Journal of the Association for Research in Otolaryngology

Publications in this journal

• Article: Full-Field Thickness Distribution of Human Tympanic Membrane Obtained with Optical Coherence Tomography.

  Sam Van der Jeught, Joris J J Dirckx, Johan R M Aerts, Adrian Bradu, Adrian Gh Podoleanu, Jan A N Buytaert
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  ABSTRACT: The full-field thickness distribution, three-dimensional surface model and general morphological data of six human tympanic membranes are presented. Cross-sectional images were taken perpendicular through the membranes using a high-resolution optical coherence tomography setup. Five normal membranes and one membrane containing a pathological site are included in this study. The thickness varies strongly across each membrane, and a great deal of inter-specimen variability can be seen in the measurement results, though all membranes show similar features in their respective relative thickness distributions. Mean thickness values across the pars tensa ranged between 79 and 97 μm; all membranes were thinnest in the central region between umbo and annular ring (50-70 μm), and thickness increased steeply over a small distance to approximately 100-120 μm when moving from the central region either towards the peripheral rim of the pars tensa or towards the manubrium. Furthermore, a local thickening was noticed in the antero-inferior quadrant of the membranes, and a strong linear correlation was observed between inferior-posterior length and mean thickness of the membrane. These features were combined into a single three-dimensional model to form an averaged representation of the human tympanic membrane. 3D reconstruction of the pathological tympanic membrane shows a structural atrophy with retraction pocket in the inferior portion of the pars tensa. The change of form at the pathological site of the membrane corresponds well with the decreased thickness values that can be measured there.
  Journal of the Association for Research in Otolaryngology 05/2013;
• Article: An Energetic Limit on Spatial Release from Masking.

  Virginia Best, Eric R Thompson, Christine R Mason, Gerald Kidd
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  ABSTRACT: This study tested the hypothesis that energetic masking limits the benefits obtained from spatial separation in multiple-talker listening situations, particularly for listeners with sensorineural hearing loss. A speech target was presented simultaneously with two or four speech maskers. The target was always presented diotically, and the maskers were either presented diotically or dichotically. In dichotic configurations, the maskers were symmetrically placed by introducing interaural time differences (ITDs) or infinitely large interaural level differences (ILDs; monaural presentation). Target-to-masker ratios for 50 % correct were estimated. Thresholds in all separated conditions were poorer in listeners with hearing loss than listeners with normal hearing. Moreover, for a given listener, thresholds were similar for conditions with the same number of talkers per ear (e.g., ILD with four talkers equivalent to ITD with two talkers) and hence the same energetic masking. The results are consistent with the idea that increased energetic masking, rather than a specific spatial deficit, may limit performance for hearing-impaired listeners in spatialized speech mixtures.
  Journal of the Association for Research in Otolaryngology 05/2013;
• Article: Modulation Frequency Discrimination with Modulated and Unmodulated Interference in Normal Hearing and in Cochlear-Implant Users.

  Heather A Kreft, David A Nelson, Andrew J Oxenham
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  ABSTRACT: Differences in fundamental frequency (F0) provide an important cue for segregating simultaneous sounds. Cochlear implants (CIs) transmit F0 information primarily through the periodicity of the temporal envelope of the electrical pulse trains. Successful segregation of sounds with different F0s requires the ability to process multiple F0s simultaneously, but it is unknown whether CI users have this ability. This study measured modulation frequency discrimination thresholds for half-wave rectified sinusoidal envelopes modulated at 115 Hz in CI users and normal-hearing (NH) listeners. The target modulation was presented in isolation or in the presence of an interferer. Discrimination thresholds were strongly affected by the presence of an interferer, even when it was unmodulated and spectrally remote. Interferer modulation increased interference and often led to very high discrimination thresholds, especially when the interfering modulation frequency was lower than that of the target. Introducing a temporal offset between the interferer and the target led to at best modest improvements in performance in CI users and NH listeners. The results suggest no fundamental difference between acoustic and electric hearing in processing single or multiple envelope-based F0s, but confirm that differences in F0 are unlikely to provide a robust cue for perceptual segregation in CI users.
  Journal of the Association for Research in Otolaryngology 04/2013;
• Article: Experimental Study of Vibrations of Gerbil Tympanic Membrane with Closed Middle Ear Cavity.

