A Review of Machine Learning Approaches for the Personalization of Amplification in Hearing Aids.

This paper provides a review of various machine learning approaches that have appeared in the literature aimed at individualizing or personalizing the amplification settings of hearing aids. After stating the limitations associated with the current one-size-fits-all settings of hearing aid prescriptions, a spectrum of studies in engineering and hearing science are discussed. These studies involve making adjustments to prescriptive values in order to enable preferred and individualized settings for a hearing aid user in an audio environment of interest to that user. This review gathers, in one place, a comprehensive collection of works that have been conducted thus far with respect to achieving the personalization or individualization of the amplification function of hearing aids. Furthermore, it underscores the impact that machine learning can have on enabling an improved and personalized hearing experience for hearing aid users. This paper concludes by stating the challenges and future research directions in this area.

Noise-Induced Hearing Threshold Shift Correlated with Body Weight and External-Ear Amplification in Chinchilla: a Preliminary Analysis.

BACKGROUND: External-ear amplification (EEA) has been shown to vary from 5-19 dB-A in large datasets of pediatric, adolescent, and adult human participants. However, variable EEA is an overlooked characteristic that likely plays a role in individual noise-induced hearing loss (NIHL) susceptibility. A noise exposure varying 5-19 dB-A translates to high-EEA individuals theoretically experiencing 3-4 times greater NIHL risk than low-EEA individuals. OBJECTIVE: The purpose of this preliminary analysis was to test the hypothesis that higher EEA is correlated with increased noise-induced threshold shift susceptibility. DESIGN: Nine chinchillas were exposed to 4-kHz octave-band noise at 89 dB-SPL for 24 h. Auditory brainstem response thresholds were obtained pre-exposure, 24-h post-exposure, and 4-week post-exposure. Relationships between EEA and threshold shift were analyzed. RESULTS: Open-ear EEA ranged 11-19 dB-SPL, and occluded-ear EEA ranged 10-21 dB-SPL. Higher occluded-ear EEA was correlated with increased NIHL susceptibility (p = 0.04), as was lower body weight (p = 0.01). Male animals exhibited more threshold shift than female animals (p = 0.02), lower body weight than female animals (p = 0.02), and higher occluded-ear EEA (male mean = 18 dB; female mean = 15 dB). CONCLUSIONS: Taken together, increased threshold shift susceptibility was observed in the smallest animals, animals with the highest occluded-ear EEA, and in male animals (which tended to have higher occluded-ear EEA). Given the established relationship between smaller body size and higher occluded-ear EEA, these preliminary results suggest that body size (and occluded-ear EEA; a function of body size) could be a potential, underlying driver of NIHL susceptibility differences, rather than true sex differences.

The middle ear muscle reflex: Current and future role in assessing noise-induced cochlear damage.

The middle ear muscle reflex (MEMR) in humans is a bilateral contraction of the middle ear stapedial muscle in response to moderate-to-high intensity acoustic stimuli. Clinically, MEMR thresholds have been used for differential diagnosis of otopathologies for decades. More recently, changes in MEMR amplitude or threshold have been proposed as an assessment for noise-induced synaptopathy, a subclinical form of cochlear damage characterized by suprathreshold hearing problems that occur as a function of inner hair cell (IHC) synaptic loss, including hearing-in-noise deficits, tinnitus, and hyperacusis. In animal models, changes in wideband MEMR immittance have been correlated with noise-induced synaptopathy; however, studies in humans have shown more varied results. The discrepancies observed across studies could reflect the heterogeneity of synaptopathy in humans more than the effects of parametric differences or relative sensitivity of the measurement. Whereas the etiology and degree of synaptopathy can be carefully controlled in animal models, synaptopathy in humans likely stems from multiple etiologies and thus can vary greatly across the population. Here, we explore the evolving research evidence of the MEMR response in relation to subclinical noise-induced cochlear damage and the MEMR as an early correlate of suprathreshold deficits.

Personalization of Hearing Aid Fitting Based on Adaptive Dynamic Range Optimization.

