Project Summary/Abstract
Virally suppressed people with HIV (PWH) now have a life expectancy near that of the general population, yet
their risk of developing cognitive impairment remains substantially elevated relative to seronegative individuals.
Methamphetamine use disorder (METH) is another condition that is significantly more prevalent in PWH, and
METH is also associated with cognitive impairment. Specifically, both HIV and METH appear to have a negative
impact on the processes associated with cognitive control and emotion regulation, including decision-making,
sustained attention, and inhibiting task irrelevant stimuli. Human neuroimaging studies in this area have shown
that both PWH and people with METH exhibit inefficient neural processing within the brain networks serving
cognitive control and emotion regulation (e.g., frontoparietal, salience). However, there is a dearth of extant
literature, specifically regarding the synergistic effects of HIV and METH on executive and emotional dysfunction.
Identifying the overall impact of HIV and METH is critical, as aberrations in cognitive control networks have been
shown to have negative downstream effects on clinical outcomes, including poorer medication adherence in
PWH, more intense methamphetamine cravings, and maladaptive decision-making.
The National Institute on Drug Abuse (NIDA) recently issued a Notice of Special Interest (NOT-DA-21-030) citing
that PWH and a comorbid substance use disorder such as METH “often have exacerbated or accelerated …
cognitive/behavior deficits” relative to nonusers, and that “approaches that involve whole brain modeling or
consideration of complex systems are likely to illuminate brain network-level mechanisms underlying [these]
clinical deficits.” The proposed application directly addresses this call through a dynamic neuroimaging study
that leverages recent discoveries to identify the synergistic effects of METH and HIV on the brain regions and
networks that serve executive dysfunction and emotion dysregulation. We will enroll PWH and seronegative
controls with and without METH. Aim 1 (awarded F31 project) will quantify the impact of METH on HIV-related
aberrations in the neural oscillatory dynamics serving executive dysfunction. Aim 2 (proposed herein) will identify
how HIV and METH independently and synergistically contribute to the altered oscillatory dynamics underlying
emotion dysregulation, while Aim 3 will elucidate the bidirectional pathways whereby HIV and METH modify the
neural systems governing emotion regulation and executive function, leading to accentuated breakdowns in both
domains. The applicant is a NIDA-supported F31 predoctoral fellow studying cognitive neuroscience who has
already distinguished herself through four first-authored manuscripts directly related to the proposed work, and
numerous coauthored papers through extensive collaboration, mentoring, and postbaccalaureate research
experience. The work proposed in this application will complete the applicant’s dissertation, as part of her training
for a career in addiction science in neuroHIV, which will provide critical direction for her future work identifying
novel targets for interventions to reduce suffering in PWH and comorbid methamphetamine addiction.
