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Methods

Results

Discussion
The notion of trait hypoactivation in right aTPJ is intriguing given the temporoparietal junction\’s well-established roles in both social and attentional processes (for reviews see Carter and Huettel, 2013; Decety and Lamm, 2007). Due to the social nature of the task utilized in the current study (Cyberball), we will first discuss our results in the context of TPJ function in social cognition. Attentional theories of TPJ activation as they relate to interpretations of the current results are discussed later. Right TPJ is active across several social domains, including GSK J4 of mind (Saxe and Kanwisher, 2003; Saxe and Wexler, 2005; Saxe et al., 2009; Young et al., 2010b), moral reasoning (Young et al., 2010a) and empathy (Jackson et al., 2006). In addition, abnormal activation in right TPJ has been found in individuals with ASD during gaze processing (Pitskel et al., 2011; von dem Hagen et al., 2014), imitation (Williams et al., 2006), theory of mind (Castelli et al., 2002; Kana et al., 2014; Mason et al., 2008) and moral judgments (Koster-Hale et al., 2013). While substantial research has examined theory of mind in autism (Baron-Cohen, 2000), investigations of theory of mind in UAS is comparatively scant. One such study reported poorer performance in UAS on a behavioral test of mind-reading, suggesting that difficulties in theory of mind may be shared to some extent between ASD probands and siblings (Dorris et al., 2004). Although we did not explicitly measure theory of mind/mentalization during social exclusion, one could speculate that the shared hypoactivation between ASD probands and siblings in right aTPJ during the experience of social exclusion in the current study may reflect abnormalities in social cognitive processing (i.e. theory of mind), representing a trait-level neurocognitive profile of ASD vulnerability. Further work is necessary to support the interpretation of right aTPJ activation during social exclusion as subserving mentalization processes where the excluded participant is thinking about the intentions of the excluders.
Trait hypoactivation in the right aTPJ included a ventral extension into the right pSTS. Posterior STS, like the adjacent TPJ, holds an important role in both low-level social perception of biologically relevant stimuli such as faces, as well as high-level processing of the thoughts and intentions of others (for review see Allison et al., 2000). Consistent with the integral role of the pSTS in social cognition, abnormal activation of this region is often found in individuals with ASD (Pelphrey and Carter, 2008).
A study of neuroendophenotypes of social processing in youth with ASD reported that a region of right pSTS showed hypoactivation in response to viewing point-light displays of biological motion (Kaiser et al., 2010). Interestingly, this pattern of hypoactivation in ASD probands was not shared with UAS. Participants in the current study partially overlap with those reported on by Kaiser et al. (2010); however, the neural profile identified in the current study is inconsistent with previous results. Specifically, we found that hypoactivation in the right pSTS was shared between ASD probands and siblings, not specific to probands as was previously reported. Consistent with the literature, the ASD group in both studies showed abnormal activation in the right pSTS. In contrast, the current study also revealed atypical pSTS activation to social exclusion in UAS. It is possible that the experience of social exclusion requires more complex and elaborate socio-emotional reasoning, and capsid is only during more complex tasks involving social and emotional processing that abnormal activation is revealed in the UAS. During passive viewing of point-light displays of biological motion, participants are not required to engage in any actions. In contrast, during Cyberball, participants are required to perform socially-contingent actions in the form of deciding to which virtual player to throw the ball. Further, in Cyberball, the actions of the virtual players are directly relevant to the participant, in that the participant is only included in the game if the other players throw to him/her. However, the actions of a point-light display of biological motion are not directly relevant to the participant viewing the lights, since there is no interaction (real or virtual) between them. Finally, the social experience of playing Cyberball is designed to elicit negative emotions. In contrast, point-light displays are not intended to elicit strong emotional responses. The interactive nature of the Cyberball task makes it more likely to require participants to engage in reasoning about the actions and intentions of others (in this case, the virtual players), both to decide to whom to throw (social) and to regulate negative feelings in response to exclusion (emotional). Similar to the findings of the current investigation, another emotionally-valenced study by Spencer et al. (2011) found that UAS differed from TD adolescents in right STS activation to emotional faces, with UAS showing no significant difference from their ASD siblings in this region.