Perceptual Consequences of Cochlear Deafferentation in Humans.

Cochlear synaptopathy, a form of cochlear deafferentation, has been demonstrated in a number of animal species, including non-human primates. Both age and noise exposure contribute to synaptopathy in animal models, indicating that it may be a common type of auditory dysfunction in humans. Temporal bone and auditory physiological data suggest that age and occupational/military noise exposure also lead to synaptopathy in humans. The predicted perceptual consequences of synaptopathy include tinnitus, hyperacusis, and difficulty with speech-in-noise perception. However, confirming the perceptual impacts of this form of cochlear deafferentation presents a particular challenge because synaptopathy can only be confirmed through post-mortem temporal bone analysis and auditory perception is difficult to evaluate in animals. Animal data suggest that deafferentation leads to increased central gain, signs of tinnitus and abnormal loudness perception, and deficits in temporal processing and signal-in-noise detection. If equivalent changes occur in humans following deafferentation, this would be expected to increase the likelihood of developing tinnitus, hyperacusis, and difficulty with speech-in-noise perception. Physiological data from humans is consistent with the hypothesis that deafferentation is associated with increased central gain and a greater likelihood of tinnitus perception, while human data on the relationship between deafferentation and hyperacusis is extremely limited. Many human studies have investigated the relationship between physiological correlates of deafferentation and difficulty with speech-in-noise perception, with mixed findings. A non-linear relationship between deafferentation and speech perception may have contributed to the mixed results. When differences in sample characteristics and study measurements are considered, the findings may be more consistent.

Associations Between Physiological Correlates of Cochlear Synaptopathy and Tinnitus in a Veteran Population.

PURPOSE: Animal models and human temporal bones indicate that noise exposure is a risk factor for cochlear synaptopathy, a possible etiology of tinnitus. Veterans are exposed to high levels of noise during military service. Therefore, synaptopathy may explain the high rates of noise-induced tinnitus among Veterans. Although synaptopathy cannot be directly evaluated in living humans, animal models indicate that several physiological measures are sensitive to synapse loss, including the auditory brainstem response (ABR), the middle ear muscle reflex (MEMR), and the envelope following response (EFR). The purpose of this study was to determine whether tinnitus is associated with reductions in physiological correlates of synaptopathy that parallel animal studies. METHOD: Participants with normal audiograms were grouped according to Veteran status and tinnitus report (Veterans with tinnitus, Veterans without tinnitus, and non-Veteran controls). The effects of being a Veteran with tinnitus on ABR, MEMR, and EFR measurements were independently modeled using Bayesian regression analysis. RESULTS: Modeled point estimates of MEMR and EFR magnitude showed reductions for Veterans with tinnitus compared with non-Veterans, with the most evident reduction observed for the EFR. Two different approaches were used to provide context for the Veteran tinnitus effect on the EFR by comparing to age-related reductions in EFR magnitude and synapse numbers observed in previous studies. These analyses suggested that EFR magnitude/synapse counts were reduced in Veterans with tinnitus by roughly the same amount as over 20 years of aging. CONCLUSION: These findings suggest that cochlear synaptopathy may contribute to tinnitus perception in noise-exposed Veterans. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24347761.

Oddball paradigm complexity in multi-token auditory evoked potentials.

We developed and tested a series of novel and increasingly complex multi-token electrophysiology paradigms for evoking the auditory P3 response. The primary goal was to evaluate the degree to which more complex discrimination tasks and listening environments - which are more likely to engage the types of neural processing used in real-world speech-in-noise situations - could still evoke a robust P3 response. If so, this opens the possibility of such a paradigm making up part of the toolkit for a brain-behavioral approach to improve understanding of speech processing. Fourteen normal-hearing adults were tested using four different auditory paradigms consisting of 5 tokens, 20 tokens, 160 tokens, or 160 tokens with background babble. Stimuli were naturally produced consonant-vowel tokens varying in consonant (/d/, /b/, /g/, /v/, and /ð/; all conditions), vowel (/ɑ/, /u/, /i/, and /ɜr/; 20- and 160-token conditions), and talker (4 female, 4 male; 160-token conditions only). All four conditions evoked robust neural responses, and all peaks had visible differences across conditions. However, the more exogenous auditory evoked potentials (N1 and P2) were primarily affected not by overall complexity but by the presence of background noise specifically, the presence of which was associated with longer latencies and smaller amplitudes. The more endogenous P3 peak, as well as the paradigm behavioral measures, revealed a more graded effect of overall paradigm complexity, rather than the background noise dominating the other factors. Our conclusion was that all four complex auditory paradigms, including the most complex (160 distinct consonant-vowel tokens presented in background babble), are viable means of stimulating N1-P2 and N2b-P3 auditory evoked responses and may therefore be useful in brain-behavioral approaches to understanding speech perception in noise.

