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In 129 Sv autosomal Alport mice, the strial capillary basement membranes (SCBMs) progressively thicken between 5 and 9 weeks of age resulting in a hypoxic microenvironment with metabolic stress and induction of pro-inflammatory cytokines and chemokines. These events occur concomitant with a drop in endocochlear potential and a susceptibility to noise-induced hearing loss under conditions that do not permanently affect age/strain-matched littermates. Here we aimed to gain an understanding of events that occur before the onset of SCBM thickening. Alport stria has normal thickness and shows levels of extracellular matrix (ECM) molecules in the SCBMs commensurate with wild-type mice. Hearing thresholds in the 3-week Alport mice do not differ from those of wild-type mice. We performed RNAseq analysis using RNA from stria vascularis isolated from 3-week Alport mice and wild type littermates. Data was processed using Ingenuity Pathway Analysis software and further distilled using manual procedures. RNAseq analysis revealed significant dysregulation of genes involved in cell adhesion, cell migration, formation of protrusions, and both actin and tubulin cytoskeletal dynamics. Overall, the data suggested changes in the cellular architecture of the stria might be apparent. To test this notion, we performed dual immunofluorescence analysis on whole mounts of the stria vascularis from these same animals stained with anti-isolectin gs-ib4 (endothelial cell marker) and anti-desmin (pericyte marker) antibodies. The results showed evidence of pericyte detachment and migration as well as the formation of membrane ruffling on pericytes in z-stacked confocal images from Alport mice compared to wild type littermates. This was confirmed by TEM analysis. Earlier work from our lab showed that endothelin A receptor blockade prevents SCBM thickening and ECM accumulation in the SCBMs. Treating cultured pericytes with endothelin-1 induced actin cytoskeletal rearrangement, increasing the ratio of filamentous to globular actin. Collectively, these findings suggest that the change in type IV collagen composition in the Alport SCBMs results in cellular insult to the pericyte compartment, activating detachment and altered cytoskeletal dynamics. These events precede SCBM thickening and hearing loss in Alport mice, and thus constitute the earliest event so far recognized in Alport strial pathology.

The amplitude of the 2f1–f2 distortion product otoacoustic emission (DPOAE) can be suppressed by presenting contralateral acoustic stimulation. To test the hypothesis that DPOAE contralateral suppression is influenced by the primary frequency in DPgrams, DPgrams were recorded at resolutions of 1, 8, and 17 pts/octave, in the absence and presence of contralateral broadband noise (BBN). Participants were 20 normal-hearing human adults. In DPgrams with higher frequency resolutions, DPOAE suppression at amplitude peaks in DPgrams (8 pts/octave: Mean = − 0.92 dB, SD = 0.71 for BBN at 60 dB SPL; 17 pts/octave: Mean = − 0.25 to −1.44 dB, SD = 0.51 to 0.86 for BBN at 40 to 70 dB SPL, respectively) was larger than the suppression at the dips in DPgrams (8 pts/octave: Mean = − 0.13 dB, SD = 1.00; 17 pts/octave: Mean = − 0.03 to −0.73 dB, SD = 0.55 to 0.91). A larger intersubject variability in DPOAE contralateral suppression was observed at the dips. The results suggest that measuring DPOAE contralateral suppressio...

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

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.

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.

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.

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 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.

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.

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.

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.

Objective: 1) Determine whether radiation exposure in mice leads to measurable hearing losses similar to those seen in patients exposed to radiotherapy for acoustic neuromas, temporal bone malignancies, and nasopharyngeal carcinoma. 2) Assess for any associated pathologic changes in cochleas exposed to radiation.Method: Adult (11-13 weeks) 129Sv/J mice were exposed to radiation using an animal irradiator, ranging from a single exposure of 10 Gy to 100 Gy. Pre- and postradiation audiometric brainstem response (ABR) data were recorded to document hearing loss, with subsequent analysis of cochlear ultrastructure using transmission and scanning electron microscopy.Results: High-frequency hearing loss was noted in exposures exceeding 40 Gy. Anorexia was observed by day 6 post- irradiation in all mice exposed to doses ≥20 Gy. Normal hearing following 20 Gy exposure suggests that hearing losses seen after ≥40 Gy exposures is secondary to radiation effects rather than any confounding metabolic disturbance. Ultras...

