pBFS Guided Neuromodulation Over DMPFC for ASD Treatment: Pilot Study

Autism spectrum disorder is a neurodevelopmental disorder characterized by impaired social communication and repetitive behaviors, often co-occurring with language delay. Using the personalized Brain Functional Sectors (pBFS) technique, investigators could precisely identify individualized brain areas underlying language and social communication a based on the resting-state functional MRI data. The tailored TMS intervention target to language and default mode network which located in the left dorsal medial prefrontal cortex (DMPFC) will be selected for each participant.

The participants will receive active iTBS to the language network 5 days per week for 12 weeks. Functional MRI data will be collected pre-and post-treatment under sedation. Three behavioral evaluations will be taken pre-treatment, after 8-weeks treatment and after 12-weeks treatment.

• active iTBS (Device): Each participant will receive 1800 pulse active iTBS (100% RMT) in each session, 3 sessions per day, 5 days per week for 8 weeks.

Primary outcomes

• Language score change [Pre-treatment (baseline), after 8 weeks treatment, immediately post-treatment]: The score change of vocabulary acquisition scales (VAS) from the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) from baseline. Higher scores mean a better outcome.
• ADOS-2 SA score change [Pre-treatment (baseline), after 8 weeks treatment, immediately post-treatment]: The social affect dimension score change of autism diagnostic observation scale, 2nd edition (ADOS-2) from baseline. Higher scores mean a worse outcome.

Secondary outcomes

• Receptive vocabulary score change [Pre-treatment (baseline), after 8 weeks treatment, immediately post-treatment]: The score change of receptive vocabulary (pointing) from the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) from baseline. Higher scores mean a better outcome.
• Expressive language score change [Pre-treatment (baseline), after 8 weeks treatment, immediately post-treatment]: The score change of picture naming (naming) from the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) from baseline. Higher scores mean a better outcome.
• SCQ S score change [Pre-treatment (baseline), after 8 weeks treatment, immediately post-treatment]: The social dimension score change of the Social Communication Questionnaire (SCQ) from baseline. Higher scores mean a worse outcome.
• SCQ C score change [Pre-treatment (baseline), after 8 weeks treatment, immediately post-treatment]: The communication dimension score change of the Social Communication Questionnaire (SCQ) from baseline. Higher scores mean a worse outcome.

Other outcomes

• ADOS-2 total score change [Pre-treatment (baseline), after 8 weeks treatment, immediately post-treatment]: The total score change of autism diagnostic observation scale, 2nd edition (ADOS-2) from baseline. Higher scores mean a worse outcome.
• ADOS-2 RRB score change [Pre-treatment (baseline), after 8 weeks treatment, immediately post-treatment]: The restricted and repetitive behavior score change of autism diagnostic observation scale, 2nd edition (ADOS-2) from baseline. Higher scores mean a worse outcome.
• SCQ total score change [Pre-treatment (baseline), after 8 weeks treatment, immediately post-treatment]: The total score change of the Social Communication Questionnaire (SCQ) from baseline. Higher scores mean a worse outcome.
• SCQ R score change [Pre-treatment (baseline), after 8 weeks treatment, immediately post-treatment]: The RRB dimension score change of the Social Communication Questionnaire (SCQ) from baseline. Higher scores mean a worse outcome.
• CBCL score change [Pre-treatment (baseline), after 8 weeks treatment, immediately post-treatment]: Score change of the child behavior checklist (CBCL) from baseline. Higher scores mean a worse outcome. Higher scores mean a worse outcome.

Sex: All, ages: 6 Years to 30 Years

Inclusion Criteria:

* 6-30 years old
* Have the diagnosis of autism spectrum disorder
* ADOS-2 score is higher than the ASD cut-offs
* Have language development delay (the WISC-4 Verbal Comprehension Index lower than 70)
* Capacity to follow the study procedures, including fMRI scan under sedation, assessment, and rehabilitation training
* Participant's parents or other legal guardians give informed consent

Exclusion Criteria:

* Current or history of psychotic disorders, such as schizophrenia, schizoaffective disorder, bipolar disorder
* Severe self-injury or suicidal behavior presented in the last 1 year
* Severe visual, auditory, or motor disability that interferes with any study procedure
* Current, history or family history of epilepsy
* Known severe physical diseases, such as congenital heart defect, traumatic brain injury
* Metal implantations, which are contradicted by MRI or TMS, such as artificial cardiac pacemakers, stents, cochlear implants
* Received TMS, tCS, FUS, or other neuromodulation treatment in the last 3 months
* Currently participating in other clinical trials