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Publications using TDT

More than 6,000 published studies have used TDT systems. Find papers by research area, TDT product, species or year.

6,523 papers

PLoS ONE · Sep 2012

Normal hearing sensitivity at low-to-middle frequencies with 34% prestin-charge density (opens in a new tab)

Tetsuji Yamashita, Jie Fang, Jiangang Gao, … Jian Zuo

Abstract

The mammalian outer hair cells (OHCs) provide a positive mechanical feedback to enhance the cochlea's hearing sensitivity and frequency selectivity. Although the OHC-specific, somatic motor protein prestin is required for cochlear amplification, it remains unclear whether prestin can provide sufficient cycle-by-cycle feedback. In cochlear mechanical modeling, varying amounts of OHC motor activity should provide varying degrees of feedback efficiency to adjust the gain of cochlear amplifier at resonant frequencies. Here we created and characterized two new prestin-hypomorphic mouse models with reduced levels of wild-type prestin. OHCs from these mice exhibited length, total elementary charge movement (Q(max)), charge density, and electromotility intermediate between those of wild-type and prestin-null mice. Remarkably, measurements of auditory brainstem responses and distortion product otoacoustic emissions from these mice displayed wild-type like hearing sensitivities at 4-22 kHz. These results indicate that as low as 26.7% Q(max), 34.0% charge density and 44.0% electromotility in OHCs were sufficient for wild-type-like hearing sensitivity in mice at 4-22 kHz, and that these in vitro parameters of OHCs did not correlate linearly with the feedback efficiency for in vivo gain of the cochlear amplifier. Our results thus provide valuable data for modeling cochlear mechanics and will stimulate further mechanistic analysis of the cochlear amplifier.

PLoS ONE · Sep 2012

Muscarinic receptors in amygdala control trace fear conditioning (opens in a new tab)

Amber N. Baysinger, Brianne A. Kent, Thomas H. Brown

Abstract

Intelligent behavior requires transient memory, which entails the ability to retain information over short time periods. A newly-emerging hypothesis posits that endogenous persistent firing (EPF) is the neurophysiological foundation for aspects or types of transient memory. EPF is enabled by the activation of muscarinic acetylcholine receptors (mAChRs) and is triggered by suprathreshold stimulation. EPF occurs in several brain regions, including the lateral amygdala (LA). The present study examined the role of amygdalar mAChRs in trace fear conditioning, a paradigm that requires transient memory. If mAChR-dependent EPF selectively supports transient memory, then blocking amygdalar mAChRs should impair trace conditioning, while sparing delay and context conditioning, which presumably do not rely upon transient memory. To test the EPF hypothesis, LA was bilaterally infused, prior to trace or delay conditioning, with either a mAChR antagonist (scopolamine) or saline. Computerized video analysis quantified the amount of freezing elicited by the cue and by the training context. Scopolamine infusion profoundly reduced freezing in the trace conditioning group but had no significant effect on delay or context conditioning. This pattern of results was uniquely anticipated by the EPF hypothesis. The present findings are discussed in terms of a systems-level theory of how EPF in LA and several other brain regions might help support trace fear conditioning.

PLoS ONE · Sep 2012

Interaural level differences do not suffice for restoring spatial release from masking in simulated cochlear implant listening (opens in a new tab)

