Journal of the Association for Research in Otolaryngology 2021-02-16

Forward and Reverse Middle Ear Transmission in Gerbil with a Normal or Spontaneously Healed Tympanic Membrane

X Lin,SWF Meenderink,G Stomackin,TT Jung,GK Martin,W Dong

Publication date 16-02-2021


Tympanic membranes (TM) that have healed spontaneously after perforation present abnormalities in their structural and mechanical properties; i.e., they are thickened and abnormally dense. These changes result in a deterioration of middle ear (ME) sound transmission, which is clinically presented as a conductive hearing loss (CHL). To fully understand the ME sound transmission under TM pathological conditions, we created a gerbil model with a controlled 50% pars tensa perforation, which was left to heal spontaneously for up to 4 weeks (TM perforations had fully sealed after 2 weeks). After the recovery period, the ME sound transmission, both in the forward and reverse directions, was directly measured with two-tone stimulation. Measurements were performed at the input, the ossicular chain, and output of the ME system, i.e., at the TM, umbo, and scala vestibuli (SV) next to the stapes. We found that variations in ME transmission in forward and reverse directions were not symmetric. In the forward direction, the ME pressure gain decreased in a frequency-dependent manner, with smaller loss (within 10 dB) at low frequencies and more dramatic loss at high frequency regions. The loss pattern was mainly from the less efficient acoustical to mechanical coupling between the TM and umbo, with little changes along the ossicular chain. In the reverse direction, the variations in these ears are relatively smaller. Our results provide detailed functional observations that explain CHL seen in clinical patients with abnormal TM, e.g., caused by otitis media, that have healed spontaneously after perforation or post-tympanoplasty, especially at high frequencies. In addition, our data demonstrate that changes in distortion product otoacoustic emissions (DPOAEs) result from altered ME transmission in both the forward and reverse direction by a reduction of the effective stimulus levels and less efficient transfer of DPs from the ME into the ear canal. This confirms that DPOAEs can be used to assess both the health of the cochlea and the middle ear.

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Transient Delivery of a\xa0KCNQ2/3-Specific Channel Activator 1 Week After Noise Trauma Mitigates Noise-Induced Tinnitus

L Marinos,S Kouvaros,B Bizup,B Hambach,P Wipf,T Tzounopoulos

Publication date 11-02-2021


Exposure to loud noise can cause hearing loss and tinnitus in mice and humans. In mice, one major underlying mechanism of noise-induced tinnitus is hyperactivity of auditory brainstem neurons, due at least in part, to decreased Kv7.2/3 (KCNQ2/3) potassium channel activity. In our previous studies, we used a reflex-based mouse model of tinnitus and showed that administration of a non-specific KCNQ channel activator, immediately after noise trauma, prevented the development of noise-induced tinnitus, assessed 1 week after trauma. Subsequently, we developed RL-81, a very potent and highly specific activator of KCNQ2/3 channels. Here, to test the timing window within which RL-81 prevents tinnitus in mice, we modified and employed an operant animal model of tinnitus, where mice are trained to move in response to sound but not move in silence. Mice with behavioral evidence of tinnitus are expected to move in silence. We validated this mouse model by testing the effect of salicylate, which is known to induce tinnitus. We found that transient administration of RL-81 1 week after noise exposure did not affect hearing loss but reduced significantly the percentage of mice with behavioral evidence of tinnitus, assessed 2 weeks after noise exposure. Our results indicate that RL-81 is a promising drug candidate for further development for the treatment of noise-induced tinnitus.

