Cerebellar tDCS combined with augmented reality treadmill for freezing of gait in Parkinson's disease: a randomized controlled trial.

BACKGROUND: Parkinson's disease (PD) is often accompanied by gait disorders and freezing of gait (FoG), disabling symptoms that are resistant to conventional dopamine treatments. Given the cerebellum's connectivity with the motor cortex and basal ganglia, and its implication in PD, combining transcranial direct current stimulation targeting the cerebellum (ctDCS) with physical exercise might improve gait and balance. OBJECTIVE: This study aimed to evaluate the effectiveness of a novel rehabilitation approach that combines noninvasive cerebellar stimulation with motor-cognitive training via an augmented reality treadmill (C-Mill VR+) in individuals with PD and FoG. METHODS: Seventeen individuals with PD exhibiting FoG were enrolled in a randomized controlled trial. The participants were randomly assigned to a group receiving motor-cognitive training on the C-Mill VR+ with either ctDCS or sham ctDCS. Assessments were conducted pre-intervention (T0), post-intervention (T1) after 10 sessions, and at 4-week follow-up (T2), using various clinical scales. Additionally, C-Mill assessments of postural stability and gait were conducted at T0 and T1. RESULTS: Although no significant time*group interactions were observed for any of the clinical variables measured, some were found in the C-Mill measures. Specifically, right lower limb sway in static conditions, both with eyes open (OAD) and eyes closed (OCD), significantly improved at T1 in the ctDCS group compared with the sham group. CONCLUSIONS: C-Mill outcomes indicate that the combined treatment may enhance motor control. Participants who received ctDCS along with augmented reality motor-cognitive training showed better postural stability.

Transcranial Direct Current Stimulation for Cognitive Impairment Rehabilitation: A Bibliometric Analysis.

BACKGROUND AND AIMS: As global demographics shift toward an older population, cognitive impairment is becoming increasingly critical. Transcranial Direct Current Stimulation (tDCS), an innovative brain stimulation technique, has the potential to significantly improve cognitive function. Our main aim is to comprehensively analyze the existing literature, identify key aspects of tDCS research in the rehabilitation of cognitive impairment, and predict future trends in this field. METHODS: We used the Web of Science (WOS) database to search for English articles and reviews relevant to this topic. For visual analysis of the literature, we employed the WOS analysis tool, CiteSpace, along with VOSviewer software to ensure comprehensive analysis. RESULTS: We included 2940 articles published between 1998 and 2023. Over 25 years, annual publications and citations in this field increased steadily, peaking at 379 articles in 2021. Michael A. Nitsche was a major contributor. Most articles came from developed countries, primarily North America and Europe, and journals generally had modest impact factors. Research in this field primarily aims to treat cognitive impairment resulting from pathological aging or neuropsychiatric disorders, with a particular focus on specific brain regions. Recently, researchers have integrated various treatment modalities with tDCS techniques to actively investigate effective strategies to mitigate cognitive impairments associated with pathological aging. CONCLUSION: This study presents the first bibliometric analysis of the literature on tDCS in the rehabilitation of cognitive impairment, highlighting key areas of research and emerging trends. These findings provide critical insights for future tDCS interventions targeting cognitive impairment associated with pathological aging.

Exploring the use of bimodal transcranial direct current stimulation to enhance movement in individuals with patellofemoral pain-A sham-controlled double blinded pilot study.

