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Contribution of transcranial direct current stimulation on inhibitory control to assess the neurobiological aspects of attention deficit hyperactivity disorder: randomized controlled trial.

ABSTRACT: BACKGROUND:The applicability of transcranial direct current stimulation (tDCS) in individuals with attention deficit hyperactivity disorder (ADHD) has not yet been investigated. This low-cost, non-invasive, and safe technique optimized to modulate the inhibitory response might be a useful treatment option for those affected by this condition. OBJECTIVE:The aim of this single center, parallel, randomized, double-blinded, sham-controlled trial is to investigate the efficacy of transcranial direct current stimulation over the prefrontal cortex on the modulation of inhibitory control in adults with attention deficit hyperactivity disorder. METHODS:A total of 60 individuals will be divided into 2 groups by block randomization to receive active or sham stimulation. Anodal stimulation over the left dorsolateral prefrontal cortex will be applied at 1 mA during a single 20-minute session. Before and after interventions, subjects will perform 2 go/no go tasks and the brain electrical activity will be recorded by electroencephalogram (EEG) with 32 channels, according to the 10-20 international EEG system. RESULTS:The trial began in May 2013 and we are currently performing the statistical analysis for the secondary outcomes. CONCLUSIONS:The findings from this study will provide preliminary results about the role of prefrontal cortex activation through tDCS on ADHD patients. TRIAL REGISTRATION:Clinicaltrials.gov NCT01968512; http://clinicaltrials.gov/ct2/show/NCT01968512 (Archived by WebCite at www.webcitation.org/6YMSW2tkD).

SUBMITTER: Cosmo C

PROVIDER: S-EPMC4451261 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Contribution of transcranial direct current stimulation on inhibitory control to assess the neurobiological aspects of attention deficit hyperactivity disorder: randomized controlled trial.

Cosmo Camila C Baptista Abrahão Fontes AF de Sena Eduardo Pondé EP

JMIR research protocols 20150518 2

<h4>Background</h4>The applicability of transcranial direct current stimulation (tDCS) in individuals with attention deficit hyperactivity disorder (ADHD) has not yet been investigated. This low-cost, non-invasive, and safe technique optimized to modulate the inhibitory response might be a useful treatment option for those affected by this condition.<h4>Objective</h4>The aim of this single center, parallel, randomized, double-blinded, sham-controlled trial is to investigate the efficacy of trans ...[more]

PMID: 25986784

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Project description:ImportanceTranscranial direct current stimulation (tDCS) has the potential to be a sustainable treatment option in pediatric attention-deficit/hyperactivity disorder (ADHD), but rigorously controlled multicenter clinical trials using state-of-the-art stimulation techniques are lacking.ObjectivesTo determine effect sizes of changes in cognitive and clinical measures and to assess safety and tolerability in the course of optimized multichannel tDCS over prefrontal target regions in pediatric ADHD.Design, setting, and participantsIn the sham-controlled, double-blind, parallel-group randomized clinical trial E-StimADHD (Improving Neuropsychological Functions and Clinical Course in Children and Adolescents With ADHD With Anodal Transcranial Direct Current Stimulation of the Prefrontal Cortex: A Randomized, Double-Blind, Sham-Controlled, Parallel Group Trial Using an Uncertified Class IIa Device) with 2 independent study arms, participants were enrolled from September 15, 2018, to August 10, 2021, and follow-up was completed October 4, 2021. Data were analyzed January 26, 2022, to November 8, 2023. The trial was conducted at the departments of child and adolescent psychiatry or pediatrics of 5 university hospitals in Portugal and Germany. Youths 10 to 18 years of age with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (all presentations), an IQ of at least 80, and the ability to refrain from stimulant medication during participation in the trial were eligible.InterventionsOptimized multichannel anodal tDCS or sham stimulation (1 mA, 20 minutes) targeting the left dorsolateral prefrontal cortex (lDLPFC; study A) or the right inferior frontal gyrus (rIFG; study B) was applied in 10 sessions, concurrent with performance on a cognitive target task (study A, working memory assessed in the n-back task; study B, interference control assessed in the flanker task).Main outcomes and measuresEffect sizes for changes in accuracy measures (d-prime or flanker effect) in the target tasks assessed after the intervention. Primary analyses were based on the modified intention-to-treat set.ResultsThis study included 69 youths (54 [78%] male) with a median age of 13.3 years (IQR, 11.9-14.9 years). Compared with sham tDCS, verum stimulation of the lDLPFC led to significantly lower working memory accuracy (effect size, -0.43 [95% CI, -0.68 to -0.17]; P = .001). Stimulation of the rIFG significantly improved interference control (effect size, 0.30 [95% CI, 0.04-0.56]; P = .02). Adverse events were mostly mild and transient and did not occur more often in the verum group. For example, the most frequent adverse events were headache (sham, n = 30; verum, n = 20), nasopharyngitis (sham, n = 11; verum, n = 5), and feeling of electric discharge (sham, n = 5; verum, n = 3).Conclusions and relevanceIn this randomized clinical trial, prefrontal anodal tDCS induced small- to medium-sized effects in youths with ADHD, with only mild and transient adverse events. The optimized multichannel montage chosen to target the lDLPFC, however, decreased working memory performance. This unexpected finding stresses the importance of incorporating insights from basic research on the mechanisms and preconditions of successful tDCS in future study designs to advance application of tDCS in pediatric ADHD.Trial registrationGerman Clinical Trials Register ID: DRKS00012659.

