Brain Stimulation and Attention Control in Children With ADHD

Official title

Effects of iTBS on Cognitive Control in Children With ADHD: A Randomized, Sham-Controlled Study Integrating EEG During ANT, fNIRS, MRI, and Genetic Markers

Overview

The goal of this clinical trial is to learn if brain stimulation can help children ages 6 to 12 with attention-deficit/hyperactivity disorder (ADHD) improve their attention and self-control. The main questions it aims to answer are: Does intermittent theta burst stimulation (iTBS) improve performance on a task that tests attention and reaction times? Can brain activity and genetics help predict who benefits most from this treatment? Researchers will compare randomly assigned active iTBS to sham (inactive) stimulation groups to see if the treatment helps. Participants will: Receive 10 sessions of either active or sham iTBS over 2 weeks Complete a computer task measuring attention before and after stimulation Wear a brain cap during the task to record EEG signals, also take part in resting-state brain scans, namely magnetic resonance imaging (MRI) and functional near-infrared spectroscopy (fNIRS), and provide a saliva sample for genetic testing

Detailed description

This study explores whether noninvasive brain stimulation can improve attention control in children diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD), and how biological factors such as brain activity, brain structure, and genetics may predict individual differences in response. The primary focus is on executive attention-the ability to focus on relevant information, ignore distractions, and resolve conflicts between competing signals. These skills are often impaired in children with ADHD and closely linked to underlying differences in brain function.

To address this, the study uses intermittent theta burst stimulation (iTBS), a specialized form of transcranial magnetic stimulation (TMS). This method delivers rapid bursts of magnetic energy in intervals that are designed to increase the excitability of the targeted brain region. The stimulation is applied to the right dorsolateral prefrontal cortex (DLPFC), a key area involved in attention regulation, response inhibition, and cognitive control-functions that are often altered in ADHD.

A total of 40 children between the ages of 6 and 12 will participate. All must have a confirmed diagnosis of ADHD, verified through structured clinical evaluation. To ensure task comprehension and protocol tolerance, all participants must meet a minimum cognitive ability threshold based on a brief IQ screening.

Participants are randomly assigned to receive either active iTBS or sham stimulation. In the sham condition, the procedures and equipment appear identical, but the stimulation coil is positioned in a way that does not affect brain activity. This ensures that results can be attributed to the stimulation itself rather than expectations or placebo effects. Both participants and researchers conducting assessments are unaware of group assignments to maintain blinding.

Each participant undergoes ten sessions of either active or sham iTBS, typically spaced across two weeks. The stimulation protocol is brief-each session lasting only a few minutes-and individualized according to motor threshold testing, which ensures the intensity is appropriate and safe for each child. All procedures are delivered under professional supervision in a child-friendly environment with appropriate hearing protection.

To assess attentional performance, children complete the Attention Network Test (ANT) before and after the stimulation phase. This computerized task measures three key domains of attention: alerting, orienting, and executive control. During the task, children respond to the direction of arrows on the screen, which may be surrounded by distracting cues. This allows researchers to calculate specific reaction-time profiles associated with attention and conflict resolution.

While the ANT is being performed, the study also records electroencephalographic (EEG) data to capture the brain's electrical responses to each trial. EEG is a noninvasive method that tracks fast neural signals in real time using a cap placed on the child's head. It allows for detailed analysis of how the brain prepares for, reacts to, and regulates attentional demands-especially in the milliseconds following stimulus presentation.

In addition, resting-state fNIRS recordings are collected before and after the intervention. fNIRS is a child-friendly brain imaging method that uses near-infrared light to measure blood oxygen levels in the cortex. When the child is at rest, this technique provides insight into the baseline functional state of the DLPFC, allowing researchers to detect changes in regional activation associated with the stimulation.

To explore whether structural brain features may predict stimulation outcomes, each participant also undergoes a one-time MRI scan. This provides high-resolution images of brain anatomy and can reveal differences in cortical thickness, brain volume, or regional structure that may relate to ADHD symptoms or treatment response.

Finally, the study collects genetic material from saliva samples to investigate specific single-nucleotide polymorphisms in genes linked to dopamine signaling, synaptic function, or neurodevelopment. These include candidate genes such as DRD4, DAT1, COMT, and SLC6A3, which have been associated with attentional control and ADHD phenotypes. Genetic data will be used to explore biological moderators of iTBS efficacy.

This multimodal approach-combining behavioral, electrophysiological, neuroimaging, and genetic methods-aims to move beyond the question of whether iTBS is effective for ADHD. Instead, it seeks to understand how and for whom it works, contributing to the long-term development of individualized, evidence-based neuromodulation strategies for children with attentional difficulties.

The study complies with ethical standards for pediatric research and brain stimulation, and is overseen by the Local Ethical Committee of Al-Farabi Kazakh National University. It is funded by the Ministry of Science and Higher Education of the Republic of Kazakhstan under grant number IRN BR27198099. No U.S. FDA-regulated products are involved.

