Thymoquinone ameliorates age-related hearing loss in C57BL/6J mice by modulating Sirt1 activity and Bak1 expression.

Age-related hearing loss (AHL) is the most common sensory disorder of aged population. Currently, one of the most important sources of experimental medicine for AHL is medicinal plants. This study performed the first investigation of the effect of thymoquinone (TQ), a potent antioxidant, on AHL. Here, we used inbred C57BL/6J mice (B6 mice) as a successful experimental model of the early onset of AHL. The behavioral assessment of hearing revealed that the injection of a high dose of TQ (40 mg/kg; TQ40) significantly improved the auditory sensitivity of B6 mice at all tested frequencies (8, 16 and 22 kHz). Histological sections of cochlea from B6 mice injected with a low dose (20 mg/kg; TQ20) and high dose showed relatively less degenerative signs in the modiolus, hair cells and spiral ligaments, the main constituents of the cochlea. In addition, TQ40 completely restored the normal pattern of hair cells in B6 mice, as shown in scanning electron micrographs. Our data indicated that TQ20 and TQ40 reduced levels of Bak1-mediated apoptosis in the cochlea of B6 mice. Interestingly, the level of Sirt1, a positive regulator of autophagy, was significantly increased in B6 mice administered TQ40. In conclusion, TQ relieves the symptoms of AHL by downregulating Bak1 and activating Sirt1 in the cochlea of B6 mice.

Functional organization of mouse primary auditory cortex in adult C57BL/6 and F1 (CBAxC57) mice.

The primary auditory cortex (A1) plays a key role for sound perception since it represents one of the first cortical processing stations for sounds. Recent studies have shown that on the cellular level the frequency organization of A1 is more heterogeneous than previously appreciated. However, many of these studies were performed in mice on the C57BL/6 background which develop high frequency hearing loss with age making them a less optimal choice for auditory research. In contrast, mice on the CBA background retain better hearing sensitivity in old age. Since potential strain differences could exist in A1 organization between strains, we performed comparative analysis of neuronal populations in A1 of adult (~ 10 weeks) C57BL/6 mice and F1 (CBAxC57) mice. We used in vivo 2-photon imaging of pyramidal neurons in cortical layers L4 and L2/3 of awake mouse primary auditory cortex (A1) to characterize the populations of neurons that were active to tonal stimuli. Pure tones recruited neurons of widely ranging frequency preference in both layers and strains with neurons in F1 (CBAxC57) mice exhibiting a wider range of frequency preference particularly to higher frequencies. Frequency selectivity was slightly higher in C57BL/6 mice while neurons in F1 (CBAxC57) mice showed a greater sound-level sensitivity. The spatial heterogeneity of frequency preference was present in both strains with F1 (CBAxC57) mice exhibiting higher tuning diversity across all measured length scales. Our results demonstrate that the tone evoked responses and frequency representation in A1 of adult C57BL/6 and F1 (CBAxC57) mice are largely similar.

Reduced suprathreshold auditory nerve responses are associated with slower processing speed and thinner temporal and parietal cortex in presbycusis.

Epidemiological evidence shows an association between hearing loss and dementia in elderly people. However, the mechanisms that connect hearing impairments and cognitive decline are still unknown. Here we propose that a suprathreshold auditory-nerve impairment is associated with cognitive decline and brain atrophy. METHODS: audiological, neuropsychological, and brain structural 3-Tesla MRI data were obtained from elders with different levels of hearing loss recruited in the ANDES cohort. The amplitude of waves I (auditory nerve) and V (midbrain) from auditory brainstem responses were measured at 80 dB nHL. We also calculated the ratio between wave V and I as a proxy of suprathreshold brainstem function. RESULTS: we included a total of 101 subjects (age: 73.5 ± 5.2 years (mean ± SD), mean education: 9.5 ± 4.2 years, and mean audiogram thresholds (0.5-4 kHz): 25.5 ± 12.0 dB HL). We obtained reliable suprathreshold waves V in all subjects (n = 101), while replicable waves I were obtained in 92 subjects (91.1%). Partial Spearman correlations (corrected by age, gender, education and hearing thresholds) showed that reduced suprathreshold wave I responses were associated with thinner temporal and parietal cortices, and with slower processing speed as evidenced by the Trail-Making Test-A and digit symbol performance. Non-significant correlations were obtained between wave I amplitudes and other cognitive domains. CONCLUSIONS: These results evidence that reduced suprathreshold auditory nerve responses in presbycusis are associated with slower processing speed and brain structural changes in temporal and parietal regions.