Objective: 1) Determine whether a type II diabetic mouse model demonstrates hearing loss. 2) Examine cochlear ultrastructure of a type II diabetic mouse model for evidence of pathology.Method: The Leprdb/Leprdb (db/db) mouse has a leptin receptor point mutation which manifests as polyphagia, hyperglycemia, and obesity, mimicking type II diabetes. Db/db and wild type mice from the parent strain underwent auditory brainstem response measurements followed by cochlear ultrastructure analysis using scanning and transmission electron microscopy.Results: At 12 weeks of age, the mutant animals demonstrate a profound hearing loss from 8 to 32 kHz, which is in contrast to published data of a 10 dB shift at 8 kHz and 30 dB shift at 16 to 32 kHz for age-matched, wild type C57BL/6J counterparts. In addition, fine structure analysis reveals evidence of morphological alterations in multiple locations within the cochlea, including loss of neuron density in the spiral ganglion, stria vascularis edema, and endothelial abno...

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.

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.

The combined effects of noise and sodium salicylate on auditory sensitivity were examined in the chinchilla. Sensitivity was monitored by recording the evoked response recorded with an electrode implanted in the inferior colliculus. Sodium salicylate (300 mg/kg/day), an octave band of noise centered at 500 Hz (80 or 105 dB SPL), or both of these agents were delivered for 15 days. Threshold testing was performed at 7 frequencies before, during, and after exposure to the ototraumatic agent(s). The salicylate alone caused an average temporary threshold shift of less than 10 dB and essentially no permanent shift. Animals exposed to noise alone had temporary and permanent threshold shifts which were not significantly different from those observed in animals exposed to noise plus salicylate. The data suggest that a single daily injection of sodium salicylate, resulting in peak serum salicylate concentrations of 28 to 34 mg% 2 to 4 hours after delivery, does not exacerbate the temporary or permanent threshold shifts induced by 15-day, 24-hour-per day exposure to either a moderate- or high-level, low-frequency noise. A second series of experiments utilizing a higher dose of salicylate (450 mg/kg/day) was not completed due to a high mortality rate among subjects that received salicylate and were exposed to noise. This result was consistent with other recent examinations of the interaction of these agents.

The auditory steady-state evoked response (ASSR) is a scalp-recorded potential elicited by modulated sounds or repetitive transient sounds presented at a high rate. The binaural interaction component (BIC) of the ASSR equals the difference between the response to binaural stimuli and the sum of the responses to a monaural stimulus presented to the left ear and the right ear. This study examined the effect of the interaural time (ITD) and level (ILD) difference on the BIC of the 80 Hz ASSR. Sixteen human participants with normal hearing were tested. The ITD and ILD were varied from -1.6 to +1.6 msec and from 0 to +12 dB, respectively. The ITD function of the BIC showed a "V" shape, with a 0 value of BIC at ITD 0 msec and a positive BIC at ITD +0.8 to +1.6 msec. For ILD conditions, the BIC displayed negative values, and its amplitude became more negative as the ILD was increased. The results indicate that the ITD and ILD may be processed by different groups of binaural neurons in different pathways. It is suggested that the 80 Hz ASSR provides an objective means for evaluating binaural functions in patients such as those with central auditory processing disorders. Las respuestas evocadas auditivas de estado estable (ASSR) son potenciales de registro en el cráneo generados por sonidos modulados o sonidos repetitivos transitorios presentados a una tasa alta. El componente de interacción biauricular (BIC) de los ASSR iguala la diferencia entre la respuesta a estímulos bi-auriculares y la suma de respuestas a estímulos mono-auriculares presentados al oído derecho y al oído izquierdo. Este estudio examinó el efecto de la diferencia interauricular de tiempo (ITD) y de nivel (ILD) a partir del BIC de un ASSR de 80 Hz. Se evaluaron dieciséis participantes humanos con audición normal. Las ITD y ILD se variaron de -1.6 a +1.6 mseg y de 0 a + 12 dB, respectivamente. La función ITD del BIC mostró una forma en "V", con un valor 0 del BIC con un ITD de 0 mseg y un BIC positivo con un ITD +0.8 a +1.6 mseg. Para condiciones ILD, el BIC mostró valores negativos, y su amplitud se hizo más negativa conforme aumento el ILD. Los resultados indican que el ITD y el ILD pueden ser procesados por grupos diferentes de neuronas bi-auriculares en diferentes vías. Se sugiere que el ASSR de 80 Hz proporciona un medio objetivo para evaluar las funciones bi-auriculares en pacientes como aquellos con trastornos centrales de procesamiento auditivo.

