performance before and after acute aerobic exercise (a single session for 30 min) or a control intervention. The results show significantly enhanced intracortical facilitation (ICF) and decreased short intracortical inhibition (SICI) after aerobic exercise in healthy subjects. In contrast, SICI was significantly enhanced following acute aerobic exercise in ADHD. In ADHD, furthermore inhibitory control and motor learning were significantly improved after the acute aerobic exercise intervention. Alterations of SICI induced by aerobic exercise, and inhibitory control and motor learning improvement were significantly positively correlated in the ADHD group. Aerobic exercise had partially antagonistic effects in healthy controls, and ADHD patients. Furthermore, aerobic exercise-induced cognition-enhancing effects in ADHD depend on specific alterations of brain physiology, which differ from healthy humans.

Transcranial Direct-Current Stimulation Over the Primary Motor Cortex and Cerebellum Improves Balance and Shooting Accuracy in Elite Ice Hockey Players.

PURPOSE: To investigate the effects of transcranial direct-current stimulation (tDCS) applied over the primary motor cortex (M1) and cerebellum on balance control and shooting accuracy in elite ice hockey players. METHODS: Twenty-one elite ice hockey players underwent anodal tDCS over the M1 (a-tDCSM1), anodal tDCS over the cerebellum (a-tDCSCB), concurrent dual-site anodal tDCS over the M1 and the cerebellum (a-tDCSM1+CB), and sham stimulation (tDCSSHAM). Before and after receiving tDCS (2 mA for 15 min), participants completed an ice hockey shooting-accuracy test, Pro-Kin balance test (includes stance test and proprioceptive assessment), and Y-balance test in randomized order. RESULTS: For static balance performance, the ellipse area in the 2-legged stance with eyes open and the 1-legged stance with the dominant leg significantly improved following a-tDCSM1, a-tDCSCB, and concurrent dual-site a-tDCSM1+CB, compared with tDCSSHAM (all P < .05, Cohen d = 0.64-1.06). In dynamic balance performance, the average trace error of the proprioceptive assessment and the composite score of the Y-balance test with the dominant leg significantly improved following a-tDCSM1 and concurrent dual-site a-tDCSM1+CB (all P < .05, Cohen d = 0.77-1.00). For the ice hockey shooting-accuracy test, shooting-accuracy while standing on the unstable platform significantly increased following a-tDCSM1 (P = .010, Cohen d = 0.81) and a-tDCSCB (P = .010, Cohen d = 0.92) compared with tDCSSHAM. CONCLUSION: tDCS could potentially be a valuable tool in enhancing static and dynamic balance and shooting accuracy on unstable platforms in elite ice hockey players.

Temporal gamma tACS and auditory stimulation affect verbal memory in healthy adults.

Research suggests a potential of gamma oscillation entrainment for enhancing memory in Alzheimer's disease and healthy subjects. Gamma entrainment can be accomplished with oscillatory electrical, but also sensory stimulation. However, comparative studies between sensory stimulation and transcranial alternating current stimulation (tACS) effects on memory processes are lacking. This study examined the effects of rhythmic gamma auditory stimulation (rAS) and temporal gamma-tACS on verbal long-term memory (LTM) and working memory (WM) in 74 healthy individuals. Participants were assigned to two groups according to the stimulation techniques (rAS or tACS). Memory was assessed in three experimental blocks, in which each participant was administered with control, 40, and 60 Hz stimulation in counterbalanced order. All interventions were well-tolerated, and participants reported mostly comparable side effects between real stimulation (40 and 60 Hz) and the control condition. LTM immediate and delayed recall remained unaffected by stimulations, while immediate recall intrusions decreased during 60 Hz stimulation. Notably, 40 Hz interventions improved WM compared to control stimulations. These results highlight the potential of 60 and 40 Hz temporal cortex stimulation for reducing immediate LTM recall intrusions and improving WM performance, respectively, probably due to the entrainment of specific gamma oscillations in the auditory cortex. The results also shed light on the comparative effects of these neuromodulation tools on memory functions, and their potential applications for cognitive enhancement and in clinical trials.

