Explore the Impacts of Theta Burst Stimulation Over the Right Inferior Frontal Gyrus in Autism Spectrum Disorder: Combination of Clinical Symptoms, Neuropsychological Function and MRI

Exploring the therapeutic efficacy of Theta Burst Stimulation (TBS) over the right inferior frontal gyrus (RIFG) in autism, including changes in core symptoms, adaptive functioning, neuropsychological performance, and neurophysiological signals.

Study Overview

• Status: Recruiting
• Conditions: Autism Spectrum Disorder; Theta Burst Stimulation; Right Inferior Frontal Gyrus
• Intervention / Treatment: Device: intermittent theta burst stimulation

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hsing-Chang Ni, Ph.D; Phone Number: 2479 88633281200; Email: alanni0918@yahoo.com.tw

Study Locations

• Taiwan
  • Taoyuan, Taiwan
    • Recruiting
    • Chang Gung Memorial Hospital
    • Contact: Hsing Chang Ni, PhD; Phone Number: 2479 886-3-3281200; Email: alanni0918@yahoo.com.tw
    • Principal Investigator: Hsing Chang Ni, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants aged 8 to 30 years with a clinical diagnosis of Autism Spectrum Disorder (ASD), confirmed by the ADOS-2 (Autism Diagnostic Observation Schedule, Second Edition).
• DSM-5 severity level of ASD: level 1 or level 2
• Participants who have been on a stable treatment regimen prior to the study, or those for whom conventional treatments have been assessed as ineffective by a physician, or those who decline conventional treatment.
• A score of ≥ 15 on the University of California Brief Assessment of Capacity to Consent (UBACC) and demonstrated understanding of study aims and risks via the teach-back method.

Exclusion Criteria:

• Previous or current severe neurological disorders, especially epilepsy, visual or auditory impairments
• Previous or current severe systemic diseases such as cardiovascular disease, diabetes or hypertension
• Previous or current severe brain injury
• Implementation of metal materials such as a pacemaker or medication pump
• Previous or current severe psychiatric disorders such as schizophrenia, bipolar disorder or substance abuse
• Pregnancy
• Presence of significant brain abnormalities, such as intracranial space-occupying lesions
• Previous brain surgery or central nerve system infection
• Concurrent use of medications which increased the risk of seizure attack
• Participate in another clinical trial within one month
• With damaged skin at the stimulated region
• With multiple sclerosis
• With large ischemic scars
• Have experienced sleep disorders during brain stimulation
• Severe alcoholism
• Concurrent use of antiepileptic drugs
• Uncontrollable migraines due to increased intracranial pressure
• Unsuitable for MRI (e.g. those with claustrophobia)
• Unsuitable for EEG
• DSM-5 severity level of ASD: level 3
• Current major depressive disorder
• Suicidal ideation within one year
• Currently taking tricyclic antidepressants (TCAs), analgesics, or any medications known to lower the seizure threshold.

Withdrawal Criteria:

