Brain, Hearing and Tinnitus Science

(1) Background: Tinnitus, often related to hearing loss, is an addressable public health concern affecting health-related quality of life (HRQoL). This study aimed to explore the influence of bone conduction hearing aid (BCHA) implantation on HRQoL and hearing disability in patients with hearing loss suffering from tinnitus. (2) Methods: Data were collected from an international hearing implant registry. Health Utilities Index Mark 3 (HUI-3), Spatial and Qualities of Hearing- 49 Questionnaire (SSQ) and self-reported tinnitus burden data for adult patients implanted with a BCHA (n = 42) who provided baseline as well as follow-up data 1-year post-implantation were extracted from the registry. Wilcoxon signed rank tests and paired samples t-tests were used to analyse outcomes data. (3) Results: Patients, with or without tinnitus, demonstrated clinically important mean improvements in HUI-3 multi-attribute utility scores, HUI-3 hearing attribute and SSQ scores. Hearing loss patients with tinnitus presented with a lower HRQoL than patients without tinnitus. (4) Conclusions: These findings demonstrate the importance of hearing rehabilitation in improving the quality of life and hearing disability of patients with or without tinnitus and in providing tinnitus relief in some patients with hearing loss and tinnitus. Full article

Purpose: To examine the prevalence of adherence to hearing aids and determine their rejection causes. Methods: This study was conducted according to the Preferred Reporting terms for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed an electronic search using PubMed, BVS, and Embase. Results: 21 studies that met the inclusion criteria were selected. They analyzed a total of 12,696 individuals. We observed that the most common causes for positive adherence to hearing aid use included having a higher degree of hearing loss, patients being aware of their condition, and requiring the device in their daily life. The most common causes for rejection were the lack of perceived benefits or discomfort with the use of the device. The results from the meta-analysis show a prevalence of patients who used their hearing aid of 0.623 (95% CI 0.531, 0.714). Both groups are highly heterogeneous (I2 = 99.31% in each group, p < 0.05). Conclusions: A significant proportion of patients (38%) do not use their hearing aid devices. Homogeneous multicenter studies using the same methodology are needed to analyze the causes of rejection of hearing aids. Full article

There is currently increasing awareness of third-party disability, defined as the disability and functioning of a significant other (SO) due to a health condition of one of their family members. The effects of third-party disability on the SOs of individuals with tinnitus has received little attention. To address this knowledge gap, this study investigated third-party disability in the significant others (SOs) of individuals with tinnitus. A cross-sectional survey design included 194 pairs of individuals from the USA with tinnitus and their significant others. The SO sample completed the Consequences of Tinnitus on Significant Others Questionnaire (CTSOQ). Individuals with tinnitus completed standardized self-reported outcome measures for tinnitus severity, anxiety, depression, insomnia, hearing-related quality of life, tinnitus cognitions, hearing disability, and hyperacusis. The CTSOQ showed that 34 (18%) of the SOs were mildly impacted, 59 (30%) were significantly impacted, and 101 (52%) were severely impact. The clinical variables of tinnitus severity, anxiety, and hyperacusis in individuals with tinnitus were the best predictors of the impact of tinnitus on SOs. These results show that the SOs of individuals with tinnitus may experience third-party disability. The effect of the individual’s tinnitus on their SO may be greater when the individual with tinnitus has a higher level of tinnitus severity, anxiety, and hyperacusis. Full article

Around 30% of the general population experience subjective tinnitus, characterized by conscious attended awareness perception of sound without an external source. Clinical distress tinnitus is more than just experiencing a phantom sound, as it can be highly disruptive and debilitating, leading those affected to seek clinical help. Effective tinnitus treatments are crucial for psychological well-being, but our limited understanding of the underlying neural mechanisms and a lack of a universal cure necessitate further treatment development. In light of the neurofunctional tinnitus model predictions and transcranial electrical stimulation, we conducted an open-label, single-arm, pilot study that utilized high-definition transcranial direct current stimulation (HD-tDCS) concurrent with positive emotion induction (PEI) techniques for ten consecutive sessions to down-regulate tinnitus negative valence in patients with clinical distress tinnitus. We acquired resting-state functional magnetic resonance imaging scans of 12 tinnitus patients (7 females, mean age = 51.25 ± 12.90 years) before and after the intervention to examine resting-state functional connectivity (rsFC) alterations in specific seed regions. The results showed reduced rsFC at post-intervention between the attention and emotion processing regions as follows: (1) bilateral amygdala and left superior parietal lobule (SPL), (2) left amygdala and right SPL, (3) bilateral dorsolateral prefrontal cortex (dlPFC) and bilateral pregenual anterior cingulate cortex (pgACC), and (4) left dlPFC and bilateral pgACC (FWE corrected p < 0.05). Furthermore, the post-intervention tinnitus handicap inventory scores were significantly lower than the pre-intervention scores (p < 0.05). We concluded that concurrent HD-tDCS and PEI might be effective in reducing tinnitus negative valence, thus alleviating tinnitus distress. Full article

