Neurobiological correlates of theory of mind in psychosis proneness

Theory of mind (ToM) refers to the capacity to infer one's own and other persons’ mental states. ToM abilities are compromised in schizophrenia, in association with dysfunctional activity in predominantly prefrontal brain regions. Prior behavioral studies have also suggested ToM deficits in healthy individuals with psychosis proneness (PP), although no study to date had investigated the associated neural mechanisms in such a sample. Here we used functional magnetic resonance imaging (fMRI) to compare brain activation of subjects with high versus low scores on positive-dimension PP and a ToM task. The ToM task involved first and second order attribution of cognitive and affective mental states to a cartoon character based on verbal and eye-gaze cues. No between-group differences were found on behavioral performance. fMRI analyses revealed a group interaction in anterior prefrontal cortex (BA 10), with the high PP group showing significantly more activity thereof, relative to the low PP, during second order mentalizing than during first order mentalizing. Further between-group differences were observed in dorsomedial and lateral prefrontal regions (BA 46/9), with the high PP group also showing greater activation during second order mentalizing. These results suggest that subjects with positive-dimension PP require more activation of prefrontal areas to adequately mentalize. Differences in the neural mechanisms underlying ToM might be associated with vulnerability to psychosis.