Relative contributions of auditory and cognitive functions on speech recognition in quiet and in noise among older adults / Contribuições relativas das funções auditivas e cognitivas no reconhecimento da fala no silêncio e no ruído entre idosos

Abstract Introduction: Hearing acuity, central auditory processing and cognition contribute to the speech recognition difficulty experienced by older adults. Therefore, quantifying the contribution of these factors on speech recognition problem is important in order to formulate a holistic and effective rehabilitation. Objective: To examine the relative contributions of auditory functioning and cognition status to speech recognition in quiet and in noise. Methods: We measured speech recognition in quiet and in composite noise using the Malay Hearing in noise test on 72 native Malay speakers (60-82 years) older adults with normal to mild hearing loss. Auditory function included pure tone audiogram, gaps-in-noise, and dichotic digit tests. Cognitive function was assessed using the Malay Montreal cognitive assessment. Results: Linear regression analyses using backward elimination technique revealed that had the better ear four frequency average (0.5-4 kHz) (4FA), high frequency average and Malay Montreal cognitive assessment attributed to speech perception in quiet (total r2 = 0.499). On the other hand, high frequency average, Malay Montreal cognitive assessment and dichotic digit tests contributed significantly to speech recognition in noise (total r2 = 0.307). Whereas the better ear high frequency average primarily measured the speech recognition in quiet, the speech recognition in noise was mainly measured by cognitive function. Conclusions: These findings highlight the fact that besides hearing sensitivity, cognition plays an important role in speech recognition ability among older adults, especially in noisy environments. Therefore, in addition to hearing aids, rehabilitation, which trains cognition, may have a role in improving speech recognition in noise ability of older adults.

Resumo Introdução: A alteração da acuidade auditiva, do processamento auditivo central e da cognição são fatores que contribuem para a dificuldade de reconhecimento da fala em idosos. Portanto, quantificar a contribuição desses fatores no problema de reconhecimento da fala é importante para a formulação de uma reabilitação holística e efetiva. Objetivo: Examinar as contribuições relativas do funcionamento auditivo e do estado cognitivo para o reconhecimento da fala no silêncio e no ruído. Método: Nós medimos o reconhecimento de fala no silêncio e no ruído composto com o teste Malay hearing in noise test em 72 idosos malaios nativos falantes (60-82 anos) com audição normal a perda auditiva de grau leve. A avaliação da função auditiva incluiu audiograma de tons puros, teste gaps-in-noise e testes dicótico de dígitos. A função cognitiva foi avaliada pelo teste Malay Montreal cognitive assessment. Resultados: Análises de regressão linear com técnicas de eliminação backward na orelha melhor revelaram média de quatro frequências (0,5-4 kHz) (4AF), média de alta frequência e teste Malay Montreal cognitive assessment na orelha melhor, mensurada pela percepção da fala no silêncio (r2 total = 0,499). Por outro lado, a média de alta frequência, Malay Montreal cognitive assessment e o teste dicótico de dígitos contribuíram significativamente para o reconhecimento da fala no ruído (r2 total = 0,307). Enquanto a média de alta frequência da melhor orelha mediu principalmente o reconhecimento da fala no silêncio, o reconhecimento da fala no ruído foi mensurado principalmente pela função cognitiva. Conclusões: Esses achados destacam o fato de que, além da sensibilidade auditiva, a cognição desempenha um papel importante na capacidade de reconhecimento da fala em idosos, principalmente em ambientes ruidosos. Portanto, além de aparelhos auditivos, a reabilitação, que treina a cognição, pode ter um papel na melhoria da capacidade do reconhecimento da fala no ruído entre os idosos.

Relative contributions of auditory and cognitive functions on speech recognition in quiet and in noise among older adults.

