5.3 SOCIAL COGNITIVE TRAINING IMPROVES MOTIVATION TO EARN REWARDING OUTCOMES IN PSYCHOSIS

Abstract

Background Amotivation in schizophrenia is a central predictor of poor functioning and is thought to occur due to deficits in anticipating future rewards, suggesting that impairments in anticipating pleasure can contribute to functional disability in schizophrenia. In healthy comparison (HC) participants, reward motivation is associated with anticipatory activity in frontal-striatal networks. By contrast, schizophrenia (SZ) participants show hypoactivation within these frontal-striatal networks during this motivated anticipatory brain state. Here, we investigated whether intensive computerized social cognitive training in schizophrenia could increase activity within frontal-striatal circuits to improve motivation during the anticipatory phase of stimuli that predicted upcoming reward. Methods In our double-blind randomized clinical controlled trial, SZ were randomly assigned to either social cognitive training or cognitive training (without the social training component). We used a standard Monetary Incentive Delay task (MID), to assay the neural patterns associated with immediate anticipation and outcome of monetary reward (gain) in each group, at baseline and after training intervention. In the MID paradigm, at the beginning of each trial, a cue (i.e. marking the onset of an anticipatory period) indicates the amount of money at stake on that trial: Win cues indicate potential monetary gain and Null cues indicate no monetary gain/no outcome. When the cue is presented, participants anticipate making a speeded response to the target (a white square). After participants respond to the target, they receive feedback on how they performed on that trial in terms of receiving rewarding or neutral feedback. Specifically, on Win trials, participants are informed as to whether or not they won money, and on Null trials, participants receive neutral feedback that they did not win money. We assayed whole-brain activity specifically relating to immediate reward anticipation by contrasting neural activity during the anticipation to win money with no outcome trials (i.e. Win cue vs. Null cue). Group analyses focused on mixed effects repeated measures ANOVA to delineate neural activation that mediated reward motivation, which was specific to the social cognitive group. Results After 16 weeks of social cognitive training, we found that patients showed significant increases in the medial prefrontal cortex, which had been initially hypoactive at baseline (i.e. not activated during reward anticipation). Further, increased medial prefrontal activity induced improvements in patients' ability to earn rewarding outcomes after social cognitive training compared to baseline. These neural improvements were not observed in our control patients who completed cognitive training (without the social training portion), suggesting that these brain-behavioral improvements were specific to the social cognitive training patient group. Conclusions Together, our promising results indicate that cognitive and neural impairments in schizophrenia are not fixed. Promisingly, we can target the points of neural system dysfunction with behavioral interventions to induce significant improvements in social cognition that have critical relevance for real-world functioning.