bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.04.06.716813

HIV-exposure related disruptions in functional and structural connectivity in the central auditory system in adolescence

Madzime, J. S.·Jankiewicz, M.·Meintjes, E. M.·Torre, P.·Laughton, B.·Holmes, M. J.
View original source ↗Export metadata ↓

Abstract

BackgroundChildren who are HIV-exposed but uninfected (CHEU) face elevated risks of hearing loss and language deficits compared to HIV-unexposed peers. The central auditory system (CAS) undergoes substantial maturational changes during adolescence, yet no neuroimaging study has examined its structural or functional integrity in CHEU. Prior work in this cohort identified white matter (WM) alterations in regions adjacent to the CAS at age 7, and reduced auditory working memory in CHEU relative to unexposed children (CHUU). AimTo characterise WM integrity and functional connectivity (FC) of the CAS and related regions in CHEU at age 11, to investigate structural and functional network topology, and to examine associations between imaging outcomes and neurocognitive function. MethodsForty-eight children aged 11-12 (20 CHEU, 28 CHUU) from an ongoing longitudinal neurodevelopmental cohort underwent 3T MRI including diffusion tensor imaging (DTI) and resting-state fMRI (RS-fMRI). CAS regions (cochlear nucleus/superior olivary complex, inferior colliculus [IC], medial geniculate nucleus [MGN], and primary auditory cortex [PAC]) were manually segmented and combined with an automated atlas. DTI probabilistic tractography was performed, extracting FA, MD, AD, RD, fractional number of tracts, and tract volume. FC was computed using Pearson correlations between regional time series. Graph theory measures (degree, strength, transitivity, nodal and local efficiency) were derived for structural and functional networks. RS-fMRI group comparisons used Bayesian multilevel modelling (matrix-based and region-based analyses), while DTI comparisons used linear models with FDR correction. Neurocognitive testing employed the KABC-II. ResultsNo significant group differences in DTI WM metrics (FA, MD, AD, RD) were observed after FDR correction. CHEU demonstrated higher structural nodal strength in the left IC (FDR-significant) and in the bilateral rostral middle frontal cortex (rMFC) and right cuneus. RS-fMRI revealed lower FC between the bilateral IC in CHEU, alongside reduced FC in the left caudate, left hippocampus CA3, left pericalcarine, and left lingual gyrus. CHEU showed higher FC between the left MGN and right precentral, left postcentral, and right rMFC; the right PAC also showed higher FC to the right rMFC and left postcentral gyrus. No significant group differences were observed in functional nodal measures. No significant associations were found between structural or functional imaging outcomes and neurocognitive scores after multiple comparison correction. DiscussionStructural and functional alterations within the CAS were most prominent in the IC, with increased nodal strength in CHEU potentially reflecting compensatory structural connectivity, and reduced interhemispheric FC between the bilateral IC suggesting disrupted auditory integration. Altered FC between the MGN/PAC and cortical regions, including the rMFC and sensorimotor cortices, may reflect differences in top-down auditory processing. The absence of imaging-cognition associations at age 11 suggests that these connectivity differences do not, at this stage, translate into measurable deficits in auditory or language-related neurocognitive performance. ConclusionThis is the first study to examine functional and structural connectivity of the CAS in CHEU children. HIV exposure is associated with subtle but discernible alterations in IC connectivity and in CAS links to cortical regions at age 11, without detectable neurocognitive correlates. Longitudinal follow-up and inclusion of audiological and ART exposure data are needed to clarify the developmental and functional consequences of these findings.

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Madzime, J. S., Jankiewicz, M., Meintjes, E. M., Torre, P., Laughton, B., Holmes, M. J.. 2026-04-09. HIV-exposure related disruptions in functional and structural connectivity in the central auditory system in adolescence. https://doi.org/10.64898/2026.04.06.716813

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Neurodegeneration-inducing macromolecules exit the brain via nanovascular conduits formed by reticular fibroblasts