Introduction: This study aimed to explore whether body mass index (BMI), systolic blood pressure (RR syst), diastolic blood pressure (RR diast) or heart rate (HR) are associated with tinnitus status and/or severity. Methods: To that end, we evaluated the influence of tinnitus status and Tinnitus Handicap Inventory (THI) score on BMI, RR syst, RR diast and HR by comparing data from a large sample of patients presenting to a specialized tertiary referral clinic (N = 1066) with data from a population-based control group (N = 9885) by means of linear models. Results: Tinnitus patients had a significantly lower BMI and higher RR syst, RR diast and HR than non-tinnitus patients; however, the contribution of the case–control status to R² was very small (0.1%, 0.7%, 1.4% and 0.4%, respectively). BMI had little predictive power for the THI score (higher BMI scores were related to higher THI scores; R² = 0.5%) and neither RR syst, RR diast, nor HR showed a statistically significant association with THI. Discussion: Our findings suggest that HR, RR and BMI are at most marginally associated with tinnitus status and severity. Full article

It is widely accepted that extracts of St. John’s wort (Hypericum perforatum) improve depressive symptoms, and tinnitus patients commonly presented with either mild depression or anxiety. We investigated whether co-administration of St. John’s wort and Ginkgo biloba extracts can suppress tinnitus. Participants with subjective tinnitus aged 30–70 years were randomly assigned to the experimental (co-administration of St. John’s wort and Ginkgo biloba extract; n = 20) or control (Ginkgo biloba extract only; n = 26) group for 12 weeks. Participants were blinded to the group assignments. After 12 weeks of treatment, no significant change in the minimum masking level on the tinnitogram was observed in either group. In the co-administration group, the Tinnitus Handicap Inventory (THI) score decreased from 34.7 (SD, 15.9) to 29.6 (16.0) (p = 0.102). However, the control group showed a significant decrease in THI score, from 30.5 (16.7) to 25.6 (17.1) (p = 0.046). Regarding the Short Form-36 Health Survey (SF-36), only the “Social Functioning” domain score changed significantly after extract co-administration, from 74.5 (21.5) to 83.9 (20.5) (p = 0.047). Co-administration of St. John’s wort and Ginkgo biloba extracts did not improve the symptoms of subjective tinnitus compared to administration of Ginkgo biloba extract alone. Full article

The understanding of tinnitus has always been elusive and is largely prevented by its intrinsic heterogeneity. To address this issue, scientific research has aimed at defining stable and easily identifiable subphenotypes of tinnitus. This would allow better disentangling the multiple underlying pathophysiological mechanisms of tinnitus. In this study, three-dimensionality reduction techniques and two clustering methods were benchmarked on a database of 2772 tinnitus patients in order to obtain a reliable segmentation of subphenotypes. In this database, tinnitus patients’ endotypes (i.e., parts of a population with a condition with distinct underlying mechanisms) are reported when diagnosed by an ENT expert in tinnitus management. This partial labeling of the dataset enabled the design of an original semi-supervised framework. The objective was to perform a benchmark of different clustering methods to get as close as possible to the initial ENT expert endotypes. To do so, two metrics were used: a primary one, the quality of the separation of the endotypes already identified in the database, as well as a secondary one, the stability of the obtained clusterings. The relevance of the results was finally reviewed by two ENT experts in tinnitus management. A 20-cluster clustering was selected as the best-performing, the most-clinically relevant, and the most-stable through bootstrapping. This clustering used a T-SNE method as the dimensionality reduction technique and a k-means algorithm as the clustering method. The characteristics of this clustering are presented in this article. Full article

