Auditory Deprivation during Development Alters Efferent Neural Feedback and Perception.

Auditory experience plays a critical role in hearing development. Developmental auditory deprivation because of otitis media, a common childhood disease, produces long-standing changes in the central auditory system, even after the middle ear pathology is resolved. The effects of sound deprivation because of otitis media have been mostly studied in the ascending auditory system but remain to be examined in the descending pathway that runs from the auditory cortex to the cochlea via the brainstem. Alterations in the efferent neural system could be important because the descending olivocochlear pathway influences the neural representation of transient sounds in noise in the afferent auditory system and is thought to be involved in auditory learning. Here, we show that the inhibitory strength of the medial olivocochlear efferents is weaker in children with a documented history of otitis media relative to controls; both boys and girls were included in the study. In addition, children with otitis media history required a higher signal-to-noise ratio on a sentence-in-noise recognition task than controls to achieve the same criterion performance level. Poorer speech-in-noise recognition, a hallmark of impaired central auditory processing, was related to efferent inhibition, and could not be attributed to the middle ear or cochlear mechanics.SIGNIFICANCE STATEMENT Otitis media is the second most common reason children go to the doctor. Previously, degraded auditory experience because of otitis media has been associated with reorganized ascending neural pathways, even after middle ear pathology resolved. Here, we show that altered afferent auditory input because of otitis media during childhood is also associated with long-lasting reduced descending neural pathway function and poorer speech-in-noise recognition. These novel, efferent findings may be important for the detection and treatment of childhood otitis media.

A Multi-Sample Comparison and Rasch Analysis of the Evaluation of Children's Listening and Processing Skills Questionnaire.

OBJECTIVES: Assessing listening difficulties and associated complaints can be challenging. Often, measures of peripheral auditory functions are within normal ranges, making clinicians feel unsure about proper management strategies. The range and nature of observed or experienced difficulties might be better captured using a qualitative measure. The Evaluation of Children's Listening and Processing Skills (ECLiPS) questionnaire was designed to broadly profile the auditory and cognitive problems often present in children with listening difficulties. This 38-item questionnaire was initially standardized in British children aged 6 to 11 years, was subsequently modified for use with North-American children, and was recently translated into Flemish-Dutch. This study aimed to compare typical scores of the Flemish version with the UK and US versions, and to evaluate and compare its psychometric quality based on Rasch analysis. DESIGN: We selected 112 Flemish children aged 6 to 11 years with verified normal hearing and typical development, and asked two caregivers of every child to fill out the ECLiPS. Data from two comparator samples were analyzed, including responses for 71 North-American children and 650 British children. Typical values for ECLiPS factors and aggregates were determined as a function of age and gender, and meaningful differences across samples were analyzed. Rasch analyses were performed to evaluate whether ECLiPS response categories work as intended, and whether item scores fit a linear equal interval measurement scale that works the same way for everyone. Item and person metrics were derived, including separation and reliability indices. We investigated whether items function similarly across linguistically and culturally different samples. RESULTS: ECLiPS scores were relatively invariant to age. Girls obtained higher scores compared with boys, mainly for items related to memory and attention, and pragmatic and social skills. Across ECLiPS versions, the most pronounced differences were found for items probing social skills. With respect to its psychometric quality, ECLiPS response categories work as intended, and ECLiPS items were found to fit the Rasch measurement scale. Cultural differences in responses were noted for some items, belonging to different factors. Item separation and reliability indices generally pointed toward sufficient variation in item difficulty. In general, person separation (and reliability) metrics, quantifying the instrument's ability to distinguish between poor and strong performers (in a reproducible manner), were low. This is expected from samples of typically developing children with homogeneous and high levels of listening ability. CONCLUSIONS: Across the languages assessed here, the ECLiPS caregiver questionnaire was verified to be a psychometrically valid qualitative measure to assess listening and processing skills, which can be used to support the assessment and management of elementary school children referred with LiD.

Childhood Listening and Associated Cognitive Difficulties Persist Into Adolescence.

