Computational models of neurophysiological correlates of tinnitus

The understanding of tinnitus has progressed considerably in the past decade, but the details of the mechanisms that give rise to this phantom perception of sound without a corresponding acoustic stimulus have not yet been pinpointed. It is now clear that tinnitus is generated in the brain, not in the ear, and that it is correlated with pathologically altered spontaneous activity of neurons in the central auditory system. Both increased spontaneous firing rates and increased neuronal synchrony have been identified as putative neuronal correlates of phantom sounds in animal models, and both phenomena can be triggered by damage to the cochlea. Various mechanisms could underlie the generation of such aberrant activity. At the cellular level, decreased synaptic inhibition and increased neuronal excitability, which may be related to homeostatic plasticity, could lead to an over-amplification of natural spontaneous activity. At the network level, lateral inhibition could amplify differences in spontaneous activity, and structural changes such as reorganization of tonotopic maps could lead to self-sustained activity in recurrently connected neurons. However, it is difficult to disentangle the contributions of different mechanisms in experiments, especially since not all changes observed in animal models of tinnitus are necessarily related to tinnitus. Computational modeling presents an opportunity of evaluating these mechanisms and their relation to tinnitus. Here we review the computational models for the generation of neurophysiological correlates of tinnitus that have been proposed so far, and evaluate predictions and compare them to available data. We also assess the limits of their explanatory power, thus demonstrating where an understanding is still lacking and where further research may be needed. Identifying appropriate models is important for finding therapies, and we therefore, also summarize the implications of the models for approaches to treat tinnitus

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

Reversible Induction of Phantom Auditory Sensations through Simulated Unilateral Hearing Loss

Tinnitus, a phantom auditory sensation, is associated with hearing loss in most cases, but it is unclear if hearing loss causes tinnitus. Phantom auditory sensations can be induced in normal hearing listeners when they experience severe auditory deprivation such as confinement in an anechoic chamber, which can be regarded as somewhat analogous to a profound bilateral hearing loss. As this condition is relatively uncommon among tinnitus patients, induction of phantom sounds by a lesser degree of auditory deprivation could advance our understanding of the mechanisms of tinnitus. In this study, we therefore investigated the reporting of phantom sounds after continuous use of an earplug. 18 healthy volunteers with normal hearing wore a silicone earplug continuously in one ear for 7 days. The attenuation provided by the earplugs simulated a mild high-frequency hearing loss, mean attenuation increased from <10 dB at 0.25 kHz to >30 dB at 3 and 4 kHz. 14 out of 18 participants reported phantom sounds during earplug use. 11 participants presented with stable phantom sounds on day 7 and underwent tinnitus spectrum characterization with the earplug still in place. The spectra showed that the phantom sounds were perceived predominantly as high-pitched, corresponding to the frequency range most affected by the earplug. In all cases, the auditory phantom disappeared when the earplug was removed, indicating a causal relation between auditory deprivation and phantom sounds. This relation matches the predictions of our computational model of tinnitus development, which proposes a possible mechanism by which a stabilization of neuronal activity through homeostatic plasticity in the central auditory system could lead to the development of a neuronal correlate of tinnitus when auditory nerve activity is reduced due to the earplug

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

Einfluss der Kräuterfutterkomponente eines kommerziellen Ergänzungsfuttermittels auf Serumparameter, Fruchtbarkeit und Langlebigkeit von Milchkühen

A randomized placebo controlled trial investigates an herbal mixture containing mainly Urtica dioica L. (herba), Trigonella foenum-greacum L. (semen), Silybum marianum (L.) Gaert. (fructus) and Achillea millefolium L. (herba). The herbal mixture was fed daily (50g per cow) about 60d from dry off to calving date. 63 dairy cows (32 in the herb-(h)- and 31 in the placebo-(p)-group) of one organic farm were included in the study. Cows were differentiated depending on their lactation number: 19 first lactating cows (L1; h: n=10, p: n=9), 23 cows of second to fourth lactation (L2-4; h: n=11, p: n=12) and 21 cows with more than four lactations (L>4; h: n=11, p: n=10). The herbal group showed the following significant differences (p4 were higher; abnormalities in at least one of 7 tested serum parameters in lactating group L1 were less; in L>4 less ovarian follicles and larger uteri could be found in early lactation; a longer intercalving period (h: 387 days; p: 344 days) but a lower overall culling rate (h: 17%; p: 50%) and culling rate for fertility reasons (h: 3%; p: 23%). The herbal mixture seemed 1. to improve the postpartal metabolic status of dairy cows, 2. to prolong the postnatal anoestrus but 3. to decrease the culling rate particularly for fertility reasons. Overall the prolonged intercalving period will have a lower economic effect than the decreased culling rate

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

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 hours 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 hours. 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

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