Control of hearing sensitivity by tectorial membrane calcium.

When sound stimulates the stereocilia on the sensory cells in the hearing organ, Ca2+ ions flow through mechanically gated ion channels. This Ca2+ influx is thought to be important for ensuring that the mechanically gated channels operate within their most sensitive response region, setting the fraction of channels open at rest, and possibly for the continued maintenance of stereocilia. Since the extracellular Ca2+ concentration will affect the amount of Ca2+ entering during stimulation, it is important to determine the level of the ion close to the sensory cells. Using fluorescence imaging and fluorescence correlation spectroscopy, we measured the Ca2+ concentration near guinea pig stereocilia in situ. Surprisingly, we found that an acellular accessory structure close to the stereocilia, the tectorial membrane, had much higher Ca2+ than the surrounding fluid. Loud sounds depleted Ca2+ from the tectorial membrane, and Ca2+ manipulations had large effects on hair cell function. Hence, the tectorial membrane contributes to control of hearing sensitivity by influencing the ionic environment around the stereocilia.

D-methionine immediate and continued rescue after noise exposure does not prevent temporary threshold shift but alters cochlear and serum antioxidant levels.

OBJECTIVE: Determine if D-methionine (D-met) rescue prevents temporary threshold shift (TTS) from steady-state or impulse noise and determine D-met's impact on serum and cochlear antioxidant levels. DESIGN: D-met at 50, 100 or 200 mg/kg/doses were administered 0, 6 and 18 hours-post noise. ABRs at baseline and 24 hours post-noise measured TTS. Serum (SOD, CAT, GR, GPx) and cochlear (GSH, GSSG) antioxidant levels measured physiological influence. Three control groups, with impulse or steady-state or without noise, were saline-injected. STUDY SAMPLE: Ten Chinchillas/group. RESULTS: D-met rescue did not significantly reduce TTS or impact serum CAT, SOD, GPx or GR levels vs. noise-exposed control groups, but TTS was greater in all groups relative to no-noise controls. D-met significantly elevated CAT at 50 mg/kg vs. steady-state controls and SOD at 200 mg/kg vs. impulse noise controls. D-met significantly reduced cochlear GSH/GSSG ratios in the 100 mg/kg D-met group vs. impulse noise controls. CONCLUSIONS: While D-met rescue has reduced permanent threshold shift in previous studies, it did not reduce TTS in this study. However, D-met rescue did alter selective serum and cochlear oxidative state changes 24 hours post-noise relative to controls. Results demonstrate TTS studies do not always predict PTS protection in otoprotectant experimental designs.

Prevention of Noise-Induced Hearing Loss In Vivo: Continuous Application of Insulin-like Growth Factor 1 and Its Effect on Inner Ear Synapses, Auditory Function and Perilymph Proteins.

As noise-induced hearing loss (NIHL) is a leading cause of occupational diseases, there is an urgent need for the development of preventive and therapeutic interventions. To avoid user-compliance-based problems occurring with conventional protection devices, the pharmacological prevention is currently in the focus of hearing research. Noise exposure leads to an increase in reactive oxygen species (ROS) in the cochlea. This way antioxidant agents are a promising option for pharmacological interventions. Previous animal studies reported preventive as well as therapeutic effects of Insulin-like growth factor 1 (IGF-1) in the context of NIHL. Unfortunately, in patients the time point of the noise trauma cannot always be predicted, and additive effects may occur. Therefore, continuous prevention seems to be beneficial. The present study aimed to investigate the preventive potential of continuous administration of low concentrations of IGF-1 to the inner ear in an animal model of NIHL. Guinea pigs were unilaterally implanted with an osmotic minipump. One week after surgery they received noise trauma, inducing a temporary threshold shift. Continuous IGF-1 delivery lasted for seven more days. It did not lead to significantly improved hearing thresholds compared to control animals. Quite the contrary, there is a hint for a higher noise susceptibility. Nevertheless, changes in the perilymph proteome indicate a reduced damage and better repair mechanisms through the IGF-1 treatment. Thus, future studies should investigate delivery methods enabling continuous prevention but reducing the risk of an overdosage.

