Objectives: Permanent threshold elevation after noise exposure, ototoxic drugs or aging is caused by loss of sensory cells; however, animal studies show that hair cell loss is often preceded by degeneration of synapses between sensory cells and auditory nerve fibers. The silencing of these neurons, especially those with high thresholds and low spontaneous rates, degrades auditory processing and may contribute to difficulties understanding speech in noise. Although cochlear synaptopathy can be diagnosed in animals by measuring suprathreshold auditory brainstem responses, its diagnosis in humans remains a challenge. In mice, cochlear synaptopathy is also correlated with measures of middle-ear muscle (MEM) reflex strength, possibly because the missing high-threshold neurons are important drivers of this reflex. We hypothesized that measures of the MEM reflex might be better than other assays of peripheral function in predicting difficulties hearing in difficult listening environments in human subjects. Design:We recruited 165 normal-hearing healthy subjects, between the ages of 18 and 63, with no history of ear or hearing problems, no history of neurologic disorders and unremarkable otoscopic examinations. Word recognition in quiet and in difficult listening situations was measured in four ways: using isolated words from the NU-6 corpus with either a) 0 dB signal-to noise, b) 45% time compression with reverberation, or c) 65% time compression with reverberation and d) with a modified version of the QuickSIN. Audiometric thresholds were assessed at standard and extended high frequencies (EHFs). Outer hair cell function was assessed by distortion product otoacoustic emissions (DPOAEs). Middle-ear function and reflexes were assessed using three methods: the acoustic reflex threshold as measured clinically, wideband tympanometry as measured clinically and a custom wideband method that uses a pair of click probes flanking an ipsilateral noise elicitor. Other aspects of peripheral auditory function were

Hearing loss caused by noise exposure, ototoxic drugs or aging results from the loss of sensory cells, as reflected in audiometric threshold elevation. Animal studies show that loss of hair cells can be preceded by loss of auditory-nerve peripheral synapses, which likely degrades auditory processing. While this condition, known as cochlear synaptopathy, can be diagnosed in mice by a reduction of suprathreshold cochlear neural responses, its diagnosis in humans remains challenging. To look for evidence of cochlear nerve damage in normal hearing subjects, we measured their word-recognition performance in difficult listening environments and compared them to cochlear function as assessed by otoacoustic emissions and click-evoked electrocochleography. Several electrocochleographic markers were correlated with word scores, whereas distortion product otoacoustic emissions were not. Specifically, the summating potential (SP) was larger, and the cochlear nerve action potential (AP) was smaller in those with the worst word scores. Adding a forward masker or increasing stimulus rate reduced SP in the worst performers, suggesting that this potential includes post-synaptic components as well as hair-cell receptor potentials. Results suggests that some of the variance in word scores among listeners with normal audiometric threshold arises from cochlear neural damage.

Permanent threshold elevation after noise exposure or aging is caused by loss of sensory cells; however, animal studies show that hair cell loss is often preceded by degeneration of the synapses between sensory cells and auditory nerve fibers. Silencing these neurons is likely to degrade auditory processing and may contribute to difficulties understanding speech in noisy backgrounds. Reduction of suprathreshold ABR amplitudes can be used to quantify synaptopathy in inbred mice. However, ABR amplitudes are highly variable in humans, and thus more challenging to use. Since noise-induced neuropathy preferentially targets fibers with high thresholds and low-spontaneous rate, and because phase locking to temporal envelopes is particularly strong in these fibers, measuring envelope following responses (EFRs) might be a more robust measure of cochlear synaptopathy. A recent auditory model further suggests that modulation of carrier tones with rectangular envelopes should be less sensitive to cochlear amplifier dysfunction and therefore a better metric of cochlear neural damage than sinusoidal amplitude modulation. Here, we measure performance scores on a variety of difficult word-recognition tasks among listeners with normal audiograms and assess correlations with EFR magnitudes to rectangular vs. sinusoidal modulation. Higher harmonics of EFR magnitudes evoked by a rectangular-envelope stimulus were significantly correlated with word scores, whereas those evoked by sinusoidally modulated tones did not. These results support previous reports that individual differences in synaptopathy may be a source of speech recognition variability despite the presence of normal thresholds at standard audiometric frequencies.