Adaptive dynamic range optimization (ADRO) is a hearing aid fitting rationale which involves adjusting the gains in a number of frequency bands by using a series of rules. The rules reflect the comparison of the estimated percentile occurrences of the sound levels with the audibility and comfort hearing levels of a person suffering from hearing loss. In the study reported in this paper, a previously developed machine learning method was utilized to personalize the ADRO fitting in order to provide an improved hearing experience as compared to the standard ADRO hearing aid fitting. The personalization was carried out based on the user preference model within the framework of maximum likelihood inverse reinforcement learning. The testing of ten subjects with hearing loss was conducted, which indicated that the personalized ADRO was preferred over the standard ADRO on average by about 10 times. Furthermore, a word recognition experiment was conducted, which showed that the personalized ADRO had no adverse impact on speech understanding as compared to the standard ADRO.

No Reduction in the 226-Hz Probe Tone Acoustic Reflex Amplitude Following Severe Inner Hair Cell Loss in Chinchillas.

The relationship between the middle ear acoustic reflex (AR) and inner hair cell (IHC) loss is currently unknown. Given that IHC are believed to convey nearly all acoustic information to the central auditory nervous system, it has been assumed that loss of IHC would significantly impact the AR. To evaluate this relationship, we assessed the presence and amplitude of the AR in chinchillas before and after treatment with carboplatin, an anticancer drug that reliably and selectively destroys IHC in this species. Baseline measures of hearing sensitivity, including auditory brainstem response (ABR) thresholds and distortion product otoacoustic emissions (DPOAE), were assessed and then re-evaluated following carboplatin treatment. Post-carboplatin ABR thresholds and DPOAE were found to be unchanged or slightly elevated; results were consistent with published reports. Our main hypothesis was that loss of IHC would abolish the reflex or significantly reduce its amplitude. Contrary to our hypothesis, the ipsilateral 226-Hz AR continued to be reliably elicited following carboplatin treatment. Post-mortem histological analysis confirmed significant IHC loss (65-85 %), but no measurable loss of outer hair cells (OHCs). Given that loss of IHC alone does not significantly reduce the 226-Hz AR, our results suggest that few IHC are needed to maintain the 226-Hz AR response. These results suggest additional studies are needed to better understand the role of IHC in the reflex arc, present opportunities to further study the reflex pathway, and could change how we use the clinical AR as a potential diagnostic tool for IHC dysfunction, including those related to IHC synaptopathy.

Effect of Selective Carboplatin-Induced Inner Hair Cell Loss on Temporal Integration in Chinchillas.

Integration of acoustic information over time is essential for processing complex stimuli, such as speech, due to its continuous variability along the time domain. In both humans and animals, perception of acoustic stimuli is a function of both stimulus intensity and duration. For brief acoustic stimuli, as duration increases, thresholds decrease by approximately 3 dB for every doubling in duration until stimulus duration reaches 500 ms, a phenomenon known as temporal integration. Although hearing loss and damage to outer hair cells (OHC) have been shown to alter temporal integration in some studies, the role of cochlear inner hair cells (IHC) on temporal integration is unknown. Because IHC transmit nearly all acoustic information to the central auditory system and are believed to code both intensity and timing information, these sensory cells likely play a critical role in temporal integration. To test the hypothesis that selective IHC loss degrades the temporal integration function, behaviorally trained chinchillas were treated with carboplatin, a drug known to selectively destroy IHC with little to no effect on OHC in this species. Pure-tone thresholds were assessed across frequencies (1, 2, 4, 8, 12 kHz) as a function of signal duration (500, 100, 50, 10, and 5 ms). Baseline testing showed a significant effect of duration on thresholds. Threshold decreased as a function of increasing duration, as expected. Carboplatin treatment (75 mg/kg) produced a moderate to severe loss of IHC (45-85%) with little-to-no loss of OHC. Contrary to our hypothesis, post-carboplatin temporal integration thresholds showed no significant differences from baseline regardless of stimulus duration or frequency. These data suggest that few IHC are necessary for temporal integration of simple stimuli. Temporal integration may be sensitive to loss of OHC and loss of cochlear non-linearities but does not appear to be sensitive to selective IHC loss.

Current topics in hearing research: Deafferentation and threshold independent hearing loss.