Investigating the neural mechanisms of transcranial direct current stimulation effects on human cognition: current issues and potential solutions.

Transcranial direct current stimulation (tDCS) has been studied extensively for its potential to enhance human cognitive functions in healthy individuals and to treat cognitive impairment in various clinical populations. However, little is known about how tDCS modulates the neural networks supporting cognition and the complex interplay with mediating factors that may explain the frequently observed variability of stimulation effects within and between studies. Moreover, research in this field has been characterized by substantial methodological variability, frequent lack of rigorous experimental control and small sample sizes, thereby limiting the generalizability of findings and translational potential of tDCS. The present manuscript aims to delineate how these important issues can be addressed within a neuroimaging context, to reveal the neural underpinnings, predictors and mediators of tDCS-induced behavioral modulation. We will focus on functional magnetic resonance imaging (fMRI), because it allows the investigation of tDCS effects with excellent spatial precision and sufficient temporal resolution across the entire brain. Moreover, high resolution structural imaging data can be acquired for precise localization of stimulation effects, verification of electrode positions on the scalp and realistic current modeling based on individual head and brain anatomy. However, the general principles outlined in this review will also be applicable to other imaging modalities. Following an introduction to the overall state-of-the-art in this field, we will discuss in more detail the underlying causes of variability in previous tDCS studies. Moreover, we will elaborate on design considerations for tDCS-fMRI studies, optimization of tDCS and imaging protocols and how to assure high-level experimental control. Two additional sections address the pressing need for more systematic investigation of tDCS effects across the healthy human lifespan and implications for tDCS studies in age-associated disease, and potential benefits of establishing large-scale, multidisciplinary consortia for more coordinated tDCS research in the future. We hope that this review will contribute to more coordinated, methodologically sound, transparent and reproducible research in this field. Ultimately, our aim is to facilitate a better understanding of the underlying mechanisms by which tDCS modulates human cognitive functions and more effective and individually tailored translational and clinical applications of this technique in the future.

The impact of the left inferior frontal gyrus on fear extinction: A transcranial direct current stimulation study.

INTRODUCTION: Fear extinction is a fundamental component of exposure-based therapies for anxiety-related disorders. The renewal of fear in a different context after extinction highlights the importance of contextual factors. In this study, we aimed to investigate the causal role of the left inferior frontal gyrus (LiFG) in the context-dependency of fear extinction learning via administration of transcranial direct current stimulation (tDCS) over this area. METHODS: 180 healthy subjects were assigned to 9 groups: 3 tDCS conditions (anodal, cathodal, and sham) × 3 context combinations (AAA, ABA, and ABB). The fear conditioning/extinction task was conducted over three consecutive days: acquisition, extinction learning, and extinction recall. tDCS (2 mA, 10min) was administered during the extinction learning phase over the LiFG via a 4-electrode montage. Skin conductance response (SCR) data and self-report assessments were collected. RESULTS: During the extinction learning phase, groups with excitability-enhancing anodal tDCS showed a significantly higher fear response to the threat cues compared to cathodal and sham stimulation conditions, irrespective of contextual factors. This effect was stable until the extinction recall phase. Additionally, excitability-reducing cathodal tDCS caused a significant decrease of the response difference between the threat and safety cues during the extinction recall phase. The self-report assessments showed no significant differences between the conditions throughout the experiment. CONCLUSION: Independent of the context, excitability enhancement of the LiFG did impair fear extinction, and led to preservation of fear memory. In contrast, excitability reduction of this area enhanced fear extinction retention. These findings imply that the LiFG plays a role in the fear extinction network, which seems to be however context-independent.

Does a single session of transcranial direct current stimulation enhance both physical and psychological performance in national- or international-level athletes? A systematic review.