  Nima Maftoon, W Robert J Funnell, Sam J Daniel, Willem F Decraemer
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  ABSTRACT: The purpose of the present work is to investigate the spatial vibration pattern of the gerbil tympanic membrane (TM) as a function of frequency. In vivo vibration measurements were done at several locations on the pars flaccida and pars tensa, and along the manubrium, on surgically exposed gerbil TMs with closed middle ear cavities. A laser Doppler vibrometer was used to measure motions in response to audio frequency sine sweeps in the ear canal. Data are presented for two different pars flaccida conditions: naturally flat and retracted into the middle ear cavity. Resonance of the flat pars flaccida causes a minimum and a shallow maximum in the displacement magnitude of the manubrium and pars tensa at low frequencies. Compared with a flat pars flaccida, a retracted pars flaccida has much lower displacement magnitudes at low frequencies and does not affect the responses of the other points. All manubrial and pars tensa points show a broad resonance in the range of 1.6 to 2 kHz. Above this resonance, the displacement magnitudes of manubrial points, including the umbo, roll off with substantial irregularities. The manubrial points show an increasing displacement magnitude from the lateral process toward the umbo. Above 5 kHz, phase differences between points along the manubrium start to become more evident, which may indicate flexing of the tip of the manubrium or a change in the vibration mode of the malleus. At low frequencies, points on the posterior side of the pars tensa tend to show larger displacements than those on the anterior side. The simple low-frequency vibration pattern of the pars tensa becomes more complex at higher frequencies, with the breakup occurring at between 1.8 and 2.8 kHz. These observations will be important for the development and validation of middle ear finite-element models for the gerbil.
  Journal of the Association for Research in Otolaryngology 04/2013;
• Article: Behavioral Sensitivity to Broadband Binaural Localization Cues in the Ferret.

  Peter Keating, Fernando R Nodal, Kohilan Gananandan, Andreas L Schulz, Andrew J King
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  ABSTRACT: Although the ferret has become an important model species for studying both fundamental and clinical aspects of spatial hearing, previous behavioral work has focused on studies of sound localization and spatial release from masking in the free field. This makes it difficult to tease apart the role played by different spatial cues. In humans and other species, interaural time differences (ITDs) and interaural level differences (ILDs) play a critical role in sound localization in the azimuthal plane and also facilitate sound source separation in noisy environments. In this study, we used a range of broadband noise stimuli presented via customized earphones to measure ITD and ILD sensitivity in the ferret. Our behavioral data show that ferrets are extremely sensitive to changes in either binaural cue, with levels of performance approximating that found in humans. The measured thresholds were relatively stable despite extensive and prolonged (>16 weeks) testing on ITD and ILD tasks with broadband stimuli. For both cues, sensitivity was reduced at shorter durations. In addition, subtle effects of changing the stimulus envelope were observed on ITD, but not ILD, thresholds. Sensitivity to these cues also differed in other ways. Whereas ILD sensitivity was unaffected by changes in average binaural level or interaural correlation, the same manipulations produced much larger effects on ITD sensitivity, with thresholds declining when either of these parameters was reduced. The binaural sensitivity measured in this study can largely account for the ability of ferrets to localize broadband stimuli in the azimuthal plane. Our results are also broadly consistent with data from humans and confirm the ferret as an excellent experimental model for studying spatial hearing.
  Journal of the Association for Research in Otolaryngology 04/2013;
• Article: Conductive Hearing Loss Induced by Experimental Middle-Ear Effusion in a Chinchilla Model Reveals Impaired Tympanic Membrane-Coupled Ossicular Chain Movement.