Hearing research findings in recent years have begun to change how we think about hearing loss and how we consider the risk of auditory damage from noise exposure. These findings include evidence of noise-induced cochlear damage in the absence of corresponding permanent threshold elevation or evidence of hair cell loss. Animal studies in several species have shown that noise exposures that produce robust but only temporary threshold shifts can permanently damage inner hair cell synaptic ribbons. This type of synaptic degeneration has also been shown to occur as a result of aging in animals and humans. The emergence of these data has motivated a number of clinical studies aimed at identifying the perceptual correlates associated with synaptopathy. The deficits believed to arise from synaptopathy include poorer hearing in background noise, tinnitus and hyperacusis (loudness intolerance). However, the findings from human studies have been mixed. Key questions remain as to whether synaptopathy reliably produces suprathreshold perceptual deficits or whether it serves as an early indicator of auditory damage with suprathreshold deficits emerging later as a function of further cochlear damage. Here, we provide an overview of both human and animal studies that explore the relationship among inner hair cell damage, including loss of afferent synapses, auditory thresholds, and suprathreshold measures of hearing.

Cochlear Preconditioning as a Modulator of Susceptibility to Hearing Loss.

Significance: Acquired sensorineural hearing loss is a major public health problem worldwide. The leading causes of sensorineural hearing loss are noise, aging, and ototoxic medications, with the key underlying pathology being damage to the cochlea. The review focuses on the phenomenon of preconditioning, in which the susceptibility to cochlear injury is reduced by exposing the ear to a stressful stimulus. Recent Advances: Cochlear conditioning has focused on the use of mono-modal conditioning, specifically conditioning the cochlea with moderate noise exposures before a traumatic exposure that causes permanent hearing loss. Recently, cross-modal conditioning has been explored more thoroughly, to prevent not only noise-induced hearing loss, but also age-related and drug-induced hearing losses. Critical Issues: Noise exposures that cause only temporary threshold shifts (TTSs) can cause long-term synaptopathy, injury to the synapses between the inner hair cells and spiral ganglion cells. This discovery has the potential to significantly alter the field of cochlear preconditioning with noise. Further, cochlear preconditioning can be the gateway to the development of clinically deployable therapeutics. Therefore, understanding the underlying mechanisms of conditioning is crucial for optimizing clinical protection against sensorineural hearing loss. Future Directions: Before the discovery of synaptopathy, noise exposures that caused only TTSs were believed to be either harmless or potentially beneficial. Any considerations of preconditioning with noise must consider the potential for injury to the synapses. Further, the discovery of different methods to precondition the cochlea against injury will yield new avenues for protection against hearing loss in the vulnerable populations. Antioxid. Redox Signal. 36, 1215-1228.

Gap Detection Deficits in Chinchillas with Selective Carboplatin-Induced Inner Hair Cell Loss.

Temporal resolution is essential for processing complex auditory information such as speech. In hearing impaired persons, temporal resolution, often assessed by detection of brief gaps in continuous sound stimuli, is typically poorer than in individuals with normal hearing. At low stimulus presentation levels, hearing impaired individuals perform poorly but the deficits are greatly reduced when the sensation level of the stimuli are adjusted to match their normal hearing peers. In the present study, we evaluated the effect of selective inner hair cell loss on gap detection in chinchillas treated with carboplatin, an anticancer drug that selectively damages inner hair cells and afferents in this species. Treatment with carboplatin-induced inner hair cell loss of ~ 70 % but had little effect on audiometric thresholds in quiet and produced no evidence of outer hair cell loss. In contrast, selective inner hair cell loss had a significant effect on gap detection ability across a wide range of presentation levels. These results suggest that gap detection tasks are more sensitive to inner hair cell pathology than audiometric thresholds.

The rat animal model for noise-induced hearing loss.

