Auditory Research publications

In many situations, listeners with sensorineural hearing loss demonstrate reduced spatial release from masking compared to listeners with normal hearing. This deficit is particularly evident in the “symmetric masker” paradigm in which competing talkers are located to either side of a central target talker. However, there is some evidence that reduced target audibility (rather than a spatial deficit per se) under conditions of spatial separation may contribute to the observed deficit. In this study a simple “glimpsing” model (applied separately to each ear) was used to isolate the target information that is potentially available in binaural speech mixtures. Intelligibility of these glimpsed stimuli was then measured directly. Differences between normally hearing and hearing-impaired listeners observed in the natural binaural condition persisted for the glimpsed condition, despite the fact that the task no longer required segregation or spatial processing. This result is consistent with the idea that the performance of listeners with hearing loss in the spatialized mixture was limited by their ability to identify the target speech based on sparse glimpses, possibly as a result of some of those glimpses being inaudible.

In contrast to static sounds, spatially dynamic sounds have received little attention in psychoacoustic research so far. This holds true especially for acoustically complex (reverberant, multisource) conditions and impaired hearing. The current study therefore investigated the influence of reverberation and the number of concurrent sound sources on source movement detection in young normal-hearing (YNH) and elderly hearing-impaired (EHI) listeners. A listening environment based on natural environmental sounds was simulated using virtual acoustics and rendered over headphones. Both near-far (‘radial’) and left-right (‘angular’) movements of a frontal target source were considered. The acoustic complexity was varied by adding static lateral distractor sound sources as well as reverberation. Acoustic analyses confirmed the expected changes in stimulus features that are thought to underlie radial and angular source movements under anechoic conditions and suggested a special role of monaural spectral changes under reverberant conditions. Analyses of the detection thresholds showed that, with the exception of the single-source scenarios, the EHI group was less sensitive to source movements than the YNH group, despite adequate stimulus audibility. Adding static sound sources clearly impaired the detectability of angular source movements for the EHI (but not the YNH) group. Reverberation, on the other hand, clearly impaired radial source movement detection for the EHI (but not the YNH) listeners. These results illustrate the feasibility of studying factors related to auditory movement perception with the help of the developed test setup.

The purpose of this study was to test the hypothesis that listeners with frequent exposure to loud music exhibit deficits in suprathreshold auditory performance consistent with cochlear synaptopathy. Young adults with normal audiograms were recruited who either did ( n = 31) or did not ( n = 30) have a history of frequent attendance at loud music venues where the typical sound levels could be expected to result in temporary threshold shifts. A test battery was administered that comprised three sets of procedures: (a) electrophysiological tests including distortion product otoacoustic emissions, auditory brainstem responses, envelope following responses, and the acoustic change complex evoked by an interaural phase inversion; (b) psychoacoustic tests including temporal modulation detection, spectral modulation detection, and sensitivity to interaural phase; and (c) speech tests including filtered phoneme recognition and speech-in-noise recognition. The results demonstrated that a history of loud music exposure can lead to a profile of peripheral auditory function that is consistent with an interpretation of cochlear synaptopathy in humans, namely, modestly abnormal auditory brainstem response Wave I/Wave V ratios in the presence of normal distortion product otoacoustic emissions and normal audiometric thresholds. However, there were no other electrophysiological, psychophysical, or speech perception effects. The absence of any behavioral effects in suprathreshold sound processing indicated that, even if cochlear synaptopathy is a valid pathophysiological condition in humans, its perceptual sequelae are either too diffuse or too inconsequential to permit a simple differential diagnosis of hidden hearing loss.

