A Dissociation In Function: Brain Regions Hypoactive to Social Exclusion and Hyperactive to Rule Violation In Children with ASD

Background: Cyberball, a virtual ball-tossing game, elicits feelings of social exclusion in typically developing (TD) children, adolescents, and adults. One behavioral study exploring the psychological effects of social exclusion in adolescents with autism spectrum disorder (ASD) found that arousal but not mood was modulated by exclusion in adolescents with ASD, whereas both were modulated in TD counterparts. Social exclusion, while threatening to interpersonal relationships, also involves expectancy violation, in that one generally expects to be included. The expectancy violation inherent in Cyberball might elicit the sensitivity to environmental change which is characteristic of ASD. No study to date has explored the underlying brain mechanisms for processing social exclusion and/or rule violation in ASD.

Objectives: Using a novel adaptation of Cyberball (Cybershape) with a shape-matching rule dictating the correct recipient of the ball, along with the original Cyberball, we examined neural responses to social exclusion and rule violation. During a functional magnetic resonance imaging (fMRI) scan of age- and IQ-matched children and adolescents with and without ASD, we sought to identify differences in brain responses to social exclusion compared to rule violation within and between groups.

Methods: Participants with (n = 24) and without (n = 24) ASD played Cyberball in alternating blocks of fair play and exclusion. In fair play, the participant received the ball on one-third of the throws; in exclusion the participant did not receive the ball. Participants also played Cybershape in alternating blocks of fair play and rule violation. In fair play, the participant received the shape one-third of the time; the shape rule was never broken. In rule violation, the participant received the shape one-third of the time; but one of the players consistently violated the shape rule by throwing the shape to the wrong player. After playing, participants were given ten questions addressing emotional distress to exclusion or rule violation.

Results: Though both groups reported equal distress following exclusion, a Group by Condition interaction analysis revealed regions of activation that were differentially modulated by inclusion and exclusion in children with and without ASD. Regions previously implicated in processing exclusion, including the right insula and ventral anterior cingulate cortex, were hypoactive in children with ASD relative to their TD peers. In rule violation compared to fair play, the same interaction revealed regions that were hyperactive in ASD, including the right temporoparietal junction, insula, and dorsal prefrontal cortex. A dissociation in activation was identified in the right insula, where it was hypoactive to social exclusion and hyperactive to rule violation in the ASD group. Further probed, different regions of right insula were active in each group, highlighting subtle differences in regional specificity for which subsequent analyses revealed differences in patterns of functional connectivity.

Conclusions: These results demonstrate neurobiological differences in processing social exclusion and rule violation in children with ASD. Specifically, brain regions found to be hypoactive to social stimuli in ASD were hyperactive to rule violation, suggesting that “deficits” in activation of these regions may be contextually specific.