Previous research indicates that the size of interpersonal space at which the other is perceived as intrusive (permeability) and the ability to adapt interpersonal distance based on contextual factors (flexibility) are altered in Autism Spectrum Disorder (ASD). However, the neurophysiological basis of these alterations remains poorly understood. To fill this gap, we used fMRI and assessed interpersonal space preferences of individuals with ASD before and after engaging in cooperative and non-cooperative social interactions. Compared to matched controls, ASDs showed lower comfort in response to an approaching confederate, indicating preference for larger interpersonal space in autism (altered permeability). This preference was accompanied by reduced activity in bilateral dorsal intraparietal sulcus (dIPS) and left fusiform face area (FFA), regions previously shown to be involved in interpersonal space regulation. Furthermore, we observed differences in effective connectivity among dIPS, FFA, and amygdala in ASDs compared to controls, depending on the level of experienced comfort. No differences between groups were observed in interpersonal space regulation after an experienced social interaction (flexibility). Taken together, the present findings suggest that a dysregulation of the activity and connectivity of brain areas involved in interpersonal space processing may contribute to avoidance of physical proximity and social impairments in ASD.

Many autistic children suffer from social communication problems, reduced participation, and mental health issues. Music therapy has beneficial but heterogeneous effects; its mechanisms are incompletely understood. The Music for Autism (M4A) trial aims to replicate and expand a previous trial examining brain mechanisms and clinical outcomes of music versus play-based therapy for autistic children. This paper presents M4A’s design and implementation; we examine feasibility of this replication trial based on the first wave of recruitment. M4A is a crossover randomised controlled trial currently conducted at two sites (Bergen, Norway; Vienna, Austria). Children aged 6-12 years diagnosed with autism spectrum disorder will be randomised to a sequence of weekly individual music and play-based therapy (3 months for each intervention; 3-month washout period). Outcomes assessed before and after each intervention period include communication (blinded, assessed by teachers); functional brain connectivity (from functional magnetic resonance imaging, fMRI); and further behavioural and biological outcomes. The planned total sample size of 80 will ensure adequate power. Recruitment in the first wave (14 randomised) was below expectations. Baseline characteristics were similar to the previous study, but some variables (severity, functioning) were difficult to assess and compare. A range of functioning levels were included. Interventions were well accepted; fidelity was adequate. Timing of interventions and assessments was challenging when blinded assessors were hard to reach. Blinding was successful. Movement in fMRI was an issue in some children, but we developed preparation strategies to help also low-functioning children to successfully complete the scans. No study-related adverse events occurred. M4A has a strong design, appears feasible, and promises important new insights into the mechanisms and outcomes of music therapy for ASD. Multinational replicability of controlled trials of complex psychosocial interventions in ASD combining clinical and brain imaging outcomes can be challenging and requires careful planning. Trial registration: Clinicaltrials.gov NCT04936048

Interpersonal space can be defined as a safety zone immediately surrounding our body, which allows us to feel comfortable during social interactions. Previous studies indicate that the size of interpersonal space at which the other is perceived as intrusive (permeability) and the ability to adapt interpersonal distance based on contextual factors (flexibility) are altered in children and adults with Autism Spectrum Disorder (ASD). The present fMRI study aimed at extending the previous findings by investigating the behavioral and neurophysiological underpinnings of interpersonal space permeability and flexibility in adults with ASD. Individuals with ASD and matched controls (CTR) performed a modified version of the stop-distance paradigm for measuring interpersonal space preferences. Participants observed prerecorded videos of two confederates moving towards them and rated their comfort to the observed distance. The assessment of interpersonal space preferences was performed before and after engaging in cooperative and non-cooperative social interactions with the confederates, experimentally induced by means of a repeated trust game. We observed general lower comfort in response to an approaching confederate in the ASD group compared to the CTR group, indicating preference for larger interpersonal space in autism (altered permeability). This preference was accompanied by reduced activity in bilateral dorsal intraparietal sulcus (dIPS) and left fusiform face area (FFA), regions previously shown to be involved in interpersonal space regulation. Furthermore, we observed differences in effective connectivity among dIPS, FFA, and amygdala in ASDs compared to CTRs, depending on the level of experienced comfort. No differences between ASDs and CTRs were observed in the adaptation of interpersonal space following a cooperative and non-cooperative social interaction, suggesting preserved interpersonal space flexibility in the ASD adult population. The present study provides evidence for impaired permeability of interpersonal space in adults with ASD. The findings suggest that a dysregulation of the activity and connectivity of brain areas involved in the processing of interpersonal space may contribute to preference for larger distance and avoidance of physical proximity in ASDs. Future research is needed to examine whether the observed alteration of interpersonal space processing is an effect of or a contributing factor to the social disabilities characterizing autism.