Animal models have played a major role in understanding noise-induced hearing loss, a major cause of hearing loss in industrialized societies. Behavioral models using positive and negative reinforcement techniques have played an important role in delineating the relationship between the physical characteristic of the noise, namely intensity, spectral content, and duration, and the magnitude of the resulting hearing loss. An important contribution from these studies was the discovery that the hearing loss reaches an asymptotic value of threshold shift for exposures lasting 24 h or more. Animal models of noise-induced hearing loss have revealed a significant loss of frequency sensitivity, making it difficult to discriminate signals in noise, and a breakdown in temporal resolution that makes it difficult to perceive the temporal information contained in complex signals such as speech. Animal models have shown that prolonged exposure to high-level noise mainly damages the sensory hair cells in the inner ear. The stereocilia bundles on the sensory hair cells, which contain the mechanically gated ion channels responsible for converting sound into neural activity, are especially vulnerable to acoustic overstimulation. High-level noise can obliterate or damage the stereocilia. More severe sound exposures can result in degeneration of the hair cell body, beginning with the outer hair cells followed by the inner hair cells. The functional status of the outer hair cells can be evaluated in noise-exposed animals using distortion product otoacoustic emissions. When healthy ears are stimulated with two primary tones, f 1 and f2, the inner ear generates a distortion tone, the most prominent of which occurs at 2f1–f2. Acoustic overstimulation that primarily damages the outer hair cells and leads to mild to moderate hearing loss almost completely abolishes the distortion product otoacoustic emission. The type I spiral ganglion neurons, which make synaptic contact with single inner hair cells, can be used to assess the functional status of a very narrow region of the cochlea. The functional status of small populations of type I neurons can be evaluated using tone bursts to elicit the compound action potential. Narrow band noise exposures that damage specific regions of the cochlea cause an increase in the compound action potential threshold at frequencies associated with the region of cochlear pathology. Microelectrode recordings from single type I auditory nerve fibers can be used to delineate the pathophysiology at specific sites along the cochlea. Sound exposures that selectively damage the outer hair cells lead to an elevation of threshold and loss of tuning. In cases in which acoustic overstimulation destroys both the outer hair cells and inner hair cells, nerve fibers associated with the damaged region are unresponsive to sound resulting in a dead region. The biological mechanisms that lead to noise-induced degeneration of hair cells is not fully understood, but there is growing awareness that hair cell death may be initiated by oxidative stress that leads to hair cell death by necrosis or apoptosis.

Recovery from short-term adaptation was measured in single neurons in the cochlear nucleus using a forward masking stimulus paradigm. The response to a short-duration, low-level probe tone at a unit's characteristic frequency (CF) was measured before and after presentation of a masker tone at the unit's CF. The degree of adaptation was defined as the ratio of firing to the probe in the adapted and unadapted conditions. The level of the masker and time difference between the masker offset and probe onset ('DT') were varied. As DT increased, the response to the probe increased in most Primarylike, Primarylike-notch, and Chopper units. Recovery was approximately linear in log time for most of these units. However, approximately half the Pauser/Buildup and On units showed very different recovery patterns, ranging from no adaptation to very non-linear recovery patterns. The results suggest that little alteration in the recovery process occurs between the auditory nerve and Primarylike, Primarylike-notch, and Chopper units, but that significant changes in the recovery process occur in Pauser-Buildup and On units.

