R21: Promoting Adaptive Decision-Making in Schizophrenia Through Improved Evidence Integration: A Combined Neuroimaging and Experience Sampling Study

PROJECT SUMMARY/ABSTRACT Schizophrenia (SZ) is a chronic condition characterized by cognitive impairment, atypical beliefs, and reduced reward/goal pursuit, which contribute to ongoing functional impairment even when other active phase symptoms subside. Symptom severity has been associated with poor decision-making with respect to integrating information about potential rewards and associated uncertainty, often manifesting as maladaptive unwillingness to tolerate the risk of failure. This risk-aversion limits opportunities to gain new or additional rewards or resources (i.e., nothing ventured, nothing gained). How an individual attends to and accrues information critically impacts subsequent decisions. While research has identified neural circuits implicated in impaired decision-making during choice in SZ, less is known about the processes by which information is attended to and accrued from the environment and integrated before a choice is made. This project will identify how decision- making in SZ is impacted by attentional, behavioral, and cognitive processes preceding decision choice, and whether associated neural signals predict daily, real-world decisions. Isolating these antecedents of impaired decision-making allows for the implementation of ameliorative interventions, empowering those with SZ to make choices that could reduce the burden of illness. First, leveraging concurrent functional magnetic resonance imaging (fMRI) and eye-tracking, the project will characterize attentional processes underlying evidence integration prior to decision choice. It will determine if SZ is associated with visual attentional biases toward aversive, and away from potentially rewarding, stimuli, and whether these biases underlie differences in associated brain activation in regions such as the nucleus accumbens (NAcc), insula, and anterior cingulate. Second, during fMRI it will test whether implementing cognitive strategies prior to decision-making upregulate reward-related brain activation and ameliorate disadvantageous choice in SZ. During upregulation via cognitive strategies, those with SZ are hypothesized to improve decision-making while increasing connectivity between NAcc and prefrontal regions, and during decision-making they are predicted to exhibit increased NAcc activation underserving adaptive reward pursuit. Such a result would suggest the feasibility of teaching these strategies as a clinical intervention for excessive risk aversion. Third, real-world daily behavior will be assessed using experience sampling methods to ascertain how daily decisions are impacted by perceived risks and symptom expression. Those with negative symptoms are predicted to endorse greater perceived risk of failure before potential activity engagement and those with positive symptoms are predicted to have less perceived risk of failure, despite impaired engagement. Finally, combined data will establish whether brain activation and task behavior predict real-world decisions to pursue rewards despite potential risk of failure. The project will establish the foundation for a novel interventional program of research into improving decision- making in SZ by elucidating distinct targets of behavioral and neuromodulatory intervention.