Peripheral Auditory System Research Articles

Early growth response protein 1 regulates promoter activity of \u03b1-plasma membrane calcium ATPase 2, a major calcium pump in the brain and auditory system

BackgroundAlong with sodium/calcium (Ca2+) exchangers, plasma membrane Ca2+ ATPases (ATP2Bs) are main regulators of intracellular Ca2+ levels. There are four ATP2B paralogs encoded by four different genes. Atp2b2 encodes the protein pump with the fastest activation, ATP2B2. In mice, the Atp2b2 transcript has several alternate transcriptional start site variants: α, β, µ and δ. These variants are expressed in developmental and tissue specific manners. The α and β Atp2b2 transcripts are equally expressed in the brain. αAtp2b2 is the only transcript found in the outer hair cells of young mice (Silverstein RS, Tempel BL. in Neuroscience 141:245–257, 2006). Mutations in the coding region of the mouse Atp2b2 gene indicate a narrow window for tolerated dysfunction of the ATP2B2 protein, specifically in the auditory system. This highlights the necessity of tight regulation of this gene for normal cell physiology.ResultsAlthough ATP2Bs are important regulators of Ca2+ in many cell types, little is known about their transcriptional regulation. This study identifies the proximal promoter of the αAtp2b2 transcript. Further investigations indicate that ATOH1 and EGR1 modulate promoter activity. Additionally, we report that EGR1 increases endogenous expression of Atp2b2 transcript in two cell lines. Electrophoretic mobility shift assays (EMSA) indicate that EGR1 binds to a specific site in the CpG island of the αAtp2b2 promoter.ConclusionThis study furthers our understanding of Atp2b2 regulation by: (I) elucidating transcriptional regulatory mechanisms for Atp2b2, and (II) identifying transcription factors that modulate expression of Atp2b2 in the brain and peripheral auditory system and (III) allows for future studies modulating gene expression of Atp2b2.

Connectivity and ultrastructure of dopaminergic innervation of the inner ear and auditory efferent system of a vocal fish.

Dopamine (DA) is a conserved modulator of vertebrate neural circuitry, yet our knowledge of its role in peripheral auditory processing is limited to mammals. The present study combines immunohistochemistry, neural tract tracing, and electron microscopy to investigate the origin and synaptic characteristics of DA fibers innervating the inner ear and the hindbrain auditory efferent nucleus in the plainfin midshipman, a vocal fish that relies upon the detection of mate calls for reproductive success. We identify a DA cell group in the diencephalon as a common source for innervation of both the hindbrain auditory efferent nucleus and saccule, the main hearing endorgan of the inner ear. We show that DA terminals in the saccule contain vesicles but transmitter release appears paracrine in nature, due to the apparent lack of synaptic contacts. In contrast, in the hindbrain, DA terminals form traditional synaptic contacts with auditory efferent neuronal cell bodies and dendrites, as well as unlabeled axon terminals, which, in turn, form inhibitory-like synapses on auditory efferent somata. Our results suggest a distinct functional role for brain-derived DA in the direct and indirect modulation of the peripheral auditory system of a vocal nonmammalian vertebrate.

Identifying the Origin of Effects of Contralateral Noise on Transient Evoked Otoacoustic Emissions in Unanesthetized Mice

Descending neural pathways in the mammalian auditory system are known to modulate the function of the peripheral auditory system. These pathways include the medial olivocochlear (MOC) efferent innervation to outer hair cells (OHCs) and the acoustic reflex pathways mediating middle ear muscle (MEM) contractions. Based on measurements in humans (Marks and Siegel, companion paper), we applied a sensitive method to attempt to differentiate MEM and MOC reflexes using contralateral acoustic stimulation in mice under different levels of anesthesia. Separation of these effects is based on the knowledge that OHC-generated transient evoked otoacoustic emissions (TEOAE) are delayed relative to the stimulus, and that the MOC reflex affects the emission through its innervation of OHC. In contrast, the MEM-mediated changes in middle ear reflectance alter both the stimulus (with a short delay) and the emission. Using this approach, time averages to transient stimuli were evaluated to determine if thresholds for a contralateral effect on the delayed emission, indicating potential MOC activation, could be observed in the absence of a change in the stimulus pressure. This outcome was not observed in the majority of cases. There were also no statistically significant differences between MEM and putative MOC thresholds, and variability was high for both thresholds regardless of anesthesia level. Since the two reflex pathways could not be differentiated on the basis of activation thresholds, it was concluded that the MEM reflex dominates changes in TEOAEs induced by contralateral noise. This result complicates the identification of purely MOC-induced changes on OAEs in mice unless the MEM reflex is inactivated surgically or pharmacologically.

