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.

Acoustic differences in tinnitus between noise-induced and non-noise-induced hearing loss.

BACKGROUND: Tinnitus, the perception of sound without external stimuli, varies across hearing loss types. The present study compared the acoustic characteristics of tinnitus in patients with noise-induced hearing loss (NIHL) and in those with hearing loss unrelated to noise exposure. OBJECTIVE: This study compared the acoustic characteristics of tinnitus in patients with noise-induced and non-noise-induced hearing loss. METHODS: A total of 403 patients with tinnitus were divided into those with noise-induced and non-noise-induced hearing loss. Patients were evaluated by pure tone audiometry (PTA), tinnitogram, transient evoked otoacoustic emission (TEOAE), distortion product otoacoustic emission (DPOAE), and auditory brainstem evoked response (ABR) tests. RESULTS: Patients with NIHL exhibited significantly higher hearing thresholds across all frequencies (125-8000 Hz) (p < .05) and reported significantly higher tinnitus intensity (p < .05). Otoacoustic emission tests showed that response rates were significantly lower (p < .05), and ABR tests found that latency periods were significantly more prolonged (p < .05), in patients with NIHL. CONCLUSIONS: Tinnitus differs acoustically between patients with NIHL and those with non-noise-induced hearing loss, with specific patterns of intensity and auditory responses. These findings emphasize the need for tailoring the management of tinnitus according to the underlying type of hearing loss.

Adult mice with noise-induced hearing loss exhibited temporal ordering memory deficits accompanied by microglia-associated neuroplastic changes in the medial prefrontal cortex.

Acquired peripheral hearing loss in midlife is considered the primary modifiable risk factor for dementia, while the underlying pathological mechanism remains poorly understood. Excessive noise exposure is the most common cause of acquired peripheral hearing loss in modern society. This study was designed to investigate the impact of noise-induced hearing loss (NIHL) on cognition, with a focus on the medial prefrontal cortex (mPFC), a brain region that is involved in both auditory and cognitive processes and is highly affected in patients with cognitive impairment. Adult C57BL/6 J mice were randomly assigned to a control group and seven noise groups: 0HPN, 12HPN, 1DPN, 3DPN, 7DPN, 14DPN, and 28DPN, which were exposed to broadband noise at a 123 dB sound pressure level (SPL) for 2 h and sacrificed immediately (0 h), 12 h, or 1, 3, 7, 14, or 28 days post-noise exposure (HPN, DPN), respectively. Hearing assessment, behavioral tests, and neuromorphological studies in the mPFC were performed in control and 28DPN mice. All experimental animals were included in the time-course analysis of serum corticosterone (CORT) levels and mPFC microglial morphology. The results illustrated that noise exposure induced early-onset transient serum CORT elevation and permanent moderate-to-severe hearing loss in mice. 28DPN mice, in which permanent NIHL has been verified, exhibited impaired performance in temporal order object recognition tasks concomitant with reduced structural complexity of mPFC pyramidal neurons. The time-course immunohistochemical analysis in the mPFC revealed significantly higher morphological microglial activation at 14 and 28 DPN, preceded by a remarkably higher amount of microglial engulfed postsynaptic marker PSD95 at 7 DPN. Additionally, lipid accumulation in microglia was observed in 7DPN, 14DPN and 28DPN mice, suggesting a driving role of lipid handling deficits following excessive phagocytosis of synaptic elements in delayed and sustained microglial abnormalities. These findings provide fundamentally novel information concerning mPFC-related cognitive impairment in mice with NIHL and empirical evidence suggesting the involvement of microglial malfunction in the mPFC neurodegenerative consequences of NIHL.

Predicting secondary endolymphatic hydrops in patients with noise-induced hearing loss.

BACKGROUND: Long-term noise exposure may damage the cochlea and endolymph resorption system, which induces episodic vertigo and/or fluctuating hearing loss in later years. OBJECTIVE: This study adopted clinical symptoms, inner ear test battery, and/or magnetic resonance (MR) imaging to evaluate development of secondary endolymphatic hydrops (EH) in patients with noise-induced hearing loss (NIHL). METHODS: Forty NIHL patients with secondary EH were assigned to Group A. Another 40 age-and sex-matched NIHL patients without EH were assigned to Group B. All patients underwent an inner ear test battery. MR imaging was performed when diagnosis of EH was equivocal via above testing. RESULTS: Group A had significantly higher mean hearing levels (MHLs) than Group B at 1000, 2000, 4000, and 8000 Hz. Both groups displayed a significantly declining sequence of abnormality rates of the inner ear test battery. Under receiver operating characteristic (ROC) curve analysis, the cutoff threshold at 4 kHz for predicting the presence of secondary EH in NIHL patients was 52 dBHL, with a sensitivity of 62% and a specificity of 69%. CONCLUSIONS: NIHL patients revealing a typical 4 kHz dip-type audiogram with dip threshold >52 dBHL may predict development of secondary EH. A longitudinal follow-up coupled with MR imaging is required for confirmation.

Comparison of the risks of occupational diseases, avoidable hospitalization, and all-cause deaths between firefighters and non-firefighters: A cohort study using national health insurance claims data.