OBJECTIVE: Listening difficulty (LiD) refers to the challenges individuals face when trying to hear and comprehend speech and other sounds. LiD can arise from various sources, such as hearing sensitivity, language comprehension, cognitive function, or auditory processing. Although some children with LiD have hearing loss, many have clinically normal audiometric thresholds. To determine the impact of hearing and cognitive factors on LiD in children with a clinically normal audiogram, we conducted a longitudinal study. The Evaluation of Children's Listening & Processing Skills (ECLiPS), a validated and standardized caregiver evaluation tool, was used to group participants as either LiD or typically developing (TD). Our previous study aimed to characterize LiD in 6- to 13-year-old children during the project's baseline, cross-sectional phase. We found that children with LiD needed a higher signal-to-noise ratio during speech-in-speech tests and scored lower on all assessed components of the NIH Cognition Toolbox than TD children. The primary goal of this study was to examine if the differences between LiD and TD groups are temporary or enduring throughout childhood. DESIGN: This longitudinal study had three data collection waves for children with LiD and TD aged 6 to 13 years at Wave 1, followed by assessments at 2-year (Wave 2) and 4-year (Wave 3) intervals. Primary analysis focused on data from Waves 1 and 2. Secondary analysis encompassed all three waves despite high attrition at Wave 3. Caregivers completed the ECLiPS, while participants completed the Listening in Spatialized Noise-Sentences (LiSN-S) test and the NIH-Toolbox Cognition Battery during each wave. The analysis consisted of (1) examining longitudinal differences between TD and LiD groups in demographics, listening, auditory, and cognitive function; (2) identifying functional domains contributing to LiD; and (3) test-retest reliability of measures across waves. Mixed-effect models were employed to analyze longitudinal data. RESULTS: The study enrolled 169 participants, with 147, 100, and 31 children completing the required testing during Waves 1, 2, and 3, respectively. The mean ages at these waves were 9.5, 12.0, and 14.0 years. On average, children with LiD consistently underperformed TD children in auditory and cognitive tasks across all waves. Maternal education, auditory, and cognitive abilities independently predicted caregiver-reported listening skills. Significant correlations between Waves 1 and 2 confirmed high, long-term reliability. Secondary analysis of Wave 3 was consistent with the primary analyses of Waves 1 and 2, reinforcing the enduring nature of listening difficulties. CONCLUSION: Children with LiD and clinically normal audiograms experience persistent auditory, listening, and cognitive challenges through at least adolescence. The degree of LiD can be independently predicted by maternal education, cognitive processing, and spatial listening skills. This study underscores the importance of early detection and intervention for childhood LiD and highlights the role of socioeconomic factors as contributors to these challenges.

Smartphone-Facilitated In-Situ Hearing Aid Audiometry for Community-Based Hearing Testing.

OBJECTIVES: Hearing loss prevalence is increasing, with an estimated 2.5 billion people affected globally by 2050. Scalable service delivery models using innovative technologies and task-shifting are World Health Organization priorities to improve access to hearing care, particularly in low- and middle-income countries. Smartphone-facilitated audiometry in the community using hearing aids covered by noise-attenuating ear cups ("in-situ") could support more accessible hearing care when provided by less trained individuals such as community health workers (CHWs). This study aimed to determine the validity of this method for potential hearing aid fitting. Study objectives included determining the maximum permissible ambient noise level (MPANL), inter-device reliability, clinical threshold accuracy, reliability, and performance in real-world settings. DESIGN: Experiment 1: 15 normal-hearing adult participants were evaluated to determine MPANLs for circumaural Peltor 3M earcups covering Lexie Lumen hearing aids with smartphone-facilitated in-situ audiometry. MPANLs were calculated by measuring the difference in attenuation between thresholds obtained with standard headphones and in-situ hearing aids. Experiment 2: Pure-tone frequency and intensity output of 14 same-model Lexie Lumen hearing aids were measured to determine inter-device reliability. Pure-tone stimuli were measured and analyzed to determine sound pressure levels in decibels and pure-tone frequency when connected to a test box 2cc coupler. Experiment 3: 85 adult participants were tested in a sound booth to determine the accuracy of automated in-situ pure-tone audiometry (PTA) compared to clinical PTA (500, 1000, 2000, 3000, 4000, 6000 Hz) facilitated by an audiologist. The first 39 participants were tested twice to determine test-retest reliability. Experiment 4: In a community setting, 144 adult participants were tested with automated in-situ audiometry facilitated by CHWs using a smartphone app. These participants were subsequently tested with automated mobile PTA (500, 1000, 2000, 4000 Hz). An additional 44 participants were tested twice to determine test-retest reliability. RESULTS: Experiment 1: MPANLs of the Peltor 3M earcup-covered hearing aids were higher than standard headphones across all frequencies, ranging from 24 to 47.3 dB SPL. Experiment 2: Inter-device performance reliability was high, with all inter-device differences across all intensities and frequencies less than 3 dB. Frequency output was consistent and differed less than 0.7% between devices. Experiments 3 and 4: 85.2% and 83.3% of automated in-situ audiometry thresholds were within 10 dB of thresholds obtained in the sound booth and in a community setting, respectively. Acceptable test-retest intraclass correlation coefficient (ICC) was evident across all thresholds obtained in a sound booth (ICC = 0.85 to 0.93) and in a community setting (ICC = 0.83 to 0.97). CONCLUSIONS: Smartphone-facilitated in-situ audiometry allows for reliable and valid community-based testing. A simple smartphone user interface and automated in-situ audiometry allow CHWs with minimal training to facilitate the testing. With the additional capability to program hearing aids via the smartphone after the initial test, this approach would have the potential to support widespread access to personalized hearing aid fittings facilitated by CHWs in low- and middle-income countries. This approach also supports self-fitting options based on in-situ thresholds, enabling testing and fitting via over the counter hearing aids.