  Jennifer L Thornton, Keely M Chevallier, Kanthaiah Koka, Sandra A Gabbard, Daniel Tollin
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  ABSTRACT: Otitis media with effusion (OME) occurs when fluid collects in the middle-ear space behind the tympanic membrane (TM). As a result of this effusion, sounds can become attenuated by as much as 30-40 dB, causing a conductive hearing loss (CHL). However, the exact mechanical cause of the hearing loss remains unclear. Possible causes can include altered compliance of the TM, inefficient movement of the ossicular chain, decreased compliance of the oval window-stapes footplate complex, or altered input to the oval and round window due to conduction of sound energy through middle-ear fluid. Here, we studied the contribution of TM motion and umbo velocity to a CHL caused by middle-ear effusion. Using the chinchilla as an animal model, umbo velocity (V U) and cochlear microphonic (CM) responses were measured simultaneously using sinusoidal tone pip stimuli (125 Hz-12 kHz) before and after filling the middle ear with different volumes (0.5-2.0 mL) of silicone oil (viscosity, 3.5 Poise). Concurrent increases in CM thresholds and decreases in umbo velocity were noted after the middle ear was filled with 1.0 mL or more of fluid. Across animals, completely filling the middle ear with fluid caused 20-40-dB increases in CM thresholds and 15-35-dB attenuations in umbo velocity. Clinic-standard 226-Hz tympanometry was insensitive to fluid-associated changes in CM thresholds until virtually the entire middle-ear cavity had been filled (approximately >1.5 mL). The changes in umbo velocity, CM thresholds, and tympanometry due to experimentally induced OME suggest CHL arises primarily as a result of impaired TM mobility and TM-coupled umbo motion plus additional mechanisms within the middle ear.
  Journal of the Association for Research in Otolaryngology 04/2013;
• Article: Perception of Across-Frequency Asynchrony by Listeners with Cochlear Hearing Loss.

  Magdalena Wojtczak, Jordan A Beim, Christophe Micheyl, Andrew J Oxenham
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  ABSTRACT: Cochlear hearing loss is often associated with broader tuning of the cochlear filters. Cochlear response latencies are dependent on the filter bandwidths, so hearing loss may affect the relationship between latencies across different characteristic frequencies. This prediction was tested by investigating the perception of synchrony between two tones exciting different regions of the cochlea in listeners with hearing loss. Subjective judgments of synchrony were compared with thresholds for asynchrony discrimination in a three-alternative forced-choice task. In contrast to earlier data from normal-hearing (NH) listeners, the synchronous-response functions obtained from the hearing-impaired (HI) listeners differed in patterns of symmetry and often had a very low peak (i.e., maximum proportion of "synchronous" responses). Also in contrast to data from NH listeners, the quantitative and qualitative correspondence between the data from the subjective and the forced-choice tasks was often poor. The results do not provide strong evidence for the influence of changes in cochlear mechanics on the perception of synchrony in HI listeners, and it remains possible that age, independent of hearing loss, plays an important role in temporal synchrony and asynchrony perception.
  Journal of the Association for Research in Otolaryngology 04/2013;
• Article: p27Kip1 Knockdown Induces Proliferation in the Organ of Corti in Culture after Efficient shRNA Lentiviral Transduction.

  Juan C Maass, F Andrés Berndt, José Cánovas, Manuel Kukuljan
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  ABSTRACT: The cells in the organ of Corti do not exhibit spontaneous cell regeneration; hair cells that die after damage are not replaced. Supporting cells can be induced to transdifferentiate into hair cells, but that would deplete their numbers, therefore impairing epithelium physiology. The loss of p27Kip1 function induces proliferation in the organ of Corti, which raises the possibility to integrate it to the strategies to achieve regeneration. Nevertheless, it is not known if the extent of this proliferative potential, as well as its maintenance in postnatal stages, is compatible with providing a basis for eventual therapeutic manipulation. This is due in part to the limited success of approaches to deliver tools to modify gene expression in the auditory epithelium. We tested the hypothesis that the organ of Corti can undergo significant proliferation when efficient manipulation of the expression of regulators of the cell cycle is achieved. Lentiviral vectors were used to transduce all cochlear cell types, with efficiencies around 4 % for hair cells, 43 % in the overall supporting cell population, and 74 % within lesser epithelial ridge (LER) cells. Expression of short hairpin RNA targeting p27Kip1 encoded by the lentiviral vectors led to measurable proliferation in the organ of Corti and increase in LER cells number but not hair cell regeneration. Our results revalidate the use of lentiviral vectors in the study and in the potential therapeutic approaches for inner ear diseases, as well as demonstrate that efficient manipulation of p27Kip1 is sufficient to induce significant proliferation in the postnatal cochlea.
  Journal of the Association for Research in Otolaryngology 04/2013;
• Article: Early Development of Hearing in Zebrafish.