Antje Ihlefeld, Ruth Y. Litovsky

Abstract

Spatial release from masking refers to a benefit for speech understanding. It occurs when a target talker and a masker talker are spatially separated. In those cases, speech intelligibility for target speech is typically higher than when both talkers are at the same location. In cochlear implant listeners, spatial release from masking is much reduced or absent compared with normal hearing listeners. Perhaps this reduced spatial release occurs because cochlear implant listeners cannot effectively attend to spatial cues. Three experiments examined factors that may interfere with deploying spatial attention to a target talker masked by another talker. To simulate cochlear implant listening, stimuli were vocoded with two unique features. First, we used 50-Hz low-pass filtered speech envelopes and noise carriers, strongly reducing the possibility of temporal pitch cues; second, co-modulation was imposed on target and masker utterances to enhance perceptual fusion between the two sources. Stimuli were presented over headphones. Experiments 1 and 2 presented high-fidelity spatial cues with unprocessed and vocoded speech. Experiment 3 maintained faithful long-term average interaural level differences but presented scrambled interaural time differences with vocoded speech. Results show a robust spatial release from masking in Experiments 1 and 2, and a greatly reduced spatial release in Experiment 3. Faithful long-term average interaural level differences were insufficient for producing spatial release from masking. This suggests that appropriate interaural time differences are necessary for restoring spatial release from masking, at least for a situation where there are few viable alternative segregation cues.

PLoS ONE · Sep 2012

Plasticity of peripheral auditory frequency sensitivity in Emei music frog (opens in a new tab)

Dian Zhang, Jianguo Cui, Yezhong Tang

RM2RA4PA4ABR/DPOAE
Abstract

In anurans reproductive behavior is strongly seasonal. During the spring, frogs emerge from hibernation and males vocalize for mating or advertising territories. Female frogs have the ability to evaluate the quality of the males' resources on the basis of these vocalizations. Although studies revealed that central single torus semicircularis neurons in frogs exhibit season plasticity, the plasticity of peripheral auditory sensitivity in frog is unknown. In this study the seasonally plasticity of peripheral auditory sensitivity was test in the Emei music frog Babina daunchina, by comparing thresholds and latencies of auditory brainstem responses (ABRs) evoked by tone pips and clicks in the reproductive and non-reproductive seasons. The results show that both ABR thresholds and latency differ significantly between the reproductive and non-reproductive seasons. The thresholds of tone pip evoked ABRs in the non-reproductive season increased significantly about 10 dB than those in the reproductive season for frequencies from 1 KHz to 6 KHz. ABR latencies to waveform valley values for tone pips for the same frequencies using appropriate threshold stimulus levels are longer than those in the reproductive season for frequencies from 1.5 to 6 KHz range, although from 0.2 to 1.5 KHz range it is shorter in the non-reproductive season. These results demonstrated that peripheral auditory frequency sensitivity exhibits seasonal plasticity changes which may be adaptive to seasonal reproductive behavior in frogs.

PLoS ONE · Sep 2012

Prepulse inhibition of acoustic startle reflex as a function of the frequency difference between prepulse and background sounds in mice (opens in a new tab)

Sidhesh Basavaraj, Jun Yan

Abstract

Background: Prepulse inhibition (PPI) depicts the effects of a weak sound preceding strong acoustic stimulus on acoustic startle response (ASR). Previous studies suggest that PPI is influenced by physical parameters of prepulse sound such as intensity and preceding time. The present study characterizes the impact of prepulse tone frequency on PPI. Methods: Seven female C57BL mice were used in the present study. ASR was induced by a 100 dB SPL white noise burst. After assessing the effect of background sounds (white noise and pure tones) on ASR, PPI was tested by using prepulse pure tones with the background tone of either 10 or 18 kHz. The inhibitory effect was assessed by measuring and analyzing the changes in the first peak-to-peak magnitude, root mean square value, duration and latency of the ASR as the function of frequency difference between prepulse and background tones. Results: Our data showed that ASR magnitude with pure tone background varied with tone frequency and was smaller than that with white noise background. Prepulse tone systematically reduced ASR as the function of the difference in frequency between prepulse and background tone. The 0.5 kHz difference appeared to be a prerequisite for inducing substantial ASR inhibition. The frequency dependence of PPI was similar under either a 10 or 18 kHz background tone. Conclusion: PPI is sensitive to frequency information of the prepulse sound. However, the critical factor is not tone frequency itself, but the frequency difference between the prepulse and background tones.