Rats make excellent models for the study of medical, biological, genetic, and behavioral phenomena given their adaptability, robustness, survivability, and intelligence. The rat's general anatomy and physiology of the auditory system is similar to that observed in humans, and this has led to their use for investigating the effect of noise overexposure on the mammalian auditory system. The current paper provides a review of the rat model for studying noise-induced hearing loss and highlights advancements that have been made using the rat, particularly as these pertain to noise dose and the hazardous effects of different experimental noise types. In addition to the traditional loss of auditory function following acoustic trauma, recent findings have indicated the rat as a useful model in observing alterations in neuronal processing within the central nervous system following noise injury. Furthermore, the rat provides a second animal model when investigating noise-induced cochlear synaptopathy, as studies examining this in the rat model resemble the general patterns observed in mice. Together, these findings demonstrate the relevance of this animal model for furthering the authors' understanding of the effects of noise on structural, anatomical, physiological, and perceptual aspects of hearing.

The chinchilla animal model for hearing science and noise-induced hearing loss.

The chinchilla animal model for noise-induced hearing loss has an extensive history spanning more than 50 years. Many behavioral, anatomical, and physiological characteristics of the chinchilla make it a valuable animal model for hearing science. These include similarities with human hearing frequency and intensity sensitivity, the ability to be trained behaviorally with acoustic stimuli relevant to human hearing, a docile nature that allows many physiological measures to be made in an awake state, physiological robustness that allows for data to be collected from all levels of the auditory system, and the ability to model various types of conductive and sensorineural hearing losses that mimic pathologies observed in humans. Given these attributes, chinchillas have been used repeatedly to study anatomical, physiological, and behavioral effects of continuous and impulse noise exposures that produce either temporary or permanent threshold shifts. Based on the mechanistic insights from noise-exposure studies, chinchillas have also been used in pre-clinical drug studies for the prevention and rescue of noise-induced hearing loss. This review paper highlights the role of the chinchilla model in hearing science, its important contributions, and its advantages and limitations.

No Reliable Association Between Recreational Noise Exposure and Threshold Sensitivity, Distortion Product Otoacoustic Emission Amplitude, or Word-in-Noise Performance in a College Student Population.

OBJECTIVES: The purpose of this study was to evaluate the relationship between recreational sound exposure and potentially undiagnosed or subclinical hearing loss by assessing sound exposure history, threshold sensitivity, distortion product otoacoustic emission (DPOAE) amplitudes, and performance on the words-in-noise (WIN) test. DESIGN: Survey data were collected from 74 adult participants (14 male and 60 female), 18 to 27 years of age, recruited via advertisements posted throughout the University of Florida campus. Of these participants, 70 completed both the survey and the additional functional test battery, and their preferred listening level was measured in a laboratory setting. RESULTS: There were statistically significant relationships between hearing thresholds and DPOAE amplitude. In contrast, performance on the WIN was not reliably related to threshold sensitivity within this cohort with largely normal hearing. The two most common exposures included bars or dance clubs, followed by music player use. There were no statistically significant relationships between individual or composite measures of recreational sound exposure, including preferred listening level, years of music player use, number of reported sound exposures, previous impulse noise exposure, or previous noise-induced change in hearing, and functional measures including threshold, DPOAE amplitude, and WIN measures. Some subjects were highly consistent in listening level preferences, while others were more variable from song to song. CONCLUSIONS: No reliable relationships between common recreational sound exposure or previous noise-induced changes in hearing were found during analysis of threshold sensitivity, DPOAE amplitude, or WIN performance in this cohort. However, the study sample was predominantly female and Caucasian, which limits generalizability of the results.

Effects of Recreational Noise on Threshold and Suprathreshold Measures of Auditory Function.

Noise exposure that causes a temporary threshold shift but no permanent threshold shift can cause degeneration of synaptic ribbons and afferent nerve fibers, with a corresponding reduction in wave I amplitude of the auditory brainstem response (ABR) in animals. This form of underlying damage, hypothesized to also occur in humans, has been termed synaptopathy , and it has been hypothesized that there will be a hidden hearing loss consisting of functional deficits at suprathreshold stimulus levels. This study assessed whether recreational noise exposure history was associated with smaller ABR wave I amplitude and poorer performance on suprathreshold auditory test measures. Noise exposure histories were collected from 26 men and 34 women with hearing thresholds ≤ 25 dB hearing loss (HL; 250 Hz to 8 kHz), and a variety of functional suprathreshold hearing tests were performed. Wave I amplitudes of click-evoked ABR were obtained at 70, 80, 90, and 99 dB (nHL) and tone-burst evoked ABR were obtained at 90 dB nHL. Speech recognition performance was measured in quiet and in competing noise, using the Words in Noise test, and the NU-6 word list in broadband noise (BBN). In addition, temporal summation to tonal stimuli was assessed in quiet and in competing BBN. To control for the effects of subclinical conventional hearing loss, distortion product otoacoustic emission amplitude, an indirect measure of outer hair cell integrity, was measured. There was no statistically significant relationship between noise exposure history scores and ABR wave I amplitude in either men or women for any of the ABR conditions. ABR wave I amplitude and noise exposure history were not reliably correlated with suprathreshold functional hearing tests. Taken together, this study found no evidence of noise-induced decreases in ABR wave I amplitude or signal processing in noise in a cohort of subjects with a history of recreational noise exposure.

