Evaluation of low-frequency repetitive transcranial magnetic stimulation intervention among children with autism spectrum disorder
LIU Renchuan1,2, XU Yi2, HUANG Bochao1,2, LI Shangda2,3
1. Hangzhou Xinyue Clinic, Hangzhou, Zhejiang 310003, China; 2. School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China; 3. The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China
Abstract：Objective To evaluate the intervention effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) among children with autism spectrum disorder (ASD), so as to provide the reference for the treatment scheme of ASD children. Methods From May to September 2021, children with ASD aged 3 to 12 years were recruited from Elim Training and Ability Development Center as the research subjects and randomly assigned to the intervention group and the control group at ratio of a 1∶1 ratio. The control group only received behavioral training intervention. The intervention group received low-frequency rTMS treatment once a day (5 times/week) on the left dorsolateral prefrontal cortex for 1 month, a total of 20 times, as well as behavioral training. The Autism Behavior Scale (ABC), the Clancy Autism Behavior Scale (CABS), and the Social Responsiveness Scale (SRS) were used to evaluate the behavioral characteristics, symptoms, and social functioning of ASD before and after the intervention, respectively. Adverse events occurring during the intervention period in the intervention group were also collected. The generalized estimation equation was used to compare the differences in scores of each scale between the two groups of children before and after intervention, and to evaluate the intervention effect. Results Sixty children with ASD were included, with 26 in the intervention group (4 dropouts) and 27 in the control group (3 dropouts). There were 20 and 22 male children in the intervention and control groups, respectively, accounting for 76.92% and 81.48%. The median ages were 5.00 (interquartile range, 1.13) years and 4.50 (interquartile range, 2.00) years, respectively. There were no statistically significant differences between the two groups of children in terms of gender, age, preschool special education time, and total raw scores of Autism Diagnostic Observation Schedule Second Edition (all P>0.05). After one month of intervention, the ABC, CABS, and SRS scores of the intervention group decreased by 16.70, 1.50, and 3.75 points compared to before intervention, respectively, while the control group decreased by 1.07, 0.50, and 1.70 points, respectively (all P<0.05). There was an interaction between the groups and time for ABC scores (P<0.05), while there was no interactions between the groups and time for CABS or SRS scores (both P>0.05). No serious adverse events occurred in the intervention group during the intervention period. Conclusions Low-frequency rTMS treatment has an improvement effect on the behavioral characteristics of children with ASD and shows good safety, and its effect is superior to that of behavioral training treatment. However, it has no obvious improvement effect on social functioning.
[1] ZWAIGENBAUM L,PENNER M.Autism spectrum disorder:advances in diagnosis and evaluation[J/OL].BMJ,2018,361[2025-09-05].https://doi.org/10.1136/bmj.k1674. [2] MAENNER M J,SHAW K A,BAIO J,et al.Prevalence of autism spectrum disorder among children aged 8 years-autism and developmental disabilities monitoring network,11 sites,United States,2016[J].MMWR Surveill Summ,2020,69(4):1-12. [3] ROSSI S,HALLETT M,ROSSINI P M,et al.Safety,ethical considerations,and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research[J].Clin Neurophysiol,2009,120(12):2008-2039. [4] COLE E J,ENTICOTT P G,OBERMAN L M,et al.The potential of repetitive transcranial magnetic stimulation for autism spectrum disorder:a consensus statement[J].Biol Psychiatry,2019,85(4):21-22. [5] CASANOVA M F,HENSLEY M K,SOKHADZE E M,et al.Effects of weekly low-frequency rTMS on autonomic measures in children with autism spectrum disorder[J/OL].Front Hum Neurosci,2014[2025-09-05].https://doi.org/10.3389/fnhum.2014.00851. [6] DESARKAR P,RAJJI T K,AMEIS S H,et al.Assessing and stabilizing atypical plasticity in autism spectrum disorder using rTMS:results from a proof-of-principle study[J].Clin Neurophysiol,2022,141:109-118. [7] GOTHAM K,PICKLES A,LORD C.Standardizing ADOS scores for a measure of severity in autism spectrum disorders[J].J Autism Dev Disord,2009,39(5):693-705. [8] HUS V,GOTHAM K,LORD C.Standardizing ADOS domain scores:separating severity of social affect and restricted and repetitive behaviors[J].J Autism Dev Disord,2014,44(10):2400-2412. [9] GÓMEZ L,VIDAL B,MARAGOTO C,et al.Non-invasive brain stimulation for children with autism spectrum disorders:a short-term outcome study[J/OL].Behav Sci(Basel),2017,7(3)[2025-09-05].https://doi.org/10.3390/bs7030063. [10] 殷青云,陈劲梅,罗学荣,等.孤独症常用量表的信度和效度检验[J].国际医药卫生导报,2011,17(12):1470-1475. YIN Q Y,CHEN J M,LUO X R,et al.Reliability and validity of Childhood Autism Rating Scale and Autism Behaviour Checklist[J].Int Med Health Guidance News,2011,17(12):1470-1475.(in Chinese) [11] RELLINI E,TORTOLANI D,TRILLO S,et al.Childhood Autism Rating Scale(CARS)and Autism Behavior Checklist(ABC)correspondence and conflicts with DSM-IV criteria in diagnosis of autism[J].J Autism Dev Disord,2004,34(6):703-708. [12] 李建华,钟建民,蔡兰云,等.三种儿童孤独症行为评定量表临床应用比较[J].中国当代儿科杂志,2005,7(1):59-62. LI J H,ZHONG J M,CAI L Y,et al.Comparison of clinical application of three autism rating scales[J].Chin J Contemp Pediatr,2005,7(1):59-62.(in Chinese) [13] WU X Y,TAO S M,RUTAYISIRE E,et al.The relationship between screen time,nighttime sleep duration,and behavioural problems in preschool children in China[J].Eur Child Adolesc Psychiatry,2017,26(5):541-548. [14] CEN C Q,LIANG Y Y,CHEN Q R,et al.Investigating the validation of the Chinese Mandarin version of the Social Responsiveness Scale in a Mainland China child population[J/OL].BMC Psychiatry,2017,17(1)[2025-09-05].https://doi.org/10.1186/s12888-016-1185-y. [15] AMEIS S H,BLUMBERGER D M,CROARKIN P E,et al.Treatment of Executive Function Deficits in autism spectrum disorder with repetitive transcranial magnetic stimulation:a double-blind,sham-controlled,pilot trial[J].Brain Stimul,2020,13(3):539-547. [16] 朱莎,钟燕,江淑娟,等.孤独症行为量表和克氏孤独症行为量表在孤独症谱系障碍中的应用分析[J].医学临床研究,2017,34(5):1026-1028. ZHU S,ZHONG Y,JIANG S J,et al.Analysis of the application of Autism Behaviour Checklist and Clancy Autism Behavior Scale in autism spectrum disorder[J].J Clin Res,2017,34(5):1026-1028.(in Chinese) [17] FORTIER A V,MEISNER O C,NAIR A R,et al.Prefrontal circuits guiding social preference:implications in autism spectrum disorder [J/OL].Neurosci Biobehav Rev,2022,141[2025-09-05].https://doi.org/10.1016/j.neubiorev.2022.104803.
