Neural correlates of theory of mind and empathy in schizophrenia: An activation likelihood estimation meta-analysis

Social cognition impairment predicts social functioning in schizophrenia. Several studies have found abnormal brain activation in patients with schizophrenia during social cognition tasks. Nevertheless, no coordinate-based meta-analysis comparing the neural correlates of theory of mind and empathy had been done in this population. Our aim was to explore neural correlates related to theory of mind and empathy in patients with schizophrenia compared to healthy controls, in order to identify abnormal brain activation related to emotional content during mental state attribution in schizophrenia. We performed a neural-coordinate-based Activation Likelihood Estimation (ALE) meta-analysis of existing neuroimaging data in the literature to distinguish between abnormal brain maps associated with emotional attribution and those associated with intention/belief inference. We found that brain activation in patients group was significantly decreased in the right ventrolateral prefrontal cortex (VLPFC) during emotional attribution, while there was a significant decrease in the left posterior temporo-parietal junction (TPJ) during intention/belief attribution. Using a meta-analytic connectivity modeling approach (MACM), we demonstrated that both regions are coactivated with other brain regions known to play a role in social cognition, including the bilateral anterior insula, right TPJ, left amygdala and dorsolateral prefrontal cortex. In addition, abnormal activation in both the left TPJ and right VLPFC was previously reported in association with verbal-auditory hallucinations and a “jumping to conclusions” cognitive bias. Thus, these regions could be valuable targets for therapeutic interventions in schizophrenia.