Neural Mechanisms of Risky Sexual Decision-Making in METH and non-METH Using MSM

使用 MSM 进行冰毒和非冰毒中危险性决策的神经机制

• 批准号: 8460977
• 负责人: STEPHEN J READ
• 金额: $ 52.77万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8460977
• 关键词: Address; African American; Amygdaloid structure; Anterior; Anus; Area; Behavior; Behavioral; Brain; Caucasians; Caucasoid Race; Chronic; Computer Simulation; Contracts; Corpus striatum structure; Cues; Decision Making; Diffusion Magnetic Resonance Imaging; Dopamine; Dorsal; Emotions; Environment; Ethnic group; Exposure to; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Gray unit of radiation dose; HIV; Hypersensitivity; Image; Imaging Techniques; Individual Differences; Insula of Reil; Intervention; Knowledge; Lateral; Latino; MRI Scans; Magnetic Resonance Imaging; Maps; Measures; Methamphetamine; Modeling; Nature; Neural Network Simulation; Neurophysiology - biologic function; Nucleus Accumbens; Pattern; Play; Population; Prefrontal Cortex; Probability; Process; Public Health; Reaction Time; Research; Resolution; Rewards; Risk; Risk Behaviors; Risk-Taking; Role; Sampling; Services; Shock; Signal Transduction; Somatosensory Cortex; Stimulus; System; Technology; Testing; Translating; Underweight; base; blood oxygenation level dependent response; craving; density; deprivation; executive function; experience; high risk; high risk sexual behavior; improved; innovation; knowledge of results; men; men who have sex with men; neural circuit; neuromechanism; novel; positive emotional state; relating to nervous system; response; sex; virtual; white matter

DESCRIPTION (provided by applicant): HIV cases continue to rise among men who have sex with men (MSM) with methamphetamine (METH) use contributing. But, we lack understanding of the neural processes underlying MSM's decisions. How might the neural circuitry differ for sexually risky vs. non-sexually risky MSM? How might chronic METH use modify it? We aim to address this gap, using the resulting knowledge to develop novel interventions to reduce risk-taking. Three key neural systems are hypothesized to play a central role in risky decision making: (1) an amygdala- striatal (dopamine-dependent) neural system, which promotes cue-induced habitual behaviors; (2) a prefrontal cortex neural system, which subserves decision-making, executive functioning, and impulse control capacities; and (3) an insular cortex system, which responds to homeostatic and interoceptive signals triggered by states of deprivation, or by exposure to environmental cues that elicit craving. The resulting "urge" may exacerbate the hypersensitivity of the amygdala-striatal system, or weaken the inhibitory function of the prefrontal system. Magnetic Resonance Imaging techniques applied to decisions, often in virtual environments, in conjunction with computational modeling afford an innovative mix of technologies to systematically investigate, in more realistic contexts, the decision-making processes of METH and non-METH using MSM who chronically engage in risky sex. The volume and gray/white matter density of brain areas in the proposed neural circuit will be quantified for each subject from high resolution MRI scans. DTI (diffusion tensor imaging) will be used to map out the connectivity among the target regions. In addition, the fMRI BOLD responses of these regions will be measured when subjects perform both standard decision-making tasks and make risky sexual decisions in a virtual environment. We will compare: (1) sexually risky MSM who use METH, (2) sexually risky MSM who do not use METH, and (3) non-risky MSM. We will sample from Caucasian, African-American, and Latino MSM. The overarching aim of this proposal is to develop a model of the brain systems involved in risky sexual decision-making for MSM and to understand how dysfunctions in those systems may be related to increases in sexually risky decision-making by both METH using and non-METH using MSM. Our main hypotheses are: H1: Sexually risky MSM will show differential functioning in the dopaminergic, habitual system compared to non-sexually risky men: (H1a) they will take longer to acquire negative contingencies to risky behavior (e.g., money loss or shock) and more quickly acquire positive contingencies, and (H1b) show a tendency to overvalue rewards and underweight risks. H2: Sexual risk takers will show greater activation in the insular cortex (and greater craving or urgency) in response to rewarding stimuli and especially sexual stimuli. H3: Sexual risk takers will show dysfunctions in inhibitory control and executive functioning. Our results on gray/white matter density and connectivity will corroborate those differences between groups. H4: METH use will increase risky sexual decision-making and impact each of the three components of the decision-making circuitry.

描述（由申请人提供）：与甲基苯丙胺（甲基苯丙胺）使用促成的男性（MSM）的男性，艾滋病毒病例继续增加。但是，我们对MSM决定的基础神经过程缺乏了解。性风险与非性风险的MSM的神经回路有何不同？慢性甲基苯丙胺的使用将如何修改？我们旨在利用由此产生的知识来解决这一差距，以开发新的干预措施以减少冒险。 假设三个关键的神经系统在危险决策中起着核心作用：（1）杏仁核（依赖多巴胺依赖性）神经系统，可促进提示提示引起的习惯行为； （2）一个前额叶皮层神经系统，它可以支持决策，执行功能和冲动控制能力； （3）一个岛状皮质系统，该系统对剥夺状态或暴露于引起渴望的环境线索引发的体内平衡和感知信号做出了反应。由此产生的“冲动”可能会加剧杏仁核 - 纹状体系统的过敏性，或削弱前额叶系统的抑制功能。 磁共振成像技术通常在虚拟环境中，与计算建模相结合，提供了技术的创新组合，以在更现实的环境中系统地研究METH和NON-METH的决策过程。通过高分辨率MRI扫描，将对所提出的神经回路中大脑区域的体积和灰色/白质密度进行量化。 DTI（扩散张量成像）将用于绘制目标区域之间的连通性。此外，当受试者执行标准决策任务并在虚拟环境中做出风险的性决策时，将衡量这些区域的fMRI大胆反应。我们将比较：（1）使用METH的性风险的MSM，（2）不使用METH的性风险的MSM，以及（3）非风险的MSM。我们将从白种人，非裔美国人和拉丁裔MSM中采样。 该提案的总体目的是开发一种涉及MSM性决策的大脑系统模型，并了解这些系统中的功能障碍与使用MSM使用METH和非METH的性危险决策的增加有关。我们的主要假设是：H1：与非性风险的男人相比，性风险的MSM在多巴胺能，习惯性系统中表现出差异功能：（H1A）他们将需要更长的时间来获得对风险行为的负面影响，例如，货币损失或更快地获得了积极的危险和（H1B）的倾向和（H1B）的倾向和倾向越来越多。 H2：对性风险的人将在响应奖励刺激，尤其是性刺激的响应中显示出更大的激活（以及更大的渴望或紧迫性）。 H3：接受性风险者将在抑制性控制和执行功能中表现出功能障碍。我们关于灰色/白质密度和连通性的结果将证实组之间的差异。 H4：甲基苯丙胺的使用将增加风险的性决策，并影响决策回路的三个组成部分中的每一个。