Tinnitus Perception Research Articles

Behavioural and Electrophysiological Evaluation of Loudness Growth in Clinically Normal Hearing Tinnitus Patients with and without Hyperacusis

Introduction: The common mechanism of tinnitus, hyperacusis, and loudness perception is hypothesized to be related to central gain. Although central gain increases with attempts to compensate hearing loss, reduced input can also be observed in those with clinically normal hearing. This study aimed to evaluate the loudness growth function of tinnitus patients with and without hyperacusis using behavioural and electrophysiological methods. Methods: The study consists of three groups with a total of 60 clinically normal hearing subjects, including the control group (10 men and 10 women; mean age 39.8, SD 11.8 years), tinnitus group (10 men and 10 women; mean age 40.9, SD 12.2 years), and hyperacusis group (also have tinnitus) (7 men and 13 women; mean age 38.7, SD 14.6 years). Loudness discomfort levels (LDLs), categorical loudness scaling (CLS), and cortical auditory evoked potentials were used for the evaluation of loudness growth. N1-P2 component amplitudes and latencies were measured. Results: LDL results of 500, 1,000, 2,000, 4,000, and 8,000 Hz showed a significant difference between the hyperacusis group and the other two groups (p < 0.001). In the loudness scale test performed with 500 Hz and 2,000 Hz narrow-band noise (NBN) stimulus, a significant difference was observed between the hyperacusis group and the other two groups in the “medium,” “loud,” and “very loud” categories (p < 0.001). In the cortical examination performed with 500 Hz and 2,000 Hz NBN stimulus at 40, 60, and 80 dB nHL intensities, no significant difference was observed between the groups in the N1, P2 latency, and N1-P2 peak-to-peak amplitude. Conclusion: Although the hyperacusis group is significantly different between groups in behavioural tests, the same cannot be said for electrophysiological tests. In our attempt to differentiate tinnitus and hyperacusis with electrophysiological tests over the loudness growth function, N1 and P2 responses were not seen as suitable methods. However, it appears to be beneficial to use CLS in addition to LDLs in behavioural tests.

Small molecule modulation of the large-conductance calcium-activated potassium channel suppresses salicylate-induced tinnitus in mice

Tinnitus is the phantom perception of sound that has no external source. A neurological signature of tinnitus, and the frequently associated hyperacusis, is an imbalance between excitatory and inhibitory activity in the central auditory system (CAS), leading to dysregulated network excitability. The large conductance, calcium-activated potassium (BK) channel is a key player in pre- and post-synaptic excitability through its mediation of K+ currents. Changes in BK channel activity are associated with aberrant network activity in sensory regions of the CNS, raising the possibility that BK channel modulation could regulate activity associated with tinnitus and hyperacusis. To test whether BK channel openers are able to suppress biomarkers of drug-induced tinnitus and hyperacusis, the 1,3,4 oxadiazole BMS-191011 was given to young adult CBA mice that had been administered 250 mg/kg sodium salicylate (SS). Systemic treatment with BMS-191011 reduced behavioral manifestations of SS-induced tinnitus, but not hyperacusis, probed via the gap-in-noise startle response method. Systemic BMS-191011 treatment did not influence SS-induced increases in auditory brainstem response functions, but local application at the inferior colliculus did reverse SS-suppressed spontaneous activity, particularly in the frequency region of the tinnitus percept. Thus, action of BMS-191011 in the inferior colliculus may contribute to the reduction in behaviorally measured tinnitus. Together, these findings support the utility of BK channel openers in reducing central auditory processing changes associated with the formation of the tinnitus percept.

Estimation of Tinnitus-Related Socioeconomic Costs in Germany.