Remote self-report and speech-in-noise measures predict clinical audiometric thresholds.

OBJECTIVE: Developments in smartphone technology and the COVID-19 pandemic have highlighted the feasibility and need for remote, but reliable hearing tests. Previous studies used remote testing but did not directly compare results in the same listeners with standard lab or clinic testing. This study investigated validity and reliability of remote, self-administered digits-in-noise (remote-DIN) compared with lab-based, supervised (lab-DIN) testing. Predictive validity was further examined in relation to a commonly used self-report, Speech, Spatial, and Qualities of Hearing (SSQ-12), and lab-based, pure tone audiometry. DESIGN: DIN speech reception thresholds (SRTs) of adults (18-64 y/o) with normal hearing (NH, N = 16) and hearing loss (HL, N = 18), were measured using English-language digits (0-9), binaurally presented as triplets in one of four speech-shaped noise maskers (broadband, low-pass filtered at 2, 4, 8 kHz) and two phases (diotic, antiphasic). RESULTS: High, significant intraclass correlation coefficients indicated strong internal consistency of remote-DIN SRTs, which also correlated significantly with lab-DIN SRTs. There was no significant mean difference between remote- and lab-DIN on any tests. NH listeners had significantly higher SSQ scores and remote- and lab-DIN SRTs than listeners with HL. All versions of remote-DIN SRTs correlated significantly with pure-tone-average (PTA), with the 2-kHz filtered test being the best predictor, explaining 50% of the variance in PTA. SSQ total score also significantly and independently predicted PTA (17% of variance) and all test versions of the remote-DIN, except the antiphasic BB test. CONCLUSIONS: This study underscores the effectiveness of remote DIN test and SSQ-12 in assessing auditory function. These findings suggest the potential for wider access to reliable hearing assessment, particularly in remote or underserved communities.

Sensitivity of the antiphasic digits-in-noise test to simulated unilateral and bilateral conductive hearing loss.

OBJECTIVES: The objective of this study is (1) to assess whether the presentation level of the antiphasic digits-in-noise (DIN) test affects the speech recognition threshold (SRT), (2) to evaluate how accurately simulated unilateral and bilateral conductive hearing loss is detected (CHL) and (3) to determine whether increasing the presentation level normalises the antiphasic DIN SRT. DESIGN: Participants performed antiphasic and diotic DINs at different presentation levels with unilateral, bilateral or no earplugs. STUDY SAMPLE: Twenty-four and twelve normal hearing adults. RESULTS: Without earplugs, antiphasic DIN SRTs did not differ between 60 and 80 dB SPL. At 60 dB SPL, the antiphasic DIN correctly classified 92% of the unilateral earplug cases; the diotic DIN 25%. The binaural intelligibility level difference did not differ between the no-earplug condition and the condition with bilateral earplugs when the presentation was increased with the attenuation level. CONCLUSIONS: In normal hearing participants, diotic and antiphasic DIN SRTs are independent of presentation level above a minimum level of 60 dB SPL. The antiphasic DIN is more sensitive than the diotic DIN for detecting unilateral CHL; not for bilateral CHL. The effect of CHL on DIN SRTs can be largely compensated by increasing the presentation level. Audibility plays an important role in the antiphasic and diotic DIN.

Web- and app-based tools for remote hearing assessment: a scoping review.

OBJECTIVE: Remote hearing screening and assessment may improve access to, and uptake of, hearing care. This review, the most comprehensive to date, aimed to (i) identify and assess functionality of remote hearing assessment tools on smartphones and online platforms, (ii) determine if assessed tools were also evaluated in peer-reviewed publications and (iii) report accuracy of existing validation data. DESIGN: Protocol was registered in INPLASY and reported according to PRISMA-Extension for Scoping Reviews. STUDY SAMPLE: In total, 187 remote hearing assessment tools (using tones, speech, self-report or a combination) and 101 validation studies met the inclusion criteria. Quality, functionality, bias and applicability of each app were assessed by at least two authors. RESULTS: Assessed tools showed considerable variability in functionality. Twenty-two (12%) tools were peer-reviewed and 14 had acceptable functionality. The validation results and their quality varied greatly, largely depending on the category of the tool. CONCLUSION: The accuracy and reliability of most tools are unknown. Tone-producing tools provide approximate hearing thresholds but have calibration and background noise issues. Speech and self-report tools are less affected by these issues but mostly do not provide an estimated pure tone audiogram. Predicting audiograms using filtered language-independent materials could be a universal solution.

