Normal Audiogram Does Not Confirm Intact Cochlear Amplification: Compressive Nonlinearity Reveals Incipient Cochlear...

The cochlear amplifier, mediated by outer hair cell-driven nonlinear mechanics, enables the remarkable sensitivity and dynamic range of human hearing. Cochlear compression is a defining feature of this active process and is known to deteriorate with hearing loss. Among individuals with normal audiograms, cochlear compression is generally presumed to be invariant, an assumption that has not been systematically examined. If incipient cochlear changes precede measurable threshold shifts, variability in compressive nonlinearity may represent an early peripheral correlate of emerging dysfunction and a potential mechanistic contributor to auditory processing differences. Whether cochlear compression varies meaningfully among individuals with normal audiograms, and what such variability reveals about the earliest stages of cochlear dysfunction, remains unknown. Here, we quantified compressive nonlinearity using distortion-product otoacoustic emission (DPOAE) input/output functions with stringent signal-to-noise criteria, applying covariate-controlled mixed-effects models within a dimensional framework that treated compression as a continuous outcome to isolate structured individual differences (n=144 ears, male=46, female=98). Compression metrics demonstrated substantial interindividual variability despite normal hearing thresholds. Subtle differences in standard-frequency thresholds were associated with variations in cochlear gain. Extended high-frequency sensitivity, an index of basal cochlear integrity, showed additional associations with DPOAE input/output function, implicating basal vulnerability in shaping cochlear nonlinearity. Age-related effects were detectable even within a restricted young-adult cohort, indicating that cochlear operating characteristics may begin to diverge early in adulthood. These findings challenge the assumption of invariant compression in normal hearing and suggest that alterations in cochlear nonlinear processing may reflect incipient cochlear dysfunction that precedes overt hearing loss.Significance Statement Hearing has traditionally been defined by audiometric thresholds, with normal results interpreted as evidence of an intact auditory periphery. This study challenges that assumption by demonstrating meaningful physiological variation within the clinically normal-hearing range. Specifically, cochlear nonlinear amplification, the core mechanism regulating sensitivity and dynamic range, differs across individuals and is associated with subtle biological factors, including age-related variation detectable in early adulthood. These findings indicate that cochlear function reflects a continuum of underlying biological states, some of which may represent incipient dysfunction preceding measurable hearing loss.