Feasibility, Safety, and Exploratory fNIRS and Behavioral Outcomes of Transcranial-Focused Ultrasound in Children with Autism Spectrum Disorders: A Pilot Study

Background: Overactivation of the left dorsolateral prefrontal cortex (L-DLPFC) has been hypothesized to contribute to repetitive stereotyped behaviors in hyperactive autism spectrum disorder (ASD). This pilot study adopted transcranial-focused ultrasound (tFUS) targeting the L-DLPFC, combined with functional near-infrared spectroscopy (fNIRS) collected during a cartoon-viewing resting-like condition, to evaluate intervention feasibility and explore prefrontal functional connectivity (FC) plasticity. Methods: Nine children aged 4–9 years with hyperactive ASD completed a 4-week tFUS protocol. Behavioral assessments were conducted at pre-tFUS, post-tFUS, and during follow-ups. Cartoon-viewing resting-like oxygenated hemoglobin (HbO) signals covering bilateral prefrontal regions were analyzed using Network-Based Statistics (NBS), seed-based FC, and aggregated network indices. Results: Data on intervention feasibility and safety were collected. Descriptive within-group changes in the Autism Treatment Evaluation Checklist (ATEC) and the Repetitive Behavior Scale-Revised (RBS-R) subscale scores were observed across time points. No statistically significant differences were found in corrected whole-network FC analyses. Global and interhemispheric FC exhibited a biphasic trajectory: transient post-treatment decline followed by 1-month rebound, with interhemispheric connectivity elevated relative to the post-tFUS time point (Δ = 0.14, p = 0.03). Conclusions: This pilot demonstrates the feasibility of L-DLPFC-targeted tFUS combined with fNIRS assessment in young children with hyperactive ASD. Observed behavioral score trends and exploratory neuroimaging findings are hypothesis-generating only. Larger, sham-controlled trials are required to evaluate the safety and potential effects of this intervention.