Carbon Dioxide Capture Chemistry of Amino Acid Functionalized Metal-Organic Frameworks in Humid Flue Gas.

Metal-organic framework-808 has been functionalized with 11 amino acids (AA) to produce a series of MOF-808-AA structures. The adsorption of CO2 under flue gas conditions revealed that glycine- and dl-lysine-functionalized MOF-808 (MOF-808-Gly and -dl-Lys) have the highest uptake capacities. Enhanced CO2 capture performance in the presence of water was observed and studied by using single-component sorption isotherms, CO2/H2O binary isotherm, and dynamic breakthrough measurements. The key to the favorable performance was uncovered by deciphering the mechanism of CO2 capture in the pores and attributed to the formation of bicarbonate as evidenced by 13C and 15N solid-state nuclear magnetic resonance spectroscopy studies. On the basis of these results, we examined the performance of MOF-808-Gly in simulated coal flue gas conditions and found that it is possible to capture and release CO2 by vacuum swing adsorption. MOF-808-Gly was cycled at least 80 times with full retention of performance. This study significantly advances our understanding of CO2 chemistry in MOFs by revealing how strongly bound amine moieties to the MOF backbone create the chemistry and environment within the pores, leading to the binding and release of CO2 under mild conditions without application of heat.

GWAS Identifies 44 Independent Associated Genomic Loci for Self-Reported Adult Hearing Difficulty in UK Biobank.

Age-related hearing impairment (ARHI) is the most common sensory impairment in the aging population; a third of individuals are affected by disabling hearing loss by the age of 65. It causes social isolation and depression and has recently been identified as a risk factor for dementia. The genetic risk factors and underlying pathology of ARHI are largely unknown, meaning that targets for new therapies remain elusive, yet heritability estimates range between 35% and 55%. We performed genome-wide association studies (GWASs) for two self-reported hearing phenotypes, using more than 250,000 UK Biobank (UKBB) volunteers aged between 40 and 69 years. Forty-four independent genome-wide significant loci (p < 5E-08) were identified, considerably increasing the number of established trait loci. Thirty-four loci are novel associations with hearing loss of any form, and only one of the ten known hearing loci has a previously reported association with an ARHI-related trait. Gene sets from these loci are enriched in auditory processes such as synaptic activities, nervous system processes, inner ear morphology, and cognition, while genetic correlation analysis revealed strong positive correlations with multiple personality and psychological traits for the first time. Immunohistochemistry for protein localization in adult mouse cochlea implicate metabolic, sensory, and neuronal functions for NID2, CLRN2, and ARHGEF28. These results provide insight into the genetic landscape underlying ARHI, opening up novel therapeutic targets for further investigation. In a wider context, our study also highlights the viability of using self-report phenotypes for genetic discovery in very large samples when deep phenotyping is unavailable.

Diotic and Antiphasic Digits-in-noise Testing as a Hearing Screening and Triage Tool to Classify Type of Hearing Loss.

OBJECTIVES: The digits-in-noise test (DIN) is a popular self-test measure that has traditionally been used to screen for hearing loss by providing either a pass or refer result. Standard approaches either tested each ear monaurally or used a binaural diotic version where identical digits and noise were presented simultaneously to both ears. Recently, a dichotic, antiphasic version was developed, increasing sensitivity of the DIN to unilateral or asymmetric sensorineural hearing loss (SNHL) and conductive hearing loss (CHL). The purpose of this study was to determine predictors and normative ranges of the antiphasic and diotic DIN and to determine if a combination of diotic and antiphasic DIN could accurately categorize hearing into (1) normal, (2) bilateral SNHL, or (3) unilateral SNHL or CHL. DESIGN: The analytical sample consisted of 489 participants between the ages of 18 and 92 years with varying types, symmetry, and degrees of hearing loss. Degree and type of hearing loss were determined based on standard clinical four-frequency (0.5-4 kHz) pure-tone air and bone conduction threshold averages. The sample consisted of bilateral normal hearing (n = 293), bilateral SNHL (n = 172), unilateral SNHL (n = 42), and CHL (n = 32). All participants (n = 489) first completed an antiphasic DIN (digit stimuli 180° out-of-phase between ears), while 393 of the sample also completed a diotic DIN. Two procedures were assessed for their ability to categorize hearing into one of the three hearing groups. The first used a fixed antiphasic cutoff combined with a cutoff formed by a linear combination of antiphasic and diotic speech recognition threshold (SRT) or binaural intelligibility-level difference. RESULTS: Poorer ear pure-tone average was the strongest predictor of antiphasic DIN score, whereas better ear pure-tone average explained more of the variance in diotic SRT. The antiphasic DIN sensitivity and specificity was 90% and 84%, respectively, for detecting hearing loss, with outstanding area under the receiver operating characteristics values exceeding 0.93 to identify hearing loss in the poorer ear. The first fixed SRT cutoff procedure could categorize 75% of all participants correctly, while the second procedure increased correct categorization to 79%. False negative rates for both procedures were below 10%. CONCLUSIONS: A sequential antiphasic and diotic DIN could categorize hearing to a reasonable degree into three groups of (1) normal hearing; (2) bilateral SNHL; and (3) unilateral asymmetric SNHL or CHL. This type of approach could optimize care pathways using remote and contactless testing, by identifying unilateral SNHL and CHL as cases requiring medical referral. In contrast, bilateral SNHL cases could be referred directly to an audiologist, or nontraditional models like OTC hearing aids.

