Noise-induced cochlear synaptopathy has been demonstrated in numerous rodent studies. In these animal models, the disorder is characterized by a reduction in amplitude of wave I of the auditory brainstem response (ABR) to high-level stimuli, whereas the response at threshold is unaffected. The aim of the present study was to determine if this disorder is prevalent in young adult humans with normal audiometric hearing. One hundred and twenty six participants (75 females) aged 18–36 were tested. Participants had a wide range of lifetime noise exposures as estimated by a structured interview. Audiometric thresholds did not differ across noise exposures up to 8 kHz, although 16-kHz audiometric thresholds were elevated with increasing noise exposure for females but not for males. ABRs were measured in response to high-pass (1.5 kHz) filtered clicks of 80 and 100 dB peSPL. Frequency-following responses (FFRs) were measured to 80 dB SPL pure tones from 240 to 285 Hz, and to 80 dB SPL 4 kHz pure tones amplitude modulated at frequencies from 240 to 285 Hz (transposed tones). The bandwidth of the ABR stimuli and the carrier frequency of the transposed tones were chosen to target the 3–6 kHz characteristic frequency region which is usually associated with noise damage in humans. The results indicate no relation between noise exposure and the amplitude of the ABR. In particular, wave I of the ABR did not decrease with increasing noise exposure as predicted. ABR wave V latency increased with increasing noise exposure for the 80 dB peSPL click. High carrier-frequency (envelope) FFR signal-to-noise ratios decreased as a function of noise exposure in males but not females. However, these correlations were not significant after the effects of age were controlled. The results suggest either that noise-induced cochlear synaptopathy is not a significant problem in young, audiometrically normal adults, or that the ABR and FFR are relatively insensitive to this disorder in young humans, although it is possible that the effects become more pronounced with age.

People with high-frequency sensorineural hearing loss differ in the benefit they gain from amplification of high frequencies when listening to speech. Using vowel-consonant-vowel (VCV) stimuli in quiet that were amplified and then low pass filtered with various cutoff frequencies, Vickers et aL [J. Acoust. Soc. Am. 110, 1164-1175 (2001)] found that the benefit from amplification of high-frequency components was related to the presence or absence of a cochlear dead region at high frequencies. For hearing-impaired subjects without dead regions, performance improved with increasing cutoff frequency up to 7.5 kHz (the highest value tested). Subjects with high-frequency dead regions showed no improvement when the cutoff frequency was increased above about 1.7 times the edge frequency of the dead region. The present study was similar to that of Vickers et al. but used VCV stimuli presented in background noise. Ten subjects with high-frequency hearing loss, including eight from the study of Vickers et al., were tested. Five had dead regions starting below 2 kHz, and five had no dead regions. Speech stimuli at a nominal level of 65 dB were mixed with spectrally matched noise, amplified according to the "Cambridge" prescriptive formula for each subject and then low pass filtered. The noise level was chosen separately for each subject to give a moderate reduction in intelligibility relative to listening in quiet. For subjects without dead regions, performance generally improved with increasing cutoff frequency up to 7.5 kHz, on average more so in noise than in quiet. For most subjects with dead regions, performance improved with cutoff frequency up to 1.5-2 times the edge frequency of the dead region, but hardly changed with further increases. Calculations of speech audibility using a modified version of the articulation index showed that application of the Cambridge formula was at least partially successful in making high-frequency components of the speech audible for subjects with dead regions, and that such subjects often failed to benefit from increased audibility of the speech at high frequencies.

Although there is strong histological evidence for age-related synaptopathy in humans, evidence for the existence of noise-induced cochlear synaptopathy in humans is inconclusive. Here, we sought to evaluate the relative contributions of age and noise exposure to cochlear synaptopathy using a series of electrophysiological and behavioral measures. We extended an existing cohort by including 33 adults in the age range 37 to 60, resulting in a total of 156 participants, with the additional older participants resulting in a weakening of the correlation between lifetime noise exposure and age. We used six independent regression models (corrected for multiple comparisons), in which age, lifetime noise exposure, and high-frequency audiometric thresholds were used to predict measures of synaptopathy, with a focus on differential measures. The models for auditory brainstem responses, envelope-following responses, interaural phase discrimination, and the co-ordinate response measure of speech perception were not statistically significant. However, both age and noise exposure were significant predictors of performance on the digit triplet test of speech perception in noise, with greater noise exposure (unexpectedly) predicting better performance in the 80 dB sound pressure level (SPL) condition and greater age predicting better performance in the 40 dB SPL condition. Amplitude modulation detection thresholds were also significantly predicted by age, with older listeners performing better than younger listeners at 80 dB SPL. Overall, the results are inconsistent with the predicted effects of synaptopathy.

