Peripheral-central interactions shape the decoupling between auditory brainstem response amplitudes and auditory thresholds during aging and noise exposure: a computational modeling study.

Age-related and noise-induced hearing loss reflect progressive cochlear degeneration and adaptive changes in central auditory pathways, yet their joint effects on auditory brainstem response (ABR) amplitudes and auditory thresholds remain unclear. We developed the Auditory Homeostatic Dynamics Model (AHDM), a three-state ordinary differential equation model of hair-cell sensory function, cochlear synaptic integrity, and activity-dependent central compensation across low-, mid-, and high-frequency domains. The model includes multiplicative peripheral gating, constrained ABR outputs, and targeted peripheral and central ablations. Robustness was assessed across 4,096 parameter sets. The aging component was calibrated to published data and evaluated without refitting in independent longitudinal and noise-exposure datasets. Central compensation robustly increased relative Wave II preservation and attenuated threshold expression, while neural-threshold dissociation depended on the balance between peripheral compartments. Calibration reduced balanced prediction error by 78.2%. Transfer to the independent non-exposed 2019 cohort improved Wave I and Wave II errors by 65.5% and 72.9%, although decline was predicted prematurely. Protocol-mapped simulations captured cumulative exposure effects in 2019, and persistent threshold shifts in 2020, with a root mean square error of 5.60 dB in untreated animals. The results identify parameter-dependent peripheral dissociation, robust downstream central modulation, and a defined empirical domain for the AHDM.