This study investigates the effects of high and low-frequency paired associative deep transcranial magnetic stimulation (dTMS) on adults with Attention Deficit Hyperactivity Disorder (ADHD). The study aims to explore whether targeting the prefrontal cortex with paired stimulation can improve symptoms of ADHD by balancing cortical arousal between the brain hemispheres. A total of 90 participants with ADHD will be recruited. Participants with ADHD will undergo three weeks of daily TMS treatment, while participants who receive a sham treatment will be included for baseline comparisons. The study will measure electrophysiological, cognitive, and clinical outcomes using a variety of assessments, including EEG, cognitive tests, and CAARS to evaluate the treatment's efficacy.
Men and women aged 21-65.
Aligned with the diagnosis of ADHD according to the criteria of the DSM-5.
Participants taking medication for the treatment of attention deficit hyperactivity disorder will be asked, starting one week before the start of the treatment until the end, to take Ritalin IR 10mg (provided that the taking of the medication will be done at least 8 hours before the start of the treatment or at least one hour after it. This instruction is also valid for taking the medication on the days of the follow-up sessions (4 and 8 weeks from the end of the daily treatment phase). Ritalin is given as the only option because a drug with a short half-life is needed. The dose can be increased up to 20 mg per dose). The choice of this drug is to ensure that changes in brain function/activity are not the result of the Ritalin medication but of the research intervention.
Give their written and oral consent to participate in the study.
Additional active psychiatric disorders in Axis I of the DSM-5.
Antipsychotic treatment, antidepressants, or mood stabilizers.
History of intolerance to TMS.
Diagnosis of severe personality disorder according to the DSM-5.
Parallel
Paired Associative Transcranial Magnetic Stimulation (TMS)
DeviceTranscranial Magnetic Stimulation (TMS) is a non-invasive technique that uses magnetic fields to stimulate nerve cells in the brain. By placing a coil on the scalp, TMS generates magnetic pulses that induce electrical currents in specific brain regions. This can alter brain activity and potentially influence behavior and symptoms of various neurological and psychiatric conditions. PAS involves the use of transcranial magnetic stimulation (TMS) at a low and high frequency to stimulate the prefrontal cortex at different areas of the brain. The goal is to assess its effects on cortical arousal and ADHD symptoms. Participants will receive daily sessions of this stimulation for three weeks, with the stimulation designed to influence brain activity and potentially alleviate symptoms of ADHD.
Change in ADHD Symptoms Assessed by the Conners' Adult ADHD Rating Scale (CAARS)
This measure evaluates the change in ADHD symptom severity using the Conners' Adult ADHD Rating Scale (CAARS), a standardized and validated assessment tool. The CAARS provides subscale scores (e.g., Inattention, Hyperactivity-Impulsivity, ADHD Index) on a scale ranging from 0 to 100, with higher scores indicating greater symptom severity. Change will be assessed by comparing scores obtained at baseline (pre-treatment) and following the intervention (post-treatment), as well as at 1-month and 2-month follow-up visits.
Change in Cognitive Control Assessed by Stroop Task Performance
This measure assesses changes in participants' cognitive control by comparing pre-treatment and post-treatment performance on the Stroop Task. Performance is evaluated based on reaction time (milliseconds) and accuracy (% correct responses) in congruent and incongruent trials. Lower reaction times and higher accuracy typically indicate better cognitive control, but outcome-neutral interpretation will be used to assess change.
Change in Working Memory Assessed by N-back Task Performance
This measure evaluates working memory by comparing participants' pre-treatment and post-treatment performance on the N-back task (2-back condition). Performance is quantified by reaction time (milliseconds) and accuracy (% correct target detections). Lower reaction times and higher accuracy reflect stronger working memory performance, but results will be analyzed in a directionally neutral manner.
Change in EEG Power Spectral Density Across Frequency Bands
This outcome assesses changes in EEG power spectral density (PSD) in the delta (0.5-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), and beta (13-30 Hz) frequency bands during resting-state EEG. PSD will be calculated using Fourier-based spectral analysis and reported in microvolts squared per hertz (µV²/Hz) at frontal and motor cortex sites.
Long-Term Change in ADHD Symptoms Assessed at Follow-Up by Conners' Adult ADHD Rating Scale (CAARS)
This outcome assesses the persistence of treatment-related changes in ADHD symptoms using the Conners' Adult ADHD Rating Scale (CAARS). The CAARS includes multiple subscale scores (e.g., Inattention, Hyperactivity-Impulsivity) ranging from 0 to 100, with higher scores indicating greater symptom severity. Scores will be compared between post-treatment and follow-up time points to evaluate sustained changes. Unit of Measure: CAARS Subscale Score (0-100).
Long-Term Change in Cognitive Control Assessed at Follow-Up by Stroop Task Performance
This outcome evaluates long-term effects of TMS on cognitive control using the Stroop Task. Performance will be measured by reaction time (milliseconds) and accuracy (% correct responses) during congruent and incongruent trials. Comparisons will be made between post-treatment and follow-up time points to assess sustained changes in executive function. Unit of Measure: Milliseconds (reaction time), Percent correct (% accuracy).
Long-Term Change in Working Memory Assessed at Follow-Up by N-back Task Performance
This outcome evaluates the persistence of treatment-related changes in working memory using the 2-back condition of the N-back Task. Performance will be assessed based on reaction time (milliseconds) and accuracy (% correct target detections). Results from post-treatment and follow-up assessments will be compared. Unit of Measure: Milliseconds (reaction time), Percent correct (% accuracy).
Change in Amplitude of TMS-Evoked Potential (TEP) Components
This outcome assesses the amplitude of specific TMS-evoked potential (TEP) components (e.g., P30, N45, N100) extracted from EEG data recorded during TMS stimulation sessions. These components reflect cortical excitability and inhibition. Unit of Measure: Microvolts (µV).
Incidence of Adverse Events Reported During and After TMS Treatment
Adverse events (AEs) will be monitored and documented throughout the TMS intervention and follow-up periods. AEs will be identified using a structured adverse event reporting form completed by study staff during each session and follow-up. Events will be categorized by severity (mild, moderate, severe) and by relation to the intervention (definitely, possibly, or not related). Each participant's number and type of AEs will be recorded. Unit of Measure: Number of adverse events per participant.
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Ben-Gurion University of the Negev
Lead sponsor
Soroka University Medical Center
Collaborator