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Sensitivity to Pulse Phase Duration as a Marker of Neural Health Across Cochlear Implant Recipients and Electrodes

N Zhou,Z Zhu,L Dong,J Galvin

Publication date 08-02-2021


In cochlear implants, loudness has been shown to grow more slowly with increasing pulse phase duration (PPD) than with pulse amplitude (PA), possibly due to “leaky” charge integration. This leakiness has been recently quantified in terms of “charge integration efficiency,” defined as the log difference between the PPD dynamic range and PA dynamic range (both expressed in charge units), relative to a common threshold anchor. Such leakiness may differ across electrodes and/or test ears, and may reflect underlying neural health. In this study, we examined the across-site variation of charge integration in recipients of Cochlear© devices. PPD and PA dynamic ranges were measured relative to two threshold anchors with either a 25- or 50-microsecond PPD. Strength-duration functions, previously shown to relate to survival of spiral ganglion cells and peripheral processes, were compared to charge integration efficiency on selected electrodes. Results showed no significant or systematic relationship between the across-site variation in charge integration efficiency and electrode position or threshold levels. Charge integration efficiency was poorer with the 50-μs threshold anchor, suggesting that greater leakiness was associated with larger PPD dynamic ranges. Poorer and more variable charge integration efficiency across electrodes was associated with longer duration of any hearing loss, consistent with the idea that poor integration is related to neural degeneration. More variable integration efficiency was also associated with poorer speech recognition performance across test ears. The slopes of the strength-duration functions at maximum acceptable loudness were significantly correlated with charge integration efficiency. However, the strength-duration slopes were not predictive of duration of any hearing loss or speech recognition performance in our participants. As such, charge integration efficiency may be a better candidate to measure leakiness in neural populations across the electrode array, as well as the general health of the auditory nerve in human cochlear implant recipients.

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Residual Hair Cell Responses in Electric-Acoustic Stimulation Cochlear Implant Users with Complete Loss of Acoustic Hearing After Implantation

VD Tejani,JS Kim,JJ Oleson,PJ Abbas,CJ Brown,MR Hansen,BJ Gantz

Publication date 04-02-2021


Changes in cochlear implant (CI) design and surgical techniques have enabled the preservation of residual acoustic hearing in the implanted ear. While most Nucleus Hybrid L24 CI users retain significant acoustic hearing years after surgery, 6–17 % experience a complete loss of acoustic hearing (Roland et al. Laryngoscope. 126(1):175-81. (2016), Laryngoscope. 128(8):1939-1945 (2018); Scheperle et al. Hear Res. 350:45-57 (2017)). Electrocochleography (ECoG) enables non-invasive monitoring of peripheral auditory function and may provide insight into the pathophysiology of hearing loss. The ECoG response is evoked using an acoustic stimulus and includes contributions from the hair cells (cochlear microphonic—CM) as well as the auditory nerve (auditory nerve neurophonic—ANN). Seven Hybrid L24 CI users with complete loss of residual hearing months after surgery underwent ECoG measures before and after loss of hearing. While significant reductions in CMs were evident after hearing loss, all participants had measurable CMs despite having no measurable acoustic hearing. None retained measurable ANNs. Given histological data suggesting stable hair cell and neural counts after hearing loss (e.g., Quesnel et al. Hear Res. 333:225-234. (2016)), the loss of ECoG and audiometric hearing may reflect reduced synaptic input. This is consistent with the theory that residual CM responses coupled with little to no ANN responses reflect a “disconnect” between hair cells and auditory nerve fibers (Fontenot et al. Ear Hear. 40(3):577-591. 2019). This “disconnection” may prevent proper encoding of auditory stimulation at higher auditory pathways, leading to a lack of audiometric responses, even in the presence of viable cochlear hair cells.

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Effects of Kainic Acid-Induced Auditory Nerve Damage on Envelope-Following Responses in the Budgerigar ( Melopsittacus undulatus )

