Generalizable Sample-Efficient Siamese Autoencoder for Tinnitus Diagnosis in Listeners With Subjective Tinnitus.

Electroencephalogram (EEG)-based neurofeedback has been widely studied for tinnitus therapy in recent years. Most existing research relies on experts' cognitive prediction, and studies based on machine learning and deep learning are either data-hungry or not well generalizable to new subjects. In this paper, we propose a robust, data-efficient model for distinguishing tinnitus from the healthy state based on EEG-based tinnitus neurofeedback. We propose trend descriptor, a feature extractor with lower fineness, to reduce the effect of electrode noises on EEG signals, and a siamese encoder-decoder network boosted in a supervised manner to learn accurate alignment and to acquire high-quality transferable mappings across subjects and EEG signal channels. Our experiments show the proposed method significantly outperforms state-of-the-art algorithms when analyzing subjects' EEG neurofeedback to 90dB and 100dB sound, achieving an accuracy of 91.67%-94.44% in predicting tinnitus and control subjects in a subject-independent setting. Our ablation studies on mixed subjects and parameters show the method's stability in performance.

Impact of tDCS and HD-tDCS on tinnitus perception: A scoping review.

Tinnitus is the auditory phantom perception of a sound that severely affects the quality of life of over 300,000 people in the United Kingdom alone. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation tool, which has been investigated as a potential tinnitus management option since 2006. This study aimed to investigate the impact of tDCS and high-definition transcranial direct current stimulation (HD-tDCS) on tinnitus perception. A scoping review was undertaken using the framework by Arksey and O'malley (2005). After consideration of relevance, 38 primary research studies were included in the data charting to examine the impact of (HD-)tDCS on tinnitus. Twenty-two of the primary research studies reported significant therapeutic effects of (HD)-tDCS on tinnitus perception. However, only eight of these included a sham-control condition. The tDCS protocols in the studies were highly heterogeneous and sample sizes were generally small. More double-blind, sham-controlled trials are needed that use similar protocols and outcome measures before definitive conclusions about the efficacy of (HD-)tDCS for tinnitus can be drawn.

Hidden Hearing Loss Impacts the Neural Representation of Speech in Background Noise.

Many individuals with seemingly normal hearing abilities struggle to understand speech in noisy backgrounds. To understand why this might be the case, we investigated the neural representation of speech in the auditory midbrain of gerbils with "hidden hearing loss" through noise exposure that increased hearing thresholds only temporarily. In noise-exposed animals, we observed significantly increased neural responses to speech stimuli, with a more pronounced increase at moderate than at high sound intensities. Noise exposure reduced discriminability of neural responses to speech in background noise at high sound intensities, with impairment most severe for tokens with relatively greater spectral energy in the noise-exposure frequency range (2-4 kHz). At moderate sound intensities, discriminability was surprisingly improved, which was unrelated to spectral content. A model combining damage to high-threshold auditory nerve fibers with increased response gain of central auditory neurons reproduced these effects, demonstrating that a specific combination of peripheral damage and central compensation could explain listening difficulties despite normal hearing thresholds.

Earplug-induced changes in acoustic reflex thresholds suggest that increased subcortical neural gain may be necessary but not sufficient for the occurrence of tinnitus.

The occurrence of tinnitus is associated with hearing loss and neuroplastic changes in the brain, but disentangling correlation and causation has remained difficult in both human and animal studies. Here we use earplugs to cause a period of monaural deprivation to induce a temporary, fully reversible tinnitus sensation, to test whether differences in subcortical changes in neural response gain, as reflected through changes in acoustic reflex thresholds (ARTs), could explain the occurrence of tinnitus. Forty-four subjects with normal hearing wore an earplug in one ear for either 4 (n = 27) or 7 days (n = 17). Thirty subjects reported tinnitus at the end of the deprivation period. ARTs were measured before the earplug period and immediately after taking the earplug out. At the end of the earplug period, ARTs in the plugged ear were decreased by 5.9 ±â€¯1.1 dB in the tinnitus-positive group, and by 6.3 ±â€¯1.1 dB in the tinnitus-negative group. In the control ear, ARTs were increased by 1.3 ±â€¯0.8 dB in the tinnitus-positive group, and by 1.6 ±â€¯2.0 dB in the tinnitus-negative group. There were no significant differences between the groups with 4 and 7 days of auditory deprivation. Our results suggest that either the subcortical neurophysiological changes underlying the ART reductions might not be related to the occurrence of tinnitus, or that they might be a necessary component of the generation of tinnitus, but with additional changes at a higher level of auditory processing required to give rise to tinnitus. This article is part of a Special Issue entitled: Hearing Loss, Tinnitus, Hyperacusis, Central Gain.

