Targeted genome editing restores auditory function in adult mice with progressive hearing loss caused by a human microRNA mutation.

Mutations in microRNA-96 (MIR96) cause autosomal dominant deafness-50 (DFNA50), a form of delayed-onset hearing loss. Genome editing has shown efficacy in hearing recovery through intervention in neonatal mice, yet editing in the adult inner ear is necessary for clinical applications, which has not been done. Here, we developed a genome editing therapy for the MIR96 mutation 14C>A by screening different CRISPR systems and optimizing Cas9 expression and the sgRNA scaffold for efficient and specific mutation editing. AAV delivery of the KKH variant of Staphylococcus aureus Cas9 (SaCas9-KKH) and sgRNA to the cochleae of presymptomatic (3-week-old) and symptomatic (6-week-old) adult Mir9614C>A/+ mutant mice improved hearing long term, with efficacy increased by injection at a younger age. Adult inner ear delivery resulted in transient Cas9 expression without evidence of AAV genomic integration, indicating the good safety profile of our in vivo genome editing strategy. We developed a dual-AAV system, including an AAV-sgmiR96-master carrying sgRNAs against all known human MIR96 mutations. Because mouse and human MIR96 sequences share 100% homology, our approach and sgRNA selection for efficient and specific hair cell editing for long-term hearing recovery lay the foundation for the development of treatment for patients with DFNA50 caused by MIR96 mutations.

Development and Evaluation of the Italian Version of the Dichotic Digit Test: Insights from 39 Normal-Hearing Children Aged 11 to 13 years.

BACKGROUND The dichotic digit test (DDT) is one of the tests for the behavioral assessment of central auditory processing. Dichotic listening tests are sensitive ways of assessing cortical structures, the corpus callossum, and binaural integration mechanisms, showing strong correlations with learning difficulties. The DDT is presently available in a number of languages, each appropriate for the subject's native language. However, there is presently no test in the Italian language. The goal of this study was to develop an Italian version of the one-pair dichotic digit test (DDT-IT) and analyze results in 39 normal-hearing Italian children 11 to 13 years old. We used 2 conditions of presentation: free recall and directed attention (left or right ear), and looked at possible effects of sex and ear side. MATERIAL AND METHODS This study involved 3 steps: creation of the stimuli, checking their quality with Italian speakers, and assessment of the DDT-IT in our subject pool. The study involved 39 children (26 girls and 13 boys), aged 11-13 years. All participants underwent basic audiological assessment, auditory brainstem response, and then DDT-IT. RESULTS Results under free recall and directed attention conditions were similar for right and left ears, and there were no sex or age effects. CONCLUSIONS The Italian version of DDT (DDT-IT) has been developed and its performance on 39 normal-hearing Italian children was assessed. We found there were no age or sex effects for either the free recall condition or the directed attention condition.

Easy as 1-2-3: Development and Evaluation of a Simple yet Valid Audiogram-Classification System.

Almost since the inception of the modern-day electroacoustic audiometer a century ago the results of pure-tone audiometry have been characterized by an audiogram. For almost as many years, clinicians and researchers have sought ways to distill the volume and complexity of information on the audiogram. Commonly used approaches have made use of pure-tone averages (PTAs) for various frequency ranges with the PTA for 500, 1000, 2000 and 4000 Hz (PTA4) being the most widely used for the categorization of hearing loss severity. Here, a three-digit triad is proposed as a single-number summary of not only the severity, but also the configuration and bilateral symmetry of the hearing loss. Each digit in the triad ranges from 0 to 9, increasing as the level of the pure-tone hearing threshold level (HTL) increases from a range of optimal hearing (< 10 dB Hearing Level; HL) to complete hearing loss (≥ 90 dB HL). Each digit also represents a different frequency region of the audiogram proceeding from left to right as: (Low, L) PTA for 500, 1000, and 2000 Hz; (Center, C) PTA for 3000, 4000 and 6000 Hz; and (High, H) HTL at 8000 Hz. This LCH Triad audiogram-classification system is evaluated using a large United States (U.S.) national dataset (N = 8,795) from adults 20 to 80 + years of age and two large clinical datasets totaling 8,254 adults covering a similar age range. Its ability to capture variations in hearing function was found to be superior to that of the widely used PTA4.