JL Wilson,KS Abrams,KS Henry

Publication date 01-02-2021


Sensorineural hearing loss is a prevalent problem that adversely impacts quality of life by compromising interpersonal communication. While hair cell damage is readily detectable with the clinical audiogram, this traditional diagnostic tool appears inadequate to detect lost afferent connections between inner hair cells and auditory nerve (AN) fibers, known as cochlear synaptopathy. The envelope-following response (EFR) is a scalp-recorded response to amplitude modulation, a critical acoustic feature of speech. Because EFRs can have greater amplitude than wave I of the auditory brainstem response (ABR; i.e., the AN-generated component) in humans, the EFR may provide a more sensitive way to detect cochlear synaptopathy. We explored the effects of kainate- (kainic acid) induced excitotoxic AN injury on EFRs and ABRs in the budgerigar (Melopsittacus undulatus), a parakeet species used in studies of complex sound discrimination. Kainate reduced ABR wave I by 65–75 % across animals while leaving otoacoustic emissions unaffected or mildly enhanced, consistent with substantial and selective AN synaptic loss. Compared to wave I loss, EFRs showed similar or greater percent reduction following kainate for amplitude-modulation frequencies from 380 to 940 Hz and slightly less reduction from 80 to 120 Hz. In contrast, forebrain-generated middle latency responses showed no consistent change post-kainate, potentially due to elevated “central gain” in the time period following AN damage. EFR reduction in all modulation frequency ranges was highly correlated with wave I reduction, though within-animal effect sizes were greater for higher modulation frequencies. These results suggest that even low-frequency EFRs generated primarily by central auditory nuclei might provide a useful noninvasive tool for detecting synaptic injury clinically.

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Noninvasive Measures of Distorted Tonotopic Speech Coding Following Noise-Induced Hearing Loss

S Parida,MG Heinz

Publication date 01-02-2021


Animal models of noise-induced hearing loss (NIHL) show a dramatic mismatch between cochlear characteristic frequency (CF, based on place of innervation) and the dominant response frequency in single auditory-nerve-fiber responses to broadband sounds (i.e., distorted tonotopy, DT). This noise trauma effect is associated with decreased frequency-tuning-curve (FTC) tip-to-tail ratio, which results from decreased tip sensitivity and enhanced tail sensitivity. Notably, DT is more severe for noise trauma than for metabolic (e.g., age-related) losses of comparable degree, suggesting that individual differences in DT may contribute to speech intelligibility differences in patients with similar audiograms. Although DT has implications for many neural-coding theories for real-world sounds, it has primarily been explored in single-neuron studies that are not viable with humans. Thus, there are no noninvasive measures to detect DT. Here, frequency following responses (FFRs) to a conversational speech sentence were recorded in anesthetized male chinchillas with either normal hearing or NIHL. Tonotopic sources of FFR envelope and temporal fine structure (TFS) were evaluated in normal-hearing chinchillas. Results suggest that FFR envelope primarily reflects activity from high-frequency neurons, whereas FFR-TFS receives broad tonotopic contributions. Representation of low- and high-frequency speech power in FFRs was also assessed. FFRs in hearing-impaired animals were dominated by low-frequency stimulus power, consistent with oversensitivity of high-frequency neurons to low-frequency power. These results suggest that DT can be diagnosed noninvasively. A normalized DT metric computed from speech FFRs provides a potential diagnostic tool to test for DT in humans. A sensitive noninvasive DT metric could be used to evaluate perceptual consequences of DT and to optimize hearing-aid amplification strategies to improve tonotopic coding for hearing-impaired listeners.

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Interpreting the Effect of Stimulus Parameters on the Electrically Evoked Compound Action Potential and on Neural Health Estimates

T Brochier,CM McKay,RP Carlyon

Publication date 01-02-2021


Variations in the condition of the neural population along the length of the cochlea can degrade the spectral and temporal representation of sounds conveyed by CIs, thereby limiting speech perception. One measurement that has been proposed as an estimate of neural survival (the number of remaining functional neurons) or neural health (the health of those remaining neurons) is the effect of stimulation parameters, such as the interphase gap (IPG), on the amplitude growth function (AGF) of the electrically evoked compound action potential (ECAP). The extent to which such measures reflect neural factors, rather than non-neural factors (e.g. electrode orientation, electrode-modiolus distance, and impedance), depends crucially upon how the AGF data are analysed. However, there is currently no consensus in the literature for the correct method to interpret changes in the ECAP AGF due to changes in stimulation parameters. We present a simple theoretical model for the effect of IPG on ECAP AGFs, along with a re-analysis of both animal and human data that measured the IPG effect. Both the theoretical model and the re-analysis of the animal data suggest that the IPG effect on ECAP AGF slope (IPG slope effect), measured using either a linear or logarithmic input-output scale, does not successfully control for the effects of non-neural factors. Both the model and the data suggest that the appropriate method to estimate neural health is by measuring the IPG offset effect, defined as the dB offset between the linear portions of ECAP AGFs for two stimuli differing only in IPG.