Adaptive Hearing Aid Benefit in Children With Mild/Moderate Hearing Loss: A Registered, Double-Blind, Randomized Clinical Trial.

OBJECTIVES: We completed a registered double-blind randomized control trial to compare acclimatization to two hearing aid fitting algorithms by experienced pediatric hearing aid users with mild to moderate hearing loss. We hypothesized that extended use (up to 13 months) of an adaptive algorithm with integrated directionality and noise reduction, OpenSound Navigator (OSN), would result in improved performance on auditory, cognitive, academic, and caregiver- or self-report measures compared with a control, omnidirectional algorithm (OMNI). DESIGN: Forty children aged 6 to 13 years with mild to moderate/severe symmetric sensorineural hearing loss completed this study. They were all experienced hearing aid users and were recruited through the Cincinnati Children's Hospital Medical Center Division of Audiology. The children were divided into 20 pairs based on similarity of age (within 1 year) and hearing loss (level and configuration). Individuals from each pair were randomly assigned to either an OSN (experimental) or OMNI (control) fitting algorithm group. Each child completed an audiology evaluation, hearing aid fitting using physically identical Oticon OPN hearing aids, follow-up audiological appointment, and 2 research visits up to 13 months apart. Research visit outcome measures covered speech perception (in quiet and in noise), novel grammar and word learning, cognition, academic ability, and caregiver report of listening behaviors. Analysis of outcome differences between visits, groups, ages, conditions and their interactions used linear mixed models. Between 22 and 39 children provided useable data for each task. RESULTS: Children using the experimental (OSN) algorithm did not show any significant performance differences on the outcome measures compared with those using the control (OMNI) algorithm. Overall performance of all children in the study increased across the duration of the trial on word repetition in noise, sentence repetition in quiet, and caregivers' assessment of hearing ability. There was a significant negative relationship between age at first hearing aid use, final Reading and Mathematical ability, and caregiver rated speech hearing. A significant positive relationship was found between daily hearing aid use and study-long change in performance on the Flanker test of inhibitory control and attention. Logged daily use of hearing aids related to caregiver rated spatial hearing. All results controlled for age at testing/evaluation and false discovery rate. CONCLUSIONS: Use of the experimental (OSN) algorithm neither enhanced nor reduced performance on auditory, cognitive, academic or caregiver report measures compared with the control (OMNI) algorithm. However, prolonged hearing aid use led to benefits in hearing, academic skills, attention, and caregiver evaluation.

Extended high-frequency hearing enhances speech perception in noise.

Young healthy adults can hear tones up to at least 20 kHz. However, clinical audiometry, by which hearing loss is diagnosed, is limited at high frequencies to 8 kHz. Evidence suggests there is salient information at extended high frequencies (EHFs; 8 to 20 kHz) that may influence speech intelligibility, but whether that information is used in challenging listening conditions remains unknown. Difficulty understanding speech in noisy environments is the most common concern people have about their hearing and usually the first sign of age-related hearing loss. Digits-in-noise (DIN), a widely used test of speech-in-noise perception, can be sensitized for detection of high-frequency hearing loss by low-pass filtering the broadband masking noise. Here, we used standard and EHF audiometry, self-report, and successively higher cutoff frequency filters (2 to 8 kHz) in a DIN test to investigate contributions of higher-frequency hearing to speech-in-noise perception. Three surprising results were found. First, 74 of 116 "normally hearing," mostly younger adults had some hearing loss at frequencies above 8 kHz. Early EHF hearing loss may thus be an easily measured, preventive warning to protect hearing. Second, EHF hearing loss correlated with self-reported difficulty hearing in noise. Finally, even with the broadest filtered noise (≤8 kHz), DIN hearing thresholds were significantly better (P < 0.0001) than those using broadband noise. Sound energy above 8 kHz thus contributes to speech perception in noise. People with "normal hearing" frequently report difficulty hearing in challenging environments. Our results suggest that one contribution to this difficulty is EHF hearing loss.