PLoS ONE · Sep 2012

Dissociation of detection and discrimination of pure tones following bilateral lesions of auditory cortex (opens in a new tab)

Andrew R. Dykstra, Christine K. Koh, Louis D. Braida, Mark Jude Tramo

Abstract

It is well known that damage to the peripheral auditory system causes deficits in tone detection as well as pitch and loudness perception across a wide range of frequencies. However, the extent to which to which the auditory cortex plays a critical role in these basic aspects of spectral processing, especially with regard to speech, music, and environmental sound perception, remains unclear. Recent experiments indicate that primary auditory cortex is necessary for the normally-high perceptual acuity exhibited by humans in pure-tone frequency discrimination. The present study assessed whether the auditory cortex plays a similar role in the intensity domain and contrasted its contribution to sensory versus discriminative aspects of intensity processing. We measured intensity thresholds for pure-tone detection and pure-tone loudness discrimination in a population of healthy adults and a middle-aged man with complete or near-complete lesions of the auditory cortex bilaterally. Detection thresholds in his left and right ears were 16 and 7 dB HL, respectively, within clinically-defined normal limits. In contrast, the intensity threshold for monaural loudness discrimination at 1 kHz was 6.5 ± 2.1 dB in the left ear and 6.5 ± 1.9 dB in the right ear at 40 dB sensation level, well above the means of the control population (left ear: 1.6 ± 0.22 dB; right ear: 1.7 ± 0.19 dB). The results indicate that auditory cortex lowers just-noticeable differences for loudness discrimination by approximately 5 dB but is not necessary for tone detection in quiet. Previous human and Old-world monkey experiments employing lesion-effect, neurophysiology, and neuroimaging methods to investigate the role of auditory cortex in intensity processing are reviewed.

Journal of the Association for Research in Otolaryngology · Sep 2012

Auditory nerve frequency tuning measured with forward-masked compound action potentials (opens in a new tab)

Eric Verschooten, Luis Robles, Damir Kovačić, Philip X. Joris

Abstract

Frequency selectivity is a fundamental cochlear property. Recent studies using otoacoustic emissions and psychophysical forward masking suggest that frequency selectivity is sharper in human than in common laboratory species. This has been disputed based on reports using compound action potentials (CAPs), which reflect activity in the auditory nerve and can be measured in humans. Comparative data of CAPs, obtained with a variety of simultaneous masking protocols, have been interpreted to indicate similarity of frequency tuning across mammals and even birds. Unfortunately, there are several issues with the available CAP measurements which hamper a straightforward comparison across species. We investigate sharpness of CAP tuning in cat and chinchilla using a forward masking notched-noise paradigm--which is less confounded by cochlear nonlinearities than simultaneous masking paradigms and similar to what was used in the psychophysical study reporting sharper tuning in humans. Our parametric study, using different probe frequencies and notch widths, shows relationships consistent with those of auditory nerve fibers (ANFs). The sharpness of tuning, quantified by Q(10) factors, is negatively correlated with probe level and increases with probe frequency, but the Q(10) values are generally lower than the average trend for ANFs. Like the single fiber data, tuning for CAPs is sharper in cat than in chinchilla, but the two species are similar in the dependence of tuning on probe frequency and in the relationship between tuning in ANFs and CAP. Growth-of-maskability functions show slopes <1 indicating that with increasing probe level the probe is more susceptible to cochlear compression than the masker. The results support the use of forward-masked CAPs as an alternative measure to estimate ANF tuning and to compare frequency tuning across species.

