Neural and Behavioral Representations of a Transdisciplinary Model of Craving in Normative and Substance Use Populations

Project Summary Craving, the intense desire for drugs, is a pivotal cause of relapse in substance use disorders and is known to grow during abstinence known as the incubation of craving. This phenomenon is prominent in both humans and animals yet is measured divergently—through instrumental behavior tasks in animals and subjective

assessments in humans. This discrepancy underscores the differing cognitive factors driving craving where animal models focus on habitual behaviors driven by striatal learning systems whereas human models assess self-reported feelings associated with craving driven putatively by the hippocampus, a neural system associated

with reward memory. The traditional understanding of reward learning, driven by the striatum, posits that memory for rewards should fade during abstinence, but the plethora of incubation data shows an escalation. Hippocampal memory systems provide a mechanism by which reward memories can intensify over time via systems

consolidation processes which replay memories to transform their traces into cortical regions such as the prefrontal cortex (PFC), another region implicated in cue-induced craving. Novel methods are needed to relate trans-species methods of craving in a single paradigm capable of teasing apart cognitive-emotional mechanisms

that may comprise different elements of craving. F99 Phase: The proposed pre-doctoral research will utilize a novel fMRI paradigm exploring craving in a normative human population characterizing the incubation of craving for non-drug rewards, i.e. foods, using subjective and instrumental assessments of craving. In this way, we can

leverage idiosyncratic items that individuals have a history of naturalistic encounters and display a range of liking and times of abstinence since last consumption. Utilizing fMRI, we will examine the mesolimbic circuitry related to habitual elements of craving, hippocampal activation related to cue-induced craving, and prefrontal

involvement in storing memories over varying lengths of time. Additionally, through natural language processing of reward memory narratives, we aim to construct linguistic profiles correlating subjective craving with behavioral expressions, broadening our tools to understand craving. This will enable a multifaceted understanding of

craving, integrating instrumental and subjective dimensions. K00 Phase: This phase extends this integrated model to study craving I will have developed in graduate school to individuals with nicotine use disorders, investigating how craving memories differ across natural and drug rewards and their impact on craving intensity

and duration. This approach aims to delineate the complex dynamics of craving in SUDs, contributing to the development of targeted interventions. This comprehensive exploration will advance our understanding of craving's neurobiological underpinnings, bridging the gap between subjective experiences and observable

behaviors. The findings will have significant implications for developing effective treatments for addiction, aligning with the applicant's long-term objective of pioneering a research lab dedicated to the cognitive neuroscience of addiction and substance use disorders.