Neural Substrates Associated with Excutive Functioning in Marijuana and HIV
Marijuana is the most common drug of abuse among HIV-infected persons in the United States. Of the 1.2 million Americans living with HIV/AIDS, over half experience neurocognitive impairment, including deficits in decision making and behavioral inhibition. Previous research has documented that marijuana and HIV independently disrupt functioning in the fronto-parietal executive control network of the brain, and HIV also causes damage to relevant sub-cortical nuclei. However, the interactions of marijuana and HIV on brain functioning and structure have not been well characterized. In this theory-driven proposal, we hypothesize that marijuana use among HIV-infected persons will accelerate declines in neurocognitive functioning, with specific deficits in executive control, and that these impairments will be greater in individuals with advanced versus early HIV disease. In this Imaging Science Track Award for Research Transition (I/START) grant, we propose to combine multi-modal magnetic resonance imaging (MRI) and neuropsychological testing to investigate in vivo whether marijuana use among HIV-infected persons is associated with greater neurocognitive impairment, specifically in executive control functions. Using a cross-sectional design of HIV- infected persons, we will compare neurocognitive functioning in 25 marijuana only users and 25 non drug users at varying stages of HIV disease. The neuroimaging protocol includes task-evoked functional MRI (fMRI), resting state functional connectivity MRI (fcMRI), and diffusion tensor imaging (DTI). Analyses will test whether marijuana users have reduced neural activity, functional connectivity, and structural integrity within regions of the executive control network. Results of this study will culminate in an R01 application for a larger, prospective study investigating the role of marijuana in predicting cognitive decline in the context of HIV disease. The overarching goals of this research are to elucidate the neural mechanisms underlying cognitive processes altered by HIV and marijuana. This research will also inform the development of neural biomarkers for early identification of neurocognitive decline in drug users and has direct implications for HIV clinical practice (e.g., use of medical marijuana to treat HIV-related symptoms and integration of substance abuse treatment).