The search for noise-induced cochlear synaptopathy in humans: Mission impossible?

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.

Increased auditory cortex neural response amplitude in adults with chronic unilateral conductive hearing impairment.

Animal studies have demonstrated that unilateral hearing loss can induce changes in neural response amplitude of the mature central auditory system (CAS). However, there is limited physiological evidence of these neural gain changes in the auditory cortex of human adults. The present study investigated the impact of chronic, unilateral conductive hearing impairment on cortical auditory evoked potentials (CAEPs) recorded from 15 adults (21-65 years old) in response to a 1 kHz tone (80 ms duration) presented to the impaired ear via a bone conduction transducer. The amplitude and latency of the main CAEP components were compared to those obtained from normal hearing age-matched control participants. Both P1-N1 and N1-P2 amplitudes were significantly larger in the hearing impaired relative to the control participants. Differences between groups in the mean latencies of P1, N1, and P2 were not statistically significant. These results are the first to provide direct evidence of increased neural response amplitude in the adult human auditory cortex in the presence of unilateral conductive hearing loss. Importantly, the study shows that central gain changes are a direct result of deprivation of sound rather than cochlear or neural pathology.

Hidden hearing loss selectively impairs neural adaptation to loud sound environments.

Exposure to even a single episode of loud noise can damage synapses between cochlear hair cells and auditory nerve fibres, causing hidden hearing loss (HHL) that is not detected by audiometry. Here we investigate the effects of noise-induced HHL on functional hearing by measuring the ability of neurons in the auditory midbrain of mice to adapt to sound environments containing quiet and loud periods. Neurons from noise-exposed mice show less capacity for adaptation to loud environments, convey less information about sound intensity in those environments, and adaptation to the longer-term statistical structure of fluctuating sound environments is impaired. Adaptation comprises a cascade of both threshold and gain adaptation. Although noise exposure only impairs threshold adaptation directly, the preserved function of gain adaptation surprisingly aggravates coding deficits for loud environments. These deficits might help to understand why many individuals with seemingly normal hearing struggle to follow a conversation in background noise.

Increased spontaneous firing rates in auditory midbrain following noise exposure are specifically abolished by a Kv3 channel modulator.

Noise exposure has been shown to produce long-lasting increases in spontaneous activity in central auditory structures in animal models, and similar pathologies are thought to contribute to clinical phenomena such as hyperacusis or tinnitus in humans. Here we demonstrate that multi-unit spontaneous neuronal activity in the inferior colliculus (IC) of mice is significantly elevated four weeks following noise exposure at recording sites with frequency tuning within or near the noise exposure band, and this selective central auditory pathology can be normalised through administration of a novel compound that modulates activity of Kv3 voltage-gated ion channels. The compound had no statistically significant effect on IC spontaneous activity without noise exposure, nor on thresholds or frequency tuning of tone-evoked responses either with or without noise exposure. Administration of the compound produced some reduction in the magnitude of evoked responses to a broadband noise, but unlike effects on spontaneous rates, these effects on evoked responses were not specific to recording sites with frequency tuning within the noise exposure band. Thus, the results suggest that modulators of Kv3 channels can selectively counteract increases in spontaneous activity in the auditory midbrain associated with noise exposure.

Mindfulness-Based Cognitive Therapy as a Treatment for Chronic Tinnitus: A Randomized Controlled Trial.

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.

Using acoustic reflex threshold, auditory brainstem response and loudness judgments to investigate changes in neural gain following acute unilateral deprivation in normal hearing adults.