An Adaptive Neural Mechanism for Acoustic Motion Perception with Varying Sparsity.

Biological motion-sensitive neural circuits are quite adept in perceiving the relative motion of a relevant stimulus. Motion perception is a fundamental ability in neural sensory processing and crucial in target tracking tasks. Tracking a stimulus entails the ability to perceive its motion, i.e., extracting information about its direction and velocity. Here we focus on auditory motion perception of sound stimuli, which is poorly understood as compared to its visual counterpart. In earlier work we have developed a bio-inspired neural learning mechanism for acoustic motion perception. The mechanism extracts directional information via a model of the peripheral auditory system of lizards. The mechanism uses only this directional information obtained via specific motor behaviour to learn the angular velocity of unoccluded sound stimuli in motion. In nature however the stimulus being tracked may be occluded by artefacts in the environment, such as an escaping prey momentarily disappearing behind a cover of trees. This article extends the earlier work by presenting a comparative investigation of auditory motion perception for unoccluded and occluded tonal sound stimuli with a frequency of 2.2 kHz in both simulation and practice. Three instances of each stimulus are employed, differing in their movement velocities–0.5°/time step, 1.0°/time step and 1.5°/time step. To validate the approach in practice, we implement the proposed neural mechanism on a wheeled mobile robot and evaluate its performance in auditory tracking.

Frogs Exploit Statistical Regularities in Noisy Acoustic Scenes to Solve Cocktail-Party-like Problems

Noise is a ubiquitous source of errors in all forms of communication [1]. Noise-induced errors in speech communication, for example, make it difficult for humans to converse in noisy social settings, a challenge aptly named the "cocktail party problem" [2]. Many nonhuman animals also communicate acoustically in noisy social groups and thus face biologically analogous problems [3]. However, we know little about how the perceptual systems of receivers are evolutionarily adapted to avoid the costs of noise-induced errors in communication. In this study of Cope's gray treefrog (Hyla chrysoscelis; Hylidae), we investigated whether receivers exploit a potential statistical regularity present in noisy acoustic scenes to reduce errors in signal recognition and discrimination. We developed an anatomical/physiological model of the peripheral auditory system to show that temporal correlation in amplitude fluctuations across the frequency spectrum ("comodulation") [4-6] is a feature of the noise generated by large breeding choruses of sexually advertising males. In four psychophysical experiments, we investigated whether females exploit comodulation in background noise to mitigate noise-induced errors in evolutionarily critical mate-choice decisions. Subjects experienced fewer errors in recognizing conspecific calls and in selecting the calls of high-quality mates in the presence of simulated chorus noise that was comodulated. These data show unequivocally, and for the first time, that exploiting statistical regularities present in noisy acoustic scenes is an important biological strategy for solving cocktail-party-like problems in nonhuman animal communication.

Genetic variants in the peripheral auditory system significantly affect adult cochlear implant performance

BackgroundCochlear implantation is an effective habilitation modality for adults with significant hearing loss. However, post-implant performance is variable. A portion of this variance in outcome can be attributed to clinical factors. Recent physiological studies suggest that the health of the spiral ganglion also impacts post-operative cochlear implant outcomes. The goal of this study was to determine whether genetic factors affecting spiral ganglion neurons may be associated with cochlear implant performance. MethodsAdults with post-lingual deafness who underwent cochlear implantation at the University of Iowa were studied. Pre-implantation evaluation included comprehensive genetic testing for genetic diagnosis. A novel score of genetic variants affecting genes with functional effects in the spiral ganglion was calculated. A Z-scored average of up to three post-operative speech perception tests (CNC, HINT, and AzBio) was used to assess outcome. ResultsGenetically determined spiral ganglion health affects cochlear implant outcomes, and when considered in conjunction with clinically determined etiology of deafness, accounts for 18.3% of the variance in postoperative speech recognition outcomes. Cochlear implant recipients with deleterious genetic variants that affect the cochlear sensory organ perform significantly better on tests of speech perception than recipients with deleterious genetic variants that affect the spiral ganglion. ConclusionEtiological diagnosis of deafness including genetic testing is the single largest predictor of postoperative speech outcomes in adult cochlear implant recipients. A detailed understanding of the genetic underpinning of hearing loss will better inform pre-implant counseling. The method presented here should serve as a guide for further research into the molecular physiology of the peripheral auditory system and cochlear implants.

