Discussion
mentalizing deficits, schizophrenia and deficits in social cognition, schizophrenia, with reduced neurocognitive functioning, social cognitive dysfunction
DISORDER, MRS, CORTEX
The present study indicates that a dose of ketamine inducing positive and negative symptoms associated with schizophrenia impairs mentalizing during the observation of social interactions and increases neural activity in right pSTS as well as connectivity between right pSTS and anterior precuneus during this task. These findings suggest that intravenous subanesthetic ketamine impairs social cognition and affects its neural correlates, supporting a link between a proposed psychopathological mechanism in schizophrenia and deficits in social cognition associated with that disorder. However, it should be mentioned that these deficits were not limited to social cognition, as participants were also presenting with reduced neurocognitive functioning in the control-condition.The MASC task used here allows to characterize mentalizing deficits specifically by differentiating over- from undermentalizingWhile no study has investigated the causal effects of acute blockade of NMDA-receptors on mentalizing in healthy volunteers, several correlational studies have linked high glutamate concentration, or high glutamate to GABA ratios, with social cognitive dysfunction. For example, glutamate concentration in dorsolateral prefrontal cortex of healthy participants measured with magnetic resonance spectroscopy (MRS) was negatively correlated with perspective taking scores in a task designed to assess empathy in people with schizophrenia and ASDOur results support this hypothesis by demonstrating causal alteration of mentalizing in participants undergoing NMDA-receptor blockade by ketamine. We note that we cannot make conclusions specific to mentalizing, as performance in the non-social condition of our task was also reduced under ketamine. The lower performance observed in both the control and social cognition conditions within the ketamine group can possibly be partly attributed to the dissociative effects of ketamineAt the neural level, we found activation in left pSTS, cuneus, middle occipital gyrus, precuneus and right pSTS during the question phase of the MASC in the placebo group during our manipulation check. Some of these regions (pSTS and precuneus) are part of the mentalizing network and are thus typical of activations expected in a social cognition taskSeveral regions showed changes in functional connectivity with the seed cluster under placebo during the question phase (social > physical): connectivity with STG and posterior cingulate increased, possibly reflecting reasoning about mental states of others and oneselfCoactivation of pSTS and precuneus in healthy participants has been observed during naturalistic social tasks involving reasoning about emotional and mental states of others