  Zhongmin Lu, Alexandra A Desmidt
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  ABSTRACT: The zebrafish (Danio rerio) has become a valuable vertebrate model for human hearing and balance disorders because it combines powerful genetics, excellent embryology, and exceptional in vivo visualization in one organism. In this study, we investigated auditory function of zebrafish at early developmental stages using the microphonic potential method. This is the first study to report ontogeny of response of hair cells in any fish during the first week post fertilization. The right ear of each zebrafish embedded in agarose was linearly stimulated with a glass probe that was driven by a calibrated piezoelectric actuator. Using beveled micropipettes filled with standard fish saline, extracellular microphonic potentials were recorded from hair cells in the inner ear of zebrafish embryos or larvae in response to 20, 50, 100, and 200-Hz stimulation. Saccular hair cells expressing green fluorescent protein of the transgenic zebrafish from 2 to 7 days post fertilization (dpf) were visualized and quantified using confocal microscopy. The otic vesicles' areas, otoliths' areas, and saccular hair cell count and density increased linearly with age and standard body length. Microphonic responses increased monotonically with stimulus intensity, stimulus frequency, and age of zebrafish. Microphonic threshold at 200 Hz gradually decreased with zebrafish age. The increases in microphonic response and sensitivity correlate with the increases in number and density of hair cells in the saccule. These results enhance our knowledge of early development of auditory function in zebrafish and provide the control data that can be used to evaluate hearing of young zebrafish morphants or mutants.
  Journal of the Association for Research in Otolaryngology 04/2013;
• Article: Direct Recordings from the Auditory Cortex in a Cochlear Implant User.

  Kirill V Nourski, Christine P Etler, John F Brugge, Hiroyuki Oya, Hiroto Kawasaki, Richard A Reale, Paul J Abbas, Carolyn J Brown, Matthew A Howard
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  ABSTRACT: Electrical stimulation of the auditory nerve with a cochlear implant (CI) is the method of choice for treatment of severe-to-profound hearing loss. Understanding how the human auditory cortex responds to CI stimulation is important for advances in stimulation paradigms and rehabilitation strategies. In this study, auditory cortical responses to CI stimulation were recorded intracranially in a neurosurgical patient to examine directly the functional organization of the auditory cortex and compare the findings with those obtained in normal-hearing subjects. The subject was a bilateral CI user with a 20-year history of deafness and refractory epilepsy. As part of the epilepsy treatment, a subdural grid electrode was implanted over the left temporal lobe. Pure tones, click trains, sinusoidal amplitude-modulated noise, and speech were presented via the auxiliary input of the right CI speech processor. Additional experiments were conducted with bilateral CI stimulation. Auditory event-related changes in cortical activity, characterized by the averaged evoked potential and event-related band power, were localized to posterolateral superior temporal gyrus. Responses were stable across recording sessions and were abolished under general anesthesia. Response latency decreased and magnitude increased with increasing stimulus level. More apical intracochlear stimulation yielded the largest responses. Cortical evoked potentials were phase-locked to the temporal modulations of periodic stimuli and speech utterances. Bilateral electrical stimulation resulted in minimal artifact contamination. This study demonstrates the feasibility of intracranial electrophysiological recordings of responses to CI stimulation in a human subject, shows that cortical response properties may be similar to those obtained in normal-hearing individuals, and provides a basis for future comparisons with extracranial recordings.
  Journal of the Association for Research in Otolaryngology 03/2013;
• Article: Detection of Tones and Their Modification by Noise in Nonhuman Primates.