An acoustic key to eight languages/dialects: Factor analyses of critical-band-filtered speech

The peripheral auditory system functions like a frequency analyser, often modelled as a bank of non-overlapping band-pass filters called critical bands; 20 bands are necessary for simulating frequency resolution of the ear within an ordinary frequency range of speech (up to 7,000 Hz). A far smaller number of filters seemed sufficient, however, to re-synthesise intelligible speech sentences with power fluctuations of the speech signals passing through them; nevertheless, the number and frequency ranges of the frequency bands for efficient speech communication are yet unknown. We derived four common frequency bands—covering approximately 50–540, 540–1,700, 1,700–3,300, and above 3,300 Hz—from factor analyses of spectral fluctuations in eight different spoken languages/dialects. The analyses robustly led to three factors common to all languages investigated—the low & mid-high factor related to the two separate frequency ranges of 50–540 and 1,700–3,300 Hz, the mid-low factor the range of 540–1,700 Hz, and the high factor the range above 3,300 Hz—in these different languages/dialects, suggesting a language universal.

The characteristic of lexical tone perception in native Mandarin speakers with mild and moderate sensorineural hearing loss

Objective:To explore the characteristic of lexical tone perception in native-Mandarin speakers with mild to moderate sensorineural hearing loss. Method:Three types of continuum(Tone1/tone2, tone1/tone4 and tone2/tone3) were constructed and each of them includes a 15 stimuli. All speech stimuli in these three continua were resynthesized by applying the Pitch-Synchronous OverLap and Add(PSOLA) method implemented in Praat to the same mandarin syllable, /a/, with a high level tone produced by a female native-mandarin speaker. Twenty-three native-mandarin sensory hearing loss people were recruited for this study and identification task was used to acquire the tonal perceptual data. SPSS 19.0 software was used to get the fitting curves of lexical tone perception. Result:①Each tone perception curves owns the characteristic of categorical perception, including an obvious boundary, a definite intersection and the abrupt performance change at intersection. The tone perception curves were S-shape in SNHL people which were same as that in normal hearing people.②No significant performance difference of each continuum was observed between SNHL and NH in this study(P=0.811 in T1/T2 continuum, P=0.528 in T1/T4 continuum, P=0.555 in T2/T3 continuum). Conclusion:There is the categorical perception of lexical tone identification in native-mandarin sensorineural hearing loss people. The slight damage in peripheral auditory system did not changed characteristic of lexical tone perception.

Self-Assessed Hearing Handicap in Older Adults With Poorer-Than-Predicted Speech Recognition in Noise.

Even older adults with relatively mild hearing loss report hearing handicap, suggesting that hearing handicap is not completely explained by reduced speech audibility. We examined the extent to which self-assessed ratings of hearing handicap using the Hearing Handicap Inventory for the Elderly (HHIE; Ventry & Weinstein, 1982) were significantly associated with measures of speech recognition in noise that controlled for differences in speech audibility. One hundred sixty-two middle-aged and older adults had HHIE total scores that were significantly associated with audibility-adjusted measures of speech recognition for low-context but not high-context sentences. These findings were driven by HHIE items involving negative feelings related to communication difficulties that also captured variance in subjective ratings of effort and frustration that predicted speech recognition. The average pure-tone threshold accounted for some of the variance in the association between the HHIE and audibility-adjusted speech recognition, suggesting an effect of central and peripheral auditory system decline related to elevated thresholds. The accumulation of difficult listening experiences appears to produce a self-assessment of hearing handicap resulting from (a) reduced audibility of stimuli, (b) declines in the central and peripheral auditory system function, and (c) additional individual variation in central nervous system function.

Foreword to the special issue on “Recent studies of the peripheral auditory system.”

Foreword to the special issue on “Recent studies of the peripheral auditory system.”

An overview of the peripheral auditory system

An overview of the peripheral auditory system

Prelingual auditory verbal agnosia, A rare condition

Auditory agnosia, agnosia for speech is a rare condition, caused mostly by stroke, in adults, while in children it is often a sequel of herpes simplex encephalitis or is associated with epilepsy, in Landau–Kleffner syndrome. This article presents a rare case of verbal auditory agnosia as a result of meningoencephalitis, caused probably by herpes simplex virus. The patient's developed encephalitis at the age of 1 year and 4 months. After her recovery, the family noticed the absence of language development. She was initially diagnosed with profound hearing loss, and the hearing aids did not help her. The speech therapy developed her lip-reading skills with a hard-to-understand pronunciation. Later, audiometry showed a nearly normal peripheral auditory system and magnetic resonance imaging revealed the characteristic brain lesions in both the temporal lobes, explaining the patient's evolution. Assessment of children with delayed speech development must consider the central hearing disorders as a differential diagnosis.

