fMRI Identifies Neural Damage Due to HIV Before Symptoms Present

Neuroscientists and clinicians reported that a five-minute functional magnetic resonance imaging (fMRI) scan can identify neuronal dysfunction in human immunodeficiency virus (HIV)-positive individuals who do not yet exhibit cognitive decline.

The study, published online December 13, 2014, in the journal Neuroimaging: Clinical, provides proof-of-concept findings that imaging can help monitor neural functioning in this population, known to be affected by the virus and potentially by the treatments meant to suppress HIV. The matter of neural dysfunction in the HIV-positive population is important, according to Georgetown University Medical Center (Washington DC, USA) neuroscientist Xiong Jiang, PhD, the study’s senior investigator. “About half of people living with HIV are affected by HIV-associated neurocognitive disorders, or HAND, and we expect this condition will escalate as the current HIV-positive generation ages,” he stated.

However, testing for cognitive decline that is not yet noticeable is complex. “There is no one clinical screening tool that has been found to be appropriately sensitive or specific for HAND yet,” said coauthor Mary Young, MD, director of Georgetown University Medical Center’s HIV Women’s Program. “Therefore, there has been great interest in developing biomarkers of overall brain health and disease in HIV to streamline diagnosis and monitoring.”

Dr. Young collaborated with Dr. Jiang on a potential biomarker based on fMRI techniques Dr. Jiang and his collaborators had developed, which have been shown to be sensitive to slight behavioral alterations. To evaluate whether these fMRI techniques might be capable of detecting and assessing neural injury due to HIV before symptoms occur, Drs. Jiang and Young examined 28 women (15 who were HIV-positive, with an average age of 50) from the US National Institutes of Health (NIH; Bethesda, MD, USA)-funded Washington DC Metropolitan Interagency Women’s HIV Study (WIHS) cohort. WIHS at Georgetown, led by Dr. Young since 1993, includes 300 participants and is one of nine national sites designed to follow HIV infected women along with a control population.

In this proof-of-concept study, the researchers used face processing and its associated brain region, fusiform face area (FFA), as the mean to probe neural injury in HIV. They found that the neural specificity in the FFA—estimated via fMRI-adaptation, an established technique, and local regional heterogeneity analysis (Hcorr), a novel technique—is reduced in the HIV-positive participants. “FFA neurons were not as finely tuned in this group, compared to uninfected participants,” Dr. Jiang said. “We are very excited about this finding because Hcorr, which can estimate neural specificity rapidly, holds the promise to serve as a research tool to examine neural injury and a clinical tool to assess and monitor HAND progression. It could also be useful for drug development as it is safe and noninvasive.”

Currently, there are no methods to treat HAND other than to control HIV replication, Dr. Young stated, “Developing defined treatments guided by biomarkers would be the next step. Imaging techniques like Hcorr could help identify dysfunction before deficits are in place. Based on the nature of those deficits, we could then try treatments used in other conditions and or begin to develop specific compounds to study. In the meantime imaging could help identify a group that might need additional psychosocial supports to successfully navigate older age.”

The researchers reported that their findings also support the hypothesis that HIV-positive individuals are aging faster compared with a non-infected population. “Our data, demonstrating the decrease in neural
specificity before the onset of behavioral symptoms, is in line with reports from aging studies and provides supports
to the accelerated aging theory,” Dr. Jiang concluded.

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