The amplitude of the 2f1-f2 distortion product otoacoustic emission (DPOAE) can be suppressed by presenting contralateral acoustic stimulation. To test the hypothesis that DPOAE contralateral suppression is influenced by the primary frequency in DPgrams, DPgrams were recorded at resolutions of 1, 8, and 17 pts/octave, in the absence and presence of contralateral broadband noise (BBN). Participants were 20 normal-hearing human adults. In DPgrams with higher frequency resolutions, DPOAE suppression at amplitude peaks in DPgrams (8 pts/octave: Mean = - 0.92 dB, SD = 0.71 for BBN at 60 dB SPL; 17 pts/octave: Mean = - 0.25 to -1.44 dB, SD = 0.51 to 0.86 for BBN at 40 to 70 dB SPL, respectively) was larger than the suppression at the dips in DPgrams (8 pts/octave: Mean = - 0.13 dB, SD = 1.00; 17 pts/octave: Mean = - 0.03 to -0.73 dB, SD = 0.55 to 0.91). A larger intersubject variability in DPOAE contralateral suppression was observed at the dips. The results suggest that measuring DPOAE contralateral suppression at the primary frequencies corresponding to the peaks in DPgrams with higher frequency resolutions may improve the assessment of the efferent system function.

Decrement detection is a commonly used psychophysical technique in which a subject is required to detect partially filled gaps in an ongoing sound. The paradigm provides information regarding both temporal resolution and intensity discrimination. The purpose of this project was to determine if an evoked-potential paradigm using decrements in an ongoing noise approximates psychophysical data. If so, the evoked-response paradigm would be useful in estimating decrement detection in laboratory animals, where training time for a psychophysical model of decrement detection might prove prohibitive. In this study, Mongolian gerbils aged 3–10 months were used as subjects. The stimulus was a broadband noise (low-pass filtered at 5 or 30 kHz, overall level of 70 dB SPL), interrupted for durations of 2–32 ms. Within each off period, a second, identically filtered noise at levels of 0–70 dB SPL was presented. In a manner qualitatively similar to previous human and animal psychophysical studies, the ABR threshold decreased as the duration of the decrement was increased. Latency and amplitudes changed as a function of decrement duration when the decrement depth was held constant, but minimal change as a function of decrement depth occurred when the decrement duration was held constant. The results suggest that ABR paradigm for decrement detection is a qualitative alternative to psychophysical techniques, but that amplitude and latency data may not provide more information on temporal and intensity coding than ABR measures of gap detection.

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 (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.

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".

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.

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.

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.

The compound action potential (AP) was recorded from one group of chinchillas exposed to interrupted noise (95 dB SPL, octave band centered at 500 Hz, 3 h on, 9 h off) for 15 days. A second group of chinchillas was exposed to the same interrupted noise for 1, 2 or 15 days and their cochleas were analyzed by scanning electron microscopy (SEM). During the first few days of the exposure, the AP threshold was elevated approximately 40 dB at the low-to-mid frequencies; however, the threshold shifts decreased with increasing exposure duration so that the threshold shift was only about 10 dB after the 15th day of exposure. The amplitude of the AP also recovered with exposure time. In contrast to the improvement in AP threshold, the number of missing hair cells increased and the condition of the stereocilia on inner and outer hair cells deteriorated between the first and 15th day of the exposure.

