Identification of induced and naturally occurring conductive hearing loss in mice using bone conduction.

While many mouse models of hearing loss have been described, a significant fraction of the genetic defects in these models affect both the inner ear and middle ears. A common method used to separate inner-ear (sensory-neural) from middle-ear (conductive) pathologies in the hearing clinic is the combination of air-conduction and bone-conduction audiometry. In this report, we investigate the use of air- and bone-conducted evoked auditory brainstem responses to perform a similar separation in mice. We describe a technique by which we stimulate the mouse ear both acoustically and via whole-head vibration. We investigate the sensitivity of this technique to conductive hearing loss by introducing middle-ear lesions in normal hearing mice. We also use the technique to investigate the presence of an age-related conductive hearing loss in a common mouse model of presbycusis, the BALB/c mouse.

The neurobiology of speech perception decline in aging.

Speech perception difficulties are common among elderlies; yet the underlying neural mechanisms are still poorly understood. New empirical evidence suggesting that brain senescence may be an important contributor to these difficulties has challenged the traditional view that peripheral hearing loss was the main factor in the etiology of these difficulties. Here, we investigated the relationship between structural and functional brain senescence and speech perception skills in aging. Following audiometric evaluations, participants underwent MRI while performing a speech perception task at different intelligibility levels. As expected, with age speech perception declined, even after controlling for hearing sensitivity using an audiological measure (pure tone averages), and a bioacoustical measure (DPOAEs recordings). Our results reveal that the core speech network, centered on the supratemporal cortex and ventral motor areas bilaterally, decreased in spatial extent in older adults. Importantly, our results also show that speech skills in aging are affected by changes in cortical thickness and in brain functioning. Age-independent intelligibility effects were found in several motor and premotor areas, including the left ventral premotor cortex and the right supplementary motor area (SMA). Age-dependent intelligibility effects were also found, mainly in sensorimotor cortical areas, and in the left dorsal anterior insula. In this region, changes in BOLD signal modulated the relationship between age and speech perception skills suggesting a role for this region in maintaining speech perception in older ages. These results provide important new insights into the neurobiology of speech perception in aging.

Noise and age-related hearing loss: a study of 40 123 gold miners in South Africa.

OBJECTIVE AND DESIGN: This retrospective cohort study aimed to describe the differential effect of noise exposure and age-related hearing loss in a large sample of gold miners in South Africa. STUDY SAMPLE: Audiological data of 40 123 South African mine workers were investigated. Data of a non-noise-exposed control group (n = 6162) and group exposed to underground noise (≥ 85 dB A (TWA) (n = 33 961) were included. Within these two larger noise-exposed groups two homogenous exposure groups (HEG) were also selected for analyses, namely the driller group (n = 4399) and the administration group (administrative workers) (n = 2211). Participants were categorized in terms of noise exposure, age, and race. RESULTS: Significantly different thresholds (worse for underground noise group) with respect to the median for all frequencies after adjusting for age was evident between the noise-exposed and control groups (ANCOVA). The largest differences in hearing thresholds between the noise-exposed and control groups were observed at 3 and 4 kHz in the age group 36 to 45 years. Administration and driller group differed significantly (driller group worse results) with respect to the mean LFA512 and HFA346 after adjusting for age (ANCOVA). Black males had significantly better high-frequency hearing compared with white male counterparts but significantly worse low-frequency hearing. CONCLUSION: Age was the most important influence on hearing thresholds for the noise and control groups. Race was shown to be a very significant factor determining susceptibility to NIHL and ARHL.

A neural basis of speech-in-noise perception in older adults.