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Acoustic Trauma Increases Ribbon Number and Size in Outer Hair Cells of the Mouse Cochlea

MB Wood,N Nowak,K Mull,A Goldring,M Lehar,PA Fuchs

Publication date 01-02-2021


Outer hair cells (OHCs) in the mouse cochlea are contacted by up to three type II afferent boutons. On average, only half of these are postsynaptic to presynaptic ribbons. Mice of both sexes were subjected to acoustic trauma that produced a threshold shift of 44.2 ± 9.1 dB 7 days after exposure. Ribbon synapses of OHCs were quantified in post-trauma and littermate controls using immunolabeling of CtBP2. Visualization with virtual reality was used to determine 3-D cytoplasmic localization of CtBP2 puncta to the synaptic pole of OHCs. Acoustic trauma was associated with a statistically significant increase in the number of synaptic ribbons per OHC. Serial section TEM was carried out on similarly treated mice. This also showed a significant increase in the number of ribbons in post-trauma OHCs, as well as a significant increase in ribbon volume compared to ribbons in control OHCs. An increase in OHC ribbon synapses after acoustic trauma is a novel observation that has implications for OHC:type II afferent signaling. A mathematical model showed that the observed increase in OHC ribbons considered alone could produce a significant increase in action potentials among type II afferent neurons during strong acoustic stimulation.

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Evaluating and Comparing Behavioural and Electrophysiological Estimates of Neural Health in Cochlear Implant Users

T Brochier,F Guérit,JM Deeks,C Garcia,M Bance,RP Carlyon

Publication date 01-02-2021


Variations in neural health along the cochlea can degrade the spectral and temporal representation of sounds conveyed by cochlear implants (CIs). We evaluated and compared one electrophysiological measure and two behavioural measures that have been proposed as estimates of neural health patterns, in order to explore the extent to which the different measures provide converging and consistent neural health estimates. All measures were obtained from the same 11 users of the Cochlear Corporation CI. The two behavioural measures were multipulse integration (MPI) and the polarity effect (PE), both measured on each of seven electrodes per subject. MPI was measured as the difference between thresholds at 80 pps and 1000 pps, and PE as the difference in thresholds between cathodic- and anodic-centred quadraphasic (QP) 80-pps pulse trains. It has been proposed that good neural health corresponds to a large MPI and to a large negative PE (lower thresholds for cathodic than anodic pulses). The electrophysiological measure was the effect of interphase gap (IPG) on the offset of the ECAP amplitude growth function (AGF), which has been correlated with spiral ganglion neuron density in guinea pigs. This ‘IPG offset’ was obtained on the same subset of electrodes used for the behavioural measures. Despite high test–retest reliability, there were no significant correlations between the neural health estimates for either within-subject comparisons across the electrode array, or between-subject comparisons of the means. A phenomenological model of a population of spiral ganglion neurons was then used to investigate physiological mechanisms that might underlie the different neural health estimates. The combined experimental and modelling results provide evidence that PE, MPI and IPG offset may reflect different characteristics of the electrode-neural interface.

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Characterization of the Sheep Round Window Membrane

S Han,H Suzuki-Kerr,M Suwantika,RS Telang,DA Gerneke,PV Anekal,P Bird,SM Vlajkovic,PR Thorne

