A review of auditory gain, low-level noise and sound therapy for tinnitus and hyperacusis.

Objective: This article reviews: (1) the evidence related to enhanced central gain as a potential mechanism for the generation of tinnitus and hyperacusis, (2) the neuroplastic changes induced by prolonged, low-level sound stimulation and (3) the clinical effectiveness of various sound therapies and amplification for the treatment of tinnitus and hyperacusis.Design: General literature review.Study sample: Peer-reviewed articles related to auditory neural gain, prolonged low-level noise exposure and effectiveness of sound therapy.Results: A large body of literature exists supporting the enhanced neural gain model of tinnitus and hyperacusis. Neuroplastic changes associated with prolonged low-level noise show evidence of reversing enhanced neural gain, which should theoretically reduce percepts of tinnitus and/or hyperacusis. However, the available clinical evidence assessing the efficacy of sound therapy to reduce tinnitus or hyperacusis lacks controlled clinical trials to accurately assess the effectiveness of sound therapy.Conclusions: The available literature from basic science studies supports the neural gain model of tinnitus and hyperacusis, which conceivably should be effectively managed with sound therapy. However, well-controlled clinical trials are needed before conclusions can be made on the effectiveness of sound therapy for tinnitus and hyperacusis.

Tone-in-noise detection deficits in elderly patients with clinically normal hearing.

PURPOSE: One of the most common complaints among the elderly is the inability to understand speech in noisy environments. In many cases, these deficits are due to age-related hearing loss; however, some of the elderly that have difficulty hearing in noise have clinically normal pure-tone thresholds. While speech in noise testing is informative, it fails to identify specific frequencies responsible for the speech processing deficit. Auditory neuropathy patients and animal models of hidden hearing loss suggest that tone-in-noise thresholds may provide frequency specific information for those patients who express difficulty, but have normal thresholds in quiet. Therefore, we aimed to determine if tone-in-noise thresholds could be a useful measure in detecting age-related hearing deficits, despite having normal audiometric thresholds. MATERIALS & METHODS: We tested this hypothesis by measuring tone-in-noise thresholds in 11 Old (62.4 ±â€¯5 years) and 21 Young (23.1 ±â€¯2.2 years) patients with clinically normal thresholds. Tone thresholds were measured in a quite sound field, then in 20, 30 and 40 dB HL broadband noise. RESULTS: Despite having normal hearing (thresholds ≤25 dB HL), the Old patients had significantly worse tone-in-noise thresholds than the Young patients at 0.125, 4, and 8 kHz. Linear regression analysis showed that the growth of masking in Old and Young patients was nearly identical at all frequencies. However, the amount of masking at low and high frequencies was typically 10-18 dB greater in the Old patients compared to the Young, except near 1 kHz. The frequency-dependent changes in masking are discussed in the context of a "line busy" model and temporal bone studies of auditory nerve fiber loss.

Psychophysical changes in temporal processing in chinchillas with noise-induced hearing loss: A literature review.

It is well-established that excessive noise exposure can systematically shift audiometric thresholds (i.e., noise-induced hearing loss, NIHL) making sounds at the lower end of the dynamic range difficult to detect. An often overlooked symptom of NIHL is the degraded ability to resolve temporal fluctuations in supra-threshold signals. Given that the temporal properties of speech are highly dynamic, it is not surprising that NIHL greatly reduces one's ability to clearly decipher spoken language. However, systematic characterization of noise-induced impairments on supra-threshold signals in humans is difficult given the variability in noise exposure among individuals. Fortunately, the chinchilla is audiometrically similar to humans, making it an ideal animal model to investigate noise-induced supra-threshold deficits. Through a series of studies using the chinchilla, the authors have elucidated several noise-induced deficits in temporal processing that occur at supra-threshold levels. These experiments highlight the importance of the chinchilla model in developing an understanding of noise-induced deficits in temporal processing.

Tinnitus Assessment and Management: A Survey of Practicing Audiologists in the United States and Canada.

