RESUMO
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.
RESUMO
Introduction: Even with the increased access and early initiation of combination antiretroviral therapy, children with perinatally acquired human immunodeficiency virus (CPHIV) continue to demonstrate white matter alterations. Children perinatally HIV-exposed, but uninfected (CHEU) alike show differences in white matter integrity compared with children who are HIV-unexposed and uninfected (CHUU). Objectives: Mapping white matter connections that link gray matter regions that form resting-state (RS) functional networks may demonstrate whether structural and functional connectivity alterations in HIV infection and exposure may be related. We hypothesized reduced structural connectivity in CPHIV within the default mode network (DMN), visual, ventral DMN (vDMN), somatosensory, salience, auditory, motor, executive, basal ganglia, and posterior DMN (pDMN). We also hypothesized that CHEU will have increased structural connectivity compared with CHUU in the vDMN, somatosensory, pDMN, dorsal attention, salience, auditory, motor and basal ganglia. Methods: Study participants were 61 seven-year-old CPHIV and 46 age-matched children who are HIV uninfected (CHU) (19 CHEU). We used diffusion tensor imaging-based tractography to investigate white matter connections that link gray matter regions within RS functional networks. Results: We found altered white matter integrity in the somatosensory, salience, default mode, and motor networks of CPHIV compared with CHU. The superior temporal cortex, superior frontal cortex, and putamen were affected in all four networks and have also been reported to demonstrate morphological alterations in the same cohort. In CHEU, white matter integrity was higher in the visual network, pDMN, and motor network compared with CHUU. Conclusion: Our results suggest that altered white matter integrity may influence gray matter morphology and functional network alterations. Impact statement The long-term effects of human immunodeficiency virus (HIV) and exposure on the developing brain in the combination antiretroviral therapy era are still not well known. We use diffusion tensor imaging-based tractography to explore these effects on white matter connections that link gray matter regions within functional networks. Our findings provide a context for HIV-associated white matter and connectivity abnormalities.