Safety and efficacy of ebselen for the prevention of noise-induced hearing loss: a randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: Noise-induced hearing loss is a leading cause of occupational and recreational injury and disease, and a major determinant of age-related hearing loss. No therapeutic agent has been approved for the prevention or treatment of this disorder. In animal models, glutathione peroxidase 1 (GPx1) activity is reduced after acute noise exposure. Ebselen, a novel GPx1 mimic, has been shown to reduce both temporary and permanent noise-induced hearing loss in preclinical studies. We assessed the safety and efficacy of ebselen for the prevention of noise-induced hearing loss in young adults in a phase 2 clinical trial. METHODS: In this single-centre, randomised, double-blind, placebo-controlled phase 2 trial, healthy adults aged 18-31 years were randomly assigned (1:1:1:1) at the University of Florida (Gainsville, FL, USA) to receive ebselen 200 mg, 400 mg, or 600 mg, or placebo orally twice daily for 4 days, beginning 2 days before a calibrated sound challenge (4 h of pre-recorded music delivered by insert earphones). Randomisation was done with an allocation sequence generated by an independent third party. The primary outcome was mean temporary threshold shift (TTS) at 4 kHz measured 15 min after the calibrated sound challenge by pure tone audiometry; a reduction of 50% in an ebselen dose group compared with the placebo group was judged to be clinically relevant. All participants who received the calibrated sound challenge and at least one dose of study drug were included in the efficacy analysis. All randomly assigned patients were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT01444846. FINDINGS: Between Jan 11, 2013, and March 24, 2014, 83 participants were enrolled and randomly assigned to receive ebselen 200 mg (n=22), 400 mg (n=20), or 600 mg (n=21), or placebo (n=20). Two participants in the 200 mg ebselen group were discontinued from the study before the calibrated sound challenge because they no longer met the inclusion criteria; these participants were excluded from the efficacy analysis. Mean TTS at 4 kHz was 1·32 dB (SE 0·91) in the 400 mg ebselen group compared with 4·07 dB (0·90) in the placebo group, representing a significant reduction of 68% (difference -2·75 dB, 95% CI -4·54 to -0·97; p=0·0025). Compared with placebo, TTS at 4 kHz was non-significantly reduced by 21% in the 200 mg ebselen group (3·23 dB [SE 0·91] vs 4·07 dB [0·90] in the placebo group; difference -0·84 dB, 95% CI -2·63 to 0·94; p=0·3542) and by 7% in the 600 mg ebselen group (3·81 dB [0·90] vs 4·07 dB [0·90] in the placebo group; difference -0·27, 95% CI -2·03 to 1·50; p=0·7659). Ebselen treatment was well tolerated across all doses and no significant differences were seen in any haematological, serum chemistry, or radiological assessments between the ebselen groups and the placebo group. INTERPRETATION: Treatment with ebselen was safe and effective at a dose of 400 mg twice daily in preventing a noise-induced TTS. These data lend support to a role of GPx1 activity in acute noise-induced hearing loss. FUNDING: Sound Pharmaceuticals.

Noise History and Auditory Function in Young Adults With and Without Type 1 Diabetes Mellitus.