Despite the high prevalence of tinnitus in Germany of nearly 12% of the general population, there have been no systematic studies on the socioeconomic costs for German society caused by tinnitus so far. Here we analyzed data from 258 chronic tinnitus patients—namely tinnitus severity and health utility index (HUI)—and correlated them with their tinnitus-related public health care costs, private expenses, and economic loss due to their tinnitus percept as assessed by questionnaires. We found correlations of the HUI with health care costs and calculated the mean socioeconomic costs per tinnitus patient in Germany. According to our most conservative estimate, these sum up to EUR 4798.91 per year. Of that EUR 2206.95 account for the public health care, EUR 290.45 are carried by the patient privately and the remaining EUR 2301.51 account for economical loss due to sick leave. With a prevalence of 5.5% with at least bothersome tinnitus, this sums up to 21.9 billion Euro per year and with 25.82 sick leave days; tinnitus patients miss work more than double the time of the average German employee (10.9 days). The findings fit within the cost ranges of studies from other European countries and the USA and show that the socioeconomic burden of this disease-like symptom is a global problem. In comparison with the costs of other major chronic diseases in Germany—such as chronic obstructive pulmonary diseases (ca. 16 billion Euro) or diabetes mellitus (ca. 42 billion Euro)—the relevance of the ‘symptom’ tinnitus for the German social economy becomes even more obvious.

Neuroanatomical alterations in middle frontal gyrus and the precuneus related to tinnitus and tinnitus distress

Tinnitus is the phantom perception of sound when there is no external auditory input. This sound is mostly perceived as a ringing, whistling or buzzing in the ear. There is evidence of neural changes in both central auditory regions as well as other brain areas like the prefrontal cortex and the limbic system. However, brain morphological studies assessing gray matter volume and cortical thickness have shown inconsistent results. We here investigated neuroanatomical alterations in tinnitus related to the tinnitus perception along with tinnitus distress and cognitive abilities. Twenty tinnitus patients and 20 control participants matched in age, sex and hearing loss participated in the study. They underwent magnetic resonance imaging and audiometric as well as cognitive assessments. Our results demonstrate increased gray matter volume in the middle frontal gyrus and frontal pole in tinnitus compared to control participants. Moreover, we found increased cortical thickness in the precuneus associated with tinnitus distress as well as an interaction between group and cognitive assessment scores in cortical thickness of the middle frontal gyrus, indicating higher cortical thickness with better scores in controls and lower scores in tinnitus patients. These findings indicate that increased tinnitus awareness and annoyance is reflected in increased brain structural changes in the precuneus, frontal pole and middle frontal gyrus that may also have implications on general cognitive abilities.

COVID-19 and tinnitus: an initiative to improve tinnitus care

Objective To investigate the effects of COVID-19 on individuals with tinnitus and their views to guide future tinnitus care. Design A mixed-methods cross-sectional research design. Study sample An online survey was completed by 365 individuals with tinnitus from Australia and other countries. Results Tinnitus was reported to be more bothersome during the pandemic by 36% of respondents, whereas 59% reported no change and 5% reported less bothersome tinnitus. Nearly half of the respondents had received COVID-19 vaccination(s) and 12% of them reported more bothersome tinnitus while 2% developed tinnitus post-vaccination. Australian respondents spent less time in self-isolation or quarantine and saw fewer change in in-person social contact than respondents from other countries. More than 70% of respondents thought that tinnitus care services were insufficient both before and during the pandemic. Regarding their opinions on how to improve tinnitus care in the future, five themes including alleviation of condition, government policies, reduced barriers, self- and public-awareness, and hearing devices were identified. Conclusions A majority of respondents did not perceive any change in tinnitus perception and one-third of respondents had worsened tinnitus during the pandemic. To improve tinnitus care, better awareness and more accessible resources and management are crucial.

A Narrative Review of Auditory Categorisation and Its Potential Role in Tinnitus Perception

Auditory categorisation is a phenomenon reflecting the non-linear nature of human perceptual spaces which govern sound perception. Categorisation training paradigms may reduce sensitivity toward training stimuli, decreasing the representation of these stimuli in auditory perceptual maps. Reduced cortical representation may have clinical implications for conditions that arise from disturbances in cortical activation, such as tinnitus. This review explores the categorisation of sound, with a particular focus on tinnitus. The potential of categorisation training as a sound-based tinnitus therapy is discussed. A narrative review methodological framework was followed. Four databases (PubMed, Google Scholar, Scopus, and ScienceDirect) were extensively searched for the following key words: categorisation, categorical perception, perceptual magnet effect, generalisation, and categorisation OR categorical perception OR perceptual magnet effect OR generalisation AND sound. Given the exploratory nature of the review and the fact that early works on categorisation are crucial to the understanding and development of auditory categorisation, all study types were selected for the period 1950–2022. Reference lists of articles were reviewed to identify any further relevant studies. The results of the review were catalogued and organised into themes. In total, 112 articles were reviewed in full, from which 59 were found to contain relevant information and were included in the review. Key themes identified included categorical perception of speech stimuli, warping of the auditory perceptual space, categorisation versus discrimination, the presence of categorisation across several modalities, and categorisation as an innate versus learned feature. Although a substantial amount of work focused on evaluating the effects of categorisation training on sound perception, only two studies investigated the effects of categorisation training on tinnitus. Implementation of a categorisation-based perceptual training paradigm could serve as a promising means of tinnitus management by reversing the changes in cortical plasticity that are seen in tinnitus, in turn altering the representation of sound within the auditory cortex itself. In the instance that the categorisation training is successful, this would likely mean a decrease in the level of activity within the auditory cortex (and other associated cortical areas found to be hyperactive in tinnitus) as well as a reduction in tinnitus salience.