Publication date 01-02-2021


Intratympanic injection is a clinically used approach to locally deliver therapeutic molecules to the inner ear. Drug diffusion, at least in part, is presumed to occur through the round window membrane (RWM), one of the two openings to the inner ear. Previous studies in human temporal bones have identified a three-layered structure of the RWM with a thickness of 70–100 μm. This is considerably thicker than the RWM in rodents, which are mostly used to model RWM permeability and assess drug uptake. The sheep has been suggested as a large animal model for inner ear research given the similarities in structure and frequency range for hearing. Here, we report the structure of the sheep RWM. The RWM is anchored within the round window niche (average vertical diameter of 2.1 ± 0.3 mm and horizontal diameter of 2.3 ± 0.4 mm) and has a curvature that leans towards the scala tympani. The centre of the RWM is the thinnest (55–71 μm), with increasing thickness towards the edges (< 171 μm), where the RWM forms tight attachments to the surrounding bony niche. The layered RWM structure, including an outer epithelial layer, middle connective tissue and inner epithelial layer, was identified with cellular features such as wavy fibre bundles, melanocytes and blood vessels. An attached “meshwork structure” which extends over the cochlear aqueduct was seen, as in humans. The striking anatomical similarities between sheep and human RWM suggest that sheep may be evaluated as a more appropriate system to predict RWM permeability and drug delivery in humans than rodent models.

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Stem Cells and Gene Therapy in Progressive Hearing Loss: the State of the Art

A Nourbakhsh,BM Colbert,E Nisenbaum,A El-Amraoui,DM Dykxhoorn,KR Koehler,ZY Chen,XZ Liu

Publication date 28-01-2021


Progressive non-syndromic sensorineural hearing loss (PNSHL) is the most common cause of sensory impairment, affecting more than a third of individuals over the age of 65. PNSHL includes noise-induced hearing loss (NIHL) and inherited forms of deafness, among which is delayed-onset autosomal dominant hearing loss (AD PNSHL). PNSHL is a prime candidate for genetic therapies due to the fact that PNSHL has been studied extensively, and there is a potentially wide window between identification of the disorder and the onset of hearing loss. Several gene therapy strategies exist that show potential for targeting PNSHL, including viral and non-viral approaches, and gene editing versus gene-modulating approaches. To fully explore the potential of these therapy strategies, a faithful in vitro model of the human inner ear is needed. Such models may come from induced pluripotent stem cells (iPSCs). The development of new treatment modalities by combining iPSC modeling with novel and innovative gene therapy approaches will pave the way for future applications leading to improved quality of life for many affected individuals and their families.

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Using Interleaved Stimulation to Measure the Size and Selectivity of the Sustained Phase-Locked Neural Response to Cochlear Implant Stimulation

RP Carlyon,F Guérit,JM Deeks,A Harland,R Gransier,J Wouters,SR de Rijk,M Bance

Publication date 25-01-2021


We measured the sustained neural response to electrical stimulation by a cochlear implant (CI). To do so, we interleaved two stimuli with frequencies F1 and F2 Hz and recorded a neural distortion response (NDR) at F2-F1 Hz. We show that, because any one time point contains only the F1 or F2 stimulus, the instantaneous nonlinearities typical of electrical artefact should not produce distortion at this frequency. However, if the stimulus is smoothed, such as by charge integration at the nerve membrane, subsequent (neural) nonlinearities can produce a component at F2-F1 Hz. We stimulated a single CI electrode with interleaved sinusoids or interleaved amplitude-modulated pulse trains such that F2 = 1.5F1, and found no evidence for an NDR when F2-F1 was between 90 and 120 Hz. However, interleaved amplitude-modulated pulse trains with F2-F1~40 Hz revealed a substantial NDR with a group delay of about 45 ms, consistent with a thalamic and/or cortical response. The NDR could be measured even from recording electrodes adjacent to the implant and at the highest pulse rates (> 4000 pps) used clinically. We then measured the selectivity of this sustained response by presenting F1 and F2 to different electrodes and at different between-electrode distances. This revealed a broad tuning that, we argue, reflects the overlap between the excitation elicited by the two electrodes. Our results also provide a glimpse of the neural nonlinearity in the auditory system, unaffected by the biomechanical cochlear nonlinearities that accompany acoustic stimulation. Several potential clinical applications of our findings are discussed.

