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

Joanah Madzime; Marcin Jankiewicz; Ernesta M Meintjes; Peter Torre 3rd; Barbara Laughton; Andre J W van der Kouwe; Martha Holmes

doi:10.3389/fnimg.2024.1341607

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

Front Neuroimaging. 2024 Mar 6:3:1341607. doi: 10.3389/fnimg.2024.1341607. eCollection 2024.

Authors

Joanah Madzime^{1

2}, Marcin Jankiewicz^{1

3}, Ernesta M Meintjes^{1

2

3}, Peter Torre 3rd⁴, Barbara Laughton⁵, Andre J W van der Kouwe⁶, Martha Holmes^{1

2}

Affiliations

¹ Biomedical Engineering Research Centre, Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, Cape Town, South Africa.
² Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
³ Cape Universities Body Imaging Centre, University of Cape Town, Cape Town, South Africa.
⁴ School of Speech, Language, and Hearing Sciences, College of Health and Human Services, San Diego, CA, United States.
⁵ Family Centre for Research with Ubuntu, Department of Paediatrics and Child Health, Stellenbosch University, Stellenbosch, South Africa.
⁶ A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States.

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.

Keywords: HIV; auditory working memory; central auditory system; diffusion tensor imaging; graph theory.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Institute on Deafness And Other Communication Disorders of the National Institutes of Health under Award Number R01DC015984; South African Medical Research Council (SAMRC); South African National Research Foundation (NRF) Grants CPR20110614000019421 and CPRR150723129691; and the NRF/DST South African Research Chairs Initiative; Support for the CHER study, which provided the infrastructure for the neurodevelopmental study, was provided by the US National Institute of Allergy and Infectious Diseases through the CIPRA network, Grant U19 AI53217; the Departments of Health of the Western Cape and Gauteng, South Africa; and GlaxoSmithKline/Viiv Healthcare. Additional support was provided with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States Department of Health and Human Services, under Contract No. HHSN272200800014C.