OBJECTIVE: We investigated a neural basis of speech-in-noise perception in older adults. Hearing loss, the third most common chronic condition in older adults, is most often manifested by difficulty understanding speech in background noise. This trouble with understanding speech in noise, which occurs even in individuals who have normal-hearing thresholds, may arise, in part, from age-related declines in central auditory processing of the temporal and spectral components of speech. We hypothesized that older adults with poorer speech-in-noise (SIN) perception demonstrate impairments in the subcortical representation of speech. DESIGN: In all participants (28 adults, age 60-73 yr), average hearing thresholds calculated from 500 to 4000 Hz were ≤ 25 dB HL. The participants were evaluated behaviorally with the Hearing in Noise Test (HINT) and neurophysiologically using speech-evoked auditory brainstem responses recorded in quiet and in background noise. The participants were divided based on their HINT scores into top and bottom performing groups that were matched for audiometric thresholds and intelligent quotient. We compared brainstem responses in the two groups, specifically, the average spectral magnitudes of the neural response and the degree to which background noise affected response morphology. RESULTS: In the quiet condition, the bottom SIN group had reduced neural representation of the fundamental frequency of the speech stimulus and an overall reduction in response magnitude. In the noise condition, the bottom SIN group demonstrated greater disruption in noise, reflecting reduction in neural synchrony. The role of brainstem timing is particularly evident in the strong relationship between SIN perception and quiet-to-noise response correlations. All physiologic measures correlated with SIN perception. CONCLUSION: Adults in the bottom SIN group differed from the audiometrically matched top SIN group in how speech was neurally encoded. The strength of subcortical encoding of the fundamental frequency appears to be a factor in successful speech-in-noise perception in older adults. Given the limitations of amplification, our results suggest the need for inclusion of auditory training to strengthen central auditory processing in older adults with SIN perception difficulties.

Early subclinical cochlear dysfunction in myotonic dystrophy type 1.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is an autosomal-dominant inherited disorder clinically characterized by variable systemic manifestations. Among clinical features of the disease, 'precocious presbyacusis' has been previously reported. The underlying mechanism of this auditory impairment remains still poorly understood. Hearing is an active process located in the cochlea, where the outer hair cells (OHCs) play an important role in sound perception through a 'contractile' like movement resembling skeletal muscle fibers dynamics. OHCs status has not yet been investigated in DM1 patients. OHCs integrity can be assessed by measuring transient-evoked otoacoustic emissions (TEOAE), a non-invasive, repeatable, and objective quantitative tool. METHODS: We recruited 25 patients with a genetically confirmed diagnosis of DM1, and 28 age-matched control subjects. All of them underwent a routine audiological evaluation and TEOAE recordings. RESULTS: We detected a high prevalence of sensorineural high-frequency hearing loss (HFHL) in DM1 patients, significantly different if compared to control subjects. Interestingly, the accurate analysis of DM1 recorded data showed a marked impairment of TEOAE both in HFHL+ and unexpectedly in HFHL- group. Cochlear dysfunction was restricted to frequencies above 2000 Hz in the HFHL- group, but it extended to 1000 Hz in HFHL+ DM1 patients. CONCLUSIONS: Our study indicates that cochlear impairment in DM1 is present, even in patients without evidence of hearing loss at a standard audiometric analysis. Hence, in the current clinical practice, an assessment of cochlear function by TEOAE recording may be useful in DM1 patients to identify precocious signs of cochlear dysfunction.

Impact of noise or styrene exposure on the kinetics of presbycusis.

Presbycusis, or age-related hearing loss is a growing problem as the general population ages. In this longitudinal study, the influence of noise or styrene exposure on presbycusis was investigated in Brown Norway rats. Animals were exposed at 6 months of age, either to a band noise centered at 8 kHz at a Lex,8h = 85 dB (86.2 dB SPL for 6 h), or to 300 ppm of styrene for 6 h per day, five days per week, for four weeks. Cubic distortion product otoacoustic emissions (2f1-f2 DPOAEs) were used to test the capacity of the auditory receptor over the lifespan of the animals. 2f1-f2DPOAE measurements are easy to implement and efficiently track the age-related deterioration of mid- and high-frequencies. They are good indicators of temporary auditory threshold shift, especially with a level of primaries close to 60 dB SPL. Post-exposure hearing defects are best identified using moderate, rather than high, levels of primaries. Like many aging humans, aging rats lose sensitivity to high-frequencies faster than to medium-frequencies. Although the results obtained with the styrene exposure were not entirely conclusive, histopathological data showed the presbycusis process to be enhanced. Noise-exposed rats exhibit a loss of spiral ganglion cells from 12 months and a 7 dB drop in 2f1-f2DPOAEs at 24 months, indicating that even moderate-intensity noise can accelerate the presbycusis process. Even though the results obtained with the styrene exposure are less conclusive, the histopathological data show an enhancement of the presbycusis process.