Sialyllactose preserves residual hearing after cochlear implantation.

In individuals with hearing loss, protection of residual hearing is essential following cochlear implantation to facilitate acoustic and electric hearing. Hearing preservation requires slow insertion, atraumatic electrode and delivery of the optimal quantity of a pharmacological agent. Several studies have reported variable hearing outcomes with osmotic pump-mediated steroid delivery. New drugs, such as sialyllactose (SL) which have anti-inflammatory effect in many body parts, can prevent tissue overgrowth. In the present study, the positive effects of the pharmacological agent SL against insults were evaluated in vitro using HEI-OC1 cells. An animal model to simulate the damage due to electrode insertion during cochlear implantation was used. SL was delivered using osmotic pumps to prevent loss of the residual hearing in this animal model. Hearing deterioration, tissue fibrosis and ossification were confirmed in this animal model. Increased gene expressions of inflammatory cytokines were identified in the cochleae following dummy electrode insertion. Following the administration of SL, insertion led to a decrease in hearing threshold shifts, tissue reactions, and inflammatory markers. These results emphasize the possible role of SL in hearing preservation and improve our understanding of the mechanism underlying hearing loss after cochlear implantation.

A genome-wide association study reveals a polygenic architecture of speech-in-noise deficits in individuals with self-reported normal hearing.

Speech-in-noise (SIN) perception is a primary complaint of individuals with audiometric hearing loss. SIN performance varies drastically, even among individuals with normal hearing. The present genome-wide association study (GWAS) investigated the genetic basis of SIN deficits in individuals with self-reported normal hearing in quiet situations. GWAS was performed on 279,911 individuals from the UB Biobank cohort, with 58,847 reporting SIN deficits despite reporting normal hearing in quiet. GWAS identified 996 single nucleotide polymorphisms (SNPs), achieving significance (p < 5*10-8) across four genomic loci. 720 SNPs across 21 loci achieved suggestive significance (p < 10-6). GWAS signals were enriched in brain tissues, such as the anterior cingulate cortex, dorsolateral prefrontal cortex, entorhinal cortex, frontal cortex, hippocampus, and inferior temporal cortex. Cochlear cell types revealed no significant association with SIN deficits. SIN deficits were associated with various health traits, including neuropsychiatric, sensory, cognitive, metabolic, cardiovascular, and inflammatory conditions. A replication analysis was conducted on 242 healthy young adults. Self-reported speech perception, hearing thresholds (0.25-16 kHz), and distortion product otoacoustic emissions (1-16 kHz) were utilized for the replication analysis. 73 SNPs were replicated with a self-reported speech perception measure. 211 SNPs were replicated with at least one and 66 with at least two audiological measures. 12 SNPs near or within MAPT, GRM3, and HLA-DQA1 were replicated for all audiological measures. The present study highlighted a polygenic architecture underlying SIN deficits in individuals with self-reported normal hearing.

Age, preoperative tumor volume and widening of the internal acoustic meatus are independent factors associated with poor preoperative hearing in vestibular schwannoma patients - results of a single-center retrospective analysis.