Some studies showed that a single session of transcranial direct current stimulation (tDCS) has the potential of modulating motor performance in healthy and athletes. To our knowledge, previously published systematic reviews have neither comprehensively investigated the effects of tDCS on athletic performance in both physical and psychological parameters nor investigated the effects of tDCS on high-level athletes. We examined all available research testing a single session of tDCS on strength, endurance, sport-specific performance, emotional states and cognitive performance for better application in competition and pre-competition trainings of national- or international-level athletes. A systematic search was conducted in PubMed, Web of Science, EBSCO, Embase, and Scopus up until to June 2023. Studies were eligible when participants had sports experience at a minimum of state and national level competitions, underwent a single session of tDCS without additional interventions, and received either sham tDCS or no interventions in the control groups. A total of 20 experimental studies (224 participants) were included from 18 articles. The results showed that a single tDCS session improved both physical and psychological parameters in 12 out of the 18 studies. Of these, six refer to the application of tDCS on the motor system (motor cortex, premotor cortex, cerebellum), five on dorsolateral prefrontal cortex and two on temporal cortex. The most sensitive to tDCS are strength, endurance, and emotional states, improved in 67%, 75%, and 75% of studies, respectively. Less than half of the studies showed improvement in sport-specific tasks (40%) and cognitive performance (33%). We suggest that tDCS is an effective tool that can be applied to competition and pre-competition training to improve athletic performance in national- or international-level athletes. Further research would explore various parameters (type of sports, brain regions, stimulation protocol, athlete level, and test tasks) and neural mechanistic studies in improving efficacy of tDCS interventions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326989, identifier CRD42022326989.

Effects of high-intensity interval training combined with dual-site transcranial direct current stimulation on inhibitory control and working memory in healthy adults.

Transcranial direct current stimulation (tDCS) and high-intensity interval training (HIIT) have been demonstrated to enhance inhibitory control and working memory (WM) performance in healthy adults. However, the potential benefits of combining these two interventions have been rarely explored and remain largely speculative. This study aimed to explore the effects of acute HIIT combined with dual-site tDCS over the dorsolateral prefrontal cortex (DLPFC, F3 and F4) on inhibitory control and WM in healthy young adults. Twenty-five healthy college students (20.5 ± 1.3 years; 11 females) were recruited to complete HIIT + tDCS, HIIT + sham-tDCS, rest + tDCS, and rest + sham-tDCS (CON) sessions in a randomized crossover design. tDCS or sham-tDCS was conducted after completing HIIT or a rest condition of the same duration. The Stroop and 2-back tasks were used to evaluate the influence of this combined intervention on cognitive tasks involving inhibitory control and WM performance in post-trials, respectively. Response times (RTs) of the Stroop task significantly improved in the HIIT + tDCS session compared to the CON session across all conditions (all p values <0.05), in the HIIT + tDCS session compared to the rest + tDCS session in the congruent and neutral conditions (all p values <0.05), in the HIIT + sham-tDCS session compared to the CON session in the congruent and neutral conditions (all p values <0.05), in the HIIT + sham-tDCS session compared to the rest + tDCS session in the congruent condition (p = 0.015). No differences were found between sessions in composite score of RT and accuracy in the Stroop task (all p values >0.05) and in the 2-back task reaction time and accuracy (all p values >0.05). We conclude that acute HIIT combined with tDCS effectively improved inhibitory control but it failed to yield cumulative benefits on inhibitory control and WM in healthy adults. These preliminary findings help to identify beneficial effects of combined interventions on cognitive performance and might guide future research with clinical populations.

Microstructural differences in the cingulum and the inferior longitudinal fasciculus are associated with (extinction) learning.

Cognitive functions, such as learning and memory processes, depend on effective communication between brain regions which is facilitated by white matter tracts (WMT). We investigated the microstructural properties and the contribution of WMT to extinction learning and memory in a predictive learning task. Forty-two healthy participants completed an extinction learning paradigm without a fear component. We examined differences in microstructural properties using diffusion tensor imaging to identify underlying neural connectivity and structural correlates of extinction learning and their potential implications for the renewal effect. Participants with good acquisition performance exhibited higher fractional anisotropy (FA) in WMT including the bilateral inferior longitudinal fasciculus (ILF) and the right temporal part of the cingulum (CNG). This indicates enhanced connectivity and communication between brain regions relevant to learning and memory resulting in better learning performance. Our results suggest that successful acquisition and extinction performance were linked to enhanced structural connectivity. Lower radial diffusivity (RD) in the right ILF and right temporal part of the CNG was observed for participants with good acquisition learning performance. This observation suggests that learning difficulties associated with increased RD may potentially be due to less myelinated axons in relevant WMT. Also, participants with good acquisition performance were more likely to show a renewal effect. The results point towards a potential role of structural integrity in extinction-relevant WMT for acquisition and extinction.