Transient peripheral vestibular hypofunction measured with vestibular short-latency evoked potentials following noise exposure in rats.

Exposure to 120 dB sound pressure level (SPL) band-limited noise results in delayed onset latency and reduced vestibular short-latency evoked potential (VsEP) responses. These changes are still present 4 wk after noise overstimulation. Noise-induced hearing loss (NIHL) has been shown to vary in extent and duration based on the noise intensity. This study investigated whether noise-induced peripheral vestibular hypofunction (NPVH) would also decrease in extent and/or duration with less intense noise exposure. In the present study, rats were exposed to a less intense noise (110 dB SPL) but for the same duration (6 h) and frequency range (500-4,000 Hz) as used in previous studies. The VsEP was assessed 1, 3, 7, 14, 21, and 28 days after noise exposure. In contrast to 120 dB SPL noise exposure, the 110 dB SPL noise exposures produced smaller deficits in VsEP responses that fully recovered in 62% (13/21) of animals within 1 wk. These findings suggest that NPVH, a loss or attenuation of VsEP responses with a requirement for elevated stimulus intensity to elicit measurable responses, is similar to NIHL, that is, lower sound levels produce a smaller or transient deficit. These results show that it will be important to determine the extent and duration of vestibular hypofunction for different noise exposure conditions and their impact on balance.NEW & NOTEWORTHY This is the first study to show a temporary noise-induced peripheral vestibular hypofunction that recovers following exposure to continuous noise.

Temporary threshold shift after noise exposure in hypobaric hypoxia at high altitude: results of the ADEMED expedition 2011.

OBJECTIVES: To evaluate whether there is an increased risk for noise-induced hearing loss at high altitude rsp. in hypobaric hypoxia. METHODS: Thirteen volunteers got standard audiometry at 125, 250, 500, 750, 1000, 1500, 2000, 3000, 4000, 6000, and 8000 Hz before and after 10 min of white noise at 90 dB. The system was calibrated for the respective altitude. Measurements were performed at Kathmandu (1400 m) and at Gorak Shep (5300 m) (Solo Khumbu/Nepal) after 10 days of acclimatization while on trek. Temporary threshold shift (TTS) was analyzed by descriptive statistics and by factor analysis. RESULTS: TTS is significantly more pronounced at high altitudes. Acclimatization does not provide any protection of the inner ear, although it increases arterial oxygen saturation. CONCLUSION: The thresholds beyond which noise protection is recommended (> 80 dB) or necessary (> 85 dB) are not sufficient at high altitudes. We suggest providing protective devices above an altitude of 1500 m ("ear threshold altitude") when noise level is higher than 75 dB and using them definitively above 80 dB. This takes the individual reaction on hypobaric hypoxia at high altitude into account.

Temporary threshold shift following ear canal microsuction.

Objectives: To investigate a temporary threshold shift (TTS) of hearing and pain/discomfort caused by the microsuction procedure. Hearing loss induced by impacted cerumen was also investigated.Design: Impacted cerumen was removed from patients using microsuction. Hearing assessments were carried out before the procedure, immediately after and 1-week later. Hearing thresholds measured in different sessions were compared to determine the TTS caused by the microsuction procedure and hearing loss induced by impacted cerumen. A questionnaire was used to evaluate the pain/discomfort experienced by patients.Study Sample: 30 patients (50 ears) were recruited from a cerumen removal clinic.Results: Significant hearing loss caused by impacted earwax was found across individual frequencies (mean 11.4 dB, maximum 38.1 dB). A TTS appeared in 43/50 (86%) ears, ranging from 0 to 16.2 dB averaged across frequencies between 0.25 and 8 kHz, with the highest TTS at 6 kHz. Pain and discomfort levels were both rated low, the mean levels were 1.2 (SD = 0.5) and 1.6 (SD = 0.5) respectively on a scale from 1 to 10.Conclusions: Microsuction appears to be a well-tolerated and preferred procedure for removing impacted cerumen. Because of the significant TTS induced by the microsuction procedure, safety concerns from a hearing perspective should be raised with the patient.