Preventive Effects of Ginkgo-Extract EGb 761® on Noise Trauma-Induced Cochlear Synaptopathy.

Noise trauma-induced loss of ribbon synapses at the inner hair cells (IHC) of the cochlea may lead to hearing loss (HL), resulting in tinnitus. We are convinced that a successful and sustainable therapy of tinnitus has to treat both symptom and cause. One of these causes may be the mentioned loss of ribbon synapses at the IHC of the cochlea. In this study, we investigated the possible preventive and curative effects of the Ginkgo biloba extract EGb 761® on noise-induced synaptopathy, HL, and tinnitus development in Mongolian gerbils (Meriones unguiculatus). To this end, 37 male animals received EGb 761® or placebo orally 3 weeks before (16 animals) or after (21 animals) a monaural acoustic noise trauma (2 kHz, 115 dB SPL, 75 min). Animals’ hearing thresholds were determined by auditory brainstem response (ABR) audiometry. A possible tinnitus percept was assessed by the gap prepulse inhibition acoustic startle reflex (GPIAS) response paradigm. Synaptopathy was quantified by cochlear immunofluorescence histology, counting the ribbon synapses of 15 IHCs at 11 different cochlear frequency locations per ear. We found a clear preventive effect of EGb 761® on ribbon synapse numbers with the surprising result of a significant increase in synaptic innervation on the trauma side relative to placebo-treated animals. Consequently, animals treated with EGb 761® before noise trauma did not develop a significant HL and were also less affected by tinnitus compared to placebo-treated animals. On the other hand, we did not see a curative effect (EGb 761® treatment after noise trauma) of the extract on ribbon synapse numbers and, consequently, a significant HL and no difference in tinnitus development compared to the placebo-treated animals. Taken together, EGb 761® prevented noise-induced HL and tinnitus by protecting from noise trauma-induced cochlear ribbon synapse loss; however, in our model, it did not restore lost ribbon synapses.

Prediction of Tinnitus Perception Based on Daily Life MHealth Data Using Country Origin and Season.

Tinnitus is an auditory phantom perception without external sound stimuli. This chronic perception can severely affect quality of life. Because tinnitus symptoms are highly heterogeneous, multimodal data analyses are increasingly used to gain new insights. MHealth data sources, with their particular focus on country- and season-specific differences, can provide a promising avenue for new insights. Therefore, we examined data from the TrackYourTinnitus (TYT) mHealth platform to create symptom profiles of TYT users. We used gradient boosting engines to classify momentary tinnitus and regress tinnitus loudness, using country of origin and season as features. At the daily assessment level, tinnitus loudness can be regressed with a mean absolute error rate of 7.9% points. In turn, momentary tinnitus can be classified with an F1 score of 93.79%. Both results indicate differences in the tinnitus of TYT users with respect to season and country of origin. The significance of the features was evaluated using statistical and explainable machine learning methods. It was further shown that tinnitus varies with temperature in certain countries. The results presented show that season and country of origin appear to be valuable features when combined with longitudinal mHealth data at the level of daily assessment.

The Effectiveness of Targeted Electrical Stimulation via Cochlear Implant on Tinnitus-Perceived Loudness.

