An Integration of fMRI Neural Effects of Oxytocin in Children with ASD: Insights from Three Paradigms of Social Processing

Background:  Discoveries regarding the impact of acutely modulating the neuropeptide oxytocin (OT) have led to exciting avenues for translational research efforts in autism spectrum disorders (ASD). Novel reports on the neural mechanism involved in intranasal administration of OT to adults with ASD highlight OT’s positive impact on key nodes of “the social brain” such as the amygdala and the medial prefrontal cortex (mPFC). Considering the early onset of ASD and the young age of diagnosis and treatment and considering the positive impact acute manipulation of OT has had on various social behaviors, such as emotion recognition and theory of mind, it is crucial to achieve a crystalized understanding of the neural mechanism underlying OT administration in children and adolescents with ASD. 

Objectives: Using several fMRI paradigms that assess different modalities of social processing, we aimed to pinpoint the neural mechanism underlying a single OT administration in children with ASD. We further aimed to identify neural networks and connectivity measures that are associated with OT's impact compared to placebo.  We expected neural effects of OT administration to be apparent in key nodes of the social brain, such as the amygdala, the posterior superior temporal sulcus and the mPFC. We also expected OT to enhance activation in neural circuits that process reward and motivation such as the striatum.

Methods: Seventeen children with ASD (ages 7-18) received acute administration of OT in this placebo-controlled study of changes in brain activity and behavior. Forty-five minutes following OT administration, an fMRI scan ensued in which three fMRI paradigms for social processing were presented: Reading the Mind in the Eyes, Biologicl Motion and Affective Voices.  fMRI data was analyzed to assess the neural impact of OT.

Results: Results from brain function analysis of a mentalization task indicate that OT increased activity in the striatum, the middle frontal gyrus, the medial prefrontal cortex, the right orbitofrontal cortex, and the left superior temporal sulcus. In the striatum, nucleus accumbens, the left posterior superior temporal sulcus, and the left premotor cortex, oxytocin increased activity during social judgments and decreased activity during non-social judgments. All of these regions have previously been implicated in their involvement in social perception and cognition, mentalizing abilities, and theory of mind.  In both the mentalization and the biological motion task, we show that OT can enhance connectivity between striatal regions and frontal cortical regionscebo, an effect that may underlie the processing of the rewarding value of social-emotional stimuli. Finally, we also show that for affective voice processing OT enhances saliency by increasing activity in the left superior frontal gyrus, middle temporal gyrus, cuneus, cerebellar lobule VI, the right inferior frontal gyrus and the right caudate. 

Conclusions: These results provide essential and critical steps in the integrative understanding of the neural mechanism underlying a single administration of intranasal OT has in youth with ASD. We believe this will advance translational progress in support of more effective treatments for core social deficits in ASD.