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Self-Reported Sense of Direction and Vestibular Function in the Baltimore Longitudinal Study of Aging (BLSA)

P Gandhi,K Biju,BN Klatt,E Simonsick,Y Agrawal

Publication date 15-01-2021


Sense of direction is an individual’s ability to navigate within an environment and generate a mental map of novel environments. Although sense of direction is correlated with psychometric tests of spatial ability, it also reflects an individual’s real-world spatial ability that is not fully captured by laboratory-based assessments. Sense of direction is known to vary widely in the population and has been shown to decline with age. However, other factors that contribute to an individual’s sense of direction have not been well-characterized. Vestibular impairment has been linked to reduced spatial cognitive ability, which encompasses spatial memory and navigation skills. Several studies have shown that vestibular input is necessary for effective spatial cognition, notably accurate spatial navigation ability. These studies have typically considered laboratory-based spatial navigation assessments; however, the influence of vestibular function on variation in real-world sense of direction is unknown. In this study, we evaluated whether vestibular function is associated with self-reported sense of direction. Participants for this cross-sectional study were recruited from the Baltimore Longitudinal Study of Aging, a longstanding cohort study of healthy aging. In a modified version of the Santa Barbara Sense-of-Direction (SBSOD) Scale, participants rated statements about spatial and navigational abilities. A lower average score indicates poorer self-reported sense of direction. Vestibular function testing included cervical vestibular-evoked myogenic potential (VEMP) to assess saccular function, ocular VEMP to assess utricular function, and the video head-impulse test to assess semicircular canal function based on vestibular ocular reflex. The study sample included 82 participants with mean age of 71.0 (± 16.9) years and mean SBSOD score of 4.95(± 1.07). In a multivariate linear regression model, female sex and bilateral saccular loss were associated with a lower average SBSOD score. These data suggest that vestibular impairment contributes to the known variation in spatial navigation ability.

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Early Physiological and Cellular Indicators of Cisplatin-Induced Ototoxicity

Y Chen,EC Bielefeld,JG Mellott,W Wang,AM Mafi,EN Yamoah,J Bao

Publication date 07-01-2021


Cisplatin chemotherapy often causes permanent hearing loss, which leads to a multifaceted decrease in quality of life. Identification of early cisplatin-induced cochlear damage would greatly improve clinical diagnosis and provide potential drug targets to prevent cisplatin’s ototoxicity. With improved functional and immunocytochemical assays, a recent seminal discovery revealed that synaptic loss between inner hair cells and spiral ganglion neurons is a major form of early cochlear damage induced by noise exposure or aging. This breakthrough discovery prompted the current study to determine early functional, cellular, and molecular changes for cisplatin-induced hearing loss, in part to determine if synapse injury is caused by cisplatin exposure. Cisplatin was delivered in one to three treatment cycles to both male and female mice. After the cisplatin treatment of three cycles, threshold shift was observed across frequencies tested like previous studies. After the treatment of two cycles, beside loss of outer hair cells and an increase in high-frequency hearing thresholds, a significant latency delay of auditory brainstem response wave 1 was observed, including at a frequency region where there were no changes in hearing thresholds. The wave 1 latency delay was detected as early cisplatin-induced ototoxicity after only one cycle of treatment, in which no significant threshold shift was found. In the same mice, mitochondrial loss in the base of the cochlea and declining mitochondrial morphometric health were observed. Thus, we have identified early spiral ganglion-associated functional and cellular changes after cisplatin treatment that precede significant threshold shift.

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Does the “Reticular Lamina Nonlinearity” Contribute to the Basal DPOAE Source?

