Abstract/Project Summary
This application describes the research plan and program of study leading to a PhD as part of a combined MD-
PhD Program at the University of Nebraska Medical Center. The central goal of the research plan is to identify
how aberrant brain dynamics related to HIV infection differ in those who use cannabis. People living with HIV
(PLWH) are at a significant risk for developing neurologic comorbidities such as HIV-associated neurocognitive
disorder (HAND). Additionally, many PLWH are chronic cannabis users, and such use itself is thought to alter
long-term brain function, and potentially modulate the neural changes associated with HIV. Advanced neuro-
imaging studies using magnetoencephalography (MEG) have identified specific changes in the neural dynamics
related to HIV infection and HAND, however, it is unknown whether these dynamics differ in those who
chronically use cannabis. Thus, the proposed line of research aims to address this knowledge gap by using MEG
imaging in a group of PLWH who are chronic cannabis users and comparing them to PLWH who are non-users,
chronic cannabis users without HIV, and a non-user uninfected control group. All participants will undergo neuro-
psychological testing to relate cognitive performance to neural measures. Using MEG, we will identify the neuro-
physiological dynamics altered by HIV and cannabis use by quantifying task-based and spontaneous neural
oscillatory activity during three cognitive paradigms, which are known to elicit neural activity related to visual-
spatial processing, selective attention, and verbal working memory. Each of these tasks have been shown to
elicit differences in neural oscillatory activity between PLWH and uninfected controls. MEG data will be imaged
using an advanced beamforming approach to generate dynamic functional maps, and groups will be compared
using ANOVAs, with between-subjects factors of HIV infection and chronic cannabis use. This will not only allow
for the identification of neural changes associated with HIV and cannabis use independently, but also determine
the interaction between HIV infection and cannabis use. Additionally, alcohol use will be examined as a factor of
interest to determine the effect of increasing alcohol use within our sample. Our specific aims are: (1) To quantify
the neural dynamics associated with chronic cannabis use and HIV-infection in regards to activity serving spatial
processing, attention, and working memory, and examine how HIV-related aberrations differ in cannabis users
by studying cannabis users and nonusers with and without HIV-infection., and (2) to determine the interaction
between chronic cannabis and alcohol use in regards to brain and cognitive function in PLWH. In summary, we
will utilize MEG, advanced source reconstruction methods, neural oscillatory analyses, and neuropsychological
testing to delineate the neurophysiological relationship between chronic cannabis use and HIV infection. The
program of study is designed to support this research plan by incorporating rigorous training by established
mentors who are leaders in the fields of HIV and drug use, with the primary goal of developing and expanding
the research and clinical skills of the applicant to produce a successful physician-scientist.