Hearing Research最新文献

Hearing impairment is the most prevalent sensory disease in humans and can have dramatic effects on the development, and preservation, of our cognitive abilities and social interactions. Currently 20 % of the world's population suffer from a form of hearing impairment; this is predicted to rise to 25 % by 2050. Despite this staggering disease load, and the vast damage it inflicts on the social, medical and economic fabric of humankind, our ability to predict, or prevent, the loss of hearing is very poor indeed. We here make the case for a paradigm shift in our approach to studying deafness. By exploiting more forcefully the molecular-genetic conservation between human hearing and hearing in morphologically distinct models, such as the fruit fly Drosophila melanogaster, we believe, a deeper understanding of hearing and deafness can be achieved. An understanding that moves beyond the surface of the ‘deafness genes’ to probe the underlying bedrock of hearing, which is shared across taxa, and partly shared across modalities. When it comes to understanding the workings (and failings) of human sensory function, a simple fruit fly has a lot to offer and a fly eye might sometimes be a powerful model for a human ear. Particularly the use of fly avatars, in which specific molecular (genetic or proteomic) states of humans (e.g. specific patients) are experimentally reproduced, in order to study the corresponding molecular mechanisms (e.g. specific diseases) in a controlled yet naturalistic environment, is a tool that promises multiple unprecedented insights. The use of the fly – and fly avatars – would benefit humans and will help enhance the power of other scientific models, such as the mouse.

Spoken language development after pediatric cochlear implantation requires rapid and efficient processing of novel, degraded auditory signals and linguistic information. These demands for rapid adaptation tax the information processing speed ability of children who receive cochlear implants. This study investigated the association of speed of information processing ability with spoken language outcomes after cochlear implantation in prelingually deaf children aged 4–6 years. Two domain-general (visual, non-linguistic) speed of information processing measures were administered to 21 preschool-aged children with cochlear implants and 23 normal-hearing peers. Measures of speech recognition, language (vocabulary and comprehension), nonverbal intelligence, and executive functioning skills were also obtained from each participant. Speed of information processing was positively associated with speech recognition and language skills in preschool-aged children with cochlear implants but not in normal-hearing peers. This association remained significant after controlling for hearing group, age, nonverbal intelligence, and executive functioning skills. These findings are consistent with models suggesting that domain-general, fast-efficient information processing speed underlies adaptation to speech perception and language learning following implantation. Assessment and intervention strategies targeting speed of information processing may provide better understanding and development of speech-language skills after cochlear implantation.

Cholinergic signaling is essential to mediate the auditory prepulse inhibition (PPI), an operational measure of sensorimotor gating, that refers to the reduction of the acoustic startle reflex (ASR) when a low-intensity, non-startling acoustic stimulus (the prepulse) is presented just before the onset of the acoustic startle stimulus. The cochlear root neurons (CRNs) are the first cells of the ASR circuit to receive cholinergic inputs from non-olivocochlear neurons of the ventral nucleus of the trapezoid body (VNTB) and subsequently decrease their neuronal activity in response to auditory prepulses. Yet, the contribution of the VNTB-CRNs pathway to the mediation of PPI has not been fully elucidated. In this study, we used the immunotoxin anti-choline acetyltransferase (ChAT)-saporin as well as electrolytic lesions of the medial olivocochlear bundle to selectively eliminate cholinergic VNTB neurons, and then assessed the ASR and PPI paradigms. Retrograde track-tracing experiments were conducted to precisely determine the site of lesioning VNTB neurons projecting to the CRNs. Additionally, the effects of VNTB lesions and the integrity of the auditory pathway were evaluated via auditory brain responses tests, ChAT- and FOS-immunohistochemistry. Consequently, we established three experimental groups: 1) intact control rats (non-lesioned), 2) rats with bilateral lesions of the olivocochlear bundle (OCB-lesioned), and 3) rats with bilateral immunolesions affecting both the olivocochlear bundle and the VNTB (OCB/VNTB-lesioned). All experimental groups underwent ASR and PPI tests at several interstimulus intervals before the lesion and 7, 14, and 21 days after it. Our results show that the ASR amplitude remained unaffected both before and after the lesion across all experimental groups, suggesting that the VNTB does not contribute to the ASR. The%PPI increased across the time points of evaluation in the control and OCB-lesioned groups but not in the OCB/VNTB-lesioned group. At the ISI of 50 ms, the OCB-lesioned group exhibited a significant increase in%PPI (p < 0.01), which did not occur in the OCB/VNTB-lesioned group. Therefore, the ablation of cholinergic non-olivocochlear neurons in the OCB/VNTB-lesioned group suggests that these neurons contribute to the mediation of auditory PPI at the 50 ms ISI through their cholinergic projections to CRNs. Our study strongly reinforces the notion that auditory PPI encompasses a complex mechanism of top-down cholinergic modulation, effectively attenuating the ASR across different interstimulus intervals within multiple pathways.