Physiological recordings were made of the compound action potential from the round window and single neurons in the cochlear ganglion of normal adult chickens (Gallus domesticus). The compound action potential threshold to tone bursts decreased from approximately 42 dB at 0.25 kHz to 30 dB between 1 and 2 kHz and then increased to 51 dB at 4 kHz. Most of the cochlear ganglion cells had characteristic frequencies below 2 kHz and the thresholds of most neurons were roughly 30-35 dB lower than the compound action potential thresholds. At any given characteristic frequency, thresholds varied by as much as 60 dB and units with the highest thresholds tended to have the lowest spontaneous rates. Spontaneous discharge rates ranged from 0 to 200 spikes/s with a mean rage of 86 spikes/s. Interspike interval histograms of spontaneous activity often contained regular peaks with the time interval between peaks approximately equal to 1/(characteristic frequency). Tuning curves were sharply tuned and V-shaped with approximately equal slopes to the curves above and below characteristic frequency. Q10dB and Q30dB values for the tuning curves increased with characteristic frequency. Post stimulus time histograms showed sustained firing during the stimulus and were characterized by a slight-to-moderate peak at stimulus onset. Most units showed vigorous phase-locking to tones at characteristic frequency although the degree of phase-locking declined sharply with increasing characteristic frequency. Discharge rate-level functions at characteristic frequency had a mean dynamic range of 42 dB and a mean saturation firing rate of 327 spikes/s. In general, the firing patterns of cochlear ganglion neurons are similar in most respects to those reported in other avians, but differ in several important respects from those seen in mammals.

Recent data from several labs have suggested that acoustic trauma may result in enhanced evoked response amplitudes in the central auditory system ( Saunders et al ., 1972 ; Gerken et al ., 1984 ; Powers and Salvi, 1989 ; Salvi et al ., 1990 , 1991 ). One mechanism that could potentially account for the enhanced evoked potentials is a loss of sideband inhibition in the central auditory system. The present study was designed to determine a possible mechanism for the enhanced evoked potentials by examining the effects of acoustic trauma on firing rates of single neurons in the ventral cochlear nucleus (VCN) of the chinchilla. For each single neuron, rate-level functions were measured at the characteristic frequency (CF) and +1/2 octave re CF of the unit. The functions were repeated after exposure to an intense tone placed 0.25 to 1.5 octaves above CF. Following acoustic trauma to frequencies above CF, a significant percentage of VCN units showed increased maximal firing rate at CF, despite little concomitant change in threshold at CF. The units with enhanced firing rate after exposure were typically those with distinct inhibitory sidebands. Furthermore, the occurrence of enhanced excitatory response was commonly associated with a loss of sideband inhibition above CF.

Temporal integration functions were measured, before and after a sound-induced hearing loss, in 5 cats using trains of electrical pulses applied to auditory nuclei in the brainstem. The 8 stimuli ranged from 1 pulse (0.25 ms duration) to 16 pulses (0.25 ms pulses spaced over 240 ms). The stimuli were applied to inferior colliculus or cochlear nucleus via permanently implanted electrodes. One electrode was tested extensively in each animal to obtain 10 sets of behaviorally-measured electrical detection thresholds counterbal-anced across stimuli. The animal was then exposed to a 110 dB SPL, 2 kHz tone for 48 h and pre- and post-exposure audiograms were measured. The mean permanent threshold shift for acoustic stimuli was 48.5 dB. Another 10 thresholds for each of the 8 electrical stimuli were then measured. In the normal hearing animals, the mean slope of the temporal integration function for electrical stimulation was −7.6 dB per factor of 10 pulses. Alternatively, the mean time constant was 139 ms. In the hearing impaired animals, the slope was reduced to −1.5 dB per factor of 10 pulses, which corresponded to a mean time constant of 17 ms. In addition, the hearing impaired animals showed a decreased threshold for the electrical stimuli (stimulation hypersensitivity) as well as reduced variability across electrical stimulation thresholds. The results suggest that a major contribution to temporal integration occurs in inferior colliculus or higher. In addition, the results suggest that the reduction in temporal integration that follows hearing impairment is a peripherally-induced, central effect.

The effects of salicylates on the auditory system are reviewed. The clinical manifestations of aspirin ototoxicity are described, including changes in the sensitivity and suprathreshold characteristics of hearing, as well as tinnitus. The results of animal experiments on salicylate ototoxicity are discussed, including behavioral, anatomic, and physiologic studies examining the mechanisms of salicylate ototoxicity. The use of salicylates in the study of the basic mechanisms of hearing and hearing loss is also considered.

