High-Frequency Cochlear Amplifier Dysfunction: A Dominating Contribution to the Cognitive-Ear Link

Objective: The objective of this study was to investigate the role of the high-frequency cochlear dysfunction in the cognitive-ear link.Methods: Seventy-four presbycusis patients (PC group) and seventy-one age-, sex-, and education-level matched normal hearing controls (NH group) were recruited in this study. Participants underwent a battery of cognitive tests estimated by Montreal Cognitive Assessment (MoCA), Stroop Color-Word Interference Test (Stroop), Symbol Digit Modalities Test (SDMT), Auditory Verbal Learning Test (AVLT), and Trail-Making Test (TMT-A and B), as well as auditory tests including distortion product otoacoustic emission (DPOAE), pure tone (PT) thresholds, and speech reception thresholds (SRT). Data were analyzed using the factor analysis, partial correlation analysis, multiple linear regression models, and mediation models.Results: Distortion product otoacoustic emission detection amplitudes and PT thresholds performed worse gradually from low to high frequencies in both the NH and PC groups. High-frequency DPOAE (H-DPOAE) was significantly correlated with cognitive domains in the PC group (AVLT: r = 0.30, p = 0.04; SDMT: r = 0.36, p = 0.01; Stroop: r = –0.32, p = 0.03; TMT-A: r = –0.40, p = 0.005; TMT-B: r = –0.34, p = 0.02). Multiple linear regression models showed that H-DPOAE predicted cognitive impairment effectively for aspects of memory (R2 = 0.27, 95% CI, 0.03 to 1.55), attention (R2 = 0.32, 95% CI, –6.18 to –0.40), processing speed (R2 = 0.37, 95% CI, 0.20 to 1.64), and executive function (TMT-A: R2 = 0.34, 95% CI, –5.52 to 1.03; TMT-B: R2 = 0.29, 95% CI, –11.30 to –1.12). H-DPOAE directly affected cognition and fully mediated the relationship between pure tone average (PTA)/SRT and cognitive test scores, excluding MoCA.Conclusion: This study has demonstrated that the high-frequency cochlear amplifier dysfunction has a direct predictive effect on the cognitive decline and makes a large contribution to the cognitive-ear link.

Evaluation of the effects of Covid-19 on cochleovestibular system with audiovestibular tests

Purpose The purpose of the present study was to investigate the effects of COVID-19 on audiovestibular system with Transiently Evoked Distortion Otoacoustic Emissions (TOAE), Distortion Product Otoacoustic Emissions (DPOAE), video head impulse test (vHIT) and caloric test. Methods Audiovestibular findings of 24 patients with moderate/severe COVID-19 and 24 healthy controls were compared using pure tone audiometry, tympanometry, TOAE, DPOAE, caloric test, and vHIT. Results On audiometry, the pure tone averages of the COVID-19 patients were higher than the controls ( P = .038). The TEOAE amplitudes at 4000 and 5000 Hz ( P = .006 and P < .01), and DPOAE amplitudes at 3000, 6000, and 8000 Hz ( P < .001, P = .003 and P < .001) were significantly lower in COVID-19 patients compared to the controls. On vestibular tests, there was no significant difference between the caloric test results of the patients and the controls ( P > .05). On vHIT testing, amplitudes of right semicircular canal was found to be significantly lower in COVID-19 group compared to the control group ( P = .008). Conclusion COVID-19 may affect inner ear functions causing a subtle damage in the outer hair cells and lateral semicircular canals. It must be kept in mind that COVID-19 may cause cochleovestibular problems.

Assessment of Distortion Product Otoacoustic Emissions Input-Output Function in Individuals with and without Musical Abilities

Background and Aim: Musical training has shown to bring about superior performance in several auditory and non-auditory tasks compared to those without musical exposure. Distortion product otoacoustic emissions (DPOAE) input-output function can be an indicator of the non-linear functioning of the cochlea. The objective of this study was to evaluate and compare the differences in the slope of DPOAE input-output function in individuals with and without musical abilities. Methods: Twenty normal-hearing individuals were considered in the age range of 18–25 years. They were divided based on the scores obtained on the questionnaire of musical abilities, as individuals with and without musical abilities. DPOAE input-output function was done for each of the two groups. The slope of the DPOAE input-output function was compared at different frequencies between the groups. Results: The results of the Mann Whitney test revealed that the slope was significantly steeper at 2000, 3000, 4000 and 6000 Hz in individuals with musical abilities. There was no significant difference in slope at 1000 and 1500 Hz. Conclusion: The increased steepness of the slope indicates a relatively better functioning of the cochlea in individuals with musical abilities. The enhanced perception of music may induce changes in the cochlea resulting in a better appreciation of music.