Targeting the left DLPFC and right VLPFC in unmarried romantic relationship breakup (love trauma syndrome) with intensified electrical stimulation: A randomized, single-blind, parallel-group, sham-controlled study.

BACKGROUND: Ending a romantic relationship is one of the most painful losses an adult experience. Neuroimaging studies suggest that there is a neuropsychological link between breakup experiences and bereaved individuals, and that specific prefrontal regions are involved. The aim of this study was to determine whether enhancement of left DLPFC and right VLPFC activity with a novel intensified anodal transcranial direct current stimulation protocol reduces core symptoms of love trauma syndrome (LTS) and improves treatment-related variables. METHODS: In this randomized, sham-controlled, single-blind parallel trial, we assessed the efficacy of an intensified anodal stimulation protocol (20 min, twice-daily sessions with 20 min intervals, 5 consecutive days) with two montages (left DLPFC vs right VLPFC) to reduce love trauma symptoms. 36 participants with love trauma syndrome were randomized in three tDCS condition (left DLPFC, right VLPFC, sham stimulation). LTS symptoms, treatment-related outcome variables (depressive state, anxiety, emotion regulation, positive and negative affect), and cognitive functions were assessed before, right after, and one month after intervention. RESULTS: Both DLPFC and VLPFC protocols significantly reduced LTS symptoms, and improved depressive state and anxiety after the intervention, as compared to the sham group. The improving effect of the DLPFC protocol on love trauma syndrome was significantly larger than that of the VLPFC protocol. For emotion regulation and positive and negative affect, improved regulation of emotions and positive affect and reduced negative affect were revealed after intervention in the two real stimulation conditions compared to the sham. For cognitive functions, no significant difference was observed between the groups, but again a positive effect of intervention within groups in the real stimulation conditions (DLPFC and VLPFC) was found for most components of the cognitive tasks. CONCLUSIONS: Enhancement of left DLPFC and right VLPFC activity with intensified stimulation improves LTS symptoms and treatment-related variables. For LTS symptoms, DLPFC stimulation was more efficient than VLPFC stimulation., For the other variables, no significant difference was observed between these two stimulation groups. These promising results require replication in larger trials.

Neurochemical mechanisms underlying serotonergic modulation of neuroplasticity in humans.

BACKGROUND: Studies in animals and humans have shown that cortical neuroplasticity can be modulated by increasing serotonin levels by administering selective serotonin reuptake inhibitors (SSRI). However, little is known about the mechanistic background, especially the contribution of intracortical inhibition and facilitation, which depend on gamma-aminobutyric acid (GABA) and glutamate. OBJECTIVE: We aimed to explore the relevance of drivers of plasticity (glutamate- and GABA-dependent processes) for the effects of serotonin enhancement on tDCS-induced plasticity in healthy humans. METHODS: A crossover, partially double-blinded, randomized, and sham-controlled study was conducted in 21 healthy right-handed individuals. In each of the 7 sessions, plasticity was induced via transcranial direct current stimulation (tDCS). Anodal, cathodal, and sham tDCS were applied to the left motor cortex under SSRI (20 mg/40 mg citalopram) or placebo. Short-interval cortical inhibition (SICI) and intracortical facilitation (ICF) were monitored by paired-pulse transcranial magnetic stimulation for 5-6 h after intervention. RESULTS: Under placebo, anodal tDCS-induced LTP-like plasticity decreased SICI and increased ICF. In contrast, cathodal tDCS-elicited LTD-like plasticity induced the opposite effect. Under 20 mg and 40 mg citalopram, anodal tDCS did not affect SICI largely, while ICF was enhanced and prolonged. For cathodal tDCS, citalopram converted the increase of SICI and decrease of ICF into antagonistic effects, and this effect was dosage-dependent since it lasted longer under 40 mg when compared to 20 mg. CONCLUSION: We speculate that the main effects of acute serotonergic enhancement on tDCS-induced plasticity, the increase and prolongation of LTP-like plasticity effects, involves mainly the glutamatergic system.