Objectives: National Health Insurance claims data were used to compare the incidence of occupational diseases, avoidable hospitalization, and all-cause death standardized incidence ratio and hazard ratio between firefighters and non-firefighters. Methods: The observation period of the study was from 2006 to 2015 and a control group (general workers and national and regional government officers/public educational officers) and a firefighter group was established. The dependent variables were occupational diseases, avoidable hospitalization (AH), and all-cause death. The analysis was conducted in three stages. First, the standardized incidence ratios were calculated using the indirect standardization method to compare the prevalence of the disease between the groups (firefighter and non-firefighter groups). Second, propensity score matching was performed for each disease in the control group. Third, the Cox proportional hazards model was applied by matching the participants. Results: The standardized incidence ratio and Cox regression analyses revealed higher rates of noise-induced hearing loss, ischemic heart disease, asthma, chronic obstructive pulmonary disease, cancer, back pain, admission due to injury, mental illness, depression, and AH for firefighters than general workers. Similarly, the rates of noise-induced hearing loss, ischemic heart disease, asthma, chronic obstructive pulmonary disease, back pain, admission due to injury, mental illness, depression, and AH were higher in the firefighter group than in the national and regional government officer/public educational officer group. Conclusions: The standardized incidence ratios and hazard ratios for most diseases were high for firefighters. Therefore, besides the prevention and management of diseases from a preventive medical perspective, management programs, including social support and social prescriptions in the health aspect, are needed.

Metabolic changes in the brain and blood of rats following acoustic trauma, tinnitus and hyperacusis.

It has been increasingly recognized that tinnitus is likely to be generated by complex network changes. Acoustic trauma that causes tinnitus induces significant changes in multiple metabolic pathways in the brain. However, it is not clear whether those metabolic changes in the brain could also be reflected in blood samples and whether metabolic changes could discriminate acoustic trauma, hyperacusis and tinnitus. We analyzed brain and serum metabolic changes in rats following acoustic trauma or a sham procedure using metabolomics. Hearing levels were recorded before and after acoustic trauma and behavioral measures to quantify tinnitus and hyperacusis were conducted at 4 weeks following acoustic trauma. Tissues from 11 different brain regions and serum samples were collected at about 3 months following acoustic trauma. Among the acoustic trauma animals, eight exhibited hyperacusis-like behavior and three exhibited tinnitus-like behavior. Using Gas chromatography-mass spectrometry and multivariate statistical analysis, significant metabolic changes were found in acoustic trauma animals in both the brain and serum samples with a number of metabolic pathways significantly perturbated. Furthermore, metabolic changes in the serum were able to differentiate sham from acoustic trauma animals, as well as sham from hyperacusis animals, with high accuracy. Our results suggest that serum metabolic profiling in combination with machine learning analysis may be a promising approach for identifying biomarkers for acoustic trauma, hyperacusis and potentially, tinnitus.

Can auditory brain stem response accurately reflect the cochlear function?

Auditory brain stem response (ABR) and compound action potential (CAP) recordings have been used in animal research to determine hearing sensitivity. Because of the relative ease of testing, the ABR test has been more commonly used in assessing cochlear lesions than the CAP test. The purpose of this experiment is to examine the difference between these two methods in monitoring the dynamic changes in auditory function after cochlear damage and in detecting asymmetric hearing loss due to unilateral cochlear damage. ABR and CAP were measured in two models of cochlear damage: acoustic trauma induced by exposure to a narrowband noise centered at 4 kHz (2,800-5,600 Hz) at 105 dB sound pressure level for 5 h in chinchillas and unilateral cochlear damage induced by surgical destruction of one cochlea in guinea pigs. Cochlear hair cells were quantified after completing the evoked potential testing. In the noise-damaged model, we found different recovery patterns between ABR and CAP. At 1 day after noise exposure, the ABR and CAP assessment revealed a similar level of threshold shifts. However, at 30 days after noise exposure, ABR thresholds displayed an average of 20-dB recovery, whereas CAP thresholds showed no recovery. Notably, the CAP threshold signifies the actual condition of sensory cell pathogenesis in the cochlea because sensory cell death is known to be irreversible in mammals. After unilateral cochlear damage, we found that both CAP and ABR were affected by cross-hearing when testing the damaged ear with the testing stimuli delivered directly into the canal of the damaged ear. When cross-hearing occurred, ABR testing was not able to reveal the presence of cross-hearing because the ABR waveform generated by cross-stimulation was indistinguishable from that generated by the test ear (damaged ear), should the test ear be intact. However, CAP testing can provide a warning sign, since the typical CAP waveform became an ABR-like waveform when cross-hearing occurred. Our study demonstrates two advantages of the CAP test over the ABR test in assessing cochlear lesions: contributing evidence for the occurrence of cross-hearing when subjects have asymmetric hearing loss and providing a better assessment of the progression of cochlear pathogenesis.NEW & NOTEWORTHY Auditory brain stem response (ABR) is more commonly used to evaluate cochlear lesions than cochlear compound action potential (CAP). In a noise-induced cochlear damage model, we found that the reduced CAP and enhanced ABR caused the threshold difference. In a unilateral cochlear destruction model, a shadow curve of the ABR from the contralateral healthy ear masked the hearing loss in the destroyed ear.