• The concentration of salicylate in serum and perilymph was measured in chinchillas after intraperitoneal administration of sodium salicylate. Serum salicylate concentration peaked 2 to 4 hours after a single injection. Clearance was approximately complete after 16 hours. The within-subject variability of serum concentration 4 hours after injection was very low. Subject weight significantly affected serum salicylate concentration, with heavier animals showing higher serum levels. The relationship of perilymph to serum salicylate concentration was approximately linear, with a high correlation between measures. ( Arch Otolaryngol Head Neck Surg . 1990;116:681-684)

Tone-on-tone masking patterns were measured at 0.5, 1, and 4 kHz using the auditory-evoked response from the inferior colliculus of the chinchilla. Masking profiles obtained with a masking level of 30 dB SPL were relatively symmetrical; however, as masker level increased, masking spread toward the high frequencies, particularly with the 0.5-kHz masker. For masker frequencies of 1 and 4 kHz, a low-threshold notch was observed in the masking profile 2/3 of an octave above the frequency of the masker. The low-threshold notch may represent a response to the distortion tone 2F1-F2. The notch was absent in the 0.5-kHz masking profile. The masking profiles obtained with the evoked response are somewhat wider, but otherwise qualitatively similar to those measured psychophysically in humans. Thus, the evoked-response procedure may provide a convenient way of evaluating the spread of masking and the presence of distortion tones in difficult-to-test subjects.

The purpose of this comment is to propose a peak‐labeling nomenclature for the gerbil brain‐stem auditory‐evoked response (BAER) which is different than that used by Burkard and Voigt [J. Acoust. Soc. Am. 85, 2514–2525 (1989)]. This proposed nomenclature is a compromise between the use of five primary peaks (i–v) used by Burkard and Voigt (herein called the ‘‘Boston group’’) and the use of three primary peaks (I–III) proposed by Mills and colleagues (herein called the ‘‘Charleston group’’). This proposed standardization recognizes four peaks occurring within 4 to 5 ms of stimulus onset, labeled i through iv. This standardization will allow easier comparisons of gerbil BAER data obtained across laboratories.

Two issues will be reviewed: (1) combined effects of noise and aging on hearing and (2) protective effects of calcium‐channel blockers (CCBs). There are no empirical data on the auditory effects of noise exposure and the aging process in humans. The only sources of information on combined effects of noise and age have been epidemiological studies. In recent experiments, gerbils were exposed monaurally at middle age to an intense tone which caused approximately 20 dB of noise‐induced permanent threshold shift (NIPTS). At 36 months (lifespan of the gerbil), the threshold in the unexposed ear was considered the age‐related loss and that in the exposed ear was considered the loss caused by aging plus noise. Data were examined in terms of published models which attempt to discriminate between NIPTS and presbycusis in older individuals. Most models significantly overestimated the noise‐induced component of the hearing loss in the aged subjects. In the second series of experiments, gerbils were exposed to an intense noise while concurrently receiving CCBs or placebos. Nimodipine (a potent CCB) reduced the NIPTS. Furthermore, epidemiological data suggest that aged women taking CCBs have hearing levels 10–12 dB better than average. [Work supported by NIH‐NIDCD and NOHR.]

To account for higher masked ABR thresholds, input–output (I/O) functions of the ABR were examined. For both aging humans and gerbils, amplitudes of the ABR were smaller and slopes of ABR I/O functions were less steep than those of young subjects. Smaller amplitudes could indicate abnormal function of the brainstem or an altered input to the brain stem from the periphery. Analysis of I/O functions of the compound action potential (CAP) of the auditory nerve of aging gerbils also showed a decrease in slope. Decreases in the slope of the CAP can be attributed to a loss of 10%–30% of spiral ganglion cells, to a reduction in synchronous neural activity of the remaining nerve fibers, and to a reduction of the endocochlear potential. Thus, our hypothesis is that the unusual amounts of masking observed in the ABR of both aging humans and gerbils can be accounted for by age‐related alterations in the auditory periphery. It is also our hypothesis that behavioral measurements of normal quiet and masked thresholds in aging humans do not necessarily reflect an intact auditory periphery. [Work supported by NIDCD.]