Longitudinal changes in hearing sensitivity among men: the Veterans Affairs Normative Aging Study.

Over 35 years (1962-1996), participants of the Veterans Affairs Normative Aging Study (NAS), a study of healthy aging in men, completed up to eight audiometric assessments. This report describes the age-related hearing trajectories of screened men (n=953) aged 23 to 81 years at enrollment, estimates the typical rate of change per decade in hearing sensitivity, and compares longitudinal and cross-sectional estimates of change in hearing sensitivity. The men were followed 14 years on average. The hearing trajectories, based on a mixed-effects model analytical approach to the data, provide converging evidence that hearing loss in aging is pervasive and progressive even among men initially selected for good physical health. Typically the men accrued early losses (>25 dB HL) in hearing sensitivity at the higher frequencies beginning in the early 40s, but maintained hearing thresholds better than 25 dB HL for lower frequencies into old age. The average rate of change per year across frequencies and age was 0.69 dB. Predicted cross-sectional estimates of change in hearing sensitivity reliably approximated longitudinal trajectories, with slight misestimations in the 8th decade.

Plasma very long-chain n-3 polyunsaturated fatty acids and age-related hearing loss in older adults.

OBJECTIVES: Age-related hearing loss is a common social and health problem in the older adult population. Up until now, very little scientific attention has been given to the potential role of fatty acids in age-related hearing loss. In this study we investigated whether plasma very long-chain n-3 polyunsaturated fatty acids (PUFAs) are associated with age-related hearing loss over three years. DESIGN: Cross-sectional and 3-year longitudinal analyses. SETTING: Wageningen, the Netherlands. PARTICIPANTS: 720 men and postmenopausal women (50-70 years of age) without middle ear dysfunction or unilateral hearing loss. MEASUREMENTS: Fatty acid proportions were measured in plasma cholesteryl esters. Hearing thresholds (in decibels, dB) at baseline and after three years were measured with pure-tone audiometry. Hearing loss was calculated as the increase in mean hearing thresholds in the low (0.5-kHz, 1-kHz, and 2-kHz) and high (4-kHz, 6-kHz, and 8-kHz) frequencies over three years. RESULTS: Subjects in the highest quartile of plasma very long-chain n-3 PUFA had less hearing loss in the low frequencies over three years than subjects in the lowest quartile (p < 0.01, ANCOVA, difference in mean adjusted hearing thresholds= -1.2 dB). There were no significant differences between the quartiles of plasma very long-chain n-3 PUFA in hearing loss in the high frequencies (p=0.49, ANCOVA). These associations are adjusted for baseline mean hearing thresholds, age, sex, level of education and alcohol consumption. CONCLUSION: This study is the first to show an inverse association between plasma very long-chain n-3 PUFAs and age-related hearing loss. These results are encouraging, but require confirmation from future studies.

Effects of dietary restriction and antioxidants on presbyacusis.

