PROJECT SUMMARY/ABSTRACT Despite psychoeducational efforts highlighting consequences of opioid use, relapse remains common for individuals with opioid use disorder (OUD). This clinical observation indicates a need for better understanding how undesirable information about drug use is evaluated and incorporated into patient’s beliefs about personal risk. People hold biased beliefs about their personal risk in various life domains, expecting more good outcomes to happen to them than bad outcomes. This “optimism bias” can be explained by a biased belief updating process that weighs better-than-expected past outcomes more heavily than worse-than-expected past outcomes when forming future expectations. This “optimism bias” could explain mechanisms that drive opioid use despite well- recognized risks for harm. Such biased beliefs in OUD have primarily been studied using self-report measures. Additionally, neuroimaging work on these biases has been restricted to healthy individuals. The psychological and neural determinants of these biases as they relate to drug use in OUD remain unknown. I propose to, for the first time, quantify domain-specific optimism biases in OUD and to re-assess these biases as participants engage with their daily life outside of the lab. Here, I will study the behavioral, neural, and longitudinal mechanisms of biased beliefs in treatment-seeking individuals with OUD and matched healthy controls. Using a neurocomputational framework, during functional magnetic resonance imaging (fMRI), subjects will estimate their likelihood of drug- and nondrug-related negative events occurring to them (e.g., overdose, bone fracture). They will then be shown the true base rate of these negative events and will be given the opportunity to update their estimates. In Aim 1, I will use this approach to test whether opioid users underestimate their likelihood for negative events and whether they would update their beliefs more after receiving better-than expected vs. worse- than-expected information, especially when outcomes are related to their drug use. To test how biased belief updating emerges in the brain, in Aim 2, I will record brain activity during the initial estimation and updating period of the task in Aim 1, which I hypothesize to involve cortico-limbic-striatal circuitry centered on the inferior frontal gyrus and ventral striatum. Following the MRI session, in Aim 3, subjects will be enrolled in a 4-week ecological momentary assessment (EMA) study and complete an abridged version of the optimism bias task to determine the maintenance and durability of domain-specific optimistic beliefs. The proposed Diversity-F31 training and research plan will support the formal training I will receive in my doctoral program by: (1) increasing my knowledge in human addiction neuroscience; (2) increasing proficiency in methods and concepts in cognitive neuroscience and advanced neuroimaging techniques; and (3) developing training in advanced multi-level statistical and computational modeling. By using a rigorous decision neuroscience approach, this research has the potential to inform future efforts to refine and develop more robust psychoeducational interventions for OUD.

PROJECT NARRATIVE Despite psychoeducational efforts about the potential consequences of drug use, relapse remains the modal outcome among treatment-engaged individuals with opioid use disorder (OUD).This clinical observation indicates a need for better understanding how undesirable information about drug use is evaluated and incorporated into patient’s beliefs about personal risk. Combining neuroimaging and real-world experience sampling, I will test whether individuals with OUD hold domain-specific optimistic beliefs about drug use in a way that can uniquely inform future efforts to develop more robust psychoeducational interventions for OUD.