Prevalence of Somatosensory Tinnitus in Veterans With Tinnitus.

OBJECTIVES: The primary objective was to estimate the prevalence of somatosensory tinnitus (ST) among Veterans with tinnitus. DESIGN: Three hundred four Veterans with tinnitus were phone screened for ST by performing and reporting on a series of head/neck/jaw maneuvers. A random sample of 12 individuals who screened positive and five who screened negative attended an in-person visit to confirm the presence/absence of ST. RESULTS: Of the 304 Veterans, 12 could not complete the screening maneuvers, 205 screened positive, and 87 screened negative. A Bayesian estimator that combines phone screening and in-person exam results establishes the prevalence of ST among Veterans with tinnitus at 56% with a 90% Bayesian confidence interval of 45% to 65%. CONCLUSIONS: At least half of Veterans with tinnitus have ST, suggesting that a sizable at-need population exists. Treatment addressing the biomechanical component has the potential to improve tinnitus symptoms.

Predicting synapse counts in living humans by combining computational models with auditory physiology.

Aging, noise exposure, and ototoxic medications lead to cochlear synapse loss in animal models. As cochlear function is highly conserved across mammalian species, synaptopathy likely occurs in humans as well. Synaptopathy is predicted to result in perceptual deficits including tinnitus, hyperacusis, and difficulty understanding speech-in-noise. The lack of a method for diagnosing synaptopathy in living humans hinders studies designed to determine if noise-induced synaptopathy occurs in humans, identify the perceptual consequences of synaptopathy, or test potential drug treatments. Several physiological measures are sensitive to synaptopathy in animal models including auditory brainstem response (ABR) wave I amplitude. However, it is unclear how to translate these measures to synaptopathy diagnosis in humans. This work demonstrates how a human computational model of the auditory periphery, which can predict ABR waveforms and distortion product otoacoustic emissions (DPOAEs), can be used to predict synaptic loss in individual human participants based on their measured DPOAE levels and ABR wave I amplitudes. Lower predicted synapse numbers were associated with advancing age, higher noise exposure history, increased likelihood of tinnitus, and poorer speech-in-noise perception. These findings demonstrate the utility of this modeling approach in predicting synapse counts from physiological data in individual human subjects.

Randomised controlled trial of interventions for bothersome tinnitus: DesyncraTM versus cognitive behavioural therapy.

OBJECTIVE: Compare the relative efficacy of DesyncraTM and Cognitive Behavioural Therapy (CBT). DESIGN AND STUDY SAMPLE: Sixty-one participants were randomly assigned to receive either DesyncraTM (n = 29) or CBT (n = 32). Randomisation included stratification regarding current hearing aid (HA) use. Depending on group assignment, participants attended approximately 7-12 visits. Tinnitus distress was measured using the Tinnitus Questionnaire (TQ). RESULTS: Mean TQ scores decreased post-baseline from 5-15 points across treatment arms and strata. Model-based findings for the no-HA stratum showed a difference of -2.0 TQ points favouring Desyncra at 24-weeks, with a 90% posterior interval varying from -5.4 points favouring Desyncra to 0.8 TQ points favouring CBT. For the HA stratum, results show a difference of -1.0 TQ points favouring Desyncra, with a 90% posterior interval ranging from -4.7 points favouring Desyncra to 2.9 points favouring CBT. CONCLUSIONS: The difference between Desyncra and CBT on average showed greater improvement with Desyncra in the no-HA stratum by about 2 TQ points. To the extent that the study sample represents a clinical population and recognising the assumptions in the design and analysis, these results suggest Desyncra is just as effective or more so than CBT in reducing tinnitus distress.