Introduction: In individuals with patellofemoral pain (PFP), addressing increased knee valgus during weight-bearing activities typically involves strengthening weak hip muscles. However, recent literature highlights the role of altered descending central control in abnormal movements associated with PFP. While transcranial direct current stimulation (tDCS) has demonstrated the capacity to enhance neuroplasticity, its application targeting the corticomotor function of gluteal muscles in PFP remains unexplored. This study aimed to investigate the effects of combining bimodal tDCS with exercise on frontal plane kinematics in individuals with PFP. The hypothesis was that bimodal tDCS, specifically targeting the corticomotor function of the gluteal muscles, would augment the effectiveness of exercise interventions in improving frontal plane kinematics compared to sham stimulation. Methods: Ten participants with PFP participated in two sessions involving either bimodal tDCS or sham stimulation, concurrently with hip strengthening exercises. Weight-bearing tasks, including single leg squat, single leg landing, single leg hopping, forward step-down, and lateral step-down, were performed and recorded before and after each session. Pain visual analog scale (VAS) scores were also documented. A one-way ANOVA with repeated measures was employed to compare kinematics, while a Friedman test was used to compare VAS across the three conditions (pre-test, post-tDCS, and post-Sham). Results: We observed no significant differences in trunk lean angle, hip and knee frontal plane projection angles, or dynamic valgus index among the three conditions during the five weight-bearing tasks. VAS scores did not differ across the three conditions. Discussion and conclusion: A single session of tDCS did not demonstrate immediate efficacy in enhancing frontal plane kinematics or relieving pain in individuals with PFP. Considering observed positive outcomes in other neurological and orthopedic populations with multi-session tDCS applications, suggesting potential cumulative effects, further research is essential to explore the effects of multi-session tDCS on weight-bearing movement and underlying neurophysiology in individuals with PFP.

Investigating the effect of brain atrophy on transcranial direct current stimulation: A computational study using ADNI dataset.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that uses weak electrical currents to modulate brain activity, thus potentially aiding the treatment of brain diseases. Although tDCS offers convenience, it yields inconsistent electric-field distributions among individuals. This inconsistency may be attributed to certain factors, such as brain atrophy. Brain atrophy is accompanied by increased cerebrospinal fluid (CSF) volume. Owing to the high electrical conductivity of CSF, its increased volume complicates current delivery to the brain, thus resulting in greater inter-subject variability. OBJECTIVE: We aim to investigate the differences in tDCS-induced electric fields between groups with different severities of brain atrophy. METHODS: We classified 180 magnetic resonance images into four groups based on the presence of Alzheimer's disease and sex. We used two montages, i.e., F-3 & Fp-2 and TP-9 & TP-10, to target the left rostral middle frontal gyrus and the hippocampus/amygdala complex, respectively. Differences between the groups in terms of regional volume variation, stimulation effect, and correlation were analyzed. RESULTS: Significant differences were observed in the geometrical variations of the CSF and two target regions. Electric fields induced by tDCS were similar in both sexes. Unique patterns were observed in each group in the correlation analysis. CONCLUSION: Our findings show that factors such as brain atrophy affect the tDCS results and that the factors present complex relationships. Further studies are necessary to better understand the relationships between these factors and optimize tDCS as a therapeutic tool.

TMS and tDCS as potential tools for the treatment of cognitive deficits in Parkinson's disease: a meta-analysis.

BACKGROUND: Cognitive deficits are common nonmotor symptoms in Parkinson's disease (PD). Non-Invasive Brain Stimulation (NIBS) could be a potential aid to prevent or delay dementia progression in this clinical population. However, previous studies reported controversial results concerning their efficacy on cognitive symptoms of PD. Hence, the present meta-analysis aims to systematically examine the effects of NIBS as possible treatments for PD cognitive impairments. Understanding NIBS' impact on these symptoms may be of outstanding importance to implement new therapeutic strategies and improve the patients' quality of life. METHODS: EMBASE, Scopus, and PubMed databases were systematically searched for consecutive studies published from 2000 to March 2023 describing Randomized Controlled Trials studies evaluating the effect of NIBS on PD cognitive symptoms. From the included studies, data concerning neuropsychological tests were extracted and grouped into six cognitive domains, separately analyzed. Hedge's method was computed as the effect size measure of the extracted data; heterogeneity among studies and publication bias were also assessed. The Cochrane's RoB2 tool was used to evaluate the risk of bias for each of the included studies. RESULTS: After database searching and screening of texts, sixteen studies met the inclusion criteria. No significant results emerged from any investigated cognitive domain when comparing NIBS and sham treatments. CONCLUSION: Several factors may have contributed to the lack of effects; among these, methodological choices, the small sample of studies, the high heterogeneity of data and stimulation protocols pose the need for more controlled studies to highlight the potentiality of NIBS as a future treatment for PD cognitive impairments.

