Evidence of functional connectivity disruptions between auditory and non-auditory regions in adolescents living with HIV

Joanah Madzime^1,2*Marcin Jankiewicz^1,2,3Ernesta Meintjes^1,2,3Peter Torre⁴Barbara Laughton⁵Martha Holmes^1,2,6,7

• ¹Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa
• ²Division of Biomedical Engineering, Faculty of Health Sciences, University of Cape Town, Cape Town, Western Cape, South Africa
• ³Cape Universities Body Imaging Centre, University of Cape Town, Cape Town, South Africa
• ⁴School of Speech, Language and Hearing Science, College of Health and Human Services, San Diego State University, San Diego, California, United States
• ⁵Family Centre for Research with Ubuntu (FAMCRU), Stellenbosch University, Cape Town, South Africa
• ⁶Department of Biomedical Physiology and Kinesiology, Faculty of Science, Simon Fraser University, Burnaby, British Columbia, Canada
• ⁷Simon Fraser University, Burnaby, British Columbia, Canada

Children living with perinatally acquired HIV (CPHIV) demonstrate hearing impairments and language processing delays even in the presence of combination antiretroviral therapy (cART). Investigations on the effect of HIV on the auditory system have predominantly focused on the peripheral auditory system. Additionally, language processing requires the efficient interaction between central auditory system (CAS) brain regions and non-auditory regions. Investigating the functional connectivity (FC) within the CAS and between the CAS and non-auditory regions may reveal the influence of HIV on regions involved in auditory function. Within a Bayesian stastical framework, we used resting-state functional magnetic resonance imaging to map FC in the CAS as well as between CAS regions and non-auditory regions of 11-year-old CPHIV. Graph theory was used to investigate the regional effects of HIV on brain network properties. We explored the relationships between FC and neurocognitive outcomes. We hypothesized that CPHIV would show disruptions in FC between CAS regions as well as between CAS and non-auditory regions. Secondly, we hypothesized that in CPHIV, regional brain network properties would be altered compared to their uninfected peers (CHUU). Finally we hypothesized that FC and functional network regional outcomes would be related to neurocognitive outcomes. Our investigation revealed lower FC of the primary auditory cortex (PAC) in CPHIV as well as disruptions in FC between CAS regions and non-auditory regions including hippocampal sub-regions, the lingual gyri and basal ganglia. Functional network analysis reavealed lower nodal degree and efficiency in CAS regions including the cochlear nucleus/superior olivary complex and the inferior colliculus. We also report associations between the nodal efficiency of middle temporal and superior frontal regions and delayed recall, a neurocognitive marker of working memory, present in CHUU but not in CPHIV. Our results demonstrate FC alterations in the PAC and between CAS regions and non-auditory regions involved in limbic, visual and motor processing, as well as disruptions to the regional properties of the CAS regions in the functional brain network. These results provide insight into the state of the CAS FC in the presence of HIV and its possible role in the hearing and language impairments seen in this population.