The Therapeutic Effect of TBS Stimulation on Emotion Regulation in Autism Spectrum Disorder

Study Overview
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Brief Summary
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The investigator would like to investigate the impact of intermittent theta burst stimulation over left dorsolateral prefrontal cortex on emotion regulation in autism spectrum disorder

Official Title
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The Therapeutic Effect of TBS Stimulation Over Left Dorsolateral Prefrontal Cortex on Emotion Regulation in Autism Spectrum Disorder

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Device: intermittent theta burst stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: autism spectrum disorder, confirmed by ADOS Exclusion Criteria: Previous or current severe neurological disorder such as epilepsy, visual or hearing impairment Previous or current severe systemic disease such as cardiovascular disease, diabetes or infection Previous or current severe brain injury Implementation of metal materials such as pacemaker or medication pump Previous or current severe psychiatric disorders such as schizophrenia, bipolar disorder or substance abuse Pregnancy Individuals with a significant brain abnormality such as intracranial space occupied lesions Individuals with a family history of epilepsy Previous febrile seizures Current taking antiepileptic drugs Concurrent use of medications which increased the risk of seizure attack Individuals suffering from sleep deprivation during rTMS procedures Skin trauma on application site Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to participate in the study Participate another clinical trial within one month

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Participants received the real intervention of TBS (iTBS 600) over the left dorsolateral prefrontal cortex for 4 weeks (5 days/week). *iTBS = intermittent theta burst stimulation | Device: intermittent theta burst stimulation<br>* stimulatory protocol<br>|
| Sham Comparator: Sham<br>Participants received the sham intervention of TBS (sham-coil) over the left dorsolateral prefrontal cortex for 4 weeks (5 days/week). | Device: intermittent theta burst stimulation<br>* stimulatory protocol<br>|

What is the study measuring?
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Primary 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 (4 weeks after post TBS); Two months follow up (8 weeks after post TBS) | 
| Changes of total scores of Aberrant Behavior Checklist | ABC is a parents' report questionnaire for aberrant behavior. The lower scores stand for less aberrant behavior. | baseline; post TBS (4 weeks after baseline); One month follow up (4 weeks after post TBS); Two months follow up (8 weeks after post TBS) | 
| 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 (4 weeks after post TBS); Two months follow up (8 weeks after post TBS) | 

Secondary 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 (4 weeks after post TBS); Two months follow up (8 weeks after post TBS) | 
| 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 (4 weeks after post TBS); Two months follow up (8 weeks after post TBS) | 
| 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 9-171. The higher scores stand for better adaptive behavior. | baseline; post TBS (4 weeks after baseline); One month follow up (4 weeks after post TBS); Two months follow up (8 weeks after post TBS) | 
| Changes in 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 (4 weeks after post TBS); Two months follow up (8 weeks after post TBS) | 
| Changes in 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 (4 weeks after post TBS); Two months follow up (8 weeks after post TBS) | 
| Changes in 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 (4 weeks after post TBS); Two months follow up (8 weeks after post TBS) | 
| 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 86-258. The lower scores stand for better executive function. | baseline; post TBS (4 weeks after baseline); One month follow up (4 weeks after post TBS); Two months follow up (8 weeks after post TBS) | 
| 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 (4 weeks after post TBS); Two months follow up (8 weeks after post TBS) | 
| 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) | 
| Diffusion Tensor Imaging (DTI) - FA | Fractional anisotropy (FA) is a measurement used in DTI, which reflects the movement of water molecules. FA ranges from 0 to 1, the higher FA value may represent more intact axons. | baseline; post TBS (4 weeks after baseline) | 
| Electroencephalography | Resting state EEG (alpha power / frontal gamma power) | baseline; post TBS (4 weeks after baseline) |