Neuroimaging multiple memory processes, glucocorticoids and alcoholism risk

神经影像学多重记忆过程、糖皮质激素和酗酒风险

• 批准号: 9977375
• 负责人: Elizabeth Goldfarb
• 金额: $ 17.79万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-07 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9977375
• 关键词: Acute; Address; Affective; Alcohol consumption; Alcoholic beverage heavy drinker; Alcoholism; Alcohols; Amygdaloid structure; Attenuated; Behavior; Behavioral; Biological; Biological Assay; Cellular Phone; Chronic Disease; Cognitive; Computer Models; Corpus striatum structure; Cues; Data; Development; Dorsal; Ecological momentary assessment; Emotional; Functional Magnetic Resonance Imaging; Glucocorticoids; Goals; Growth; Habits; Heavy Drinking; Hippocampus (Brain); Hormones; Human; Hydrocortisone; Impairment; Intervention; Investigation; Laboratories; Learning; Light; Link; Measurement; Measures; Memory; Memory impairment; Mentors; Modeling; Monitor; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Neurosecretory Systems; Participant; Play; Population; Prefrontal Cortex; Process; Protocols documentation; Public Health; Recording of previous events; Reporting; Research; Research Training; Response to stimulus physiology; Retrieval; Risk; Role; Salivary; Scientist; Signal Transduction; Stress; System; Testing; Time; Training; Woman; Work; acute stress; addiction; alcohol cue; alcohol exposure; alcohol response; base; biological adaptation to stress; blood oxygen level dependent; career; career development; cognitive neuroscience; collaborative environment; craving; design; drinking; drinking behavior; experience; flexibility; high risk drinking; hypothalamic-pituitary-adrenal axis; improved; medical schools; memory process; memory retrieval; men; neural circuit; neurobiological mechanism; neuroimaging; neuromechanism; novel; programs; relating to nervous system; response; social; training opportunity

PROJECT SUMMARY Excessive alcohol use presents a serious public health problem and increases risk for many preventable chronic diseases. The cognitive and neural mechanisms that promote this problematic drinking behavior, especially through alcohol-related memories, are not well understood. What people remember about their prior experiences using alcohol may drive later drinking. In particular, there may be biases in what heavy drinkers (compared to light drinkers) remember about drinking experiences. For example, alcohol-related cues elicit different neural responses in memory-related regions between these groups. Crucially, there are multiple memory systems, supported by distinct neural circuits and optimized to remember different types of information, which can be modulated by biological stress responses (known to be atypical among binge/heavy drinkers). There is a pressing need to understand how different types of alcohol-related memories are formed, influenced by stress responses, and predict drinking behavior. The research and training proposed in this K01 provides an ideal interdisciplinary opportunity to facilitate the candidate’s career growth into an independent scientist focusing on memory and affective mechanisms underlying the development of alcoholism. The proposed research elucidates the cognitive and neurobiological mechanisms underlying the formation of alcohol-related memories in problematic drinkers. This proposal builds upon the candidate’s expertise in the cognitive neuroscience of stress and memory and provides essential training in the neurobiology of alcoholism, computational modeling of neural mechanisms supporting alcohol-related learning, and predicting longitudinal repeated-measures drinking behavior. The team of mentors and collaborators are leaders in these fields and, together with the stimulating and collaborative environment of Yale School of Medicine, will prepare the candidate for an independent career at the interface of cognitive neuroscience and alcoholism research. The central research hypothesis is that binge/heavy drinkers have impaired memory for alcohol-related contexts and enhanced memory for cued behaviors, associated with elevated stress responses and predictive of greater levels of drinking. To test this hypothesis, functional neuroimaging (fMRI) data will be collected as light and binge/heavy drinkers learn and retrieve alcohol-related contexts and habit-like cued behaviors. Stress responses (via salivary cortisol) will be measured during learning and retrieval, and real-world drinking behavior will be monitored using smartphone prompts for 30 days after the fMRI sessions. This comprehensive design enables the characterization of: 1) biases in how risky drinkers form and retrieve alcohol-related memories; 2) how stress hormones contribute to the formation of these memories; and 3) which types of alcohol-related memory predict real-world drinking behavior. Successful completion of this project will address critical gaps in the candidate’s training and has the potential to reveal novel memory-related behavioral and neural markers of excessive alcohol use to ultimately facilitate the design of targeted memory-based treatments to mitigate alcoholism risk.

项目摘要 过度饮酒是一个严重的公共卫生问题，并增加了许多可预防的慢性疾病的风险。 疾病促进这种有问题的饮酒行为的认知和神经机制，特别是 通过酒精相关的记忆，并没有得到很好的理解。人们对先前经历的记忆 使用酒精可能会导致以后饮酒。特别是，在重度饮酒者（与 轻度饮酒者）记住饮酒经历。例如，与酒精相关的线索会引发不同的神经刺激 在这些群体之间的记忆相关区域的反应。至关重要的是，有多个记忆系统， 由不同的神经回路支持，并优化以记住不同类型的信息，这些信息可以是 由生物应激反应调节（已知在狂饮/重度饮酒者中是非典型的）。有一个 迫切需要了解不同类型的酒精相关记忆是如何形成的，受到压力的影响 反应，并预测饮酒行为。本K 01中提出的研究和培训提供了一个理想的 跨学科的机会，以促进候选人的职业发展成为一个独立的科学家，重点是 记忆和情感机制是酒精中毒发展的基础。拟议的研究阐明了 酒精相关记忆形成的认知和神经生物学机制， 有问题的酒鬼这个建议建立在候选人在压力认知神经科学方面的专业知识基础上 和记忆，并提供必要的培训，在神经生物学的酗酒，计算模型的神经 支持酒精相关学习和预测纵向重复测量饮酒的机制 行为导师和合作者团队是这些领域的领导者， 耶鲁医学院的合作环境，将为候选人的独立职业生涯做好准备 在认知神经科学和酗酒研究的界面上。中心研究假设是， 酗酒者对酒精相关环境的记忆受损，对线索的记忆增强。 行为，与压力反应升高有关，并预示着更高水平的饮酒。为了验证这一 假设，功能性神经成像（fMRI）数据将被收集为轻度和狂饮/重度饮酒者学习， 检索与酒精相关的上下文和习惯性暗示行为。压力反应（通过唾液皮质醇）将是 在学习和检索过程中进行测量，并使用智能手机监测真实世界的饮酒行为 功能性磁共振成像后30天的提示。这种全面的设计能够表征：1） 对危险饮酒者如何形成和恢复与酒精有关的记忆的偏见; 2）压力激素如何有助于 这些记忆的形成; 3）哪些类型的酒精相关记忆预测现实世界的饮酒 行为成功完成该项目将解决候选人培训中的关键差距， 揭示新的记忆相关的行为和神经标记物的潜力， 促进设计有针对性的基于记忆的治疗方法，以减轻酗酒风险。