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Abnormal brain activation on functional MRI in cognitively asymptomatic HIV patients

From the Medical Department (Drs. Ernst and Chang, and S. Arnold) and Chemistry Department (Dr. Ernst), Brookhaven National Laboratory, Upton, NY; Department of Brain and Cognitive Sciences (Dr. Jovicich), Massachusetts Institute of Technology, Cambridge; and Department of Neurology (N. Ames), Harbor–University of California, Los Angeles Medical Center, Torrance.

Address correspondence and reprint requests to Dr. Thomas Ernst, Medical Department, Brookhaven National Laboratory, Bldg. 490, Upton, NY, 11973-5000; e-mail: TErnst{at}bnl.gov

Background/Objectives: A previous fMRI study demonstrated increased brain activation during working memory tasks in patients with HIV with mild dementia. The current study aims to determine whether patients who are HIV-1 positive and have normal cognitive function also show increased brain activation on fMRI.

Methods: Blood oxygenation level-dependent (BOLD) fMRI was performed in 10 patients with HIV (CD <500) and 10 age-, sex-, education-, and handedness-matched seronegative subjects. Each subject performed a battery of neuropsychological tests and fMRI with three tasks (0-back, 1-back, and 2-back) that required different levels of attention for working memory.

Results: Compared with control subjects, patients with HIV showed greater magnitude of brain activation (BOLD signal intensity changes, p 0.001) in the lateral prefrontal cortex, with normal performance during fMRI and on a battery of neuropsychological tests. The patients with HIV also showed increased activated brain volume in the lateral prefrontal cortex (p = 0.007) but not in other activated regions, including the posterior parietal cortex, supplementary motor area, thalamus, caudate, and occipital cortex. The increase in activated brain volume was independent of task difficulty.

Conclusion: Increased brain activation in subjects who are positive for HIV precedes clinical signs or deficits on cognitive tests. Early injury to the neural substrate may necessitate increased usage of brain reserve to maintain normal cognitive function. BOLD fMRI appears to be more sensitive than clinical and neuropsychological evaluations for detecting early HIV-associated brain injury.

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