Ear & Hearing · Sep 2012

Spatial acuity in 2-to-3-year-old children with normal acoustic hearing, unilateral cochlear implants, and bilateral cochlear implants (opens in a new tab)

Tina M. Grieco-Calub, Ruth Y. Litovsky

Abstract

Objectives: : To measure spatial acuity on a right-left discrimination task in 2-to-3-year-old children who use a unilateral cochlear implant (UCI) or bilateral cochlear implants (BICIs); to test the hypothesis that BICI users perform significantly better when they use two CIs than when using a single CI, and that they perform better than the children in the UCI group; to determine how well children with CIs perform compared with children who have normal acoustic hearing (NH); to determine the effect of intensity roving on spatial acuity. Design: : Three groups of children between 26 and 36 months of age participated in this study: 8 children with NH (mean age: 30.9 months), 12 children who use a UCI (mean age: 31.9 months), and 27 children who use BICIs (mean age: 30.7 months). Testing was conducted in a large sound-treated booth with loudspeakers positioned in a horizontal arc with a radius of 1.2 m. The observer-based psychophysical procedure was used to measure the children's ability to identify the hemifield containing the sound source (right versus left). Two methods were used for quantifying spatial acuity, an adaptive-tracking method and a fixed-angle method. In Experiment 1 an adaptive tracking algorithm was used to vary source angle, and the minimum audible angle (MAA), the smallest angle at which right-left discrimination performance is better than chance, was estimated. All three groups participated in Experiment 1. In Experiment 2 source angles were fixed at ±50 degrees, and performance was evaluated by computing the number of SDs above chance. Children in the UCI and BICI groups participated in Experiment 2. Results: : In Experiment 1, when stimulus intensity was roved by 8 dB, MAA thresholds were 3.3 degrees to 30.2 degrees (mean = 14.5 degrees) and 5.7 degrees to 69.6 degrees (mean = 30.9 degrees) in the NH group and in the BICI group, respectively. When the intensity level was fixed for the BICI group, performance did not improve. Within the BICI group, 5 out of 27 children obtained MAA thresholds within one SD of their peers who have NH; all five had >12 months of bilateral listening experience. In Experiment 2, BICIs provided some advantages when the intensity level was fixed. First, the BICI group outperformed the UCI group. Second, children in the BICI group who repeated the task with their 1st CI alone had statistically significantly better performance when using both devices. In addition, when intensity roving was introduced, a larger percentage of children who had 12 or more months of BICI experience continued to perform above chance than children who had <12 months of BICI experience. Taken together, the results suggest that children with BICIs have spatial acuity that is better than when using their first CI alone and than that of their peers who use UCIs. In addition, longer durations of BICI use tend to result in better performance, although this cannot be generalized to all participants. Conclusion: : This report is consistent with a growing body of evidence that spatial-hearing skills can emerge in young children who use BICIs. The observation that these skills are not concomitantly emerging in age- and experience-matched children who use UCIs suggests that BICIs provide cues that are necessary for these spatial-hearing skills that UCIs do not provide.

The Journal of the Acoustical Society of America · Sep 2012

Onset- and offset-specific effects in interaural level difference discrimination (opens in a new tab)

G. Christopher Stecker, Andrew D. Brown

Abstract

The relative sensitivity of human listeners to interaural level differences (ILDs) carried by the onsets, offsets, and interior portions of brief sounds was examined. Stimuli consisted of single 4000-Hz Gabor clicks (Gaussian-windowed tone bursts) or trains of 16 such clicks repeating at an interclick interval (ICI) of 2 or 5 ms. In separate conditions, ILDs favored the right ear by a constant amount for all clicks (condition RRRR) or a changing amount that was maximal at sound onset (condition R000), offset (condition 000R), both onset and offset (condition R00R), or at the temporal midpoint of the stimulus (condition 0RR0). ILD increases and decreases were implemented as linear decibel sweeps across four clicks to minimize transient distortion. Threshold ILDs were determined adaptively for each of these conditions and for single clicks. Thresholds were similar for ILDs presented near sound onset or offset (condition R000 vs 000R) but lower when ILDs were carried by both onset and offset clicks (condition R00R) than for ILDs carried by interior clicks alone (condition 0RR0). The results suggest that similar sensitivity to onset and offset ILD does not reflect uniform temporal weighting; instead, ILD sensitivity favors onsets and offsets over the interior portions of sounds.

