According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impaired social interaction and communication as well as restricted and repetitive patterns of behavior [1,2]. Individuals with ASD may also exhibit abnormal responses to sensory stimuli, unusual emotional behaviors, difficulties with speech and language comprehension, and challenges with self-care and social adjustment [3]. The prevalence of ASD is a significant public health concern. According to the World Health Organization, approximately 1 in 100 children worldwide is diagnosed with ASD [4]. Data released by the US Centers for Disease Control and Prevention in 2023 showed a sharp increase in the prevalence of autism among children in the United States over the past 20 years [5,6]. Epidemiological survey data from a large sample population in China also indicate a prevalence rate of 0.7% for ASD [7]. Given the growing prevalence of ASD, early assessment, diagnosis, and intervention are crucial. However, the pathogenesis of ASD remains unclear, and there is a lack of specific drug treatments. It is necessary to actively explore effective clinical intervention methods to address this pressing public health challenge.

In recent years, noninvasive brain stimulation, particularly repetitive transcranial magnetic stimulation (rTMS), has been widely applied in the treatment of ASD and has gained recognition among researchers [8,9]. Transcranial magnetic stimulation (TMS) is believed to induce lasting neuroplastic changes in the brain, thereby potentially normalizing social and cognitive functioning in individuals with ASD by stabilizing abnormal neuroplasticity [10]. A meta-analysis by Smith et al [11] of 12 studies demonstrated that TMS improved social withdrawal, repetitive behaviors, and executive function in adolescents with ASD who had an IQ greater than 65, highlighting the significant therapeutic potential of TMS for ASD. Current TMS interventions for ASD primarily target the dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex, and temporo-parietal junction [12,13]. The DLPFC is involved in multiple higher-order cognitive functions, including emotional regulation, decision-making, attentional control, and adaptive adjustment. In ASD, the core symptoms of repetitive, stereotyped behaviors and social impairments are closely associated with DLPFC dysfunction. Studies using low-frequency rTMS targeting the bilateral DLPFC have demonstrated significant reductions in Repetitive Behavior Scale–Revised (RBS-R) scores following intervention [14,15]. Another study using low-frequency rTMS on the bilateral DLPFC in individuals with ASD showed significant improvements in social behavior after 18 treatment sessions. Similarly, Masuda et al [16] and Casanova et al [17] have indicated that low-frequency rTMS may exert therapeutic effects on social interaction and repetitive behaviors in ASD. In summary, DLPFC dysfunction represents a key neural mechanism underlying the core symptoms of ASD, with particularly pronounced effects on social skills and behavioral regulation. Given its favorable safety profile and emerging evidence of efficacy, rTMS offers a promising intervention for addressing the challenges faced by individuals with ASD.

Studies have shown that most children with ASD experience sensory integration dysfunction [18]. Moreover, the core symptoms of ASD are closely related to abnormal sensory processing, with auditory processing abnormalities being a primary concern [19]. Auditory integration training (AIT), a novel audio therapy initially proposed by French physician Guy Bérard [20], filters out hypersensitive frequencies to reduce auditory cortex sensitivity to sound stimuli, thereby significantly improving auditory attention in children with ASD [21]. Studies indicate that AIT effectively improves language, social interaction, communication, and behavioral skills in children with ASD who also have auditory attention deficits. International studies have explored the physiological effects of AIT on plasma glial cell–derived neurotrophic factor levels. Results demonstrate that AIT significantly elevates plasma glial cell–derived neurotrophic factor levels, thereby improving abnormal sensory processing in affected children [22]. Multiple studies support the efficacy of this method, indicating that when children with ASD can more accurately perceive and process auditory information, their comprehension and expression abilities improve, leading to enhanced functioning in social skills, communication, and related domains [18,23]. However, AIT is considered limited in its capacity to fundamentally activate and repair the nervous system, which may hinder sustained functional recovery [24]. Given this limitation, current research predominantly combines AIT with traditional behavioral training to evaluate treatment outcomes [25,26]. Furthermore, previous studies have often lacked appropriate control groups, necessitating additional research to validate AIT’s efficacy. Nevertheless, AIT can be easily implemented in laboratory or clinic settings, facilitating researchers’ collection of physiological data for objective assessment of treatment outcomes.

