Otoacoustic Emissions as a Promising Diagnostic Tool for the Early Detection of Mild Hearing Impairment - Technical Advances in Acquisition, Analysis and Modeling

Otoacoustic emissions are a by-product of the active nonlinear amplification mechanism located in the cochlear outer hair cells, which provides high sensitivity and frequency resolution to human hearing. Being intrinsically sensitive to hearing loss at a cochlear level, they represent a promising non-invasive, fast, and objective diagnostic tool. On the other hand, the complexity of their linear and nonlinear generation mechanisms and other confounding physical phenomena (e.g., interference between different otoacoustic components, acoustical resonances in the ear canal, transmission of the middle ear) introduce a large inter-subject variability in their measured levels, which makes it difficult using them as a direct measure of the hearing threshold using commercially available devices. Nonlinear cochlear modeling has been successfully used to understand the complexity of the otoacoustic generation mechanisms, and to design new acquisition and analysis techniques that help disentangling the different components of the otoacoustic response, therefore improving the correlation between measured otoacoustic levels and audiometric thresholds. In particular, nonlinear cochlear modeling was able to effectively describe the complex (amplitude and phase) response of the basilar membrane, and the generation of otoacoustic emissions by two mechanisms, nonlinear distortion and linear reflection by cochlear roughness. Different phase-frequency relations are predicted for the otoacoustic components generated by the two mechanisms, so they can be effectively separated according to their different phase-gradient delay, using an innovative time-frequency domain filtering technique based on the wavelet transform. A brief introduction to these topics and some new theoretical and experimental results are presented and discussed in this study.

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Amplification lags nonlinearity in the recovery from reduced endocochlear potential

10.1101/2020.05.11.089789 ◽

2020 ◽

Author(s):

C. Elliott Strimbu ◽

Yi Wang ◽

Elizabeth S. Olson

Keyword(s):

Hair Cells ◽

Otoacoustic Emissions ◽

Basilar Membrane ◽

Frequency Tuning ◽

Organ Of Corti ◽

Endocochlear Potential ◽

Outer Hair Cells ◽

Frequency Resolution ◽

Operating Condition ◽

Distortion Product

ABSTRACTThe mammalian hearing organ, the cochlea, contains an active amplifier to boost the vibrational response to low level sounds. Hallmarks of this active process are sharp location-dependent frequency tuning and compressive nonlinearity over a wide stimulus range. The amplifier relies on outer hair cell (OHC) generated forces driven in part by the endocochlear potential (EP), the ~ +80 mV potential maintained in scala media, generated by the stria vascularis. We transiently eliminated the EP in vivo by an intravenous injection of furosemide and measured the vibrations of different layers in the cochlea’s organ of Corti using optical coherence tomography. Distortion product otoacoustic emissions (DPOAE) were monitored at the same times. Following the injection, the vibrations of the basilar membrane lost the best frequency (BF) peak and showed broad tuning similar to a passive cochlea. The intra-organ of Corti vibrations measured in the region of the OHCs lost their BF peak and showed low-pass responses, but retained nonlinearity, indicating that OHC electromotility was still operational. Thus, while electromotility is presumably necessary for amplification, its presence is not sufficient for amplification. The BF peak recovered nearly fully within 2 hours, along with a non-monotonic DPOAE recovery that suggests that physical shifts in operating condition are a final step in the recovery process.SIGNIFICANCEThe endocochlear potential, the +80 mV potential difference across the fluid filled compartments of the cochlea, is essential for normal mechanoelectrical transduction, which leads to receptor potentials in the sensory hair cells when they vibrate in response to sound. Intracochlear vibrations are boosted tremendously by an active nonlinear feedback process that endows the cochlea with its healthy sensitivity and frequency resolution. When the endocochlear potential was reduced by an injection of furosemide, the basilar membrane vibrations resembled those of a passive cochlea, with broad tuning and linear scaling. The vibrations in the region of the outer hair cells also lost the tuned peak, but retained nonlinearity at frequencies below the peak, and these sub-BF responses recovered fairly rapidly. Vibration responses at the peak recovered nearly fully over 2 hours. The staged vibration recovery and a similarly staged DPOAE recovery suggests that physical shifts in operating condition are a final step in the process of cochlear recovery.