Onset kinetics of noise-induced purinergic adaptation of the 'cochlear amplifier'.

A major component of slowly reversible hearing loss which develops with sustained exposure to noise has been attributed to release of ATP in the cochlea activating P2X2 receptor (P2X2R) type ATP-gated ion channels. This purinergic humoral adaptation is thought to enable the highly sensitive hearing organ to maintain function with loud sound, protecting the ear from acoustic overstimulation. In the study that established this hearing adaptation mechanism as reported by Housley et al. (Proc Natl Acad Sci U S A 110:7494-7499, 2013), the activation kinetics were determined in mice from auditory brainstem response (ABR) threshold shifts with sustained noise presentation at time points beyond 10 min. The present study was designed to achieve finer resolution of the onset kinetics of purinergic hearing adaptation, and included the use of cubic (2f1-f2) distortion product otoacoustic emissions (DPOAEs) to probe whether the active mechanical outer hair cell 'cochlear amplifier' contributed to this process. We show that the ABR and DPOAE threshold shifts were largely complete within the first 7.5 min of moderate broadband noise (85 dB SPL) in wildtype C57Bl/6J mice. The ABR and DPOAE adaptation rates were both best fitted by a single exponential function with ~ 3 min time constants. ABR and DPOAE threshold shifts with this noise were minimal in mice null for the P2rx2 gene encoding the P2X2R. The findings demonstrate a considerably faster purinergic hearing adaptation to noise than previously appreciated. Moreover, they strongly implicate the outer hair cell as the site of action, as the DPOAEs stem from active cochlear electromotility.

Treatment of military acoustic accidents with N-Acetyl-L-cysteine (NAC).

OBJECTIVE: To study if the antioxidant (AO) N-Acetyl-L-cysteine (NAC) reduces the risk of hearing loss after acoustic accidents in humans. DESIGN: A retrospective, observational study. STUDY SAMPLE: Personnel of the Swedish Armed Forces (SAF) exposed to military acoustic accidents during a 5 year period. Included in the study were 221 cases (mean age: 22.9 years). Most of the exposures, 84%, were weapon related. NAC (400 mg) was given directly after the accident in 146 cases; 75 had not received NAC. RESULTS: The prevalence of hearing thresholds ≥25 dB HL, and the incidence of threshold shifts ≥10 dB, was lower in the NAC group than in the non-NAC group directly after the noise exposure. The deterioration was temporary and not discernable a long time after the accident. The difference was most pronounced in the right ear. The risk reduction to get a temporary hearing loss (TTS), affecting one or both ears was 39% (significant) in the NAC group. CONCLUSIONS: The study has demonstrated a significant reduction of the incidence of TTS by the use of NAC. Since cases of both permanent hearing loss (PTS) and noise-induced tinnitus are recruited from cases with TTS, the demonstrated risk reduction indicates a positive effect of NAC.

Impacts of broadband sound on silver (Hypophthalmichthys molitrix) and bighead (H. nobilis) carp hearing thresholds determined using auditory evoked potential audiometry.

Invasive silver (Hypophthalmichthys molitrix) and bighead (H. nobilis) carp, collectively referred to as bigheaded carps, threaten aquatic ecosystems of the Upper Midwestern USA. Due to the extensive ecological impacts associated with these species, prevention of their further range expansion is the aim for fisheries management. Recent behavioral studies indicate bigheaded carps are deterred by acoustic barriers and exhibit negative phonotaxis in response to anthropogenic sound sources (≥ 150 dB re 1 µPa). However, the impact of long-term exposure to these sounds on the hearing capabilities of bigheaded carps has not been well documented. In this study, the auditory evoked potential (AEP) technique was used to determine auditory thresholds among bigheaded carps before and after exposure to high intensity (155.7 ± 4.7 dB re 1 µPa SPLrms; - 8.0 ± 4.7 dB re 1 ms-2 PALrms; mean ± SD) broadband sound. Fish were exposed to sound for 30 min or 24 h and AEP measurements were taken at three time points: immediately after exposure, 48 h, or 96 h later. Results indicate that silver and bighead carp experience temporary threshold shifts (TTSs) in frequency detection following sound exposure with the magnitude and length of TTS correlated with exposure duration. The findings from this study will be used to increase the long-term efficacy of acoustical deterrent measures aimed at preventing further range expansion of bigheaded carps.

