BRAIN ACTIVATION STUDIES WITH EARLY HIV DEMENTIA

Brookhaven Science Assoc-Brookhaven Lab, Upton NY

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Abstract

(This is an application written in response to RFA MH-99-012.) HIV infects the brain and can cause a dementia called HIV- cognitive motor complex (HIV-CMC). Patients with HIV-CMC have decreased concentration, attention and reaction times, and deficits in short-term and working memory. The aims of this study are: 1) to determine the neural correlates of attentional impairment in HIV-CMC using functional MRI (fMRI), a powerful technique that allows simultaneous, non-invasive measurement of brain activation and cognitive performance; and 2) to show that fMRI may detect abnormal brain activation in HIV patients with normal neuropsychological function. We designed a battery of cognitive tasks evaluating simple and choice reaction times, working memory, and visual attention. We will study four groups of subjects (20 / group): 1) seronegative healthy controls, 2) patients with HIV-CMC, 3) HIV patients without CMC, and 4) drug-naive patients with HIV-CMC. We hypothesize: 1) Compared to seronegative controls, HIV patients will show increased regional brain activation on fMRI in accordance with increased attentional modulation (parietal and, to a greater degree, in the dorsolateral frontal cortex). 2) Progressively more difficult tasks will cause more activation in the dorsolateral frontal and parietal cortex; however, HIV-CMC patients will reach maximal brain activation with only moderately difficult tasks. 3) Brain activation will inversely correlate with task performance. 4) The abnormally increased brain activation in the patients will not be due to the effect of antiretroviral medications. Our study will show that the neural correlates of cognitive deficits in HIV patients are injury to primarily the frontal lobe, or projections to the frontal and parietal lobes, causing increased attentional modulation during task performance. This leads to an early saturation of attentional modulation in HIV patients (exhaustion of functional brain reserve capacity); therefore, the patients cannot perform the more difficult tasks. Furthermore, fMRI will provide a quantitative assessment for the extent and location of brain injury due to HIV infection, even in patients with normal neuropsychological tests. fMRI may be useful for monitoring treatment efficacy.