The Sex-specific Roles and Neural Processing Correlates of Future Outcome Estimation in the Drug Addiction Process

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Project Summary Our daily decisions are rooted in the ability to forecast possible decision consequences into our future. This ability to mentally simulate a future event, referred to as prospection, enables self-control by biasing decisions by their projected future gains or costs. The working hypothesis of the revised proposal is that addiction’s onset and chronically relapsing nature reflect developmental immaturity and disorders, respectively, of the human faculty of future-oriented thinking. Project hypotheses would be tested via core project tools of temporal delay discounting to weigh future-oriented thinking on the valuation of behavioral reinforcers, task- related fMRI as a means of mapping neural processing mechanisms underlying future-oriented thinking, assessments evaluating individual differences in future-oriented perspectives, and the use of “episodic tags” as framing stimuli to engage episodic future thinking (EFT). These tools would define individual, sex, and developmental group differences across three specific aims to test the project overall and component hypotheses. Aim 1 would explore the sex-dependent relationship between behavioral and neural correlates of future-oriented thinking [assessed using delay discounting (DD) tasks] and conditioned drug cue-related cognitive bias [assessed by the cocaine attentional bias effect (cocAb)] among men and women with cocaine addiction. Ecological relevance is enhanced by the characterization of both DD gains and losses, with losses being more typical of addiction-related futures. Adolescence is associated with developmentally immature behavioral and neural processing representations of future-oriented thinking, representing a period associated with greatest risk for the onset and escalation of drug misuse. Aim 2 would extend project goals to explore sex-dependent developmental processes related future orientation during early to mid-adolescence with the initiation of the addiction (and well-recognized addiction risk factors) – thus testing if addiction-related EFT deficits reflect acquired versus pre-existing traits. Samples of adolescent girls and boys would be compared across stratified levels of addiction risk. An interesting aspect of EFT relates to its ability, when explicitly engaged by episodic cues (“tags”) promoting future orientation, to reduce both temporal discounting rates and real-world health risk behaviors. Aim 3 would define the sex-dependent impact and mechanisms of the induction of EFT (EFTi) on gain and loss DD among at-risk adolescents and cocaine-addicted adults. This translational aim would initiate the evidence basis for the potential use of EFT training in prevention strategies for adolescents at-risk for drug use disorders or as an adjunctive approach to relapse prevention in treatment- seeking individuals with drug use disorders. Across project Aims, 6-month follow-up assessments would assess the relationship of future orientation to future drug misuse. The proposed project would characterize an underexplored facet of decisional impulsivity – its regulation by prospection – in the drug addiction process.