The Journal of the Acoustical Society of America · Sep 2012

A correlational method to concurrently measure envelope and temporal fine structure weights: effects of age, cochlear pathology, and spectral shaping (opens in a new tab)

Daniel Fogerty, Larry E. Humes

Abstract

The speech signal may be divided into spectral frequency-bands, each band containing temporal properties of the envelope and fine structure. This study measured the perceptual weights for the envelope and fine structure in each of three frequency bands for sentence materials in young normal-hearing listeners, older normal-hearing listeners, aided older hearing-impaired listeners, and spectrally matched young normal-hearing listeners. The availability of each acoustic property was independently varied through noisy signal extraction. Thus, the full speech stimulus was presented with noise used to mask six different auditory channels. Perceptual weights were determined by correlating a listener’s performance with the signal-to-noise ratio of each acoustic property on a trial-by-trial basis. Results demonstrate that temporal fine structure perceptual weights remain stable across the four listener groups. However, a different weighting typography was observed across the listener groups for envelope cues. Results suggest that spectral shaping used to preserve the audibility of the speech stimulus may alter the allocation of perceptual resources. The relative perceptual weighting of envelope cues may also change with age. Concurrent testing of sentences repeated once on a previous day demonstrated that weighting strategies for all listener groups can change, suggesting an initial stabilization period or susceptibility to auditory training.

The Journal of the Acoustical Society of America · Sep 2012

The relative importance of consonant and vowel segments to the recognition of words and sentences: effects of age and hearing loss (opens in a new tab)

Daniel Fogerty, Diane Kewley-Port, Larry E. Humes

Abstract

This study investigated the ability to use cues contained within vowel and consonant segments by older listeners with normal or impaired hearing. Spectral shaping restored audibility for the hearing-impaired group. Word and sentence materials were processed to contain primarily consonants or vowels by replacing segments with low-level speech-shaped noise. The proportion of the total duration of preserved speech was varied by manipulating the amount of transitional information contained within vowel and consonant segments. Older listeners performed more poorly than young listeners on all conditions except when listening to sentences with only the vowels preserved. Results confirmed a greater contribution to intelligibility of vowel segments in sentences, but not in words, for young normal-hearing, older normal-hearing, and older hearing-impaired listeners. Older listeners received a greater benefit than young listeners from vowels presented in a sentence context. Correlation analyses among the older listeners demonstrated an association between consonant and vowel performance in isolated words but not in sentences. In addition, the use of vowel cues in sentences was relatively independent of age and auditory sensitivity when audibility is ensured. Combined, results argue that older listeners are able to use essential cues carried by vowels for sentence intelligibility.

Hearing Research · Sep 2012

Frequency-specific, location-nonspecific adaptation of interaural time difference sensitivity (opens in a new tab)

Andrew D. Brown, Marina S. Kuznetsova, William J. Spain, G. Christopher Stecker

Abstract

Human listeners' sensitivity to interaural time differences (ITD) was assessed for 1000 Hz tone bursts (500 ms duration) preceded by trains of 500-ms "adapter" tone bursts (7 s total adapter duration, frequencies of 200, 665, 1000, or 1400 Hz) carrying random ITD, or by an equal-duration period of silence. Presentation of the adapter burst train reduced ITD sensitivity in a frequency-specific manner. The observed effect differs from previously described forms of location-specific psychophysical adaptation, as it was produced using a binaurally diffuse sequence of tone bursts (i.e., a location-nonspecific adapter stimulus). Results are discussed in the context of pre-binaural adaptation.

