Dissertation Defense: Shiva Hassanzadeh-Behbahani

Candidate: Shiva Hassanzadeh-Behbahani

Major: Neuroscience

Advisors: Xiong Jiang, Ph.D. and Ashley S. VanMeter, Ph.D.

Title: Functional and Structural Brain Imaging Evidence of Frontostriatal Alterations in HIV and Aging

Over 38 million people are living with human immunodeficiency virus (HIV) worldwide. Although advances in medical treatments have converted HIV from a fatal disease to a chronic manageable condition, the aging population of people with HIV (PWH) is more susceptible to cognitive difficulties. Up to half of all PWH suffer from neurologic complications of HIV, known as HIV-associated neurocognitive disorders (HAND). While the brain mechanisms of this disorder remain unclear, frontostriatal circuitry is a brain system hypothesized to play a key role. This dissertation presents three studies that apply functional and structural brain imaging to examine the impacts of HIV disease and aging on the brain’s frontostriatal circuits. The first study demonstrated that a history of severe immune suppression was associated with widespread cortical thinning in PWH, especially in the frontal and temporal regions. In addition, decreased global neurocognitive function was linked to bilateral frontal cortical thinning. These results are consistent with the hypothesis that PWH may suffer irreversible neural injury to the frontal cortex during advanced immunosuppression and that this injury persists despite subsequent immune recovery on antiretroviral therapy. The second study observed both reductions in frontostriatal functional connectivity in PWH compared to controls and, despite immune recovery on antiretroviral therapy, an accelerated decline in frontostriatal brain function in aging PWH who met diagnostic criteria for HAND. These findings suggest that PWH may suffer ongoing reductions in frontostriatal brain function and that, if this represents potentially reversible neural injury, it could be specifically targeted by therapeutic interventions. The third study confirmed that HIV disease and aging were associated with deterioration of the frontostriatal white matter connections. Together, these findings highlight the vulnerability of the frontostriatal brain system in aging PWH and suggest adverse and potentially compounding effects of HIV and advanced age on this circuitry.