Adjunctive transcranial direct current stimulation to improve swallowing functions in Parkinson's disease.

Swallowing problems are frequent in Parkinson's disease (PD). The aim of this study was to determine the effectiveness of combined transcranial Direct Current Stimulation (tDCS) and Conventional Dysphagia Therapy (CDT) on dysphagia in PD patients. Twenty PD patients with dysphagia were randomized into two groups: combination therapy (anodal tDCS plus CDT) and sham tDCS combined with CDT. Anodal or sham tDCS, bilaterally over the pharyngeal motor cortex, was applied with one mA during the first 20 min (real) or 30 s (sham) of CDT, which was delivered for 30 min. Both groups received twice-daily treatment sessions within two weeks. Swallowing functions were evaluated before, immediately, and one month after the intervention via the Penetration-Aspiration Scale (PAS), and the Swallowing Disorder Questionnaire (SDQ) as the primary outcome measures, and the Dysphagia Handicap Index (DHI) as the secondary outcome measure. The results showed a significant improvement of PAS scores from baseline to post-intervention and baseline to follow-up in both groups without significant differences between groups (t=0.03, p=0.973, and t=1.27, p=0.22 for post-intervention and follow-up time points, respectively). The results showed a significant reduction of SDQ and DHI scores in both groups after the intervention, but the magnitude of the change was significantly larger in the anodal tDCS group at the post-intervention (ta=2.58, pa=0.019 and tb=2.96, pb=0.008) and follow-up (ta=2.65, pa=0.016 and tb=2.97, pb=0.008) time points. This study provides preliminary evidence that bi-hemispheric anodal tDCS combined with CDT enhances swallowing functions in patients with Parkinson's disease more than CDT alone.

Application of transcranial alternating current stimulation to improve eSports-related cognitive performance.

Introduction: Electronic Sports (eSports) is a popular and still emerging sport. Multiplayer Online Battle Arena (MOBA) and First/Third Person Shooting Games (FPS/TPS) require excellent visual attention abilities. Visual attention involves specific frontal and parietal areas, and is associated with alpha coherence. Transcranial alternating current stimulation (tACS) is a principally suitable tool to improve cognitive functions by modulation of regional oscillatory cortical networks that alters regional and larger network connectivity. Methods: In this single-blinded crossover study, 27 healthy college students were recruited and exposed to 10 Hz tACS of the right frontoparietal network. Subjects conducted a Visual Spatial Attention Distraction task in three phases: T0 (pre-stimulation), T1 (during stimulation), T2 (after-stimulation), and an eSports performance task which contained three games ("Exact Aiming," "Flick Aiming," "Press Reaction") before and after stimulation. Results: The results showed performance improvements in the "Exact Aiming" task and hint for a prevention of reaction time performance decline in the "Press Reaction" task in the real, as compared to the sham stimulation group. We also found a significant decrease of reaction time in the visual spatial attention distraction task at T1 compared to T0 in the real, but not sham intervention group. However, accuracy and inverse efficiency scores (IES) did not differ between intervention groups in this task. Discussion: These results suggest that 10 Hz tACS over the right frontal and parietal cortex might improve eSports-related skill performance in specific tasks, and also improve visual attention in healthy students during stimulation. This tACS protocol is a potential tool to modulate neurocognitive performance involving tracking targets, and might be a foundation for the development of a new concept to enhance eSports performance. This will require however proof in real life scenarios, as well optimization.

Transcranial random noise stimulation (tRNS) improves hot and cold executive functions in children with attention deficit-hyperactivity disorder (ADHD).