Background & rationale

In prior work using non-speech stimuli, children with hearing loss show impaired perception of binaural cues and no significant change in cortical responses to bilateral versus unilateral stimulation. Aims of the present study were to: 1) identify bilateral responses to envelope and spectral components of a speech syllable using the frequency-following response (FFR), 2) determine if abnormalities in the bilateral FFR occur in children with hearing loss, and 3) assess functional consequences of abnormal bilateral FFR responses on perception of binaural timing cues.

Methods

A single-syllable speech stimulus (/dα/) was presented to each ear individually and bilaterally. Participants were 9 children with normal hearing (M_Age = 12.1 ± 2.5 years) and 6 children with bilateral hearing loss who were experienced bilateral hearing aid users (M_Age = 14.0 ± 2.6 years). FFR temporal and spectral peak amplitudes were compared between listening conditions and groups using linear mixed model regression analyses. Behavioral sensitivity to binaural cues were measured by lateralization responses as coming from the right or left side of the head.

Results

Both temporal and spectral peaks in FFR responses increased in amplitude in the bilateral compared to unilateral listening conditions in children with normal hearing. These measures of “bilateral advantage” were reduced in the group of children with bilateral hearing loss and associated with decreased sensitivity to interaural timing differences.

Conclusion

This study is the first to show that bilateral responses in both temporal and spectral domains can be measured in children using the FFR and is altered in children with hearing loss with consequences to binaural hearing.

Many neurons in the central nucleus of the inferior colliculus (IC) show sensitivity to interaural time differences (ITDs), which is thought to be relayed from the brainstem. However, studies with interaural phase modulation of pure tones showed that IC neurons have a sensitivity to changes in ITD that is not present at the level of the brainstem. This sensitivity has been interpreted as a form of sensitivity to motion.

A new type of stimulus is used here to study the sensitivity of IC neurons to dynamic changes in ITD, in which broad- or narrowband stimuli are swept through a range of ITDs with arbitrary start-ITD, end-ITD, speed, and direction. Extracellular recordings were obtained under barbiturate anesthesia in the cat. We applied the same analyses as previously introduced for the study of responses to tones.

We find effects of motion which are similar to those described in response to interaural phase modulation of tones. The size of the effects strongly depended on the motion parameters but was overall smaller than reported for tones. We found that the effects of motion could largely be explained by the temporal response pattern of the neuron such as adaptation and build-up. Our data add to previous evidence questioning true coding of motion at the level of the IC.

The study aimed to explore the auditory temporal resolution and dichotic listening skills in patients with type 2 diabetes mellitus (T2DM) and identify associated health-related factors. Using a cross-sectional design, 87 adults with T2DM and 48 non-diabetic controls, all with normal hearing, participated. The two central auditory processing (CAP) skills were assessed through the Gaps-In-Noise (GIN) and Dichotic-Digits Listening (DDL) tests. T2DM participants underwent blood tests to measure various health-related factors. In the GIN test, the shortest gap threshold (GapTh) obtained across both ears was significantly higher in the diabetic group (9.1 ± 2.4 ms) compared to the non-diabetic group (7.5 ± 1.5 ms), and the score of correctly identified gaps (GapSc) in the diabetic group (45±11 %) was significantly lower than GapSc in the non-diabetic group (52±9 %), p < 0.001. In the DDL test, the free-recall score (73.8 ± 18.5 %) across both ears and the right-ear advantage (-1.3 ± 20.6 %) in the diabetic group were significantly lower than the free-recall score (85.8 ± 11.9 %) and right-ear advantage (6.9 ± 11.9 %) in the non-diabetic group, p < 0.005. Furthermore, the duration of diabetes, eGFR level, retinopathy, carotid plaque, fasting blood glucose level, and HDL-C (good cholesterol) level were factors significantly associated with performances in the GIN and/or DDL tests for T2DM participants. In conclusion, individuals with T2DM are at risk of reduced auditory processing skills in temporal resolution and dichotic listening, impacting their speech understanding. Six health-related factors were identified as significantly associated with CAP skills in T2DM patients.

Since the presence of tinnitus is not always associated with audiometric hearing loss, it has been hypothesized that hidden hearing loss may act as a potential trigger for increased central gain along the neural pathway leading to tinnitus perception. In recent years, the study of hidden hearing loss has improved with the discovery of cochlear synaptopathy and several objective diagnostic markers. This study investigated three potential markers of peripheral hidden hearing loss in subjects with tinnitus: extended high-frequency audiometric thresholds, the auditory brainstem response, and the envelope following response. In addition, speech intelligibility was measured as a functional outcome measurement of hidden hearing loss. To account for age-related hidden hearing loss, participants were grouped according to age, presence of tinnitus, and audiometric thresholds. Group comparisons were conducted to differentiate between age- and tinnitus-related effects of hidden hearing loss. All three markers revealed age-related differences, whereas no differences were observed between the tinnitus and non-tinnitus groups. However, the older tinnitus group showed improved performance on low-pass filtered speech in noise tests compared to the older non-tinnitus group. These low-pass speech in noise scores were significantly correlated with tinnitus distress, as indicated using questionnaires, and could be related to the presence of hyperacusis. Based on our observations, cochlear synaptopathy does not appear to be the underlying cause of tinnitus. The improvement in low-pass speech-in-noise could be explained by enhanced temporal fine structure encoding or hyperacusis. Therefore, we recommend that future tinnitus research takes into account age-related factors, explores low-frequency encoding, and thoroughly assesses hyperacusis.