BACKGROUND: Tinnitus is a prevalent auditory disorder that can become severely debilitating. Despite decades of investigation, there remains no conclusive cure for tinnitus. Clinical practice guidelines (CPGs) are available for assessing and managing tinnitus. Even though such guidelines have been available for several years, the degree that audiologists adhere to them has remained unexplored. PURPOSE OF STUDY: To determine what clinical practices are commonly used by audiologists in the assessment and management of the patient population with tinnitus, we administered an online survey to audiologists practicing in the United States and Canada. RESULTS: Among the audiologists that completed the survey and were included in the final analysis (n = 61), 70% were from the United States and 30% were from Canada. The audiologists represented a wide range of clinical experience (1-35 years). On average, those who completed the survey were relatively confident in their ability to assess and manage tinnitus patients indicated by a 0 to 100 Likert scale, with 0 representing no confidence (mean 72.5, ± 21.5 standard deviation). The most commonly reported tinnitus assessment tools were pure tone audiogram (0.25-8 kHz), administration of standardized questionnaires, and tinnitus pitch and loudness matching. Approximately half (55%) of audiologists indicated they include otoacoustic emissions, while less audiologists (<40%) reported measuring high-frequency thresholds, minimum masking levels, or loudness discomfort levels. The most common recommendation for tinnitus patients was amplification (87%), followed by counseling (80%) and sound therapy (79%). CONCLUSION: Few audiologists administer a truly comprehensive tinnitus assessment and ∼20% indicated not recommending counseling or sound therapy to manage tinnitus. The results are discussed in the context of what is explicitly indicated in published CPGs, professional organization recommendations, and recent findings of peer-reviewed literature.

Occupational Noise: Auditory and Non-Auditory Consequences.

Occupational noise exposure accounts for approximately 16% of all disabling hearing losses, but the true value and societal costs may be grossly underestimated because current regulations only identify hearing impairments in the workplace if exposures result in audiometric threshold shifts within a limited frequency region. Research over the past several decades indicates that occupational noise exposures can cause other serious auditory deficits such as tinnitus, hyperacusis, extended high-frequency hearing loss, and poor speech perception in noise. Beyond the audiogram, there is growing awareness that hearing loss is a significant risk factor for other debilitating and potentially life-threatening disorders such as cardiovascular disease and dementia. This review discusses some of the shortcomings and limitations of current noise regulations in the United States and Europe.

Intermittent Low-level Noise Causes Negative Neural Gain in the Inferior Colliculus.

The central auditory system shows a remarkable ability to rescale its neural representation of loudness following long-term, low-level acoustic exposures; even when the noise is presented intermittently. Circadian rhythms exert potent biological effects, but it remains unclear if acoustic exposures occurring during the light or dark cycle affect the neurophysiological changes involved in loudness rescaling. To address this issue we exposed rats to intermittent (12 h/day), low-level noise (10-20 kHz, 75 dB SPL) for 5 weeks; exposures occurred during either the light (inactive) or dark (active) phase of the circadian cycle. The 12-h exposures, whether occurring during the light or dark phase, did not significantly alter cochlear function as reflected in distortion product otoacoustic emissions and compound action potential responses. However, neural activity in the inferior colliculus demonstrated negative gain in a frequency- and intensity-specific manner compared to unexposed controls; the magnitude and direction of the neuroplastic changes in the inferior colliculus were largely the same regardless of whether the 12-h noise exposures occurred during the light or dark phase of the circadian cycle. These neuroplastic changes could become relevant for low-level sound therapies used to treat hyperacusis.

Auditory central gain compensates for changes in cochlear output after prolonged low-level noise exposure.

Remarkably, the central auditory system can modify the strength of its sound-evoked neural response based on prior acoustic experiences, a phenomenon referred to as central gain. Gain changes are well documented following traumatic noise exposure, but much less is known about central gain dynamics following prolonged exposure to low-level noise, a common acoustic experience in many urban and work environments. We recently reported that the neural output of the cochlea is reduced, while gain was enhanced in the inferior colliculus (IC) following a 5-week exposure to 75 dB noise. To determine if similar effects were present at even lower intensities, we exposed rats to a 65 dB noise expecting to see little to no change in the cochlea or IC. The exposure had little effect on distortion product otoacoustic emissions and did not cause any hair cell loss. However, the amplitude of the CAP, which reflects the neural output of cochlea, was depressed by 50-75%. Surprisingly, neural responses from the IC were enhanced up to 70%, mainly at frequencies within the noise exposure band. One-week post-exposure, CAP amplitudes returned to normal at frequencies within or above the exposure band, whereas responses evoked by frequencies below the exposure band were enhanced by more than 80%. In contrast, IC responses below the exposure frequency were depressed 10-20% whereas responses within the exposure frequency band were enhanced 10-20%. Thus, the central auditory system dynamically up- and down-regulates its gain to maintain supra-threshold neural responses within a narrow homeostatic range; a function that likely contributes to the prevention of sounds from being perceived as muffled or too loud.