IntroductionThe cause of tinnitus improvement in cochlear implant (CI) users is not understood. On the basis that a spatially limited dysfunction in the auditory pathway could cause tinnitus, we used single-channel stimulation to evaluate any variation of tinnitus-perceived loudness and identify the cochlear regions involved.Materials and MethodsIt was an observational prospective case-crossover study. After the first mapping, 21 adults with unilateral CI and chronic tinnitus expressed their tinnitus loudness based on the Visual Analog Scale (VAS) score (0–10) at baseline (L0), during a 10 s single-channel stimulation with C-level of electric current (L1) and 30 min after CI activation (L2). Tinnitus reduction [RT = (L0 – L1) × 100/L0] > 50% was considered significant. VAS outcomes were compared between baseline (L0) and (each) single-channel stimulation (L1) to find the channel with the greatest RT (suppressive channel-SC), whose frequency range revealed the cochlear region involved. Seven patients with asymmetric hearing loss underwent the pitch-matching test to identify the actual frequency evoked by the SC. We compared selective (L1) and non-selective (L2) intracochlear stimulation using paired t-test. Preoperative Tinnitus Handicap Inventory (THI) score was compared with those at 1, 6, and 12 months with paired t-tests to evaluate long-term tinnitus perception.ResultsWe observed a significant reduction of tinnitus loudness during the experimental procedure [L0 (6.4 ± 2.4) vs. L1 (1.7 ± 2.7), p = 0.003]. A total of 15/21 patients (71.4%) had a significant (RT > 50%) and selective improvement, reporting a mean L1 of 0.4 ± 2.0 (p = 0.0001). In 10/15 (66.6%) patients, the SC was in the apical turn, within 1,000 Hz; in 5/15 patients (33.4%) within 4,000 Hz. The cochlear region 125–313 Hz was the most affected by tinnitus improvement (p = 0.0074). Targeted stimulation was more effective than non-selective stimulation [L1 vs. L2 (4.3 ± 2.5), p = 0.0022]. In 3/7 patients, the perceived pitch did not fall within the SC frequency ranges. All patients with selective attenuation described tinnitus as monotone. Patients with non-selective attenuation had polyphonic tinnitus and better THI results after 1 year.ConclusionTargeted intracochlear electrical stimulation improved chronic tinnitus perception, especially in monotone tinnitus, and the apical region was mainly involved. Our results provide new insights into the pathophysiological mechanisms of tinnitus and targets for innovative therapeutic strategies.

Random Forest Classification to Predict Response to High-Definition Transcranial Direct Current Stimulation for Tinnitus Relief: A Preliminary Feasibility Study.

Objectives:Transcranial direct current stimulation (tDCS) of the right dorsolateral prefrontal cortex has been hypothesized to reduce tinnitus severity by modifying cortical activity in brain regions associated with the perception of tinnitus. However, individual response to tDCS has proven to be variable. We investigated the feasibility of using random forest classification to predict the response to high-definition (HD) tDCS for tinnitus relief.Design:A retrospective analysis was performed on a dataset consisting of 99 patients with subjective tinnitus receiving six consecutive sessions of HD-tDCS at the Antwerp University Hospital. A baseline assessment consisted of pure-tone audiometry and a set of questionnaires including the Tinnitus Functional Index (TFI), Hospital Anxiety and Depression Scale, and Edinburgh Handedness Inventory. Random forest classification was applied to predict, based on baseline questionnaire scores and hearing levels, whether each individual responded positively to the treatment (defined as a decrease of at least 13 points on the TFI). Further testing of the model was performed on an independent cohort of 32 patients obtained from the tinnitus center at the University of Regensburg.Results:Twenty-four participants responded positively to the HD-tDCS treatment. The random forest classifier predicted treatment response with an accuracy of 85.71% (100% sensitivity, 81.48% specificity), significantly outperforming a more traditional logistic regression approach. Performance of the classifier on an independent cohort was slightly but not significantly above chance level (71.88% accuracy, 66.67% sensitivity, 73.08% specificity). Feature importance analyses revealed that baseline tinnitus severity, co-occurrence of depressive symptoms and handedness were the most important predictors of treatment response. Baseline TFI scores were significantly higher in responders than in nonresponders.Conclusions:The proposed random forest classifier predicted treatment response with a high accuracy, significantly outperforming a more traditional statistical approach. Machine learning methods to predict treatment response might ultimately be used in a clinical setting to guide targeted treatment recommendations for individual tinnitus patients.

Circadian Sensitivity of Noise Trauma-Induced Hearing Loss and Tinnitus in Mongolian Gerbils.