Effects of Cardiovascular Health Factors and Personal Listening Behaviors on Hearing Sensitivity in College-Aged students.

OBJECTIVES: This study examined the association between pure tone hearing sensitivity and music listening behaviors among traditional college-aged students and sought to determine factors that mediate hearing sensitivity, including health and fitness levels, gender, and personal listening device (PLD) use. METHODS: A convenience sample of college students (N = 182; 133 females, 49 males, mean age = 19.8 ± 1.4 year, average PLD use = 1.52 ± 7.1 hours•day-1) completed hearing assessments, music listening behavior questionnaires, and health and fitness tests. RESULTS: Most students listened to music at safe intensity levels (<80 dBA), though 18% had higher hearing levels (≥25 dB HL at one of the measured frequencies). Longer listening duration behavior approached but did not reach a statistical association with compromised hearing sensitivity. Of all variables measured, including cardiovascular health, fitness, and music listening, two variables: total cholesterol: triglycerides (TC:TG) and total cholesterol: high-density lipoproteins (TC:HDL) significantly associated with hearing sensitivity at 2 kHz. The odds hearing loss occurring at 4 kHz was 59% lower in females compared with males. CONCLUSION: The majority of college students had healthy music listening behavior and fitness, contributing to normal hearing sensitivity in most. In cases where greater hearing threshold levels at one or more frequencies was detected, TC:HDL and TC:TG were statistically related and at 2 kHz, males were more likely to demonstrate higher listening levels compared with females of similar health and fitness level.

Anxiety-like behavior induced by salicylate depends on age and can be prevented by a single dose of 5-MeO-DMT.

Salicylate intoxication is a cause of tinnitus and comorbidly associated with anxiety in humans. In a previous work, we showed that salicylate induces anxiety-like behavior and hippocampal type 2 theta oscillations (theta2) in mice. Here we investigate if the anxiogenic effect of salicylate is dependent on age and previous tinnitus experience. We also tested whether a single dose of DMT can prevent this effect. Using microwire electrode arrays, we recorded local field potential in young (4-5- month-old) and old (11-13-month-old) mice to study the electrophysiological effect of tinnitus in the ventral hippocampus (vHipp) and medial prefrontal cortex (mPFC) in an open field arena and elevated plus maze 1h after salicylate (300mg/kg) injection. We found that anxiety-like behavior and increase in theta2 oscillations (4-6 Hz), following salicylate pre-treatment, only occurs in young (normal hearing) mice. We also show that theta2 and slow gamma oscillations increase in the vHipp and mPFC in a complementary manner during anxiety tests in the presence of salicylate. Finally, we show that pre-treating mice with a single dose of the hallucinogenic 5-MeO-DMT prevents anxiety-like behavior and the increase in theta2 and slow gamma oscillations after salicylate injection in normal hearing young mice. This work further support the hypothesis that anxiety-like behavior after salicylate injection is triggered by tinnitus and require normal hearing. Moreover, our results show that hallucinogenic compounds can be effective in treating tinnitus-related anxiety.

Noise-induced hearing loss in the military dental setting: a UK legislative perspective.

INTRODUCTION: Health professionals working in the dental environment are potentially at risk of noise-induced hearing loss (NIHL) due to the use of clinical and laboratory equipment. Workplaces engaging in the practice of dentistry within the UK are subject to legislation from the Control of Noise at Work (CNW) regulations 2005. Clinicians working in the military are at further increased risk of NIHL due to exposure from additional risk factors such as rifles or aircraft engines. To our knowledge, no authors have previously studied the noise levels experienced in a military dental setting or compared noise levels in a typical dental practice with current UK legislation. METHOD: Measurements of noise levels experienced by a dentist, dental nurse and dental hygienist during a standard conservation procedure were assessed using wearable noise dose-badges. Furthermore, noise levels within a dental technician's work space were also assessed. Noise levels produced by representative clinical and laboratory equipment were assessed and compared with CNW legislation. RESULTS: The highest level for clinical equipment was produced by the suction apparatus while aspirating up a cup of water at 76 dB. For laboratory equipment, the lower exposure action value (LEAV) of 80 dB would be exceeded in 2.1 hours' use of the trimmer, 3.6 hours' use of the vibrating table and 9 min use of the airline. CONCLUSIONS: Noise levels experienced by clinicians within the dental surgery were well below the legislative LEAV thresholds for both peak and continuous noise. However, noise levels produced by laboratory equipment were far higher and there is clearly the potential for excessive noise exposure for dental professional in the everyday setting. Dental professionals responsible for dental laboratory settings must be familiar with the CNW regulations and measures put in place that control the inadvertent breach of legislation. Hearing protection must be mandated when using equipment that exceeds the LEAV and an educational programme is required to explain both their correct use and the rationale behind it. Methods of mitigating that risk further require exploration such as alternative methods of completing the tasks performed by the airline or reducing the noise generated by it, such as by reducing the supply pressure or using an alternative nozzle design.