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DPOAE-Grams in Patients with Acute Tonal Tinnitus

Otolaryngology ◽

10.1016/j.otohns.2004.09.031 ◽

2005 ◽

Vol 132 (4) ◽

pp. 550-553 ◽

Cited By ~ 24

Author(s):

Haralampos Gouveris ◽

Jan Maurer ◽

Wolf Mann

Keyword(s):

Otoacoustic Emissions ◽

Outer Hair Cell ◽

Cell Function ◽

Hearing Threshold ◽

Normal Hearing ◽

Outer Hair Cells ◽

Controlled Study ◽

High Frequency Region ◽

Mean Values ◽

Distortion Products

OBJECTIVE: To investigate cochlear outer hair cell function in patients with acute tonal tinnitus and normal or near-normal hearing threshold. STUDY DESIGN AND SETTING: Prospective controlled study in an academic tertiary health center. Distortion products of otoacoustic emissions (DPOAE)-grams of 32 ears with acute tonal tinnitus and normal hearing or minimal hearing loss were compared with those of 17 healthy nontinnitus ears. RESULTS: Tinnitus ears exhibited relatively increased amplitudes of DPOAE at high frequencies (4-6.3 kHz) when compared with the group of healthy ears and relatively decreased DPOAE amplitudes at middle frequencies (1650-2400 Hz). Statistically significant ( P < 0.01) increased mean values of DPOAE amplitudes were observed only at a frequency of f2 equal to 4.9 kHz. CONCLUSIONS AND SIGNIFICANCE: These findings suggest an altered functional state of the outer hair cells at a selected high-frequency region of the cochlea in ears with acute tonal tinnitus and normal or near-normal hearing threshold.

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Reflex Control of the Human Inner Ear: A Half-Octave Offset in Medial Efferent Feedback That Is Consistent With an Efferent Role in the Control of Masking

Journal of Neurophysiology ◽

10.1152/jn.90925.2008 ◽

2009 ◽

Vol 101 (3) ◽

pp. 1394-1406 ◽

Cited By ~ 59

Author(s):

Watjana Lilaonitkul ◽

John J. Guinan

Keyword(s):

Otoacoustic Emissions ◽

High Sensitivity ◽

Outer Hair Cells ◽

Tuning Curves ◽

Cochlear Amplification ◽

Inhibitory Feedback ◽

Probe Frequency ◽

Medial Olivocochlear ◽

Human Inner Ear

The high sensitivity and frequency selectivity of the mammalian cochlea is due to amplification produced by outer hair cells (OHCs) and controlled by medial olivocochlear (MOC) efferents. Data from animals led to the view that MOC fibers provide frequency-specific inhibitory feedback; however, these studies did not measure intact MOC reflexes. To test whether MOC inhibition is primarily at the frequency that elicits the MOC activity, acoustically elicited MOC effects were quantified in humans by the change in otoacoustic emissions produced by 60-dB SPL tone and half-octave-band noise elicitors at different frequencies relative to a 40-dB SPL, 1-kHz probe tone. On average, all elicitors produced MOC effects that were skewed (elicitor frequencies -1 octave below the probe produced larger effects than those -1 octave above). The largest MOC effects were from elicitors below the probe frequency for contra- and bilateral elicitors but were from elicitors centered at the probe frequency for ipsilateral elicitors. Typically, ipsilateral elicitors produced larger effects than contralateral elicitors and bilateral elicitors produced effects near the ipsi+contra sum. Elicitors at levels down to 30-dB SPL produced similar patterns. Tuning curves (TCs) interpolated from these data were V-shaped with Q10s ∼2. These are sharper than MOC-fiber TCs found near 1 kHz in cats and guinea pigs. Because cochlear amplification is skewed (more below the best frequency of a cochlear region), these data are consistent with an anti-masking role of MOC efferents that reduces masking by reducing the cochlear amplification seen at 1 kHz.

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Relationship Between Behavioral and Stimulus Frequency Otoacoustic Emissions Delay-Based Tuning Estimates

Journal of Speech Language and Hearing Research ◽

10.1044/2020_jslhr-19-00386 ◽

2020 ◽

Vol 63 (6) ◽

pp. 1958-1968

Author(s):

Uzma Shaheen Wilson ◽

Jenna Browning-Kamins ◽

Sriram Boothalingam ◽

Arturo Moleti ◽

Renata Sisto ◽

...