Impacts of Diabetes, Aging, and Hearing Loss on Speech-on-Speech Masking and Spatial Release in a Large Veteran Cohort.

PURPOSE: Type 2 diabetes mellitus (DM2) is associated with impaired hearing. However, the evidence is less clear if DM2 can lead to difficulty understanding speech in complex acoustic environments, independently of age and hearing loss effects. The purpose of this study was to estimate the magnitude of DM2-related effects on speech understanding in the presence of competing speech after adjusting for age and hearing. METHOD: A cross-sectional study design was used to investigate the relationship between DM2 and speech understanding in 190 Veterans (M age = 47 years, range: 25-76). Participants were classified as having no diabetes (n = 74), prediabetes (n = 19), or DM2 that was well controlled (n = 24) or poorly controlled (n = 73). A test of spatial release from masking (SRM) was presented in a virtual acoustical simulation over insert earphones with multiple talkers using sentences from the coordinate response measure corpus to determine the target-to-masker ratio (TMR) required for 50% correct identification of target speech. A linear mixed model of the TMR results was used to estimate SRM and separate effects of diabetes group, age, and low-frequency pure-tone average (PTA-low) and high-frequency pure-tone average. A separate model estimated the effects of DM2 on PTA-low. RESULTS: After adjusting for hearing and age, diabetes-related effects remained among those whose DM2 was well controlled, showing an SRM loss of approximately 0.5 dB. Results also showed effects of hearing loss and age, consistent with the literature on people without DM2. Low-frequency hearing loss was greater among those with DM2. CONCLUSIONS: In a large cohort of Veterans, low-frequency hearing loss and older age negatively impact speech understanding. Compared with nondiabetics, individuals with controlled DM2 have additional auditory deficits beyond those associated with hearing loss or aging. These results provide a potential explanation for why individuals who have diabetes and/or are older often report difficulty understanding speech in real-world listening environments. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.16746475.

A Randomized Controlled Trial Using Automated Technology for Improving Ototoxicity Monitoring in VA Oncology Patients.

Purpose Determine the efficacy of ototoxicity monitoring (OM) administered as automated protocols with the Oto-ID mobile audiometer (automated ototoxicity monitoring [A-OM]), compared with usual care (UC) OM in cancer patients receiving cisplatin. Method Participants were patients (n = 46, mean age 64.7 years; range: 30-78 years) receiving cisplatin-based chemotherapy at the Department of Veterans Affairs Portland Health Care System. A randomized controlled trial contrasted A-OM and UC at up to three program evaluations (PEs) conducted by the study audiologist who was blinded to arm through PE1. PE1 occurred before randomization or oncology treatment; PE2 and PE3 occurred during and/or after treatment at 35 and 365 days postrandomization. The A-OM group (n = 24) used Oto-ID to screen their hearing before each cisplatin dose. Oto-ID results were sent to the study audiologist for interpretation, follow-up, and care coordination. The UC group (n = 22) received a consult for OM services through the audiology clinic. Outcomes included hearing shift near each patient's high-frequency hearing limit, revised hearing-handicap inventory score, and survival time from the start of treatment. Adherence to OM protocols, patients' use of aural rehabilitation services, and oncologists' treatment decisions were also examined. Results Ototoxicity was identified at a high overall rate (46% and 76% at 35 and 365 days, respectively, postrandomization). Adherence to monitoring prior to each cisplatin dose was 83.3% for those randomized to A-OM compared with 4.5% for UC. Randomization to A-OM was not associated with reduced ototoxic hearing shifts or self-reported hearing handicap relative to UC; neither did it compromise participants' survival. Half of participants in each arm accessed aural rehabilitation services. One in each arm had a documented ototoxicity-related cisplatin dose reduction. Conclusions Auditory impairment was an actionable concern for the participants and their oncology providers. A dedicated surveillance program using the Oto-ID's automated protocols improved adherence to OM recommendations over a traditional UC service delivery model. Supplemental Material https://doi.org/10.23641/asha.16649602.

