pBFS Guided aiTBS Over Language Network for ASD Child

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder often accompanied by language delay. Emerging evidence indicates that Transcranial Magnetic Stimulation (TMS) has been effective in restoring language ability in post-stroke aphasia, but its efficacy in developmental language disorders remains unknown.

By leveraging the personalized Brain Functional Sector (pBFS) technique and task-free functional MRI scans, we can accurately locate the individual language function brain network. Considering the accessibility and comfort of neuromodulation, we will stimulate the language network node in the superior frontal gyrus (SFG) for 12 weeks.

In this study, participants meeting the inclusion and exclusion criteria will be randomly assigned to either the active or sham iTBS (intermittent theta burst stimulation) groups at a ratio of 2:1. The treatment protocol lasts for 12 weeks, with sessions held 5 days a week and 3 iTBS sessions over the SFG per day. The inter-session interval is set at 50 minutes, along with speech therapy. Clinical evaluations focusing on language and ASD symptoms will be conducted at baseline, after the 12-week treatment period, and at 24-week follow-up after the start of treatment.

• active iTBS (Device): Participants will undergo three iTBS sessions per day, with 1800 pulses per session, over a 12-week period. Individualized targets will be generated using the pBFS technique.
• Sham iTBS (Device): Participants will undergo three sham iTBS sessions per day, with 1800 pulses per session, over a 12-week period. Sham stimulation will be delivered through a sham coil with the identical appearance as real coil. Individualized targets will be generated using the pBFS technique.
• speech therapy (Behavioral): Speech therapy will be delivered between iTBS/sham sessions. Two 30-minutes trainings every day.

Primary outcomes

• CLAS-TP score change after treatment [Pre-treatment (baseline), post-treatment (12-week)]: The score changes of combined CLAS-TP (Child Language Assessment Scale - Test for Preschoolers) score at 12-week from baseline. Higher scores mean a better outcome.

Secondary outcomes

• CLAS-TP total score change from baseline to follow-up [Pre-treatment (baseline), post-treatment (12-week), follow-up (24-week)]: Higher scores mean a better outcome.
• CLAS-TP subscale score change from baseline to follow-up [Pre-treatment (baseline), post-treatment (12-week), follow-up (24-week)]: For the story comprehension subscale, only participants who had non-zero point were included. Higher scores mean a better outcome.
• WPPSI language score change from baseline to follow-up [Pre-treatment (baseline), post-treatment (12-week), follow-up (24-week)]: Higher scores mean a better outcome.
• ADOS-2 SA score change from baseline to follow-up [Pre-treatment (baseline), post-treatment (12-week), follow-up (24-week)]: Higher scores mean a worse outcome.

Other outcomes

• SCQ score change from baseline to follow-up [Pre-treatment (baseline), post-treatment (12-week), follow-up (24-week)]: Higher scores mean a worse outcome.
• ATEC score change from baseline to follow-up [Pre-treatment (baseline), post-treatment (12-week), follow-up (24-week)]: Higher scores mean a worse outcome.
• CBCL score change from baseline to follow-up [Pre-treatment (baseline), post-treatment (12-week), follow-up (24-week)]: Higher scores mean a worse outcome.
• QoL score change from baseline to follow-up [Pre-treatment (baseline), post-treatment (12-week), follow-up (24-week)]: Higher scores mean a better outcome.

Sex: All, ages: 3 Years to 6 Years

Inclusion Criteria:

1. Professionally diagnosed with ASD per DSM - 5 criteria.
2. Aged 3 - 6.5 years, either gender.
3. ADOS-2 results meet ASD standard cut - off.
4. SCQ score: ≥15 (age ≥ 4 years) or ≥11 (age < 4 years).
5. Co-existing language disorder not explaining ASD symptoms. No organic speech organ lesions. CNBS-R2016 and CLAS-TP language-related equivalent age > 18 months; any CLAS-TP dimension score < 6.
6. Mandarin is the daily communication language.
7. May have intellectual/global developmental delay not explaining ASD symptoms.
8. Guardians volunteer, can cooperate in treatment and sign informed consent.

Exclusion Criteria:

1. Identified genetic pathogenic factors; current/past comorbid severe disorders (ADHD, Tourette's, etc.).
2. Serious self-harm in the past year.
3. Severe sensory/motor disorders precluding cooperation.
4. History of epileptic seizures.
5. Serious organic diseases, especially brain related.
6. Contraindications for MRI/TMS (metal/implants).
7. Respiratory/circulatory diseases with sedation risk.
8. Illiterate guardians unable to handle informed consent/questionnaires.
9. Received neuromodulation in the past 3 months.
10. Currently in other clinical trials.
11. Deemed unfit by the researcher.