Auditory brainstem responses in younger and older adults for broadband noises separated by a silent gap.

Wave V of the auditory brainstem response was measured to two 50-ms broadband noise bursts separated by silent gaps of varied duration (4, 8, 32, or 64 ms) for younger and older adults with normal hearing. All subjects had measurable wave V responses to the first noise burst. However, for the second noise burst, three of eight older adults did not have responses with gap durations of 4 and 8 ms, and one of eight younger adults did not have a measurable response with a gap duration of 4 ms. When responses were present for older adults, latencies were similar to those of younger subjects but amplitudes were smaller. These results suggest age-related deficits in gap detection at the level of the brainstem in a group of aged subjects with no threshold elevation. Results are similar to those of Boettcher et al. (1996) using an identical paradigm in young and aged Mongolian gerbils.

The amplitude-modulation following response in young and aged human subjects.

The amplitude-modulation following response (AMFR) is a steady-state auditory response which may be an objective measure of intensity discrimination. Aged subjects with normal hearing have poorer intensity discrimination for low-frequency tones measured behaviorally, which would predict poorer AMFRs for low-frequency carriers. Experiment 1 was designed to assess age-related differences in AMFR characteristics. Response amplitudes were not significantly different among the young and aged groups for either carrier frequency (520 or 4000 Hz) or modulation depth (0--100%). Response phase did not vary systematically among groups. These results suggest that the AMFR may not be directly comparable to behavioral measures of intensity discrimination in aged subjects with normal hearing. To assess the contribution of high-frequency hearing loss on the AMFR in aged subjects, Experiment 2 compared AMFR amplitudes in aged subjects and in young subjects under the condition of high-pass masking. The amplitude of the AMFR was reduced at 520 Hz for both aged subjects and masked young subjects compared to unmasked young subjects, suggesting that reduced amplitudes in aged subjects with high-frequency hearing loss were associated with threshold elevations. Furthermore, the results suggest that the base of the cochlea contributes to the AMFR for low carrier frequencies.

Effects of nimodipine on noise-induced hearing loss.

The effects of nimodipine, a calcium channel blocker, on noise-induced hearing loss were examined in gerbils. Animals were implanted subcutaneously with a timed-release pellet containing either nimodipine (approximately 10 mg/kg/day) or placebo and exposed to either 102 or 107 dBA noise. Serum levels were tested in two subjects and were in the range known to protect humans from cerebral artery vasospasm and ischemia-related neurologic deficits. Nimodipine and control groups had similar amounts of noise-induced (a) permanent threshold shift; (b) reductions in distortion product otoacoustic emissions; (c) reductions in tuning and suppression of the compound action potential; and (d) loss of outer hair cells. The results suggest that nimodipine, at a dose which results in clinically relevant serum levels, does not provide protection from the effects of moderately intense noise exposures.

Effectiveness of intermittent and continuous acoustic stimulation in preventing noise-induced hearing and hair cell loss.

Resistance to noise-induced hearing loss (NIHL) was studied in gerbils exposed either to intermittent or continuous low-level noise prior to an intense noise. Auditory-evoked brainstem response (ABR) thresholds, distortion product otoacoustic emissions (DPOAEs), Q10dB values from compound action potential (CAP) tuning curves, and outer hair cell (OHC) loss were measured for each group. Subjects were exposed to A-weighted noise (octave band noise centered at 2 kHz) on an intermittent (80 dB, 6 h/day) or continuous schedule (74 dB, 24 h/day) for 10 days, allowed to rest in quiet for 2 days, then exposed to intense A-weighted noise (107 dB, 24 h/day) for 2 days. A "noise-only" group was exposed only to the intense noise. Gerbils exposed in both the "intermittent" and "continuous" groups had less (15-30 dB) temporary threshold shift (TTS) than those in the noise-only group. In addition, the continuous group had less (10-15 dB) permanent threshold shift (PTS) than the other groups. These data suggest that resistance to NIHL is evident in both the intermittent and continuous groups when TTS is measured, but resistance to PTS is afforded only by the continuous paradigm. Both paradigms decreased OHC loss as compared to the noise-only group, with the continuous paradigm being most effective. However, neither paradigm conserved DPOAE amplitudes or tuning curve Q10dB values relative to the noise-only group.

Interaction of noise-induced hearing loss and presbyacusis.

