Cisplatin-induced vestibular hair cell lesion-less damage at high doses.

Cisplatin, a widely used anticancer drug, damages hair cells in cochlear organotypic cultures at low doses, but paradoxically causes little damage at high doses resulting in a U-shaped dose-response function. To determine if the cisplatin dose-response function for vestibular hair cells follows a similar pattern, we treated vestibular organotypic cultures with doses of cisplatin ranging from 10 to 1000 μM. Vestibular hair cell lesions progressively increased as the dose of cisplatin increased with maximum damage occurring around 50-100 μM, but the lesions progressively decreased at higher doses resulting in little hair cell loss at 1000 μM.

Aberrant thalamocortical coherence in an animal model of tinnitus.

Electrophysiological and imaging studies from humans suggest that the phantom sound of tinnitus is associated with abnormal thalamocortical neural oscillations (dysrhythmia) and enhanced gamma band activity in the auditory cortex. However, these models have seldom been tested in animal models where it is possible to simultaneously assess the neural oscillatory activity within and between the thalamus and auditory cortex. To explore this issue, we used multichannel electrodes to examine the oscillatory behavior of local field potentials recorded in the rat medial geniculate body (MBG) and primary auditory cortex (A1) before and after administering a dose of sodium salicylate (SS) that reliably induces tinnitus.

Synaptic Reorganization Response in the Cochlear Nucleus Following Intense Noise Exposure.

The cochlear nucleus, located in the brainstem, receives its afferent auditory input exclusively from the auditory nerve fibers of the ipsilateral cochlea. Noise-induced neurodegenerative changes occurring in the auditory nerve stimulate a cascade of neuroplastic changes in the cochlear nucleus resulting in major changes in synaptic structure and function. To identify some of the key molecular mechanisms mediating this synaptic reorganization, we unilaterally exposed rats to a high-intensity noise that caused significant hearing loss and then measured the resulting changes in a synaptic plasticity gene array targeting neurogenesis and synaptic reorganization.

Bilirubin-induced neurotoxic and ototoxic effects in rat cochlear and vestibular organotypic cultures.

Exposure to high levels of bilirubin in hyperbilirubinemia patients and animal models can result in sensorineural deafness. However, the mechanisms underlying bilirubin-induced damage to the inner ear, including the cochlear and vestibular organs, remain unknown. The present analyses of cochlear and vestibular organotypic cultures obtained from postnatal day 3 rats exposed to bilirubin at varying concentrations (0, 10, 50, 100, or 250 μM) for 24 h revealed that auditory nerve fibers (ANFs) and vestibular nerve endings were destroyed even at low doses (10 and 50 μM).

Isoflurane anesthesia suppresses distortion product otoacoustic emissions in rats.

A commonly used anesthetic, isoflurane, can impair auditory function in a dose-dependent manner. However, in rats, isoflurane-induced auditory impairments have only been assessed with auditory brainstem responses; a measure which is unable to distinguish if changes originate from the central or peripheral auditory system. Studies performed in other species, such as mice and guinea-pigs, suggests auditory impairment stems from disrupted OHC amplification.

Hidden cochlear impairments.

Pure tone audiometry is a routine clinical examination used to identify hearing loss. A normal pure tone audiogram is usually taken as evidence of normal hearing. Auditory deficits detected in subjects with normal audiograms, such as poor sound discrimination and auditory perceptual disorders, are generally attributed to central problems.

Abnormal functional connectivity and degree centrality in anterior cingulate cortex in patients with long-term sensorineural hearing loss.

Wide-ranging functional remodeling is involved in sensorineural hearing loss (SNHL), which has been demonstrated to have accumulated risk of cognitive and emotional dysfunction. Anterior cingulate cortex (ACC) has close connections with the auditory area and plays a vital role in regulating the cognitive, emotional and auditory processing. However, the functional reorganization of the ACC and its associations with potential cognitive and emotional impairments involved in SNHL have never been explored.

Intermittent Low-level Noise Causes Negative Neural Gain in the Inferior Colliculus.

The central auditory system shows a remarkable ability to rescale its neural representation of loudness following long-term, low-level acoustic exposures; even when the noise is presented intermittently. Circadian rhythms exert potent biological effects, but it remains unclear if acoustic exposures occurring during the light or dark cycle affect the neurophysiological changes involved in loudness rescaling. To address this issue we exposed rats to intermittent (12 h/day), low-level noise (10-20 kHz, 75 dB SPL) for 5 weeks; exposures occurred during either the light (inactive) or dark (active) phase of the circadian cycle.