Although preliminary findings from these individual interventions are encouraging, the evidence base for their combined application remains limited and is subject to methodological constraints. To our knowledge, the few existing studies on combined rTMS and AIT lack adequate control conditions and are susceptible to placebo effects and observer bias [27,28]. A critical and pervasive limitation in recent studies of noninvasive brain stimulation interventions for ASD is the absence of high-quality sham-controlled trials [29,30]. This significant methodological gap prevents definitive conclusions about the true synergistic efficacy of these combined interventions. Consequently, there is an urgent need for rigorous, well-controlled research evaluating the synergistic effects of these 2 treatment modalities to provide stronger evidence-based support for ASD interventions.

The primary objective of this study is to investigate whether the combination of rTMS and AIT produces superior effects on brain activity and behavior outcomes in children with ASD compared to sham-controlled conditions. We hypothesize that the combined intervention will yield synergistic benefits, and the findings from this study are expected to provide a scientific foundation for optimizing clinical interventions for ASD.

We hypothesize that, compared to the sham stimulation control group, participants with ASD receiving the active rTMS combined with AIT intervention will exhibit significant improvements in core symptoms such as social difficulties and stereotyped behaviors as measured using standardized scales such as the ABC, CARS, RBS-R, and SDQ. This study aims to provide the latest evidence-based support for the efficacy of this combined intervention approach.

Although preliminary studies have reported positive effects of rTMS combined with AIT in ASD, most have lacked blinding and placebo controls. By implementing a double-blind, sham-controlled design, this trial will address that key methodological limitation. If the results align with our hypotheses, they will provide the first clear demonstration of the specific therapeutic benefits of this combined intervention, thereby advancing the evidence level in this field from the exploratory stage to preliminary validation.

The core strength of this study lies in its rigorous methodological design. As a prospective randomized controlled trial, it uses a double-blind, sham stimulus–controlled approach, which minimizes the potential for expectation and observer biases during the evaluation process, thereby strengthening the causal inferences that can be drawn from the observed efficacy differences. Additionally, the study uses recognized, standardized assessment tools, including the ABC, CARS, SDQ, and RBS-R, to provide a comprehensive and objective evaluation of the core symptom domains in ASD. This assessment combination ensures good reliability and clinical relevance of the study results. Finally, the rTMS and AIT interventions are noninvasive, well tolerated, and easy to implement in clinical settings. These features support participant compliance and trial feasibility and, if the interventions prove effective, will facilitate wider clinical translation as a safe, scalable treatment option for children with ASD.

This study also has some important limitations. First, while rigorous behavioral assessments are used, neurophysiological indicators (eg, EEG and functional near-infrared spectroscopy) are not included. Therefore, this study cannot directly reveal the underlying neural mechanisms of the combined intervention. Future studies should verify these mechanisms in conjunction with neuroimaging techniques. Second, the primary objective is to preliminarily evaluate whether adding AIT to rTMS could yield superior clinical efficacy. As a result, a separate control group receiving AIT alone was not established. Subsequent studies will need to expand the sample size to explore this question. Additionally, the follow-up period after the intervention may be insufficient to assess the long-term durability of the effects, so our conclusions will be limited to discussing the short-term efficacy.

On the basis of the expected results and limitations of this study, future research should focus on the following directions. First, at the mechanistic level, follow-up studies should integrate neuroimaging techniques such as EEG, functional near-infrared spectroscopy, or functional magnetic resonance imaging to directly observe the effects of the combined intervention on brain network connectivity and neural activity. Second, at the level of efficacy optimization, trials with larger sample sizes, longer follow-up periods (eg, 6 months or 1 year), and inclusion of an AIT-only group will be needed to verify the durability of the intervention’s benefits and clarify the individual vs additive benefits of rTMS and AIT.