Dual-target iTBS for Youth With ADHD

ADHD is the most common neurodevelopmental disorder in childhood. First-line clinical treatments primarily rely on psychostimulants, yet approximately 30% of adolescents with ADHD show inadequate response to current therapies. There is an urgent need to develop novel, practical, and sensitive intervention strategies.

Repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive technique that modulates neural activity via magnetic fields applied to brain regions beneath the skull, can induce long-lasting positive changes in neuroplasticity. This provides an alternative therapeutic approach for ADHD. In clinical research, rTMS has demonstrated potential value in treating children with ADHD. Notably, current studies have limitations: lack of control groups makes it difficult to exclude placebo effects, and the commonly used DLPFC target shows suboptimal efficacy in improving both clinical symptoms and cognitive functions, indicating room for improvement.

This study will be conducted in two phases:

* Phase 1 is an open-label, single-arm study to explore the preliminary efficacy, safety, and acceptability of aiTBS for youth with ADHD. * Phase 2 is a randomized, double-masked, controlled trial that will rigorously validate the efficacy and safety of dual-target aiTBS and establish causal conclusions through a controlled design.

The decision to proceed depends on Phase 1 results:

* If Phase 1 demonstrates positive outcomes in clinical symptoms, cognitive functioning, safety, and acceptability, Phase 2 will be implemented. * If Phase 1 fails to show positive results, Phase 2 will be discontinued.

The study will utilize MRI-guided neuronavigation to precisely locate the target brain regions (the right inferior frontal gyrus and the left inferior parietal lobule) for each participant. An aiTBS protocol will be employed. Based on a 90% resting motor threshold (adjusted for cortical depth), each participant will receive 10 iTBS sessions (1,800 pulses per session, with 60-minute inter-session intervals), administered twice daily over five consecutive days.

• Safety as measured by number of participants with Adverse Events [Time frame: Each afternoon after treatment during the 5 days of treatment]
• Acceptability as assessed by treatment-related dropout rates [Time frame: Each afternoon after treatment during the 5 days of treatment]
• BRIEF（Behavior Rating Inventory of Executive Function） [Time frame: Will be measured before the TMS treatment, immediately after completion of the TMS treatment.]
• PedsQL（Pediatric Quality of Life Inventory） [Time frame: Will be measured before the TMS treatment, immediately after completion of the TMS treatment.]
• A cognitive task battery [Time frame: Will be measured before the TMS treatment, immediately after completion of the TMS treatment.]
• Cortical excitability and cortical inhibition function indicators [Time frame: Will be measured before the TMS treatment, immediately after completion of the TMS treatment.]