Efficacy and Mechanism of rTMS in Children With ASD: an Open-label Clinical Trial(Ⅱ)

Social Response Scale (SRS) is a parent questionnaire used to assess the presence and severity of social impairment. The SRS generates a total score and five subscale scores (social awareness, social cognition, social communication, social motivation, and autistic mannerisms), and 5 subscales scores are summed to compute the total score; higher scores indicate greater social impairment. The SRS total score range is 0-195, the social awareness subscale score range is 0-24, the social cognition subscale score range is 0-36, the social communication subscale score range is 0-66, the social motivation subscale score range is 0-33, and the autistic mannerisms subscale score range is 0-36. We collected the SRS from baseline to 1 month follow-up to evaluate the effect of rTMS treatment on ASD syptoms among these children.

Time frame: Baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention.

BRIEF is a quick and efficient measure of executive function(have school-age version (BRIEF-S) and preschool version (BRIEF-P)), we asked parents to complete the 86-item (BRIEF-S) or 63-item (BRIEF-P) form to rate a child's executive functions (1-3 score) within the context of his everyday environments (home or school). Here we report the BRIEF composite score, BRIEF-S score range is 86 -258 and BRIEF-P score range is 63-189. The higer scores indicate more impairment in executive function. We evaluate the changes in executive function (EF) scores before and after cTBS treatment.

Time frame: Baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention.

Population: Three parents of participants did not complete the questionnaire

CARS is a behaviour-rating scale used to assess the presence and severity of the symptoms of autism spectrum disorder(ASD), with scores ranging from 15 to 60 and high scores indicating severe symptoms. Change of the CARS from baseline to 1 months after treatment to evaluate the effect of rTMS treatment on ASD. children.

Time frame: Baseline, and 4 weeks after the completion of intervention.

CCDI provides a powerful tool to assess early vocabulary development and the language skills of older children with developmental disorders and the effectiveness of their intervention. Here we collected the CCDI words produced score, it ranges from 0-798. The higher scores mean a better outcome.

Time frame: Baseline and 4 weeks after the completion of intervention.

Population: 8 subjects whose parents did not complete the follow-up scale or who had reached the highest measurable score on the scale in terms of ability (ceiling effect) were not included in the analysis

CGI is a scale used to assess the severity of the illness and the global improvement of the patient under intervention. Here we used Clinical Global Impression of Improvement (CGI-I) to rate how much the patient's illness has improved or worsened relative to baseline (a seven-point scale: 1 = very much improved to 7 = very much worse). The CGI was carried out by trained clinical assessors according to children's CARS、ADOS assessment results and parent interviews before and after intervention. We calculated the number of subjects with improvement (CGI-I≤3).

Time frame: After the completion of 5-days intervention and 4 weeks after the completion of intervention.

Conners Parent Symptom Questionnaire (PSQ) is a questionnaire screening for children's behavioral problems (especially with ADHD), it has 48 items（4-stage: 0-3) that can be divided into 6 factors (conduct problems, learning problems, psychosomatic problems, impulsive-hyperactivity, anxiety, and hyperactivity index). Add the scores and divide by the item numbers of each factor to get Z score. Here we mainly observe the changes in Hyperactivity Index (HI) Z scores, it ranges from 0-3, a higher score mean a worse outcome.

Time frame: Baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention.

The Peabody Picture Vocabulary Test is one of the most commonly used assessment tests for measuring single-word comprehension. The raw score ranges from 0-110, the higher scores mean a better outcome. we collected the PPVT raw score from baseline to 1 months after treatment to evaluate the effect of rTMS treatment on ASD children's words comprehension.

Time frame: Baseline, and 4 weeks after the completion of intervention.

Population: Three subjects did not cooperate with the test, so their data were excluded from the analysis

The Repetitive Behaviors Scale - Revised (RBS-R) is a 44-item (rated 0-3) questionnaire that is used to measure the breadth of repetitive behavior in children, adolescents, and adults with Autism Spectrum disorders. The RBS-R provides a quantitative, continuous measure of the full spectrum of repetitive behaviors. The RBS-R consists of six subscales including: Stereotyped Behavior, Self-injurious Behavior, Compulsive Behavior, Routine Behavior, Sameness Behavior, and Restricted Behavior, that have no overlap of item content. Here we use the RBS-R total score, it ranges from 0-132, the higher score means worse repetitive behavior.

Time frame: baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention.

For a subset of ASD children with adequate expressive ability (those able to at least use phrases), we use Multilingual Assessment Instrument for Narratives (MAIN) tool to assess their narrative comprehension and production skills. In this test, children were asked to tell and retell the story and answer comprehension questions, and then assessors scored children's performance from four dimensions (i.e., story structure, structural complexity, and internal state terms and comprehension questions). The story structure score range is 0-18, structural complexity score range is 0-4, internal state terms score range is 0-no limit, and comprehension questions score range is 0-10. The higher score means better performance.

Time frame: Baseline, and 4 weeks after the completion of intervention.

Population: 14 children having certain expression ability to complete MAIN test.

For EEG data, we caculated the power spectral density (PSD) within the alpha frequency band (8-13 Hz) for all channels.

Time frame: Baseline, immediately after the completion of 5-days intervention.

Population: We successfully collected EEG data from 26 children before and after the intervention, and one patient was excluded after a quality control procedure. Due to limited implementation conditions (e.g., epidemics, installations) , we did not collect EEG data at 1-month follow-up. The phase locking value(PLV) and coherence (Coh) were not analyzed due to data and analyst issues.