{
  "abstract": "Abstract Objectives To investigate the efficacy and safety of a five day accelerated continuous theta burst stimulation (a-cTBS) protocol in improving social communication impairment in children with autism spectrum disorder.Design Multicentre randomised sham controlled trial. Setting Three academic hospitals across three provinces in China, conducted from July 2023 to October 2024.Participants 200 children aged 4-10 years with autism spectrum disorder (167 boys and 33 girls) all with a full scale intelligence quotient ≥50.Interventions Participants were randomised 1:1 to receive active a-cTBS (n=100) or sham (n=100) treatment stratified by full scale intelligence quotient (≥70 or <70) and study site. Participants received 10 sessions each day for five consecutive days, targeting the left primary motor cortex. Participants and evaluators were masked to interventions.Main outcome measures Two primary outcomes were assessed using the Social Responsiveness Scale, second edition (SRS-2): changes in social communication impairment from baseline to post-intervention and from baseline to one month follow-up. Primary analyses were conducted on a modified intention-to-treat population, including participants who received at least one stimulation session. Secondary outcomes included language improvements assessed from baseline to one month follow-up and changes in SRS-2 subscales.Results Of the 200 participants, 198 were included in the modified intention-to-treat analysis (99 in each group) and 193 completed the full intervention. Compared with the sham group, the a-cTBS group showed significantly greater reductions in SRS-2 scores post-intervention (−6.25, 95% confidence interval −8.69 to −3.81; Cohen’s d −0.92; P<0.001) and at one month follow-up (−6.17, −8.65 to −3.70; −0.90; P<0.001). Secondary outcomes also favoured a-cTBS, with significant improvements observed in language abilities (Cohen’s d 0.12-0.47; all P<0.02; measured by Multilingual Assessment Instrument for Narratives). Reported adverse events were all mild to moderate and resolved without intervention.Conclusions A five day a-cTBS protocol targeting the left primary motor cortex significantly improved social communication in children with autism spectrum disorder and showed a favourable safety profile. These findings support a-cTBS as a viable and scalable therapeutic option for children with autism spectrum disorder.Trial registration ClinicalTrials.gov NCT05927792",
  "authors": [
    {
      "affiliations": [
        "Department of Developmental and Behavioural Paediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Hangyu Tan"
    },
    {
      "affiliations": [
        "Department of Developmental and Behavioural Paediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Tai Ren"
    },
    {
      "affiliations": [
        "Department of Paediatrics, Qilu Hospital of Shandong University, Jinan, Shandong, China"
      ],
      "name": "Aihua Cao"
    },
    {
      "affiliations": [
        "Department of Developmental and Behavioural Paediatric & Child Primary Care, Zhengzhou Children’s Hospital affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, Henan, China"
      ],
      "name": "Shuanfeng Fang"
    },
    {
      "affiliations": [
        "Department of Developmental and Behavioural Paediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Lin Deng"
    },
    {
      "affiliations": [
        "Department of Developmental and Behavioural Paediatric & Child Primary Care, Zhengzhou Children’s Hospital affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, Henan, China"
      ],
      "name": "Bo Hu"
    },
    {
      "affiliations": [
        "Department of Paediatrics, Qilu Hospital of Shandong University, Jinan, Shandong, China"
      ],
      "name": "Mei Wang"
    },
    {
      "affiliations": [
        "Department of Developmental and Behavioural Paediatric & Child Primary Care, Zhengzhou Children’s Hospital affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, Henan, China"
      ],
      "name": "Ye Cheng"
    },
    {
      "affiliations": [
        "Clinical Research and Innovation Unit, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Xi Zhang"
    },
    {
      "affiliations": [
        "Department of Paediatrics, Qilu Hospital of Shandong University, Jinan, Shandong, China"
      ],
      "name": "Yawen Li"
    },
    {
      "affiliations": [
        "Department of Developmental and Behavioural Paediatric & Child Primary Care, Zhengzhou Children’s Hospital affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, Henan, China"
      ],
      "name": "Yixia Zhang"
    },
    {
      "affiliations": [
        "Department of Developmental and Behavioural Paediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Lingli Zhang"
    },
    {
      "affiliations": [
        "Department of Developmental and Behavioural Paediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Luan Chen"
    },
    {
      "affiliations": [
        "Department of Developmental and Behavioural Paediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Wei Zhou"
    },
    {
      "affiliations": [
        "Department of Developmental and Behavioural Paediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Qianlong Zhang"
    },
    {
      "affiliations": [
        "Department of Developmental and Behavioural Paediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China",
        "Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China"
      ],
      "name": "Jiong Li"
    },
    {
      "affiliations": [
        "Department of Developmental and Behavioural Paediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Xin Zhou"
    },
    {
      "affiliations": [
        "Department of Psychiatry, University of Cambridge, Cambridge, UK",
        "Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK"
      ],
      "name": "Christelle Langley"
    },
    {
      "affiliations": [
        "Institute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China"
      ],
      "name": "Qiang Luo"
    },
    {
      "affiliations": [
        "Department of Developmental and Behavioural Paediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Jun Zhang"
    },
    {
      "affiliations": [
        "Department of Psychiatry, University of Cambridge, Cambridge, UK",
        "Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK"
      ],
      "name": "Barbara J Sahakian"
    },
    {
      "affiliations": [
        "Shanghai Key Laboratory of Psychotic Disorders, Brain Health Institute, National Center for Mental Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine and School of Psychology, Shanghai, China"
      ],
      "name": "Ti-Fei Yuan"
    },
    {
      "affiliations": [
        "Department of Developmental and Behavioural Paediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Fei Li"
    }
  ],
  "title": "Accelerated continuous theta burst stimulation targeting left primary motor cortex for children with autism spectrum disorder: multicentre randomised sham controlled trial",
  "uid": "39c4f1d2-d2c2-5306-a1cf-d3e3f594e92c"
}