OBJECTIVES/HYPOTHESIS: The premise of this study is that the membrane hypothesis of aging, also known as the mitochondrial clock theory of aging, is the basis for presbyacusis. Furthermore, it is proposed that treatment with antioxidants or dietary restriction can attenuate age-related hearing loss. Many studies have demonstrated a reduction in blood flow to specific tissues, including the cochlea, with aging. Hypoperfusion leads to the formation of reactive oxygen metabolites (ROM). ROM are highly toxic molecules that directly affect tissues including inner ear structures. In addition, ROM can damage mitochondrial DNA (mtDNA), resulting in the production of specific mtDNA deletions (mtDNA del4977 [human] or mtDNA del4834 [rat]; also known as the common aging deletion]. Previous corroborating data suggest that the common aging deletion mtDNA4834 may be associated not only with aging but also with presbyacusis, thus further strengthening the basis of the current studies. In this study, experiments provide compelling evidence that long-term treatment with compounds that block or scavenge reactive oxygen metabolites attenuate age-related hearing loss and reduce the impact of associated deleterious changes at the molecular level. STUDY DESIGN: Prospective randomized study. METHODS: One hundred thirty rats were randomly assigned to one of six groups with appropriate controls. Animals were divided into the following treatment arms: group 1, 30% caloric restriction; group 2, vitamin E oversupplementation; group 3, vitamin C over-supplementation; group 4, melatonin treatment; group 5, lazaroid treatment; and group 6, placebo. In addition, 10 animals were used to determine the appropriate caloric restriction. All subjects underwent baseline and every-3-month testing until their health failed (range, 18-28 mo; average, 25 mo). This testing included auditory sensitivity studies using auditory brainstem response (ABR) testing, as well as tissue analysis for mtDNA deletions using molecular biological techniques. At the conclusion of the study, animals underwent a final ABR test and were tested for mtDNA deletions in brain and inner ear tissues, and the opposite ear was used for histological analysis. RESULTS: Results indicated that the 30%-caloric-restricted group maintained the most acute auditory sensitivities, the lowest quantity of mtDNA deletions, and the least amount of outer hair cell loss. The antioxidant-treated subjects had improved auditory sensitivities, and a trend for fewer mtDNA deletions was observed compared with the placebo subjects. The placebo subjects had the poorest auditory sensitivity, the most mtDNA deletions, and the greatest degree of outer hair cell loss. CONCLUSIONS: Intervention designed to reduce reactive oxygen metabolite damage appears to protect against age-related hearing loss specifically and aging in general. This is reflected by an overall reduction in mtDNA deletions. These data also suggest that the common aging deletion appears to be associated with presbyacusis, as demonstrated by an increased frequency of the mtDNA del4834 in the cochleae with the most significant hearing loss. Nutritional and pharmacological strategies may very well provide rational treatment options that would limit the age-associated increase in ROM generation, reduce mtDNA damage, and reduce the degree of hearing loss as the organism advances in age.

A holistic model for matching high-tech hearing aid features to elderly patients.

Successful hearing aid fittings using high-technology features for elderly patients require consideration of factors beyond results obtained from routine audiologic evaluations. A holistic hearing aid selection, fitting, and evaluation approach that considers patient characteristics from communication, physical, psychological, and social assessment domains is presented here along with a checklist and flowcharts for matching high-tech hearing aid features to older persons who are hearing aid candidates.

Effects of noise on inferior colliculus evoked potentials and cochlear anatomy in young and aged chinchillas.

Like many aging humans, the aging chinchilla tends to lose high-frequency sensitivity at a faster rate than low-frequency sensitivity. This feature, combined with its excellent low-frequency hearing, makes the chinchilla attractive as an animal model for studying the relationship between noise-induced hearing loss (NIHL) and age-related hearing loss (AHL). In the present study, we examined susceptibility to noise in 15 aged (10-15 years old) and 15 young chinchillas. Two levels of noise were used, with the aim of determining whether age-related differences exist in the magnitude and rate of recovery from temporary threshold shifts produced by a moderate-level (95 dB) noise exposure, or in susceptibility to permanent threshold shifts and cochlear damage caused by a high-level (106 dB) noise exposure. Thresholds and response amplitudes at 0.5, 1, 2, 4, 8 and 16 kHz were determined from evoked potentials recorded from the inferior colliculus. Cochlear histology was performed on animals exposed to high-level noise. The results suggest that older animals are equally vulnerable to moderate-level noise, but may be slightly more vulnerable to high-level noise. For moderate-level exposures, there appears to be a simple additive relationship (in dB) between AHL and NIHL. For high-level exposures, the relationship may be more complex.