Characterizing the Access of Cholinergic Antagonists to Efferent Synapses in the Inner Ear

Stimulation of cholinergic efferent neurons innervating the inner ear has profound, well-characterized effects on vestibular and auditory physiology, after activating distinct ACh receptors (AChRs) on afferents and hair cells in peripheral endorgans. Efferent-mediated fast and slow excitation of vestibular afferents are mediated by α4β2*-containing nicotinic AChRs (nAChRs) and muscarinic AChRs (mAChRs), respectively. On the auditory side, efferent-mediated suppression of distortion product otoacoustic emissions (DPOAEs) is mediated by α9α10nAChRs. Previous characterization of these synaptic mechanisms utilized cholinergic drugs, that when systemically administered, also reach the CNS, which may limit their utility in probing efferent function without also considering central effects. Use of peripherally-acting cholinergic drugs with local application strategies may be useful, but this approach has remained relatively unexplored. Using multiple administration routes, we performed a combination of vestibular afferent and DPOAE recordings during efferent stimulation in mouse and turtle to determine whether charged mAChR or α9α10nAChR antagonists, with little CNS entry, can still engage efferent synaptic targets in the inner ear. The charged mAChR antagonists glycopyrrolate and methscopolamine blocked efferent-mediated slow excitation of mouse vestibular afferents following intraperitoneal, middle ear, or direct perilymphatic administration. Both mAChR antagonists were effective when delivered to the middle ear, contralateral to the side of afferent recordings, suggesting they gain vascular access after first entering the perilymphatic compartment. In contrast, charged α9α10nAChR antagonists blocked efferent-mediated suppression of DPOAEs only upon direct perilymphatic application, but failed to reach efferent synapses when systemically administered. These data show that efferent mechanisms are viable targets for further characterizing drug access in the inner ear.

Deletion of Oncomodulin Gives Rise to Early Progressive Cochlear Dysfunction in C57 and CBA Mice

Ca2+ signaling is a major contributor to sensory hair cell function in the cochlea. Oncomodulin (OCM) is a Ca2+ binding protein (CaBP) preferentially expressed in outer hair cells (OHCs) of the cochlea and few other specialized cell types. Here, we expand on our previous reports and show that OCM delays hearing loss in mice of two different genetic backgrounds: CBA/CaJ and C57Bl/6J. In both backgrounds, genetic disruption of Ocm leads to early progressive hearing loss as measured by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). In both strains, loss of Ocm reduced hearing across lifetime (hearing span) by more than 50% relative to wild type (WT). Even though the two WT strains have very different hearing spans, OCM plays a considerable and similar role within their genetic environment to regulate hearing function. The accelerated age-related hearing loss (ARHL) of the Ocm KO illustrates the importance of Ca2+ signaling in maintaining hearing health. Manipulation of OCM and Ca2+ signaling may reveal important clues to the systems of function/dysfunction that lead to ARHL.

Effects of Calcitonin-Gene-Related-Peptide on Auditory Nerve Activity

Calcitonin-gene-related peptide (CGRP) is a lateral olivocochlear (LOC) efferent neurotransmitter. Depression of sound-driven auditory brainstem response amplitude in CGRP-null mice suggests the potential for endogenous CGRP release to upregulate spontaneous and/or sound-driven auditory nerve (AN) activity. We chronically infused CGRP into the guinea pig cochlea and evaluated changes in AN activity as well as outer hair cell (OHC) function. The amplitude of both round window noise (a measure of ensemble spontaneous activity) and the synchronous whole-nerve response to sound (compound action potential, CAP) were enhanced. Lack of change in both onset adaptation and steady state amplitude of sound-evoked distortion product otoacoustic emission (DPOAE) responses indicated CGRP had no effect on OHCs, suggesting the origin of the observed changes was neural. Combined with results from the CGRP-null mice, these results appear to confirm that endogenous CGRP enhances auditory nerve activity when released by the LOC neurons. However, infusion of the CGRP receptor antagonist CGRP (8–37) did not reliably influence spontaneous or sound-driven AN activity, or OHC function, results that contrast with the decreased ABR amplitude measured in CGRP-null mice.