A Moleti,R Sisto

Publication date 01-12-2020


The spatial extent of the cochlear region that actually contributes to the DPOAE signal measured in the ear canal may be evaluated experimentally using interference tones or computed numerically using nonlinear cochlear models. A nonlinear transmission-line cochlear model is used in this study to evaluate whether the recently reported nonlinear behavior of the reticular lamina (RL) over a wide basal region may be associated with generation of a significant distortion product otoacoustic emission (DPOAE) component. A two-degrees-of-freedom 1-D nonlinear model was used as discussed by Sisto et al. (2019), in which each local element consists of two coupled oscillators, roughly representing the basilar membrane (BM) and the RL. In this model, the RL shows a strongly nonlinear response over a wide region basal to the characteristic place, whereas the BM response is linear outside the narrow peak region. Such a model may be considered as that using the minimal number of degrees of freedom necessary to separately predict the motion of the BM and RL, while preserving important cochlear symmetries, such as the zero-crossing invariance of the impulse response. In the numerical simulations, the RL nonlinearity generates indeed a large intracochlear distortion product source, extended down to very basal cochlear regions. Nevertheless, due to the weak and indirect coupling between the RL motion and the differential fluid pressure in the basal part of the traveling wave path, no significant contribution from this mechanism is predicted by the model to the generation of the DPOAE signal that is eventually measured in the ear canal.

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Effect of the Relative Timing between Same-Polarity Pulses on Thresholds and Loudness in Cochlear Implant Users

F Guérit,J Marozeau,B Epp,RP Carlyon

Publication date 01-12-2020


The effect of the relative timing between pairs of same-polarity monophasic pulses has been studied extensively in single-neuron animal studies and has revealed fundamental properties of the neurons. For human cochlear implant listeners, the requirement to use charge-balanced stimulation and the typical use of symmetric, biphasic pulses limits such measures, because currents of opposite polarities interact at the level of the neural membrane. Here, we propose a paradigm to study same-polarity summation of currents while keeping the stimulation charge-balanced within a short time window. We used pairs of mirrored pseudo-monophasic pulses (a long-low phase followed by a short-high phase for the first pulse and a short-high phase followed by a long-low phase for the second pulse). We assumed that most of the excitation would stem from the two adjacent short-high phases, which had the same polarity. The inter-pulse interval between the short-high phases was varied from 0 to 345 μs. The inter-pulse interval had a significant effect on the perceived loudness, and this effect was consistent with both passive (membrane-related) and active (ion-channel-related) neuronal mechanisms contributing to facilitation. Furthermore, the effect of interval interacted with the polarity of the pulse pairs. At threshold, there was an effect of polarity, but, surprisingly, no effect of interval nor an interaction between the two factors. We discuss possible peripheral origins of these results.

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The Temporal Fine Structure of Background Noise Determines the Benefit of Bimodal Hearing for Recognizing Speech

HC Stronks,JJ Briaire,JHM Frijns

Publication date 01-12-2020


Cochlear implant (CI) users have more difficulty understanding speech in temporally modulated noise than in steady-state (SS) noise. This is thought to be caused by the limited low-frequency information that CIs provide, as well as by the envelope coding in CIs that discards the temporal fine structure (TFS). Contralateral amplification with a hearing aid, referred to as bimodal hearing, can potentially provide CI users with TFS cues to complement the envelope cues provided by the CI signal. In this study, we investigated whether the use of a CI alone provides access to only envelope cues and whether acoustic amplification can provide additional access to TFS cues. To this end, we evaluated speech recognition in bimodal listeners, using SS noise and two amplitude-modulated noise types, namely babble noise and amplitude-modulated steady-state (AMSS) noise. We hypothesized that speech recognition in noise depends on the envelope of the noise, but not on its TFS when listening with a CI. Secondly, we hypothesized that the amount of benefit gained by the addition of a contralateral hearing aid depends on both the envelope and TFS of the noise. The two amplitude-modulated noise types decreased speech recognition more effectively than SS noise. Against expectations, however, we found that babble noise decreased speech recognition more effectively than AMSS noise in the CI-only condition. Therefore, we rejected our hypothesis that TFS is not available to CI users. In line with expectations, we found that the bimodal benefit was highest in babble noise. However, there was no significant difference between the bimodal benefit obtained in SS and AMSS noise. Our results suggest that a CI alone can provide TFS cues and that bimodal benefits in noise depend on TFS, but not on the envelope of the noise.

