Oxytocin enhances basolateral amygdala activation and functional connectivity in autistic women while processing emotional faces

Background: Oxytocin is hypothesized to promote positive social interactions by enhancing the salience of social stimuli, which may be reflected by altered amygdala activation. While previous neuroimaging studies have reported that oxytocin enhances amygdala activation to emotional face stimuli in autistic men, effects in autistic women remain unclear. Methods: The influence of intranasal oxytocin on neural response to emotional faces vs. shapes were tested in 16 autistic and 21 non-autistic women by fMRI in a placebo-controlled, within-subjects, cross-over design. Effects of group (autistic vs. non-autistic) and drug condition (oxytocin vs. placebo) on the activation and functional connectivity of the basolateral amygdala, the brain’s “salience detector”, were assessed. Relationships between individual differences in autistic-like traits, social anxiety, salivary oxytocin levels, and amygdala activation were also explored.Results: Autistic and non-autistic women showed minimal activation differences in the placebo condition. Significant drug × group interactions were observed for both amygdala activation and functional connectivity. Oxytocin increased left basolateral amygdala activation among autistic women (35 voxel cluster, MNI coordinates of peak voxel = -22 -10 -28; mean change=+0.079%, t=3.159, ptukey=0.0166), but not non-autistic women (mean change =+0.003%, t=0.153, ptukey=0.999). Furthermore, oxytocin increased functional connectivity of the right basolateral amygdala with brain regions associated with socio-emotional information processing in autistic women, but not non-autistic women, thereby attenuating group connectivity differences observed in the placebo condition. Conclusions: This work demonstrates that intranasal oxytocin increases basolateral amygdala activation and connectivity in autistic women while processing emotional faces, which extends and specifies previous findings in autistic men.