This study will employ accelerated intermittent theta burst stimulation (aiTBS) targeting two transcranial magnetic stimulation (TMS) sites: the right inferior frontal gyrus and left inferior parietal lobule.

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.

Inclusion Criteria:

1. ADHD Diagnosis: Meets the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5);
2. Inadequate Response to Medication: After a full course of pharmacological treatment, the SNAP-IV Parent Rating Scale (first 18 items, assessing inattention/hyperactivity-impulsivity) score >1, and the Clinical Global Impression-Severity Scale (CGI-S) score >2;
3. Age and Gender: 10-18 years old; males or females;
4. Intellectual Functioning: Full-scale intelligence quotient (IQ) >70 on the China-Wechsler Intelligence Scale for Children (C-WISC) (excluding participants with intellectual disability);
5. Symptom Severity: A score of ≥1.6 on either the Inattention or Hyperactivity/Impulsivity subscale of the SNAP-IV Parent Rating Scale;
6. Medication Requirements:

1) Medication-naïve or currently off medication; 2) If currently on medication, must be on a stable medication regimen for at least 4 weeks prior to the baseline visit and throughout the study duration; 3) Prohibited medications: Psychostimulants; 7. Right-handed.

Exclusion Criteria:

1. Contraindications for TMS therapy include epilepsy, cardiac pacemakers, cochlear implants, and metal implants.
2. Contraindications for MRI include metal implants in the body, claustrophobia, and tattoos.
3. Significant medical history: history of epilepsy, organic brain disorders, traumatic brain injury (TBI), or severe physical illnesses.
4. Behavioral risks: history of violent or suicidal behavior.
5. Comorbid neurodevelopmental disorders, such as autism spectrum disorder (ASD), tic disorders, etc.
6. Comorbid psychiatric disorders: any other primary psychiatric disorders, except conduct disorder/oppositional defiant disorder, mild anxiety, or depression.
7. Substance abuse.
8. Currently receiving any non-medical treatments, such as cognitive behavioral therapy (CBT), neurofeedback, etc.
9. Female participants must not be pregnant or breastfeeding.

This requires approval from our institution's ethics committee.

Phase 1：open label；Phase 2: double-blind masking