Unilateral auditory deprivation induces a reduction in the acoustic reflex threshold (ART) and an increase in loudness. These findings have been interpreted as a compensatory change in neural gain, governed by changes in excitatory and inhibitory neural inputs. There is also evidence to suggest that changes in neural gain can be measured using the auditory brainstem response (ABR). The present study extended Munro et al. (2014) [J. Acoust. Soc. Am. 135, 315-322] by investigating changes after 4 days of unilateral earplug use to: (i) ART, (ii) ABR and (iii) loudness. Because changes may occur during the post-deprivation test session (day 4), ART measurements were taken 1 h and 2 h post-earplug removal. There was a significant reduction in ART in the treatment ear immediately after the removal of the earplug, which is consistent with a compensatory increase in neural gain. A novel finding was the significant return of ARTs to baseline within 2 h of earplug removal. A second novel finding was a significant decrease in the mean amplitude of ABR wave V in the treatment ear, but a significant increase in the control ear, both after 4 days of deprivation. These changes in the ABR are in the opposite direction to those predicted. We were unable to replicate the change in loudness reported in previous deprivation studies; however, the short period of earplug use may have contributed to this null finding.

No change in the acoustic reflex threshold and auditory brainstem response following short-term acoustic stimulation in normal hearing adults.

Unilateral auditory deprivation or stimulation can induce changes in loudness and modify the sound level required to elicit the acoustic reflex. This has been explained in terms of a change in neural response, or gain, for a given sound level. However, it is unclear if these changes are driven by the asymmetry in auditory input or if they will also occur following bilateral changes in auditory input. The present study used a cross-over trial of unilateral and bilateral amplification to investigate changes in the acoustic reflex thresholds (ARTs) and the auditory brainstem response (ABR) in normal hearing listeners. Each treatment lasted 7 days and there was a 7-day washout period between the treatments. There was no significant change in the ART or ABR with either treatment. This null finding may have occurred because the amplification was insufficient to induce experience-related changes to the ABR and ART. Based on the null findings from the present study, and evidence of a change in ART in previous unilateral hearing aid use in normal hearing listeners, the threshold to trigger adaptive changes appears to be around 5 days of amplification with real ear insertion gain greater than 13-17 dB.

Time course and frequency specificity of sub-cortical plasticity in adults following acute unilateral deprivation.

Auditory deprivation and stimulation can change the threshold of the acoustic reflex, but the mechanisms underlying these changes remain largely unknown. In order to elucidate the mechanism, we sought to characterize the time-course as well as the frequency specificity of changes in acoustic reflex thresholds (ARTs). In addition, we compared ipsilateral and contralateral measurements because the pattern of findings may shed light on the anatomical location of the change in neural gain. Twenty-four normal-hearing adults wore an earplug continuously in one ear for six days. We measured ipsilateral and contralateral ARTs in both ears on six occasions (baseline, after 2, 4 and 6 days of earplug use, and 4 and 24 h after earplug removal), using pure tones at 0.5, 1, 2 and 4 kHz and a broadband noise stimulus, and an experimenter-blinded design. We found that ipsi- as well as contralateral ARTs were obtained at a lower sound pressure level after earplug use, but only when the reflex was elicited by stimulating the treatment ear. Changes in contralateral ARTs were not the same as changes in ipsilateral ARTs when the stimulus was presented to the control ear. Changes in ARTs were present after 2 days of earplug use, and reached statistical significance after 4 days, when the ipsilateral and contralateral ARTs were measured in the treatment ear. The greatest changes in ARTs occurred at 2 and 4 kHz, the frequencies most attenuated by the earplug. After removal of the earplug, ARTs started to return to baseline relatively quickly, and were not significantly different from baseline by 4-24 h. There was a trend for the recovery to occur quicker than the onset. The changes in ARTs are consistent with a frequency-specific gain control mechanism operating around the level of the ventral cochlear nucleus in the treatment ear, on a time scale of hours to days. These findings, specifically the time course of change, could be applicable to other sensory systems, which have also shown evidence of a neural gain control mechanism.

Non-Monotonic Relation between Noise Exposure Severity and Neuronal Hyperactivity in the Auditory Midbrain.