The one-up one-down adaptive (staircase) procedure in speech-in-noise testing: Standard error of measurement and fluctuations in the track.

The one-up one-down adaptive (staircase or up-down) procedure is often used to estimate the speech recognition threshold (SRT) in speech-in-noise testing. This article provides a brief historical overview of the one-up one-down procedure in psychophysics, discussing the groundbreaking early work that is still relevant to clinical audiology and scientific research. Next, this article focuses on two aspects of the one-up one-down adaptive procedure: first, the standard error of measurement (SEM) and, second, the fluctuations in the track [i.e., the standard deviation of the signal-to-noise ratios of the stimuli within the track (SDtrack)]. Simulations of ideal and non-ideal listeners and experimental data are used to determine and evaluate different relationships between the parameters slope of the speech recognition function, SRT, SEM, and SDtrack. Hearing loss and non-ideal behavior (inattentiveness, fatigue, and giving up when the task becomes too difficult) slightly increase the average value of SDtrack. SDtrack, however, poorly discriminates between reliable and unreliable SRT estimates.

Speech-in-noise testing: Innovative applications for pediatric patients, underrepresented populations, fitness for duty, clinical trials, and remote services.

Speech perception testing, defined as providing standardized speech stimuli and requiring a listener to provide a behavioral and scored response, has been an integral part of the audiologic test battery since the beginning of the audiology profession. Over the past several decades, limitations in the diagnostic and prognostic validity of standard speech perception testing as routinely administered in the clinic have been noted, and the promotion of speech-in-noise testing has been highlighted. This review will summarize emerging and innovative approaches to speech-in-noise testing with a focus on five applications: (1) pediatric considerations promoting the measurement of sensory and cognitive components separately; (2) appropriately serving underrepresented populations with special attention to racial, ethnic, and linguistic minorities, as well as considering biological sex and/or gender differences as variables of interest; (3) binaural fitness for duty assessments of functional hearing for occupational settings that demand the ability to detect, recognize, and localize sounds; (4) utilization of speech-in-noise tests in pharmacotherapeutic clinical trials with considerations to the drug mechanistic action, the patient populations, and the study design; and (5) online and mobile applications of hearing assessment that increase accessibility and the direct-to-consumer market.

A neurotrophic approach to treating hearing loss: Translation from animal models to clinical proof-of-concept.

Currently, there are no approved medicines available for the treatment of hearing loss. However, research over the past two decades has contributed to a growing understanding of the pathological mechanisms in the cochlea that result in hearing difficulties. The concept that a loss of the synapses connecting inner hair cells with the auditory nerve (cochlear synaptopathy) contributes to hearing loss has gained considerable attention. Both animal and human post-mortem studies support the idea that these synapses (ribbon synapses) are highly vulnerable to noise, ototoxicity, and the aging process. Their degeneration has been suggested as an important factor in the speech-in-noise difficulties commonly experienced by those suffering with hearing loss. Neurotrophins such as brain derived neurotrophic factor (BDNF) have the potential to restore these synapses and provide improved hearing function. OTO-413 is a sustained exposure formulation of BDNF suitable for intratympanic administration that in preclinical models has shown the ability to restore ribbon synapses and provide functional hearing benefit. A phase 1/2 clinical trial with OTO-413 has provided initial proof-of-concept for improved speech-in-noise hearing performance in subjects with hearing loss. Key considerations for the design of this clinical study, including aspects of the speech-in-noise assessments, are discussed.

Identifying barriers and facilitators of hearing protection use in early-career musicians: a basis for designing interventions to promote uptake and sustained use.

OBJECTIVE: The current study aimed to: i) determine the patterns of hearing protection device (HPD) use in early-career musicians, ii) identify barriers to and facilitators of HPD use, and iii) use the Behaviour Change Wheel (BCW) to develop an intervention to increase uptake and sustained use of HPDs. DESIGN: A mixed-methods approach using questionnaires and semi-structured interviews. STUDY SAMPLE: Eighty early-career musicians (age range = 18-26 years; women n = 39), across all categories of musical instrument. RESULTS: 42.5% percent of participants reported using HPDs at least once a week, 35% less than once a week, and 22.5% reported never using HPDs for music-related activities. Six barriers and four facilitators of HPD use were identified. Barriers include the impact of HPDs on listening to music and performing, and a lack of concern about noise exposure. Barriers/facilitators were mapped onto the Theoretical Domains Framework. Following the systematic process of the BCW, our proposed intervention strategies are based on 'Environmental Restructuring', such as providing prompts to increase awareness of noisy settings, and 'Persuasion/Modelling', such as providing credible role models. CONCLUSIONS: For the first time, the present study demonstrates the use of the BCW for designing interventions in the context of hearing conservation.

