Effects of Cocaine and HIV on Decision Making Involving Potential Losses

描述（由申请人提供）：对可卡因等兴奋剂成瘾的人有很高的风险从事有助于获得艾滋病毒的性行为，一旦感染，就会将艾滋病毒传染给他人。与艾滋病毒有关的决策，像大多数现实世界的决策一样，涉及在不确定结果的情况下对潜在收益和损失的评估。可卡因依赖和艾滋病毒感染都会破坏大脑回路，这些回路调节着参与决策的执行功能。我们假设这些神经变化影响了奖励评估和结果不确定性的处理，并有助于性风险行为。我们的初步研究表明，可卡因依赖增加了损失厌恶（即，潜在损失相对于潜在收益的超重），并且艾滋病毒感染与可卡因依赖者更大的风险承担倾向有关。此外，损失厌恶与性风险行为正相关，这表明基本的决策过程可能预测更复杂的现实世界行为。本研究将功能神经成像、行为风险评估和计算建模相结合，旨在：(1)分离可卡因依赖和HIV感染对决策过程的影响，特别是损失厌恶和模糊容忍；(2)研究这些决策过程与性风险行为之间的关系。使用病例对照设计，我们将检查行为选择和大脑活动在货币赌博中独立变化的收益和损失的价值和结果的确定性。样本将包括80名可卡因和艾滋病毒状况不同的成年人，分为四组（20人/组）。我们的多学科团队拥有临床心理学、认知神经科学、行为神经经济学和MR物理学方面的专业知识，在药物依赖者中开展以患者为导向的艾滋病毒风险行为研究方面拥有丰富的经验，并且具有独特的优势，能够成功实施这一创新且临床上重要的项目。这项R21提案的结果将为HIV相关决策的潜在机制提供独特的见解，为随后的R01申请提供支持，以进一步研究HIV疾病进展如何影响导致可卡因使用者“风险”决策的神经过程。这项研究具有很强的转化为临床实践的潜力，为开发新的干预措施提供信息，通过直接针对潜在的神经认知缺陷，更有效地减少风险行为，最终目标是降低药物使用障碍患者中与HIV相关的发病率和死亡率。

DESCRIPTION (provided by applicant): Individuals addicted to stimulant drugs like cocaine are at high risk for engaging in sexual behaviors that contribute to the acquisition of HIV and, once infected, to the forward transmission of HIV to others. HIV-related decision making, like most real-world decisions, involves the valuation of potential gains and losses in the context of uncertain outcomes. Cocaine dependence and HIV infection can each disrupt brain circuits that regulate executive functions involved in decision making. We postulate that these neural changes affect the processing of reward evaluation and outcome uncertainty and contribute to sexual risk behavior. Our preliminary work suggests that cocaine dependence increases loss aversion (i.e., overweighting of potential losses relative to potential gains), and that HIV infecton is associated with greater risk taking propensity among persons with cocaine dependence. Moreover, loss aversion is positively correlated with sexual risk behavior, suggesting that basic decision making processes may be predictive of more complex real-world behavior. The proposed research builds upon our prior work by combining functional neuroimaging, behavioral risk assessment, and computational modeling to: (1) isolate the effects of cocaine dependence and HIV infection on decision making processes, specifically loss aversion and ambiguity tolerance, and (2) examine the relationship between these decision making processes and sexual risk behavior. Using a case-control design, we will examine behavioral choice and brain activity during monetary gambles that vary independently on the value of gains and losses and the certainty of outcomes. The sample will include 80 adults who differ on cocaine and HIV status, comprising four distinct groups (20/group). Our multidisciplinary team, with expertise in clinical psychology, cognitive neuroscience, behavioral neuroeconomics, and MR physics, has extensive experience conducting patient-oriented research on HIV risk behavior in persons with drug dependence and is uniquely poised to successfully implement this innovative and clinically important project. Results of this R21 proposal will provide unique insights into the mechanisms underlying HIV-related decision making, providing support for a subsequent R01 application to further investigate how HIV disease progression may affect neural processes that contribute to "risky" decision making among cocaine users. This research has strong potential for translation to clinical practice, informing the development of novel interventions to more effectively reduce risk behavior by directly targeting underlying neurocognitive deficits, with the ultimate goal of reducing HIV- related morbidity and mortality in persons with drug use disorders.