The occurrence of tinnitus can be linked to hearing loss in the majority of cases, but there is nevertheless a large degree of unexplained heterogeneity in the relation between hearing loss and tinnitus. Part of the problem might be that hearing loss is usually quantified in terms of increased hearing thresholds, which only provides limited information about the underlying cochlear damage. Moreover, noise exposure that does not cause hearing threshold loss can still lead to "hidden hearing loss" (HHL), i.e., functional deafferentation of auditory nerve fibers (ANFs) through loss of synaptic ribbons in inner hair cells. While it is known that increased hearing thresholds can trigger increases in spontaneous neural activity in the central auditory system, i.e., a putative neural correlate of tinnitus, the central effects of HHL have not yet been investigated. Here, we exposed mice to octave-band noise at 100 and 105 dB SPL to generate HHL and permanent increases of hearing thresholds, respectively. Deafferentation of ANFs was confirmed through measurement of auditory brainstem responses and cochlear immunohistochemistry. Acute extracellular recordings from the auditory midbrain (inferior colliculus) demonstrated increases in spontaneous neuronal activity (a putative neural correlate of tinnitus) in both groups. Surprisingly, the increase in spontaneous activity was most pronounced in the mice with HHL, suggesting that the relation between hearing loss and neuronal hyperactivity might be more complex than currently understood. Our computational model indicated that these differences in neuronal hyperactivity could arise from different degrees of deafferentation of low-threshold ANFs in the two exposure groups. Our results demonstrate that HHL is sufficient to induce changes in central auditory processing, and they also indicate a non-monotonic relationship between cochlear damage and neuronal hyperactivity, suggesting an explanation for why tinnitus might occur without obvious hearing loss and conversely why hearing loss does not always lead to tinnitus.

Abnormal Auditory Gain in Hyperacusis: Investigation with a Computational Model.

Hyperacusis is a frequent auditory disorder that is characterized by abnormal loudness perception where sounds of relatively normal volume are perceived as too loud or even painfully loud. As hyperacusis patients show decreased loudness discomfort levels (LDLs) and steeper loudness growth functions, it has been hypothesized that hyperacusis might be caused by an increase in neuronal response gain in the auditory system. Moreover, since about 85% of hyperacusis patients also experience tinnitus, the conditions might be caused by a common mechanism. However, the mechanisms that give rise to hyperacusis have remained unclear. Here, we have used a computational model of the auditory system to investigate candidate mechanisms for hyperacusis. Assuming that perceived loudness is proportional to the summed activity of all auditory nerve (AN) fibers, the model was tuned to reproduce normal loudness perception. We then evaluated a variety of potential hyperacusis gain mechanisms by determining their effects on model equal-loudness contours and comparing the results to the LDLs of hyperacusis patients with normal hearing thresholds. Hyperacusis was best accounted for by an increase in non-linear gain in the central auditory system. Good fits to the average patient LDLs were obtained for a general increase in gain that affected all frequency channels to the same degree, and also for a frequency-specific gain increase in the high-frequency range. Moreover, the gain needed to be applied after subtraction of spontaneous activity of the AN, which is in contrast to current theories of tinnitus generation based on amplification of spontaneous activity. Hyperacusis and tinnitus might therefore be caused by different changes in neuronal processing in the central auditory system.

Pump up the volume: could excessive neural gain explain tinnitus and hyperacusis?

Naturally occurring stimuli can vary over several orders of magnitude and may exceed the dynamic range of sensory neurons. As a result, sensory systems adapt their sensitivity by changing their responsiveness or 'gain'. While many peripheral adaptation processes are rapid, slow adaptation processes have been observed in response to sensory deprivation or elevated stimulation. This adaptation process alters neural gain in order to adjust the basic operating point of sensory processing. In the auditory system, abnormally high neural gain may result in higher spontaneous and/or stimulus-evoked neural firing rates, and this may have the unintended consequence of presenting as tinnitus and/or sound intolerance, respectively. Therefore, a better understanding of neural gain, in health and disease, may lead to more effective treatments for these aberrant auditory perceptions. This review provides a concise summary of (i) evidence for changes in neural gain in the auditory system of animals, (ii) physiological and perceptual changes in adult human listeners following an acute period of enhanced acoustic stimulation and/or deprivation, (iii) physiological evidence of excessive neural gain in tinnitus and hyperacusis patients, and (iv) the relevance of neural gain in the clinical treatment of tinnitus and hyperacusis.

Audiometric characteristics of hyperacusis patients.

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.

