Hearing Research最新文献

Afferent inputs from the cochlea transmit auditory information to the central nervous system, where information is processed and passed up the hierarchy, ending in the auditory cortex. Through these brain pathways, spectral and temporal features of sounds are processed and sent to the cortex for perception. There are also many mechanisms in place for modulation of these inputs, with a major source of modulation being based in the medial prefrontal cortex (mPFC). Neurons of the rodent mPFC receive input from the auditory cortex and other regions such as thalamus, hippocampus and basal forebrain, allowing them to encode high-order information about sounds such as context, predictability and valence. The mPFC then exerts control over auditory perception via top-down modulation of the central auditory pathway, altering perception of and responses to sounds. The result is a higher-order control of auditory processing that produces such characteristics as deviance detection, attention, avoidance and fear conditioning. This review summarises connections between mPFC and the primary auditory pathway, responses of mPFC neurons to auditory stimuli, how mPFC outputs shape the perception of sounds, and how changes to these systems during hearing loss and tinnitus may contribute to these conditions.

The present study investigates effects of current focusing and pulse shape on threshold, dynamic range, spread of excitation and channel interaction in the time domain using cochlear implant stimulation. The study was performed on 20 adult guinea pigs using a 6-channel animal cochlear implant, recording was performed in the auditory midbrain using a multielectrode array. After determining the best frequencies for individual recording contacts with acoustic stimulation, the ear was deafened and a cochlear implant was inserted into the cochlea. The position of the implant was controlled by x-ray. Stimulation with biphasic, pseudomonophasic and monophasic stimuli was performed with monopolar, monopolar with common ground, bipolar and tripolar configuration in two sets of experiments, allowing comparison of the effects of the different stimulation strategies on threshold, dynamic range, spread of excitation and channel interaction. Channel interaction was studied in the temporal domain, where two electrodes were activated with pulse trains and phase locking to these pulse trains in the midbrain was quantified. The results documented multifactorial influences on the response properties, with significant interaction between factors. Thresholds increased with increasing current focusing, but decreased with pseudomonophasic and monophasic pulse shapes. The results documented that current focusing, particularly tripolar configuration, effectively reduces channel interaction, but that also pseudomonophasic and monophasic stimulation and phase duration intensity coding reduce channel interactions.

The barn owl, a nocturnal raptor with remarkably efficient prey-capturing abilities, has been one of the initial animal models used for research of brain mechanisms underlying sound localization. Some seminal findings made from their specialized sound localizing auditory system include discoveries of a midbrain map of auditory space, mechanisms towards spatial cue detection underlying sound-driven orienting behavior, and circuit level changes supporting development and experience-dependent plasticity. These findings have explained properties of vital hearing functions and inspired theories in spatial hearing that extend across diverse animal species, thereby cementing the barn owl's legacy as a powerful experimental system for elucidating fundamental brain mechanisms. This concise review will provide an overview of the insights from which the barn owl model system has exemplified the strength of investigating diversity and similarity of brain mechanisms across species. First, we discuss some of the key findings in the specialized system of the barn owl that elucidated brain mechanisms toward detection of auditory cues for spatial hearing. Then we examine how the barn owl has validated mathematical computations and theories underlying optimal hearing across species. And lastly, we conclude with how the barn owl has advanced investigations toward developmental and experience dependent plasticity in sound localization, as well as avenues for future research investigations towards bridging commonalities across species. Analogous to the informative power of Astrophysics for understanding nature through diverse exploration of planets, stars, and galaxies across the universe, miscellaneous research across different animal species pursues broad understanding of natural brain mechanisms and behavior.

Auditory sensation is based in nanoscale vibration of the sensory tissue of the cochlea, the organ of Corti complex (OCC). Motion within the OCC is now observable due to optical coherence tomography. In a previous study (Cooper et al., 2018), the region that includes the electro-motile outer hair cells (OHC) and Deiters cells (DC) was observed to move with larger amplitude than the basilar membrane (BM) and surrounding regions and was termed the "hotspot." In addition to this quantitative distinction, the hotspot moved qualitatively differently than the BM, in that its motion scaled nonlinearly with stimulus level at all frequencies, evincing sub-BF activity. Sub-BF activity enhances non-BF motion; thus the frequency tuning of the OHC/DC region was reduced relative to the BM. In this work we further explore the motion of the gerbil basal OCC and find that regions that lack significant sub-BF activity include the BM, the medial and lateral OCC, and the reticular lamina (RL) region. The observation that the RL region does not move actively sub-BF (already observed in Cho and Puria 2022), suggests that hair cell stereocilia are not exposed to sub-BF activity in the cochlear base. The observation that the lateral and RL regions move approximately linearly sub-BF indicates that linear forces dominate non-linear OHC-based forces on these components at sub-BF frequencies. A complex difference analysis was performed to reveal the internal motion of the OHC/DC region and showed that amplitude structure and phase shifts in the directly measured OHC/DC motion emerge due to the internal OHC/DC motion destructively interfering with BM motion.

