Predicting Auditory Nerve Survival Using the Compound Action Potential

Abstract

Advances in cochlear hair-cell regeneration, neural regeneration, and genetic therapy encourage continued development of diagnostic tests that can accurately specify the appropriate target within the cochlea and auditory nerve for delivery of therapeutic agents. In this study, we test the hypothesis that the morphology of the acoustically evoked compound action potential (CAP) may reflect the condition of the auditory nerve in individuals with sensorineural hearing loss. CAPs to tone burst stimuli at octave frequencies from 1 to 16 kHz were recorded at low- to high-stimulus levels from sedated Mongolian gerbils with partial lesions of the auditory nerve (n = 10). Distortion-product otoacoustic emissions were measured to ensure preservation of normal outer hair-cell function. CAPs were analyzed with conventional measures of N1 latency and amplitude and by fitting the CAPs with a mathematical model that includes a parameter (N) representing the number of nerve fibers contributing to the CAP and a parameter (f) representing the oscillation frequency of the CAP waveform. Nerve fiber density and percent normal nerve area were estimated from cross-sections of the auditory nerve bundle. Despite substantial lesions in the auditory nerve, CAP thresholds remained within normal or were only moderately elevated and were not correlated with histological measures of nerve fiber density and normal nerve area. At high-stimulus levels, the model parameter N was strongly correlated with nerve fiber density for three of the five test frequencies and with normal nerve area for all five test frequencies. Correlations between N1 amplitude measures at high-stimulus levels and our histological measures were also significant for the majority of test frequencies, but they were generally weaker than the correlations for the model parameter N. The model parameter f, at low- and high-stimulus levels, was also positively correlated with measures of normal nerve area. Consistent with previous findings, physiological measures of threshold were not correlated with partial lesions of the auditory nerve. The model parameter N at high-stimulus levels was strongly correlated with normal nerve area suggesting, that it is a good predictor of auditory nerve survival. The model parameter N also seemed to be a better predictor of the condition of the auditory nerve than the conventional measure of N1 amplitude. Because the model parameter f was correlated with normal nerve area at low- and high-stimulus levels, it may provide information on the functional status of the auditory nerve.