Project description:Transcranial direct current stimulation (tDCS) is a promising method for altering cortical excitability with clinical implications in neuropsychiatric diseases. Its application in neurodevelopmental disorders especially attention-deficit hyperactivity disorder (ADHD), is in early stage and promising but its effectiveness has not been systematically examined yet. We conducted a meta-analysis on the effectiveness of tDCS on the most studied neuropsychological symptoms of ADHD, which is the first reported meta-analysis of tDCS studies on ADHD. Data from 10 randomized controlled studies (including 11 separate experiments) targeting inhibitory control, and/or working memory (WM) in ADHD were included. Results show that overall tDCS significantly improved inhibitory control. Sub-analyses further show that dorsolateral prefrontal cortex (dlPFC) (but not right inferior frontal gyrus) tDCS and anodal (but not cathodal) tDCS significantly improved inhibitory control with a small effect size. Anodal dlPFC-tDCS had the largest significant effect on inhibitory control with a small-to-medium effect size. Additionally, a significant improving effect of tDCS on inhibitory control accuracy (but not response time) and WM speed (but not accuracy) were found. Overall, this meta-analysis supports a beneficial effect of tDCS on inhibitory control and WM in ADHD with a small-to-medium effect size. TDCS seems to be a promising method for improving neuropsychological and cognitive deficits in ADHD. However, there might be a dissociation between neuropsychological deficits and clinical symptoms of ADHD and therefore, the significance of this meta-analysis for clinical purposes is limited. Future studies should systematically evaluate the role of inter-individual factors (i.e., ADHD subtype, types of the deficit) and stimulation parameters (i.e., site, polarity, intensity, duration, repetition rate) on tDCS efficacy in ADHD population and examine whether benefits are long-term.

Project description:BackgroundA challenge facing clinical neuroscientists is how best to synthesize diverse and sometimes inconsistent evidence for neuropsychological deficits and brain system dysfunction found in psychiatric disorders into models that guide etiological and treatment research. Multiple-pathway models suggest that psychiatric symptoms might arise from pathophysiology in different neural systems. This study tested dual-pathway model predictions for attention-deficit/hyperactivity disorder (ADHD) that reward and executive function cognitive deficits should be related to abnormalities in corresponding functionally specialized neural systems.MethodsBehavioral inhibition and preference for immediate rewards were assessed in N = 251 adolescent boys and girls ages 12 to 18 diagnosed with DSM-IV combined-subtype ADHD or non-ADHD control subjects. Following taxometric analyses of test performance, the resulting subgroups were compared on a functional magnetic resonance imaging monetary incentive delay task probing reward anticipation and go/no-go task of motor response inhibition.ResultsThree ADHD subgroups were identified consistent with different proposed pathways-ADHD with executive function/motor inhibition deficits, ADHD with both executive and reward deficits, and ADHD with relatively normal test performance. Each cognitive domain mapped to different ADHD brain dysfunction features as expected. However, no brain abnormalities were found common to all ADHD subgroups despite the fact they had nearly identical ADHD-related clinical characteristics.ConclusionsThe results suggest that combined-subtype ADHD is a collection of discrete disorders for which a comparable behavioral end point arises through different neurobiological pathways. The findings raise caution about applying common cause, single-deficit conceptual models to individual ADHD patients and should prompt researchers to consider biologically defined, multifactorial etiological models for other psychiatric diagnoses.