Feasibility of interleaved Bayesian adaptive procedures in estimating the equal-loudness contour.

A Bayesian adaptive procedure, the interleaved-equal-loudness contour (IELC) procedure, was developed to improve the efficiency in estimating the equal-loudness contour. Experiment 1 evaluated the test-retest reliability of the IELC procedure using six naive normal-hearing listeners. Two IELC runs of 200 trials were conducted and excellent test-retest reliability was found at both the group and individual levels.

The Relationship between Severity of Hearing Loss and Subjective Tinnitus Loudness among Patients Seen in a Specialist Tinnitus and Hyperacusis Therapy Clinic in UK.

Background: Hearing loss is often associated with the phantom sound of tinnitus. However, the degree of the association between severity of hearing loss and tinnitus loudness taking into account the impact of other variables (e.g.

Tone-in-noise detection deficits in elderly patients with clinically normal hearing.

Purpose: One of the most common complaints among the elderly is the inability to understand speech in noisy environments. In many cases, these deficits are due to age-related hearing loss; however, some of the elderly that have difficulty hearing in noise have clinically normal pure-tone thresholds. While speech in noise testing is informative, it fails to identify specific frequencies responsible for the speech processing deficit.

Testing the Central Gain Model: Loudness Growth Correlates with Central Auditory Gain Enhancement in a Rodent Model of Hyperacusis.

The central gain model of hyperacusis proposes that loss of auditory input can result in maladaptive neuronal gain increases in the central auditory system, leading to the over-amplification of sound-evoked activity and excessive loudness perception. Despite the attractiveness of this model, and supporting evidence for it, a critical test of the central gain theory requires that changes in sound-evoked activity be explicitly linked to perceptual alterations of loudness. Here we combined an operant conditioning task that uses a subject's reaction time to auditory stimuli to produce reliable measures of loudness growth with chronic electrophysiological recordings from the auditory cortex and inferior colliculus of awake, behaviorally-phenotyped animals.

Cochlear hair cell densities in the rabbit.

A typical cochleogram was plotted to investigate hair cell densities as a percentage along the whole length of the basilar membrane (BM) of the rabbit, the length of the BM and the width of the organ of Corti. We generated surface preparations of cochlea from adult, healthy New Zealand White (NZW) rabbits. The numbers of inner hair cells (IHCs) and outer hair cells (OHCs) were counted from images acquired from a digital camera attached to an Olympus light microscope with a scale of 100 μm as a primary unit drawn continuously, and the numbers of IHCs and OHCs were converted to densities at 10% intervals along the length of the cochlea.

Auditory central gain compensates for changes in cochlear output after prolonged low-level noise exposure.

Remarkably, the central auditory system can modify the strength of its sound-evoked neural response based on prior acoustic experiences, a phenomenon referred to as central gain. Gain changes are well documented following traumatic noise exposure, but much less is known about central gain dynamics following prolonged exposure to low-level noise, a common acoustic experience in many urban and work environments. We recently reported that the neural output of the cochlea is reduced, while gain was enhanced in the inferior colliculus (IC) following a 5-week exposure to 75 dB noise.

Hearing Loss, Tinnitus, Hyperacusis, and Diplacusis in Professional Musicians: A Systematic Review.

Professional musicians (PMs) are at high risk of developing hearing loss (HL) and other audiological symptoms such as tinnitus, hyperacusis, and diplacusis. The aim of this systematic review is to (A) assess the risk of developing HL and audiological symptoms in PMs and (B) evaluate if different music genres (Pop/Rock Music-PR; Classical Music-CL) expose PMs to different levels of risk of developing such conditions. Forty-one articles including 4618 PMs were included in the study.

Lower level noise exposure that produces only TTS modulates the immune homeostasis of cochlear macrophages.

Noise exposure producing temporary threshold shifts (TTS) has been demonstrated to cause permanent changes to cochlear physiology and hearing function. Several explanations have been purported to underlie these long-term changes in cochlear function, such as damage to sensory cell stereocilia and synaptic connections between sensory cells and their innervation by spiral ganglion neurons, and demyelination of the auditory nerve. Though these structural defects have been implicated in hearing difficulty, cochlear responses to this stress damage remains poorly understood.

