Energy-independent factors influencing noise-induced hearing loss in the chinchilla model.

The effects on hearing and the sensory cell population of four continuous, non-Gaussian noise exposures each having an A-weighted L(eq)=100 dB SPL were compared to the effects of an energy-equivalent Gaussian noise. The non-Gaussian noise conditions were characterized by the statistical metric, kurtosis (beta), computed on the unfiltered, beta(t), and the filtered, beta(f), time-domain signals. The chinchilla (n=58) was used as the animal model. Hearing thresholds were estimated using auditory-evoked potentials (AEP) recorded from the inferior colliculus and sensory cell populations were obtained from surface preparation histology. Despite equivalent exposure energies, the four non-Gaussian conditions produced considerably greater hearing and sensory cell loss than did the Gaussian condition. The magnitude of this excess trauma produced by the non-Gaussian noise was dependent on the frequency content, but not on the average energy content of the impacts which gave the noise its non-Gaussian character. These results indicate that beta(t) is an appropriate index of the increased hazard of exposure to non-Gaussian noises and that beta(f) may be useful in the prediction of the place-specific additional outer hair cell loss produced by non-Gaussian exposures. The results also suggest that energy-based metrics, while necessary for the prediction of noise-induced hearing loss, are not sufficient.

Correlations among evoked potential thresholds, distortion product otoacoustic emissions and hair cell loss following various noise exposures in the chinchilla.

Changes in cubic distortion product otoacoustic emissions (DeltaDPOAEs), evoked potential threshold shifts (TSs) and outer hair cell (OHC) losses were measured in a population of 95 noise-exposed chinchillas. Each animal was exposed to one of 23 different noises in an asymptotic threshold shift (ATS) producing paradigm or an interrupted noise paradigm which typically produced a toughening effect. Noises were narrow band (400 Hz) impacts with center frequencies of 0.5, 1.0, 2.0, 4.0 or 8.0 kHz presented 1 impact/s at peak SPLs of 109, 115, 121 or 127 dB. The duration of the exposures was 24 h/day for 5 days (ATS paradigm) or 6 h/day for 20 days (toughening paradigm). Based on a linear regression analysis of individual subject and group mean data, correlations among the following dependent variables were made: DeltaDPOAEs, ATS, toughening or TS recovery (TS(r)), permanent threshold shift (PTS) and OHC loss. Correlations among these metrics were generally highest for DPOAE primary frequency levels, L(1)=L(2)=70 dB. Correlation between DeltaDPOAE and TS(r) was typically low, while a considerably higher correlation was found between DeltaDPOAE and ATS. Correlations among the permanent measures of noise-induced effects, i.e. for DeltaDPOAE/PTS and DeltaDPOAE/OHC loss were typically poor when there was only a small or a moderate noise-induced effect (PTS<25 dB and DeltaDPOAE<20 dB). However, for PTS<25 dB the correlation between PTS and OHC loss was considerably better than the correlation between DeltaDPOAE and OHC loss. For more severe noise-induced changes there was generally a good correspondence between OHC loss, PTS and DeltaDPOAE metrics.

The effects of interrupted noise exposures on the noise-damaged cochlea.

A variety of interrupted noise exposure paradigms will produce a toughening effect in the mammalian auditory system. That is, the threshold shift will gradually become smaller with each successive daily exposure. The ability of the system to be toughened has not been explored in subjects with a pre-existing noise-induced hearing loss. Using the chinchilla as the experimental animal, evoked potential audiometry to obtain thresholds, and surface preparation histology to quantify the sensory cell population, the issue of toughening was examined in the noise-damaged auditory system. Toughening was produced by a 1.0 kHz, narrow-band impact at 115 dB peak SPL for 10 days, 6 h/day, and trauma was produced by a 1.0 kHz, narrow-band impact at 121 dB peak SPL for 5 days, 24 h/day. Four groups of animals were used. Group 1: traumatic exposure followed 30 days later by the toughening exposure. Group 2: toughening exposure followed 30 days later by the traumatic exposure. Group 3: a trauma-only control. Group 4: a toughening-only control. Group 2 that received the toughening exposure 30 days prior to the traumatic exposure showed a 10 to more than 20 dB toughening effect between the 0.5 and 4.0 kHz test frequencies, while Group 1 that received the traumatic exposure followed 30 days later by the toughening exposure showed no toughening. The permanent changes in the evoked response audiograms and sensory cell populations were the same in Groups 1, 2 and 3 that were exposed to the traumatic noise, regardless of whether or not the animals were ever subjected to the toughening noise or whether the toughening noise preceded or followed the traumatic noise.