Objective: There is currently no accepted method of mapping bilateral cochlear-implant (BiCI) users to maximize binaural performance, but the current approach of mapping one ear at a time could produce spatial perceptions that are not consistent with a sound’s physical location in space. The goal of this study was to investigate the perceived intracranial lateralization of bilaterally synchronized electrical stimulation with a range of interaural level differences (ILDs) and to determine a method to produce relatively more centered auditory images when provided multielectrode stimulation. Design: Using direct stimulation, lateralization curves were measured in nine BiCI listeners using 1000-pulses per second (pps), 500-msec constant-amplitude pulse trains with ILDs that ranged from −20 to +20 clinical current units (CUs). The stimuli were presented bilaterally at 70 to 80% of the dynamic range on single or multiple electrode pairs. For the multielectrode pairs, the ILD was applied consistently across all the pairs. The lateralization response range and the bias magnitude at 0 CU ILD (i.e., the number of CUs needed to produce a centered auditory image) were computed. Then the levels that elicit a centered auditory image with single-electrode stimulation were used with multielectrode stimulation to determine if this produced fewer significant biases at 0 CU ILD. Lastly, a multichannel ILD processing model was used to predict lateralization for the multielectrode stimulation from the single-electrode stimulation. Results: BiCI listeners often perceived both single- and multielectrode stimulation at 0-CU ILD as not intracranially centered. For single-electrode stimulation, 44% of the lateralization curves had relatively large (≥5 CU) bias magnitudes. For the multielectrode stimulation, 25% of the lateralization curves had large bias magnitudes. After centering the single-electrode pairs, the percentage of multielectrode combinations that produced large biases significantly decreased to only 4% ( p < 0.001, McNemar’s test). The lateralization with multielectrode stimulation was well predicted by a model that used unweighted or weighted average single-electrode lateralization percepts across electrode pairs (87 or 90%, respectively). Conclusion: Current BiCI mapping procedures can produce an inconsistent association between a physical ILD and the perceived location across electrodes for both single- and multielectrode stimulation. Explicit centering of single-electrode pairs using the perceived centered intracranial location almost entirely corrects this problem and such an approach is supported by our understanding and model of across-frequency ILD processing. Such adjustments might be achieved by clinicians using single-electrode binaural comparisons. Binaural abilities, like sound localization and understanding speech in noise, may be improved if these across-electrode perceptual inconsistencies are removed.

Objectives . As a homing factor of stem cell, stromal derived factor-1 (SDF-1) is important for the regenerative research in ototoxicity. Mice models with aminoglycoside ototoxicity have been widely used to study the regeneration capacity of MSCs in repair of cochlear injury. We developed a mouse model with maximal increase in SDF-1 levels in the inner ear, according to the “one-shot” doses of kanamycin and furosemide. Methods . C57BL/6 mice had kanamycin (420, 550, and 600 mg/kg) dissolved in PBS, followed by an intraperitoneal injection of furosemide (130 mg/kg). The injuries of inner ear were measured with hearing thresholds, histology, and outer hair cell counts at 0, 3, 5, 7, 10, and 14 days before the sacrifice. The levels of SDF-1 in the inner ear were tested by real-time RT-PCR and immunohistochemistry. Results . There were a significant reduction in hearing thresholds and a maximal increase of SDF-1 levels in the furosemide 130 mg/kg + kanamycin 550 mg/kg group, but severe hearing deterioration over time was observed in the furosemide 130 mg/kg + kanamycin 600 mg/kg group and four mice were dead. SDF-1 was detected mostly in the stria vascularis and organ of Corti showing the highest increase in expression. Conclusion . We observed optimal induction of the stem cell homing factor in the newly generated aminoglycoside-induced ototoxicity mouse model using a “one-shot” protocol. This study regarding high SDF-1 levels in our mouse model of ototoxicity would play a major role in the development of therapeutic agents using MSC homing.