Envelope following response measurements in young veterans are consistent with noise-induced cochlear synaptopathy.

Animal studies have demonstrated that noise exposure can lead to the loss of the synapses between the inner hair cells and their afferent auditory nerve fiber targets without impacting auditory thresholds. Although several non-invasive physiological measures appear to be sensitive to cochlear synaptopathy in animal models, including auditory brainstem response (ABR) wave I amplitude, the envelope following response (EFR), and the middle ear muscle reflex (MEMR), human studies of these measures in samples that are expected to vary in terms of the degree of noise-induced synaptopathy have resulted in mixed findings. One possible explanation for the differing results is that synaptopathy risk is lower for recreational noise exposure than for occupational or military noise exposure. The goal of this analysis was to determine if EFR magnitude and ABR wave I amplitude are reduced among young Veterans with a history of military noise exposure compared with non-Veteran controls with minimal noise exposure. EFRs and ABRs were obtained in a sample of young (19-35 years) Veterans and non-Veterans with normal audiograms and robust distortion product otoacoustic emissions (DPOAEs). The statistical analysis is consistent with a reduction in mean EFR magnitude and ABR wave I amplitude (at 90 dB peSPL) for Veterans with a significant history of noise exposure compared with non-Veteran controls. These findings are in agreement with previous ABR wave I amplitude findings in young Veterans and are consistent with animal models of noise-induced cochlear synaptopathy.

Occupational Noise Exposure and Longitudinal Hearing Changes in Post-9/11 US Military Personnel During an Initial Period of Military Service.

OBJECTIVES: Auditory impairments, particularly those resulting from hazardous occupational noise exposures, are pressing concerns for the US Departments of Defense (DoD) and Veterans Affairs (VA). However, to date, no studies have estimated the rate of hearing threshold change that occurs during service or how changes may vary by military occupation. Hearing threshold changes during military service have historically been reported as the proportion of Service members demonstrating a significant threshold shift. This approach does not capture the rate of the hearing threshold change or the specific audiometric frequencies impacted. Determining the rate of hearing threshold change, and factors that affect the rate of change, is important to elucidate the impact of military service on hearing and to guide prevention strategies and subsequent hearing health care. Our primary objective was to estimate the annual rate of hearing threshold change during military service as a consequence of military occupational noise exposure ranking. DESIGN: We linked audiometric data, collected from military personnel as part of a DoD hearing conservation program, to data describing demographic and military-service characteristics obtained from individuals enrolled in the Noise Outcomes In Service members Epidemiology Study. The analytic cohort included Veterans who enlisted in military service after September 2001 (n = 246). We examined the longitudinal association between military occupations categorized as having a low, moderate, or high noise exposure ranking and pure-tone hearing thresholds (500 to 6000 Hz) using a hierarchical linear model. The average annual rate of hearing threshold change and their 95% confidence intervals were estimated by service branch, military occupational noise exposure ranking, and audiometric test frequency. RESULTS: On average, hearing threshold change ranged between -0.5 and 1.1 dB/year and changes over time varied by service branch, audiometric test frequency, and military occupation noise ranking. Generally, higher test frequencies (3000 to 6000 Hz) and military occupations with moderate or high noise exposure rankings had the greatest average annual rates of hearing threshold change; however, no dose-response relationship was observed. Among Marine Corps personnel, those exposed to occupations with high noise rankings demonstrated the greatest average annual rate of change (1.1 dB/year at 6000 Hz). Army personnel exposed to occupations with moderate noise rankings demonstrated the greatest average annual rate of change (0.6 dB/year at 6000 Hz). CONCLUSIONS: This study (1) demonstrates the unique use of DoD hearing conservation program data, (2) is the first analysis of hearing threshold changes over time using such data, and (3) adds to the limited literature on longitudinal changes in hearing. The difference in hearing threshold changes across military branches is likely indicative of their varying noise exposures, hearing protection device use and enforcement, and surveillance practices. Results suggest Marine Corps and Army personnel are at risk for hearing threshold changes and that, among Army personnel, this is most pronounced among those exposed to moderate levels of occupational noise exposure. Estimates of the rate of hearing threshold change by frequency and factors that impact hearing are useful to inform the DoD's efforts to protect the hearing of their Service members and to the Veterans Affairs's efforts to identify and rehabilitate those most likely to experience hearing threshold change.

