The proposed 4-year Supplement project will incorporate functional magnetic resonance imaging (fMRI) into
a recently funded multiphase optimization strategy (MOST) trial of a Pre-Exposure Prophylaxis (PrEP)-
focused intervention for people who inject drugs (PWID) who are newly enrolled in medication for opioid
use disorder (MOUD) treatment (R01DA055534; Copenhaver, PI). The scientific premise for this
supplement builds directly on evidence summarized in the parent grant - that cognitive dysfunction is
common among PWID and disrupts PrEP-focused HIV prevention outcomes, if not properly
accommodated. The neuroimaging battery will include tasks of specific relevance to cognitive dysfunction
and to PrEP and MOUD outcomes as well as data specifically acquired during exposure to PrEP educational
videos and during resting state. Based on our prior work conducted in the same MOUD clinics as the parent
trial, we anticipate that ~80% of individuals enrolled in the parent trial will be interested in and eligible for
fMRI scanning. Thus, we anticipate scanning approximately 200 individuals over 4-years, with the following
aims: (1) Specifying brain-based mechanisms of cognitive dysfunction among individuals entering PrEP-
focused intervention. During fMRI scanning, participants will complete cognitive function tasks with specific
relevance to compensatory intervention components being tested in the parent trial (i.e., validated tasks of
cognitive/executive function,, attention, memory, and information processing). Data will be analyzed using
advanced, network-based approaches (e.g., independent component analysis) to provide the first ever
comprehensive characterization of neural processes subserving cognitive dysfunction among PWID entering
MOUD and PrEP, and (2) Identifying predictive neuromarkers of return to risk behaviors (i.e., PrEP and
MOUD outcomes). We will use an interpretable, connectivity-based approach, connectome-based predictive
modeling (CPM), to identify predictive neuromarkers of PrEP and MOUD outcomes. The proposed
supplemental work will provide mechanistic insight into clinical individual difference factors among
individuals with multiple high-risk behaviors (e.g., condomless sex, needle sharing) among individuals in
MOUD, and is an essential precursor to the development of optimized, biologically based, prevention and
intervention efforts to combat the current opioid epidemic.