Cognitive behavioral therapy (CBT) was shown to be effective in reducing tinnitus-related distress in numerous controlled trials. Real-world data from tinnitus treatment centers are an important addition to controlled trials for demonstrating the ecological validity of the results from the randomized controlled trials. Thus, we provided the real-world data of 52 patients participating in CBT group therapies during the time period from 2010 to 2019. The groups consisted of five to eight patients with typical CBT content such as counseling, relaxation, cognitive restructuring, attention training, etc. applied through 10–12 weekly sessions. The mini tinnitus questionnaire, different tinnitus numeric rating scales and the clinical global impression were assessed in a standardized way and were analyzed retrospectively. All outcome variables showed clinically relevant changes from before to after the group therapy, which were still evident in the follow-up visit after three months. Amelioration of distress was correlated to all numeric rating scales, including tinnitus loudness but not annoyance. The observed positive effects were in a similar range as effects of controlled and uncontrolled studies. Somewhat unexpected was the observed reduction in loudness, which was associated with distress and the missing association of changes in distress with annoyance as it is generally assumed that standard CBT concepts reduce annoyance and distress, but not tinnitus loudness. Apart from confirming the therapeutic effectiveness of CBT in real-world settings, our results highlight the need for a clear definition/operationalization of outcome measures when investigating psychological interventions of tinnitus. Full article

(1) Background: Vestibular migraine (VM) and Menière’s disease (MD) share multiple features in terms of clinical presentations and auditory-vestibular functions, and, therefore, more accurate diagnostic tools to distinguish between the two disorders are needed. (2) Methods: The study was of retrospective design and examined the data of 69 MD patients, 79 VM patients and 72 MD with migraine patients. Five vestibular autorotation test (VAT) parameters, i.e., horizontal gain/phase, vertical gain/phase and asymmetry were subjected to logistic regression. The receiver operating characteristic (ROC) curves were generated to determine the accuracy of the different parameters in the differential diagnosis of MD and VM. (3) Results: Our results showed that the horizontal gain of VAT significantly outperformed other parameters in distinguishing MD and VM. In addition, the sensitivity, specificity and accuracy of the horizontal gain were 95.7%, 50.6% and 71.6%, respectively, for the differentiation between VM and MD. In most MD patients, the horizontal gain decreased in the range of 3–4 Hz, while in most VM patients, horizontal gain increased in the range between 2–3 Hz. More MD with migraine patients had an increased horizontal gain when the frequency was less than 5.0 Hz and had a decreased horizontal gain when the frequency was greater than 5.0 Hz. (4) Conclusion: Our study suggested the VAT, especially the horizontal gain, as an indicator, may serve as a sensitive and objective indicator that helps distinguish between MD and VM. Moreover, VAT, due to its non-invasive and all-frequency nature, might be an important part of a test battery. Full article

Sound therapy is one of the most common tinnitus treatments that can be used either to mask or to shift attention away from the tinnitus percept. However, the actual benefit of sound therapy and the mechanisms leading to the benefits remain limited. The objective of this study was to investigate the short-term (15 min) and long-term (2 months) effects of sound therapy on visual attention in chronic tinnitus patients. Visual attention was evaluated with the behavioral Attention Network Task, while the tinnitus-related distress was evaluated with the Tinnitus Handicap Inventory (THI) to quantify the effect of sound therapy. The study included 20 participants with chronic and bothersome tinnitus (>6 months, THI > 18) and 20 matched control participants. All participants took part in a first session consisting of a baseline condition, a short-term sound therapy condition and a silent control condition. The tinnitus participants also took part in a second session that evaluated the long-term effect of the therapy. A reduction in the tinnitus-related distress was found after the long-term use of sound therapy. Furthermore, a reduction in the differential index of the executive control (EC) attention network, indicating improved attention, was found after long-term use of sound therapy in the sound condition but not in the silent control condition. In contrast to earlier research, no differences were found between the tinnitus group and the control group for the baseline measurement of the EC attention network. Overall, the results suggest that there is no link between the visual attention networks and the sound therapy’s effect on tinnitus-related distress. Full article

