Chronic use of methamphetamine has been linked to disadvantageous decision-making, especially with respect to balancing cost and potential reward. The goal of this project is to clarify the precise nature of choice impairments in individuals with Methamphetamine Use Disorder (MUD) by characterizing their decision-making and neural activity when reward-based decisions present different types of costs: uncertainty about the probabilities of possible outcomes, delay in the receipt of the reward, and effort involved in making the decision. Individuals with MUD will be compared to healthy controls during performance of two reward-based decision tasks paired with functional magnetic resonance imaging (fMRI). The first is a Probability Choice Task that presents choices between winning $5 for sure, or gambling on a lottery that offers different amounts of reward with varying amounts of risk. In some trials, the probability of the outcome will be known (known risk, e.g. 50% chance of $12). In other trials, the probability of the outcome will be unknown (unknown risk, e.g. unknown chance of $12). The second task is a Delay Discounting Task that presents choices between smaller sooner rewards and larger later rewards. The effort involved in choosing between options on both tasks will be estimated by modeling the difference in the subjective values between each option on a trial. The hypotheses that individuals with MUD behave differently than healthy control participants in the face of known and unknown risk, that differences in tolerance for known/unknown risk underlies some of the differences observed during delay discounting tasks, and that differences will be exaggerated when choices are harder rather than easier, will be tested (Aim 1). Differences in task-related neural activation and resting-state functional connectivity between individuals with MUD and healthy controls, and associations with choice behavior, will be tested (Aim 2), as will associations with methamphetamine use severity (Aim 3). Attaining a detailed multivariate profile of behavioral and neural aspects of decision-making, and delineating the differences between individuals with MUD and healthy controls, will help clarify which components of reward-based choice show dysfunction in the context of the disorder, helping to identify behavioral and neural targets for intervention.
Methamphetamine Use Disorder is a major public health problem that accounts for a dramatic increase in overdose deaths in recent years. Disadvantageous decision-making can contribute to the development and the maintenance of this disorder, but the precise nature of impaired choice behavior remains unknown. The proposed work will disentangle different types of reward-based choices that present negative costs in order to determine which components are disrupted in methamphetamine users and can thus act as potential future therapeutic targets.