Subclinical Auditory Dysfunction: Relationship Between Distortion Product Otoacoustic Emissions and the Audiogram.

Purpose Distortion product otoacoustic emissions (DPOAEs) and audiometric thresholds have been used to account for the impacts of subclinical outer hair cell (OHC) dysfunction on auditory perception and measures of auditory physiology. However, the relationship between DPOAEs and the audiogram is unclear. This study investigated this relationship by determining how well DPOAE levels can predict the audiogram among individuals with clinically normal hearing. Additionally, the impacts of age, noise exposure, and the perception of tinnitus on the ability of DPOAE levels to predict the audiogram were evaluated. Method Suprathreshold DPOAE levels from 1 to 10 kHz and pure-tone thresholds from 0.25 to 16 kHz were measured in 366 ears from 194 young adults (19-35 years old) with clinically normal audiograms and middle ear function. The measured DPOAE levels at all frequencies were used to predict pure-tone thresholds at each frequency. Participants were grouped by age, self-reported noise exposure/Veteran status, and self-report of tinnitus. Results Including DPOAE levels in the pure-tone threshold prediction model improved threshold predictions at all frequencies from 0.25 to 16 kHz compared with a model based only on sample mean pure-tone thresholds, but these improvements were modest. DPOAE levels for f 2 frequencies of 4 and 5 kHz were particularly influential in predicting pure-tone thresholds above 4 kHz. However, prediction accuracy varied based on participant characteristics. On average, predicted pure-tone thresholds were better than measured thresholds among Veterans, individuals with tinnitus, and the oldest age group. Conclusions These results indicate a complex relationship between DPOAE levels and the audiogram. Underestimation of pure-tone thresholds for some groups suggests that additional factors other than OHC damage may impact thresholds among individuals within these categories. These findings suggest that DPOAE levels and pure-tone thresholds may differ in terms of how well they reflect subclinical OHC dysfunction. Supplemental Material https://doi.org/10.23641/asha.13564745.

Evoked Potentials Reveal Noise Exposure-Related Central Auditory Changes Despite Normal Audiograms.

Purpose Complaints of auditory perceptual deficits, such as tinnitus and difficulty understanding speech in background noise, among individuals with clinically normal audiograms present a perplexing problem for audiologists. One potential explanation for these "hidden" auditory deficits is loss of the synaptic connections between the inner hair cells and their afferent auditory nerve fiber targets, a condition that has been termed cochlear synaptopathy. In animal models, cochlear synaptopathy can occur due to aging or exposure to noise or ototoxic drugs and is associated with reduced auditory brainstem response (ABR) wave I amplitudes. Decreased ABR wave I amplitudes have been demonstrated among young military Veterans and non-Veterans with a history of firearm use, suggesting that humans may also experience noise-induced synaptopathy. However, the downstream consequences of synaptopathy are unclear. Method To investigate how noise-induced reductions in wave I amplitude impact the central auditory system, the ABR, the middle latency response (MLR), and the late latency response (LLR) were measured in 65 young Veterans and non-Veterans with normal audiograms. Results In response to a click stimulus, the MLR was weaker for Veterans compared to non-Veterans, but the LLR was not reduced. In addition, low ABR wave I amplitudes were associated with a reduced MLR, but with an increased LLR. Notably, Veterans reporting tinnitus showed the largest mean LLRs. Conclusions These findings indicate that decreased peripheral auditory input leads to compensatory gain in the central auditory system, even among individuals with normal audiograms, and may impact auditory perception. This pattern of reduced MLR, but not LLR, was observed among Veterans even after statistical adjustment for sex and distortion product otoacoustic emission differences, suggesting that synaptic loss plays a role in the observed central gain. Supplemental Material https://doi.org/10.23641/asha.11977854.

