Ever since Pliny the Elder coined the term tinnitus, the perception of sound in the absence of an external sound source has remained enigmatic. Traditional theories assume that tinnitus is triggered by cochlear damage, but many tinnitus patients present with a normal audiogram, i.e., with no direct signs of cochlear damage. Here, we report that in human subjects with tinnitus and a normal audiogram, auditory brainstem responses show a significantly reduced amplitude of the wave I potential (generated by primary auditory nerve fibers) but normal amplitudes of the more centrally generated wave V. This provides direct physiological evidence of "hidden hearing loss" that manifests as reduced neural output from the cochlea, and consequent renormalization of neuronal response magnitude within the brainstem. Employing an established computational model, we demonstrate how tinnitus could arise from a homeostatic response of neurons in the central auditory system to reduced auditory nerve input in the absence of elevated hearing thresholds.

Tinnitus, the perception of a sound in the absence of acoustic stimulation, is often associated with hearing loss. Animal studies indicate that hearing loss through cochlear damage can lead to behavioral signs of tinnitus that are correlated with pathologically increased spontaneous firing rates, or hyperactivity, of neurons in the auditory pathway. Mechanisms that lead to the development of this hyperactivity, however, have remained unclear. We address this question by using a computational model of auditory nerve fibers and downstream auditory neurons. The key idea is that mean firing rates of these neurons are stabilized through a homeostatic plasticity mechanism. This homeostatic compensation can give rise to hyperactivity in the model neurons if the healthy ratio between mean and spontaneous firing rate of the auditory nerve is decreased, for example through a loss of outer hair cells or damage to hair cell stereocilia. Homeostasis can also amplify non-auditory inputs, which then contribute to hyperactivity. Our computational model predicts how appropriate additional acoustic stimulation can reverse the development of such hyperactivity, which could provide a new basis for treatment strategies.

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Tinnitus is often related to hearing loss, but how hearing loss could lead to tinnitus has remained unclear. Animal studies show that the occurrence of tinnitus is correlated to increased spontaneous firing rates of central auditory neurons, but mechanisms that give rise to such hyperactivity have not been identified yet. Here we present a computational model that reproduces tinnitus-related hyperactivity and predicts tinnitus pitch from the audiograms of tinnitus patients with noise-induced hearing loss and tone-like tinnitus. Our key assumption is that the mean firing rates of central auditory neurons are controlled by homeostatic plasticity. Decreased auditory nerve activity after hearing loss is counteracted through an increase of the neuronal response gain, which restores the mean rate but can also lead to hyperactivity. Hyperactivity patterns calculated from patients' audiograms exhibit distinct peaks at frequencies close to the perceived tinnitus pitch, corroborating hyperactivity through homeostatic plasticity as a mechanism for the development of tinnitus after hearing loss. The model suggests that such hyperactivity, and thus also tinnitus caused by cochlear damage, could be alleviated through additional stimulation.

Animal studies demonstrate that noise exposure can permanently damage the synapses between inner hair cells and auditory nerve fibers, even when outer hair cells are intact and there is no clinically relevant permanent threshold shift. Synaptopathy disrupts the afferent connection between the cochlea and the central auditory system and is predicted to impair speech understanding in noisy environments and potentially result in tinnitus and/or hyperacusis. While cochlear synaptopathy has been demonstrated in numerous experimental animal models, synaptopathy can only be confirmed through post-mortem temporal bone analysis, making it difficult to study in living humans. A variety of non-invasive measures have been used to determine whether noise-induced synaptopathy occurs in humans, but the results are conflicting. The overall objective of this article is to synthesize the existing data on the functional impact of noise-induced synaptopathy in the human auditory system. The first section of the article summarizes the studies that provide evidence for and against noise-induced synaptopathy in humans. The second section offers potential explanations for the differing results between studies. The final section outlines suggested methodologies for diagnosing synaptopathy in humans with the aim of improving consistency across studies.

Hyperacusis is a frequent auditory disorder where sounds of normal volume are perceived as too loud or even painfully loud. There is a high degree of co-morbidity between hyperacusis and tinnitus, most hyperacusis patients also have tinnitus, but only about 30–40% of tinnitus patients also show symptoms of hyperacusis. In order to elucidate the mechanisms of hyperacusis, detailed measurements of loudness discomfort levels (LDLs) across the hearing range would be desirable. However, previous studies have only reported LDLs for a restricted frequency range, e.g., from 0.5 to 4 kHz or from 1 to 8 kHz. We have measured audiograms and LDLs in 381 patients with a primary complaint of hyperacusis for the full standard audiometric frequency range from 0.125 to 8 kHz. On average, patients had mild high-frequency hearing loss, but more than a third of the tested ears had normal hearing thresholds (HTs), i.e., ≤20 dB HL. LDLs were found to be significantly decreased compared to a normal-hearing reference group, with average values around 85 dB HL across the frequency range. However, receiver operating characteristic analysis showed that LDL measurements are neither sensitive nor specific enough to serve as a single test for hyperacusis. There was a moderate positive correlation between HTs and LDLs (r = 0.36), i.e., LDLs tended to be higher at frequencies where hearing loss was present, suggesting that hyperacusis is unlikely to be caused by HT increase, in contrast to tinnitus for which hearing loss is a main trigger. Moreover, our finding that LDLs are decreased across the full range of audiometric frequencies, regardless of the pattern or degree of hearing loss, indicates that hyperacusis might be due to a generalized increase in auditory gain. Tinnitus on the other hand is thought to be caused by neuroplastic changes in a restricted frequency range, suggesting that tinnitus and hyperacusis might not share a common mechanism.

Background: Tinnitus is experienced by up to 15% of the population and can lead to significant disability and distress. There is rarely a medical or surgical target and psychological therapies are recommended. We investigated whether mindfulness-based cognitive therapy (MBCT) could offer an effective new therapy for tinnitus. Methods: This single-site randomized controlled trial compared MBCT to intensive relaxation training (RT) for chronic, distressing tinnitus in adults. Both treatments involved 8 weekly, 120-min sessions focused on either relaxation (RT) or mindfulness meditation (MBCT). Assessments were completed at baseline and at treatment commencement 8 weeks later. The primary outcomes were tinnitus severity (Tinnitus Questionnaire) and psychological distress (Clinical Outcomes in Routine Evaluation - Non-Risk, CORE-NR), 16 weeks after baseline. The analysis utilized a modified intention-to-treat approach. Results: A total of 75 patients were randomly allocated to MBCT (n = 39) or RT (n = 36). Both groups showed significant reductions in tinnitus severity and loudness, psychological distress, anxiety, depression, and disability. MBCT led to a significantly greater reduction in tinnitus severity than RT, with a mean difference of 6.3 (95% CI 1.3-11.4, p = 0.016). Effects persisted 6 months later, with a mean difference of 7.2 (95% CI 2.1-2.3, p = 0.006) and a standardized effect size of 0.56 (95% CI 0.16-0.96). Treatment was effective regardless of initial tinnitus severity, duration, or hearing loss. Conclusions: MBCT is effective in reducing tinnitus severity in chronic tinnitus patients compared to intensive RT. It also reduces psychological distress and disability. Future studies should explore the generalizability of this approach and how outcome relates to different aspects of the intervention.

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