Commentary on the regulatory implications of noise-induced cochlear neuropathy.

OBJECTIVE: A discussion on whether recent research on noise-induced cochlear neuropathy in rodents justifies changes in current regulation of occupational noise exposure. DESIGN: Informal literature review and commentary, relying on literature found in the authors' files. No formal literature search was performed. STUDY SAMPLE: Published literature on temporary threshold shift (TTS) and cochlear pathology, in humans and experimental animals, as well as the regulations of the US Occupational Safety and Health Administration (OSHA). RESULTS: Humans are less susceptible to TTS, and probably to cochlear neuropathy, than rodents. After correcting for inter-species audiometric differences (but not for differences in susceptibility), exposures that caused cochlear neuropathy in rodents already exceed OSHA limits. Those exposures also caused "pathological TTS" (requiring more than 24 h to recover), which does not appear to occur with human broadband noise exposure permissible under OSHA. CONCLUSION: It would be premature to conclude that noise exposures permissible under OSHA can cause cochlear neuropathy in humans.

A faceoff with hazardous noise: Noise exposure and hearing threshold shifts of indoor hockey officials.

Noise exposure and hearing thresholds of indoor hockey officials of the Western States Hockey League were measured to assess the impact of hockey game noise on hearing sensitivity. Twenty-nine hockey officials who officiated the league in an arena in southeastern Wyoming in October, November, and December 2014 participated in the study. Personal noise dosimetry was conducted to determine if officials were exposed to an equivalent sound pressure level greater than 85 dBA. Hearing thresholds were measured before and after hockey games to determine if a 10 dB or greater temporary threshold shift in hearing occurred. Pure-tone audiometry was conducted in both ears at 500, 1000, 2000, 3000, 4000, 6000, and 8000 Hz. All noise exposures were greater than 85 dBA, with a mean personal noise exposure level of 93 dBA (SD = 2.2), providing 17.7% (SD = 6.3) of the officials' daily noise dose according to the OSHA criteria. Hearing threshold shifts of 10 dB or greater were observed in 86.2% (25/29) of officials, with 36% (9/25) of those threshold shifts equaling 15 dB or greater. The largest proportion of hearing threshold shifts occurred at 4000 Hz, comprising 35.7% of right ear shifts and 31.8% of left ear shifts. The threshold shifts between the pre- and post-game audiometry were statistically significant in the left ear at 500 (p=.019), 2000 (p=.0009), 3000 (p<.0001) and 4000 Hz (p=.0002), and in the right ear at 2000 (p=.0001), 3000 (p=.0001) and 4000 Hz (p<.0001), based on Wilcoxon-ranked sum analysis. Although not statistically significant at alpha = 0.05, logistic regression indicated that with each increase of one dB of equivalent sound pressure measured from personal noise dosimetry, the odds of a ≥ 10 dB TTS were increased in the left ear at 500 (OR=1.33, 95% CI 0.73-2.45), 3000 (OR=1.02, 95% CI 0.68-1.51), 4000 (OR=1.26, 95% CI 0.93-1.71) and 8000 Hz (OR=1.22, 95% CI 0.76-1.94) and in the right ear at 6000 (OR=1.03, 95% CI 0.14-7.84) and 8000 Hz (OR=1.29, 95% CI 0.12-13.83). These findings suggest that indoor hockey officials are exposed to hazardous levels of noise, experience temporary hearing loss after officiating games, and a hearing conservation program is warranted. Further temporary threshold shift research has the potential to identify officials of other sporting events that are at an increased risk of noise-induced hearing loss.

Aging after noise exposure: acceleration of cochlear synaptopathy in "recovered" ears.

