Age-dependent hearing loss has been well documented in gerbils exceeding 2 years of age using physiological methods (e.g. [Mills et al. (1990) Hear. Res. 46, 201–210]). We determined behavioral thresholds for broad-band noise and pure-tone pulses in gerbils as a function of age. Contrary to expectations based on previously published physiological data, we found no significant (broad-band noise and 10 kHz) or only a very small hearing loss (7 dB at 2 kHz) in 30–36-month-old animals. In animals over 3 years of age we observed an increased spread of thresholds and threshold shifts exceeding 20 dB in some individuals. Behavioral thresholds of old gerbils from two breeding colonies (University of Regensburg and Medical University of South Carolina) were similar. Data from individual animals where thresholds were determined physiologically and behaviorally indicate that results from auditory brainstem response measurements show no shift at 18 months while subsequent measurements at 28–29 months revealed age-dependent threshold shifts of 10–15 dB. In contrast, thresholds determined by behavioral methods in these same individuals at 31–33 months of age remained stable.

Age-related hearing loss (ARHL or presbyacusis) is an increasingly common form of sensorineural hearing loss (SNHL) as a result of changing demographics, and the auditory brainstem response (ABR) is a common experimental and clinical tool in audiology and neurology. Some of the changes that occur in the aging auditory system may significantly influence the interpretation of the ABR in comparison to the ABRs of younger adults. The approach of this review will be to integrate physiological and histopathological data from human and animal studies to provide a better understanding of the array of age-related changes in the ABR and to determine how age-related changes in the auditory system may influence how the ABR should be interpreted in presbyacusis. Data will be described in terms of thresholds, latencies, and amplitudes, as well as more complex auditory functions such as masking and temporal processing. Included in the review of data will be an attempt to differentiate between age-related effects that may strictly be due to threshold elevation from those that may be due to the aging process.

The effect of age on susceptibility to noise-induced hearing loss (NIHL), the effect of gender on the interaction of age-related hearing loss (ARHL) and NIHL, and the relative contributions of ARHL and NIHL to total hearing loss are poorly understood. The issues are difficult to resolve empirically in human subjects because of lack of control over extrinsic variables and for ethical reasons. Accordingly, these issues were examined in a well-studied animal model of both ARHL and NIHL, the Mongolian gerbil. Animals were exposed to an intense tone (3.5 kHz, 113 dB SPL, 1 h) either as young adults (6-8 months) or near the end of the average lifespan of the species (34-38 months). Hearing thresholds were determined with the auditory brainstem response (ABR). ARHL was approximately 5-10 dB, with slightly more observed in males at 16 kHz (p<0.05). NIHL of approximately 15-20 dB was similar for the young and old groups, suggesting no differences in susceptibility as a function of age. There were no gender differences in NIHL. The relative contributions of ARHL and NIHL to total hearing loss in aged, noise-exposed gerbils were predicted by an addition of ARHL and NIHL in dB, similar to an international standard on hearing loss allocation, ISO-1999 [Determination of Occupational Noise Exposure and Estimation of Noise-Induced Hearing Impairment (1990)]. Previous evaluations of ISO-1999 using the gerbil animal model concluded that addition of ARHL and NIHL in dB overpredicts total hearing loss. However, in these studies, ARHL was large and nearly equal to NIHL. In the current study, where ARHL was much less than NIHL, addition of the two factors in dB, as recommended by ISO-1999, results in fairly accurate predictions of total hearing loss.

The frequency-modulation following response (FMFR) is a steady-state evoked response which may be a neural correlate of frequency discrimination. Aged subjects with normal hearing have abnormal frequency discrimination for low carrier frequencies and thus it might be predicted that aged individuals would have reduced FMFR amplitudes compared to young subjects. In this study, FMFR amplitudes were measured for frequency-modulated sinusoids with a carrier frequency of 0.5 kHz (80 dB SPL). In Experiment 1, the modulation depth was held constant (80%) and the modulation rate was varied (4–38 Hz), whereas in Experiment 2 the modulation rate was held constant (38 Hz) and the modulation depth was varied (0–80%). Aged subjects had significantly larger FMFR amplitudes than young subjects for certain stimulus parameters, although individual variability was large. Such results would not be predicted given previous data regarding frequency discrimination, but are consistent with several reports of larger-than-normal amplitudes of middle latency and late responses in aged subjects.

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 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.

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.

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.

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".

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.

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.

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 (TTS) 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 (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.

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.

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.

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.

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.