The dual neural effects of oxytocin in autistic youth: results from a randomized trial

Abstract

Recent discoveries have highlighted the effects of oxytocin (OT) on social behavior and perception among autistic individuals. However, a gap persists in the literature regarding the potential effects of OT and the neural temporal dynamics due to OT administration. We explored the effect of OT on autistic individuals using magnetoencephalography (MEG), focusing on M100, M170, and M250, social perception-related components that tend to show atypical patterns in autistic individuals. Twenty-five autistic adolescents participated in this randomized, double-blind MEG study. Autistic individuals arrived at the lab twice and received an acute dose of intranasal OT or placebo in each session. During the scans, participants were asked to identify pictures of social and non-social stimuli. Additionally, 23 typically developing (TD) adolescents performed the same task in the MEG as a benchmark that allowed us to better characterize neural regions of interest and behavioral results for this age group in this task. A source-model beamformer analysis revealed that OT enhanced neural activity for social stimuli in frontal regions during M170. Additionally, in each of the preselected time windows, OT increased activation in the left hemisphere, regardless of the content of the presented stimuli. We suggest that OT increased the processing of social stimuli through two separate mechanisms. First, OT increased neural activity in a nonspecific manner, allowing increased allocation of attention toward the stimuli. Second, OT enhanced M170 activity in frontal regions only in response to social stimuli. These results reveal the temporal dynamics of the effects of OT on the early stages of social and non-social perception in autistic adolescents.Trial registration: This study was a part of a project registered as clinical trial October 27th, 2021. ClinicalTrials.gov Identifier: NCT05096676.

Intranasal Oxytocin in Pediatric Populations: Exploring the Potential for Reducing Irritability and Modulating Neural Responses: A Mini Review

“…Gordon et al [ 1 ] found that the administration of OXT led to increased activity in brain regions crucial for processing social-emotional information and enhanced the connectivity between nodes of the brain’s reward and social-emotional processing systems specifically during social stimuli, including increased functional connectivity of the amygdala with the ventromedial PFC, the orbitofrontal cortex and the precuneus. Similarly, Korisky et al [ 73 ] found that OXT increased neural activity in the frontal regions of the brain in response to social stimuli, as well as in the left hemisphere regardless of the stimulus. Takiguchi et al [ 77 ] discovered that OXT administration enhanced activation in the right middle frontal gyrus and striatum, consistent with enhancements in the mesolimbic dopaminergic reward system.…”

“…Damen et al [ 42 ] administered doses ranging from 16–40 IU daily and provided higher doses to participants with larger body surface areas. Gordon et al [ 1 ] and Korisky et al [ 73 ] stratified dosages based on the ages of their participants, while Dadds et al [ 25 ] provided 24 IU daily to participants weighing more than 40 kg and 12 IU daily to participants weighing under 40 kg. Miller et al [ 43 ] provided all participants with 16 IU daily.…”

“…The social responsiveness scale (SRS) was used by eight of the fifteen studies [ 25 , 26 , 42 , 70 , 71 , 72 , 74 , 75 ], five of which [ 25 , 42 , 70 , 71 , 75 ] found that OXT improved the SRS scores of participants, suggesting that intranasal OXT may improve the social functioning of pediatric patients with ASD or PWS. One study (Daniels et al [ 73 ]) reported no significant differences were observed in SRS-2 or RBS-R between the groups receiving OXT and placebo during double-blind procedures. However, improvement was noted during the single-blind phase of the trial in the SRS-2.…”

“…Four studies [ 1 , 69 , 73 , 77 ] used brain imaging (fMRI [ 1 , 69 , 77 ] and MEG [ 73 ]) to examine the effects of intranasal OXT administration on pediatric ASD patients. In these, intranasal OXT was found to increase activation of reward processing brain systems in response to nonsocial stimuli [ 69 ] and enhance activity and connectivity in brain regions involved in perceiving social-emotional information during social stimuli [ 1 , 73 ].…”

“…Four studies [ 1 , 69 , 73 , 77 ] used brain imaging (fMRI [ 1 , 69 , 77 ] and MEG [ 73 ]) to examine the effects of intranasal OXT administration on pediatric ASD patients. In these, intranasal OXT was found to increase activation of reward processing brain systems in response to nonsocial stimuli [ 69 ] and enhance activity and connectivity in brain regions involved in perceiving social-emotional information during social stimuli [ 1 , 73 ]. Gordon et al [ 1 ] found that the administration of OXT led to increased activity in brain regions crucial for processing social-emotional information and enhanced the connectivity between nodes of the brain’s reward and social-emotional processing systems specifically during social stimuli, including increased functional connectivity of the amygdala with the ventromedial PFC, the orbitofrontal cortex and the precuneus.…”