The post-game measures confirmed that participants felt distress following the experiences of social exclusion and rule violation, and also identified group differences in distress levels. In TD children, the average total score on the social exclusion distress questionnaire (SED-Q) was 25.70 (± 7.68, n = 20; a score of 10 indicates no distress, while a score of 50 indicates extreme distress), while the average total score on the rule violation distress questionnaire (RVD-Q) was 22.17 (± 4.76, n = 17, a score of 10 indicates no distress, while a score of 50 indicates extreme distress). In children with ASD, the average total score on the SED-Q was 29.57 (± 7.76, n = 14), and the average total score on the RVD-Q was 25.59 (± 4.37, n = 17). Scores on the SED-Q did not differ between groups (p > .05). However, the ASD group reported significantly higher distress than the TD group on the RVD-Q (t = -2.10, p = .04).
To investigate brain regions modulated by the experience of social exclusion in each group, random-effects multi-participant-GLM analyses comparing social exclusion > fair play were performed in TD children and children with ASD separately (). Peak coordinates, statistical values, size, and anatomical labels for the regions of differential activation in Cyberball are displayed in . TD children showed significant activation in regions previously implicated in processing exclusion in adults, including bilateral posterior insula, bilateral posterior cingulate cortex (PCC), and ventral anterior cingulate cortex (vACC). In addition, left vlPFC, left anterior superior temporal sulcus, and left parahippocampal gyrus (PHG) were also more active to social exclusion. Regions that showed preferential activation to fair play in Cyberball included left cerebellum, parietal cortex, and right precentral gyrus.
Figure 1 Top: whole-brain comparison of social exclusion and fair play in TD (n = 21; left) and ASD participants (n = 16; right). Regions in orange showed greater activation in social exclusion compared to fair play. Regions in blue showed greater activation in (more ...)
Table 2 Activation in Cyberball. Regions identified in a full brain contrast of social exclusion to fair play within each group (TD and ASD). Talairach coordinates and statistics refer to the voxel with the maximum signal change in each region of interest. Abbreviations: (more ...)
In children with ASD, only left retrosplenial cortex and left precentral gyrus showed increased activation to social exclusion during Cyberball. Regions that were more active during fair play included bilateral parietal cortex, bilateral ventrolateral prefrontal cortex (vlPFC), right anterior insula, right middle frontal gyrus (MFG), right dorsomedial prefrontal cortex (dmPFC), left cerebellum, and right precentral gyrus.
In Cybershape, both groups showed significant brain differences in the contrast of rule violation versus fair play (, ). TD children showed increased activation to rule violation in orbitofrontal cortex, parietal cortex, bilateral dorsolateral prefrontal cortex (dlPFC), dmPFC, and right inferior temporal gyrus. In contrast, this group showed increased activation during Cybershape fair play in bilateral insula, bilateral hippocampus, bilateral paracentral lobule, right cerebellum and cerebellar vermis, right posterior cingulate cortex, left precentral gyrus, dorsal anterior cingulate cortex (ACC), left retrosplenial cortex and cuneus, and pons. Children with ASD showed increased activation to rule violation in dorsomedial and lateral prefrontal cortex, bilateral insula, bilateral STS and supramarginal gyrus, bilateral caudate, right cerebellum, middle occipital gyrus (MOG), and cuneus. This group showed increased activation during Cybershape fair play in subgenual ACC, vACC, left anterior middle temporal gyrus, bilateral paracentral lobule, bilateral hippocampus, bilateral PCC, and right posterior insula. A 2 × 2 whole-brain GLM analysis in Cyberball identified regions showing a Group × Condition interaction (, ). Regions of interaction driven by significant modulation during Cyberball in only the TD group included right posterior insula, left PCC, right hippocampus, precuneus, and left vACC. Regions showing an interaction driven by significant modulation during Cyberball in only the children with ASD included right postcentral gyrus, right anterior insula, right MFG, and left SFG. Left MOG was modulated by the experimental manipulation during Cyberball in both groups. All of these regions except for precuneus showed greater activation to social exclusion in TD children compared to children with ASD.
Table 3 Activation in Cybershape. Regions identified in a full brain contrast of rule violation to fair play within each group (TD and ASD). Talairach coordinates and statistics refer to the voxel with the maximum signal change in each region of interest. Abbreviations: (more ...)
Figure 2 Regions showing significant Group by Condition interactions in Cyberball (top) and Cybershape (bottom; p < .05, k = 20). Bar graphs depict beta value differences (social exclusion – fair play or rule violation – fair play) in regions (more ...)
Table 4 Regions showing significant group (TD versus ASD) by Condition (Social Exclusion or Rule Violation versus Fair Play) interactions in Cyberball and Cybershape. Talairach coordinates and statistics refer to the voxel with the maximum signal change in each (more ...)
In an identical 2 × 2 whole-brain GLM analysis in Cybershape (, ), regions showing a Group × Condition interaction driven by significant modulation during Cybershape in only the TD group included bilateral vlPFC, cerebellar vermis, and left precuneus. Regions of interaction driven by significant modulation during Cybershape in only the children with ASD included bilateral dlPFC, right precentral gyrus, bilateral supramarginal gyrus, dorsal ACC, left SFG, and left cerebellum. Regions that were modulated by the experimental manipulation in Cybershape in both groups included bilateral anterior insula and left precentral gyrus (both more active to rule violation in the ASD group), as well as subgenual ACC (more active to rule violation in the TD group).
Group × Game interaction analyses were performed in structurally defined regions of vACC and right insula, chosen a priori to be of interest in processing social exclusion (). These analyses revealed a significant Group (TD versus ASD) × Game (social exclusion – fair play versus rule violation – fair play) interaction in a structurally defined region of right insula (F = 7.78, p = .007) but not in vACC (p > .05).
Figure 3 Group by Game interaction in a structurally defined region of right insula (left panel). Beta value differences in each group were graphed for Cyberball (social exclusion – fair play; middle panel) and Cybershape (rule violation – fair (more ...)
Further probing of the right insula guided by the finding that this region showed a group by game interaction, revealed that the area of right insula active in TD children during social exclusion is regionally distinct from (posterior to) the region of right insula that is active in children with ASD during rule violation. An exploration of the task-dependent functional connectivity of these regions using PPI analyses revealed two distinct brain networks associated with right insula activation in each game. The area showing greater functional connectivity during social exclusion (compared to fair play) to the posterior region of right insula active in TD children was bilateral paracentral lobule. Regions showing greater functional connectivity during rule violation (compared to fair play) to the anterior region of right insula active in children with ASD included dorsal ACC, medial prefrontal cortex, and mid-cingulate cortex, as well as left SFG, bilateral IFG, right precentral gyrus, and left anterior insula.
A whole-brain voxel-wise covariate analysis including all participants analyzed in the Cyberball contrast (social exclusion - fair play) using raw SRS score as a covariate, revealed several regions that showed a negative correlation between activation to social exclusion and SRS score included right posterior superior temporal sulcus (STS), right anterior insula, left anterior STS, left cerebellum, and right postcentral gyrus. This negative correlation indicates that the more socially responsive the participant (lower SRS score), the more activation during social exclusion in the identified regions. No regions showed a positive correlation with SRS scores.