INTRODUCTION: Hearing acuity, central auditory processing and cognition contribute to the speech recognition difficulty experienced by older adults. Therefore, quantifying the contribution of these factors on speech recognition problem is important in order to formulate a holistic and effective rehabilitation. OBJECTIVE: To examine the relative contributions of auditory functioning and cognition status to speech recognition in quiet and in noise. METHODS: We measured speech recognition in quiet and in composite noise using the Malay Hearing in noise test on 72 native Malay speakers (60-82 years) older adults with normal to mild hearing loss. Auditory function included pure tone audiogram, gaps-in-noise, and dichotic digit tests. Cognitive function was assessed using the Malay Montreal cognitive assessment. RESULTS: Linear regression analyses using backward elimination technique revealed that had the better ear four frequency average (0.5-4kHz) (4FA), high frequency average and Malay Montreal cognitive assessment attributed to speech perception in quiet (total r2=0.499). On the other hand, high frequency average, Malay Montreal cognitive assessment and dichotic digit tests contributed significantly to speech recognition in noise (total r2=0.307). Whereas the better ear high frequency average primarily measured the speech recognition in quiet, the speech recognition in noise was mainly measured by cognitive function. CONCLUSIONS: These findings highlight the fact that besides hearing sensitivity, cognition plays an important role in speech recognition ability among older adults, especially in noisy environments. Therefore, in addition to hearing aids, rehabilitation, which trains cognition, may have a role in improving speech recognition in noise ability of older adults.

Auditory-frontal Channeling in α and ß Bands is Altered by Age-related Hearing Loss and Relates to Speech Perception in Noise.

Difficulty understanding speech-in-noise (SIN) is a pervasive problem faced by older adults particularly those with hearing loss. Previous studies have identified structural and functional changes in the brain that contribute to older adults' speech perception difficulties. Yet, many of these studies use neuroimaging techniques that evaluate only gross activation in isolated brain regions. Neural oscillations may provide further insight into the processes underlying SIN perception as well as the interaction between auditory cortex and prefrontal linguistic brain regions that mediate complex behaviors. We examined frequency-specific neural oscillations and functional connectivity of the EEG in older adults with and without hearing loss during an active SIN perception task. Brain-behavior correlations revealed listeners who were more resistant to the detrimental effects of noise also demonstrated greater modulation of α phase coherence between clean and noise-degraded speech, suggesting α desynchronization reflects release from inhibition and more flexible allocation of neural resources. Additionally, we found top-down ß connectivity between prefrontal and auditory cortices strengthened with poorer hearing thresholds despite minimal behavioral differences. This is consistent with the proposal that linguistic brain areas may be recruited to compensate for impoverished auditory inputs through increased top-down predictions to assist SIN perception. Overall, these results emphasize the importance of top-down signaling in low-frequency brain rhythms that help compensate for hearing-related declines and facilitate efficient SIN processing.

Auditory Evoked Responses in Older Adults With Normal Hearing, Untreated, and Treated Age-Related Hearing Loss.

OBJECTIVES: The goal of this study was to identify the effects of auditory deprivation (age-related hearing loss) and auditory stimulation (history of hearing aid use) on the neural registration of sound across two stimulus presentation conditions: (1) equal sound pressure level and (2) equal sensation level. DESIGN: We used a between-groups design, involving three groups of 14 older adults (n = 42; 62 to 84 years): (1) clinically defined normal hearing (≤25 dB from 250 to 8000 Hz, bilaterally), (2) bilateral mild-moderate/moderately severe sensorineural hearing loss who have never used hearing aids, and (3) bilateral mild-moderate/moderately severe sensorineural hearing loss who have worn bilateral hearing aids for at least the past 2 years. RESULTS: There were significant delays in the auditory P1-N1-P2 complex in older adults with hearing loss compared with their normal hearing peers when using equal sound pressure levels for all participants. However, when the degree and configuration of hearing loss were accounted for through the presentation of equal sensation level stimuli, no latency delays were observed. These results suggest that stimulus audibility modulates P1-N1-P2 morphology and should be controlled for when defining deprivation and stimulus-related neuroplasticity in people with hearing loss. Moreover, a history of auditory stimulation, in the form of hearing aid use, does not appreciably alter the neural registration of unaided auditory evoked brain activity when quantified by the P1-N1-P2. CONCLUSIONS: When comparing auditory cortical responses in older adults with and without hearing loss, stimulus audibility, and not hearing loss-related neurophysiological changes, results in delayed response latency for those with age-related hearing loss. Future studies should carefully consider stimulus presentation levels when drawing conclusions about deprivation- and stimulation-related neuroplasticity. Additionally, auditory stimulation, in the form of a history of hearing aid use, does not significantly affect the neural registration of sound when quantified using the P1-N1-P2-evoked response.