Sound-induced priming of the chinchilla auditory system.

Exposure of the auditory system to either continuous or interrupted nontraumatic noises, often collectively referred to as priming exposures, has been shown, in a number of experimental paradigms, to reduce the susceptibility of the auditory system to noise-induced hearing and sensory cell loss from a subsequent traumatic exposure. Using auditory evoked potentials to obtain pure-tone thresholds and cochleograms to quantify sensory cell losses, the issue of priming-induced protective effects was examined in the chinchilla. Priming was accomplished with either a continuous noise or with a continuous noise followed by an interrupted noise. Trauma was induced by exposure to high-level impacts over a 5-day period that resulted in an asymptotic threshold shift. A comparison of the two groups of primed subjects with an unprimed control group showed that there were some statistically significant reductions in the asymptotic response of the primed groups to the traumatic exposure but no differences in permanent changes in thresholds among the three groups 30 days following the traumatic exposure. There were, however, some statistically significant, frequency-specific, reductions in outer hair cell loss in the primed groups. When conditioning was followed by the interrupted exposure that produced a threshold shift toughening effect, the conditioning protocol had no effect on the response of subjects to the interrupted exposure. There were also no differences in thresholds or sensory cell loss between the two primed groups 30 days post-trauma. Priming protocols may have different effects on the development of noise-induced trauma that are dependent on the nature of the traumatic stimulus, that is, long-term high-level impact noise exposure versus acute continuous noise exposure.

Susceptibility of the noise-toughened auditory system to noise-induced trauma.

The auditory system 'toughened' by an interrupted noise exposure has been shown in several reports, to be less affected by (or protected from) a subsequent high level noise exposure. A group of chinchillas (n = 12) was exposed to an interrupted noise at 95 dB SPL, 0.5 kHz octave band, 6 h/day for 10 days. Threshold shifts measured over the 10 day exposure showed that the animals responded by either (1) developing a large toughening effect (i.e., thresholds after day 10 of the exposure were considerably better than at the end of day 1) (n = 5) or (2) not showing any toughening, instead thresholds continued to get worse over the course of the exposure (n = 7). After a 5 day interval, during which thresholds of all the animals returned to normal, they, along with a control group (n = 10) not exposed to the interrupted noise, were exposed to an asymptotic threshold shift producing traumatic noise (127 dB peak SPL narrow band impact, 1 kHz center frequency, 24 h/day for 5 days). Auditory evoked potential audiometry and surface preparation histology showed that there were no statistically significant differences in the response of any of the above groups to the traumatic noise. The interrupted noise exposure, whether it produced a toughening or not, did not provide any protection from a subsequent high-level noise.

Noise-induced hearing loss in the noise-toughened auditory system.

The auditory system, toughened by an interrupted noise exposure, has been shown in several reports to be less affected by (or protected from) a subsequent high-level noise exposure. Exposure to 115 dB peak SPL, 1 kHz narrow band (400 Hz) transients presented l/s, 6 h/day, to four groups of chinchillas produced a 10-28 dB toughening effect across the 0.5-8.0 kHz test frequency range. Following either a 30 day or an 18 h recovery period the animals were exposed to the same impulses but presented at 121 or 127 dB peak SPL for five uninterrupted days, thus producing an asymptotic threshold shift (ATS) condition. Comparisons between toughened and untoughened control subjects showed: (1) During the 121 dB exposure there was a statistically significant reduction of 10-25 dB in ATS across the entire test frequency range. Thirty days following the 121 dB exposure there were no significant differences in the postexposure permanent effects on thresholds and sensory cell loss. (2) During the 127 dB exposure only the group with the 30 day interval between the toughening and traumatic exposures showed a small (approximately 10 dB), statistically significant, frequency-specific (8 kHz), reduction in ATS. Thirty days following the 127 dB exposure a statistically significant protective effect on threshold was measured only at 16.0 kHz. However, both toughened groups showed less inner hair cell loss at and above 1.0 kHz, while only the group with the 18 h interval between the toughening and traumatic exposures showed less outer hair cell loss at and above 1.0 kHz. There were no systematic differences in the response of the toughened animals that could be attributed to the 30 day or 18 h post-toughening interval.