Journal of the Association for Research in Otolaryngology · Aug 2012

Basilar membrane responses to tones and tone complexes: nonlinear effects of stimulus intensity (opens in a new tab)

Corstiaen P. C. Versteegh, Marcel van der Heijden

Abstract

The mammalian inner ear combines spectral analysis of sound with multiband dynamic compression. Cochlear mechanics has mainly been studied using single-tone and tone-pair stimulation. Most natural sounds, however, have wideband spectra. Because the cochlea is strongly nonlinear, wideband responses cannot be predicted by simply adding single-tone responses. We measured responses of the gerbil basilar membrane to single-tone and wideband stimuli and compared them, while focusing on nonlinear aspects of the response. In agreement with previous work, we found that frequency selectivity and its dependence on stimulus intensity were very similar between single-tone and wideband responses. The main difference was a constant shift in effective sound intensity, which was well predicted by a simple gain control scheme. We found expansive nonlinearities in low-frequency responses, which, with increasing frequency, gradually turned into the more familiar compressive nonlinearities. The overall power of distortion products was at least 13 dB below the overall power of the linear response, but in a limited band above the characteristic frequency, the power of distortion products often exceeded the linear response. Our results explain the partial success of a "quasilinear" description of wideband basilar membrane responses, but also indicate its limitations.

PLoS ONE · Aug 2012

Human neural stem cell replacement therapy for amyotrophic lateral sclerosis by spinal transplantation (opens in a new tab)

Michael P. Hefferan, Jan Galik, Osamu Kakinohana, … Martin Marsala

Abstract

Background: Mutation in the ubiquitously expressed cytoplasmic superoxide dismutase (SOD1) causes an inherited form of Amyotrophic Lateral Sclerosis (ALS). Mutant synthesis in motor neurons drives disease onset and early disease progression. Previous experimental studies have shown that spinal grafting of human fetal spinal neural stem cells (hNSCs) into the lumbar spinal cord of SOD1(G93A) rats leads to a moderate therapeutical effect as evidenced by local α-motoneuron sparing and extension of lifespan. The aim of the present study was to analyze the degree of therapeutical effect of hNSCs once grafted into the lumbar spinal ventral horn in presymptomatic immunosuppressed SOD1(G93A) rats and to assess the presence and functional integrity of the descending motor system in symptomatic SOD1(G93A) animals. Methods/principal findings: Presymptomatic SOD1(G93A) rats (60-65 days old) received spinal lumbar injections of hNSCs. After cell grafting, disease onset, disease progression and lifespan were analyzed. In separate symptomatic SOD1(G93A) rats, the presence and functional conductivity of descending motor tracts (corticospinal and rubrospinal) was analyzed by spinal surface recording electrodes after electrical stimulation of the motor cortex. Silver impregnation of lumbar spinal cord sections and descending motor axon counting in plastic spinal cord sections were used to validate morphologically the integrity of descending motor tracts. Grafting of hNSCs into the lumbar spinal cord of SOD1(G93A) rats protected α-motoneurons in the vicinity of grafted cells, provided transient functional improvement, but offered no protection to α-motoneuron pools distant from grafted lumbar segments. Analysis of motor-evoked potentials recorded from the thoracic spinal cord of symptomatic SOD1(G93A) rats showed a near complete loss of descending motor tract conduction, corresponding to a significant (50-65%) loss of large caliber descending motor axons. Conclusions/significance: These data demonstrate that in order to achieve a more clinically-adequate treatment, cell-replacement/gene therapy strategies will likely require both spinal and supraspinal targets.

PLoS ONE · Aug 2012

Inner ear gene transfection in neonatal mice using adeno-associated viral vector: a comparison of two approaches (opens in a new tab)

