Origin of cubic difference tones generated by high-intensity stimuli: effect of ischemia and auditory fatigue on the gerbil cochlea.

Cubic difference tone (CDT) otoacoustic emissions are thought to arise from the feedback loop allowing outer hair cells to enhance the sensitivity and tuning of the organ of Corti. The existence of residual CDTs during complete cochlear ischemia is therefore disturbing. That stimulus intensities must exceed 50-60 dB SPL for residual CDTs to be recorded and for level notches to be present in CDT growth functions is often cited as evidence for a two-component, "active/passive" model: one component, the residual one, would originate from a passive, hardly vulnerable mechanism and thus be unsuitable for hearing screening purposes. This model was probed in gerbil ears after complete interruption of the cochlear blood flow. Cochlear potentials and CDTs were controlled simultaneously through continuous monitoring of CDT level and phase for 50 and 60 dB SPL stimuli and group-delay measurements. After a clear initial decay, CDT levels elicited at 60 dB SPL plateaued for several minutes at about 20 dB below initial level, and when early level notches were observed, CDT phase changes remained minor. The CDT group delays decreased by less than 30%. Later CDT level notches were associated with sharp phase reversals but the similarity between CDT characteristics before and after a notch was hardly consistent with a two-component interpretation. When mild sound overexposure (pure tone, 90-95 dB SPL, 15-30 min) had been performed prior to ischemia, little or no ischemic CDT came from the frequency bands where auditory fatigue had been detected (within 1 kHz), irrespective of the stimulus intensity. It suggests that instead of being passive, residual ischemic CDTs were vulnerable and produced according to a near-normal tonotopy by the same mechanisms that were sensitive to auditory fatigue. All the results lined up with a simple feedback model of cochlear function assuming a single CDT source related to mechano-electrical transduction in outer hair cells. More parsimonious than a two-component model, it posits that although early stages of ischemia dramatically impair the overall performance of the cochlea, the nonlinear mechanical stages responsible for the existence of CDTs keep working albeit at higher intensities.