Auditory neural processing in children living with HIV uncovers underlying central nervous system dysfunction

Abstract

Objective: Central nervous system (CNS) damage from HIV infection or treatment can lead to developmental delays and poor educational outcomes in children living with HIV (CLWH). Early markers of central nervous system dysfunction are needed to target interventions and prevent life-long disability. The frequency following response (FFR) is an auditory electrophysiology test that can reflect the health of the central nervous system. In this study, we explore whether the FFR reveals auditory central nervous system dysfunction in CLWH. Study design: Cross-sectional analysis of an ongoing cohort study. Data were from the child's first visit in the study. Setting: The infectious disease center in Dar es Salaam, Tanzania. Methods: We collected the FFR from 151 CLWH and 151 HIV-negative children. To evoke the FFR, three speech syllabi (/da/, /ba/, /ga/) were played monaurally to the child's right ear. Response measures included neural timing (peak latencies), strength of frequency encoding (fundamental frequency and first formant amplitude), encoding consistency (inter-response consistency), and encoding precision (stimulus-to-response correlation). Results: CLWH showed smaller first formant amplitudes (P < 0.0001), weaker inter-response consistencies (P < 0.0001) and smaller stimulus to response correlations (P < 0.0001) than FFRs from HIV-negative children. These findings generalized across the three speech stimuli with moderately strong effect sizes (partial η 2 ranged from 0.061 to 0.094). Conclusion: The FFR shows auditory central nervous system dysfunction in CLWH. Neural encoding of auditory stimuli was less robust, more variable, and less accurate. As the FFR is a passive and objective test, it may offer an effective way to assess and detect central nervous system function in CLWH.