Noise-induced hearing loss (HL) has a circadian component: In nocturnal mice, hearing thresholds (HT) have a significantly stronger effect to acoustic trauma when induced during the night compared to rather mild effects on hearing when induced during daytime. Here, we investigate whether such effects are also present in diurnal Mongolian gerbils and determined whether trauma-induced HL correlated with the development of a tinnitus percept in these animals. In particular, we investigated the effects of acoustic trauma (2 kHz, 115 dB SPL, 75 min) on HT and tinnitus development in 34 male gerbils exposed either at 9 AM, 1 PM, 5 PM, or 12 PM. HT was measured by acoustic brainstem response audiometry at defined times 1 day before and 1 week after the trauma. Possible tinnitus percepts were assessed behaviorally by the gap prepulse inhibition of the acoustic startle response at defined times 1 day before and 1 week after the trauma. We found daytime-dependent changes due to trauma in mean HT in a frequency-dependent manner comparable to the results in mice, but the results temporally shifted according to respective activity profiles. Additionally, we found linear correlations of these threshold changes with the strength of the tinnitus percept, with the most prominent correlations in the 5 PM trauma group. Taken together, circadian sensitivity of the HT to noise trauma can also be found in gerbils, and tinnitus strength correlates most strongly with HL only when the trauma is applied at the most sensitive times, which seem to be the evening.

Sequential Prefrontal and Temporoparietal Repetitive Transcranial Magnetic Stimulation (rTMS) for Treatment of Tinnitus With and Without Comorbid Depression: A Case Series and Systematic Review.

BackgroundTinnitus distress is related to both the loudness and intrusiveness of the tinnitus percept. Treatment approaches targeting both attentional/limbic and auditory systems may better alleviate tinnitus distress than approaches targeting the auditory system alone.Materials and MethodsTen subjects with chronic tinnitus received sequential rTMS treatment involving: 1) excitatory stimulation administered to the left dorsolateral prefrontal cortex (DLPFC) or inhibitory stimulation administered to the right DLPFC, followed by 2) inhibitory stimulation administered to primary auditory cortex (Heschel's gyrus or HG). A systematic literature review was performed to evaluate the existing literature on sequential repetitive Transcranial Magnetic Stimulation (rTMS) treatment approaches for tinnitus. Results of the case series are interpreted in the context of tinnitus neurobiology and the extant literature.ResultsSubjects experienced a significant decrease (average 21.7%) in symptoms on the Tinnitus Functional Index (TFI). Those with tinnitus alone experienced a greater mean symptom reduction than those with comorbid MDD (27.7 vs. 17.0%, respectively). Adverse effects were transient and minor. Literature review confirmed that sequential approaches had some advantages compared to single site rTMS; in general, the addition of 1 Hz treatment at DLPFC was superior to single site rTMS in the short term (1–12 weeks), while the addition of 20 Hz treatment at DLPFC appeared superior in the long term (90–180 days).ConclusionsSequential rTMS approaches for the treatment of tinnitus—particularly those administering low-frequency treatment at left DLPFC—merit further investigation.

Dose-Response Transcranial Electrical Stimulation Study Design: A Well-Controlled Adaptive Seamless Bayesian Method to Illuminate Negative Valence Role in Tinnitus Perception.