Enhanced network synchronization connectivity following transcranial direct current stimulation (tDCS) in bipolar depression: Effects on EEG oscillations and deep learning-based predictors of clinical remission.

AIM: To investigate oscillatory networks in bipolar depression, effects of a home-based tDCS treatment protocol, and potential predictors of clinical response. METHODS: 20 participants (14 women) with bipolar disorder, mean age 50.75 ±â€¯10.46 years, in a depressive episode of severe severity (mean Montgomery-Åsberg Rating Scale (MADRS) score 24.60 ±â€¯2.87) received home-based transcranial direct current stimulation (tDCS) treatment for 6 weeks. Clinical remission defined as MADRS score < 10. Resting-state EEG data were acquired at baseline, prior to the start of treatment, and at the end of treatment, using a portable 4-channel EEG device (electrode positions: AF7, AF8, TP9, TP10). EEG band power was extracted for each electrode and phase locking value (PLV) was computed as a functional connectivity measure of phase synchronization. Deep learning was applied to pre-treatment PLV features to examine potential predictors of clinical remission. RESULTS: Following treatment, 11 participants (9 women) attained clinical remission. A significant positive correlation was observed with improvements in depressive symptoms and delta band PLV in frontal and temporoparietal regional channel pairs. An interaction effect in network synchronization was observed in beta band PLV in temporoparietal regions, in which participants who attained clinical remission showed increased synchronization following tDCS treatment, which was decreased in participants who did not achieve clinical remission. Main effects of clinical remission status were observed in several PLV bands: clinical remission following tDCS treatment was associated with increased PLV in frontal and temporal regions and in several frequency bands, including delta, theta, alpha and beta, as compared to participants who did not achieve clinical remission. The highest deep learning prediction accuracy 69.45 % (sensitivity 71.68 %, specificity 66.72 %) was obtained from PLV features combined from theta, beta, and gamma bands. CONCLUSIONS: tDCS treatment enhances network synchronization, potentially increasing inhibitory control, which underscores improvement in depressive symptoms. Baseline EEG-based measures might aid predicting clinical response.

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.

Effects of Non-Invasive Brain Stimulation for Degenerative Cerebellar Ataxia: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis aimed to assess the effectiveness of non-invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES), as a neurological intervention for degenerative cerebellar ataxia (DCA) based on preregistration (PROSPERO: CRD42023379192). OBJECTIVE: We aimed to explore clinical outcomes and examine the parameters associated with NIBS efficacy in DCA patients. METHODS: The PubMed, Cochrane Library, CHINAL, and PEDro databases were searched for relevant randomized controlled trials (RCTs). Data extraction, quality assessment, and heterogeneity analyses were conducted; the Grading, Recommendations, Assessment, Development, and Evaluation was used to assess the quality of evidence and a meta-analysis was performed. RESULTS: Seventeen RCTs that included 661 patients on the scale for assessment and rating of ataxia (SARA) and 606 patients on the International Cooperative Ataxia Rating Scale (ICARS) were included. These RCTs showed a serious risk of bias (RoB) and low certainty of evidence for both outcomes. NIBS significantly reduced SARA (MD = -2.49, [95% confidence interval: -3.34, -1.64]) and ICARS (-5.27 [-7.06, -3.47]); the subgroup analysis showed significant effects: rTMS and tES reduced both outcomes. However, there were no significant differences in the effects of rTMS and tES. Additional subgroup analysis indicated the impact of rTMS frequency and the total number of tES sessions on ataxia. CONCLUSION: Non-invasive brain stimulation may reduce ataxia in DCA patients, but the estimated effect size may change in future studies because the RoB was serious and the certainty of evidence was low, and the heterogeneity was high. To establish evidence for selecting NIBS methods and parameters, continued high-quality RCTs are required.