Improved Sensitivity of Digits-in-Noise Test to High-Frequency Hearing Loss.

OBJECTIVES: Hearing loss is most commonly observed at high frequencies. High-frequency hearing loss (HFHL) precedes and predicts hearing loss at lower frequencies. It was previously shown that an automated, self-administered digits-in-noise (DIN) test can be sensitized for detection of HFHL by low-pass filtering the speech-shaped masking noise at 1.5 kHz. This study was designed to investigate whether sensitivity of the DIN to HFHL can be enhanced further using low-pass noise filters with higher cutoff frequencies. DESIGN: The US-English digits 0 to 9, homogenized for audibility, were binaurally presented in different noise maskers including one broadband and three low-pass (cutoff at 2, 4, and 8 kHz) filtered speech-shaped noises. DIN-speech reception thresholds (SRTs) were obtained from 60 normal hearing (NH), and 40 mildly hearing impaired listeners with bilateral symmetric sensorineural hearing loss. Standard and extended high-frequency audiometric pure-tone averages (PTAs) were compared with the DIN-SRTs. RESULTS: Narrower masking noise bandwidth generally produced better (more sensitive) mean DIN-SRTs. There were strong and significant correlations between SRT and PTA in the hearing impaired group. Lower frequency PTALF 0.5,1, 2, 4 kHz had the highest correlation and the steepest slope with SRTs obtained from the 2-kHz filter. Higher frequency PTAHF 4,8,10,12.5 kHz correlated best with SRTs obtained from 4- and 8-kHz filtered noise. The 4-kHz low-pass filter also had the highest sensitivity (92%) and equally highest (with the 8-kHz filter) specificity (90%) for detecting an average PTAHF of 20 dB or more. CONCLUSIONS: Of the filters used, DIN sensitivity to higher frequency hearing loss was greatest using the 4-kHz low-pass filter. These results suggest that low-pass filtered noise may be usefully substituted for broadband noise to improve earlier detection of HFHL using DIN.

Peripheral Auditory Involvement in Childhood Listening Difficulty.

OBJECTIVES: This study tested the hypothesis that undetected peripheral hearing impairment occurs in children with idiopathic listening difficulties (LiDs), as reported by caregivers using the Evaluation of Children"s Listening and Processing Skills (ECLiPS) validated questionnaire, compared with children with typically developed (TD) listening abilities. DESIGN: Children with LiD aged 6-14 years old (n = 60, mean age = 9.9 yr) and 54 typical age matched children were recruited from audiology clinical records and from IRB-approved advertisements at hospital locations and in the local and regional areas. Both groups completed standard and extended high-frequency (EHF) pure-tone audiometry, wideband absorbance tympanometry and middle ear muscle reflexes, distortion product and chirp transient evoked otoacoustic emissions. Univariate and multivariate mixed models and multiple regression analysis were used to examine group differences and continuous performance, as well as the influence of demographic factors and pressure equalization (PE) tube history. RESULTS: There were no significant group differences between the LiD and TD groups for any of the auditory measures tested. However, analyses across all children showed that EHF hearing thresholds, wideband tympanometry, contralateral middle ear muscle reflexes, distortion product, and transient-evoked otoacoustic emissions were related to a history of PE tube surgery. The physiologic measures were also associated with EHF hearing loss, secondary to PE tube history. CONCLUSIONS: Overall, the results of this study in a sample of children with validated LiD compared with a TD group matched for age and sex showed no significant differences in peripheral function using highly sensitive auditory measures. Histories of PE tube surgery were significantly related to EHF hearing and to a range of physiologic measures in the combined sample.

Listening Difficulties in Children With Normal Audiograms: Relation to Hearing and Cognition.