Noise-induced enhancement of envelope following responses in normal-hearing adults.

Measures of signal-in-noise neural encoding may improve understanding of the hearing-in-noise difficulties experienced by many individuals in everyday life. Usually noise results in weaker envelope following responses (EFRs); however, some studies demonstrate EFR enhancements. This experiment tested whether noise-induced enhancements in EFRs are demonstrated with simple 500- and 1000-Hz pure tones amplitude modulated at 110 Hz. Most of the 12 young normal-hearing participants demonstrated enhanced encoding of the 110-Hz fundamental in a noise background compared to quiet; in contrast, responses at the harmonics were decreased in noise relative to quiet conditions. Possible mechanisms of such an enhancement are discussed.

Long-Term Variability of Distortion-Product Otoacoustic Emissions in Infants and Children and Its Relation to Pediatric Ototoxicity Monitoring.

OBJECTIVE: Distortion-product otoacoustic emissions (DPOAEs) provide a rapid, noninvasive measure of outer hair cell damage associated with chemotherapy and are a key component of pediatric ototoxicity monitoring. Serial monitoring of DPOAE levels in reference to baseline measures is one method for detecting ototoxic damage. Interpreting DPOAE findings in this context requires that test-retest differences be considered in relation to normal variability, data which are lacking in children. This study sought to (1) characterize normal test-retest variability in DPOAE level over the long time periods reflective of pediatric chemotherapy regimens for a variety of childhood ages and f2 primary frequencies using common clinical instrumentation and stimulus parameters; (2) develop level-shift reference intervals; and (3) account for any age-related change in DPOAE level or measurement error that may occur as the auditory system undergoes maturational change early in life. DESIGN: Serial DPOAE measurements were obtained in 38 healthy children (25 females and 13 males) with normal hearing and ranging in age from one month to 10 years at the initial (baseline) visit. On average, children were tested 5.2 times over an observation period of 6.5 months. Data were collected in the form of DP grams, in which DPOAE level was measured for f2 ranging from 1.4 to 10 kHz, using a fixed f2/f1 ratio of 1.22 and stimulus level of 65/55 dB SPL for L1/L2. Age effects on DPOAE level and measurement error were estimated using Bayesian regression of the longitudinal data. The raw and model-based distribution of DPOAE test-retest differences were characterized using means and standard error of the measurement for several ages and f2's. RESULTS: DPOAE test-retest differences for the children in this study are at the high end of those previously observed in adults, as reflected in the associated shift reference intervals. Further, although we observe substantial child-specific variation in DPOAE level, the pattern of age-related changes is highly consistent across children. Across a wide range of f2's, DPOAE level decreases by 3 to 4 dB from 1 to 13 months of age followed by a more gradual decline of <1 dB/year. An f2 of 6 kHz shows the smallest decrease during the early rapid maturation period. DPOAE measurement error is fairly constant with age. It is 3 to 4 dB at most f2's and is greater (indicating poorer reliability) at 1.5, 8, and 10 kHz. CONCLUSIONS: DPOAE level decreases with childhood age, with the greatest changes observed in the first year of life. Maturational effects during infancy and greater measurement error at very low and high f2's affect test-retest variability in children. An f2 of 6 kHz shows minimal maturation and measurement error, suggesting it may be an optimal sentinel frequency for ototoxicity monitoring in pediatric patients. Once validated with locally developed normative data, reference intervals provided herein could be used to determine screen fail criteria for serial monitoring using DPOAEs. Employing state-of-the-art calibration techniques might reduce variability, allowing for more sensitive screen fail criteria.

Auditory brainstem response demonstrates that reduced peripheral auditory input is associated with self-report of tinnitus.