A medical-legal and scientific topic of longstanding interest is the interaction between presbyacusis and noise-induced permanent threshold shift (NIPTS). Current medical-legal practices as well as international standard, ISO 1999 International Organization for Standards: Acoustics: Determination of Occupational Noise Exposure and Estimation of Noise-Induced Hearing Impairment. ISO 1999. Geneva, International for Standards, 1990 assume that NIPTS and hearing loss caused by the aging process add in dB. Results of laboratory studies with animals are inconsistent in their support of the "additivity assumption". When intense, short-duration exposures are used, the predictions of the combined effects of noise and age are too large. The additivity model appears to be supported with long-duration exposures, but we question the accuracy of such predictions. The animal studies reviewed here suggest that the allocation of hearing loss in an older individual into a noise component and an aging component is much more complex than "additivity in dB".

Decline in the endocochlear potential corresponds to decreased Na,K-ATPase activity in the lateral wall of quiet-aged gerbils.

The ion transport-mediating enzyme, Na,K-ATPase, is abundantly present in the cochlear lateral wall. This enzyme is essential for the generation and maintenance of the endocochlear potential. Diminished enzyme activity has been observed previously in the lateral wall of quiet-aged gerbils. The present study was designed to investigate the impact of the age-related decline in Na,K-ATPase specific activity upon auditory function. Measures of the resting endocochlear potential value and the level of Na,K-ATPase specific activity were made in cochleae obtained from gerbils aged in quiet conditions. Analysis revealed a high degree of correspondence between the level of lateral wall Na,K-ATPase specific activity and the value of the endocochlear potential measured in the round window/turn 1 region of the cochlea. Nonlinear regression models showed a strong relationship between the age-related reductions in enzyme activity and the magnitude of the endocochlear potential. The data suggest that during metabolic presbyacusis a decrease in Na,K-ATPase specific activity can explain most, but not all, of the decline in the endocochlear potential.

Interaction of noise-induced permanent threshold shift and age-related threshold shift.

Current medical-legal practices as well as an international standard (ISO 1999) assume the permanent threshold shifts produced by exposure to noise add (in dB) to the threshold shifts caused by increased chronological age (presbyacusis). This assumption, known as the additivity rule, was tested in an animal model. Mongolian gerbils, born and raised in a quiet vivarium, were exposed at age 18 months to a 3.5-kHz pure tone for 1 h at 113 dB SPL. At 6-weeks post-exposure, permanent threshold shifts in the exposed ear were approximately 20 dB in the 4- to 8-kHz region. Thresholds in the nonexposed, control ear were unaffected by the exposure. Animals were then allowed to age in the quiet vivarium until age 36 months and then were retested. Thus in a given animal, aging-only effects were assessed in one ear (internal control) and noise-plus-aging effects were assessed in the other (test) ear. A second control was mean age-related threshold shift measured in 48 gerbils who were born and raised in the quiet vivarium. This group is referred to as a non-noise-exposed population (population control). Using the additivity rule, predictions with either the internal or population control significantly overestimated noise-plus-aging effects. Use of the ISO 1999 compression factor reduced the overestimations by 0-5 dB. The intensity rule produced the most accurate predictions. These results suggest that the interaction of noise-induced permanent threshold shift and age-related threshold shift is not straightforward and that current medical-legal methods using the additivity rule overestimate the contribution of "noise effects".

Auditory evoked potentials in aged gerbils: responses elicited by noises separated by a silent gap.

The compound action potential (CAP) and the auditory brainstem response (ABR; waves ii and iv) were recorded in young (4-8 month) and aged (33-37 month) gerbils using a paradigm similar to that used in some psychophysical studies of gap detection (a pair of identical low-pass noises separated by a silent gap). Response amplitudes were analyzed in terms of absolute amplitudes and the 'amplitude ratio' (the amplitude of the response to the second noise of a pair divided by that to the first). Response latencies were analyzed in terms of the absolute latencies as well as the 'latency shift' (the latency of the response to the second noise minus that to the first). Response amplitudes were much smaller in the aged subjects for both the first and second stimuli of a pair. There were minimal changes in amplitude ratios across age for both the CAP and ABR. Absolute latencies were similar between groups for the first stimulus of a pair, but latencies to wave iv were much longer for the aged subjects when the gap was short. Thus, the latency shift for the aged group was much longer for wave iv in the aged compared to the young group, but were similar between groups for the CAP or wave ii of the ABR. The results suggest that there may be changes in coding of temporal information in the auditory brainstem of aged gerbils which are not a direct result of abnormal temporal processing in the auditory periphery.

