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

描述（由申请人提供）：开发药物滥用障碍（包括尼古丁依赖）治疗方法的主要挑战是，药物的理想效果是立即的，并且通常超过其主要延迟的不良影响。对奖励偏好的降低作为其延迟的函数（“延迟折扣”）是冲动性的一个概念。延迟折扣的评估是基于对大后方案和小早方案的偏好。大量药物滥用者的高延迟折扣表明，高折扣可能是药物滥用障碍的一个风险因素。然而，目前尚不清楚，贴现的异常是否直接反映了延迟奖励估值的异常，或者更确切地说，是延迟奖励权衡过程中决策过程的异常。一组由60名吸烟者和另一组40名不吸烟者组成的对照对象将完成一系列与冲动有关的行为评估，并将参加两个功能磁共振成像探测任务。在第一个任务（“选择延迟折扣任务”）中，参与者将根据既定程序在较小-较早和较大-较晚的货币奖励之间进行选择，其中每个人都会根据其预定的延迟折扣水平进行选择（Monterosso et al, 2007）。在第二个任务（“奖励延迟任务”）中，参与者获得的奖励在数量和延迟上都有所不同。之前的研究（Knutson et al, 2001）表明，在预期奖励时腹侧纹状体中测量到的信号增加与奖励大小有关，我们的初步研究表明，在奖励即时性方面也是如此。这两个任务将使我们能够测量：1)延迟对奖励评估的直接影响（通过腹侧纹状体的反应来衡量）；2)在延迟量权衡的决策过程中招募的大脑活动。我们将比较吸烟者和非吸烟者的评估数据，以确定评估和决策对吸烟者表现出的异常延迟折扣的贡献。相关性：药物滥用对公众健康造成了巨大的影响，在美国，吸烟每年导致40万人死亡。非正常延迟折扣似乎是一个重要因素。我们将分离评估和决策在这一现象中所扮演的角色，并将它们与吸烟者的临床特征联系起来，从而确定更好的治疗目标。公共卫生相关性：在美国，吸烟每年导致40万人死亡，研究表明，吸烟与延迟满足困难有关。这项拟议中的研究使用脑成像技术来检查吸烟者在延迟满足方面的缺陷的基础，然后可以有针对性地进行治疗。

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.