Neuroimaging multiple memory processes, glucocorticoids and alcoholism risk

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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.