Oxytocin's Impact on Social Cognitive Brain Function in Youth with ASD

Background:  

Social dysfunction is a core deficit in individuals with Autism Spectrum Disorders (ASD) and yet the underlying neural mechanisms remain unclear. Novel avenues of translational research come from recent discoveries regarding the effects of the neuropeptide Oxytocin (OT) on a wide range of social behaviors in humans, especially increased sociability, empathy and theory-of-mind. Additionally, variations in the OT receptor gene (OXTR) have been linked to ASD in several studies. Considering the known social deficits in ASD, it is important to seek a deeper understanding of the mechanisms underlying OT's effects using functional magnetic resonance imaging (fMRI).

Objectives:  

This study aims to identify the impact of OT on brain regions linked to social motivation, social perception, and social cognition. We hypothesize that during fMRI tasks that require processing of social information, OT administration will result in  increased activity in regions who play a key role in reward circuitry (such as the striatum, caudate and nucleus accumbens) as well as key nodes of the social brain (specifically, the anterior cingulate and prefrontal cortex, superior temporal sulcus, amygdala). We also expect increased connectivity between these brain regions due to OT’s impact.

Methods:  

We are currently performing a double blind, crossover, and randomized controlled study, in which 40 children and adolescents (ages 7-18) with ASD are randomly assigned to OT and placebo nasal sprays on two consecutive visits. To our knowledge, this is the first ever intranasal OT and fMRI study in ASD with such a young age group. After administration, we are testing participants’ ability to detect biological motion and read others’ emotions from the eye region using well-validated fMRI paradigms: Reading the Mind in the Eyes (RMET-R) and Biological Motion Detection.

Results:  

Preliminary results are indicating that in children and adolescents with ASD, intranasal administration of OT results in enhanced activation of the superior temporal sulcus (STS) region during perception of biological motion compared to placebo. When going through RMET-R, OT seems to improve the ability to accurately define and describe other’s mental states as well as enhance brain activation in medial prefrontal cortex, STS, temporal parietal junction and fusifrom – all regions previously implicated in social perception and cognition, mentalizing, and theory of mind abilities.

Conclusions:  

These initial results are currently being expended, but they provide a very promising and exciting indicator of the neural mechanisms’ underlying OT’s impact on social perception and cognition in children with ASD. At IMFAR, final results will be presented and discussed. Should this study show that modulating OT levels can induce specific effects on brain functioning and behavior in tasks linked to the social world, it would be possible to explore novel more optimal treatment strategies in ASD.