Interrupted noise exposures: threshold shift dynamics and permanent effects.

A parametric study of the reduction of threshold shift (toughening phenomena) that takes place during the course of an interrupted noise exposure is described. 266 chinchillas randomly assigned to one of 32 experimental groups were exposed to one of the following: a 400-Hz narrow-band impact noise having a center frequency of 0.5, 1.0, 2.0, 4.0, or 8.0 kHz and peak sound-pressure levels of 109, 115, 121, or 127 dB. The impacts were presented for 5 d, 24 h/d or for 20 d, 6 h/d. corresponding pairs of exposures had equal energy. Group mean noise effects were estimated from pure-tone threshold obtained form inferior colliculus evoked potentials and from surface preparation histology. The threshold shift (TS) toughening phenomena is shown to occur in response to all stimuli that produce a TS and at all audiometric test frequencies. The amount of toughening, which is limited to less than 35 dB, varies with noise frequency and intensity. Based on group mean data the auditory system is not protected from the permanent effects of an interrupted noise exposure as a result of the toughening effect but rather differences in permanent effects between the 5- and 20-d exposures are attributed to the spreading of the exposure energy over an extended period of time.

Noise-induced threshold shift dynamics measured with distortion-product otoacoustic emissions and auditory evoked potentials in chinchillas with inner hair cell deficient cochleas.

Chinchillas (n = 6) were treated with carboplatin and, following a 30-day recovery period, were exposed to a 115 dB peak SPL impact noise presented at a rate of l/s for 6 h/day for 10 days. A second group (n = 6) received only the noise treatment. Cubic distortion product otoacoustic emissions (2f1-f2) and auditory evoked potential (AEP) detection thresholds in response to tone bursts were measured before and 30 days after drug treatment and following the first and 10th day of the noise exposure. Thirty days after the final exposure day, permanent changes in AEP detection thresholds and emissions were measured and cochleograms constructed. The drug treatment eliminated over 80% of the inner hair cells (IHC) in the cochlea, leaving the outer hair cell (OHC) population essentially intact prior to the interrupted noise exposure. The drug treatment alone had very little or no effect on AEP detection thresholds and emission metrics. Following the noise exposure, the IHC-deficient animals showed clear 'toughening' effects in the AEP and emission measures which were the same as measured in the group receiving only the noise. After a 30-day post-exposure recovery period. AEP thresholds were elevated about 10 dB at the low frequencies in the drug-noise group whereas emissions returned to near normal despite the massive IHC losses. These results are consistent with the idea that an intact OHC population is required for toughening. However, sound-evoked efferent pathways activated by the few remaining IHCs (approximately 20%) which, in this preparation, are distributed throughout the cochlea, may still contribute significantly to the toughening phenomena.

Blast overpressure induced structural and functional changes in the auditory system.

Blast overpressure of sufficient intensity can produce injury to various organ systems. Unprotected ears result in the auditory system being the most susceptible. The injuries to the auditory system include: rupture of the tympanic membrane, dislocation or fracture of the ossicular chain, and damage to the sensory structures on the basilar membrane. All these injuries can be characterized as a form of mechanical damage to the affected structure. Injury to the sensory structures on the basilar membrane leads to temporary and permanent loss of hearing sensitivity. The temporary component of the hearing loss shows a time course after removal from the noise which frequently will include an initial increase in hearing loss followed by a recovery period during which threshold may return to preexposure levels or stabilize at a higher level which represents a permanent loss of hearing sensitivity. This type of recovery function suggests that there are damage processes which continue after the traumatic event and that intervention might mitigate some of the damage and hearing loss.

The effects of reverberant blast waves on the auditory system.

Chinchillas were exposed to 1, 10, or 100 reverberant impulses at 150, 155, or 160 dB peak SPL. The impulses were generated by one of two different shock tubes, each producing blast waves having a different spectral composition, with one emphasizing low frequencies (< 0.5 kHz) and the other midfrequencies (2-4 kHz). Impulses were presented at the rate of one per minute. This parametric paradigm yielded 18 exposure conditions with 15 animals/condition. Hearing thresholds were measured using auditory-evoked potentials and the sensory epithelium was evaluated with the surface preparation. In general, trauma increased as the total energy of the exposure, determined by the peak SPL and number of presentations, increased. The dependent variables (permanent threshold shift and sensory cell loss) varied in an orderly fashion across frequency as the peak and number of presentations were increased for both blast wave sources. There were, however, consistent differences between the effects of the low- and high-frequency energy "content" blast waves. Correlations between the dependent variables and the energy of exposure were highest for P- or A-weighted energies [Patterson et al., J. Acoust. Soc. Am. 93, 2860-2869 (1993)].