Association of cochlear outer hair cell - type II spiral ganglion afferents with protection from noise-induced hearing loss

The medial olivocochlear (MOC) efferent feedback circuit projecting to the cochlear outer hair cells (OHCs) confers protection from noise-induced hearing loss and is generally thought to be driven by inner hair cell (IHC) - type I spiral ganglion afferent (SGN) input. Knockout of the Prph gene (PrphKO) encoding the peripherin type III intermediate filament disrupted the OHC - type II SGN innervation and virtually eliminated MOC – mediated contralateral suppression from noise delivered to the opposite ear, measured as a reduction in cubic distortion product otoacoustic emissions. Electrical stimulation of the MOC pathway elicited contralateral suppression indistinguishable between wildtype (WT) and PrphKO mice, indicating that the loss of contralateral suppression was not due to disruption of the efferent arm of the circuit; IHC – type I SGN input was also normal, based on auditory brainstem responses. High-intensity, broadband noise (108 dB SPL, 1 hour) produced permanent hearing loss in PrphKO mice, but not in WT littermates. These findings associate OHC-type II input with MOC efferent - based otoprotection at loud sound levels.

Distortion Product Otoacoustic Emissions and Their Suppression as Predictors of Peripheral Auditory Damage in Migraine: A Case-Control Study

Although several cochleo-vestibular symptoms are commonly associated with migraine, only a limited number of studies have been done in this regard. Some reported abnormalities in audiometry, auditory brainstem response and vestibular tests, considering these manifestations mainly related to central etiology. However, increasing evidence also suggests a peripheral involvement of the inner ear in migraine. The aim of this study was to investigate the peripheral auditory pathway in migraineurs using otoacoustic emissions (OAEs), to detect alteration of cochlear functioning and possible relationship with disease severity. Sixty-two migraineurs and sixty matched controls were enrolled in the study and underwent a routine neuro-otolaryngology examination; self-administered questionnaires were used to evaluate subjective perception of hearing disability. DPOAE and their suppression were lower in migraineurs compared to controls and significantly related to the disease duration. Altered DPOAE exposed migraineurs to the risk of affecting by migraine without aura, of presenting with ocular and/or auditory symptoms during attack and of using more painkillers. Concomitant dopaminergic symptoms and/or allodynia such as the acute non-consumption of triptans were significant determinants of decreased contralateral suppression of DPOAE among migraineurs. This potential subclinical cochlear impairment in migraine detected by OAEs may represent the earliest sign of sensorineural damage in these patients, providing a promising tool for the initial diagnosis and an opportunity to monitor disease course and treatment response over time.

Effect of Radiofrequency Waves of Mobile Phones on Distortion Product Otoacoustic Emissions

Objective The prolonged exposure to electromagnetic fields of mobile phones can damage the cochlear hair cells, which can be detected by otoacoustic emission (OAE). To know the effect of mobile phones on hearing, the young volunteers were subjected to prolonged mobile phone usage and changes in OAE were recorded. Materials and Methods Twenty-eight volunteers with normal hearing were made to talk one full hour continuously on the mobile phone. Distortion product otoacoustic emission (DPOAE) was measured prior to the usage of mobile phones and immediately after the use (post-exposure 1) and 24 hours after the use (post-exposure 2). The values were compared. Results Out of the 28 volunteers, 20 were females and 8 were males. Twenty-one volunteers preferred the right ear while using mobile phones, 7 preferred the left ear. There was no statistically significant difference between the baseline DPOAE values and values of post-exposure 1 and 2 when only the preferred ear was taken into consideration. When the preferred ear was compared with nonpreferred ear, a statistically significant difference was found only in the low frequencies between the pre-exposure and post-exposure 1 values. Conclusion This study shows there was no significant correlation between OAE and prolonged mobile phone exposure when the preferred ear was not considered.