Interventions

• Device Intermittent Theta Burst Stimulation to Right DLPFC
  Participants receive intermittent theta burst stimulation (iTBS) applied to the right dorsolateral prefrontal cortex (DLPFC). The protocol consists of 600 pulses delivered in bursts of 3 pulses at 50 Hz, repeated at 5 Hz for 2 seconds, every 10 seconds, over approximately 3 minutes per session. Stimulation is delivered at 80% of the participant's active motor threshold. Ten sessions are administered across two weeks.
• Device Sham Intermittent Theta Burst Stimulation
  Participants receive sham intermittent theta burst stimulation (iTBS) to the right dorsolateral prefrontal cortex (DLPFC) using a placebo coil. The coil replicates the sound and scalp sensation of active stimulation without generating sufficient magnetic output to alter cortical excitability. Session length, coil placement, and stimulation parameters are matched to the active iTBS condition. To preserve blinding, both participants and administering staff wear earplugs to minimize auditory differ

Primary outcome measures

• Change in Executive Attention Efficiency as Measured by the Attention Network Test (ANT) [Time frame: Baseline and post-intervention (within 7 days of final TMS session)]

Secondary outcome measures (6)

• Change in Event-Related Potentials During ANT (EEG - N2 Component) [Time frame: Baseline and up to 7 days after the final TMS session.]
• Change in Event-Related Potentials During ANT (EEG - P3 Component) [Time frame: Baseline and up to 7 days after the final TMS session.]
• Change in Oscillatory EEG Power During ANT (Theta Band) [Time frame: Baseline and up to 7 days after the final TMS session.]
• Change in Resting-State Prefrontal Activity - Mean Oxygenation (fNIRS) [Time frame: Baseline and up to 7 days after the final TMS session.]
• Change in Resting-State Prefrontal Activity - Functional Connectivity (fNIRS) [Time frame: Baseline and up to 7 days after the final TMS session.]
• Change in ADHD Symptom Severity (Vanderbilt ADHD Diagnostic Parent Rating Scale, VADPRS) [Time frame: Baseline and up to 7 days after the final TMS session.]

Eligibility criteria

Inclusion criteria

• Children aged 6-12 years at the time of enrollment.
• Clinical diagnosis of Attention-Deficit/Hyperactivity Disorder (ADHD), any presentation type, confirmed using the Vanderbilt ADHD Diagnostic Parent Rating Scale and clinical interview.
• Intelligence quotient (IQ) ≥ 70 as measured by the General Ability Index (GAI) from the Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V).
• Ability to understand and follow instructions for the Attention Network Test (ANT) and stimulation procedure.
• Stable medication regimen for ADHD (if any) for at least 4 weeks before the start of the study.
• Written informed consent from a parent or legal guardian, and assent from the child when appropriate.

Exclusion criteria

• History of epilepsy, seizures, or abnormal EEG suggestive of seizure risk.
• Presence of metal implants, devices, or foreign bodies in or near the head (except dental fillings) that are contraindicated for TMS or MRI.
• Serious neurological disorders other than ADHD (e.g., cerebral palsy, brain injury, neurodegenerative disease).
• Severe psychiatric disorders requiring hospitalization or urgent intervention.
• Current or past history of significant head trauma with loss of consciousness > 5 minutes.
• Uncorrected hearing or vision problems that could interfere with task performance.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Kazakhstan · 2 centers

• Neurolab Plus — Almaty
• Non-profit joint-stock company "Al-Farabi Kazakh National University" — Almaty

Publications

• Yen C, Valentine EP, Chiang MC. The Use of Transcranial Magnetic Stimulation in Attention Optimization Research: A Review from Basic Theory to Findings in Attention-Deficit/Hyperactivity Disorder and Depression. Life (Basel). 2024 Feb 29;14(3):329. doi: 10.3390/life14030329. PMID 38541654
• Weaver L, Rostain AL, Mace W, Akhtar U, Moss E, O'Reardon JP. Transcranial magnetic stimulation (TMS) in the treatment of attention-deficit/hyperactivity disorder in adolescents and young adults: a pilot study. J ECT. 2012 Jun;28(2):98-103. doi: 10.1097/YCT.0b013e31824532c8. PMID 22551775
• Bussing R, Mason DM, Bell L, Porter P, Garvan C. Adolescent outcomes of childhood attention-deficit/hyperactivity disorder in a diverse community sample. J Am Acad Child Adolesc Psychiatry. 2010 Jun;49(6):595-605. doi: 10.1016/j.jaac.2010.03.006. Epub 2010 May 1. PMID 20494269
• Poliakova E, Conrad AL, Schieltz KM, O'Brien MJ. Using fNIRS to evaluate ADHD medication effects on neuronal activity: A systematic literature review. Front Neuroimaging. 2023;2:1083036. doi: 10.3389/fnimg.2023.1083036. Epub 2023 Jan 24. PMID 37033327
• Lundervold AJ, Adolfsdottir S, Halleland H, Halmoy A, Plessen K, Haavik J. Attention Network Test in adults with ADHD--the impact of affective fluctuations. Behav Brain Funct. 2011 Jul 27;7:27. doi: 10.1186/1744-9081-7-27. PMID 21794128
• Le HT, Honma K, Annaka H, Shunxiang S, Murakami T, Hiraoka T, Nomura T. Effectiveness of Transcranial Magnetic Stimulation on Executive Function, Attention, and Memory in Stroke Patients: A Systematic Review and Meta-Analysis. Cureus. 2024 Dec 6;16(12):e75194. doi: 10.7759/cureus.75194. eCollection 2024 Dec. PMID 39759598
• Hall CL, Guo B, Valentine AZ, Groom MJ, Daley D, Sayal K, Hollis C. The Validity of the SNAP-IV in Children Displaying ADHD Symptoms. Assessment. 2020 Sep;27(6):1258-1271. doi: 10.1177/1073191119842255. Epub 2019 Apr 16. PMID 30991820
• Fu B, Zhou X, Zhou X, Li X, Chen Z, Zhang Y, Du Q. Efficacy and Safety of Transcranial Magnetic Stimulation for Attention-Deficit Hyperactivity Disorder: A Systematic Review and Meta-Analysis. Brain Behav. 2025 Jan;15(1):e70246. doi: 10.1002/brb3.70246. PMID 39829146

Identifiers

NCT: NCT07182344 · 2.2.6.2 · BR27198099

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