Li Xia, Shankai Yin, Jian Wang

Abstract

Local gene transfection is a promising technique for the prevention and/or correction of inner ear diseases, particularly those resulting from genetic defects. Adeno-associated virus (AAV) is an ideal viral vector for inner ear gene transfection because of its safety, stability, long-lasting expression, and its high tropism for many different cell types. Recently, a new generation of AAV vectors with a tyrosine mutation (mut-AAV) has demonstrated significant improvement in transfection efficiency. A method for inner ear gene transfection via the intact round window membrane (RWM) has been developed in our laboratory. This method has not been tested in neonatal mice, an important species for the study of inherited hearing loss. Following a preliminary study to optimize the experimental protocol in order to reduce mortality, the present study investigated inner ear gene transfection in mice at postnatal day 7. We compared transfection efficiency, the safety of the scala tympani injection via RWM puncture, and the trans-RWM diffusion following partial digestion with an enzyme technique. The results revealed that approximately 47% of inner hair cells (IHCs) and 17% of outer hair cells (OHCs) were transfected via the trans-RWM approach. Transfection efficiency via RWM puncture (58% and 19% for IHCs and OHCs, respectively) was slightly higher, but the difference was not significant.

Animal Cognition · Aug 2012

Perception of warble song in budgerigars (Melopsittacus undulatus): evidence for special processing (opens in a new tab)

Hsiao-Wei Tu, Robert J. Dooling

Abstract

The long, rambling warble song of male budgerigars is composed of a large number of acoustically complex elements uttered in streams lasting minutes a time and accompanied by various courtship behaviors. Warble song has no obvious sequential structure or patterned repetition of elements, raising questions as to which aspects of it are perceptually salient, whether budgerigars can detect changes in natural warble streams, and to what extent these capabilities are species-specific. Using operant conditioning and a psychophysical paradigm, we examined the sensitivity of budgerigars, canaries, and zebra finches to changes in long (>6 min) natural warble sequences of a male budgerigar. All three species could detect a single insertion of pure tones, zebra finch song syllables, budgerigar contact calls, or warble elements from another budgerigar's warble. In each case, budgerigars were more sensitive to these changes than were canaries or finches. When warble elements from the ongoing warble stream were used as targets and inserted, out of order, into the natural warble stream so that the only cue available was the violation of the natural ordering of warble elements, only budgerigars performed above chance. When the experiment was repeated with all the ongoing warble stream elements presented in random order, the performance of budgerigars fell to chance. These results show species-specific advantages in budgerigars for detecting acoustic changes in natural warble sequences and indicate at least a limited sensitivity to sequential rules governing the structure of their species-specific warble songs.

Cell Death & Disease · Aug 2012

Anti-apoptotic gene Bcl2 is required for stapes development and hearing (opens in a new tab)

M R Carpinelli, A K Wise, B D Arhatari, … R A Burt

Abstract

In this paper we describe novel and specific roles for the apoptotic regulators Bcl2 and Bim in hearing and stapes development. Bcl2 is anti-apoptotic while Bim is pro-apoptotic. Characterization of the auditory systems of mice deficient for these molecules revealed that Bcl2⁻/⁻ mice suffered severe hearing loss. This was conductive in nature and did not affect sensory cells of the inner ear, with cochlear hair cells and neurons present and functional. Bcl2⁻/⁻ mice were found to have a malformed, often monocrural, porous stapes (the small stirrup-shaped bone of the middle ear), but a normally shaped malleus and incus. The deformed stapes was discontinuous with the incus and sometimes fused to the temporal bones. The defect was completely rescued in Bcl2⁻/⁻Bim⁻/⁻ mice and partially rescued in Bcl2⁻/⁻Bim⁺/⁻ mice, which displayed high-frequency hearing loss and thickening of the stapes anterior crus. The Bcl2⁻/⁻ defect arose in utero before or during the cartilage stage of stapes development. These results implicate Bcl2 and Bim in regulating survival of second pharyngeal arch or neural crest cells that give rise to the stapes during embryonic development.

