Opioid use, relative to other drug use, poses significant risk due to its high potential for overdose and long-term health consequences. Current treatments aim to reduce overdose risk through medication, psychotherapy, and psychoeducation. Despite these efforts, relapse remains the modal outcome among individuals with opioid use disorder (OUD). Research has thus focused on the cognitive mechanisms underlying risky decision-making in OUD. Decision neuroscience has been pivotal in investigating the computational and neural processes involved in these decisions, with particular attention given to how individuals' perceptions of personal risk may influence their behavior. Using this framework, the collective studies in this dissertation combine longitudinal real-world experience sampling and neuroimaging to determine whether optimistic beliefs, or the expectation that more good than bad things would happen to oneself, could be one explanation for why people with OUD continue to engage in risky drug use. First, to examine the interaction of psychological states and decision-making preferences, in Study 1, we monitored decision-making behavior on a suite of smartphone-enabled economic tasks as treatment-engaged individuals with OUD engaged with their day-to-day lives. Next, in Study 2, we tested whether individuals with OUD hold a specific form of optimism bias related to drug use and examined how biased belief updating emerges in the brain. Using cognitive tasks and models combined with fMRI, we evaluated how treatment-engaged individuals with OUD and healthy individuals think about their chances of various negative outcomes due to drug use or other reasons. Lastly, in Study 3, we re-assessed optimism biases repeatedly in a 4-week “task-based” smartphone study to examine the durability of drug-use related optimistic beliefs and their relationship to clinical states in OUD. Behavioral findings demonstrated that individuals with OUD held more optimistically biased beliefs about the risks of drug use than healthy individuals, while they did not differ in their nondrug-related optimism bias. Using fMRI, we identified that the inferior frontal gyrus and ventromedial prefrontal cortex contributed to addiction-relevant differences in drug-related optimism bias. Longitudinally, findings support a link between optimism bias and ongoing vulnerable OUD states, with drug-related optimism bias associated with increased opioid reuse during treatment. Overall, the knowledge gained from this dissertation has the unique potential to provide novel neurobehavioral and time-sensitive targets for intervention in OUD.
Emmanuel Eduardo Alvarez (Thu,) studied this question.