Noise‐induced hearing loss (NIHL) results from the damage of the delicate hair cells inside the ear after excessive stimulation of noise. Unlike certain lower animals such as amphibians, fishes, and birds, in humans, hair cells cannot be regenerated once they are killed or damaged; thus, there are no therapeutic options to cure NIHL. Therefore, it is more important to protect hair cells from the noise before the damage occurs. In this study, we report the protective effect of Yang Mi Ryung extract (YMRE) against NIHL; this novel therapeutic property of YMRE has not been reported previously. Our data demonstrates that the hearing ability damaged by noise is markedly restored in mice preadministrated with YMRE before noise exposure, to the level of normal control group. Our study also provides the molecular mechanism underlying the protective effect of YMRE against NIHL by showing that YMRE significantly blocks noise‐induced apoptotic cell death and reduces reactive oxygen species (ROS) production in cochleae. Moreover, quantitative polymerase chain reaction (qPCR) analysis demonstrates that YMRE has anti‐inflammatory properties, suppressing the mRNA levels of TNF α and IL‐1 β induced by noise exposure. In conclusion, YMRE could be a useful preventive intervention to prevent hearing impairment induced by the exposure to excessive noise.

Introduction . Most implantable hearing aids currently available were developed to compensate the sensorineural hearing loss by driving middle ear structures (e.g., the ossicles). These devices are successfully used in round window (RW) stimulation clinically, although this was initially not the intended use. Here, a novel microactuator, specifically designed for RW stimulation, was tested in human temporal bones to determine actuator performance and applicability. Methods . Stapes footplate response to RW stimulation was determined experimentally in human temporal bones and the obtained sound pressure output level was estimated. Results . The actuator had a flat displacement response between 0.125 and 4 kHz, a resonance between 4 and 7 kHz, and a roll-off above. At increasing contact force, the stapes footplate displacement decreased by 5–10 dB re μ m for forces ≥ 2 mN. The equivalent sound pressure level between 0.125 and 4 kHz amounted to 87–97 eq dB SPL and increased to 117 eq dB SPL for frequencies of 4–7 kHz. The total harmonic distortion (THD) of the actuator ranged within 15–40% for static forces of 5 mN. Conclusion . The feasibility of an electromagnetic actuator that may be placed into the RW niche was demonstrated but requires further optimization in terms of THD and static force sensitivity.

MEIS1 is a developmental transcription factor linked to restless legs syndrome (RLS) in genome-wide association studies. RLS is a movement disorder leading to severe sleep reduction and with significant impact on the quality-of-life of patients. In genome-wide association studies, MEIS1 has consistently been the gene with the highest effect size and functional studies suggest a disease-relevant downregulation. Therefore, haploinsufficiency of Meis1 could be the most potential system for modeling RLS in animals. We used heterozygous Meis1 knock-out mice to study the effects of Meis1 haploinsufficiency on mouse behavioral and neurological phenotypes, and to relate the findings to human RLS. We exposed the Meis1-deficient mice to assays of motor, sensorimotor and cognitive ability and assessed the effect of a dopaminergic receptor 2/3 agonist commonly used in the treatment of RLS. The mutant mice showed a pattern of circadian hyperactivity, compatible with human RLS. Moreover, we discovered a replicable prepulse inhibition (PPI) deficit in the Meis1-deficient animals. In addition, these mice were hyposensitive to the PPI-reducing effect of the dopaminergic receptor agonist, highlighting a role of Meis1 in the dopaminergic system. Other reported phenotypes include enhanced social recognition at an older age that was not related to alterations in adult olfactory bulb neurogenesis previously shown to be implicated in this behavior. In conclusion, the Meis1-deficient mice fulfill some of the hallmarks of an RLS animal model, and revealed the role of Meis1 in sensorimotor gating and in the dopaminergic systems modulating it.