Preoperative hearing function shows wide variations among patients diagnosed with vestibular schwannoma. Besides the preoperative tumor size there are other factors that influence the preoperative hearing function that are frequently discussed. A comprehensive analysis of a large cohort of vestibular schwannomas has the potential to describe new insights and influence the preoperative management. We analyzed clinical factors, imaging data and the expression of the proliferation marker MIB1 as potential influencing factors on the preoperative hearing function in a retrospective cohort of 523 primary sporadic vestibular schwannomas. The results of the preoperative audiometry were quantified using the Gardner-Robertson Score. Uni- and multivariate analyses were performed. Serviceable hearing (Gardner-Robertson class 1 or 2) was documented in 391 patients (74.8%). Factors associated with non-serviceable hearing (Gardner-Robertson class 3-5) were patients of older age (p < 0.0001), larger preoperative tumor volume (p = 0.0013) and widening of the internal acoustic meatus compared to the healthy side (p = 0.0353). Gender and differences in the expression of the proliferation marker MIB1 had no influence on preoperative hearing. In the multivariate nominal logistic regression older age (OR 27.60 (CI 9.17-87.18), p < 0.0001), larger preoperative tumor volume (OR 20.20 (CI 3.43-128.58), p = 0.0011) and widening of the internal acoustic canal (OR 7.86 (CI 1.77-35.46), p = 0.0079) remained independent factors associated with non-serviceable hearing. Widening of the internal acoustic canal is an independent factor for non-serviceable preoperative hearing in vestibular schwannoma patients together with older age and larger preoperative tumor volume.

Reduced Cochlear MRI Signal and Hearing Outcomes in Conservatively Managed Vestibular Schwannoma Patients.

OBJECTIVE: This study aimed to determine if hypointense cochlear magnetic resonance imaging (MRI) constructive interference in steady-state (CISS) signal correlates with hearing outcomes in conservatively managed vestibular schwannoma (VS) patients. STUDY DESIGN: Retrospective review of 657 cases from 1992 to 2020. SETTING: Tertiary academic referral center. PATIENTS: A retrospective review was performed to identify conservatively managed VS patients with appropriate baseline MRI, audiology, and at least 12-month audiological follow-up. Patients were excluded if they progressed to surgery or radiotherapy in less than 12 months, bilateral tumors, or surgery on the contralateral ear. INTERVENTION: Conservatively managed patients with CISS imaging studies and audiology testing. MAIN OUTCOME MEASURES: Primary outcome measure change in pure-tone average (PTA) and word recognition score (WRS). Secondary outcome measures tumor size, presence of lateral fluid cap, or cystic changes. RESULTS: A total of 92 individuals (47% male, 58 ± 11.6 yr) met the inclusion criteria, with 36 (39%) of patients demonstrating abnormal cochlear CISS signal. At baseline, abnormal cochlear CISS signal was associated with higher intracanalicular (IC) length (7.9 versus 6.6 mm, p = 0.0177) and lower WRS (55.7 versus 78.8 dBHL, p = 0.0054). During follow-up, individuals with abnormal cochlear CISS signal had significantly higher PTA (62.4 versus 46.4 dBHL, p = 0.0010). After adjusting for baseline covariates, abnormal cochlear CISS signal was consistently associated with a greater increase in PTA of 8.3 dBHL (95% confidence interval, 2.9-13.7; p = 0.0032) from baseline when compared with the normal group. CONCLUSIONS: Abnormal cochlear signal on MRI CISS sequences is associated with poorer hearing outcomes in conservatively managed VS patients.

The mechanism for directional hearing in fish.

Locating sound sources such as prey or predators is critical for survival in many vertebrates. Terrestrial vertebrates locate sources by measuring the time delay and intensity difference of sound pressure at each ear1-5. Underwater, however, the physics of sound makes interaural cues very small, suggesting that directional hearing in fish should be nearly impossible6. Yet, directional hearing has been confirmed behaviourally, although the mechanisms have remained unknown for decades. Several hypotheses have been proposed to explain this remarkable ability, including the possibility that fish evolved an extreme sensitivity to minute interaural differences or that fish might compare sound pressure with particle motion signals7,8. However, experimental challenges have long hindered a definitive explanation. Here we empirically test these models in the transparent teleost Danionella cerebrum, one of the smallest vertebrates9,10. By selectively controlling pressure and particle motion, we dissect the sensory algorithm underlying directional acoustic startles. We find that both cues are indispensable for this behaviour and that their relative phase controls its direction. Using micro-computed tomography and optical vibrometry, we further show that D. cerebrum has the sensory structures to implement this mechanism. D. cerebrum shares these structures with more than 15% of living vertebrate species, suggesting a widespread mechanism for inferring sound direction.

