Doctor of Philosophy (PhD)
First Advisor's Name
Dr. Matthew T. Sutherland
First Advisor's Committee Title
Second Advisor's Name
Dr. Angela R. Laird
Second Advisor's Committee Title
Third Advisor's Name
Dr. Aaron Mattfeld
Third Advisor's Committee Title
Fourth Advisor's Name
Dr. Wasim Maziak
Fourth Advisor's Committee Title
HIV, cannabis, error awareness, medication management, default mode network, insula, resting-state functional connectivity, TNF- α, inflammation, resource allocation index
Date of Defense
Neuroimaging research has identified brain alterations linked with the human immunodeficiency virus (HIV) that contribute to cognitive declines characterizing the disease. Given cannabis’s (CB’s) anti-inflammatory properties, use prevalence among people living with HIV (PLWH), and impact on neurocognition, my dissertation utilizes a between-groups study design to interrogate separate and interactive effects of HIV and CB on fMRI measures of brain activity. We investigate (1) task-based brain activity at the regional-level, (2) insular resting-state functional connectivity (rsFC) at the circuit-level, and (3) large-scale brain network interactions at the systems-level. Participants (N=114) were stratified into four groups (HIV+/CB+; HIV+/CB-; HIV-/CB+; HIV-/CB-) and underwent fMRI scanning while completing an Error Awareness Task (EAT) and while at rest. Participants also completed a battery of instruments including subjective reports of cognitive failures, and objective measures of cognition and medication management abilities. Blood samples quantified disease severity (viral load) and inflammation (tumor necrosis factor alpha [TNF-α]). Regarding task-based brain activity, PLWH displayed a lack of error-related deactivation in two default mode network (DMN) regions (posterior cingulate cortex [PCC], medial prefrontal cortex [mPFC]). Across all participants, reduced error-related PCC deactivation correlated with reduced medication management abilities and mediated the effect of HIV on such abilities. Regarding insular circuitry, we observed interactive HIVxCB effects on rsFC between two anterior insula (aI) subregions and sensorimotor cortices such that, CB use normalized altered rsFC that was observed among non-using PLWH and correlated with decreased somatic complaints and increased inflammation. Finally, regarding large-scale network interactions, PLWH displayed increased salience network (SN)-DMN rsFC that was associated with diminished error-awareness. These results demonstrate that insufficient error-related DMN suppression and heightened SN-DMN rsFC are linked with HIV and have consequences for error-processing and medication management. Additionally, these outcomes suggest a potential normalizing effect of CB on altered insula-sensorimotor neurocircuitries among PLWH and begin to elucidate inflammatory mechanisms through which CB use may impact brain function in the context of HIV.
Previously Published In
Flannery, J.S., Riedel, M.C., Salo, T., Poudel, R., Laird, A.R., Gonzalez, R. and Sutherland, M.T., 2021. HIV infection is linked with reduced error-related default mode network suppression and poorer medication management abilities. medRxiv. doi: https://doi.org/10.1101/2021.04.10.21255223
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Flannery, Jessica Shannon, "Neurobiological Impact of HIV Infection and Chronic Cannabis Use" (2021). FIU Electronic Theses and Dissertations. 4716.
In Copyright. URI: http://rightsstatements.org/vocab/InC/1.0/
This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).