Masked thresholds estimated from auditory brain‐stem responses (ABR) of aging gerbils are 20–30 dB higher than the masked thresholds of young gerbils when quiet thresholds are equal. In this presentation, we will discuss data on young (6 month) gerbils with normal hearing and aged (36 month) gerbils with a range of hearing levels. ABR thresholds were measured at 1, 2, 4, 8, and 16 kHz in quiet and in the presence of a low‐pass filtered noise (1 kHz upper bound) at levels of 50, 60, and 70 dB SPL. Young subjects had linear growth of masking of signals within the passband of the noise. At higher frequencies, only minimal masking was observed. In contrast, aged subjects showed much higher masked thresholds at 2 and 4 kHz compared to young subjects. This occurred for both aged subjects with minimal age‐related threshold elevation and those with large hearing losses. In accordance with previous studies, masked ABR thresholds in aging gerbils are much higher than those in young gerbils. This phenomenon is examined in human subjects with behavioral and ABR techniques in the companion presentations. [Work supported by NIDCD.]

The effects of sodium salicylate on auditory sensitivity, frequency selectivity, and temporal resolution were monitored in chinchillas using evoked responses recorded from the inferior colliculus. Administration of sodium salicylate (450 mg/kg/day for 5–15 days) resulted in serum salicylate levels of 25–50 mg/100 ml. The salicylate administration caused elevation of evoked response thresholds (up to 30 dB), mainly at the high frequencies. Frequency selectivity, as estimated by the Q 10 dB value of evoked-response tuning curves, was poorer at 4 kHz during drug administration than during the no drug (control) condition. Temporal resolution, as estimated by recovery from forward masking was not significantly poorer during salicylate administration than before administration. However, there was a trend toward longer recovery in animals with large threshold shifts. These results are consistent with models suggesting that salicylate affects the auditory system at the level of the organ of Corti. They also suggest that while the changes in hearing that occur after salicylate administration are consistent with those seen in sensorineural hearing loss, the changes in hearing in the chinchilla are small enough to preclude the use of the drug as a practical model for sensorineural loss.

The following is a review of the literature on interaction of noise and other agents, both ototraumatic and nonototraumatic. A short description of the anatomical effects of exposure to intense sound previews the interaction literature. The effects of exposure to combinations of continuous and impulse noise are discussed. This is followed by a review of data on interactions of noise and ototoxic drugs and noise and whole-body vibration, including discussion of putative mechanisms of synergism. In addition, preliminary results of noise-cisplatinum interaction are presented which suggest that if cisplatinum is presented during noise exposure in dose schedules simulating human chemotherapy schedules, hearing threshold shifts and histological damage is much greater than that caused by either agent in isolation. The clinical relevance of the interactions is discussed, along with potential synergistic interactions not yet investigated.

Salicylate administration exacerbates the temporary threshold shift (TTS) caused by noise exposure in humans [D. McFadden and H. S. Plattsmier, Hear. Res. 9, 295–316 (1983)]. However, results from animal experiments are conflicting as to whether salicylate administration potentiates noise‐induced TTS. Because of the controversy in the literature and the lack of data on the potential permanent interaction of noise and salicylates, chinchillas were exposed to noise (105 dB SPL, 0.5‐kHz octave band, 15 days), salicylate (300 mg/kg, daily i.p. injection), or both, concurrently. Salicylate administration resulted in a TTS of 4 to 8 dB, depending on frequency, and no permanent threshold shift (PTS). Noise exposure caused 46 to 68 dB of TTS and 10 to 26 dB of PTS. The group exposed to both agents received 57 to 70 dB of TTS and 8 to 30 dB of PTS. There was little difference between the interaction and noise‐alone groups for both TTS and PTS measures. In conclusion, salicylate did not exacerbate the temporary or ...