Brain Stimulation and Attention Control in Children With ADHD

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

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

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.

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.