Tinnitus is one of the predicted perceptual consequences of cochlear synaptopathy, a type of age-, noise-, or drug-induced auditory damage that has been demonstrated in animal models to cause homeostatic changes in central auditory gain. Although synaptopathy has been observed in human temporal bones, assessment of this condition in living humans is limited to indirect non-invasive measures such as the auditory brainstem response (ABR). In animal models, synaptopathy is associated with a reduction in ABR wave I amplitude at suprathreshold stimulus levels. Several human studies have explored the relationship between wave I amplitude and tinnitus, with conflicting results. This study investigates the hypothesis that reduced peripheral auditory input due to synaptic/neuronal loss is associated with tinnitus. Wave I amplitude data from 193 individuals [43 with tinnitus (22%), 150 without tinnitus (78%)], who participated in up to 3 out of 4 different studies, were included in a logistic regression analysis to estimate the relationship between wave I amplitude and tinnitus at a variety of stimulus levels and frequencies. Statistical adjustment for sex and distortion product otoacoustic emissions (DPOAEs) was included. The results suggest that smaller wave I amplitudes and/or lower DPOAE levels are associated with an increased probability of tinnitus.

Bayesian Applications in Auditory Research.

Purpose This article presents a basic exploration of Bayesian inference to inform researchers unfamiliar to this type of analysis of the many advantages this readily available approach provides. Method First, we demonstrate the development of Bayes' theorem, the cornerstone of Bayesian statistics, into an iterative process of updating priors. Working with a few assumptions, including normalcy and conjugacy of prior distribution, we express how one would calculate the posterior distribution using the prior distribution and the likelihood of the parameter. Next, we move to an example in auditory research by considering the effect of sound therapy for reducing the perceived loudness of tinnitus. In this case, as well as most real-world settings, we turn to Markov chain simulations because the assumptions allowing for easy calculations no longer hold. Using Markov chain Monte Carlo methods, we can illustrate several analysis solutions given by a straightforward Bayesian approach. Conclusion Bayesian methods are widely applicable and can help scientists overcome analysis problems, including how to include existing information, run interim analysis, achieve consensus through measurement, and, most importantly, interpret results correctly. Supplemental Material https://doi.org/10.23641/asha.7822592.

Telephone-Based Progressive Tinnitus Management for Persons With and Without Traumatic Brain Injury: A Randomized Controlled Trial.

OBJECTIVES: This randomized controlled trial evaluated the efficacy of delivering coping skills education from Progressive Tinnitus Management (PTM) by telephone (Tele-PTM). The trial followed a previous pilot study that showed positive results for Tele-PTM. DESIGN: Participants included individuals with bothersome tinnitus (N = 205) located anywhere within the United States. A special emphasis was given to including individuals who had experienced one or more traumatic brain injuries (TBIs). Participants were randomized to either Tele-PTM intervention or 6-month wait-list control (WLC). The Tele-PTM intervention involved five telephone appointments-two led by an audiologist (teaching how to use therapeutic sound) and three by a psychologist (teaching coping skills derived from cognitive-behavioral therapy). It was hypothesized that Tele-PTM would be more effective than WLC in reducing functional effects of tinnitus as measured with the Tinnitus Functional Index. Additional outcome measures included the Self-Efficacy for Managing Reactions to Tinnitus questionnaire and the Hospital Anxiety and Depression Scale. The effect of Tele-PTM on outcomes was estimated using linear mixed models. RESULTS: Overall results showed convincingly that the Tele-PTM group had significantly better outcomes than the WLC group. These results were consistent across all outcome measures, indicating not only a reduction of tinnitus functional distress but also increased self-efficacy. Improvements in measures of anxiety and depression were also observed. Tele-PTM participants in all TBI categories showed significant improvement. CONCLUSIONS: Results provide strong support for use of Tele-PTM methodology for persons with bothersome tinnitus, regardless of whether the person also has TBI symptoms. The effect size for Tele-PTM was high for the primary outcome measure, the Tinnitus Functional Index, and all other outcome measures showed significant improvement. Combined with our previous pilot study, the Tele-PTM method is validated for potential nationwide provision of tinnitus services.

Compensatory and Serial Processing Models for Relating Electrophysiology, Speech Understanding, and Cognition.

