Default mode network modulation by mentalizing in young adults with autism spectrum disorder or schizophrenia

Schizophrenia and autism spectrum disorder (ASD) are nosologically distinct neurodevelopmental disorders with similar deficits in social cognition, including the ability to form mental representations of others (i.e., mentalizing). However, the extent of patient deficit overlap in underlying neural mechanisms is unclear. Our goal was to examine deficits in mentalizing task-related (MTR) activity modulation in schizophrenia and ASD and the relationship of such deficits with social functioning and psychotic symptoms in patients. Adults, ages 18-34, diagnosed with either ASD or schizophrenia, and typically developed controls (n = 30/group), performed an interactive functional MRI Domino task. Using independent component analysis, we analyzed game intervals known to stimulate mentalizing in the default mode network (DMN), i.e., medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), precuneus, and temporoparietal junction (TPJ), for group differences in MTR activity and associations between MTR activity and social and psychosis measures. Compared to controls, both schizophrenia and ASD groups showed MTR activity deficits in PCC and TPJ. In TPJ and MPFC, MTR activity modulation was associated with social communication impairments only in ASD. In precuneus, MTR activity was associated with increased self-reported fantasizing only in schizophrenia. In schizophrenia, we found no indication of over-mentalizing activity or an association between MTR activity and psychotic symptoms. Results suggest shared neural deficits between ASD and schizophrenia in mentalizing-associated DMN regions; however, neural organization might correspond to different dimensional social deficits. Our results therefore indicate the importance of examining both categorical-clinical diagnosis and social functioning dimensional constructs when examining neural deficits in schizophrenia and ASD.