Inputs to a physiologically characterized region of the inferior colliculus of the young adult CBA mouse.

Presbycusis is a sensory perceptual disorder involving loss of high-pitch hearing and reduced ability to process biologically relevant acoustic signals in noisy environments. The present investigation is part of an ongoing series of studies aimed at discerning the neural bases of presbycusis. The purpose of the present experiment was to delineate the inputs to a functionally characterized region of the dorsomedial inferior colliculus (IC, auditory midbrain) in young, adult CBA mice. Focal, iontophoretic injections of horseradish peroxidase were made in the 18-24 kHz region of dorsomedial IC of the CBA strain following physiological mapping experiments. Serial sections were reacted with diaminobenzidine or tetramethylbenzidine, counterstained and examined for retrogradely labeled cell bodies. Input projections were observed contralaterally from: all three divisions of cochlear nucleus; intermediate and dorsal nuclei of the lateral lemniscus (LL); and the central nucleus, external nucleus and dorsal cortex of the IC. Input projections were observed ipsilaterally from: the medial and lateral superior olivary nuclei; the superior paraolivary nucleus; the dorsolateral and anterolateral periolivary nuclei; the dorsal and ventral divisions of the ventral nucleus of LL; the dorsal and intermediate nuclei of LL; the central nucleus, external nucleus and dorsal cortex of the IC outside the injection site; and small projections from central gray and the medial geniculate body. These findings in young, adult mice with normal hearing can now serve as a baseline for similar experiments being conducted in mice of older ages and with varying degrees of hearing loss to discover neural changes that may cause age-related hearing disorders.

Effects of aging on potassium homeostasis and the endocochlear potential in the gerbil cochlea.

Previous work has shown that the endocochlear potential (EP) decreases with age in the gerbil. Concomitant with the EP decrease is an age-related loss of activity of Na,K-ATPase in the lateral wall and stria vascularis. We hypothesized that the EP decrease is associated with a similar decrease in the endolymphatic potassium concentration [Ke+]. This hypothesis was tested using double-barrelled, K(+)-selective electrodes introduced into scala media through the round window in young and quiet-aged gerbils. Results show that the means (+/- S.D.) of the [Ke+] in young and aged gerbils were not significantly different (178.2 +/- 14.2 mM and 171.2 +/- 34.4 mM, respectively), although the intersubject variability was much greater in the aged animals than in the young. These values of [Ke+] are slightly higher than those found for other mammals and may reflect the higher plasma osmolarity found in the gerbil. The concentration of perilymphatic potassium [Kp+] in scala tympani at the round window was also similar for the young and aged groups (3.57 +/- 1.17 mM and 4.18 +/- 2.03 mM, respectively). On the other hand, mean EP values in the young and aged gerbils were 92.0 +/- 5.7 mV and 64.8 +/- 15.8 mV, respectively and were statistically different (P < 0.001). Overall, EP and [Ke+] showed little correlation (R2 = 0.23), except that when [Ke+] fell below 150 mM, the EP was always less than 60 mV. An analysis of the chemical potential for Ke+ with respect to Kp+ shows that it was similar for young and aged gerbils (overall mean of 103.1 +/- 13.7 mV) and remained constant with respect to the EP, in spite of an overall electrochemical potential of Ke+ that varied from 120 to 210 mV. Thus, the system maintains Ke+ homeostasis at the expense of the EP, even when the EP is on the verge of collapse.

Support for Corso's hearing loss model. Relating aging and noise exposure.

A brief review is provided of the variable ratio model [Corso, Audiology 1980;19:221-232] for partitioning the effects of age and noise exposure in cases of occupational hearing loss. Data are presented from Rosenhall, Pedersen, and Svanborg [Ear Hear 1990;11:257-263] which support the variable-ratio model. Suggestions are offered for the application of the model in medico-legal cases of permanent hearing damage due to excessive noise exposure.