Keyword(s):

Otoacoustic Emissions ◽

Basilar Membrane ◽

Stimulus Frequency ◽

Behavioral Measures ◽

Phase Gradient ◽

Tuning Curves ◽

Stimulus Frequency Otoacoustic Emissions ◽

The Stability ◽

Mechanical Tuning ◽

The Relationship

Purpose The phase delay of stimulus frequency otoacoustic emissions (SFOAEs) has been proposed as a noninvasive, objective, and fast source for estimating cochlear mechanical tuning. However, the implementation of SFOAEs clinically has been thwarted by the gaps in understanding of the stability of SFOAE delay-based tuning estimates and their relationship to behavioral measures of tuning. Therefore, the goals of this study were (a) to investigate the relationship between delay-based tuning estimates from SFOAEs and simultaneously masked psychophysical tuning curves (PTCs) and (b) to assess the across- and within-session repeatability of tuning estimates from behavioral and OAE measures. Method Three sets of behavioral and OAE measurements were collected in 24 normal-hearing, young adults for two probe frequencies, 1 and 4 kHz. For each participant, delay-based tuning estimates were derived from the phase gradient of SFOAEs. SFOAE-based and behavioral estimates of tuning obtained using the fast-swept PTC paradigm were compared within and across sessions. Results In general, tuning estimates were sharper at 4 kHz compared to 1 kHz for both PTCs and SFOAEs. Statistical analyses revealed a significant correlation between SFOAE delay-based tuning and PTCs at 4 kHz, but not 1 kHz. Lastly, SFOAE delay-based tuning estimates showed better intra- and intersession repeatability compared to PTCs. Conclusions SFOAE phase-gradient delays reflect aspects of cochlear mechanical tuning, in that a frequency dependence similar to that of basilar membrane tuning was observed. Furthermore, the significant correlation with PTCs at 4 kHz and the high repeatability of SFOAE-based tuning measures offer promise of an objective, nonbehavioral assay of tuning in human ears.

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All Three Rows of Outer Hair Cells Are Required for Cochlear Amplification

BioMed Research International ◽

10.1155/2015/727434 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

Michio Murakoshi ◽

Sho Suzuki ◽

Hiroshi Wada

Keyword(s):

Hair Cells ◽

Noise Exposure ◽

Dynamic Range ◽

Basilar Membrane ◽

Organ Of Corti ◽

High Sensitivity ◽

Element Model ◽

Outer Hair Cells ◽

Displacement Amplitude ◽

Cochlear Amplification

In the mammalian auditory system, the three rows of outer hair cells (OHCs) located in the cochlea are thought to increase the displacement amplitude of the organ of Corti. This cochlear amplification is thought to contribute to the high sensitivity, wide dynamic range, and sharp frequency selectivity of the hearing system. Recent studies have shown that traumatic stimuli, such as noise exposure and ototoxic acid, cause functional loss of OHCs in one, two, or all three rows. However, the degree of decrease in cochlear amplification caused by such functional losses remains unclear. In the present study, a finite element model of a cross section of the gerbil cochlea was constructed. Then, to determine effects of the functional losses of OHCs on the cochlear amplification, changes in the displacement amplitude of the basilar membrane (BM) due to the functional losses of OHCs were calculated. Results showed that the displacement amplitude of the BM decreases significantly when a single row of OHCs lost its function, suggesting that all three rows of OHCs are required for cochlear amplification.

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Vanilloid Receptors in Hearing: Altered Cochlear Sensitivity by Vanilloids and Expression of TRPV1 in the Organ of Corti

Journal of Neurophysiology ◽

10.1152/jn.00919.2002 ◽

2003 ◽

Vol 90 (1) ◽

pp. 444-455 ◽

Cited By ~ 61

Author(s):

Jiefu Zheng ◽

Chunfu Dai ◽

Peter S. Steyger ◽

Youngki Kim ◽

Zoltan Vass ◽

...

Keyword(s):