Predictive Acoustic Tracking with an Adaptive Neural Mechanism

Tracking an acoustic signal in motion is pertinent in several domains such as human-robot interaction and search-and-rescue robotics. Conventional approaches to acoustic tracking acquire time-of-arrival-difference signals from multi-microphone arrays and localise the acoustic signal using Kalman or particle filtering, generalised cross-correlation or steered response power techniques. The authors have previously developed a biologically-inspired mechanism that utilises two microphones to reactively track an acoustic signal in motion. The mechanism leverages the directional response of an mathematical model of the lizard peripheral auditory system to extract information regarding sound direction. This information is utilised by a neural machinery to learn the acoustic signal's velocity through fast and unsupervised correlation-based learning adapted from differential Hebbian learning. This approach has previously been validated in simulation and via robotic trials to track a continuous pure tone acoustic signal with a semi-circular motion trajectory and a constant but unknown angular velocity. The neural machinery has been shown to be able to learn different target angular velocities in independent trials. Here we extend our previous work by demonstrating that an identical instance of the mechanism can be used to successfully predict the future spatial location of an acoustic signal with an identical semi-circular motion trajectory and a constant but unknown angular velocity. We evaluate the prediction performance of the simulated mechanism in independent trials for three different angular velocities.

An exception to the matched filter hypothesis: A mismatch of male call frequency and female best hearing frequency in a torrent frog.

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

Ear Structures of the Naked Mole-Rat, Heterocephalus glaber, and Its Relatives (Rodentia: Bathyergidae).

Although increasingly popular as a laboratory species, very little is known about the peripheral auditory system of the naked mole-rat, Heterocephalus glaber. In this study, middle and inner ears of naked mole-rats of a range of ages were examined using micro-computed tomography and dissection. The ears of five other bathyergid species (Bathyergus suillus, Cryptomys hottentotus, Fukomys micklemi, Georychus capensis and Heliophobius argenteocinereus) were examined for comparative purposes. The middle ears of bathyergids show features commonly found in other members of the Ctenohystrica rodent clade, including a fused malleus and incus, a synovial stapedio-vestibular articulation and the loss of the stapedius muscle. Heterocephalus deviates morphologically from the other bathyergids examined in that it has a more complex mastoid cavity structure, poorly-ossified processes of the malleus and incus, a ‘columelliform’ stapes and fewer cochlear turns. Bathyergids have semicircular canals with unusually wide diameters relative to their radii of curvature. How the lateral semicircular canal reaches the vestibule differs between species. Heterocephalus has much more limited high-frequency hearing than would be predicted from its small ear structures. The spongy bone forming its ossicular processes, the weak incudo-stapedial articulation, the columelliform stapes and (compared to other bathyergids) reduced cochlear coiling are all potentially degenerate features which might reflect a lack of selective pressure on its peripheral auditory system. Substantial intraspecific differences were found in certain middle and inner ear structures, which might also result from relaxed selective pressures. However, such interpretations must be treated with caution in the absence of experimental evidence.

A window into the brain mechanisms associated with noise sensitivity.

Noise sensitive individuals are more likely to experience negative emotions from unwanted sounds and they show greater susceptibility to adverse effects of noise on health. Noise sensitivity does not originate from dysfunctions of the peripheral auditory system, and it is thus far unknown whether and how it relates to abnormalities of auditory processing in the central nervous system. We conducted a combined electroencephalography and magnetoencephalography (M/EEG) study to measure neural sound feature processing in the central auditory system in relation to the individual noise sensitivity. Our results show that high noise sensitivity is associated with altered sound feature encoding and attenuated discrimination of sound noisiness in the auditory cortex. This finding makes a step towards objective measures of noise sensitivity instead of self-evaluation questionnaires and the development of strategies to prevent negative effects of noise on the susceptible population.

Influence of high-altitude hypoxic environments on the survival of cochlear hair cells and spiral ganglion neurons in rats

