Effects of Cocaine and HIV on Decision Making Involving Potential Losses

描述(申请人提供)：对可卡因等刺激性药物上瘾的人从事有助于感染艾滋病毒的性行为的风险很高，一旦感染，就会将艾滋病毒转发给他人。与艾滋病毒有关的决策，与大多数现实世界的决策一样，涉及在不确定结果的背景下评估潜在的得失。可卡因依赖和艾滋病毒感染都会扰乱调节参与决策的执行功能的大脑电路。我们推测，这些神经变化影响了奖赏评估和结果不确定性的处理，并促成了性风险行为。我们的初步工作表明，可卡因依赖增加了损失厌恶(即，相对于潜在收益，高估了潜在损失)，艾滋病毒感染与可卡因依赖者更大的冒险倾向有关。此外，损失厌恶与性风险行为呈正相关，这表明基本的决策过程可能预示着更复杂的现实世界行为。这项拟议的研究建立在我们先前工作的基础上，通过结合功能神经成像、行为风险评估和计算模型来：(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，以及(2)检验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，我们将检查货币赌博中的行为选择和大脑活动，这些行为选择和大脑活动独立于收益和损失的价值以及结果的确定性而变化。样本将包括80名在可卡因和艾滋病毒状况方面存在差异的成年人，包括四个不同的组(20个/组)。我们的多学科团队拥有临床心理学、认知神经科学、行为神经经济学和磁共振物理学方面的专业知识，在以患者为导向对药物依赖者的艾滋病毒风险行为进行研究方面拥有丰富的经验，并有望成功实施这一创新的、具有临床重要性的项目。这项R21提案的结果将为艾滋病毒相关决策的基础机制提供独特的见解，为后续的R01应用提供支持，以进一步调查艾滋病毒疾病进展可能如何影响神经过程，这些神经过程有助于可卡因使用者做出“高风险”的决策。这项研究具有很强的转化为临床实践的潜力，有助于开发新的干预措施，通过直接针对潜在的神经认知缺陷来更有效地减少危险行为，最终目标是减少药物使用障碍患者的艾滋病毒相关发病率和死亡率。

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.