Age-related loss of activity of auditory-nerve fibers.

1. Characteristic frequencies (CF), spontaneous rates (SR), and thresholds were recorded from single fibers in the auditory nerves of gerbils aged for 36 mo in a quiet vivarium. The data from the quiet-aged animals were compared with similar data obtained previously from young controls. Fibers were classified as "low-SR" if their spontaneous rates were < or = 18 spikes/s and "high SR" for higher rates. 2. For CFs > 6 kHz, the percentage of low-SR fibers contacted declined from 57% of the population in young gerbils to 29% in the aged gerbils. This population change is statistically significant (P < 0.01). At CFs < 6 kHz, the population demographics did not change significantly with age, with the low-SR fibers comprising 30 and 39% of the population, respectively, for the young and aged animals. 3. To further test the hypothesis that low-SR fibers with CFs > 6 kHz become less active with age, additional experiments were conducted to examine the recovery of the compound action potential (CAP) response from prior high-level stimuli. Previous work has shown that the CAP recovery curve has two segments: a fast segment associated with the high-SR fibers and a slow segment associated with the low-SR fibers. The curves obtained from quiet aged gerbils show a faster recovery than young controls for probe tones at 8 and 16 kHz, but not at 2 and 4 kHz. Thus these results agree with our single-fiber data indicating that there is a loss of low-SR activity for CFs > 6 kHz in the aged animals. 4. Low-SR fibers typically have larger dynamic ranges than those of high-SR fibers, are better able to preserve information concerning stimulus timing and amplitude modulation, and their responses are more robust in the presence of masking noise. Moreover, low-SR fibers are likely inputs to the crossed-olivocochlear reflex, a reflex that serves an antimasking role in the detection of sounds in a binaural noise field. If true for humans, the loss of the low-SR system could explain many of the hearing deficits often seen in older individuals; e.g., decreased ability to understand speech in noise, changes in masking level differences, and decreased ability to localize sound sources using binaural cues.

Diltiazem does not protect the ear from noise-induced hearing loss in mongolian gerbils.

Recent data suggest that diltiazem reduces noise-induced hearing loss. Our study was designed to replicate and extend the results of Maurer et al. by using the gerbil as a model. In experiment A, subjects received diltiazem (30 mg/kg/day intraperitoneally) or saline for 3 days. After peripheral thresholds were measured, each subject was exposed to a 4-kHz tone (90-dB sound pressure level) for 20 minutes. Similar amounts of temporary threshold shifts (ITS) were measured in the saline and diltiazem groups. In experiment B, subjects were given saline or diltiazem (30 mg/kg/day intraperitoneally) for 3 days and then exposed to an octave band of noise centered at 4 kHz for 5 days, during which time the subjects continued to receive the drug or saline. The TTS and permanent threshold shifts were similar in the two groups. Measures of cochlear nonlinearities also showed no effect of diltiazem, suggesting that diltiazem does not protect the ear from the effects of noise.

Distortion-product otoacoustic emissions in Mongolian gerbils with resistance to noise-induced hearing loss.

Distortion-product otoacoustic emissions (DPOAEs) and the endocochlear potential (EP) were recorded in adult Mongolian gerbils exposed to noise for either 1 or 12 days. The exposure was an octave band of noise centered at 4 kHz at 80 dB SPL with a duty cycle of 6 h on, 18 h off. A previous study showed that a single such exposure causes 20-50 dB of temporary threshold shift (TTS) in the neural response at 4-8 kHz, but that the TTS is reduced to less than 10 dB following 12 daily exposures [Boettcher, J. Acoust. Soc. Am. 94, 3207-3214 (1993)]. This reduction in TTS is commonly referred to as resistance to noise-induced hearing loss (NIHL). To further analyze whether resistance to NIHL is caused by changes in the outer hair cell (OHC) system or the lateral wall system (or both), DPOAEs and EPs were measured in the exposed ears. The amplitudes of DPOAEs were significantly reduced in the frequency region from 4 to 10 kHz in subjects exposed to noise for 1 day, but were relatively normal in subjects exposed for 12 days. DPOAE amplitudes from frequency regions below the spectrum of the exposure were similar across the exposure and control groups except at the low-frequency edge of the noise where DPOAE amplitudes were consistently higher than normal in the exposed animals. The EP values in both exposure groups were not reduced from normal, unexposed levels. Thus there was no causal relationship between changes in the EP and the reduction of the DPOAE amplitudes. These data suggest that the development of resistance to noise is related to an initial depression of OHC activity followed by a recovery of activity to a stable level, despite an ongoing exposure.