The cubic distortion product otoacoustic emissions from the normal and noise-damaged chinchilla cochlea.

A normative study of the cubic distortion product emissions from 104 monaural and binaural chinchillas was undertaken to establish criteria upon which noise exposed animals could be evaluated. From this normative group, 47 randomly selected chinchillas were exposed to various high level (150-, 155-, and 160-db peak SPL) impulse noises. Auditory evoked potentials and cubic distortion product otoacoustic emissions were measured on each animal pre- and post-exposure and related to the sensory cell populations 30 days post-exposure. Both group mean and individual animal data indicated that the distortion product emissions were more sensitive, frequency-specific indices of noise-induced cochlear effects than pure-tone threshold measures. This was particularly evident near the threshold for noise-induced damage to the outer hair cell system.

Evoked-potential thresholds and cubic distortion product otoacoustic emissions in the chinchilla following carboplatin treatment and noise exposure.

Twenty-two chinchillas were given either a single intraperitoneal (i.p.) or intravenous (i.v.) injection (50 or 75 mg/kg) of Paraplatin, an asymptotic threshold shift-producing noise or a combination of the drug and noise in series. Auditory evoked potential (pure-tone) audiograms and cubic distortion product otoacoustic emissions were obtained on each animal before and after treatment, and the sensory epithelium of the cochlea was evaluated using the surface preparation method. Anatomical analysis indicated that the carboplatin alone caused relatively severe but scattered losses of inner hair cells throughout most of the cochlea which were dependent on dose and administration route. The outer sensory cell population remained essentially intact. In animals that had up to 40% scattered losses of only inner hair cells, evoked potential thresholds were near normal and the emission functions either were normal or showed an enhanced output. The severe losses of inner hair cells produced by the drug had no effect on the threshold shift dynamics produced by a five-day uninterrupted noise exposure. In general, there was not a consistent relation between the emission data and both the permanent threshold shift and outer hair cell losses.

Biologic bases of noise-induced hearing loss.

The effects of noise are pervasive, and pathology can be found in the neural, sensory, supporting, and vascular cells of the cochlea after certain noise exposures. Several issues need to be addressed. First, what is the source of the wide range of susceptibility seen in people and animals that have similar noise histories but markedly different response to noise? Does this suggest a genetic factor in susceptibility to NIHL? Second, given the complexity of the biologic changes following noise exposures, it is difficult to predict the underlying pathology from standard audiologic tests. However, it would be desirable to distinguish sensory and neural and strial pathology because it is likely that the success of any aural rehabilitation will depend on knowledge of the type of pathology. This chapter focuses on a number of the traditional issues surrounding NIHL. However, one of the most exciting recent findings that undoubtedly will affect people with NIHL is that it is possible for sensory cells to regenerate. Research into the fundamental biochemical processes responsible for inducing regeneration is being pursued at a number of laboratories. The hope is to be able to repopulate the mammalian sensory epithelium with viable sensory cells.

The application of frequency and time domain kurtosis to the assessment of hazardous noise exposures.

Five computer-synthesized broadband noises, each having the same average spectrum and the same unweighted Leq of 100 dB SPL but very different temporal structures, were used to produce hearing loss in chinchillas. Despite the same exposure energies and spectra, each noise exposure produced a different magnitude and frequency distribution of hearing loss and sensory cell loss. The results indicate that the statistical properties of a signal are important in the determination of hearing loss. When the audiometric and histological results are compared to a metric based upon kurtosis measured in the time and the frequency domain for each exposure, there is a clear indication that these statistical metrics are good predictors of the relative magnitude and frequency distribution of the acoustic trauma.

Hearing threshold shifts from repeated 6-h daily exposure to impact noise.

Exposure of chinchillas to broadband, high-level impact noise on an interrupted 6-h daily schedule over 20 days has shown that pure-tone thresholds measured immediately following each daily exposure improve as much as 30 dB despite the continuing noise exposure. The time constant of this recovery effect (toughening) and the magnitude of the effect are related to the audiometric test frequency and the exposure energy. The trauma, quantified by permanent threshold shifts and sensory cell losses, produced by the interrupted exposure paradigm is generally less than that produced by an equal-energy uninterrupted exposure. The wide variations in the temporal pattern of threshold shift across similarly exposed animals suggest that the toughening effect reflects the underlying susceptibility of that animal to noise trauma.

