Despite vast economic investments to mitigate the harms of opioid use disorder (OUD), the prevalence of the disorder remains high in addition to an estimated 80,000 Americans dying from opioid-related overdoses yearly. Given the significant heterogeneity across multiple dimensions of OUD, prioritizing investigations of multidimensional phenotypes such as resilience may improve our etiological understanding of the disorder. The goal of the proposed study is to develop a laboratory model of resilience, allowing the objective examination of this construct in a controlled laboratory setting. The study will employ a within-subjects, randomized design and investigate associations of resilience with heroin-seeking and decision-making behaviors. In addition, this study aims to better characterize resilience in individuals with OUD through a deep multidimensional psychological, cognitive, and affective phenotyping approach. To accomplish these goals, individuals who meet DSM-5 criteria for OUD will be recruited to achieve N=50 completers. Participants will be stabilized on oral morphine throughout their 10-day inpatient stay to diminish confounding effects of acute withdrawal symptoms on study assessments. The primary aim will be to assess whether Resilience Laboratory Tasks (control, cognitive and emotional flexibility) demonstrate convergent validity with self-reported resilience under stress (Trier Social Stress Test, TSST) and non-stress (non-stress test; NST) experimental conditions. Participants will undergo these two experimental sessions (TSST and NST) in random order. During the sessions, heart rate (HR) and HR variability, blood pressure, and galvanic skin response will be assessed as physiological measures of stress reactivity. Immediately following the TSST and NST sessions, participants will complete self-report assessments of stress (perceived stress, craving, and desire to use heroin), a Hypothetical Drug Purchase Task (proxy for heroin self- administration) and Resilience Laboratory Tasks. This proposal will allow the validation of a novel laboratory procedure to empirically examine resilience and provide preliminary data for the psychological, cognitive, emotional, and behavioral substrates of this construct. Additionally, this K08 proposal will provide critical training needed to achieve my career goal of becoming an independently funded scientist-clinician. Specifically, this mentored award will advance my research career by (1) providing essential training in study design and methodology to evaluate the convergent validity of measures of resilience using human stress paradigms, (2) supporting the development of a valid multidimensional phenotypic assessment battery to characterize heterogeneity across multiple dimensions of OUD, (3) improving my skills in advanced statistical methods and allowing me to develop a fundamental understanding of computational modeling, (4) improving my manuscript and grant record. The training goals outline...