  Margit Dylla, Andrew Hrnicek, Christopher Rice, Ramnarayan Ramachandran
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  ABSTRACT: A fundamental function of the auditory system is to detect important sounds in the presence of other competing environmental sounds. This paper describes behavioral performance in a tone detection task by nonhuman primates (Macaca mulatta) and the modification of the performance by continuous background noise and by sinusoidally amplitude modulating signals or noise. Two monkeys were trained to report detection of tones in a reaction time Go/No-Go task using the method of constant stimuli. The tones spanned a wide range of frequencies and sound levels, and were presented alone or in continuous broadband noise (40 kHz bandwidth). Signal detection theoretic analysis revealed that thresholds to tones were lowest between 8 and 16 kHz, and were higher outside this range. At each frequency, reaction times decreased with increases in tone sound pressure level. The slope of this relationship was higher at frequencies below 1 kHz and was lower for higher frequencies. In continuous broadband noise, tone thresholds increased at the rate of 1 dB/dB of noise for frequencies above 1 kHz. Noise did not change either the reaction times for a given tone sound pressure level or the slopes of the reaction time vs. tone level relationship. Amplitude modulation of tones resulted in reduced threshold for nearly all the frequencies tested. Amplitude modulation of the tone caused thresholds for detection in continuous broadband noise to be changed by smaller amounts relative to the detection of steady-state tones in noise. Amplitude modulation of background noise resulted in reduction of detection thresholds of steady-state tones by an average of 11 dB relative to thresholds in steady-state noise of equivalent mean amplitude. In all cases, the slopes of the reaction time vs. sound level relationship were not modified. These results show that macaques have hearing functions similar to those measured in humans. These studies form the basis for ongoing studies of neural mechanisms of hearing in noisy backgrounds.
  Journal of the Association for Research in Otolaryngology 03/2013;
• Article: White Matter Hyperintensities Predict Low Frequency Hearing in Older Adults.

  Mark A Eckert, Stefanie E Kuchinsky, Kenneth I Vaden, Stephanie L Cute, Maria V Spampinato, Judy R Dubno
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  ABSTRACT: Vascular disease has been proposed as a contributing factor for presbyacusis (age-related hearing loss). While this hypothesis is supported by pathological evidence of vascular decline in post-mortem human and animal studies, evidence in human subjects has been mixed with associations typically reported between a measure of vascular health and low frequency hearing in older women. Given the difficulty of characterizing the in vivo health of the cochlear artery in humans, an estimate of cerebral small vessel disease was used to test the prediction that age-related change in low frequency hearing and not high frequency hearing is related to a global decline in vascular health. We examined the extent to which these associations were specific to women and influenced by a history of high blood pressure in 72 older adults (mean age 67.12 years, SD = 8.79). Probability estimates of periventricular white matter hyperintensities (WMH) from T1- and fluid attenuated T2-weighted magnetic resonance images were significantly associated with a low frequency hearing metric across the sample, which were independent of age, but driven by women and people with a history of high blood pressure. These results support the premise that vascular declines are one mechanism underlying age-related changes in low frequency hearing.
  Journal of the Association for Research in Otolaryngology 03/2013;
• Article: Mechanisms of Tympanic Membrane and Incus Mobility Loss in Acute Otitis Media Model of Guinea Pig.

  Xiying Guan, Rong Z Gan
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  ABSTRACT: Acute otitis media (AOM) is a rapid infection of middle ear due to bacterial or viral invasion. The infection commonly leads to negative pressure and purulent effusion in the middle ear. To identify how these changes affect tympanic membrane (TM) mobility or sound transmission through the middle ear, we hypothesize that pressure, effusion, and structural changes of the middle ear are the main mechanisms of conductive hearing loss in AOM. To test the hypothesis, a guinea pig AOM model was created by injection of Streptococcus pneumoniae. Three days post inoculation, vibration of the TM at umbo in response to input sound in the ear canal was measured at three experimental stages: intact, pressure-released, and effusion-drained AOM ears. The vibration of the incus tip was also measured after the effusion was removed. Results demonstrate that displacement of the TM increased mainly at low frequencies when pressure was released. As the effusion was removed, the TM mobility increased further but did not reach the level of the normal ear at low frequencies. This was caused by middle ear structural changes or adhesions on ossicles in AOM. The structural changes also affected movement of the incus at low and high frequencies. The results provide new evidence for understanding the mechanism of conductive hearing loss in AOM.
  Journal of the Association for Research in Otolaryngology 03/2013;
• Article: Congenital and Prolonged Adult-Onset Deafness Cause Distinct Degradations in Neural ITD Coding with Bilateral Cochlear Implants.