Isoflurane anesthesia suppresses distortion product otoacoustic emissions in rats.

A commonly used anesthetic, isoflurane, can impair auditory function in a dose-dependent manner. However, in rats, isoflurane-induced auditory impairments have only been assessed with auditory brainstem responses; a measure which is unable to distinguish if changes originate from the central or peripheral auditory system. Studies performed in other species, such as mice and guinea-pigs, suggests auditory impairment stems from disrupted OHC amplification. Despite the wide use of the rat in auditory research, these observations have yet to be replicated in the rat animal model. This study used distortion product otoacoustic emissions to assess outer hair cell function in rats that were anesthetized with either isoflurane or a ketamine/xylazine cocktail for approximately 45 min. Results indicate that isoflurane can significantly reduce DPOAE amplitudes compared to ketamine/xylazine, and that responses were more variable with isoflurane than ketamine/xylazine over the 45-min test period. Based on these observations, isoflurane should be used with caution when assessing peripheral auditory function to avoid potentially confounding effects.

Prolonged low-level noise exposure reduces rat distortion product otoacoustic emissions above a critical level.

Prolonged noise exposures presented at low to moderate intensities are often used to investigate neuroplastic changes in the central auditory pathway. A common assumption in many studies is that central auditory changes occur independent of any hearing loss or cochlear dysfunction. Since hearing loss from a long term noise exposure can only occur if the level of the noise exceeds a critical level, prolonged noise exposures that incrementally increase in intensity can be used to determine the critical level for any given species and noise spectrum. Here we used distortion product otoacoustic emissions (DPOAEs) to determine the critical level in male, inbred Sprague-Dawley rats exposed to a 16-20 kHz noise that increased from 45 to 92 dB SPL in 8 dB increments. DPOAE amplitudes were largely unaffected by noise presented at 60 dB SPL and below. However, DPOAEs within and above the frequency band of the exposures declined rapidly at noise intensities presented at 68 dB SPL and above. The largest and most rapid decline in DPOAE amplitude occurred at 30 kHz, nearly an octave above the 16-20 kHz exposure band. The rate of decline in DPOAE amplitude was 0.54 for every 1 dB increase in noise intensity. Using a linear regression calculation, the estimated critical level for 16-20 kHz noise was remarkably low, approximately 60 dB SPL. These results indicate that long duration, 16-20 kHz noise exposures in the 65-70 dB SPL range likely affect the cochlea and central auditory system of male Sprague-Dawley rats.

Prolonged low-level noise-induced plasticity in the peripheral and central auditory system of rats.

Prolonged low-level noise exposure alters loudness perception in humans, presumably by decreasing the gain of the central auditory system. Here we test the central gain hypothesis by measuring the acute and chronic physiologic changes at the level of the cochlea and inferior colliculus (IC) after a 75-dB SPL, 10-20-kHz noise exposure for 5weeks. The compound action potential (CAP) and summating potential (SP) were used to assess the functional status of the cochlea and 16 channel electrodes were used to measure the local field potentials (LFP) and multi-unit spike discharge rates (SDR) from the IC immediately after and one-week post-exposure. Measurements obtained immediately post-exposure demonstrated a significant reduction in supra-threshold CAP amplitudes. In contrast to the periphery, sound-evoked activity in the IC was enhanced in a frequency-dependent manner consistent with models of enhanced central gain. Surprisingly, one-week post-exposure supra-threshold responses from the cochlea had not only recovered, but were significantly larger than normal, and thresholds were significantly better than controls. Moreover, sound-evoked hyperactivity in the IC was sustained within the noise exposure frequency band but suppressed at higher frequencies. When response amplitudes representing the neural output of the cochlea and IC activity at one-week post exposure were compared with control animal responses, a central attenuation phenomenon becomes evident, which may play a key role in understanding why low-level noise can sometimes ameliorate tinnitus and hyperacusis percepts.

