HIV infection is often accompanied by cognitive, motor, and behavioral changes that range from mild impairments of memory, concentration and motor slowing to HIV-associated dementia. These types of changes resemble the neuropsychological profiles of individuals with subcortical neuropathology, including Parkinson's disease (PD) and Huntington's disease (HD). Studies have also shown HIV to have pathology similar to PD and HD, with post-mortem, structural neuroimaging, and resting metabolic imaging studies showing damage primarily to the basal ganglia and thalamus. The only reported cognitive activation study, used PET to show prefrontal cortex dysfunction in HIV-positive subjects during a short-term memory task. All of this evidence suggests dysfunction of the circuits linking the prefrontal cortex, basal ganglia, and thalamus in the brains of HIV-infected individuals. However, there is limited data that directly links HIV-related cognitive impairments with function in any brain areas, including frontostriatal regions. The main goal of this study is to integrate functional MRI (fMRI), neuropsychological measurements, immunological markers, and measures of everyday functioning to study the relationship between HIV-related cognitive, motor, and behavioral deficits and underlying changes in functional brain circuitry. Data will be collected in a group of 150 HIV-positive, non-demented subjects and 50 HIV-negative control subjects.
The specific aims of the proposal are: 1) to characterize the relationship between viral load, CD4+ count and brain function, 2) to use fMRI to assess brain function during performance of cognitive tasks found to be impaired in HIV-infected individuals, especially those that are related to frontostriatal function, 3) to examine the relationship between brain function, standard neuropsychological tests that are sensitive to HIV, and everyday functioning and 4) to analyze whether such relationships are moderated by factors including antiretroviral therapy use, age, ethnicity, education, or premorbid intelligence. The opportunity to use current fMRI methodology is a major strength of this study as it permits examination of brain function in a single subject. As HIV is a very heterogeneous disorder, it will be important to evaluate the relationship between the experimental variables within single subjects to better understand how each variable directly impacts the others. Finally, data produced by this study may lead to a more sophisticated understanding of the nature of brain dysfunction in HIV, assisting in the development of therapies to ameliorate cognitive impairment by targeting brain regions affected earliest by the disease.
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| Castelo, J Mimi Boer; Courtney, Maureen G; Melrose, Rebecca J et al. (2007) Putamen hypertrophy in nondemented patients with human immunodeficiency virus infection and cognitive compromise. Arch Neurol 64:1275-80 |
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| Castelo, J M B; Sherman, S J; Courtney, M G et al. (2006) Altered hippocampal-prefrontal activation in HIV patients during episodic memory encoding. Neurology 66:1688-95 |
| Schendan, Haline E; Searl, Meghan M; Melrose, Rebecca J et al. (2003) An FMRI study of the role of the medial temporal lobe in implicit and explicit sequence learning. Neuron 37:1013-25 |