Cognitive Function Prediction of Performance During Dual-Tasks Across Adults With and Without Hearing Loss.

BACKGROUND: Dual-task procedures are commonly implemented to examine cognitive load and listening effort as individual differences in cognition often determine successful listening. However, which methods are most efficacious is unclear. Specifically, standardized, targeted assessment procedures for establishing cognitive function, and age-related changes that might account for changes in dual-task performance have yet to be established. Additional data are needed across aging populations, including middle-aged adults and older adults to establish the trend of performance changes throughout the aging process. Investigations of the relationship between cognitive function and dual-task performance may better inform clinical decisions. OBJECTIVE: The purpose of this study was to investigate if cognitive function predicts dual-task performance across adults with and without hearing loss. METHODS: Participants were divided into two groups based on age. Group 1: 14 listeners (Female = 11), 30-50 years old, with normal hearing. Group 2: 12 listeners (Female = 9), 60-80 years old, with normal hearing to near-normal hearing, including typical age-related hearing loss. Participants were administered four of the Woodcock-Johnson III cognitive subtests and standard hearing threshold procedures. All participants were tested in each of three experimental conditions, including two perceptual-cognitive dual-tasks: (1) Auditory word recognition + visual processing, (2) Auditory working memory (sentence) + visual processing in noise, and (3) Auditory working memory (word) + visual processing. RESULTS: Results indicated that cognitive function does predict dual-task performance regardless of age and hearing function. CONCLUSION: Cognitive function may predict dual-task performance during speech-in-noise tasks. Further research investigating the predictive value of related cognitive subtests to listening effort is warranted.

A Novel Communication Value Task Demonstrates Evidence of Response Bias in Cases with Presbyacusis.

Decision-making about the expected value of an experience or behavior can explain hearing health behaviors in older adults with hearing loss. Forty-four middle-aged to older adults (68.45 ± 7.73 years) performed a task in which they were asked to decide whether information from a surgeon or an administrative assistant would be important to their health in hypothetical communication scenarios across visual signal-to-noise ratios (SNR). Participants also could choose to view the briefly presented sentences multiple times. The number of these effortful attempts to read the stimuli served as a measure of demand for information to make a health importance decision. Participants with poorer high frequency hearing more frequently decided that information was important to their health compared to participants with better high frequency hearing. This appeared to reflect a response bias because participants with high frequency hearing loss demonstrated shorter response latencies when they rated the sentences as important to their health. However, elevated high frequency hearing thresholds did not predict demand for information to make a health importance decision. The results highlight the utility of a performance-based measure to characterize effort and expected value from performing tasks in older adults with hearing loss.

A nonsynonymous mutation in the WFS1 gene in a Finnish family with age-related hearing impairment.

Wolfram syndrome (WS) is caused by recessive mutations in the Wolfram syndrome 1 (WFS1) gene. Sensorineural hearing impairment (HI) is a frequent feature in WS and, furthermore, certain mutations in WFS1 cause nonsyndromic dominantly inherited low-frequency sensorineural HI. These two phenotypes are clinically distinct indicating that WFS1 is a reasonable candidate for genetic studies in patients with other phenotypes of HI. Here we have investigated, whether the variation in WFS1 has a pathogenic role in age-related hearing impairment (ARHI). WFS1 gene was investigated in a population sample of 518 Finnish adults born in 1938-1949 and representing variable hearing phenotypes. Identified variants were evaluated with respect to pathogenic potential. A rare mutation predicted to be pathogenic was found in a family with many members with impaired hearing. Twenty members were recruited to a segregation study and a detailed clinical examination. Heterozygous p.Tyr528His variant segregated completely with late-onset HI in which hearing deteriorated first at high frequencies and progressed to mid and low frequencies later in life. We report the first mutation in the WFS1 gene causing late-onset HI with audiogram configurations typical for ARHI. Monogenic forms of ARHI are rare and our results add WFS1 to the short list of such genes.

The impact of hearing aids and age-related hearing loss on auditory plasticity across three months - An electrical neuroimaging study.

