Effect of anticipated delay on neural response to signal of future reward

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DESCRIPTION (provided by applicant): A major challenge in developing treatments for drug abuse disorders, including nicotine dependence, derives from the fact that the desirable effects of drugs are immediate, and often outweigh their aversive effects, which are predominantly delayed. The decrease in preference for a reward as a function of its delay ("delay discounting") is one conceptualization of impulsivity. Delay discounting is assessed based on preference between larger-later and smaller-sooner alternatives. Numerous demonstrations of high delay discounting in drug abusers suggest that high discounting may be a risk-factor for drug abuse disorders. It is not known, however, whether abnormalities in discounting directly reflect abnormalities in valuation of delayed rewards, or rather abnormalities in decision-making processes engaged during delay-reward tradeoffs. A group of 60 cigarette smokers and another of 40 nonsmoker comparison subjects will complete a battery of behavioral assessments related to impulsivity, and will participate in two fMRI probe task. In the first task ("Choice Delay Discounting Task"), participants will choose between smaller-sooner and larger-later monetary rewards according to an established procedure in which each individual is given choices tailored to their predetermined level of delay discounting (Monterosso et al, 2007). In the second task ("Incentive Delay Task"), participants win rewards that vary in amount and delay. Previous work (Knutson et al, 2001) indicates that the increase in signal measured in the ventral striatum during anticipation of reward is related to reward size, and our pilot work indicates that the same is true with respect to reward immediacy. The two tasks will allow us to measure: 1) the direct effect of delay on valuation of rewards as indexed by responses in the ventral striatum, and 2) brain activity recruited during decision-making during delay-amount tradeoffs. We will compare data from both assessments in smokers and nonsmokers to determine the contributions of valuation and of decision-making to the abnormal delay discounting exhibited by cigarette smokers. Relevance: Substance abuse exacts an enormous toll on the public heath, with cigarette smoking contributing to >400,000 deaths per year in the US. Abnormal delay discounting appears to be an important factor. We will disassociate the roles that valuation and decision-making play in the phenomenon, and relate each to clinical characteristics of smokers, thereby identifying better informed therapeutic targets. PUBLIC HEALTH RELEVANCE: Cigarette smoking contributing to >400,000 deaths per year in the US, and research indicates that smoking is associated with difficulty delaying gratification. The proposed research uses brain imaging to examine the basis of smokers' deficits in delay of gratification, which can then be targeted in treatment.