OBJECTIVES: Children presenting at audiology services with caregiver-reported listening difficulties often have normal audiograms. The appropriate approach for the further assessment and clinical management of these children is currently unclear. In this Sensitive Indicators of Childhood Listening Difficulties (SICLiD) study, we assessed listening ability using a reliable and validated caregiver questionnaire (the Evaluation of Children's Listening and Processing Skills [ECLiPS]) in a large (n = 146) and heterogeneous sample of 6- to 13-year-old children with normal audiograms. Scores on the ECLiPS were related to a multifaceted laboratory assessment of the children's audiological, psycho- and physiological-acoustic, and cognitive abilities. This report is an overview of the SICLiD study and focuses on the children's behavioral performance. The overall goals of SICLiD were to understand the auditory and other neural mechanisms underlying childhood listening difficulties and translate that understanding into clinical assessment and, ultimately, intervention. DESIGN: Cross-sectional behavioral assessment of children with "listening difficulties" and an age-matched "typically developing" control group. Caregivers completed the ECLiPS, and the resulting total standardized composite score formed the basis of further descriptive statistics, univariate, and multivariate modeling of experimental data. RESULTS: All scores of the ECLiPS, the SCAN-3:C, a standardized clinical test suite for auditory processing, and the National Institutes of Health (NIH) Cognition Toolbox were significantly lower for children with listening difficulties than for their typically developing peers using group comparisons via t-tests and Wilcoxon Rank-Sum tests. A similar effect was observed on the Listening in Spatialized Noise-Sentences (LiSN-S) test for speech sentence-in-noise intelligibility but only reached significance for the Low Cue and High Cue conditions and the Talker Advantage derived score. Stepwise regression to examine the factors contributing to the ECLiPS Total scaled score (pooled across groups) yielded a model that explained 42% of its variance based on the SCAN-3:C composite, LiSN-S Talker Advantage, and the NIH Toolbox Picture Vocabulary, and Dimensional Change Card Sorting scores (F[4, 95] = 17.35, p < 0.001). High correlations were observed between many test scores including the ECLiPS, SCAN-3:C, and NIH Toolbox composite measures. LiSN-S Advantage measures generally correlated weakly and nonsignificantly with non-LiSN-S measures. However, a significant interaction was found between extended high-frequency threshold and LiSN-S Talker Advantage. CONCLUSIONS: Children with listening difficulties but normal audiograms have problems with the cognitive processing of auditory and nonauditory stimuli that include both fluid and crystallized reasoning. Analysis of poor performance on the LiSN-S Talker Advantage measure identified subclinical hearing loss as a minor contributing factor to talker segregation. Beyond auditory tests, evaluations of children with complaints of listening difficulties should include standardized caregiver observations and consideration of broad cognitive abilities.

Associations Between Hearing Health and Well-Being in Unilateral Hearing Impairment.

OBJECTIVES: To determine population-based risks of adverse effects on hearing and well-being outcomes associated with unilateral hearing impairment. DESIGN: A group of 40- to 69-year-old adults (n = 861) who reported being able to hear only in one ear and having speech reception thresholds (SRTs) in noise indicating normal hearing in that ear (SRTN/-) was selected from the UK Biobank cohort. The UK Biobank participants with SRTs indicating either normal (SRTN/N, n = 95,514) or symmetrically impaired hearing in both ears (SRTI/I, n = 17,429) were selected as comparison groups. Self-reported difficulty following conversations in noise, tinnitus presence, feeling depressed, lonely, unhappy, and being in poor health or dissatisfied with health were selected as hearing and well-being outcomes. Logistic regression models were used to evaluate the risks of reporting adverse outcomes associated with SRTN/- compared with SRTN/N and SRTI/I while controlling for numerous factors linked to hearing and general health. RESULTS: People with SRTN/- were significantly more likely to report difficulties following conversations in noise (odds ratio, 10.61; 95% confidence interval, 8.83 to 12.75), tinnitus (4.04; 3.51 to 4.66), poor health (1.35; 1.15 to 1.58), health dissatisfaction (1.22; 1.00 to 1.47), and loneliness (1.28; 1.08 to 1.51) compared with people with SRTN/N. Well-being outcomes were similar in the SRTN/- and SRTI/I groups. However, difficulties following conversations in noise (5.35; 4.44 to 6.44) and tinnitus presence (2.66; 2.31 to 3.08) were significantly more likely with SRTN/- than with SRTI/I. The SRTN/- was associated with increased risk of self-reported poor health by 18% (relative risk, 1.18; 95% confidence interval, 1.06 to 1.32) and loneliness by 24% (1.24; 1.07 to 1.43) compared with SRTN/N. The risk of reporting difficulties following conversations in noise increased by 64% (1.64; 1.58 to 1.71) and tinnitus presence by 84% (1.84; 1.69 to 2.01) compared with SRTI/I. The effect of SRTN/- on reporting poor health was similar to that from having other health problems such as hypertension or high cholesterol. CONCLUSIONS: The large increases in the risks of reporting adverse hearing-related outcomes associated with unilateral hearing impairment suggest its specific impact on hearing function in everyday situations. The increased risk of loneliness and poor health indicates that one normally functioning ear is also insufficient to protect against the adverse psychosocial impacts of unilateral hearing impairment. This impact was still significant after controlling for various health-related factors and can lead to perception of poor health comparable to that with having medical problems contributing to life-threatening conditions such as heart disease. The findings suggest the need for effective interventions to address the hearing-related problems and their impact on well-being in people with unilateral hearing impairment.