Project description:BackgroundTranscranial magnetic stimulation (TMS) is a promising neuromodulation technique that has been widely used in neuropsychiatric disorders, but there was no evidence on its effect on the improvement attention-deficit hyperactivity disorder (ADHD).ObjectiveThis systematic review and meta-analysis aimed to investigate the efficacy and safety of TMS in reducing ADHD symptoms.MethodWe systematically searched four databases (PubMed, Embase, Web of Science, and Cochrane Library databases) for randomized controlled/crossover trials on the efficacy and safety of TMS on ADHD symptom improvement compared to sham rTMS or non-TMS interventions, published until September 18, 2024. Extracted data from the included studies involved patient characteristics, intervention protocols, and main outcomes. The effect size of the TMS treatment was evaluated using the standardized mean difference (SMD) with a 95% confidence interval (CI), calculated with either a random effects model or fixed effects model depending on the level of heterogeneity.ResultEight studies (325 ADHD patients in total) were included in this systematic review and meta-analysis. According to the core symptoms, TMS significantly improved inattention (SMD = -0.94, 95% CI = -1.33 to -0.56, p < 0.001) and hyperactivity/impulsivity (SMD = -0.98, 95% CI = -1.27 to -0.69, p < 0.001) compared to non-TMS interventions after 3-6 weeks of intervention. During the 1-month follow-up, the TMS group still demonstrated a significant improvement in inattention symptoms compared to the non-TMS group (SMD = -0.67, 95% CI = -1.06 to 0.28, p < 0.001). The total symptoms in the TMS group only showed improvement in the 1-month follow-up compared to the non-TMS group. (SMD = -0.48, 95% CI = -0.82 to -0.14, p = 0.005). Only minor adverse events were reported in the included studies, comprising headache and scalp discomfort.ConclusionTMS significantly improved the inattention, hyperactivity/impulsivity, and total symptom scores in ADHD patients with minor adverse events. Future research should focus on the association between different brain regions and symptoms in ADHD patients, which is crucial for stimulation navigation in TMS interventions. The trial is registered in PROSPERO (PROSPERO registry number: CRD42023473853).

Project description:Background/objectivesAttention-deficit/hyperactivity disorder (ADHD) currently lacks a universally accepted biomarker or diagnostic test, underscoring the need for objective and effective assessment methods. Transcranial magnetic stimulation (TMS) has emerged as a promising tool for both assessing cortical excitability and providing therapeutic interventions. This study conducted two independent meta-analyses to evaluate: 1) the potential of TMS in assessing cortical excitability, and 2) its therapeutic efficacy in managing ADHD symptoms.MethodsA systematic search was conducted in EMBASE, MEDLINE, PsycINFO, ClinicalTrials, and PubMed following PRISMA guidelines. The "cortical excitability" meta-analysis included studies comparing TMS-EMG or TMS-EEG neurophysiological measures between ADHD patients and healthy controls. The "therapeutic" meta-analysis focused on randomized controlled trials (RCTs) evaluating repetitive TMS (rTMS) effects on ADHD symptoms. Standardized mean differences (SMDs) were calculated for pooled effect sizes.ResultsIn the "cortical excitability" meta-analysis, 17 studies were included, demonstrating significantly reduced short-interval intracortical inhibition (SICI) in ADHD compared to healthy controls (pooled SMD = 0.65, 95% CI: 0.41-0.88, P < 0.00001). No significant differences were observed for motor evoked potentials (MEP), motor thresholds (aMT/rMT), cortical silent period (cSP), ipsilateral silent period (iSP), or intracortical facilitation (ICF). The "therapeutic" meta-analysis, encompassing 8 samples from 7 studies, demonstrated that rTMS significantly improved ADHD symptoms compared to control conditions (pooled SMD = 0.45, 95% CI: 0.19-0.70, P = 0.0006).ConclusionsThis study highlights the potential of TMS as both a diagnostic and therapeutic tool in ADHD. Reduced SICI appears to be a key neurophysiological marker of ADHD, reflecting cortical GABAergic dysfunction. Additionally, rTMS shows promise in alleviating ADHD symptoms, though further studies are needed to confirm long-term therapeutic benefits and optimize stimulation protocols.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024507867.

Dataset Information

Contribution of transcranial direct current stimulation on inhibitory control to assess the neurobiological aspects of attention deficit hyperactivity disorder: randomized controlled trial.

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Contribution of transcranial direct current stimulation on inhibitory control to assess the neurobiological aspects of attention deficit hyperactivity disorder: randomized controlled trial.

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