Hair Cells ◽

Otoacoustic Emissions ◽

Transient Receptor Potential ◽

Basilar Membrane ◽

Organ Of Corti ◽

Receptor Potential ◽

Compound Action Potential ◽

Outer Hair Cells ◽

Vanilloid Receptors ◽

Cochlear Blood Flow

Capsaicin, the vanilloid that selectively activates vanilloid receptors (VRs) on sensory neurons for noxious perception, has been reported to increase cochlear blood flow (CBF). VR-related receptors have also been found in the inner ear. This study aims to address the question as to whether VRs exist in the organ of Corti and play a role in cochlear physiology. Capsaicin or the more potent VR agonist, resiniferatoxin (RTX), was infused into the scala tympani of guinea pig cochlea, and their effects on cochlear sensitivity were investigated. Capsaicin (20 μM) elevated the threshold of auditory nerve compound action potential and reduced the magnitude of cochlear microphonic and electrically evoked otoacoustic emissions. These effects were reversible and could be blocked by a competitive antagonist, capsazepine. Application of 2 μM RTX resulted in cochlear sensitivity alterations similar to that by capsaicin, which could also be blocked by capsazepine. A desensitization phenomenon was observed in the case of prolonged perfusion with either capsaicin or RTX. Brief increase of CBF by capsaicin was confirmed, and the endocochlear potential was not decreased. Basilar membrane velocity (BM) growth functions near the best frequency and BM tuning were altered by capsaicin. Immunohistochemistry study revealed the presence of vanilloid receptor type 1 of the transient receptor potential channel family in the hair cells and supporting cells of the organ of Corti and the spiral ganglion cells of the cochlea. The results indicate that the main action of capsaicin is on outer hair cells and suggest that VRs in the cochlea play a role in cochlear homeostasis.

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High-Resolution Audiometry: An Automated Method for Hearing Threshold Acquisition with Quality Control

Journal of the American Academy of Audiology ◽

10.3766/jaaa.23.1.4 ◽

2012 ◽

Vol 23 (01) ◽

pp. 036-045

Author(s):

Lin Bian

Keyword(s):

Quality Control ◽

High Resolution ◽

Repeated Measures ◽

Otoacoustic Emissions ◽

Hearing Threshold ◽

Test System ◽

Frequency Resolution ◽

Physiological Measures ◽

Automated Method ◽

Hearing Thresholds

Background: In clinical practice, hearing thresholds are measured at only five to six frequencies at octave intervals. Thus, the audiometric configuration cannot closely reflect the actual status of the auditory structures. In addition, differential diagnosis requires quantitative comparison of behavioral thresholds with physiological measures, such as otoacoustic emissions (OAEs) that are usually measured in higher resolution. Purpose: The purpose of this research was to develop a method to improve the frequency resolution of the audiogram. Research Design: A repeated-measure design was used in the study to evaluate the reliability of the threshold measurements. Study Sample: A total of 16 participants with clinically normal hearing and mild hearing loss were recruited from a population of university students. Intervention: No intervention was involved in the study. Data Collection and Analysis: Custom developed system and software were used for threshold acquisition with quality control (QC). With real-ear calibration and monitoring of test signals, the system provided accurate and individualized measure of hearing thresholds that were determined by an analysis based on signal detection theory (SDT). The reliability of the threshold measure was assessed by correlation and differences between the repeated measures. Results: The audiometric configurations were diverse and unique to each individual ear. The accuracy, within-subject reliability, and between-test repeatability are relatively high. Conclusions: With QC, the high-resolution audiograms can be reliably and accurately measured. Hearing thresholds measured as ear canal sound pressures with higher frequency resolution can provide more customized hearing-aid fitting. The test system may be integrated with other physiological measures, such as OAEs, into a comprehensive evaluative tool.

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Distinct roles of stereociliary links in the nonlinear sound processing and noise resistance of cochlear outer hair cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1920229117 ◽

2020 ◽

Vol 117 (20) ◽

pp. 11109-11117

Author(s):

Woongsu Han ◽

Jeong-Oh Shin ◽

Ji-Hyun Ma ◽

Hyehyun Min ◽

Jinsei Jung ◽

...

Keyword(s):

Hair Cells ◽

Otoacoustic Emissions ◽

Essential Role ◽

High Sensitivity ◽

Outer Hair Cells ◽

Tectorial Membrane ◽

Sound Processing ◽

Mechanoelectrical Transduction ◽

Distortion Product ◽

Membrane Attachment

Outer hair cells (OHCs) play an essential role in hearing by acting as a nonlinear amplifier which helps the cochlea detect sounds with high sensitivity and accuracy. This nonlinear sound processing generates distortion products, which can be measured as distortion-product otoacoustic emissions (DPOAEs). The OHC stereocilia that respond to sound vibrations are connected by three kinds of extracellular links: tip links that connect the taller stereocilia to shorter ones and convey force to the mechanoelectrical transduction channels, tectorial membrane-attachment crowns (TM-ACs) that connect the tallest stereocilia to one another and to the overlying TM, and horizontal top connectors (HTCs) that link adjacent stereocilia. While the tip links have been extensively studied, the roles that the other two types of links play in hearing are much less clear, largely because of a lack of suitable animal models. Here, while analyzing genetic combinations of tubby mice, we encountered models missing both HTCs and TM-ACs or HTCs alone. We found that the tubby mutation causes loss of both HTCs and TM-ACs due to a mislocalization of stereocilin, which results in OHC dysfunction leading to severe hearing loss. Intriguingly, the addition of the modifier allele modifier of tubby hearing 1 in tubby mice selectively rescues the TM-ACs but not the HTCs. Hearing is significantly rescued in these mice with robust DPOAE production, indicating an essential role of the TM-ACs but not the HTCs in normal OHC function. In contrast, the HTCs are required for the resistance of hearing to damage caused by noise stress.