OBJECTIVES: The purpose of this study was to examine the relationship between noise exposure history, type 1 diabetes mellitus (DM), and suprathreshold measures of auditory function. DESIGN: A cross-sectional study was conducted; 20 normal-hearing participants without type 1 DM were matched on age and sex to 20 normal-hearing participants with type 1 DM (n=40). Participants, all having normal audiometric thresholds, completed noise history questionnaires and a battery of auditory physiological tests including transient evoked otoacoustic emissions, distortion product otoacoustic emissions, and auditory brainstem responses (ABR) at 80 dB nHL and at 2 different stimulus rates in both ears. Amplitude and latency for waves I and V are presented. Statistical analysis included analysis of variance and multivariate linear regression. RESULTS: No statistically significant difference for noise exposure history, otoacoustic emissions (OAE), or ABR findings were found between type 1 DM and matched controls. Males and females showed statistically significant differences for OAE amplitudes and ABR amplitude and latencies. However, no statistically significant relationship was found between noise outcomes and OAE or ABR findings. CONCLUSIONS: No statistically significant relationship between noise history and our suprathreshold ABR or OAE findings was indicated for individuals with type 1 DM or matched controls. The lack of evidence of noise related neuropathology might be due to inadequate noise exposure or lack of comorbidities in our DM group. Implications of these findings are discussed.

Relationship between dietary quality, tinnitus and hearing level: data from the national health and nutrition examination survey, 1999-2002.

OBJECTIVE: To examine the relationship between the healthy eating index (HEI), a measure of dietary quality based on United States Department of Agriculture recommendations and report of tinnitus. DESIGN: This cross-sectional analysis was based on HEI data and report of tinnitus. STUDY SAMPLE: Data for adults between 20 and 69 years of age were drawn from the National Health and Nutrition Examination Survey (NHANES), 1999-2002. The NHANES is a programme of studies, to assess the health and nutritional status of adults and children in the United States. Two thousand one hundred and seventy-six participants were included in the analytic sample. RESULTS: Of the sample, 21.1% reported tinnitus within the past year and 11.7% reported persistent tinnitus, defined as tinnitus experienced at least monthly or greater. Controlling for age, sex, race/ethnicity, diabetes, noise exposure and smoking status, we found that with healthier diet (poorer vs. better HEI) there was decreased odds of reported persistent tinnitus [odds ratio (OR); 0.67; 95% confidence interval (CI) 0.45-0.98; p = 0.03]. CONCLUSIONS: The current findings support a possible relationship between healthier diet quality and reported persistent tinnitus.

Evidence of "hidden hearing loss" following noise exposures that produce robust TTS and ABR wave-I amplitude reductions.

In animals, noise exposures that produce robust temporary threshold shifts (TTS) can produce immediate damage to afferent synapses and long-term degeneration of low spontaneous rate auditory nerve fibers. This synaptopathic damage has been shown to correlate with reduced auditory brainstem response (ABR) wave-I amplitudes at suprathreshold levels. The perceptual consequences of this "synaptopathy" remain unknown but have been suggested to include compromised hearing performance in competing background noise. Here, we used a modified startle inhibition paradigm to evaluate whether noise exposures that produce robust TTS and ABR wave-I reduction but not permanent threshold shift (PTS) reduced hearing-in-noise performance. Animals exposed to 109 dB SPL octave band noise showed TTS >30 dB 24-h post noise and modest but persistent ABR wave-I reduction 2 weeks post noise despite full recovery of ABR thresholds. Hearing-in-noise performance was negatively affected by the noise exposure. However, the effect was observed only at the poorest signal to noise ratio and was frequency specific. Although TTS >30 dB 24-h post noise was a predictor of functional deficits, there was no relationship between the degree of ABR wave-I reduction and degree of functional impairment.

Differential effects of suppressors on hazardous sound pressure levels generated by AR-15 rifles: Considerations for recreational shooters, law enforcement, and the military.