Evaluation of Hearing Functions in Children with Celiac Disease and the Effect of Gluten-free Diet on these Functions.

OBJECTIVE: The present study aims to investigate the potential impact of celiac disease (CD) on hearing functions and assess the effect of a gluten-free diet (GFD) on this condition. MATERIALS AND METHODS: The study included 55 children with CD (110 ears) and 25 healthy controls (50 ears) matched for age and gender. The CD group was divided into adherent (n = 31) and nonadherent (n = 24) to GFD. Participants underwent tympanometry and pure tone audiometry assessments covering frequencies from 500 to 4000 Hz. RESULTS: Patients with CD showed significantly higher air and bone conduction hearing averages compared to the control group at frequencies of 500, 1000, 2000, and 4000 Hz for air conduction, and at 500 Hz for bone conduction (P < 0.05). Celiac patients, those who fully adhered to GFD, had notably higher air conduction hearing averages at 500, 2000, and 4000 Hz compared to healthy controls (P < 0.05). However, there was no difference in bone conduction hearing averages between the two groups. In contrast, celiac patients who did not comply with GFD had statistically significantly higher air and bone conduction hearing averages than the control group (P < 0.05), at frequencies of 500, 1000, and 4000 Hz for air conduction, and at 500 and 1000 Hz for bone conduction (P < 0.05). CONCLUSIONS: The study suggests that nonadherence to GFD may elevate the risk of hearing loss in children with CD. As a result, it is recommended to conduct hearing screenings for children with CD and underscore the importance of complying with GFD to mitigate further detrimental effects on hearing functions.

Preservation of Residual Hearing: Long-Term Results With a Mid-Scala Electrode.

OBJECTIVE: The long-term preservation of residual hearing after cochlear implantation has become a major goal over the past few years. The aim of the present study was to evaluate residual hearing in the long-term follow-up using mid-scala electrodes. METHODS: In this retrospective, single-center study, we collected data from 27 patients who were implanted between 2014 and 2015 with residual hearing in the low-frequency range using a mid-scala electrode. Measurements of the hearing thresholds were carried out directly postoperatively (day 1 after surgery) and in the long-term follow-up 43.7 ± 6.9 months. The calculation of the extent of audiological hearing preservation was determined using the HEARRING group formula by Skarsynski. RESULTS: Postoperative preservation of residual hearing was achieved in 69.2% of the cases in the low-frequency range between 250 Hz and 1 kHz, of which 89.5% of the patients had frequencies that suggested using electroacoustic stimulation (EAS). In the long-term follow-up, 30.8% of the patients showed residual hearing; however, 57.1% had apparently benefited from EAS. CONCLUSION: Preservation of residual hearing is feasible in the long term using mid-scala electrodes. Postoperatively, there is over the half of patients who benefit from an EAS strategy. The long-term follow-up shows a certain decrease in residual hearing. However, these results are comparable to studies relating to other types of electrodes. Further research should be conducted in future to better evaluate hearing loss in long-term follow-up, compared to direct postoperative audiological results.

In-situ Audiometry Compared to Conventional Audiometry for Hearing Aid Fitting.