The present study investigates behavioral and electrophysiological auditory and cognitive-related plasticity in three groups of healthy older adults (60-77 years). Group 1 was moderately hearing-impaired, experienced hearing aid users, and fitted with new hearing aids using non-linear frequency compression (NLFC on); Group 2, also moderately hearing-impaired, used the same type of hearing aids but NLFC was switched off during the entire period of study duration (NLFC off); Group 3 represented individuals with age-appropriate hearing (NHO) as controls, who were not different in IQ, gender, or age from Group 1 and 2. At five measurement time points (M1-M5) across three months, a series of active oddball tasks were administered while EEG was recorded. The stimuli comprised syllables consisting of naturally high-pitched fricatives (/sh/, /s/, and /f/), which are hard to distinguish for individuals with presbycusis. By applying a data-driven microstate approach to obtain global field power (GFP) as a measure of processing effort, the modulations of perceptual (P50, N1, P2) and cognitive-related (N2b, P3b) auditory evoked potentials were calculated and subsequently related to behavioral changes (accuracy and reaction time) across time. All groups improved their performance across time, but NHO showed consistently higher accuracy and faster reaction times than the hearing-impaired groups, especially under difficult conditions. Electrophysiological results complemented this finding by demonstrating longer latencies in the P50 and the N1 peak in hearing aid users. Furthermore, the GFP of cognitive-related evoked potentials decreased from M1 to M2 in the NHO group, while a comparable decrease in the hearing-impaired group was only evident at M5. After twelve weeks of hearing aid use of eight hours each day, we found a significantly lower GFP in the P3b of the group with NLFC on as compared to the group with NLFC off. These findings suggest higher processing effort, as evidenced by higher GFP, in hearing-impaired individuals when compared to those with normal hearing, although the hearing-impaired show a decrease of processing effort after repeated stimulus exposure. In addition, our findings indicate that the acclimatization to a new hearing aid algorithm may take several weeks.

Effect of age-related hearing loss on the click-rate-induced facilitation of acoustic reflex thresholds.

OBJECTIVE: This investigation was designed to evaluate the effect of age-related hearing loss on the click-rate-induced improvement in the acoustic reflex thresholds. DESIGN: Case-control study. STUDY SAMPLE: Data from five different adults ear-groups (15 ears each) were included in the study: 1. Younger with normal hearing. 2. Older with normal hearing. 3. Older with mild high-frequency loss. 4. Older with moderate high-frequency loss. 5. Older with low- and high-frequency loss. Ipsilateral acoustic reflex thresholds were obtained from the left and/or right ear/s by presenting clicks at the repetition rates of 50, 100, 150, 200 and 300 clicks/s. The rate-induced facilitation (RIF) was calculated by subtracting the lowest acoustic reflex threshold from the highest reflex threshold obtained across the various click-rates. RESULTS: The click-RIF is significantly reduced in older individuals compared to younger adults. There is no significant difference in RIF across the four older adult groups suggesting that an age-related, mild to moderate hearing loss has no significant effect on the click RIF of the acoustic reflex thresholds. CONCLUSIONS: Click-RIF may allow us to document the effect of ageing on temporal processing within the auditory brainstem area, in a time-efficient and objective manner using commercially available equipment.

Extension and evaluation of a near-end listening enhancement algorithm for listeners with normal and impaired hearing.

In many applications in which speech is played back via a sound reinforcement system such as public address systems and mobile phones, speech intelligibility is degraded by additive environmental noise. A possible solution to maintain high intelligibility in noise is to pre-process the speech signal based on the estimated noise power at the position of the listener. The previously proposed AdaptDRC algorithm [Schepker, Rennies, and Doclo (2015). J. Acoust. Soc. Am. 138, 2692-2706] applies both frequency shaping and dynamic range compression under an equal-power constraint, where the processing is adaptively controlled by short-term estimates of the speech intelligibility index. Previous evaluations of the algorithm have focused on normal-hearing listeners. In this study, the algorithm was extended with an adaptive gain stage under an equal-peak-power constraint, and evaluated with eleven normal-hearing and ten mildly to moderately hearing-impaired listeners. For normal-hearing listeners, average improvements in speech reception thresholds of about 4 and 8 dB compared to the unprocessed reference condition were measured for the original algorithm and its extension, respectively. For hearing-impaired listeners, the average improvements were about 2 and 6 dB, indicating that the relative improvement due to the proposed adaptive gain stage was larger for these listeners than the benefit of the original processing stages.