OBJECTIVE: Firearm discharges produce hazardous levels of impulse noise that can lead to permanent hearing loss. In the present study, we evaluated the effects of suppression, ammunition, and barrel length on AR-15 rifles. DESIGN: Sound levels were measured left/right of a user's head, and 1-m left of the muzzle, per MIL-STD-1474-D, under both unsuppressed and suppressed conditions. STUDY SAMPLE: Nine commercially available AR-15 rifles and 14 suppressors were used. RESULTS: Suppressors significantly decreased peak dB SPL at the 1-m location and the left ear location. However, under most rifle/ammunition conditions, levels remained above 140 dB peak SPL near a user's right ear. In a subset of conditions, subsonic ammunition produced values near or below 140 dB peak SPL. Overall suppression ranged from 7-32 dB across conditions. CONCLUSIONS: These data indicate that (1) suppressors reduce discharge levels to 140 dB peak SPL or below in only a subset of AR-15 conditions, (2) shorter barrel length and use of muzzle brake devices can substantially increase exposure level for the user, and (3) there are significant left/right ear sound pressure differences under suppressed conditions as a function of the AR-15 direct impingement design that must be considered during sound measurements to fully evaluate overall efficacy.

Inner Hair Cell Loss Disrupts Hearing and Cochlear Function Leading to Sensory Deprivation and Enhanced Central Auditory Gain.

There are three times as many outer hair cells (OHC) as inner hair cells (IHC), yet IHC transmit virtually all acoustic information to the brain as they synapse with 90-95% of type I auditory nerve fibers. Here we review a comprehensive series of experiments aimed at determining how loss of the IHC/type I system affects hearing by selectively destroying these cells in chinchillas using the ototoxic anti-cancer agent carboplatin. Eliminating IHC/type I neurons has no effect on distortion product otoacoustic emission or the cochlear microphonic potential generated by OHC; however, it greatly reduces the summating potential produced by IHC and the compound action potential (CAP) generated by type I neurons. Remarkably, responses from remaining auditory nerve fibers maintain sharp tuning and low thresholds despite innervating regions of the cochlea with ~80% IHC loss. Moreover, chinchillas with large IHC lesions have surprisingly normal thresholds in quiet until IHC losses exceeded 80%, suggesting that only a few IHC are needed to detect sounds in quiet. However, behavioral thresholds in broadband noise are elevated significantly and tone-in-narrow band noise masking patterns exhibit greater remote masking. These results suggest the auditory system is able to compensate for considerable loss of IHC/type I neurons in quiet but not in difficult listening conditions. How does the auditory brain deal with the drastic loss of cochlear input? Recordings from the inferior colliculus found a relatively small decline in sound-evoked activity despite a large decrease in CAP amplitude after IHC lesion. Paradoxically, sound-evoked responses are generally larger than normal in the auditory cortex, indicative of increased central gain. This gain enhancement in the auditory cortex is associated with decreased GABA-mediated inhibition. These results suggest that when the neural output of the cochlea is reduced, the central auditory system compensates by turning up its gain so that weak signals once again become comfortably loud. While this gain enhancement is able to restore normal hearing under quiet conditions, it may not adequately compensate for peripheral dysfunction in more complex sound environments. In addition, excessive gain increases may convert recruitment into the debilitating condition known as hyperacusis.

Selective Inner Hair Cell Dysfunction in Chinchillas Impairs Hearing-in-Noise in the Absence of Outer Hair Cell Loss.

Poorer hearing in the presence of background noise is a significant problem for the hearing impaired. Ototoxic drugs, ageing, and noise exposure can damage the sensory hair cells of the inner ear that are essential for normal hearing sensitivity. The relationship between outer hair cell (OHC) loss and progressively poorer hearing sensitivity in quiet or in competing background noise is supported by a number of human and animal studies. In contrast, the effect of moderate inner hair cell (IHC) loss or dysfunction shows almost no impact on behavioral measures of hearing sensitivity in quiet, when OHCs remain intact, but the relationship between selective IHC loss and hearing in noise remains relatively unknown. Here, a moderately high dose of carboplatin (75 mg/kg) that produced IHC loss in chinchillas ranging from 40 to 80 % had little effect on thresholds in quiet. However, when tested in the presence of competing broadband (BBN) or narrowband noise (NBN), thresholds increased significantly. IHC loss >60 % increased signal-to-noise ratios (SNRs) for tones (500-11,300 Hz) in competing BBN by 5-10 dB and broadened the masking function under NBN. These data suggest that IHC loss or dysfunction may play a significant role in listening in noise independent of OHC integrity and that these deficits may be present even when thresholds in quiet are within normal limits.