Objective: To compare the benefit of wireless contralateral routing of signal (CROS) technology to bone-anchored implant (BAI) technology in monaural listeners. Study Design: Prospective, single-subject. Setting: Tertiary academic referral center. Patients: Adult English speaking subjects using either a CROS hearing aid or BAI as treatment for unilateral severe-profound hearing loss. Interventions: Aided performance utilizing the subjects BAI or CROS hearing device. Main Outcome Measures: Outcome measures included speech-in-noise perception using the QuickSIN ™ (Etymotic Research, Elkgrove Village, IL, 2001) speech-in-noise test and localization ability using narrow and broadband stimuli. Performance was measured in the unaided and aided condition and compared with normal hearing controls. Subjective outcomes measures included the Speech Spatial and Qualities hearing scale and the Glasgow Hearing Aid Benefit Profile. Results: A significant improvement in speech-in-noise performance for monaural listeners ( p < 0.0001) was observed, but there was no improvement in localization ability of either CROS or BAI users. There was no significant difference between CROS and BAI subject groups for either outcome measure. BAI recipients demonstrate higher initial disability and handicap over CROS hearing aid users. No significant difference was observed between treatment groups for subjective measures of post-treatment residual disability or satisfaction. Conclusions: Our data demonstrate that both CROS and BAI systems provide significant benefit for monaural listeners. There is no significant difference between CROS or BAI systems for objective measures of speech-in-noise performance. CROS and BAI hearing devices do not provide any localization benefit in the horizontal plane for monaural listeners and there is no significant difference between systems.

The usual technique for measuring vibration within the cochlear partition is heterodyne interferometry. Recently, spectral domain phase microscopy (SDPM) was introduced and offers improvements over standard heterodyne interferometry. In particular, it has a penetration depth of several mm due to working in the infrared range, has narrow and steep optical sectioning due to using a wideband light source, and is able to measure from several cochlear layers simultaneously. However, SDPM is susceptible to systematic error due to “phase leakage,” in which the signal from one layer competes with the signal from other layers. Here, phase leakage is explored in vibration measurements in the cochlea and a model structure. The similarity between phase leakage and signal competition in heterodyne interferometry is demonstrated both experimentally and theoretically. Due to phase leakage, erroneous vibration amplitudes can be reported in regions of low reflectivity that are near structures of high reflectivity. When vibration amplitudes are greater than ∼0.1 of the light source wavelength, phase leakage can cause reported vibration waveforms to be distorted. To aid in the screening of phase leakage in experimental results, the error is plotted and discussed as a function of the important parameters of signal strength and vibration amplitude.

The objective was to determine the effects of a frequency-lowering algorithm (frequency composition, Fcomp) on consonant identification, word-final /s, z/ detection, the intelligibility of sentences in noise, and subjective benefit, for people with high-frequency hearing loss, including people with dead regions (DRs) in the cochlea. A single-blind randomized crossover design was used. Performance with Bernafon Acriva 9 hearing aids was compared with Fcomp off and Fcomp on. Participants wore the hearing aids in each condition in a counterbalanced order. Data were collected after at least 8 weeks of experience with a condition. Outcome measures were audibility, scores from the speech perception tests, and scores from a questionnaire comparing self-perceived hearing ability with Fcomp off and Fcomp on. Ten adults with mild to severe high-frequency hearing loss (seven with extensive DRs, one with patchy or restricted DRs, and two with no DR) were tested. Fcomp improved the audibility of high-frequency sounds for 6 out of 10 participants. There was no overall effect of Fcomp on consonant identification, but the pattern of consonant confusions varied across conditions and participants. For word-final /s, z/ detection, performance was significantly better with Fcomp on than with Fcomp off. Questionnaire scores showed no differences between conditions. In summary, Fcomp improved word-final /s, z/ detection. No benefit was found for the other measures.

The masking release (MR; i.e., better speech recognition in fluctuating compared with continuous noise backgrounds) that is evident for listeners with normal hearing (NH) is generally reduced or absent for listeners with sensorineural hearing impairment (HI). In this study, a real-time signal-processing technique was developed to improve MR in listeners with HI and offer insight into the mechanisms influencing the size of MR. This technique compares short-term and long-term estimates of energy, increases the level of short-term segments whose energy is below the average energy, and normalizes the overall energy of the processed signal to be equivalent to that of the original long-term estimate. This signal-processing algorithm was used to create two types of energy-equalized (EEQ) signals: EEQ1, which operated on the wideband speech plus noise signal, and EEQ4, which operated independently on each of four bands with equal logarithmic width. Consonant identification was tested in backgrounds of continuous and various types of fluctuating speech-shaped Gaussian noise including those with both regularly and irregularly spaced temporal fluctuations. Listeners with HI achieved similar scores for EEQ and the original (unprocessed) stimuli in continuous-noise backgrounds, while superior performance was obtained for the EEQ signals in fluctuating background noises that had regular temporal gaps but not for those with irregularly spaced fluctuations. Thus, in noise backgrounds with regularly spaced temporal fluctuations, the energy-normalized signals led to larger values of MR and higher intelligibility than obtained with unprocessed signals.

