Theory of Mind Skills Are Related to Resting-State Frontolimbic Connectivity in Schizophrenia

Patients with schizophrenia (SCH) often demonstrate impairment in social-cognitive functions as well as disturbances in large-scale network connectivity. The ventromedial prefrontal cortex (vmPFC) is a core region of the default mode network, with projections to limbic structures. It plays an important role in social and emotional decision-making. We investigated whether resting-state functional connectivity (FC) relates to the cognitive and affective domains of theory of mind (ToM). Twenty-three SCH patients and 19 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging scanning. vmPFC seed connectivity was correlated with behavioral measures assessing ToM domains. SCH performed less well than HCs in both ToM task domains. An analysis of the resting-state FC revealed that SCH had reduced connectivity from the vmPFC to the subcallosal cortex, right amygdala, and right hippocampus as a function of behavioral scores in both ToM domains. Within-group analyses indicated that in HCs, the performance in ToM was positively associated with frontoamygdalar resting-state connectivity, whereas in SCH, the performance in ToM was negatively associated with the frontosubcallosal connectivity. Differences in the pattern of the resting-state frontolimbic connectivity and its associations with performance in ToM tasks between the two study groups might represent a different setup for processing social information in patients with SCH.