The round window (RW) membrane plays an important role in normal inner ear mechanics. Occlusion or reinforcement of the RW has been described in the context of congenital anomalies or after cochlear implantation and is applied as a surgical treatment for hyperacusis. Multiple lumped and finite element models predict a low-frequency hearing loss with air conduction of up to 20 dB after RW reinforcement and limited to no effect on hearing with bone conduction stimulation. Experimental verification of these results, however, remains limited.

Here, we present an experimental study measuring the impact of RW reinforcement on the middle and inner ear mechanics with air and bone conduction stimulation. In a within-specimen repeated measures design with human cadaveric specimens (n = 6), we compared the intracochlear pressures in scala vestibuli (P_SV) and scala tympani (P_ST) before and after RW reinforcement with soft tissue, cartilage, and bone cement. The differential pressure (P_DIFF) across the basilar membrane – known to be closely related to the hearing sensation - was calculated as the complex difference between P_SV and P_ST.

With air conduction stimulation, both P_SV and P_ST increased on average up to 22 dB at frequencies below 1500 Hz with larger effect sizes for P_ST compared to P_SV. The P_DIFF, in contrast, decreased up to 11 dB at frequencies between 700 and 800 Hz after reinforcement with bone cement.

With bone conduction, the average within-specimen effects were less than 5 dB for either P_SV, P_ST, or P_DIFF. The inter-specimen variability with bone conduction, however, was considerably larger than with air conduction.

This experimental study shows that RW reinforcement impacts air conduction stimulation at low frequencies. Bone conduction stimulation seems to be largely unaffected. From a clinical point of view, these results support the hypothesis that delayed loss of air conduction hearing after cochlear implantation could be partially explained by the impact of RW reinforcement.

The Blood-Labyrinth Barrier (BLB) is pivotal for the maintenance of lymphatic homeostasis within the inner ear, yet the intricacies of its development and function are inadequately understood. The present investigation delves into the contribution of the Mfsd2a molecule, integral to the structural and functional integrity of the Blood-Brain Barrier (BBB), to the ontogeny and sustenance of the BLB. Our empirical findings delineate that the maturation of the BLB in murine models is not realized until approximately two weeks post-birth, with preceding stages characterized by notable permeability. Transcriptomic analysis elucidates a marked augmentation in Mfsd2a expression within the lateral wall of the cochlea in specimens exhibiting an intact BLB. Moreover, both in vitro and in vivo assays substantiate that a diminution in Mfsd2a expression detrimentally impacts BLB permeability and structural integrity, principally via the attenuation of tight junction protein expression and the enhancement of endothelial cell transcytosis. These insights underscore the indispensable role of Mfsd2a in ensuring BLB integrity and propose it as a viable target for therapeutic interventions aimed at the amelioration of hearing loss.

Although rats and mice are among the preferred animal models for investigating many characteristics of auditory function, they are rarely used to study an essential aspect of binaural hearing: the ability of animals to localize the sources of low-frequency sounds by detecting the interaural time difference (ITD), that is the difference in the time at which the sound arrives at each ear. In mammals, ITDs are mostly encoded in the medial superior olive (MSO), one of the main nuclei of the superior olivary complex (SOC). Because of their small heads and high frequency hearing range, rats and mice are often considered unable to use ITDs for sound localization. Moreover, their MSO is frequently viewed as too small or insignificant compared to that of mammals that use ITDs to localize sounds, including cats and gerbils. However, recent research has demonstrated remarkable similarities between most morphological and physiological features of mouse MSO neurons and those of MSO neurons of mammals that use ITDs. In this context, we have analyzed the structure and neural afferent and efferent connections of the rat MSO, which had never been studied by injecting neuroanatomical tracers into the nucleus.

The rat MSO spans the SOC longitudinally. It is relatively small caudally, but grows rostrally into a well-developed column of stacked bipolar neurons. By placing small, precise injections of the bidirectional tracer biotinylated dextran amine (BDA) into the MSO, we show that this nucleus is innervated mainly by the most ventral and rostral spherical bushy cells of the anteroventral cochlear nucleus of both sides, and by the most ventrolateral principal neurons of the ipsilateral medial nucleus of the trapezoid body. The same experiments reveal that the MSO densely innervates the most dorsolateral region of the central nucleus of the inferior colliculus, the central region of the dorsal nucleus of the lateral lemniscus, and the most lateral region of the intermediate nucleus of the lateral lemniscus of its own side. Therefore, the MSO is selectively innervated by, and sends projections to, neurons that process low-frequency sounds. The structural and hodological features of the rat MSO are notably similar to those of the MSO of cats and gerbils. While these similarities raise the question of what functions other than ITD coding the MSO performs, they also suggest that the rat MSO is an appropriate model for future MSO-centered research.