In active sensing, animals make motor adjustments to match sensory inputs to specialized neural circuitry. Here, we describe an active sensing system for sound level processing. The pallid bat uses downward frequency-modulated (FM) sweeps as echolocation calls for general orientation and obstacle avoidance. The bat’s auditory cortex contains a region selective for these FM sweeps (FM sweep-selective region, FMSR). We show that the vast majority of FMSR neurons are sensitive and strongly selective for relatively low levels (30-60 dB SPL). Behavioral testing shows that when a flying bat approaches a target, it reduces output call levels to keep echo levels between ∼30 and 55 dB SPL. Thus, the pallid bat behaviorally matches echo levels to an optimized neural representation of sound levels. FMSR neurons are more selective for sound levels of FM sweeps than tones, suggesting that across-frequency integration enhances level tuning. Level-dependent timing of high-frequency sideband inhibition in the receptive field shapes increased level selectivity for FM sweeps. Together with previous studies, these data indicate that the same receptive field properties shape multiple filters (sweep direction, rate, and level) for FM sweeps, a sound common in multiple vocalizations, including human speech. The matched behavioral and neural adaptations for low-intensity echolocation in the pallid bat will facilitate foraging with reduced probability of acoustic detection by prey.

Cochlear hair cells and the stria vascularis are critical for normal hearing. Hair cells transduce mechanical stimuli into electrical signals, whereas the stria is responsible for generating the endocochlear potential (EP), which is the driving force for hair cell mechanotransduction. We questioned whether hair cells and the stria interdepend for survival by using two mouse models. Atoh1 conditional knockout mice, which lose all hair cells within four weeks after birth, were used to determine whether the absence of hair cells would affect function and survival of stria. We showed that stria morphology and EP remained normal for long time despite a complete loss of all hair cells. We then used a mouse model that has an abnormal stria morphology and function due to mutation of the Mitf gene to determine whether hair cells are able to survive and transduce sound signals without a normal electrochemical environment in the endolymph. A strial defect, reflected by missing intermediate cells in the stria and by reduction of EP, led to systematic outer hair cell death from the base to the apex after postnatal day 18. However, an 18-mV EP was sufficient for outer hair cell survival. Surprisingly, inner hair cell survival was less vulnerable to reduction of the EP. Our studies show that normal function of the stria is essential for adult outer hair cell survival, while the survival and normal function of the stria vascularis do not depend on functional hair cells.

Aquaporins (AQPs) are a family of small membrane proteins that transport water molecules across the plasma membrane along the osmotic gradient. Mammals express 13 subtypes of AQPs, including the recently reported "subcellular AQPs", AQP11 and 12. Each organ expresses specific subsets of AQP subtypes, and in the inner ear, AQPs are essential for the establishment and maintenance of two distinct fluids, endolymph and perilymph. To evaluate the contribution of AQPs during the establishment of inner ear function, we used quantitative reverse transcription polymerase chain reaction to quantify the expression levels of all known AQPs during the entire development and maturation of the inner ear. Using systematic and longitudinal quantification, we found that AQP11 was majorly and constantly expressed in the inner ear, and that the expression levels of several AQPs follow characteristic longitudinal patterns: increasing (Aqp0, 1, and 9), decreasing (Aqp6, 8, and 12), and peak of expression on E18 (Aqp2, 5, and 7). In particular, the expression level of Aqp9 increased by 70-fold during P3-P21. We also performed in situ hybridization of Aqp11, and determined the unique localization of Aqp11 in the outer hair cells. Immunohistochemistry of AQP9 revealed its localization in the supporting cells inside the organ of Corti, and in the root cells. The emergence of AQP9 expression in these cells was during P3-P21, which was coincident with the marked increase of its expression level. Combining these quantification and localization data, we discuss the possible contributions of these AQPs to inner ear function.

