Impact of HIV and Cannabis Use on Executive Brain Function and Inflammation - Project Summary/Abstract While health outcomes for people with HIV (PWH) have greatly improved due to antiretroviral therapies, executive dysfunction continues to impact up to an estimated 50% of PWH, highlighting a pressing need for continued research in this area. Cannabis use is prevalent in this population largely for relief from peripheral HIV- related symptoms such as nausea. Cannabis may also exert neuroprotective effects for PWH due to its modulation of inflammation via the endocannabinoid system. Since systemic inflammation of the central nervous system has been associated with cognitive declines among PWH, it is important to explore this potential pathway of decreasing neuroinflammation. Recent work has attributed the use of cannabis among PWH with normalized oscillatory brain activity in frontoparietal brain regions, which are necessary for executive functioning. However, the literature is limited regarding the intersection of cannabis, neuroinflammation, and executive functioning as indexed by both neuropsychological assessment and brain activation. Given the prevalence of cognitive impairment among PWH, it is critical to characterize how the commonly used substance cannabis modulates neuroinflammation and executive function abilities. The proposed fellowship seeks to partially address this gap by utilizing the excellent spatial and temporal precision of magnetoencephalography (MEG) in conjunction with neuropsychological assessment and plasma inflammation levels. Briefly, adult PWH using and not using cannabis will be recruited in addition to demographically matched samples of using and non-using healthy controls (four total groups). Participants will undergo a blood draw for inflammatory biomarker testing, two NIH Cognitive Battery assessments for executive function, and complete two executive function tasks during MEG. The inflammatory biomarkers will be combined into one neuroinflammation index score via factor analysis and accuracy outcomes of the battery assessments will be standardized for comparison. The MEG data will be transformed into the time-frequency domain and imaged using a beamformer. The resulting dynamic functional maps will be utilized to examine spectrally specific brain responses that are supportive of executive functioning, i.e. regions of the frontoparietal network. Aim 1 will compare neuroinflammatory index scores between groups to examine the effect of cannabis on HIV-related inflammation. Aim 2 will determine the impact of cannabis use on executive function assessment performance and frontoparietal activation. To accomplish this, we will take advantage of the latest MEG and source reconstruction techniques, neural oscillatory analysis methods, and cognitive assessments to examine the influence of serostatus and cannabis usage on the neurophysiological bases of executive function. Aim 3 will explore the differential relationships between frontoparietal oscillatory activity supporting executive function and neuroinflammation among cannabis using and non-using PWH. In sum, this research will help elucidate the potential of cannabis to mitigate neuroinflammation and executive dysfunction among PWH.