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Micromechanical Responses to Tones in the Auditory Fovea of the Greater Mustached Bat’s Cochlea

Journal of Neurophysiology ◽

10.1152/jn.1999.82.2.676 ◽

1999 ◽

Vol 82 (2) ◽

pp. 676-686 ◽

Cited By ~ 33

Author(s):

I. J. Russell ◽

M. Kössl

Keyword(s):

Otoacoustic Emissions ◽

Basilar Membrane ◽

Outer Hair Cells ◽

Tectorial Membrane ◽

Phase Lag ◽

Insect Wing ◽

Distortion Product ◽

High Stimulus ◽

Membrane Resonance ◽

Echolocation Signal

An extended region of the greater mustached bat’s cochlea, the sparsely innervated (SI) zone, is located just basally to the frequency place of the dominant 61-kHz component of the echolocation signal (CF2). Anatomic adaptations in the SI zone are thought to provide the basis for cochlear resonance to the CF2 echoes and for the extremely sharp tuning throughout the auditory system that allows these bats to detect Doppler shifts in the echoes caused by insect wing beat. We measured basilar membrane (BM) displacements in the SI zone with a laser interferometer and recorded acoustic distortion products at the ear drum at frequencies represented in the SI zone. The basilar membrane in the SI region was tuned both to its characteristic frequency (62–72 kHz) and to the resonance frequency (61–62 kHz). With increasing stimulus levels, the displacement growth functions are compressive curves with initial slopes close to unity, and their properties are consistent with the mammalian cochlear amplifier working at high sound frequencies. The sharp basilar membrane resonance is associated with a phase lag of 180° and with a shift of the peak resonance to lower frequencies for high stimulus levels. Within the range of the resonance, the distortion product otoacoustic emissions, which have been attributed to the resonance of the tectorial membrane in the SI region, are associated with an abrupt phase change of 360°. It is proposed that a standing wave resonance of the tectorial membrane drives the BM in the SI region and that the outer hair cells enhance, fine tune, and control the resonance. In the SI region, cochlear micromechanics appear to be able to work in two different modes: a conventional traveling wave leads to shear displacement between basilar and tectorial membrane and to neuronal excitation for 62–70 kHz. In addition, the SI region responds to 61–62 kHz with a resonance based on standing waves and thus preprocesses signals which are represented more apically in the CF2 region of the cochlea.

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A Cascaded Approach for Correcting Ionospheric Contamination with Large Amplitude in HF Skywave Radars

The Scientific World JOURNAL ◽

10.1155/2014/693872 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9

Author(s):

Yajun Li ◽

Yinsheng Wei ◽

Rujiang Guo ◽

Rongqing Xu ◽

Zhuoqun Wang ◽

...

Keyword(s):

Frequency Distribution ◽

Large Amplitude ◽

Gradient Algorithm ◽

Frequency Resolution ◽

Good Effect ◽

Distribution Method ◽

Phase Gradient ◽

Time Frequency ◽

Phase Perturbation ◽

Time Frequency Distribution

Ionospheric phase perturbation with large amplitude causes broadening sea clutter’s Bragg peaks to overlap each other; the performance of traditional decontamination methods about filtering Bragg peak is poor, which greatly limits the detection performance of HF skywave radars. In view of the ionospheric phase perturbation with large amplitude, this paper proposes a cascaded approach based on improved S-method to correct the ionospheric phase contamination. This approach consists of two correction steps. At the first step, a time-frequency distribution method based on improved S-method is adopted and an optimal detection method is designed to obtain a coarse ionospheric modulation estimation from the time-frequency distribution. At the second correction step, based on the phase gradient algorithm (PGA) is exploited to eliminate the residual contamination. Finally, use the measured data to verify the effectiveness of the method. Simulation results show the time-frequency resolution of this method is high and is not affected by the interference of the cross term; ionospheric phase perturbation with large amplitude can be corrected in low signal-to-noise (SNR); such a cascade correction method has a good effect.

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