Countless therapeutic antibodies are currently available for the treatment of a broad range of diseases. Some target molecules of therapeutic antibodies are involved in the pathogenesis of sensorineural hearing loss (SNHL), suggesting that SNHL may be a novel target for monoclonal antibody (mAb) therapy. When considering mAb therapy for SNHL, understanding of the pharmacokinetics of mAbs after local application into the middle ear is crucial. To reveal the fundamental characteristics of mAb pharmacokinetics following local application into the middle ear of guinea pigs, we performed pharmacokinetic analyses of mouse monoclonal antibodies to FLAG-tag (FLAG-mAbs), which have no specific binding sites in the middle and inner ear. FLAG-mAbs were rapidly transferred from the middle ear to the cochlear fluid, indicating high permeability of the round window membrane to mAbs. FLAG-mAbs were eliminated from the cochlear fluid 3 h after application, similar to small molecules. Whole-body autoradiography and quantitative assessments of cerebrospinal fluid and serum demonstrated that the biodistribution of FLAG-mAbs was limited to the middle and inner ear. Altogether, the pharmacokinetics of mAbs are similar to those of small molecules when locally applied into the middle ear, suggesting the necessity of drug delivery systems for appropriate mAb delivery to the cochlear fluid after local application into the middle ear.

Spectro-temporal modulation (STM) detection sensitivity has been shown to be associated with speech-in-noise reception in hearing-impaired (HI) individuals. Based on previous research, a recent study [Zaar, Simonsen, Dau, and Laugesen (2023). Hear Res 427:108650] introduced an STM test paradigm with audibility compensation, employing STM stimulus variants using noise and complex tones as carrier signals. The study demonstrated that the test was suitable for the target population of elderly individuals with moderate-to-severe hearing loss and showed promising predictions of speech-reception thresholds (SRTs) measured in a realistic set up with spatially distributed speech and noise maskers and linear audibility compensation. The present study further investigated the suggested STM test with respect to (i) test-retest variability for the most promising STM stimulus variants, (ii) its predictive power with respect to realistic speech-in-noise reception with non-linear hearing-aid amplification, (iii) its connection to effects of directionality and noise reduction (DIR+NR) hearing-aid processing, and (iv) its relation to DIR+NR preference. Thirty elderly HI participants were tested in a combined laboratory and field study, collecting STM thresholds with a complex-tone based and a noise-based STM stimulus design, SRTs with spatially distributed speech and noise maskers using hearing aids with non-linear amplification and two different levels of DIR+NR, as well as subjective reports and preference ratings obtained in two field periods with the two DIR+NR hearing-aid settings. The results indicate that the noise-carrier based STM test variant (i) showed optimal test-retest properties, (ii) yielded a highly significant correlation with SRTs (R²=0.61) exceeding and complementing the predictive power of the audiogram, (iii) yielded significant correlation (R²=0.51) with the DIR+NR-induced SRT benefit, and (iv) did not provide significant correlation with subjective preference for DIR+NR settings in the field. Overall, the suggested STM test represents a valuable tool for diagnosing speech-reception problems that remain when hearing-aid amplification has been provided and the resulting need for and benefit from DIR+NR hearing-aid processing.

Chronic tinnitus is a debilitating condition with very few management options. Acoustic trauma that causes tinnitus has been shown to induce neuronal hyperactivity in multiple brain areas in the auditory pathway, including the inferior colliculus. This neuronal hyperactivity could be attributed to an imbalance between excitatory and inhibitory neurotransmission. However, it is not clear how the levels of neurotransmitters, especially neurotransmitters in the extracellular space, change over time following acoustic trauma and the development of tinnitus. In the present study, a range of amino acids were measured in the inferior colliculus of rats during acoustic trauma as well as at 1 week and 5 months post-trauma using in vivo microdialysis and high-performance liquid chromatography. Amino acid levels in response to sound stimulation were also measured at 1 week and 5 months post-trauma. It was found that unilateral exposure to a 16 kHz pure tone at 115 dB SPL for 1 h caused immediate hearing loss in all the animals and chronic tinnitus in 58 % of the animals. Comparing to the sham condition, extracellular levels of GABA were significantly increased at both the acute and 1 week time points after acoustic trauma. However, there was no significant difference in any of the amino acid levels measured between sham, tinnitus positive and tinnitus negative animals at 5 months post-trauma. There was also no clear pattern in the relationship between neurochemical changes and sound frequency/acoustic trauma/tinnitus status, which might be due to the relatively poorer temporal resolution of the microdialysis compared to electrophysiological responses.

