Reduced neural specificity in middle-aged HIV+ women in the absence of behavioral deficits

• We investigate early neuronal dysfunctions in cognitively normal HIV+ women.
• Conventional fMRI technique reveals normal neural activity in the FFA of HIV+ women.
• fMRI-adaptation reveals a decrease in neural specificity in the FFA of HIV+ women.
• Hcorr, a novel fMRI technique, confirms the fMRI-adaptation results
• Hcorr-estimated neural specificity might serve as a biomarker of asymptomatic HAND

In the post combination antiretroviral therapy (cART) era, the prevalence of mild forms of HIV-associated neurocognitive disorders (HAND) in individuals with HIV-infection remains high. There is a pressing need to find biomarkers that can aid clinical assessment of HAND, especially in those with mild or no neurocognitive symptoms. Here we hypothesized that a reduction in neural specificity, or the specificity of neuronal tuning, could serve as a potential biomarker of asymptomatic HAND. To directly test this hypothesis, we applied two advanced fMRI techniques to examine the difference in neural specificity between middle-aged HIV+ women and age-matched negative controls, with a focus on the fusiform face area (FFA), a critical region in face processing. Face discrimination performance was assessed outside of the scanner. While the behavioral performance of face discrimination was comparable between the two groups, a reduced neural specificity in the FFA of HIV-positive women was revealed by a novel fMRI analysis technique, local regional heterogeneity analysis, or Hcorr, as well as an established technique, fMRI-rapid adaptation. In contrast, conventional fMRI techniques were insensitive to these early changes. These results suggest that, prior to the onset of detectable behavioral deficits, significant neuronal dysfunctions are already present in HIV+ individuals, and these early neuronal dysfunctions can be detected and assessed via neural specificity, which, in combining with the novel Hcorr technique, has a strong potential to serve as a biomarker of asymptomatic HAND and other neurodegenerative diseases.