OBJECTIVES: The objective of this study was to develop a framework for investigating the roles of neural coding and cognition in speech perception. DESIGN: N1 and P3 auditory evoked potentials, QuickSIN speech understanding scores, and the Digit Symbol Coding cognitive test results were used to test the accuracy of either a compensatory processing model or serial processing model. RESULTS: The current dataset demonstrated that neither the compensatory nor the serial processing model were well supported. An additive processing model may best represent the relationships in these data. CONCLUSIONS: With the outcome measures used in this study, it is apparent that an additive processing model, where exogenous neural coding and higher order cognition contribute independently, best describes the effects of neural coding and cognition on speech perception. Further testing with additional outcome measures and a larger number of subjects is needed to confirm and further clarify the relationships between these processing domains.

Use of non-invasive measures to predict cochlear synapse counts.

Cochlear synaptopathy, the loss of synaptic connections between inner hair cells (IHCs) and auditory nerve fibers, has been documented in animal models of aging, noise, and ototoxic drug exposure, three common causes of acquired sensorineural hearing loss in humans. In each of these models, synaptopathy begins prior to changes in threshold sensitivity or loss of hair cells; thus, this underlying injury can be hidden behind a normal threshold audiogram. Since cochlear synaptic loss cannot be directly confirmed in living humans, non-invasive assays will be required for diagnosis. In animals with normal auditory thresholds, the amplitude of wave 1 of the auditory brainstem response (ABR) is highly correlated with synapse counts. However, synaptopathy can also co-occur with threshold elevation, complicating the use of the ABR alone as a diagnostic measure. Using an age-graded series of mice and a partial least squares regression approach to model structure-function relationships, this study shows that the combination of a small number of ABR and distortion product otoacoustic emission (DPOAE) measurements can predict synaptic ribbon counts at various cochlear frequencies to within 1-2 synapses per IHC of their true value. In contrast, the model, trained using the age-graded series of mice, overpredicted synapse counts in a small sample of young noise-exposed mice, perhaps due to differences in the underlying pattern of damage between aging and noise-exposed mice. These results provide partial validation of a noninvasive approach to identify synaptic/neuronal loss in humans using ABRs and DPOAEs.

Tinnitus and Auditory Perception After a History of Noise Exposure: Relationship to Auditory Brainstem Response Measures.

OBJECTIVES: To determine whether auditory brainstem response (ABR) wave I amplitude is associated with measures of auditory perception in young people with normal distortion product otoacoustic emissions (DPOAEs) and varying levels of noise exposure history. DESIGN: Tinnitus, loudness tolerance, and speech perception ability were measured in 31 young military Veterans and 43 non-Veterans (19 to 35 years of age) with normal pure-tone thresholds and DPOAEs. Speech perception was evaluated in quiet using Northwestern University Auditory Test (NU-6) word lists and in background noise using the words in noise (WIN) test. Loudness discomfort levels were measured using 1-, 3-, 4-, and 6-kHz pulsed pure tones. DPOAEs and ABRs were collected in each participant to assess outer hair cell and auditory nerve function. RESULTS: The probability of reporting tinnitus in this sample increased by a factor of 2.0 per 0.1 µV decrease in ABR wave I amplitude (95% Bayesian confidence interval, 1.1 to 5.0) for males and by a factor of 2.2 (95% confidence interval, 1.0 to 6.4) for females after adjusting for sex and DPOAE levels. Similar results were obtained in an alternate model adjusted for pure-tone thresholds in addition to sex and DPOAE levels. No apparent relationship was found between wave I amplitude and either loudness tolerance or speech perception in quiet or noise. CONCLUSIONS: Reduced ABR wave I amplitude was associated with an increased risk of tinnitus, even after adjusting for DPOAEs and sex. In contrast, wave III and V amplitudes had little effect on tinnitus risk. This suggests that changes in peripheral input at the level of the inner hair cell or auditory nerve may lead to increases in central gain that give rise to the perception of tinnitus. Although the extent of synaptopathy in the study participants cannot be measured directly, these findings are consistent with the prediction that tinnitus may be a perceptual consequence of cochlear synaptopathy.