N-acetyl-cysteine prevents age-related hearing loss and the progressive loss of inner hair cells in γ-glutamyl transferase 1 deficient mice.

Genetic factors combined with oxidative stress are major determinants of age-related hearing loss (ARHL), one of the most prevalent disorders of the elderly. Dwarf grey mice, Ggt1dwg/dwg, are homozygous for a loss of function mutation of the g-glutamyl transferase 1 gene, which encodes an important antioxidant enzyme critical for the resynthesis of glutathione (GSH). Since GSH reduces oxidative damage, we hypothesized that Ggt1dwg/dwg mice would be susceptible to ARHL. Surprisingly, otoacoustic emissions and cochlear microphonic potentials, which reflect cochlear outer hair cell (OHC) function, were largely unaffected in mutant mice, whereas auditory brainstem responses and the compound action potential were grossly abnormal. These functional deficits were associated with an unusual and selective loss of inner hair cells (IHC), but retention of OHC and auditory nerve fibers. Remarkably, hearing deficits and IHC loss were completely prevented by N-acetyl-L-cysteine, which induces de novo synthesis of GSH; however, hearing deficits and IHC loss reappeared when treatment was discontinued. Ggt1dwg/dwg mice represent an important new model for investigating ARHL, therapeutic interventions, and understanding the perceptual and electrophysiological consequences of sensory deprivation caused by the loss of sensory input exclusively from IHC.

Potassium ion channel openers, Maxipost and Retigabine, protect against peripheral salicylate ototoxicity in rats.

Sodium Salicylate (SS) reliably induces a sensorineural hearing loss and tinnitus when administered in high doses. Recent animal modeled studies indicate that potassium channel openers such as Maxipost and Retigabine (RTG) can block SS- or noise-induced tinnitus respectively; however, the origins and mechanisms are poorly understood. Since SS blocks the same potassium channels that Maxipost and RTG open, we postulated that these drugs might influence peripheral auditory function. To test this hypothesis Maxipost or RTG were administered alone or in combination with SS in rats. When administered alone, Maxipost and RTG had no effect on distortion product otoacoustic emissions (DPOAE) or compound action potentials (CAPs). However when Maxipost or RTG were administered with SS, Maxipost prevented the SS-reduced CAP amplitudes at high frequencies (≥20 kHz) and RTG prevented SS-reduced CAP amplitudes at low frequencies (≤8 kHz). These results suggest that Maxipost and RTG can protect against peripheral damage and therefore reduce the incidence of tinnitus.

Prolonged noise exposure-induced auditory threshold shifts in rats.

Noise-induced hearing loss (NIHL) initially increases with exposure duration, but eventually reaches an asymptotic threshold shift (ATS) once the exposure duration exceeds 18-24 h. Equations for predicting the ATS have been developed for several species, but not for rats, even though this species is extensively used in noise exposure research. To fill this void, we exposed rats to narrowband noise (NBN, 16-20 kHz) for 5 weeks starting at 80 dB SPL in the first week and then increasing the level by 6 dB per week to a final level of 104 dB SPL. Auditory brainstem responses (ABR) were recorded before, during, and following the exposure to determine the amount of hearing loss. The noise induced threshold shift to continuous long-term exposure, defined as compound threshold shift (CTS), within and above 16-20 kHz increased with noise level at the rate of 1.82 dB threshold shift per dB of noise level (NL) above a critical level (C) of 77.2 dB SPL i.e. CTS = 1.82(NL-77.2). The normalized amplitude of the largest ABR peak measured at 100 dB SPL decreased at the rate of 3.1% per dB of NL above the critical level of 76.9 dB SPL, i.e., %ABR Reduction = 3.1%(NL-76.9). ABR thresholds measured >30 days post-exposure only partially recovered resulting in a permanent threshold shift of 30-40 dB along with severe hair cell loss in the basal, high-frequency region of the cochlea. In the rat, CTS increases with noise level with a slope similar to humans and chinchillas. The critical level (C) in the rat is similar to that of humans, but higher than that of chinchillas.