Interventional rTMS for Improving Social Perception in Autism

Autism spectrum disorder (ASD) is a neurodevelopmental condition mainly characterized by persistent difficulties in social communication and interaction, together with restricted and repetitive patterns of behavior. Despite substantial progress in understanding the neurobiological mechanisms underlying ASD, therapeutic options specifically targeting core social difficulties remain limited. Non-invasive brain stimulation techniques, including transcranial magnetic stimulation (TMS), therefore represent a promising approach for investigating and potentially modulating neural networks involved in social functioning.

Neuroimaging studies have consistently identified structural and functional abnormalities localized in the superior temporal sulcus (STS) in individuals with ASD. The STS is a key component of the social brain network and is involved in the processing and integration of socially relevant information, including faces, gaze, voices, biological motion, and other dynamic social cues. Functional and structural abnormalities of this region, as well as altered connectivity between the STS and other components of the social brain network, have been reported in ASD. These findings provide the neurobiological rationale for targeting the STS in the present study.

Previous work by our research team has investigated whether modulation of the right posterior STS (pSTS) using TMS can influence social perception. A first study in typically developing adults established a causal relationship between modulation of pSTS activity and changes in visual exploration of socially relevant information. Subsequent studies in young adults with ASD demonstrated the feasibility and good tolerability of excitatory intermittent theta-burst stimulation (iTBS) targeting the right pSTS. More recently, a pilot randomized, double-blind, sham-controlled clinical trial in young adults with ASD evaluated repeated iTBS sessions targeting this region. The intervention was feasible and well tolerated, and preliminary findings suggested differential changes in social behavior following active compared with sham stimulation. These findings support further investigation of this approach using a more intensive stimulation protocol.

The IRIS-gaze study investigates an accelerated iTBS protocol targeting the right pSTS in pre-adolescents and adolescents with ASD. Adolescence represents a developmental period characterized by substantial brain plasticity and may therefore constitute a particularly relevant period for neuromodulatory interventions. Accelerated TMS protocols, in which several stimulation sessions are administered each day over a limited number of days, are designed to induce cumulative neuroplastic effects while substantially reducing the overall duration of treatment compared with conventional repeated TMS schedules.

IRIS-gaze is an interventional, randomized, double-blind, sham-controlled crossover clinical trial. Sixteen participants will receive both active and sham stimulation in a randomized order. Each treatment period consists of five iTBS sessions per day for four consecutive days, for a total of 20 sessions per treatment period. The two treatment periods are separated by a washout period of approximately three months (3 months ± 2 weeks), selected to minimize potential carry-over effects between active and sham stimulation. The crossover design allows each participant to serve as his or her own control, thereby reducing the influence of inter-individual variability, and insures that all participants receive the active condition.