  Kenneth E Hancock, Yoojin Chung, Bertrand Delgutte
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  ABSTRACT: Bilateral cochlear implant (CI) users perform poorly on tasks involving interaural time differences (ITD), which are critical for sound localization and speech reception in noise by normal-hearing listeners. ITD perception with bilateral CI is influenced by age at onset of deafness and duration of deafness. We previously showed that ITD coding in the auditory midbrain is degraded in congenitally deaf white cats (DWC) compared to acutely deafened cats (ADC) with normal auditory development (Hancock et al., J. Neurosci, 30:14068). To determine the relative importance of early onset of deafness and prolonged duration of deafness for abnormal ITD coding in DWC, we recorded from single units in the inferior colliculus of cats deafened as adults 6 months prior to experimentation (long-term deafened cats, LTDC) and compared neural ITD coding between the three deafness models. The incidence of ITD-sensitive neurons was similar in both groups with normal auditory development (LTDC and ADC), but significantly diminished in DWC. In contrast, both groups that experienced prolonged deafness (LTDC and DWC) had broad distributions of best ITDs around the midline, unlike the more focused distributions biased toward contralateral-leading ITDs present in both ADC and normal-hearing animals. The lack of contralateral bias in LTDC and DWC results in reduced sensitivity to changes in ITD within the natural range. The finding that early onset of deafness more severely degrades neural ITD coding than prolonged duration of deafness argues for the importance of fitting deaf children with sound processors that provide reliable ITD cues at an early age.
  Journal of the Association for Research in Otolaryngology 03/2013;
• Article: Behavioral Evidence for Possible Simultaneous Induction of Hyperacusis and Tinnitus Following Intense Sound Exposure.

  G Chen, C Lee, S A Sandridge, H M Butler, N F Manzoor, J A Kaltenbach
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  ABSTRACT: Many human subjects suffering from chronic tinnitus also suffer from hyperacusis, a heightened perception of loudness at moderate to intense sound levels. While numerous studies suggest that animals develop chronic tinnitus following intense noise exposure, it is not yet clear whether sound exposure also induces chronic hyperacusis-like responses in animals. We addressed this question by examining the chronic effects of intense sound exposure on the acoustic startle response (ASR) and its suppression by background noise containing brief gaps. We compared startle amplitudes in intense tone-exposed (10 kHz, 115 dB SPL, 4 h) and age-matched controls at 2-28 weeks post-exposure. While both groups showed similar startle thresholds, exposed animals showed a hyperacusis-like augmentation of ASR at high stimulus levels. Addition of background noise had little effect on ASR in controls but had a strong suppressive effect on startle in exposed animals, indicating a sensitization to background noise. When the background noise contained a gap preceding the startle stimulus, ASR was suppressed in control animals, but exposed animals showed a marked weakening of gap-induced suppression of ASR. This weakening of gap-induced startle suppression is consistent with the interpretation that the gap may have been masked by tinnitus. The associated hyper-responsiveness to startle stimuli presented alone and the sensitization to background noise suggest that hyperacusis may have also been induced. The results indicate that noise exposure leads to increases in the gain of auditory responsiveness and may offer a model of the association of hyperacusis with tinnitus.
  Journal of the Association for Research in Otolaryngology 02/2013;
• Article: Localization in Reverberation with Cochlear Implants : Predicting Performance from Basic Psychophysical Measures.