Journal of the Association for Research in Otolaryngology · Aug 2012

Level-dependent changes in perception of speech envelope cues (opens in a new tab)

Judy R. Dubno, Jayne B. Ahlstrom, Xin Wang, Amy R. Horwitz

Abstract

Level-dependent changes in temporal envelope fluctuations in speech and related changes in speech recognition may reveal effects of basilar-membrane nonlinearities. As a result of compression in the basilar-membrane response, the "effective" magnitude of envelope fluctuations may be reduced as speech level increases from lower level (more linear) to mid-level (more compressive) regions. With further increases to a more linear region, speech envelope fluctuations may become more pronounced. To assess these effects, recognition of consonants and key words in sentences was measured as a function of speech level for younger adults with normal hearing. Consonant-vowel syllables and sentences were spectrally degraded using "noise vocoder" processing to maximize perceptual effects of changes to the speech envelope. Broadband noise at a fixed signal-to-noise ratio maintained constant audibility as speech level increased. Results revealed significant increases in scores and envelope-dependent feature transmission from 45 to 60 dB SPL and decreasing scores and feature transmission from 60 to 85 dB SPL. This quadratic pattern, with speech recognition maximized at mid levels and poorer at lower and higher levels, is consistent with a role of cochlear nonlinearities in perception of speech envelope cues.

Journal of the Association for Research in Otolaryngology · Aug 2012

Brainstem auditory evoked potentials suggest a role for the ventral cochlear nucleus in tinnitus (opens in a new tab)

Jianwen Wendy Gu, Barbara S. Herrmann, Robert A. Levine, Jennifer R. Melcher

Abstract

Numerous studies have demonstrated elevated spontaneous and sound-evoked brainstem activity in animal models of tinnitus, but data on brainstem function in people with this common clinical condition are sparse. Here, auditory nerve and brainstem function in response to sound was assessed via auditory brainstem responses (ABR) in humans with tinnitus and without. Tinnitus subjects showed reduced wave I amplitude (indicating reduced auditory nerve activity) but enhanced wave V (reflecting elevated input to the inferior colliculi) compared with non-tinnitus subjects matched in age, sex, and pure-tone threshold. The transformation from reduced peripheral activity to central hyperactivity in the tinnitus group was especially apparent in the V/I and III/I amplitude ratios. Compared with a third cohort of younger, non-tinnitus subjects, both tinnitus, and matched, non-tinnitus groups showed elevated thresholds above 4 kHz and reduced wave I amplitude, indicating that the differences between tinnitus and matched non-tinnitus subjects occurred against a backdrop of shared peripheral dysfunction that, while not tinnitus specific, cannot be discounted as a factor in tinnitus development. Animal lesion and human neuroanatomical data combine to indicate that waves III and V in humans reflect activity in a pathway originating in the ventral cochlear nucleus (VCN) and with spherical bushy cells (SBC) in particular. We conclude that the elevated III/I and V/I amplitude ratios in tinnitus subjects reflect disproportionately high activity in the SBC pathway for a given amount of peripheral input. The results imply a role for the VCN in tinnitus and suggest the SBC pathway as a target for tinnitus treatment.

Hearing Research · Aug 2012

Deiters cells tread a narrow path–the Deiters cells-basilar membrane junction (opens in a new tab)

Arya Parsa, Paul Webster, Federico Kalinec

Abstract

Deiters cells extend from the basilar membrane to the reticular lamina and, together with pillar cells and outer hair cells, structurally define the micro-architecture of the organ of Corti. Studying vibrotome sections of the mouse organ of Corti with confocal and scanning electron microscopy we found that the basal pole of every Deiters cell, independently of their position in the organ of Corti and along the cochlear spiral, attached to the basilar membrane within a 15.1 ± 0.3 μm-wide stripe running the length of the cochlear spiral adjacent to the row of outer pillar cells. All Deiters cells' basal poles had similar diameter and general morphology, and distributed on the stripe in a precise arrangement with a center-to-center distance of 7.1 ± 0.3 μm between neighbor cells of the same row and 5.9 ± 0.4 μm for neighbor cells in adjacent rows. Complete detachment of Deiters cells revealed an elliptical imprint on the top surface of the basilar membrane consisting of a smaller central structure with a very smooth surface surrounded by a rougher area, suggesting the presence of two different anchoring junctions. These previously unidentified morphological features of Deiters cells could be critical for the mechanical response of the organ of Corti.