Non-invasive brain stimulation for core symptoms in children with autism spectrum disorder: a network meta-analysis

Abstract

OBJECTIVE: Non-invasive brain stimulation has been shown to improve restricted, repetitive behaviors and social deficits in children with autism; however, the efficacy of different stimulation protocols varies. This study systematically evaluated the efficacy of non-invasive brain stimulation on core symptoms in children with autism and compared the efficacy of different stimulation protocols. METHODS: Comprehensive electronic searches were conducted across CNKI, VIP, WanFang, CBM, PubMed, Embase, Cochrane Library, and Web of Science from database inception through March 2025 to identify randomized controlled trials evaluating non-invasive brain stimulation protocols targeting core symptoms in children with autism spectrum disorder. Two independent reviewers performed dual-phase screening, data extraction, and methodological quality assessment using the Cochrane Risk of Bias Tool version 2.0. Both conventional and network meta-analyses were implemented through Revman 5.4 and Stata 17.0. RESULTS: A total of 27 studies were finally included for review, involving 10 stimulation protocols of non-invasive brain stimulation and including 1 701 children with autism. (1) The results of conventional Meta-analysis showed that non-invasive brain stimulation was more effective than conventional rehabilitation in lowering the scores of Childhood Autism Rating Scale, Autism Behavior Checklist, Autism Treatment Evaluation Checklist, and Repetitive Behavior Scale-Revised. (2) The network meta-analysis showed that compared with conventional rehabilitation, high-frequency repetitive transcranial magnetic stimulation over the dorsolateral prefrontal cortex [MD=-6.00, 95%CI(-8.68, -3.33), P < 0.05, SUCRA=89.5%] was most effective in improving Childhood Autism Rating Scale scores, while high-frequency repetitive transcranial magnetic stimulation over Broca's area [MD=-15.11, 95%CI(-18.28, -11.95), P < 0.05, SUCRA=91.1%] was most effective in improving Autism Behavior Checklist scores. CONCLUSION: Current evidence indicates that high-frequency repetitive transcranial magnetic stimulation is most effective in improving core symptoms in children with autism. Due to the dual limitations of methodological heterogeneity and limited sample size in the included studies, large-sample, methodologically rigorous randomized controlled trials are urgently needed to further verify the reliability of these conclusions.

1. Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core symptoms of social communication and interaction deficits, restricted and repetitive behaviors or interests, and often manifests as cognitive, behavioral, emotional, and language expression disorders, accompanied by a range of psychiatric issues such as attention deficit hyperactivity disorder and sleep disorders [1]. According to data from the U.S. Centers for Disease Control and Prevention in 2020, the overall prevalence of ASD in children has risen to 1 in 44, surpassing the combined prevalence of the three major diseases worldwide, with a male-to-female ratio of 3.8:1 [2]. ASD has a significant negative impact on the well-being of affected children and their families; studies have found that parents of children with ASD report lower levels of physical health, mental health, social health, and quality of life compared to parents of typically developing children [3]. The etiology of ASD remains unclear, but it is generally believed to result from multiple factors, with genetic and environmental factors playing important roles in its onset and development [4].

Pharmacological treatments can address comorbid psychiatric issues but do not directly treat the core symptoms of ASD. Therefore, exploring non-pharmacological therapies that can improve core symptoms is crucial [5]. However, existing non-pharmacological therapies generally have limitations such as slow onset and long treatment duration. For example, behavioral therapy requires long-term high-intensity training with significant individual variability in efficacy [6], and sensory integration training lacks standardized protocols and sufficient evidence [7]. In contrast, non-invasive brain stimulation (NIBS) offers unique advantages by directly modulating neural circuits, providing targeted, rapid effects, and the potential to synergistically enhance other therapies, offering a new approach to improving core symptoms of ASD [8]. NIBS is a neuromodulation technique that applies electrical or magnetic stimulation to the scalp to modulate cortical neural activity, with mechanisms including altering cortical excitability and inducing neuroplasticity for long-term functional improvement [9]. Currently, NIBS modalities used clinically to improve core symptoms in children with ASD include repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), transcranial pulse stimulation (TPS), intermittent theta burst stimulation (iTBS), and continuous theta burst stimulation (cTBS). Studies have confirmed that NIBS can improve restricted, repetitive behaviors and social deficits in children with ASD, but the efficacy varies across different stimulation protocols [10-11]. Existing meta-analyses have mostly focused on the efficacy of a single stimulation modality on core symptoms of ASD and have not compared different NIBS protocols [12-13]. Although some network meta-analyses have explored the efficacy differences among different NIBS interventions for ASD, they have primarily focused on tDCS and have not systematically included studies on rTMS and TPS [14].