Cochlear synaptic loss, rather than hair cell death, is the earliest sign of damage in both noise- and age-related hearing impairment (Kujawa and Liberman, 2009; Sergeyenko et al., 2013). Here, we compare cochlear aging after two types of noise exposure: one producing permanent synaptic damage without hair cell loss and another producing neither synaptopathy nor hair cell loss. Adult mice were exposed (8-16 kHz, 100 or 91 dB SPL for 2 h) and then evaluated from 1 h to ∼ 20 months after exposure. Cochlear function was assessed via distortion product otoacoustic emissions and auditory brainstem responses (ABRs). Cochlear whole mounts and plastic sections were studied to quantify hair cells, cochlear neurons, and the synapses connecting them. The synaptopathic noise (100 dB) caused 35-50 dB threshold shifts at 24 h. By 2 weeks, thresholds had recovered, but synaptic counts and ABR amplitudes at high frequencies were reduced by up to ∼ 45%. As exposed animals aged, synaptopathy was exacerbated compared with controls and spread to lower frequencies. Proportional ganglion cell losses followed. Threshold shifts first appeared >1 year after exposure and, by ∼ 20 months, were up to 18 dB greater in the synaptopathic noise group. Outer hair cell losses were exacerbated in the same time frame (∼ 10% at 32 kHz). In contrast, the 91 dB exposure, producing transient threshold shift without acute synaptopathy, showed no acceleration of synaptic loss or cochlear dysfunction as animals aged, at least to ∼ 1 year after exposure. Therefore, interactions between noise and aging may require an acute synaptopathy, but a single synaptopathic exposure can accelerate cochlear aging.

Echolocation behavior in big brown bats is not impaired after intense broadband noise exposures.

Echolocating bats emit trains of intense ultrasonic biosonar pulses and listen to weaker echoes returning from objects in their environment. Identification and categorization of echoes are crucial for orientation and prey capture. Bats are social animals and often fly in groups in which they are exposed to their own emissions and to those from other bats, as well as to echoes from multiple surrounding objects. Sound pressure levels in these noisy conditions can exceed 110 dB, with no obvious deleterious effects on echolocation performance. Psychophysical experiments show that big brown bats (Eptesicus fuscus) do not experience temporary threshold shifts after exposure to intense broadband ultrasonic noise, but it is not known if they make fine-scale adjustments in their pulse emissions to compensate for any effects of the noise. We investigated whether big brown bats adapt the number, temporal patterning or relative amplitude of their emitted pulses while flying through an acoustically cluttered corridor after exposure to intense broadband noise (frequency range 10-100 kHz; sound exposure level 152 dB). Under these conditions, four bats made no significant changes in navigation errors or in pulse number, timing and amplitude 20 min, 24 h or 48 h after noise exposure. These data suggest that big brown bats remain able to perform difficult echolocation tasks after exposure to ecologically realistic levels of broadband noise.

Broadband noise exposure does not affect hearing sensitivity in big brown bats (Eptesicus fuscus).

In many vertebrates, exposure to intense sounds under certain stimulus conditions can induce temporary threshold shifts that reduce hearing sensitivity. Susceptibility to these hearing losses may reflect the relatively quiet environments in which most of these species have evolved. Echolocating big brown bats (Eptesicus fuscus) live in extremely intense acoustic environments in which they navigate and forage successfully, both alone and in company with other bats. We hypothesized that bats may have evolved a mechanism to minimize noise-induced hearing losses that otherwise could impair natural echolocation behaviors. The hearing sensitivity of seven big brown bats was measured in active echolocation and passive hearing tasks, before and after exposure to broadband noise spanning their audiometric range (10-100 kHz, 116 dB SPL re. 20 µPa rms, 1 h duration; sound exposure level 152 dB). Detection thresholds measured 20 min, 2 h or 24 h after exposure did not vary significantly from pre-exposure thresholds or from thresholds in control (sham exposure) conditions. These results suggest that big brown bats may be less susceptible to temporary threshold shifts than are other terrestrial mammals after exposure to similarly intense broadband sounds. These experiments provide fertile ground for future research on possible mechanisms employed by echolocating bats to minimize hearing losses while orienting effectively in noisy biological soundscapes.

Temporary Threshold Shifts in Naïve and Experienced Belugas: Can Dampening of the Effects of Fatiguing Sounds Be Learned?

