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 attention and cognitive control, 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 attention and
cognitive control (e.g., frontoparietal, salience). However, there is a dearth of extant literature, specifically with
regard to the synergistic effects of HIV and METH on cognitive and brain dysfunction. Identifying the overall
impact of HIV and METH is critical, as aberrations in attention and 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 fellowship application would provide advanced training in this area and initiate a
project that 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 attention and
cognitive control dysfunction in virally suppressed PWH with and without METH and matched seronegative
controls (i.e., four groups). Aim 1 will quantify the adverse synergistic impact of METH in PWH on performance
and the neural oscillatory dynamics serving attention and cognitive control, while Aim 2 will determine whether
METH accentuates the abnormally elevated spontaneous cortical activity observed in virally suppressed PWH
compared to demographically matched seronegative controls. The applicant is a promising second-year PhD
student studying neuroscience who has already distinguished herself through a first-authored manuscript directly
related to the proposed work, two first-authored manuscripts under peer review, and a high number of coauthored
papers through extensive postbaccalaureate research experience. In the proposed fellowship, she will be
mentored by Dr. Tony Wilson – an internationally known expert in human neuroimaging, HIV, and substance
use – and she will receive advanced training in addiction science, neuroHIV, and clinical cognitive neuroscience.