The use of in-situ audiometry for hearing aid fitting is appealing due to its reduced resource and equipment requirements compared to standard approaches employing conventional audiometry alongside real-ear measures. However, its validity has been a subject of debate, as previous studies noted differences between hearing thresholds measured using conventional and in-situ audiometry. The differences were particularly notable for open-fit hearing aids, attributed to low-frequency leakage caused by the vent. Here, in-situ audiometry was investigated for six receiver-in-canal hearing aids from different manufacturers through three experiments. In Experiment I, the hearing aid gain was measured to investigate whether corrections were implemented to the prescribed target gain. In Experiment II, the in-situ stimuli were recorded to investigate if corrections were directly incorporated to the delivered in-situ stimulus. Finally, in Experiment III, hearing thresholds using in-situ and conventional audiometry were measured with real patients wearing open-fit hearing aids. Results indicated that (1) the hearing aid gain remained unaffected when measured with in-situ or conventional audiometry for all open-fit measurements, (2) the in-situ stimuli were adjusted for up to 30 dB at frequencies below 1000 Hz for all open-fit hearing aids except one, which also recommends the use of closed domes for all in-situ measurements, and (3) the mean interparticipant threshold difference fell within 5 dB for frequencies between 250 and 6000 Hz. The results clearly indicated that modern measured in-situ thresholds align (within 5 dB) with conventional thresholds measured, indicating the potential of in-situ audiometry for remote hearing care.

The effects of auditory stimulation on heart rate variability in healthy individuals with normal hearing and with hearing loss: a systematic review and meta-analysis.

PURPOSE: To analyze the effects of auditory stimulation on heart rate variability (HRV) indices in healthy individuals with normal hearing and with hearing loss, regardless of type and/or grade, by means of a systematic review. RESEARCH STRATEGIES: This is a systematic review with a meta-analysis that addresses the following question: in healthy individuals with normal hearing and/or with hearing loss, what are the effects of auditory stimulation on HRV indices in comparison to silence? We consulted the Cochrane Library, Embase, LILACS, PubMed, Web of Science, and Scopus databases and the gray literature (Google Scholar, OpenGrey, and ProQuest). SELECTION CRITERIA: There were no restrictions as to period or language of publication. DATA ANALYSIS: We identified 451 records, an additional 261 in the gray literature, and five studies in a search through the references, resulting in a total of 717 records, with 171 duplicate records. After screening the titles and abstracts of 546 studies, we excluded 490 and considered 56 studies in full to assess their eligibility. RESULTS: Nine of these studies were included in the systematic review, eight of which were suitable for the meta-analysis. CONCLUSION: It is suggested that auditory stimulation may influence the RMSSD, pNN50, SDNN, RRTri and SD2 indices of HRV in healthy adults with normal hearing.

miR-130b-3p involved in the pathogenesis of age-related hearing loss via targeting PPARγ and autophagy.

The study focuses on the underlying regulatory mechanism of age-related hearing loss (ARHL), which results from autophagy dysregulation mediated by miR-130b-3p targeting PPARγ. We constructed miR-130b-3p knockout (antagomir) and PPARγ over-expression (OE-PPARγ) mice model by injecting mmu-miR-130b-3p antagomir and HBAAV2/Anc80-m-Pparg-T2A-mCHerry into the right ear' round window of each mouse, respectively. In vitro, we introduced oxidative stress within HEI-OC1 cells by H2O2 and exogenously changed the miR-130b-3p and PPARγ levels. MiRNA level was detected by RT-qPCR, proteins by western blotting and immunohistochemistry. Morphology of autophagosomes was observed by electron microscopy. In vivo, the cochlea of aged mice showed higher miR-130b-3p expression and lower PPARγ expression, while exogenous inhibition of miR-130b-3p up-regulated PPARγ expression. Autophagy-related biomarkers expression (ATG5, Beclin-1 and LC3B II/I) decreased in aged mice, which reversely increased after the inhibition of miR-130b-3p. The elevation of PPARγ demonstrated similar effects. Contrarily, exogenous overexpression of miR-130b-3p resulted in the decrease of ATG5, Beclin-1 and LC3B II/I. We created oxidative stress within HEI-OC1 by H2O2, subsequently observed the formation of autophagosomes under electron microscope, so as the elevated cell apoptosis rate and weakened cell viability. MiR-130b-3p/PPARγ contributed to the premature senescence of these H2O2-induced HEI-OC1 cells. MiR-130b-3p regulated HEI-OC1 cell growth by targeting PPARγ, thus leading to ARHL.