Transcranial direct current stimulation on hypertension: a systematic review and meta-analysis.

Background: Hypertension is a clinical condition that presents an enormous prevalence worldwide. Despite there being gold-standard treatments, several people frequently present sequelae and die. Transcranial direct current stimulation (tDCS) emerges as a cheap, easy-to-use, and portable intervention to modulate the central nervous system and control cardiovascular parameters. Objective: To evaluate the tDCS effects on the hemodynamic and autonomic parameters of hypertensive people. Methods: This systematic review included clinical trials published in databases that used tDCS as an intervention, isolated or associated, in hypertensive people to modulate the hemodynamic and autonomic parameters. We calculated the effect sizes, performed a meta-analysis, and evaluated the risk of bias in the studies. Three different researchers performed all the steps presented in the methods section. Results: Four studies suited the eligibility criteria of this review. Some studies showed that tDCS isolated after one session generated improvements in hemodynamic and autonomic parameters. Despite in meta-analysis, no statistical differences were detected between the groups, there was a tendency to reduce systolic (MD: -0.72 (CI: -1.54; 0.11; p = 0.06) and diastolic blood pressure (MD: -1.23; CI: -3.45; 0.99; p < 0.01), and root mean square of successive differences (MD: 0.73; CI: -0.30; 1.76; p < 0.01). There was no statistical difference after ten tDCS sessions. All the studies presented a low risk of bias. Conclusion: After one session, isolated tDCS might be able to modulate hypertensive people's hemodynamic and autonomic parameters. The anodic stimulation over the primary motor cortex shows signs of being the best target to generate a response.

Effect of non-invasive brain stimulation in children with acquired brain injury-a scoping review.

Background: Children and young people (CYP) with acquired brain injury (ABI) require early and effective neurorehabilitation to improve long-term functional outcomes. Non-invasive brain stimulation (NIBS), including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have been used to improve motor and sensory skills for children with cerebral palsy. However, there is limited evidence supporting its use in CYP with ABI. Objective: To systematically review the TMS and tDCS intervention effects on motor, sensory and other functional issues in CYP with ABI as reported in the literature. Methods: A comprehensive online bibliographic databases search was performed in various databases using keywords related to NIBS and CYP with ABI. Studies that examine the effect of NIBS intervention on motor function and other functional difficulties either as a primary or secondary objective were included in this review. Results: Fourteen studies (10 single case reports, one retrospective analysis, one case series, one randomised and one quasi-randomised controlled trial) published between 2006 and 2023 were identified. These studies examined the use of NIBS to manage motor disorders, hearing, vision, headaches, speech and language and memory issues. Seventy-six children with mild to severe ABI had received NIBS. The session frequency (3-20), duration (10-45 min) was variable, and NIBS delivered between 3 and 28 days. Conclusion: The literature describing NIBS interventions in CYP with ABI is scarce. An insufficient number of studies, inadequate information reported in them, and small sample sizes limit the ability to conclude how effective NIBS is in improving motor function and other functional issues in this cohort. Further studies are therefore necessary to examine the therapeutic effects of NIBS to manage various functional problems in the CYP with ABI.

Transcranial direct stimulation over left inferior frontal gyrus improves language production and comprehension in post-stroke aphasia: A double-blind randomized controlled study.