An estimate of lifetime noise exposure was used as the primary predictor of performance on a range of behavioral tasks: frequency and intensity difference limens, amplitude modulation detection, interaural phase discrimination, the digit triplet speech test, the co-ordinate response speech measure, an auditory localization task, a musical consonance task and a subjective report of hearing ability. One hundred and thirty-eight participants (81 females) aged 18–36 years were tested, with a wide range of self-reported noise exposure. All had normal pure-tone audiograms up to 8 kHz. It was predicted that increased lifetime noise exposure, which we assume to be concordant with noise-induced cochlear synaptopathy, would elevate behavioral thresholds, in particular for stimuli with high levels in a high spectral region. However, the results showed little effect of noise exposure on performance. There were a number of weak relations with noise exposure across the test battery, although many of these were in the opposite direction to the predictions, and none were statistically significant after correction for multiple comparisons. There were also no strong correlations between electrophysiological measures of synaptopathy published previously and the behavioral measures reported here. Consistent with our previous electrophysiological results, the present results provide no evidence that noise exposure is related to significant perceptual deficits in young listeners with normal audiometric hearing. It is possible that the effects of noise-induced cochlear synaptopathy are only measurable in humans with extreme noise exposures, and that these effects always co-occur with a loss of audiometric sensitivity.

Cochlear synaptopathy (or hidden hearing loss), due to noise exposure or aging, has been demonstrated in animal models using histological techniques. However, diagnosis of the condition in individual humans is problematic because of (a) test reliability and (b) lack of a gold standard validation measure. Wave I of the transient-evoked auditory brainstem response is a noninvasive electrophysiological measure of auditory nerve function and has been validated in the animal models. However, in humans, Wave I amplitude shows high variability both between and within individuals. The frequency-following response, a sustained evoked potential reflecting synchronous neural activity in the rostral brainstem, is potentially more robust than auditory brainstem response Wave I. However, the frequency-following response is a measure of central activity and may be dependent on individual differences in central processing. Psychophysical measures are also affected by intersubject variability in central processing. Differential measures may help to reduce intersubject variability due to unrelated factors. A measure can be compared, within an individual, between conditions that are affected differently by cochlear synaptopathy. Validation of the metrics is also an issue. Comparisons with animal models, computational modeling, auditory nerve imaging, and human temporal bone histology are all potential options for validation, but there are technical and practical hurdles and difficulties in interpretation. Despite the obstacles, a diagnostic test for hidden hearing loss is a worthwhile goal, with important implications for clinical practice and health surveillance.

Psychophysical tuning curves (PTCs) can be used to assess the frequency selectivity of the auditory system and to detect and delimit "dead regions" in the cochlea. However, the traditional method for determining PTCs takes too long for use in clinical practice. We evaluated a fast method for determining PTCs, using a band of noise that sweeps in centre frequency and a Békésy method to adjust the masker level required for threshold. The shapes of the PTCs were similar for the fast and traditional methods, for both normally hearing and hearing-impaired subjects. Rates of change of masker level of 2 dB/s or less gave the most reliable results. A relatively wide bandwidth (20 percent of the signal frequency or 320 Hz, whichever is the smaller) was needed to minimise the influence of beat detection. When the signal frequency fell within a dead region, the fast method gave PTCs with shifted tips.

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Todd et al. (2014) have recently demonstrated the presence of vestibular dependent changes both in the morphology and in the intensity dependence of auditory evoked potentials (AEPs) when passing through the vestibular threshold as determined by vestibular evoked myogenic potentials (VEMPs). In this paper we extend this work by comparing left vs. right ear stimulation and by conducting a source analysis of the resulting evoked potentials of short and long latency. Ten healthy, right-handed subjects were recruited and evoked potentials were recorded to both left- and right-ear sound stimulation, above and below vestibular threshold. Below VEMP threshold, typical AEPs were recorded, consisting of mid-latency (MLR) waves Na and Pa followed by long latency AEPs (LAEPs) N1 and P2. In the supra-threshold condition, the expected changes in morphology were observed, consisting of: (1) short-latency vestibular evoked potentials (VsEPs) which have no auditory correlate, i.e. the ocular VEMP (OVEMP) and inion response related potentials; (2) a later deflection, labelled N42/P52, followed by the LAEPs N1 and P2. Statistical analysis of the vestibular dependent responses indicated a contralateral effect for inion related short-latency responses and a left-ear/right-hemisphere advantage for the long-latency responses. Source analysis indicated that the short-latency effects may be mediated by a contralateral projection to left cerebellum, while the long-latency effects were mediated by a contralateral projection to right cingulate cortex. In addition we found evidence of a possible vestibular contribution to the auditory T-complex in radial temporal lobe sources. These last results raise the possibility that acoustic activation of the otolith organs could potentially contribute to auditory processing.