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Gap Detection Deficits in Chinchillas with Selective Carboplatin-Induced Inner Hair Cell Loss

E Lobarinas,R Salvi,D Ding

Publication date 01-12-2020


Temporal resolution is essential for processing complex auditory information such as speech. In hearing impaired persons, temporal resolution, often assessed by detection of brief gaps in continuous sound stimuli, is typically poorer than in individuals with normal hearing. At low stimulus presentation levels, hearing impaired individuals perform poorly but the deficits are greatly reduced when the sensation level of the stimuli are adjusted to match their normal hearing peers. In the present study, we evaluated the effect of selective inner hair cell loss on gap detection in chinchillas treated with carboplatin, an anticancer drug that selectively damages inner hair cells and afferents in this species. Treatment with carboplatin-induced inner hair cell loss of ~ 70 % but had little effect on audiometric thresholds in quiet and produced no evidence of outer hair cell loss. In contrast, selective inner hair cell loss had a significant effect on gap detection ability across a wide range of presentation levels. These results suggest that gap detection tasks are more sensitive to inner hair cell pathology than audiometric thresholds.

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The Effect of Phantom Stimulation and Pseudomonophasic Pulse Shapes on Pitch Perception by Cochlear Implant Listeners

W Lamping,JM Deeks,J Marozeau,RP Carlyon

Publication date 01-12-2020


It has been suggested that a specialized high-temporal-acuity brainstem pathway can be activated by stimulating more apically in the cochlea than is achieved by cochlear implants (CIs) when programmed with contemporary clinical settings. We performed multiple experiments to test the effect on pitch perception of phantom stimulation and asymmetric current pulses, both supposedly stimulating beyond the most apical electrode of a CI. The two stimulus types were generated using a bipolar electrode pair, composed of the most apical electrode of the array and a neighboring, more basal electrode. Experiment 1 used a pitch-ranking procedure where neural excitation was shifted apically or basally using so-called phantom stimulation. No benefit of apical phantom stimulation was found on the highest rate up to which pitch ranks increased (upper limit), nor on the slopes of the pitch-ranking function above 300 pulses per second (pps). Experiment 2 used the same procedure to study the effects of apical pseudomonophasic pulses, where the locus of excitation was manipulated by changing stimulus polarity. A benefit of apical stimulation was obtained for the slopes above 300 pps. Experiment 3 used an adaptive rate discrimination procedure and found a small but significant benefit of both types of apical stimulation. Overall, the results show some benefit for apical stimulation on temporal pitch processing at high pulse rates but reveal that the effect is smaller and more variable across listeners than suggested by previous research. The results also provide some indication that the benefit of apical stimulation may decline over time since implantation.

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Perceptual Weighting of Binaural Lateralization Cues across Frequency Bands

A Ahrens,SN Joshi,B Epp

Publication date 01-12-2020


The auditory system uses interaural time and level differences (ITD and ILD) as cues to localize and lateralize sounds. The availability of ITDs and ILDs in the auditory system is limited by neural phase-locking and by the head size, respectively. Although the frequency-specific limitations are well known, the relative contribution of ITDs and ILDs in individual frequency bands in broadband stimuli is unknown. To determine these relative contributions, or spectral weights, listeners were asked to lateralize stimuli consisting of eleven simultaneously presented 1-ERB-wide noise bands centered between 442 and 5544 Hz and separated by 1-ERB-wide gaps. Either ITDs or ILDs were varied independently across each noise band, while fixing the other interaural disparity to either 0 dB or 0 μs. The weights were obtained using a multiple linear regression analysis. In a second experiment, the effect of auditory enhancement on the spectral weights was investigated. The enhancement of single noise bands was realized by presenting ten of the noise bands as preceding and following sounds (pre- and post-cursors, respectively). Listeners were asked to lateralize the stimuli as in the first experiment. Results show that in the absence of pre- and post-cursors, only the lowest or highest frequency band received highest weight for ITD and ILD, respectively. Auditory enhancement led to significantly enhanced weights given to the band without the pre- and post-cursor. The weight enhancement could only be observed at low frequencies, when determined with ITD cues and for low and high frequencies for ILDs. Hence, the auditory system seems to be able to change the spectral weighting of binaural information depending on the information content.

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