HIV-Associated Microstructural Abnormalities in Default Mode, Executive Control, and Salience Networks: Insights from Tensor-Valued Diffusion Encoding

Cognitive impairment persists in people with HIV (PWH) despite effective combination antiretroviral therapy, possibly as a result of persistent alterations in white matter microstructural abnormalities in the brain. Noninvasive tensor-valued diffusion MRI (dMRI) is sensitive to microstructural integrity; thus, it may contribute to the understanding of HIV-associated cognitive impairment. In this exploratory cross-sectional study, 31 healthy controls (HCs) and 24 PWH underwent 3T MRI and neurocognitive assessment. Tensor-valued dMRI metrics, including microscopic fractional anisotropy (µFA) and isotropic, anisotropic, and total mean kurtosis (MKi, MKa, MKt), and conventional DTI and DKI metrics (FA, MD, and MK) were evaluated across six functionally defined brain networks. Compared with HCs, PWH exhibited reduced FA, µFA, and MKa in the dorsal default mode and anterior salience networks, along with increased MKi in the salience network and decreased MKi in the executive control network, with moderate effect sizes. Compared with HCs, PWH performed significantly worse on measures of learning, memory, and language, but showed no differences in executive function, attention, or processing speed. Additionally, significant associations and interactions between dMRI metrics and HIV status were observed, particularly for MKi and attention, executive function, and processing speed across the default mode, salience, and executive control networks. These preliminary findings underscore tensor-valued dMRI as a sensitive biomarker of network-specific neurocognitive vulnerability in HIV.