Accumulation of proteins such as amyloid beta (Abeta), hyperphosphorylated tau and alpha-synuclein within the brain alters neural information processing and causes neurodegeneration(1-3), but how toxic solutes are cleared from the brain remains highly controversial(4,5). Proposed exit routes include efflux across endothelial cells into the blood(6,7), and movement to the pial surface via vasomotion-induced pumping along spaces within arteriolar smooth muscle(8) or via outflow along the perivascular space of ascending venules promoted by water flux through astrocytes (the glymphatic system(9)). From the pial surface of the brain, drainage may continue to dural lymphatics, along the outer sheaths of exiting cranial nerves and across the cribriform plate(10-14). We now report the presence, in mice and humans, of 2 micron diameter conduits that remove fluorescently labelled tau and Abeta from the brain. These conduits form a spatially-organised mesh within the walls of penetrating arterioles and pial arteries, and around the surface of ascending venules and deep cerebral and pial veins. They course through the pial and arachnoid layers to span the CSF space, wrapping the brain and cranial nerves. They are formed of reticular fibroblasts, which label for VE-cadherin(15) and PDGFRalpha(16), the lymphatic markers(17) podoplanin, VEGFR3 and Prox1, and reticular fibroblast extracellular matrix components collagen I and VI(16,18-20). Parenchymal tau drains from the brain at a similar rate via arteriolar conduits and via conduits around venules, arguing against preferential removal by a glymphatic mechanism. In Alzheimer's disease model mice, Abeta is seen traversing these lymph node-like conduits. Modulation of molecular transfer via this route may accelerate or delay cognitive decline, and slowed transfer from arteriolar to pial-arachnoid conduits may initiate cerebral amyloid angiopathy.

neuroscience↗
bioRxiv2026

Analysis of the influence of gradual changes in matrix sentence similarity on neural envelope tracking

Neural tracking of speech is a well-established phenomenon in neuroscience. However, for speech signals with a fixed structure, significant correlations between speech envelopes and neurophysiological representations occur even for unheard sentences. We exploit a structured speech-in-noise matrix hearing test (Oldenburger Sentence Test, OLSA) to systematically quantify the relationship between acoustic sentence similarity and neural tracking. Simultaneous magnetoencephalography (MEG) and 76-channel electroencephalography (EEG) data, including 16 channels positioned directly around the ears (ear-EEG), were recorded from 21 young adults with normal hearing during the presentation of clean-speech audiobooks and OLSA sentences at six signal-to-noise ratios. A linear decoder trained on audiobooks reconstructed OLSA sentence envelopes. Reconstruction accuracies were compared using a linear mixed model across heard (matched) and unheard (mismatched) sentences of varying acoustic similarity. Significant reconstruction accuracies were achieved across MEG, EEG, and ear-EEG for both matched and mismatched sentences. For mismatched sentences, these accuracies gradually increased with their acoustic similarity to the heard speech data. The high similarity between sentences, which is especially prominent in matrix tests, can cause significant spurious tracking for mismatched stimuli. This effect can reach levels comparable to those of matched sentences and can be mistaken for true neural tracking. Robust neural tracking across modalities further supported the established viability of ear-EEG compared to whole-head systems.

neuroscience↗
bioRxiv2026

Seizures and tauopathy following neurotrauma are mediated by prion protein and metabotropic glutamate receptor 5

Traumatic brain injury (TBI) is one of the world's leading causes of death and disability and a major risk factor for dementias. The primary dementia associated with TBI is chronic traumatic encephalopathy (CTE), a neurodegenerative disease classified as a tauopathy, in which toxic tau molecules lead to disease pathologies and degeneration. The processes that lead to tauopathy and subsequent dementia after TBI remain unclear. Here, we built upon the finding that seizures after TBI may be a mechanism leading to tauopathy, by dissecting the functions of the metabotropic glutamate receptor 5 - cellular prion protein (mGluR5-PrPC) pathway. We delivered TBI to larval in a blast paradigm, and quantified aggregation of Tau via a genetically-encoded Tau-GFP fusion reporter. Zebrafish larvae lacking prp2 (homolog of mammalian cellular Prion Protein, PrPC) displayed a 168% increase in post-traumatic seizures activity after TBI. An mGluR5 agonist (CHPG) reduced post-traumatic seizures, whereas an mGluR5 antagonist (MPEP) increased post-traumatic seizures. Moreover, agonizing mGluR5 reduced tau aggregation and antagonizing mGluR5 increased tau burden. Larvae seizing from convulsants, rather than TBI, were treated with CHPG/MPEP and provided a similar pattern of outcomes, suggesting seizures may be a factor needed for mGluR5 activity to influence tau aggregation. The PrPC-mGluR5 pathway is proposed as one candidate pathomechanism linking TBI to subsequent seizures and tauopathy, and thus it warrants investigation as a target for prophylactic interventions.

neuroscience↗