Methamphetamine and HIV status modulate the neural dynamics underlying executive dysfunction and emotion dysregulation

点击翻译按钮获取中文摘要

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.