Exploring the Neural Mechanisms of Acupuncture Stimulation in Autism Spectrum Disorder: Protocol for a Randomized, Sham-Controlled, Multimodal Neuroimaging Trial.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted and repetitive behaviors and disturbances in social communication and interaction. Currently, there is no fundamental treatment for ASD, with only a few medications available for use on a limited basis to manage concomitant neuropsychiatric symptoms. The primary therapeutic goal of such treatments is to alleviate symptoms while maximizing the functional independence and quality of life of affected individuals. Many complementary and alternative medicine therapies have been reported to have effects on ASD symptoms; however, evidence is insufficient to confirm their clinical effectiveness. Acupuncture has traditionally been used as a complementary intervention to manage various neurological and neuropsychiatric diseases, including ASD, in East Asia. However, how acupuncture stimulation modulates neural activity at the macroscale level in individuals with ASD remains largely unknown. Objective: This study aims to elucidate disease-related brain alterations and explore the acute neural mechanisms underlying acupuncture stimulation in patients with ASD and in typically developing (TD) individuals, using a multimodal neuroimaging approach. Methods: This study was designed as a randomized, sham-controlled trial. In this stratified 2×2 design, 70 participants, including individuals with ASD (n=35) and TD controls (n=35), will each be randomly assigned to either the verum or sham acupuncture group, resulting in 4 groups. The verum acupuncture group will receive stimulation at specific acupoints clinically indicated for ASD, eliciting a deqi sensation. The sham acupuncture group will receive superficial needling at nonacupoints unrelated to ASD symptoms. Each group will undergo clinical assessments and multimodal neuroimaging measurements, including functional near-infrared spectroscopy and electroencephalography, before and after acupuncture stimulation. The primary outcome will be differences in resting state network metrics and relative band power in frontal areas by disease status. Secondary outcomes will include differences in these neural markers following acupuncture stimulation between the verum and sham groups, reflecting the group × intervention interaction. Exploratory outcomes will focus on identifying neural markers that correlate with clinical indicators of ASD. Results: Recruitment began in April 2025. To date, 23 individuals with ASD and 21 TD individuals have participated in this study. The recruitment process is expected to continue until December 2026. Conclusions: ASD presents a significant socioeconomic burden, with no definitive treatment established to date. Although acupuncture is a widely applied intervention for various neurological conditions, including ASD, its large-scale neural mechanisms remain poorly understood. By using multimodal neuroimaging, the present study aims to investigate the immediate neural substrates underlying acupuncture stimulation in patients with ASD. These findings are expected to provide a robust neurobiological foundation for future longitudinal research and the development of evidence-based integrative strategies.