Transcranial direct current stimulation (tDCS) targeting Broca's area has shown promise for augmenting language production in post-stroke aphasia (PSA). However, previous research has been limited by small sample sizes and inconsistent outcomes. This study employed a double-blind, parallel, randomized, controlled design to evaluate the efficacy of anodal Broca's tDCS, paired with 20-minute speech and language therapy (SLT) focused primarily on expressive language, across 5 daily sessions in 45 chronic PSA patients. Utilizing the Western Aphasia Battery-Revised, which assesses a spectrum of linguistic abilities, we measured changes in both expressive and receptive language skills before and after intervention. The tDCS group demonstrated significant improvements over sham in aphasia quotient, auditory verbal comprehension, and spontaneous speech. Notably, tDCS improved both expressive and receptive domains, whereas sham only benefited expression. These results underscore the broader linguistic benefits of Broca's area stimulation and support the integration of tDCS with SLT to advance aphasia rehabilitation.

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.

Transcranial direct current stimulation and neuronal functional connectivity in MCI: role of individual factors associated to AD.

Background: Alzheimer's disease (AD) encompasses a spectrum that may progress from mild cognitive impairment (MCI) to full dementia, characterized by amyloid-beta and tau accumulation. Transcranial direct current stimulation (tDCS) is being investigated as a therapeutic option, but its efficacy in relation to individual genetic and biological risk factors remains underexplored. Objective: To evaluate the effects of a two-week anodal tDCS regimen on the left dorsolateral prefrontal cortex, focusing on functional connectivity changes in neural networks in MCI patients resulting from various possible underlying disorders, considering individual factors associated to AD such as amyloid-beta deposition, APOE ϵ4 allele, BDNF Val66Met polymorphism, and sex. Methods: In a single-arm prospective study, 63 patients with MCI, including both amyloid-PET positive and negative cases, received 10 sessions of tDCS. We assessed intra- and inter-network functional connectivity (FC) using fMRI and analyzed interactions between tDCS effects and individual factors associated to AD. Results: tDCS significantly enhanced intra-network FC within the Salience Network (SN) and inter-network FC between the Central Executive Network and SN, predominantly in APOE ϵ4 carriers. We also observed significant sex*tDCS interactions that benefited inter-network FC among females. Furthermore, the effects of multiple modifiers, particularly the interaction of the BDNF Val66Met polymorphism and sex, were evident, as demonstrated by increased intra-network FC of the SN in female Met non-carriers. Lastly, the effects of tDCS on FC did not differ between the group of 26 MCI patients with cerebral amyloid-beta deposition detected by flutemetamol PET and the group of 37 MCI patients without cerebral amyloid-beta deposition. Conclusions: The study highlights the importance of precision medicine in tDCS applications for MCI, suggesting that individual genetic and biological profiles significantly influence therapeutic outcomes. Tailoring interventions based on these profiles may optimize treatment efficacy in early stages of AD.

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.

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.

Hand functioning in progressive multiple sclerosis improves with tDCS added to daily exercises: A home-based randomized, double-blinded, sham-controlled clinical trial.

BACKGROUND: Many individuals with progressive multiple sclerosis (PMS) are challenged by reduced manual dexterity and limited rehabilitation options. Transcranial direct current stimulation (tDCS) during motor training can improve rehabilitation outcomes. We developed a protocol for remotely supervising tDCS to deliver sessions of stimulation paired with training at home. OBJECTIVE: This study evaluated the effectiveness of at-home tDCS paired with manual dexterity training for individuals with PMS. METHODS: Sixty-five right-hand dominant participants with PMS and hand impairment were randomized to receive either active or sham M1-SO tDCS paired with manual dexterity training over 4 weeks. Clinical outcomes were measured by the changes in Nine-Hole Peg Test (9-HPT) and Dellon-Modified-Moberg-Pick-Up Test (DMMPUT). RESULTS: The intervention had high rates of adherence and completion (98% of participants completed at least 18 of 20 sessions). The active tDCS group demonstrated significant improvement for the left hand compared with baseline in 9-HPT (-5.85 ± 6.19 vs -4.23 ± 4.34, p = 0.049) and DMMPUT (-10.62 ± 8.46 vs -8.97 ± 6.18, p = 0.049). The active tDCS group reported improvements in multiple sclerosis (MS)-related quality of life (mean increase: 5.93 ± 13.04 vs -0.05 ± -8.27; p = 0.04). CONCLUSION: At-home tDCS paired with manual dexterity training is effective for individuals with PMS, with M1-SO tDCS enhancing training outcomes and offering a promising intervention for improving and preserving hand dexterity.