The use of transcranial Electrical Stimulation (tES) in the modulation of cognitive brain functions to improve neuropsychiatric conditions has extensively increased over the decades. tES techniques have also raised new challenges associated with study design, stimulation protocol, functional specificity, and dose-response relationship. In this paper, we addressed challenges through the emerging methodology to investigate the dose-response relationship of High Definition-transcranial Direct Current Stimulation (HD tDCS), identifying the role of negative valence in tinnitus perception. In light of the neurofunctional testable framework and tES application, hypotheses were formulated to measure clinical and surrogate endpoints. We posited that conscious pairing adequately pleasant stimuli with tinnitus perception results in correction of the loudness misperception and would be reinforced by concurrent active HD-tDCS on the left Dorsolateral Prefrontal Cortex (dlPFC). The dose-response relationship between HD-tDCS specificity and the loudness perception is also modeled. We conducted a double-blind, randomized crossover pilot study with six recruited tinnitus patients. Accrued data was utilized to design a well-controlled adaptive seamless Bayesian dose-response study. The sample size (n = 47, for 90% power and 95% confidence) and optimum interims were anticipated for adaptive decision-making about efficacy, safety, and single session dose parameters. Furthermore, preliminary pilot study results were sufficient to show a significant difference (90% power, 99% confidence) within the longitudinally detected self-report tinnitus loudness between before and under positive emotion induction. This study demonstrated a research methodology used to improve emotion regulation in tinnitus patients. In the projected method, positive emotion induction is essential for promoting functional targeting under HD-tDCS anatomical specificity to indicate the efficacy and facilitate the dose-finding process. The continuous updating of prior knowledge about efficacy and dose during the exploratory stage adapts the anticipated dose-response model. Consequently, the effective dose range to make superiority neuromodulation in correcting loudness misperception of tinnitus will be redefined. Highly effective dose adapts the study to a standard randomized trial and transforms it into the confirmatory stage in which active HD-tDCS protocol is compared with a sham trial (placebo-like). Establishing the HD-tDCS intervention protocols relying on this novel method provides reliable evidence for regulatory agencies to approve or reject the efficacy and safety. Furthermore, this paper supports a technical report for designing multimodality data-driven complementary investigations in emotion regulation, including EEG-driven neuro markers, Stroop-driven attention biases, and neuroimaging-driven brain network dynamics.

Decreasing dorsal cochlear nucleus activity ameliorates noise-induced tinnitus perception in mice

BackgroundThe dorsal cochlear nucleus (DCN) is a region known to integrate somatosensory and auditory inputs and is identified as a potential key structure in the generation of phantom sound perception, especially noise-induced tinnitus. Yet, how altered homeostatic plasticity of the DCN induces and maintains the sensation of tinnitus is not clear. Here, we chemogenetically decrease activity of a subgroup of DCN neurons, Ca2+/Calmodulin kinase 2 α (CaMKII α)-positive DCN neurons, using Gi-coupled human M4 Designer Receptors Exclusively Activated by Designer Drugs (hM4Di DREADDs), to investigate their role in noise-induced tinnitus.ResultsMice were exposed to loud noise (9–11kHz, 90dBSPL, 1h, followed by 2h of silence), and auditory brainstem responses (ABRs) and gap prepulse inhibition of acoustic startle (GPIAS) were recorded 2 days before and 2 weeks after noise exposure to identify animals with a significantly decreased inhibition of startle, indicating tinnitus but without permanent hearing loss. Neuronal activity of CaMKII α+ neurons expressing hM4Di in the DCN was lowered by administration of clozapine-N-oxide (CNO). We found that acutely decreasing firing rate of CaMKII α+ DCN units decrease tinnitus-like responses (p = 3e −3, n = 11 mice), compared to the control group that showed no improvement in GPIAS (control virus; CaMKII α-YFP + CNO, p = 0.696, n = 7 mice). Extracellular recordings confirmed CNO to decrease unit firing frequency of CaMKII α-hM4Di+ mice and alter best frequency and tuning width of response to sound. However, these effects were not seen if CNO had been previously administered during the noise exposure (n = 6 experimental and 6 control mice).ConclusionWe found that lowering DCN activity in mice displaying tinnitus-related behavior reduces tinnitus, but lowering DCN activity during noise exposure does not prevent noise-induced tinnitus. Our results suggest that CaMKII α-positive cells in the DCN are not crucial for tinnitus induction but play a significant role in maintaining tinnitus perception in mice.

The Rapid Screening for Somatosensory Tinnitus Tool: a Data-Driven Decision Tree Based on Specific Diagnostic Criteria.