Prolonged low-level noise exposure reduces rat distortion product otoacoustic emissions above a critical level.

Prolonged noise exposures presented at low to moderate intensities are often used to investigate neuroplastic changes in the central auditory pathway. A common assumption in many studies is that central auditory changes occur independent of any hearing loss or cochlear dysfunction. Since hearing loss from a long term noise exposure can only occur if the level of the noise exceeds a critical level, prolonged noise exposures that incrementally increase in intensity can be used to determine the critical level for any given species and noise spectrum.

Subtyping patients with somatic tinnitus: Modulation of tinnitus and history for somatic dysfunction help identify tinnitus patients with temporomandibular joint disorders.

Objective: Determine in a cohort of patients with normal hearing and chronic tinnitus if self-reported history for temporomandibular joint (TMJ) dysfunction and a positive modulation of tinnitus in the TMJ region could be suggestive of an underlying TMJ disorder.

Patients And Methods: The study included 226 patients presenting to the Head and Neck Service of our University Hospital. Following audiological and somatic tinnitus evaluation, patients were divided into two groups.

Muscarinic Receptor MR Signaling Prevents Efficient Remyelination by Human and Mouse Oligodendrocyte Progenitor Cells.

Muscarinic receptor antagonists act as potent inducers of oligodendrocyte differentiation and accelerate remyelination. However, the use of muscarinic antagonists in the clinic is limited by poor understanding of the operant receptor subtype, and questions regarding possible species differences between rodents and humans. Based on high selective expression in human oligodendrocyte progenitor cells (OPCs), we hypothesized that MR is the functionally relevant receptor.

Key Genes and Pathways Associated With Inner Ear Malformation in SOX10 Mutation Pigs.

SRY-box 10 (SOX10) mutation may lead to inner ear deformities. However, its molecular mechanisms on inner ear development are not clear. In this work, the inner ear morphology was investigated at different embryonic stages of the SOX10 mutation miniature porcine model with sensorineural hearing loss, and high-throughput RNA-seq and bioinformatics analyses were applied.

Temporary conductive hearing loss in early life impairs spatial memory of rats in adulthood.

Introduction: It is known that an interruption of acoustic input in early life will result in abnormal development of the auditory system. Here, we further show that this negative impact actually spans beyond the auditory system to the hippocampus, a system critical for spatial memory.

Methods: We induced a temporary conductive hearing loss (TCHL) in P14 rats by perforating the eardrum and allowing it to heal.

Differential fates of tissue macrophages in the cochlea during postnatal development.

The cochlea contains macrophages. These cells participate in inflammatory responses to cochlear pathogenesis. However, it is not clear how and when these cells populate the cochlea during postnatal development.

Familial nonsyndromic hearing loss with incomplete partition type II caused by novel DSPP gene mutations.

Background: Familial nonsyndromic hearing loss (NSHL) with incomplete partition type II (IP-II) is a very rare condition.

Aims/objectives: To determine the audiological feature, inheritance patterns and genetic etiology of familial NSHL with IP-II in a Chinese family with eight family members.

Material And Methods: Clinical data were collected from all eight family members, selected deafness genes were sequenced in proband and whole genome sequencing of seven family members was performed.

Presbycusis Disrupts Spontaneous Activity Revealed by Resting-State Functional MRI.

: Presbycusis, age-related hearing loss, is believed to involve neural changes in the central nervous system, which is associated with an increased risk of cognitive impairment. The goal of this study was to determine if presbycusis disrupted spontaneous neural activity in specific brain areas involved in auditory processing, attention and cognitive function using resting-state functional magnetic resonance imaging (fMRI) approach. : Hearing and resting-state fMRI measurements were obtained from 22 presbycusis patients and 23 age-, sex- and education-matched healthy controls.

Preclinical and clinical otoprotective applications of cell-penetrating peptide D-JNKI-1 (AM-111).

There is a growing interest in the auditory community to develop novel prophylactic and therapeutic drugs to prevent permanent sensorineural hearing loss following acute cochlear injury. The jun-N-terminal protein kinase (JNK) pathway plays a crucial role in acute sensory hearing loss. Blocking the JNK pathway using the cell-penetrating peptide D-JNKI-1 (AM-111/brimapitide) has shown promise as both a prophylactic and therapeutic agent for acute cochlear injury.