Masking of auditory brainstem responses in young and aged gerbils.

Auditory brainstem responses (ABR) were recorded in the presence of low-pass (1 kHz cutoff) or high-pass (8 kHz cutoff) filtered noise in young (4-8 month) and aged (36 month) gerbils. For low-pass maskers, aged gerbils had higher masked thresholds at 2 and 4 kHz than young subjects. This was true for all aged subjects, including those with quiet thresholds similar to those of young controls. For high-pass masking, the majority of aged subjects had higher masked thresholds at 2 and 4 kHz than young controls; however, aged subjects with relatively normal quiet thresholds had masked thresholds similar to those of young subjects. A modified power-law (MPL) model was used to predict masked thresholds for aged subjects. Thresholds measured in the presence of low-pass noise were higher than predicted in many of the aged subjects, particularly those with near-normal quiet thresholds. In contrast, thresholds measured in the presence of the high-pass masker were similar to the predicted thresholds. These results suggest that: (a) excess masking occurred in aged subjects for low-pass, but not high-pass, maskers; (b) the excess masking occurred independently of quiet thresholds; and (c) excess upward spread of masking was related to the spectrum of the masker and not the 2 and 4 kHz regions of the auditory periphery.

Age-related changes in auditory evoked potentials of gerbils. III. Low-frequency responses and repetition rate effects.

The auditory brainstem response (ABR) was recorded non-invasively from Mongolian gerbils ranging in age from 6 to 36 months. The ABR was elicited using gaussian tone bursts at octave intervals from 1 to 16 kHz. Responses were bandpass filtered from 30 to 300 Hz (LF-ABR; low-frequency component) and from 300 to 3000 Hz (HF-ABR; high-frequency component). In Experiment A, the thresholds of the two components (HF- and LF-ABR) were compared in 6- and 36-month subjects. The LF-ABR varied more with age than did the HF-ABR, particularly at stimulus frequencies of 2 kHz and above. As shown previously for the HF-ABR, the latencies of the LF-ABR increased as a function of hearing loss in aged gerbils whereas amplitudes of the LF-ABR were reduced in all aged gerbils, regardless of age-related threshold elevation. In Experiment B, tone bursts were presented at rates of 11-91/s to gerbils aged 6, 18, 30, and 36 months. Increased repetition rate resulted in an increase in the latency of both the HF- and LF-ABR, but to the same degree in each age group. Similarly, the interpeak intervals of the HF-ABR increased as a function of repetition rate in all subjects to the same degree. Increased age and increased repetition rate both resulted in significant reductions in ABR amplitudes, but rate did not interact with age. The data suggest that (1) the LF-ABR may be more sensitive to aging than is the HF-ABR and (2) there are no age-related changes in the HF- or LF-ABR which are dependent upon the repetition rate.

Age-related changes in auditory evoked potentials of gerbils. I. Response amplitudes.

Auditory brainstem responses (ABRs) were recorded in young (6-10 month) and aged (36 month) Mongolian gerbils. For each subject, ABR thresholds and response amplitudes were measured at octave intervals from 1 through 16 kHz. Data from the young animals served as the baselines for comparison to aged animals which were categorized on the basis of auditory brainstem response (ABR) thresholds. The aged groups included subjects with thresholds (a) at the mean of a pool of 50 aged gerbils, (b) one standard deviation (SD) lower than the mean, (c) one sd higher than the mean, and (d) near normal for young gerbils. The amplitudes of ABR waveforms for the aged gerbils were reduced compared to the young subjects, particularly at high sound pressure levels. This was true even for aged subjects with thresholds similar to those for younger subjects. The slopes of the amplitude-intensity (I/O) functions were shallower in all aged subjects compared to young subjects. The results suggest that ABR amplitudes and I/O slopes decrease as a function of age and that the decreases are not a direct result of loss of auditory sensitivity. The reductions in ABR amplitudes from aged gerbils presumably reflect age-related pathology in the auditory periphery, as previous studies have shown reductions in amplitudes of the compound action potential of aged gerbils.

Age-related changes in auditory evoked potentials of gerbils. II. Response latencies.