Plasticity and modified loudness following short-term unilateral deprivation: evidence of multiple gain mechanisms within the auditory system.

Auditory deprivation and stimulation can change the threshold of the acoustic middle ear reflex as well as loudness in adult listeners. However, it has remained unclear whether changes in these measures are due to the same mechanism. In this study, deprivation was achieved using a monaural earplug that was worn by listeners for 7 days. Acoustic reflex thresholds (ARTs) and categorical loudness ratings were measured using a blinded design in which the experimenter was unaware of which ear had been plugged. Immediately after terminating unilateral deprivation, ARTs were obtained at a lower sound pressure level in the ear that had been fitted with an earplug and at a higher sound pressure level in the control ear. In contrast, categorical judgments of loudness changed in the same direction in both ears with a given stimulus level reported as louder after unilateral deprivation. The relationship between changes to the ART and loudness judgments was not statistically significant. For both the ARTs and the categorical loudness judgments, most of the changes had disappeared within 24 h after earplug removal. The changes in ARTs, as a consequence of unilateral sound deprivation, are consistent with a gain control mechanism; however, the lack of relationship with the categorical loudness judgments, and the different pattern of findings for each measure, suggests the possibility of multiple gain mechanisms.

Tinnitus in men, mice (as well as other rodents), and machines.

The phantom auditory sensation of tinnitus is now studied in humans, animals, and computer models, and our understanding of how tinnitus is triggered and which neural mechanisms give rise to the phantom sensation in the brain has increased considerably. In most cases, tinnitus is associated with hearing loss, and even tinnitus patients with normal hearing thresholds might have cochlear damage that is not detected through conventional audiometry, as has been recently shown through auditory brainstem response measurements. Animals show behavioural signs of tinnitus after induction of hearing loss, indicating a causal relation. Moreover, surgical reduction of hearing loss in otosclerosis can reduce or even abolish tinnitus. However, hearing loss does not always lead to tinnitus. Psychophysical measurements have indicated that certain types of cochlear damage might be more closely linked to tinnitus than others. Recent animal studies have used behavioural testing to distinguish between animals with and without tinnitus after noise exposure. Comparisons between these groups of animals have helped identify neural correlates of tinnitus as well as factors that could represent a predisposition for tinnitus. Human neuroimaging studies have also begun to separate the neural signature of tinnitus from other consequences of hearing loss. The functional mechanisms that could underlie tinnitus development tinnitus have been analysed in computational modelling studies, which indicate that tinnitus could be a side-effect of the brain's attempt to compensate for hearing loss. Even though causal treatments for tinnitus are currently not available, hearing aids can provide considerable benefit when used in conjunction with counselling, tinnitus retraining therapy or cognitive behavioural therapy. Finally, animal studies demonstrate that the development of chronic noise-induced tinnitus might be prevented through timely interventions after noise exposure. This article is part of a Special Issue entitled .

Off-frequency listening in subjects with chronic tinnitus.

The occurrence of subjective tinnitus has been linked to cochlear damage, as most tinnitus patients have impaired hearing, and animal studies have shown that the induction of hearing loss can lead to behavioural signs of tinnitus. In tinnitus patients, the pure-tone audiogram is the main source of information about cochlear damage, but hearing thresholds alone may not adequately reflect its magnitude. Etchelecou et al. (2011) reported that the majority of patients with acute tinnitus post impulse noise exposure showed off-frequency listening (OFL), which is not readily observed in pure-tone audiograms. We investigated the possibility of OFL occurring in subjects with chronic tinnitus by testing twenty subjects who had experienced tinnitus for more than a year. OFL was assessed by measuring psychophysical tuning curves using a forward-masking paradigm. OFL occurred in 13 out of 20 subjects, 12 of whom also did not perceive frequencies above 8 kHz. Such unresponsive frequencies (UFs) were also present in three subjects without OFL. The tinnitus spectrum generally reached its highest values at the edge of or within the frequency regions with OFL or UFs, but there was no significant correlation between edge frequencies and the frequency with the highest tinnitus pitch similarity rating. When OFL and UFs were taken as evidence for cochlear dead regions, 16/20 subjects passed the criterion for cochlear dead regions. The remaining four subjects showed neither OFL nor UFs.