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.

Integration Analysis of miRNA Circulating Expression Following Cerebellar Transcranial Direct Current Stimulation in Patients with Ischemic Stroke.

The aim of this study was to explore the molecular mechanisms underlying cerebellar transcranial direct current stimulation (ctDCS) as a rehabilitation intervention for patients with ischemic stroke, focusing on the role of microRNAs (miRNAs). Whole-transcriptome sequencing was employed to obtain circulating expression profiles of miRNAs, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and mRNAs in patients with ischemic stroke before and after 3-week ctDCS. miRanda software was used to predict the target genes of miRNAs, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to identify biological functions and signaling pathways. Subsequently, competing endogenous RNA (ceRNA) regulatory networks comprising circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA interactions were constructed. Key miRNAs in blood samples were validated through quantitative RT-PCR. In total, 43 miRNAs, 807 lncRNAs, 1,111 circRNAs, and 201 mRNAs were differentially expressed after ctDCS compared with before ctDCS. Bioinformatics analyses revealed significant enrichment of target genes regulated by differentially expressed miRNAs across multiple biological pathways. CeRNA regulatory networks implied that several miRNAs were closely related to the ctDCS. Among them, hsa-miR-181a-5p, hsa-miR-224-5p, and hsa-miR-340-3p showed significantly downregulated expression levels as confirmed by qRT-PCR. This study conducted the first-ever assessment of miRNA expression patterns in patients with ischemic stroke undergoing ctDCS. The findings revealed that ctDCS induces alterations in miRNA levels, suggesting their potential utility as therapeutic markers.

Noninvasive brain stimulation during EEG improves machine learning classification in chronic stroke.

Background: In individuals with chronic stroke and hemiparesis, noninvasive brain stimulation (NIBS) may be used as an adjunct to therapy for improving motor recovery. Specific states of movement during motor recovery are more responsive to brain stimulation than others, thus a system that could auto-detect movement state would be useful in correctly identifying the most effective stimulation periods. The aim of this study was to compare the performance of different machine learning models in classifying movement periods during EEG recordings of hemiparetic individuals receiving noninvasive brain stimulation. We hypothesized that transcranial direct current stimulation, a form of NIBS, would modulate brain recordings correlating with movement state and improve classification accuracies above those receiving sham stimulation. Methods: Electroencephalogram data were obtained from 10 participants with chronic stroke and 11 healthy individuals performing a motor task while undergoing transcranial direct current stimulation. Eight traditional machine learning algorithms and five ensemble methods were used to classify two movement states (a hold posture and an arm reaching movement) before, during and after stimulation. To minimize compute times, preprocessing and feature extraction were limited to z-score normalization and power binning into five frequency bands (delta through gamma). Results: Classification of disease state produced significantly higher accuracies in the stimulation (versus sham) group at 78.9% (versus 55.6%, p < 0.000002). We observed significantly higher accuracies when classifying stimulation state in the chronic stroke group (77.6%) relative to healthy controls (64.1%, p < 0.0095). In the chronic stroke cohort, classification of hold versus reach was highest during the stimulation period (75.2%) as opposed to the pre- and post-stimulation periods. Linear discriminant analysis, logistic regression, and decision tree algorithms classified movement state most accurately in participants with chronic stroke during the stimulation period (76.1%). For the ensemble methods, the highest classification accuracy for hold versus reach was achieved using low gamma frequency (30-50 Hz) as a feature (74.5%), although this result did not achieve statistical significance. Conclusions: Machine learning algorithms demonstrated sufficiently high movement state classification accuracy in participants with chronic stroke performing functional tasks during noninvasive brain stimulation. tDCS improved disease state and movement state classification in participants with chronic stroke.