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.

Project Narrative People with HIV have a substantially elevated risk of developing cognitive impairment despite now having a life expectancy that approaches that of the general population. Substance use disorders are also more prevalent in people with HIV, including methamphetamine use disorder, which may play a critical role in the emergence of these cognitive deficits. The proposed fellowship will train a promising junior scientist to use an advanced dynamic functional brain mapping approach to identify the independent and synergistic effects of HIV-infection and methamphetamine use disorder on brain and cognitive function in adults.