Children with attention deficit-hyperactivity disorder (ADHD) have impaired hot and cold executive functions, which is thought to be related to impaired ventromedial and dorsolateral prefrontal cortex (vmPFC and dlPFC) functions. The present study aimed to assess the impact concurrent stimulation of dlPFC and vmPFC through transcranial random noise stimulation (tRNS), a non-invasive brain stimulation tool which enhances cortical excitability via application of alternating sinusoidal currents with random frequencies and amplitudes over the respective target regions on hot and cold executive functions. Eighteen children with ADHD received real and sham tRNS over the left dlPFC and the right vmPFC in two sessions with one week interval. The participants performed Circle Tracing, Go/No-Go, Wisconsin Card Sorting, and Balloon Analogue Risk Tasks during stimulation in each session. The results showed improved ongoing inhibition, prepotent inhibition, working memory, and decision making, but not set-shifting performance, during real, as compared to sham stimulation. This indicates that simultaneous stimulation of the dlPFC and the vmPFC improves hot and cold executive functions in children with ADHD.

Neurostimulation targeting the epileptic focus: Current understanding and perspectives for treatment.

For the one third of people with epilepsy whose seizures are not controlled with medications, targeting the seizure focus with neurostimulation can be an effective therapeutic strategy. In this focused review, we summarize a discussion of targeted neurostimulation modalities during a workshop held in Frankfurt, Germany in September 2023. Topics covered include: available devices for seizure focus stimulation; alternating current (AC) and direct current (DC) stimulation to reduce focal cortical excitability; modeling approaches to simulate DC stimulation; reconciling the efficacy of focal stimulation with the network theory of epilepsy; and the emerging concept of 'neurostimulation zones,' which are defined as cortical regions where focal stimulation is most effective for reducing seizures and which may or may not directly involve the seizure onset zone. By combining experimental data, modeling results, and clinical outcome analysis, rational selection of target regions and stimulation parameters is increasingly feasible, paving the way for a broader use of neurostimulation for epilepsy in the future.

Targeting the prefrontal-supplementary motor network in obsessive-compulsive disorder with intensified electrical stimulation in two dosages: a randomized, controlled trial.

Obsessive-compulsive disorder (OCD) is associated with a high disease burden, and treatment options are limited. We used intensified electrical stimulation in two dosages to target a main circuitry associated with the pathophysiology of OCD, left dorsolateral prefrontal cortex (l-DLPFC), and pre-supplementary motor area (pre-SMA) and assessed clinical outcomes, neuropsychological performance, and brain physiology. In a double-blind, randomized controlled trial, thirty-nine patients with OCD were randomly assigned to three groups of sham, 2-mA, or 1-mA transcranial direct current stimulation (tDCS) targeting the l-DLPFC (F3) and pre-SMA (FC2) with anodal and cathodal stimulation respectively. The treatment included 10 sessions of 20-minute stimulation delivered twice per day with 20-min between-session intervals. Outcome measures were reduction in OCD symptoms, anxiety, and depressive states, performance on a neuropsychological test battery (response inhibition, working memory, attention), oscillatory brain activities, and functional connectivity. All outcome measures except EEG were examined at pre-intervention, post-intervention, and 1-month follow-up times. The 2-mA protocol significantly reduced OCD symptoms, anxiety, and depression states and improved quality of life after the intervention up to 1-month follow-up compared to the sham group, while the 1-mA protocol reduced OCD symptoms only in the follow-up and depressive state immediately after and 1-month following the intervention. Both protocols partially improved response inhibition, and the 2-mA protocol reduced attention bias to OCD-related stimuli and improved reaction time in working memory performance. Both protocols increased alpha oscillatory power, and the 2-mA protocol decreased delta power as well. Both protocols increased connectivity in higher frequency bands at frontal-central areas compared to the sham. Modulation of the prefrontal-supplementary motor network with intensified tDCS ameliorates OCD clinical symptoms and results in beneficial cognitive effects. The 2-mA intensified stimulation resulted in larger symptom reduction and improved more converging outcome variables related to therapeutic efficacy. These results support applying the intensified prefrontal-SMA tDCS in larger trials.