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Principal Investigator: Elizabeth Goldfarb
Organization: YALE UNIVERSITY
Fiscal Year: 2024
Award: $167,088
Funding agency: National Institute on Alcohol Abuse and Alcoholism
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.
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