The aim of the present study was to observe the histological changes in the peripheral auditory system in rats at different time-points after relocating from low altitude to high altitude (3,600 m). The general physical condition of the rats was observed and cochlear tissue samples were obtained every month. The morphology and survival of the cochlear hair cells (HCs) were observed using cochlear surface preparation at 1, 30, 90, 120, 150 and 180 days after moving to the plateau area. Changes in spiral ganglion neurons (SGNs) were detected at different time-points using immunofluorescence technology on frozen sections. No obvious morphological changes were observed in the cochlear HCs within 1–3 months of the rats moving to the plateau area, and there was little loss of outer HCs (OHCs) at 3 months. Cell swelling, dislocation and loss of cochlear OHCs were apparent at 4 months, and the losses of cochlear OHCs and inner HCs (IHCs) were 54 and 39%, respectively at 6 months. The loss of SGNs was observed at 3 months, and there was a loss of 28–35% of SGNs during 3–6 months. Thus, a high-altitude hypoxic environment influenced the cochlear HCs in rats after moving to the plateau area in a time-dependent manner. The damage to SGNs occurred earlier than the HCs, although SGN damage was not aggravated with time. Furthermore, compared with cochlear HCs, cochlear SGNs were identified to be markedly more sensitive to hypoxia, and exerted an adaptive mechanism to protect neurons from hypoxia.

Contributions of Sensory Coding and Attentional Control to Individual Differences in Performance in Spatial Auditory Selective Attention Tasks.

Listeners with normal hearing thresholds (NHTs) differ in their ability to steer attention to whatever sound source is important. This ability depends on top-down executive control, which modulates the sensory representation of sound in the cortex. Yet, this sensory representation also depends on the coding fidelity of the peripheral auditory system. Both of these factors may thus contribute to the individual differences in performance. We designed a selective auditory attention paradigm in which we could simultaneously measure envelope following responses (EFRs, reflecting peripheral coding), onset event-related potentials (ERPs) from the scalp (reflecting cortical responses to sound) and behavioral scores. We performed two experiments that varied stimulus conditions to alter the degree to which performance might be limited due to fine stimulus details vs. due to control of attentional focus. Consistent with past work, in both experiments we find that attention strongly modulates cortical ERPs. Importantly, in Experiment I, where coding fidelity limits the task, individual behavioral performance correlates with subcortical coding strength (derived by computing how the EFR is degraded for fully masked tones compared to partially masked tones); however, in this experiment, the effects of attention on cortical ERPs were unrelated to individual subject performance. In contrast, in Experiment II, where sensory cues for segregation are robust (and thus less of a limiting factor on task performance), inter-subject behavioral differences correlate with subcortical coding strength. In addition, after factoring out the influence of subcortical coding strength, behavioral differences are also correlated with the strength of attentional modulation of ERPs. These results support the hypothesis that behavioral abilities amongst listeners with NHTs can arise due to both subcortical coding differences and differences in attentional control, depending on stimulus characteristics and task demands.

Detection of Tones Masked by Fluctuating Noise in Rat Auditory Cortex.

Sounds in natural settings always appear over a noisy background. The masked threshold of a pure tone in white noise (the lowest sound level at which the tone can be detected in the presence of masking noise) is largely determined by energy masking in the peripheral auditory system: when the signal-to-noise ratio within a frequency band centered at the target tone frequency is large enough, the tone can be detected. However, when additional information is supplied to the auditory system, for example in the presence of slow and coherent modulations of a broadband masker (often found in natural sounds), masked thresholds can be reduced substantially below the values expected from pure energy masking. Here, we used intracellular recordings in vivo in rat auditory cortex in order to study neuronal responses to pure tones masked by broadband maskers and amplitude-modulated broadband maskers. When tones were embedded in amplitude-modulated noise, detection thresholds were substantially lower than when embedded in unmodulated noise. The main cue for tone detection in modulated noise consisted of the suppression of the locking of the neuronal responses to the amplitude modulation of the noise by low-level tones.

Informational masking of vocal signals in a nonhuman animal

Informational masking (IM) interferes with speech perception in the presence of multiple talkers. However, its impact on vocal communication in other animals has received little attention. This talk will present behavioral and neurophysiological evidence—much of it preliminary, circumstantial, or both—suggesting that frogs are also susceptible to IM in the context of vocal communication in noisy social environments. When choosing a mate in a chorus, female treefrogs must extract information related to a male’s suitability and quality as a mate from the temporal envelope of his vocalizations. In behavioral experiments, temporally structured maskers constrain a female’s ability to process the temporal envelopes of target vocalizations, even when targets and maskers are sufficiently different in frequency to be transduced by different inner ear papillae. (The frog’s peripheral auditory system—consisting of multiple sensory papillae that encode different frequency ranges of airborne sound—provides a natural “spectral protection zone” for minimizing the impacts of energetic masking in experimental studies of IM.) In neurophysiological experiments, potential correlates of IM can be observed in the responses of single neurons in the inferior colliculus. Future work will employ a multi-tone masking paradigm to determine how spatial separation, masker uncertainty, and target-masker similarity impact “subcortical” signal processing mechanisms in the context of IM and vocal communication.