Somatosensory or somatic tinnitus (ST) is a type of tinnitus where changes in somatosensory afference from the cervical spine or temporomandibular area alter the tinnitus perception. Very recently, the diagnostic value of a set of 16 diagnostic criteria for ST was determined. The next step in the development of easily applicable diagnostic criteria is to provide an uncomplicated model, based on the existing criteria, which can easily be used in clinical practice. This study aims to construct an accurate decision tree, combining several diagnostic criteria, to optimize both sensitivity and specificity of ST diagnosis. An online survey was launched on the online forum Tinnitus Talk, managed by Tinnitus Hub in a convenience sample of participants with tinnitus. The survey included 42 questions, both on the presence of diagnostic criteria for ST and on other potentially influencing factors. A decision tree was constructed to classify participants with and without ST using the rpart package in R. Tree depth was optimized during a five-fold cross-validation. Finally, model performance was evaluated on a subset containing 20% of the original dataset. Data of 7981 participants were used to construct a decision tree for ST diagnosis. Four criteria were included in the final decision tree: 'Tinnitus and neck/jaw pain increase/decrease simultaneously', 'Tension in suboccipital muscles', 'Somatic modulation', and 'Bruxism'. The presented model has an accuracy of 82.2%, a sensitivity of 82.5%, and a specificity of 79%. Receiver operator characteristic curves demonstrated an area under the curve of 0.88. Based on a 42-item survey, a decision tree was created that was able to detect ST patients with high accuracy (82.2%) using only 4 questions. The RaSST is therefore expected to be easily implementable in clinical practice.

Higher Peripheral Inflammation Is Associated With Lower Orbitofrontal Gamma Power in Chronic Tinnitus.

Chronic tinnitus, the continuous perception of a phantom sound, is a highly prevalent audiological symptom, for which the underlying pathology has not yet been fully understood. It is associated with neurophysiological alterations in the central nervous system and chronic stress, which can be related with a disinhibition of the inflammatory system. We here investigated the association between resting-state oscillatory activity assessed with Magnetoencephalography (MEG), and peripheral inflammation assessed by C-reactive protein (CRP) in a group of patients with chronic tinnitus (N = 21, nine males, mean age: 40.6 ± 14.6 years). Additionally, CRP was assessed in an age- and sex-matched healthy control group (N = 21, nine males, mean age: 40.9 ± 15.2 years). No MEG data was available for the control group. We found a significant negative correlation between CRP and gamma power in the orbitofrontal cortex in tinnitus patients (p < 0.001), pointing to a deactivation of the orbitofrontal cortex when CRP was high. No significant clusters were found for other frequency bands. Moreover, CRP levels were significantly higher in the tinnitus group than in the healthy controls (p = 0.045). Our results can be interpreted based on findings from previous studies having disclosed the orbitofrontal cortex as part of the tinnitus distress network. We suggest that higher CRP levels and the associated deactivation of the orbitofrontal cortex in chronic tinnitus patients is maintaining the tinnitus percept through disinhibition of the auditory cortex and attentional or emotional top-down processes. Although the direction of the association (i.e., causation) between CRP levels and orbitofrontal gamma power in chronic tinnitus is not yet known, inflammation reducing interventions are promising candidates when developing treatments for tinnitus patients. Overall, our study highlights the importance of considering immune-brain communication in tinnitus research.

Spectrally Matched Near-Threshold Noise for Subjective Tinnitus Loudness Attenuation Based on Stochastic Resonance.

Recently, we proposed a model of tinnitus development based on a physiological mechanism of permanent optimization of information transfer from the auditory periphery to the central nervous system by means of neuronal stochastic resonance utilizing neuronal noise to be added to the cochlear input, thereby improving hearing thresholds. In this view, tinnitus is a byproduct of this added neuronal activity. Interestingly, in healthy subjects auditory thresholds can also be improved by adding external, near-threshold acoustic noise. Based on these two findings and a pilot study we hypostatized that tinnitus loudness (TL) might be reduced, if the internally generated neuronal noise is substituted by externally provided individually adapted acoustic noise. In the present study, we extended the data base of the first pilot and further optimized our approach using a more fine-grained adaptation of the presented noise to the patients’ audiometric data. We presented different spectrally filtered near-threshold noises (−2 dB to +6 dB HL, 2 dB steps) for 40 s each to 24 patients with tonal tinnitus and a hearing deficit not exceeding 40 dB. After each presentation, the effect of the noise on the perceived TL was obtained by patient’s response to a 5-scale question. In 21 out of 24 patients (13 women) TL was successfully subjectively attenuated during acoustic near-threshold stimulation using noise spectrally centered half an octave below the individual’s tinnitus pitch (TP). Six patients reported complete subjective silencing of their tinnitus percept during stimulation. Acoustic noise is able to reduce TL, but the TP has to be taken into account. Based on our findings, we speculate about a possible future treatment of tinnitus by near-threshold bandpass filtered acoustic noise stimulation, which could be implemented in hearing aids with noise generators.