DFNA9 is a dominantly inherited form of adult-onset progressive hearing impairment caused by mutations in the COCH gene. COCH encodes cochlin, a crucial extracellular matrix protein. We established a genomically humanized mouse model for the Dutch/Belgian c.151C>T founder mutation in COCH. Considering upcoming sequence-specific genetic therapies, we exchanged the genomic murine Coch exons 3–6 for the corresponding human sequence. Introducing human-specific genetic information into mouse exons can be risky. To mitigate unforeseen consequences on cochlin function resulting from the introduction of the human COCH protein-coding sequence, we converted all human-specific amino acids to mouse equivalents. We furthermore optimized the recognition of the human COCH exons by the murine splicing machinery during pre-mRNA splicing. Subsequent observations in mouse embryonic stem cells revealed correct splicing of the hybrid Coch transcript. The inner ear of the established humanized Coch mice displays correctly-spliced wild-type and mutant humanized Coch alleles. For a comprehensive study of auditory function, mice were crossbred with C57BL/6 Cdh23^753A>G mice to remove the Cdh23^ahl allele from the genetic background of the mice. At 9 months, all humanized Coch genotypes showed hearing thresholds comparable to wild-type C57BL/6 Cdh23^753A>G mice. This indicates that both the introduction of human wildtype COCH, and correction of Cdh23^ahl in the humanized Coch lines was successful. Overall, our approach proved beneficial in eliminating potential adverse events of genomic humanization of mouse genes, and provides us with a model in which sequence-specific therapies directed against the human mutant COCH alle can be investigated. With the hearing and balance defects anticipated to occur late in the second year of life, a long-term follow-up study is ongoing to fully characterize the humanized Coch mouse model.

Sound source localization in "cocktail-party" situations is a remarkable ability of the human auditory system. However, the neural mechanisms underlying auditory spatial attention are still largely unknown. In this study, the "cocktail-party" situations are simulated through multiple sound sources and presented through head-related transfer functions and headphones. Furthermore, the scalp time-varying network of auditory spatial attention is constructed using the high-temporal resolution electroencephalogram, and its network properties are measured quantitatively using graph theory analysis. The results show that the time-varying network of auditory spatial attention in "cocktail-party" situations is more complex and partially different than in simple acoustic situations, especially in the early- and middle-latency periods. The network coupling strength increases continuously over time, and the network hub shifts from the posterior temporal lobe to the parietal lobe and then to the frontal lobe region. In addition, the right hemisphere has a stronger network strength for processing auditory spatial information in "cocktail-party" situations, i.e., the right hemisphere has higher clustering levels, higher transmission efficiency, and more node degrees during the early- and middle-latency periods, while this phenomenon disappears and appears symmetrically during the late-latency period. These findings reveal different network patterns and properties of auditory spatial attention in "cocktail-party" situations during different periods and demonstrate the dominance of the right hemisphere in the dynamic processing of auditory spatial information.

Temporal modulations are ubiquitous features of sound signals that are important for auditory perception. The perception of temporal modulations, or temporal processing, is known to decline with aging and hearing loss and negatively impact auditory perception in general and speech recognition specifically. However, neurophysiological literature also provides evidence of exaggerated or enhanced encoding of specifically temporal envelopes in aging and hearing loss, which may arise from changes in inhibitory neurotransmission and neuronal hyperactivity. This review paper describes the physiological changes to the neural encoding of temporal envelopes that have been shown to occur with age and hearing loss and discusses the role of disinhibition and neural hyperactivity in contributing to these changes. Studies in both humans and animal models suggest that aging and hearing loss are associated with stronger neural representations of both periodic amplitude modulation envelopes and of naturalistic speech envelopes, but primarily for low-frequency modulations (<80 Hz). Although the frequency dependence of these results is generally taken as evidence of amplified envelope encoding at the cortex and impoverished encoding at the midbrain and brainstem, there is additional evidence to suggest that exaggerated envelope encoding may also occur subcortically, though only for envelopes with low modulation rates. A better understanding of how temporal envelope encoding is altered in aging and hearing loss, and the contexts in which neural responses are exaggerated/diminished, may aid in the development of interventions, assistive devices, and treatment strategies that work to ameliorate age- and hearing-loss-related auditory perceptual deficits.