  Stefan Kerber, Bernhard U Seeber
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  ABSTRACT: Users of bilateral cochlear implants (CIs) experience difficulties localizing sounds in reverberant rooms, even in rooms where normal-hearing listeners would hardly notice the reverberation. We measured the localization ability of seven bilateral CI users listening with their own devices in anechoic space and in a simulated reverberant room. To determine factors affecting performance in reverberant space we measured the sensitivity to interaural time differences (ITDs), interaural level differences (ILDs), and forward masking in the same participants using direct computer control of the electric stimulation in their CIs. Localization performance, quantified by the coefficient of determination r (2) and the root mean squared error, was significantly worse in the reverberant room than in anechoic conditions. Localization performance in the anechoic room, expressed as r (2), was best predicted by subject's sensitivity to ILDs. However, the decrease in localization performance caused by reverberation was better predicted by the sensitivity to envelope ITDs measured on single electrode pairs, with a correlation coefficient of 0.92. The CI users who were highly sensitive to envelope ITDs also better maintained their localization ability in reverberant space. Results in the forward masking task added only marginally to the predictions of localization performance in both environments. The results indicate that envelope ITDs provided by CI processors support localization in reverberant space. Thus, methods that improve perceptual access to envelope ITDs could help improve localization with bilateral CIs in everyday listening situations.
  Journal of the Association for Research in Otolaryngology 02/2013;
• Article: Regenerated Synapses Between Postnatal Hair Cells and Auditory Neurons.

  Mingjie Tong, Aurore Brugeaud, Albert S B Edge
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  ABSTRACT: Regeneration of synaptic connections between hair cells and spiral ganglion neurons would be required to restore hearing after neural loss. Here we demonstrate by immunohistochemistry the appearance of afferent-like cochlear synapses in vitro after co-culture of de-afferented organ of Corti with spiral ganglion neurons from newborn mice. The glutamatergic synaptic complexes at the ribbon synapse of the inner hair cell contain markers for presynaptic ribbons and postsynaptic densities. We found postsynaptic density protein PSD-95 at the contacts between hair cells and spiral ganglion neurons in newly formed synapses in vitro. The postsynaptic proteins were directly facing the CtBP2-positive presynaptic ribbons of the hair cells. BDNF and NT-3 promoted afferent synaptogenesis in vitro. Direct juxtaposition of the postsynaptic densities with the components of the preexisting ribbon synapse indicated that growing fibers recognized components of the presynaptic sites. Initiation of cochlear synaptogenesis appeared to be influenced by glutamate release from the hair cell ribbons at the presynaptic site since the synaptic regeneration was impaired in glutamate vesicular transporter 3 mutant mice. These insights into cochlear synaptogenesis could be relevant to regenerative approaches for neural loss in the cochlea.
  Journal of the Association for Research in Otolaryngology 02/2013;
• Article: Contralateral Efferent Reflex Effects on Threshold and Suprathreshold Psychoacoustical Tuning Curves at Low and High Frequencies.

  Enzo Aguilar, Almudena Eustaquio-Martin, Enrique A Lopez-Poveda
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  ABSTRACT: Medial olivocochlear efferent neurons can control cochlear frequency selectivity and may be activated in a reflexive manner by contralateral sounds. The present study investigated the significance of the contralateral medial olivocochlear reflex (MOCR) on human psychoacoustical tuning curves (PTCs), a behavioral correlate of cochlear tuning curves. PTCs were measured using forward masking in the presence and in the absence of a contralateral white noise, assumed to elicit the MOCR. To assess MOCR effects on apical and basal cochlear regions over a wide range of sound levels, PTCs were measured for probe frequencies of 500 Hz and 4 kHz and for near- and suprathreshold conditions. Results show that the contralateral noise affected the PTCs predominantly at 500 Hz. At near-threshold levels, its effect was obvious only for frequencies in the tails of the PTCs; at suprathreshold levels, its effects were obvious for all frequencies. It was verified that the effects were not due to the contralateral noise activating the middle-ear muscle reflex or changing the postmechanical rate of recovery from forward masking. A phenomenological computer model of forward masking with efferent control was used to explain the data. The model supports the hypothesis that the behavioral results were due to the contralateral noise reducing apical cochlear gain in a frequency- and level-dependent manner consistent with physiological evidence. Altogether, this shows that the contralateral MOCR may be changing apical cochlear responses in natural, binaural listening situations.
  Journal of the Association for Research in Otolaryngology 02/2013;