Advances in the neurobiology of hearing disorders: recent developments regarding the basis of tinnitus and hyperacusis.

The prevalence of hearing problems in the Western world has, due to aging of the population, doubled over the past 30 years. Thereby, noise-induced hearing loss is an important factor that worsens over time in addition to age-related hearing loss. Hearing loss is usually measured as an elevation of a person's hearing thresholds, expressed in decibel (dB). However, recent animal studies have unraveled a type of permanent cochlear damage, without an elevation of hearing thresholds. This subtle damage is linked to a permanent and progressive degeneration of auditory fibers that occurs in association with damage of the inner hair cell synapse. Afferent neuronal degeneration has been suggested to be involved in hyperacusis (over sensitivity to sound) and tinnitus (a phantom sound percept). Hyperacusis and tinnitus are potentially devastating conditions that are still incurable. The main risk factors to develop tinnitus or hyperacusis are hearing loss, social stress and age. Both tinnitus and hyperacusis have been discussed in the context of a pathological increased response gain in subcortical brain regions as a reaction to deprivation of sensory input. Novel studies confirm the involvement of peripheral deafferentation for tinnitus and hyperacusis, but suggest that the disorder results from different brain responses to different degrees of deafferentation: while tinnitus may arise as a failure of the brain to adapt to deprived peripheral input, hyperacusis may result from an 'over-adaptive' increase in response gain. Moreover, moderate and high stress levels at the time of acoustic trauma have been suggested to play a pivotal role in the vulnerability of the cochlea to acoustic damage and therefore for the development of tinnitus and hyperacusis.

Knipper M ，Van Dijk P ，Nunes I ，Rüttiger L ，Zimmermann U ... -  《-》

[DPOAE in tinnitus patients with cochlear hearing loss considering hyperacusis and misophonia].

Sztuka A ，Pośpiech L ，Gawron W ，Dudek K ... -  《-》

DPOAE in estimation of the function of the cochlea in tinnitus patients with normal hearing.

The most probable place generating tinnitus in the auditory pathway is the outer hair cells (OHCs) inside the cochlea. Otoacoustic emissions are used to assess their activity. The objective of the investigation was to measure the features of distortion product otoacoustic emissions (DPOAE) in a group of tinnitus patients without hearing loss, estimate the diagnostic value of the parameters for the analysis of cochlear function in the patients, emphasizing those most useful in localizing tinnitus generators, and determine the hypothetical influence of hyperacusis and misophony on DPOAE parameters in tinnitus patients. The material consisted of 44 patients with tinnitus and without hearing loss. In the control group were 33 patients without tinnitus with the same state of hearing. The tinnitus patients were divided into three subgroups: those with hyperacusis, those with misophonia, and those with neither. After collecting medical history and performing clinical examination of all the patients, tonal and impedance audiometry, ABR, and discomfort level were evaluated. Then DPOAE were measured using three procedures. First the amplitudes of two points per octave were assessed, second the "fine structure" method with 16-20 points per octave (f2/f1=1.22, L1=L2=70 dB), and the third procedure included recording the growth function in three series for input tones of f2=2002, 4004, and 6006Hz (f2/f1=1.22) and L1=L2 levels increasing by increments of 5 dB in each series. Hyperacusis was found in 63% and misophonia in 10% of the tinnitus patients with no hearing loss. DPOAE amplitudes in recordings with two points per octave and the fine structure method are very valuable parameters for estimating cochlear function in tinnitus patients with normal hearing. Function growth rate cannot be the only parameter in measuring DPOAE in tinnitus patients, including subjects with hyperacusis and misophonia. The markedly higher DPOAE amplitudes in the group of tinnitus patients without hearing loss suggest that tinnitus may be caused by increased motility of the OHCs induced by decreasing efferent fiber activity, and not by OHC failure. Hyperacusis significantly increases the amplitude of DPOAE in tinnitus patients with no hearing loss.

Sztuka A ，Pospiech L ，Gawron W ，Dudek K ... -  《-》

Effects of lifetime noise exposure on the middle-age human auditory brainstem response, tinnitus and speech-in-noise intelligibility.