The role of tuning curve variables and threshold measures in the estimation of sensory cell loss.

Auditory-evoked potential tuning curves were collected at six frequencies before and 30 days after various noise exposures in 363 chinchillas using a simultaneous masking paradigm. Traditional bivariate and multiple linear regression/correlation analyses were performed in an effort to determine the extent to which sensory cell damage could be estimated from a knowledge of audiometric and tuning curve variables. The results showed strong correlations between percent outer hair cell (%OHC) loss and permanent threshold shift (PTS) and between %OHC loss and the tuning curve variables Q10 dB and high- and low-frequency slopes (SHF, SLF). The correlations were strongest between PTS and %OHC loss. However, the proportion of variability (r2) in %OHC loss attributable to variability in the predictor variable(s) (i.e., PTS) could be increased significantly by adding the Q10 dB of the tuning curve whose probe frequency was centered in the octave band length of the cochlea corresponding to the frequency at which the PTS occurred. The r2 values could be further increased by including audiometric and tuning curve variables from frequencies adjacent to the octave band being evaluated.

Audiometric and histological differences between the effects of continuous and impulsive noise exposures.

An experiment was designed to determine if, for equal SPL and power spectrum, the effects on hearing of high-kurtosis noise exposures and a Gaussian noise exposure are different and the extent to which any differences measured in terms of audiometric and histological variables are frequency specific. Three groups of chinchillas with 10 animals/group were exposed for 5 days at 90 dB SPL to one of three types of noise, each with the same power spectrum. The impulsiveness, defined by the kurtosis, and the region of the spectrum from which the impulsive components of the noise were created differed for two of the noises, while the third was a continuous Gaussian noise. The results show that the most impulsive noise produced up to 20 dB greater permanent threshold shift at the high frequencies than did the Gaussian noise exposure. However, these audiometric results were difficult to reconcile with the pattern of sensory cell losses that showed statistically significant larger losses of outer hair cells for the impulsive exposure in the 0.25-kHz region. When the impacts in a high-kurtosis noise were created from the energy in the 1- through 6-kHz region of the spectrum, the audiometric profile of hearing loss was similar to that produced by the Gaussian noise; however, inner hair cell losses were significantly greater in the 4-kHz octave band region of the cochlea.

Complex noise exposures: an energy analysis.

Industrial noise environments usually present a complex stimulus to the exposed individual. These environments often contain mixtures of multiply reflected impact noises and a relatively Gaussian broadband noise. Noise exposure standards do not consider the possibility of interactions between the two classes of noise that can exacerbate the amount of hearing trauma. This paper presents the results of a large series of experiments designed to document the hazard posed to hearing from complex noise exposures. Twenty-three groups of chinchillas with 5 to 11 animals per group (total N = 135) were exposed for 5 days to either octave bands of noise, impacts alone, or combinations of impact and octave bands of noise. Evoked potential measures of hearing thresholds and cochleograms were used to quantify the noise-induced trauma. The results show that, for sound exposure levels (SEL) which produce less than approximately 10 dB PTS (permanent threshold shift) or 5% total sensory cell loss, equal-energy exposures tend to produce equivalent effects on hearing. However, there is a range of at least 10 dB in the SEL parameter where hearing loss from equal-energy exposures at a particular SEL can be exacerbated by increasing the repetition rate of the impacts or by the addition of a Gaussian low-level noise. The exacerbation of trauma from the addition of a Gaussian continuous noise is dependent upon the spectrum of that noise.

Frequency selectivity in noise-damaged cochleas.

Measures of auditory threshold and masked threshold were obtained at six audiometric test frequencies along with cochleograms on a total population of 363 noise-exposed chinchillas. Seventy animals were chosen from this sample and were separated into five relatively homogeneous groups based upon the amount of permanent threshold shift and sensory cell losses the animals incurred. Tuning curve (TC) metrics were compared to the mean preexposure TC metrics for each group and to the reference preexposure TC metrics obtained from the sample of 363 animals. These data show that in animals with relatively little hearing loss changes in TC metrics can provide evidence for noise-induced sensory cell losses and that the low frequency slope of the TC is a sensitive index of trauma.