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.
