Oxytocin improves behavioural and neural deficits in inferring others’ social emotions in autism

Abstract

Recent studies have suggested oxytocin's therapeutic effects on deficits in social communication and interaction in autism spectrum disorder through improvement of emotion recognition with direct emotional cues, such as facial expression and voice prosody. Although difficulty in understanding of others' social emotions and beliefs under conditions without direct emotional cues also plays an important role in autism spectrum disorder, no study has examined the potential effect of oxytocin on this difficulty. Here, we sequentially conducted both a case-control study and a clinical trial to investigate the potential effects of oxytocin on this difficulty at behavioural and neural levels measured using functional magnetic resonance imaging during a psychological task. This task was modified from the Sally-Anne Task, a well-known first-order false belief task. The task was optimized for investigation of the abilities to infer another person's social emotions and beliefs distinctively so as to test the hypothesis that oxytocin improves deficit in inferring others' social emotions rather than beliefs, under conditions without direct emotional cues. In the case-control study, 17 males with autism spectrum disorder showed significant behavioural deficits in inferring others' social emotions (P = 0.018) but not in inferring others' beliefs (P = 0.064) compared with 17 typically developing demographically-matched male participants. They also showed significantly less activity in the right anterior insula and posterior superior temporal sulcus during inferring others' social emotions, and in the dorsomedial prefrontal cortex during inferring others' beliefs compared with the typically developing participants (P < 0.001 and cluster size > 10 voxels). Then, to investigate potential effects of oxytocin on these behavioural and neural deficits, we conducted a double-blind placebo-controlled crossover within-subject trial for single-dose intranasal administration of 24 IU oxytocin in an independent group of 20 males with autism spectrum disorder. Behaviourally, oxytocin significantly increased the correct rate in inferring others' social emotions (P = 0.043, one-tail). At the neural level, the peptide significantly enhanced the originally-diminished brain activity in the right anterior insula during inferring others' social emotions (P = 0.004), but not in the dorsomedial prefrontal cortex during inferring others' beliefs (P = 0.858). The present findings suggest that oxytocin enhances the ability to understand others' social emotions that have also required second-order false belief rather than first-order false beliefs under conditions without direct emotional cues in autism spectrum disorder at both the behaviour and neural levels.

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia

“…Although there is no clinical use of minocycline in ASD, recent studies have revealed improvement of ASD symptoms by intranasal administration of oxytocin and demonstrated the association of polymorphisms in the oxytocin receptor (OXTR) gene in ASD (Andari et al, 2010;Guastella et al, 2010;Aoki et al;2014;LoParo and Waldman, 2015). Furthermore, abnormal activation of microglia and a reduction of PSD-95 expression in the Oxtr-deficient brain (Miyazaki et al, 2016) have been found.…”

Insular Cortex Mediates Approach and Avoidance Responses to Social Affective Stimuli

“…Indeed, experimenter-administered OT augments behavioral performance in emotion recognition, relieves some social deficits observed in individuals with ASD; and increases insular activity and connectivity to frontal cortex [43][44][45] . Furthermore, mutations in the OTR gene predict ASD symptoms 46 , insular activation 47 and social cognition 48,49 .…”

Does imitation act as an oxytocin nebulizer in autism spectrum disorder?

“…In an elegant paper recently published in Brain, oxytocin was shown to enhance both the score of correct inferences and the low autistic brain activity in the right anterior insula when inferring the emotions and beliefs of others (Aoki et al, 2014). Using a revisited version of the Sally-Anne Task, Aoki and colleagues suggest that reduced activity of the right anterior insula is a potential neural marker of autistic deficit in social inferences.…”

“…The following firstlevel individual t-contrast images were obtained for the haemodynamic response function estimates: 'being imitated versus observation' and 'observation versus being imitated'. We focused the second-level analysis on the insula and the default mode network with an a priori region of interest approach (Guionnet et al, 2012;Aoki et al, 2014). A paired t-test analysis was performed to assess the difference in activation of the insula and default mode network between both MRI scans.…”