Intranasal Oxytocin Enhances Connectivity in the Neural Circuitry Supporting Social Motivation and Social Perception in Children with Autism

Abstract

Oxytocin (OT) has become a focus in investigations of autism spectrum disorder (ASD). The social deficits that characterize ASD may relate to reduced connectivity between brain sites on the mesolimbic reward pathway (nucleus accumbens; amygdala) that receive OT projections and contribute to social motivation, and cortical sites involved in social perception. Using functional magnetic resonance imaging and a randomized, double blind, placebo-controlled crossover design, we show that OT administration in ASD increases activity in brain regions important for perceiving social-emotional information. Further, OT enhances connectivity between nodes of the brain’s reward and socioemotional processing systems, and does so preferentially for social (versus nonsocial) stimuli. This effect is observed both while viewing coherent versus scrambled biological motion, and while listening to happy versus angry voices. Our findings suggest a mechanism by which intranasal OT may bolster social motivation—one that could, in future, be harnessed to augment behavioral treatments for ASD.

The Social (Neural) Network: Towards a Unifying Endophenotype Between Genes and Behavior

“…In autistic children, a recent study has further shown that intranasal oxytocin acutely strengthens seed-based connectivity from the amygdala and ventral striatum to networks supporting social perception and motivation 9 . There is also evidence that differential expression of OXTR is predicted by early life experiences 135 .…”

“…Importantly, several of these reports suggested a potential therapeutic role for OT administration in cases of trauma 95 , social anxiety 92 , and autism 9,12,94 .…”

“…As a central neurotransmitter and neuromodulator, oxytocin has been associated with a number of neural phenomena in nonhuman animals, including anxiolysis 4 and the adjustment of neural signal-to-noise ratios (SNR) during long-term potentiation 5,6 . In humans, a growing body of research has demonstrated that intranasal administration of oxytocin acutely modulates the function of brain networks in support of social cognition [7][8][9][10][11][12] .…”

“…One broad explanation is that OT increases the response to positively-valenced social information while decreasing the response to aversive or threatening social information-both would suggest that oxytocin enables various types of social reinforcement learning, and the latter phenomenon is in agreement with animal and human research suggesting an anxiolytic effect of oxytocin 4,[85][86][87] In general, most evidence points to oxytocin administration enhancing functional coupling across the brain, both at rest and under task-positive states 7 . For example, intranasal OT commonly increases functional connectivity from the amygdala to areas such as the insula 91 , mPFC 12,92,93 , anterior cingulate 92 , and a number of additional brain regions relevant for social perception 9 and emotion regulation 11 . OT administration may also enhance connectivity between mesolimbic and prefrontal regions important for social motivation 9 and social evaluation 94 .…”

“…For example, intranasal OT commonly increases functional connectivity from the amygdala to areas such as the insula 91 , mPFC 12,92,93 , anterior cingulate 92 , and a number of additional brain regions relevant for social perception 9 and emotion regulation 11 . OT administration may also enhance connectivity between mesolimbic and prefrontal regions important for social motivation 9 and social evaluation 94 .…”