Hearing loss-related altered neuronal activity in the inferior colliculus.

Hearing loss is well known to cause plastic changes in the central auditory system and pathological changes such as tinnitus and hyperacusis. Impairment of inner ear functions is the main cause of hearing loss. In aged individuals, not only inner ear dysfunction but also senescence of the central nervous system is the cause of malfunction of the auditory system. In most cases of hearing loss, the activity of the auditory nerve is reduced, but that of the successive auditory centers is increased in a compensatory way. It has been reported that activity changes occur in the inferior colliculus (IC), a critical nexus of the auditory pathway. The IC integrates the inputs from the brainstem and drives the higher auditory centers. Since abnormal activity in the IC is likely to affect auditory perception, it is crucial to elucidate the neuronal mechanism to induce the activity changes of IC neurons with hearing loss. This review outlines recent findings on hearing-loss-induced plastic changes in the IC and brainstem auditory neuronal circuits and discusses what neuronal mechanisms underlie hearing-loss-induced changes in the activity of IC neurons. Considering the different causes of hearing loss, we discuss age-related hearing loss separately from other forms of hearing loss (non-age-related hearing loss). In general, the main plastic change of IC neurons caused by both age-related and non-age-related hearing loss is increased central gain. However, plastic changes in the IC caused by age-related hearing loss seem to be more complex than those caused by non-age-related hearing loss.

Effect of Age and Unaided Acoustic Hearing on Pediatric Cochlear Implant Users' Ability to Distinguish Yes/No Statements and Questions.

PURPOSE: The purpose of this study was to evaluate the ability to discriminate yes/no questions from statements in three groups of children: bilateral cochlear implant (CI) users, nontraditional CI users with aidable hearing preoperatively in the ear to be implanted, and controls with normal hearing. Half of the nontraditional CI users had sufficient postoperative acoustic hearing in the implanted ear to use electric-acoustic stimulation, and half used a CI alone. METHOD: Participants heard recorded sentences that were produced either as yes/no questions or as statements by three male and three female talkers. Three raters scored each participant response as either a question or a statement. Bilateral CI users (n = 40, 4-12 years old) and normal-hearing controls (n = 10, 4-12 years old) were tested binaurally in the free field. Nontraditional CI recipients (n = 22, 6-17 years old) were tested with direct audio input to the study ear. RESULTS: For the bilateral CI users, performance was predicted by age but not by 125-Hz acoustic thresholds; just under half (n = 17) of the participants in this group had measurable 125-Hz thresholds in their better ear. For nontraditional CI recipients, better performance was predicted by lower 125-Hz acoustic thresholds in the test ear, and there was no association with participant age. Performance approached that of the normal-hearing controls for some participants in each group. CONCLUSIONS: Results suggest that a 125-Hz acoustic hearing supports discrimination of yes/no questions and statements in pediatric CI users. Bilateral CI users with little or no acoustic hearing at 125 Hz develop the ability to perform this task, but that ability emerges later than for children with better acoustic hearing. These results underscore the importance of preserving acoustic hearing for pediatric CI users when possible.

Alpha9alpha10 knockout mice show altered physiological and behavioral responses to signals in masking noise.

Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise. Transgenic mice lacking the alpha9 subunits of these receptors (α9KOs) have normal hearing in quiet and noise, but lack classic cochlear suppression effects and show abnormal temporal, spectral, and spatial processing. Mice deficient for both the alpha9 and alpha10 receptor subunits (α9α10KOs) may exhibit more severe MOC-related phenotypes. Like α9KOs, α9α10KOs have normal auditory brainstem response (ABR) thresholds and weak MOC reflexes. Here, we further characterized auditory function in α9α10KO mice. Wild-type (WT) and α9α10KO mice had similar ABR thresholds and acoustic startle response amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. α9α10KO mice had larger ABR Wave I amplitudes than WTs in quiet and noise. Other ABR metrics of hearing-in-noise function yielded conflicting findings regarding α9α10KO susceptibility to masking effects. α9α10KO mice also had larger startle amplitudes in tone backgrounds than WTs. Overall, α9α10KO mice had grossly normal auditory function in quiet and noise, although their larger ABR amplitudes and hyperreactive startles suggest some auditory processing abnormalities. These findings contribute to the growing literature showing mixed effects of MOC dysfunction on hearing.