Auditory brainstem responses (ABR) were recorded in young (6-10 month) and aged (36 month) Mongolian gerbils. Data from the young animals served as the baselines for comparison to aged animals which were categorized on the basis of ABR thresholds. Aged gerbils with normal thresholds (re young controls) had wave i and ii latencies of the ABR which were relatively normal at 1-4 kHz and slightly reduced at 8 and 16 kHz. Wave iv latencies in the aged gerbils with normal thresholds were reduced at all frequencies. Aged gerbils with 10-30 dB of hearing loss had wave i, ii, and iv latencies which were prolonged at low sound pressure levels and normal at high stimulus levels. Aged gerbils with 30 dB or greater losses had prolonged wave i, ii, and iv latencies at most levels. Slopes of latency-intensity (L/I) functions were steeper at 1-4 kHz than controls in aged subjects with hearing losses of 10 dB or greater. Slopes of L/I functions for wave iv were normal in aged subjects. The wave i-iv interval was shorter than normal in aged subjects with no hearing loss, normal in aged subjects with 10-30 dB of loss, and prolonged in subjects with greater than 30 dB of loss.

Auditory brain-stem response correlates of resistance to noise-induced hearing loss in Mongolian gerbils.

The auditory brain-stem response (ABR) was recorded from young adult Mongolian gerbils exposed to noise (octave band of noise centered at 4 kHz, 80 dB SPL, 6 h on, 18 h off) for 12 days. Temporary threshold shift (TTS) of 20-50 dB was measured at 4-8 kHz and TTS of 10 dB or less was measured at 1-2 and 16 kHz immediately after the initial exposure. Immediately following the final (12th) exposure, each animal had 10 dB or less threshold shift at all frequencies, demonstrating as much as 40-dB resistance to TTS. Because significant TTS was limited to the high frequencies, the apical portion of the cochlea was left relatively unaffected by the exposure. Amplitudes of waves ii-iii and iv of the ABR were unaffected at low frequencies and reduced at all stimulus levels for 8 kHz on the first day of exposure; the amplitudes recovered to near-baseline levels by the 12th day of exposure. ABR latencies of waves ii and iv were prolonged at low stimulus levels on days one and six of exposure, but recovered to baseline levels by the 12th day of exposure. Because resistance to noise exposure was observed in all subjects and resistance was limited in spectrum, the results suggest that the gerbil is an excellent model for examining mechanisms of resistance to noise-induced hearing loss.

Functional changes in the ventral cochlear nucleus following acute acoustic overstimulation.

The effects of acute acoustic overstimulation on the discharge patterns of neurons in the ventral cochlear nucleus (VCN) were evaluated in anesthetized chinchillas. Response measures were obtained from the same neuron before and after presenting a 3- to 5-min intense tone (90-105 dB SPL) located one-half oct above the unit's characteristic frequency (CF). If a unit had an inhibitory response area at frequencies above CF and if the traumatizing tone reduced the magnitude of the inhibitory response, then the neuron's discharge rate to suprathreshold tones at CF increased ("enhancement") by as much as 25%. However, if a unit lacked an inhibitory response area at frequencies above CF, then the traumatizing tone typically caused either no change or a decrease in the unit's discharge rate at CF. The traumatizing tone did not alter the shape of the post-stimulus time histograms. Moreover, the width of the excitatory response area was not altered by the exposure even when traumatizing stimulus reduced the magnitude of the inhibitory response above CF. The enhanced firing rate at CF following the exposure could conceivably contribute to the enhanced evoked-potential amplitudes observed in the auditory brain stem following acoustic trauma.

Individual susceptibility to noise-induced hearing loss: an old topic revisited.

The wide range in susceptibility to noise-induced hearing loss has intrigued researchers and hearing conservationists alike. Some of these differences in variability have been attributed to various intrinsic factors such as eye color, gender, age, etc. However, a review of controlled research shows that the influence of these intrinsic variables is relatively small and cannot explain the wide range of hearing loss observed in demographic studies. Furthermore, uncontrolled variables or unrecognized drug and noise interaction may obscure the relation between noise exposure and hearing loss. With the growing understanding of the physiology of the auditory system, new possibilities are emerging that may explain the range of susceptibility. A review of the role of acoustic reflex effectiveness, cochlear efferent function, and history of noise exposure provide a perspective for future strategies in predicting susceptibility to noise-induced hearing loss.