Engagement of Language and Theory-of-Mind Networks during Self-Other Processing in Autism Spectrum Disorders

Background:  Autism Spectrum Disorder (ASD) is characterized by difficulties in social interaction and social communication (American Psychiatric Association, 2013). Self-referential processing, critical in interpersonal interactions, entails the ability to process information by incorporating self-awareness, self-judgment, and self-memory. Self-referential processing has been linked to several brain areas, including the medial prefrontal cortex (MPFC), inferior parietal lobule (IPL), anterior cingulate cortex (ACC), and left inferior frontal gyrus (LIFG). Individuals with ASD have been found to show atypical brain responses in some of these areas when engaged in self-other representation tasks (Craik et al., 1999; Chiu et al., 2008; Lombardo et al., 2010).

Objectives:  The primary objective of this fMRI study is to examine the role of language and theory-of-mind (ToM) brain networks in self-other processing across ASD and typically developing (TD) individuals.

Methods: 15 high-functioning adults with ASD and 15 age-and-IQ-matched TD control participants (mean age= 21.7; mean IQ: ASD=105, TD=111, p=.124) took part in this study. All participants were right-handed males. Participants made “yes” or “no” judgments of whether an adjective, presented visually, described them (self) or their favorite teacher (other). There was also a case judgment control condition where the participants determined whether the adjective contains the letter “e”. The data were collected using a Siemens 3T Allegra scanner and analyzed using the SPM 12 software. Participants also completed the Reading Mind in the Eyes (RMIE) task outside of the scanner to asses ToM. 

Results:  The main results of this study are: 1) Both ASD and TD participants showed significant activity in left superior temporal gyrus (LSTG), LIFG, MPFC, and LIPL during self as well as other processing (p= .001, voxels=78); 2) Between-group analyses showed significantly decreased activity in RSTG in ASD for both self as well as other processing (p= .05, voxels= 579); 3) Other related processing also elicited significantly reduced activation in the precuneus in ASD participants(p=.001, voxels=78); 4) When self and other processing were directly contrasted, ASD participants showed reduced activation in the ACC, putamen, caudate, and cerebellum (p=.001, voxels 78); and 5) A regression analysis with MIE scores as covariate significantly predicted RIFG activation for self-processing in ASD participants (p=.01, voxels=253). 

Conclusions: Increased activity in LIFG and LSTG for self and other processing, but not for case judgment, suggests greater levels of semantic processing; this is consistent with the findings of previous imaging studies (Kelley et al., 2002). Reduced RSTG and precuneus activation during other processing in ASD participants reflects poor engagement of regions that are part of the ToM network. Recent meta-analysis data underscore the role of these regions in other-related processing (Murray et al., 2015). Comprehending self-related words also seems to recruit temporal and IFG areas differently in ASD participants, as seen in previous studies (Lombardo et al., 2010, D'Argembeau et al., 2007). Overall, the findings of this study emphasize the role of social and semantic processing brain networks and their alterations in the neurobiology of autism.