Cortical auditory evoked potentials, brain signal variability and cognition as biomarkers to detect the presence of chronic tinnitus

The current limited understanding of tinnitus neurophysiology is one of the major obstacles in developing effective treatments for chronic tinnitus. As such, there is an urgent need for knowledge on underlying neural and/or neurobehavioral correlates that might function as potential biomarkers for tinnitus. We aimed to develop a model for the detection of tinnitus cases based on such potential biomarkers. In a first step, data from twenty patients suffering from chronic tinnitus, but no concurrent hearing loss or psychological complaints, were compared to data from twenty matched controls. Cortical auditory evoked potentials (CAEP) were elicited using a standard oddball paradigm. Source estimation and brain signal variability were analyzed to investigate putative differences between tinnitus patients and controls. Other examinations included standard audiometry, speech understanding in quiet and noisy conditions, and cognitive testing using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The P300 component, a response to unexpected but relevant stimuli, was significantly reduced in the tinnitus group. Source estimation revealed that the response of tinnitus patients was characterized by a decreased activity in temporal cortex, parahippocampus and insula. Brain signal variability on fine time scales was significantly higher in the tinnitus group, suggesting that tinnitus patients rely more strongly on local information processing. Furthermore, tinnitus was associated with a decreased cognitive performance, especially on tasks measuring delayed memory. In a second step, a logistic regression model was constructed based on CAEP activity, brain signal variability and RBANS scores. This model performed significantly above chance level when detecting tinnitus cases in an unseen dataset (accuracy of 75%, area under the ROC curve of 0.86). The successful classification between tinnitus cases and controls demonstrates the potential value of the proposed combination of biomarkers. Moreover, the identified associations between tinnitus, auditory evoked activity and cognitive performance point towards a significant contribution of top-down information processing in the perception of tinnitus.

Effects of the coronavirus disease 2019 pandemic on subjective tinnitus perception.

This study investigated the effects of the coronavirus disease 2019 pandemic on tinnitus severity and quality of life in individuals with subjective tinnitus. The study was carried out during the coronavirus disease 2019 pandemic. Sixty patients were evaluated with the Tinnitus Handicap Inventory and a visual analogue scale on resonance intensity and disturbance, together with questions assessing their emotional states. There was a significant difference between the visual analogue scale and the Tinnitus Handicap Inventory scores before the pandemic and during the pandemic. It was determined that tinnitus loudness and annoyance were significantly worse in the pandemic and, consequently, that the coronavirus disease 2019 pandemic negatively affected perceptions of tinnitus and quality of life. Psychological support can affect positively the perception of tinnitus and the change in moods experienced during the pandemic. Because personal contact and quotidian activities are severely limited during the pandemic, internet-based interventions should be prioritised in tinnitus therapy.

Tinnitus Perception in Light of a Parietal Operculo-Insular Involvement: A Review.

In tinnitus literature, researchers have increasingly been advocating for a clearer distinction between tinnitus perception and tinnitus-related distress. In non-bothersome tinnitus, the perception itself can be more specifically investigated: this has provided a body of evidence, based on resting-state and activation fMRI protocols, highlighting the involvement of regions outside the conventional auditory areas, such as the right parietal operculum. Here, we aim to conduct a review of available investigations of the human parietal operculo–insular subregions conducted at the microscopic, mesoscopic, and macroscopic scales arguing in favor of an auditory–somatosensory cross-talk. Both the previous literature and new results on functional connectivity derived from cortico–cortical evoked potentials show that these subregions present a dense tissue of interconnections and a strong connectivity with auditory and somatosensory areas in the healthy brain. Disrupted integration processes between these modalities may thus result in erroneous perceptions, such as tinnitus. More precisely, we highlight the role of a subregion of the right parietal operculum, known as OP3 according to the Jülich atlas, in the integration of auditory and somatosensory representation of the orofacial muscles in the healthy population. We further discuss how a dysfunction of these muscles could induce hyperactivity in the OP3. The evidence of direct electrical stimulation of this area eliciting auditory hallucinations further suggests its involvement in tinnitus perception. Finally, a small number of neuroimaging studies of therapeutic interventions for tinnitus provide additional evidence of right parietal operculum involvement.