Recent animal studies have shown that the synapses between inner hair cells and the dendrites of the spiral ganglion cells they innervate are the elements in the cochlea most vulnerable to excessive noise exposure. Particularly in rodents, several studies have concluded that exposure to high level octave-band noise for 2 h leads to an irreversible loss of around 50% of synaptic ribbons, leaving audiometric hearing thresholds unaltered. Cochlear synaptopathy following noise exposure is hypothesized to degrade the neural encoding of sounds at the subcortical level, which would help explain certain listening-in-noise difficulties reported by some subjects with otherwise 'normal' hearing. In response to this peripheral damage, increased gain of central stages of the auditory system has been observed across several species of mammals, particularly in association with tinnitus. The auditory brainstem response (ABR) wave I amplitude and waves I-V amplitude ratio have been suggested as non-invasive indicators of cochlear synaptopathy and central gain activation respectively, but the evidence for these hearing disorders in humans is inconclusive. In this study, we evaluated the influence of lifetime noise exposure (LNE) on the human ABR and on speech-in-noise intelligibility performance in a large cohort of adults aged 29 to 55. Despite large inter-subject variability, results showed a moderate, but statistically significant, negative correlation between the ABR wave I amplitude and LNE, consistent with cochlear synaptopathy. The results also showed (a) that central gain mechanisms observed in animal studies might also occur in humans, in which higher stages of the auditory pathway appear to compensate for reduced input from the cochlea; (b) that tinnitus was associated with activation of central gain mechanisms; (c) that relevant cognitive and subcortical factors influence speech-in-noise intelligibility, in particular, longer ABR waves I-V interpeak latencies were associated with poorer performance in understanding speech in noise when central gain mechanisms were active; and (d) absence of a significant relationship between LNE and tinnitus, central gain activation or speech-in-noise performance. Although this study supports the possible existence of cochlear synaptopathy in humans, the great degree of variability, the lack of uniformity in central gain activation and the significant involvement of attention in speech-in-noise performance suggests that noise-induced cochlear synaptopathy is, at most, one of several factors that play a role in humans' speech-in-noise performance.

Valderrama JT ，Beach EF ，Yeend I ，Sharma M ，Van Dun B ，Dillon H ... -  《-》

Enhanced Central Neural Gain Compensates Acoustic Trauma-induced Cochlear Impairment, but Unlikely Correlates with Tinnitus and Hyperacusis.

For successful future therapeutic strategies for tinnitus and hyperacusis, a subcategorization of both conditions on the basis of differentiated neural correlates would be of invaluable advantage. In the present study, we used our refined operant conditioning animal model to divide equally noise-exposed rats into groups with either tinnitus or hyperacusis, with neither condition, or with both conditions co-occurring simultaneously. Using click stimulus and noise burst-evoked Auditory Brainstem Responses (ABR) and Distortion Product Otoacoustic Emissions, no hearing threshold difference was observed between any of the groups. However, animals with neither tinnitus nor hyperacusis responded to noise trauma with shortened ABR wave I and IV latencies and elevated central neuronal gain (increased ABR wave IV/I amplitude ratio), which was previously assumed in most of the literature to be a neural correlate for tinnitus. In contrast, animals with tinnitus had reduced neural response gain and delayed ABR wave I and IV latencies, while animals with hyperacusis showed none of these changes. Preliminary studies, aimed at establishing comparable non-invasive objective tools for identifying tinnitus in humans and animals, confirmed reduced central gain and delayed response latency in human and animals. Moreover, the first ever resting state functional Magnetic Resonance Imaging (rs-fMRI) analyses comparing humans and rats with and without tinnitus showed reduced rs-fMRI activities in the auditory cortex in both patients and animals with tinnitus. These findings encourage further efforts to establish non-invasive diagnostic tools that can be used in humans and animals alike and give hope for differentiated classification of tinnitus and hyperacusis.

Möhrle D ，Hofmeier B ，Amend M ，Wolpert S ，Ni K ，Bing D ，Klose U ，Pichler B ，Knipper M ，Rüttiger L ... -  《-》