The matched filter hypothesis proposes that the tuning of auditory sensitivity and the spectral character of calls will match in order to maximize auditory processing efficiency during courtship. In this study, we analyzed the acoustic structure of male calls and both male and female hearing sensitivities in the little torrent frog ( Amolops torrentis ), an anuran species who transmits acoustic signals across streams. The results were in striking contradiction to the matched filter hypothesis. Auditory brainstem response results showed that the best hearing range was 1.6–2 kHz consistent with the best sensitive frequency of most terrestrial lentic taxa, yet completely mismatched with the dominant frequency of conspecific calls (4.3 kHz). Moreover, phonotaxis tests show that females strongly prefer high‐frequency (4.3 kHz) over low‐frequency calls (1.6 kHz) regardless of ambient noise levels, although peripheral auditory sensitivity is highest in the 1.6–2 kHz range. These results are consistent with the idea that A. torrentis evolved from nonstreamside species and that high‐frequency calls evolved under the pressure of stream noise. Our results also suggest that female preferences based on central auditory system characteristics may evolve independently of peripheral auditory system sensitivity in order to maximize communication effectiveness in noisy environments.

Ca2+ signaling has been implicated in the initial pathophysiologic mechanisms underlying the cochlea's response to acoustic overstimulation. Intracellular Ca2+ signaling (ICS) waves, which occur in glia and retinal cells in response to injury to activate cell regulatory pathways, have been proposed as an early event in cochlear injury. Disruption of ICS activity is thought to underlie Connexin 26-associated hearing loss, the most common genetic form of deafness, and downstream sequelae of ICS wave activity, such as MAP kinase pathway activation, have been implicated in noise-induced hearing loss. However, ICS waves have only been observed in neonatal cochlear cultures and are thought to be quiescent after the onset of hearing. In this study, we employ an acute explant model of an adult, hearing cochlea that retains many in vivo physiologic features to investigate Ca2+ changes in response to sound. We find that both slow monotonic changes in intracellular Ca2+ concentration as well as discrete ICS waves occur with acoustic overstimulation. The ICS waves share many intrinsic features with their better-described neonatal counterparts, including ATP and gap-junction dependence, and propagation velocity and distance. This identification of ICS wave activity in the adult, hearing cochlea thus confirms and characterizes an important early detection mechanism for cochlear trauma and provides a target for interventions for noise-induced and Connexin 26-associated hearing loss.

Acoustic environments are composed of complex overlapping sounds that the auditory system is required to segregate into discrete perceptual objects. The functions of distinct auditory processing stations in this challenging task are poorly understood. Here we show a direct role for mouse auditory cortex in detection and segregation of acoustic information. We measured the sensitivity of auditory cortical neurons to brief tones embedded in masking noise. By altering spectrotemporal characteristics of the masker, we reveal that sensitivity to pure tone stimuli is strongly enhanced in coherently modulated broadband noise, corresponding to the psychoacoustic phenomenon comodulation masking release. Improvements in detection were largest following priming periods of noise alone, indicating that cortical segregation is enhanced over time. Transient opsin-mediated silencing of auditory cortex during the priming period almost completely abolished these improvements, suggesting that cortical processing may play a direct and significant role in detection of quiet sounds in noisy environments. SIGNIFICANCE STATEMENT Auditory systems are adept at detecting and segregating competing sound sources, but there is little direct evidence of how this process occurs in the mammalian auditory pathway. We demonstrate that coherent broadband noise enhances signal representation in auditory cortex, and that prolonged exposure to noise is necessary to produce this enhancement. Using optogenetic perturbation to selectively silence auditory cortex during early noise processing, we show that cortical processing plays a crucial role in the segregation of competing sounds.