Modeling and modulating neural responses to reward and threat: Associations with childhood adversity and risk for substance use problems

University Of Michigan At Ann Arbor, Ann Arbor MI

Investigators

Abstract

PROJECT SUMMARY/ABSTRACT This K23 proposal seeks to provide an early-career clinical psychologist (Dr. Katherine McCurry) with the mentorship, training, and resources necessary to launch a career as an independent patient-oriented investigator focused on affective neuroscience, multivariate predictive modeling, and neuromodulatory approaches to personalized prevention and early intervention for substance use disorders (SUDs). Childhood trauma is associated with earlier initiation of substance use, faster progression to heavy drinking during adolescence, and increased risk of SUDs in emerging adulthood, making early intervention critical for reducing the burden of SUDs in trauma-exposed youth. However, significant heterogeneity in traumatic experiences may result in differential neurodevelopmental impacts and may hamper the development of efficacious interventions. Translational neuroscience provides a valuable framework for leveraging links between childhood trauma and developmental processes implicated in SUD to design and test targeted interventions. The dimensional threat-deprivation model posits, in part, that deprivation experiences (e.g., neglect) may lead to blunted behavioral and striatal responses to reward, while threat-related experiences (e.g., abuse), may lead to heightened vigilance and exaggerated amygdalar reactivity towards potential threats. However, to date, the influence of trauma type on the complex distributed networks involved in reward- and threat-processing has not been investigated within the same developmental sample. Identifying predictive multivariate neurosignatures will provide insight into the distinct and shared neurodevelopmental mechanisms underlying childhood trauma’s associations with substance use and inform novel targeted intervention strategies. Of specific interest is real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf), a promising technique that aims to facilitate learning by providing an individual with real-time information about their brain state. In the proposed project, the Candidate will conduct research using neuroimaging data from a large-scale developmental study (i.e., the Adolescent Brain Cognitive Development [ABCD] Study®) and collect pilot rtfMRI-nf data from 50 adolescents (aged 13-16; 50% female) to address the following research aims: 1) Identify reward and threat- related multivariate neurosignatures predictive of problematic substance use in adolescence; 2) Elucidate specificity of links between traumatic experiences (i.e., deprivation versus threat), aberrant neurosignatures (reward-related and threat-related circuits), and problematic substance use; and 3) Assess adolescents’ ability to modulate reward and threat-related multivariate neurosignatures using real-time fMRI neurofeedback. Completion of specialized training in 1) neurodevelopmental risk trajectories for SUD; 2) multivariate predictive analytics for large neuroimaging datasets; 3) rtfMRI-nf design, execution, and analysis; and 4) clinical trial design and analysis will ensure the Candidate’s success in achieving the proposed research aims and establishing herself as an independent translational scientist.