In belugas (Delphinapterus leucas), substantial (10-15 dB) differences in temporary threshold shifts (TTSs) were observed between the first and subsequent experimental sessions in the same subjects. In the first session (naïve subject state), the TTSs produced by exposure to fatiguing noises were larger than the TTSs produced in subsequent sessions (experienced subject state). After one to two sessions, the TTSs stabilized. The baseline hearing thresholds did not differ between the naïve and experienced states. One possible explanation for this effect is that the animals learned to dampen their hearing during exposure to fatiguing noises and thus mitigate the impact of those noises.

Is Sound Exposure Level a Convenient Metric to Characterize Fatiguing Sounds? A Study in Beluga Whales.

Both the level and duration of fatiguing sounds influence temporary threshold shifts (TTSs) in odontocetes. These two parameters were combined into a sound exposure level (SEL). In the beluga whale Delphinapterus leucas, TTSs were investigated at various sound pressure level (SPL)-to-duration ratios at a specific SEL. At low SPL-to-duration ratios, the dependence was positive: shorter high-level sounds produced greater TTSs than long low-level sounds of the same SEL. At high SPL-to-duration ratios, the dependence was negative: long low-level sounds produced greater TTSs than short high-level sounds of the same SEL. Thus, the validity of SEL as a metric for fatiguing sound efficiency is limited.

Auditory Effects of Multiple Impulses from a Seismic Air Gun on Bottlenose Dolphins (Tursiops truncatus).

Auditory thresholds were measured in three bottlenose dolphins before and after exposure to ten impulses from a seismic air gun. Thresholds were measured using behavioral and electrophysiological methods to determine the amount of temporary threshold shift induced. The results suggest that the potential for seismic surveys using air guns to cause auditory effects on dolphins may be lower than previously predicted; however, two of the three dolphins exhibited "anticipatory" behavioral changes at the highest exposure condition that suggested they were attempting to mitigate the effects of the exposures.

Relationship Between Hair Cell Loss and Hearing Loss in Fishes.

Exposure to intense sound or ototoxic chemicals can damage the auditory hair cells of vertebrates, resulting in hearing loss. Although the relationship between such hair cell damage and auditory function is fairly established for terrestrial vertebrates, there are limited data available to understand this relationship in fishes. Although investigators have measured either the morphological damage of the inner ear or the functional deficits in the hearing of fishes, very few have directly measured both in an attempt to find a relationship between the two. Those studies that have examined both auditory hair cell damage in the inner ear and the resulting hearing loss in fishes are reviewed here. In general, there is a significant linear relationship between the number of hair cells lost and the severity of hearing threshold shifts, although this varies between species and different hair cell-damaging stimuli. After trauma to the fish ear, auditory hair cells are able to regenerate to control level densities. With this regeneration also comes a restoration of hearing. Thus there is also a significant relationship between hair cell recovery and hearing recovery in fishes.

Assessment of Marine Mammal Impact Zones for Use of Military Sonar in the Baltic Sea.

Military sonars are known to have caused cetaceans to strand. Navies in shallow seas use different frequencies and sonar pulses, commonly frequencies between 25 and 100 kHz, compared with most studied NATO sonar systems that have been evaluated for their environmental impact. These frequencies match the frequencies of best hearing in the harbor porpoises and seals resident in the Baltic Sea. This study uses published temporary and permanent threshold shifts, measured behavioral response thresholds, technical specifications of a sonar system, and environmental parameters affecting sound propagation common for the Baltic Sea to estimate the impact zones for harbor porpoises and seals.

Noise Exposure Criteria for Harbor Porpoises.

Despite a major research effort, no generally accepted exposure limits are available for harbor porpoises. Recent studies of the temporary threshold shift (TTS) in porpoises indicate that the sound exposure levels (SELs) required to induce low levels of TTS depend on stimulus frequency and roughly parallel the shape of the audiogram. A number of studies on behavioral avoidance reactions (negative phonotaxis) to pingers, seal scarers, and pile driving show a similar dependence on stimulus frequency. Both TTS and behavioral data suggest that weighting sound pressure levels with a filter function resembling the inverted audiogram would be appropriate.