• Seizure attack during the study period
• Autistic symptoms worsened obviously during the study period (change of DSM-5 severity level)
• Extreme agitation or irritability during the study period
• Participants request
• Clinical symptoms worsened obviously during study period
• Start to use antiepileptic drugs during study period
• Suicidal ideation or self-harm behaviors during study period
• Changes in the frequency or dosage of concurrent treatments during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; Participants received the intervention of iTBS (The total pulse of every session is 600 pulses) over right inferior frontal gyrus for 4 weeks (5 days/week). *iTBS = intermittent theta burst stimulation	Device: intermittent theta burst stimulation; stimulatory protocol
Sham Comparator: Sham; Participants received the sham intervention of iTBS (sham-coil) over right inferior frontal gyrus for 4 weeks (5 days/week).	Device: intermittent theta burst stimulation; stimulatory protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of total scores of Social Responsiveness Scale	Social Responsiveness Scale can measure the autism clinical severity with the range from 65-260. The lower scores stand for better social responsiveness.	baseline; post TBS (4 weeks after baseline); One month follow up (8 weeks after baseline); Two months follow up (12 weeks after baseline)
Changes of total scores of Repetitive Behavior Scale-Revised	Repetitive Behavior Scale-Revised is a questionnaire that focuses on repetitive behavior. The score ranges from 0-129. The lower scores stand for lower repetitive behavior.	baseline; post TBS (4 weeks after baseline); One month follow up (8 weeks after baseline); Two months follow up (12 weeks after baseline)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of total scores of Emotional Dysregulation Inventory	Emotional Dysregulation Inventory is a parents' report questionnaire for emotional dysregulation. The score ranges from 0-120. The lower scores stand for better emotional regulation.	baseline; post TBS (4 weeks after baseline); One month follow up (8 weeks after baseline); Two months follow up (12 weeks after baseline)
Changes of total scores of Child Behavior Checklist	CBCL is a parents' report questionnaire for behavioral and emotional problems. The lower scores stand for better behavioral and emotional regulation.	baseline; post TBS (4 weeks after baseline); One month follow up (8 weeks after baseline); Two months follow up (12 weeks after baseline)
Raven's Progressive Matrices	An advanced test for for executive function. 60 questions in total, the more correct questions stand for better executive function.	baseline; post TBS (4 weeks after baseline); One month follow up (8 weeks after baseline); Two months follow up (12 weeks after baseline)
Changes of total scores of Anxiety Scale for Autism	ASA is a parents' report questionnaire for severity of anxiety in children with ASD. The score ranges from 0-72. The lower scores stand for better emotional regulation.	baseline; post TBS (4 weeks after baseline); One month follow up (8 weeks after baseline); Two months follow up (12 weeks after baseline)
Changes of total scores of Adaptive Behavior Assessment System	Adaptive Behavior Assessment System is a parents' report questionnaire for adaptive behavior. The score ranges from 40-120. The higher scores stand for better adaptive behavior.	baseline; post TBS (4 weeks after baseline); One month follow up (8 weeks after baseline); Two months follow up (12 weeks after baseline)
Accuracy of Frith-Happe Animation	A quick and objective test of Theory of Mind. 8 questions in total, the more correct questions stand for better social cognition.	baseline; post TBS (4 weeks after baseline); One month follow up (8 weeks after baseline); Two months follow up (12 weeks after baseline)
Accuracy of Eyes Task	An advanced test for Theory of Mind. 43 questions in total, the more correct questions stand for better social skills.	baseline; post TBS (4 weeks after baseline); One month follow up (8 weeks after baseline); Two months follow up (12 weeks after baseline)
Accuracy of Wisconsin Card Sorting Test	An advanced test for cognitive flexibility. 128 questions in total, the more correct questions stand for better cognitive flexibility.	baseline; post TBS (4 weeks after baseline); One month follow up (8 weeks after baseline); Two months follow up (12 weeks after baseline)
Changes of total scores of Behavior Rating Inventory of Executive Function	Behavior Rating Inventory of Executive Function is a parents' report questionnaire for executive function. The score ranges from 20-110. The lower scores stand for better executive function.	baseline; post TBS (4 weeks after baseline); One month follow up (8 weeks after baseline); Two months follow up (12 weeks after baseline)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI T1	Brain structural volumes (cm²).	baseline; post TBS (4 weeks after baseline)
Functional MRI (Resting-state/Biological Motion Task) - BOLD Signal	Blood-oxygen-level-dependent (BOLD) signal is a measurement used in fMRI, which reflects the neural activity.	baseline; post TBS (4 weeks after baseline)
DTI Mean-FA Tractometry - Left Arcuate Fasciculus (AF_left)	This outcome is the mean fractional anisotropy (FA) of the left arcuate fasciculus (AF_left) computed using DTI-based tractometry. FA is a unitless metric (range 0-1) that reflects the degree of diffusion anisotropy. A diffusion tensor was fitted to the diffusion MRI data to generate FA maps, and FA values were sampled within the AF_left tract mask/tract reconstruction and averaged to yield one mean FA value per participant per time point.	baseline; post TBS (4 weeks after baseline)
Electroencephalography	Resting state EEG (alpha power / frontal gamma power).	baseline; post TBS (4 weeks after baseline)

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2026
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: May 5, 2026
• First Submitted That Met QC Criteria: May 5, 2026
• First Posted (Actual): May 12, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder
• Other Study ID Numbers: 202401962A0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No