Speech based transmission index for all: An intelligibility metric for variable hearing ability.

A method to measure the speech intelligibility in public address systems for normal hearing and hearing impaired persons is presented. The proposed metric is an extension of the speech based Speech Transmission Index to account for accurate perceptual masking and variable hearing ability: The sound excitation pattern generated at the ear is accurately computed using an auditory filter model, and its shapes depend on frequency, sound level, and hearing impairment. This extension yields a better prediction of the intensity of auditory masking which is used to rectify the modulation transfer function and thus to objectively assess the speech intelligibility experienced by hearing impaired as well as by normal hearing persons in public spaces. The proposed metric was developed within the framework of the European Active and Assisted Living research program, and was labeled "SB-STI for All." Extensive subjective in-Lab and in vivo tests have been conducted and the proposed metric proved to have a good correlation with subjective intelligibility scores.

Hyperexcitability of inferior colliculus and acoustic startle reflex with age-related hearing loss.

Chronic tinnitus and hyperacusis often develop with age-related hearing loss presumably due to aberrant neural activity in the central auditory system (CAS) induced by cochlear pathologies. However, the full spectrum of physiological changes that occur in the CAS as a result age-related hearing loss are still poorly understood. To address this issue, neurophysiological measures were obtained from the cochlea and the inferior colliculus (IC) of 2, 6 and 12 month old C57BL/6J mice, a mouse model for early age-related hearing loss. Thresholds of the compound action potentials (CAP) in 6 and 12 month old mice were significantly higher than in 2 month old mice. The sound driven and spontaneous firing rates of IC neurons, recorded with 16 channel electrodes, revealed mean IC thresholds of 22.8 ± 6.5 dB (n = 167) at 2 months, 37.9 ± 6.2 dB (n = 132) at 6 months and 47.1 ± 15.3 dB (n = 151) at 12 months of age consistent with the rise in CAP thresholds. The characteristic frequencies (CF) of IC neurons ranged from 3 to 32 kHz in 2 month old mice; the upper CF ranged decreased to 26 kHz and 16 kHz in 6 and 12 month old mice respectively. The percentage of IC neurons with CFs between 8 and 12 kHz increased from 36.5% in 2 month old mice, to 48.8% and 76.2% in 6 and 12 month old mice, respectively, suggesting a downshift of IC CFs due to the high-frequency hearing loss. The average spontaneous firing rate (SFRs) of all recorded neurons in 2 month old mice was 3.2 ± 2.5 Hz (n = 167). For 6 and 12 month old mice, the SFRs of low CF neurons (<8 kHz) was maintained at 3-6 spikes/s; whereas SFRs of IC neurons with CFs > 8 kHz increased to 13.0 ± 15.4 (n = 68) Hz at 6 months of age and then declined to 4.8 ± 7.4 (n = 110) spikes/s at 12 months of age. In addition, sound-evoked activity at suprathreshold levels at 6 months of age was much higher than at 2 and 12 months of age. To evaluate the behavioral consequences of sound evoked hyperactivity in the IC, the amplitude of the acoustic startle reflex was measured at 4, 8 and 16 kHz using narrow band noise bursts. Acoustic startle reflex amplitudes in 6 and 12 month old mice (n = 4) were significantly larger than 2 month old mice (n = 4) at 4 and 8 kHz, but not 16 kHz. The enhanced reflex amplitudes suggest that high-intensity, low-frequency sounds are perceived as louder than normal in 6 and 12 month old mice compared to 2 month olds. The increased spontaneous activity, particularly at 6 months, may be related to tinnitus whereas the increase in sound-evoked activity and startle reflex amplitudes may be related to hyperacusis.

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.

Association Between HbA1c Level and Hearing Impairment in a Nondiabetic Adult Population.

