Neuroimaging multiple memory processes, glucocorticoids and alcoholism risk

项目总结 过量饮酒是一个严重的公共健康问题，并增加了许多可预防的慢性疾病的风险 疾病。促进这种问题饮酒行为的认知和神经机制，尤其是 通过与酒精相关的记忆，还没有被很好地理解。人们对他们以前的经历记得什么 饮酒可能会导致以后饮酒。特别是，酗酒者可能会有偏见(与 少量饮酒者)请记住饮酒经历。例如，与酒精相关的线索会引发不同的神经 这些组之间记忆相关区域的反应。重要的是，有多个存储系统， 由不同的神经电路支持，并优化为记忆不同类型的信息，这些信息可以 受生物应激反应的调节(已知在酗酒/酗酒者中不典型)。有一个 迫切需要了解不同类型的酒精相关记忆是如何在压力的影响下形成的 反应，并预测饮酒行为。K01中提出的研究和培训提供了一个理想的 跨学科机会，促进候选人的职业成长为独立科学家，专注于 酒精中毒发展的记忆和情感机制。这项拟议的研究阐明了 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。这项建议建立在候选人在应激认知神经科学方面的专业知识基础上 和记忆，并在酒精中毒的神经生物学、神经的计算模型方面提供必要的培训 支持酒精相关学习的机制，并预测纵向重复饮酒 行为。导师和合作者团队是这些领域的领导者，与激动人心的 和耶鲁医学院的协作环境，将为候选人的独立职业生涯做好准备 在认知神经科学和酒精中毒研究的交界处。研究的中心假设是 酗酒/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，与压力反应升高相关，并预示着更多的饮酒。为了测试这一点 假设，功能神经成像(FMRI)数据将在轻度和酗酒/重度饮酒者学习和 检索与酒精相关的上下文和类似习惯的提示行为。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，并使用智能手机监控真实世界的饮酒行为 在功能磁共振成像会话后提示30天。这一综合设计可实现以下特点：1) 对高风险饮酒者如何形成和找回与酒精相关的记忆的偏见；2)压力荷尔蒙如何促进 这些记忆的形成；以及3)哪些类型的酒精相关记忆可以预测现实世界中的饮酒 行为。成功完成此项目将解决候选人培训中的关键差距，并具有 可能揭示过度饮酒的新的记忆相关行为和神经标记物最终 促进基于记忆的针对性治疗的设计，以减轻酒精中毒的风险。

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.