Reduced white matter maturation in the central auditory system of children living with HIV

Abstract

Introduction School-aged children experience crucial developmental changes in white matter (WM) in adolescence. The human immunodeficiency virus (HIV) affects neurodevelopment. Children living with perinatally acquired HIV (CPHIVs) demonstrate hearing and neurocognitive impairments when compared to their uninfected peers (CHUUs), but investigations into the central auditory system (CAS) WM integrity are lacking. The integration of the CAS and other brain areas is facilitated by WM fibers whose integrity may be affected in the presence of HIV, contributing to neurocognitive impairments. Methods We used diffusion tensor imaging (DTI) tractography to map the microstructural integrity of WM between CAS regions, including the lateral lemniscus and acoustic radiation, as well as between CAS regions and non-auditory regions of 11-year-old CPHIVs. We further employed a DTI-based graph theoretical framework to investigate the nodal strength and efficiency of the CAS and other brain regions in the structural brain network of the same population. Finally, we investigated associations between WM microstructural integrity outcomes and neurocognitive outcomes related to auditory and language processing. We hypothesized that compared to the CHUU group, the CPHIV group would have lower microstructural in the CAS and related regions. Results Our analyses showed higher mean diffusivity (MD), a marker of axonal maturation, in the lateral lemniscus and acoustic radiations, as well as WM between the CAS and non-auditory regions predominantly in frontotemporal areas. Most affected WM connections also showed higher axial and radial diffusivity (AD and RD, respectively). There were no differences in the nodal properties of the CAS regions between groups. The MD of frontotemporal and subcortical WM-connected CAS regions, including the inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and internal capsule showed negative associations with sequential processing in the CPHIV group but not in the CHUU group. Discussion The current results point to reduced axonal maturation in WM, marked by higher MD, AD, and RD, within and from the CAS. Furthermore, alterations in WM integrity were associated with sequential processing, a neurocognitive marker of auditory working memory. Our results provide insights into the microstructural integrity of the CAS and related WM in the presence of HIV and link these alterations to auditory working memory.