BACKGROUND: The aim of this study was to investigate whether glycosylated hemoglobin (HbA1c) level in nondiabetic patients is associated with hearing impairment in the general Korean population. PATIENTS AND METHODS: Data from the Korean National Health and Nutrition Examination Survey 2011-2013 were used in the analyses. Participants were excluded from this study for the following reasons: they could not provide data regarding pure tone audiometry, they had ear disease, they had brain disorders, asymmetric sensory neural hearing loss (HL), or they were younger than 40 years or had diabetes mellitus. Finally, 7449 participants were included in this study. RESULTS: The mean HbA1c levels in the low, middle, and high tertiles were 5.3% ± 0.2%, 5.7% ± 0.1%, and 6.1% ± 0.2%, respectively. The numbers of participants in the low, middle, and high tertiles were 2808, 2509, and 2132, respectively. The low-frequency, mid-frequency, high-frequency, and average hearing thresholds were significantly increased with increasing HbA1c tertile. Linear regression analyses showed that HbA1c level in the nondiabetic participants was associated with components of metabolic syndrome. The mean numbers of metabolic syndrome components in the low, middle, and high HbA1c tertiles were 1.22, 1.53, and 2.02, respectively. The participants in the middle and high HbA1c tertiles had a 1.239- and 1.253-fold increased risk of HL, respectively, compared with those in the low HbA1c tertile. CONCLUSION: HbA1c level was associated with hearing impairment in the nondiabetic participants of this study. Therefore, the participants with high HbA1c levels should be closely monitored for hearing impairment.

Circulating miR-34a levels correlate with age-related hearing loss in mice and humans.

Age-related hearing loss (AHL) is a progressive neurodegenerative disease that is largely silent in its initial stages. There is no sensitive blood biomarker for diagnosis or early detection of AHL. MicroRNAs (miRNAs or miRs) are abundant and highly stable in blood, and have been recently described as powerful circulating biomarkers in a wide range of diseases. In the present study, we identified concordant increases in miR-34a levels in the cochlea, auditory cortex, and plasma of C57BL/6 mice during aging. These increases were accompanied by elevated hearing thresholds and greater loss of hair cells. Levels of miR-34a targets, silent information regulator 1 (SIRT1), B-cell lymphoma-2 (Bcl-2), and E2F transcription factor 3 (E2F3), in the cochlea, auditory cortex, and plasma decreased with aging inversely to miR-34a. Moreover, plasma miR-34a levels were significantly higher in patients with AHL compared with controls who had normal hearing and had a receiver-operating characteristic curve that distinguished AHL patients from controls. However, SIRT1, Bcl-2, and E2F3 showed no correlation with AHL in humans. In summary, circulating miR-34a level may potentially serve as a useful biomarker for early detection of AHL.

Language processing of auditory cortex revealed by functional magnetic resonance imaging in presbycusis patients.

CONCLUSION: Contralateral temporal lobe activation decreases with aging, regardless of hearing status, with elderly individuals showing reduced right ear advantage. BACKGROUND: Aging and hearing loss possibly lead to presbycusis speech discrimination decline. OBJECTIVES: To evaluate presbycusis patients' auditory cortex activation under verbal stimulation. METHOD: Thirty-six patients were enrolled: 10 presbycusis patients (mean age = 64 years, range = 60-70), 10 in the healthy aged group (mean age = 66 years, range = 60-70), and 16 young healthy volunteers (mean age = 25 years, range = 23-28). These three groups underwent simultaneous 1 kHz and 90 dB single-syllable word stimuli and (blood-oxygen-level-dependent functional magnetic resonance imaging) BOLD fMRI examinations. RESULTS: The main activation regions were superior temporal and middle temporal gyrus. For all aged subjects, the right region of interest (ROI) activation volume was decreased compared with the young group. With left ear stimulation, bilateral ROI activation intensity held. With right ear stimulation, the aged group's activation intensity was higher. Using monaural stimulation in the young group, contralateral temporal lobe activation volume and intensity were higher vs ipsilateral, while they were lower in the aged and presbycusis groups. On left and right ear auditory tasks, the young group showed right ear advantage, while the aged and presbycusis groups showed reduced right ear advantage.

A DPOAE assessment of outer hair cell integrity in ears with age-related hearing loss.

Distortion product otoacoustic emissions (DPOAEs) were used to assess outer hair cell (OHC) integrity in human ears with age-related hearing loss. Sound pressure measurements were made in the ear canal over the stimulus range 40-90 dB SPL (L2), with L1 = 0.45*L2 + 44 with F2 = 2 and 3 or 4 kHz. Model-generated DPOAE I/O functions were fit to DPOAE data to quantify the contribution of loss of nonlinearity (OHC loss) to the hearing loss. Results suggest OHC loss as a contributing cause of age-related hearing, regardless of audiogram configuration. It seems likely that OHC and strial pathology co-exist in ears with AHL.