The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder

R K Greene,G S Dichter,M Spanos,G D Stuber,C Alderman,J Bizzell,T Chandrasekhar,L C Politte,E Walsh,J L Kinard,M G Mosner,L Sikich

doi:10.1186/s11689-018-9228-y

Abstract

BackgroundIntranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, thus, has received considerable interest as a potential ASD therapeutic agent. Although preclinical research indicates that OT modulates the functional output of the mesocorticolimbic dopamine system that processes rewards, no clinical brain imaging study to date has examined the effects of OT on this system using a reward processing paradigm. To address this, we used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD.MethodsIn this placebo-controlled double-blind study, 28 children and adolescents with ASD (age: M = 13.43 years, SD = 2.36) completed two fMRI scans, one after intranasal OT administration and one after PLC administration. During both scanning sessions, participants completed social and nonsocial incentive delay tasks. Task-based neural activation and connectivity were examined to assess the impact of OT relative to PLC on mesocorticolimbic brain responses to social and nonsocial reward anticipation and outcomes.ResultsCentral analyses compared the OT and PLC conditions. During nonsocial reward anticipation, there was greater activation in the right nucleus accumbens (NAcc), left anterior cingulate cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal cortex, and right frontal pole (FP) during the OT condition relative to PLC. Alternatively, during social reward anticipation and outcomes, there were no significant increases in brain activation during the OT condition relative to PLC. A Treatment Group × Reward Condition interaction revealed relatively greater activation in the right NAcc, right caudate nucleus, left ACC, and right OFC during nonsocial relative to social reward anticipation during the OT condition relative to PLC. Additionally, these analyses revealed greater activation during nonsocial reward outcomes during the OT condition relative to PLC in the right OFC and left FP. Finally, functional connectivity analyses generally revealed changes in frontostriatal connections during the OT condition relative to PLC in response to nonsocial, but not social, rewards.ConclusionsThe effects of intranasal OT administration on mesocorticolimbic brain systems that process rewards in ASD were observable primarily during the processing of nonsocial incentive salience stimuli. These findings have implications for understanding the effects of OT on neural systems that process rewards, as well as for experimental trials of novel ASD treatments developed to ameliorate social communication impairments in ASD.

Highlights

Intranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, has received considerable interest as a potential ASD therapeutic agent
Face image ratings Participants rated the faces seen in the social reward condition on the dimensions of valence, arousal, and trust prior to and immediately following each scan
In addition to providing substantive results about the neural impact of acute intranasal OT administration on reward processing brain systems, the present study suggests that optimal approaches to evaluate novel ASD treatments with putative effects on brain systems that support social reward processing may not be constrained to evaluating responses to only social stimuli

Summary

Introduction

Intranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, has received considerable interest as a potential ASD therapeutic agent. We used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD. Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and interaction, as well as restricted and repetitive behaviors (APA [1]). The neuropeptide oxytocin (OT) has been shown to increase pro-social behaviors in human studies and in preclinical model organisms. Studies in typically developing individuals have shown that intranasal OT administration increases in-group trust [5] and interoceptive awareness [6] while reducing fear [7]. In mammalian nonhuman models, OT moderates or initiates paternal and reproductive behaviors, as well as other pro-social behaviors such as grooming and social recognition [8, 9]

Objectives

Methods

Results

Conclusion