Priming central sound processing circuits through induction of spontaneous activity in the cochlea before hearing onset.

Sensory systems experience a period of intrinsically generated neural activity before maturation is complete and sensory transduction occurs. Here we review evidence describing the mechanisms and functions of this 'spontaneous' activity in the auditory system. Both ex vivo and in vivo studies indicate that this correlated activity is initiated by non-sensory supporting cells within the developing cochlea, which induce depolarization and burst firing of groups of nearby hair cells in the sensory epithelium, activity that is conveyed to auditory neurons that will later process similar sound features. This stereotyped neural burst firing promotes cellular maturation, synaptic refinement, acoustic sensitivity, and establishment of sound-responsive domains in the brain. While sensitive to perturbation, the developing auditory system exhibits remarkable homeostatic mechanisms to preserve periodic burst firing in deaf mice. Preservation of this early spontaneous activity in the context of deafness may enhance the efficacy of later interventions to restore hearing.

Eye movements track prioritized auditory features in selective attention to natural speech.

Over the last decades, cognitive neuroscience has identified a distributed set of brain regions that are critical for attention. Strong anatomical overlap with brain regions critical for oculomotor processes suggests a joint network for attention and eye movements. However, the role of this shared network in complex, naturalistic environments remains understudied. Here, we investigated eye movements in relation to (un)attended sentences of natural speech. Combining simultaneously recorded eye tracking and magnetoencephalographic data with temporal response functions, we show that gaze tracks attended speech, a phenomenon we termed ocular speech tracking. Ocular speech tracking even differentiates a target from a distractor in a multi-speaker context and is further related to intelligibility. Moreover, we provide evidence for its contribution to neural differences in speech processing, emphasizing the necessity to consider oculomotor activity in future research and in the interpretation of neural differences in auditory cognition.

Exploring the Influence of Extended High-Frequency Hearing on Cochlear Functioning at Lower Frequencies.

PURPOSE: Diminished basal cochlear function, as indicated by elevated hearing thresholds in the extended high frequencies (EHFs), has been associated with lower levels of click-evoked and distortion-product otoacoustic emissions measured at lower frequencies. However, stimulus-frequency otoacoustic emissions (SFOAEs) at low-probe levels are reflection-source emissions that do not share the same generation mechanism as distortion-source emissions. The primary objective of the present study was to examine the influence of hearing thresholds in the EHFs on SFOAEs measured at lower frequencies. METHOD: SFOAEs were recorded from both ears in 45 individuals with normal hearing thresholds in the conventional audiometric frequencies (0.25-8 kHz). Hearing thresholds were also measured at EHFs (10, 12.5, and 16 kHz). SFOAE magnitudes and signal-to-noise ratios (SNRs) were averaged across 1, 2, and 4 kHz probe frequencies and also averaged for high-probe frequencies (2 and 4 kHz). RESULTS: SFOAE magnitudes and SNRs were significantly higher for ears with better EHF hearing relative to poorer EHF hearing, categorized based on the median split. In addition, hearing in the EHFs significantly contributed to the variance in all SFOAE measures, except for the high-frequency SFOAE magnitudes model. However, hearing thresholds at the probe frequencies did not significantly contribute to the variance in SFOAEs. CONCLUSIONS: The study findings suggest that alterations in the basal cochlea, as revealed by EHF hearing thresholds, could be associated with diminished cochlear functioning in relatively apical regions, shown by SFOAEs at lower frequencies, in individuals with normal audiograms. These findings underscore the significance of considering EHF thresholds in audiological evaluations, as alterations in these frequencies may reflect broader cochlear health status.