Previous studies have shown a high prevalence of sleep disturbances in tinnitus patients. However, no study has yet evaluated subjective sleep satisfaction. The present study aimed to investigate associations of self-reported sleep satisfaction with sociodemographic factors, tinnitus-related distress, depression, and self-reported quality of life. This is a retrospective analysis of 2344 outpatients with tinnitus presenting at a tertiary German tinnitus clinic from 2010 to 2020. Patients who filled in five questionnaires (Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ), Major Depression Inventory (MDI), Tinnitus Sample Case History Questionnaire (TSCHQ), and the World Health Organization Quality of Life Brief Version (WHOQOL-Bref)) were included. Based on the question about sleep satisfaction in the WHOQOL-Bref, group classification into (I) sleep-satisfied, (II) neither satisfied or dissatisfied, and (III) sleep-dissatisfied patients was performed. Associations between sleep satisfaction and quality of life, depression, tinnitus distress, and tinnitus characteristics were analyzed by group differences and a multinomial regression model with elastic net penalization. A total of 42.38% of patients were satisfied or very satisfied with sleep, whereas 40.91% of patients were dissatisfied or very dissatisfied with sleep. The remaining patients reported being neither satisfied nor dissatisfied with sleep. Sleep-dissatisfied patients were significantly more burdened in questionnaires on depressive symptoms (MDI), tinnitus distress (TQ, THI), and quality of life (WHOQOL-Bref). In addition, they suffered significantly more often from comorbidities such as headache, neck pain, or temporomandibular joint disorder (TMJ). The elastic net regression based on sum scores of THI, TQ, MDI, the four domains of WHOQOL-Bref, as well as all individual questions from the TSCHQ was able to classify patients satisfied with their sleep with an accuracy of 79%, 87.8% sensitivity, and 70.4% specificity. The model could not identify patients indifferent with the quality of their sleep (neither satisfied nor dissatisfied) (sensitivity: 0%; specificity: 100%). The accuracy of the model to predict patients dissatisfied with their sleep was 80.7%, with 83% sensitivity and 78.4% specificity. Poor physical and mental health (Domain I/II WHOQOL-Bref) as well as tinnitus distress were the strongest predictors of sleep dissatisfaction. Conversely, for sleep satisfaction, good physical and mental health as well as low tinnitus distress were the strongest predictors. The division into sleep-satisfied and sleep-dissatisfied tinnitus patients allows a very good discrimination regarding disease burden as indicated by depression, tinnitus distress, quality of life, and pain-related comorbidities. Physical and mental health as well as tinnitus distress seem to be strongly related to sleep satisfaction underscoring the concept of “tinnitus” versus “tinnitus disorder”, but also the importance of sleep satisfaction as a global health indicator. Moreover, these data indicate the relevance of addressing sleep disorders in the therapeutic management of chronic tinnitus patients. Full article

A cochlear implant (CI) is currently the only FDA-approved biomedical device that can restore hearing for the majority of patients with severe-to-profound sensorineural hearing loss (SNHL). While prelingually and postlingually deaf individuals benefit substantially from CI, the outcomes after implantation vary greatly. Numerous studies have attempted to study the variables that affect CI outcomes, including the personal characteristics of CI candidates, environmental variables, and device-related variables. Up to 80% of the results remained unexplainable because all these variables could only roughly predict auditory performance with a CI. Brain structure/function differences after hearing deprivation, that is, cortical reorganization, has gradually attracted the attention of neuroscientists. The cross-modal reorganization in the auditory cortex following deafness is thought to be a key factor in the success of CI. In recent years, the adaptive and maladaptive effects of this reorganization on CI rehabilitation have been argued because the neural mechanisms of how this reorganization impacts CI learning and rehabilitation have not been revealed. Due to the lack of brain processes describing how this plasticity affects CI learning and rehabilitation, the adaptive and deleterious consequences of this reorganization on CI outcomes have recently been the subject of debate. This review describes the evidence for different roles of cross-modal reorganization in CI performance and attempts to explore the possible reasons. Additionally, understanding the core influencing mechanism requires taking into account the cortical changes from deafness to hearing restoration. However, methodological issues have restricted longitudinal research on cortical function in CI. Functional near-infrared spectroscopy (fNIRS) has been increasingly used for the study of brain function and language assessment in CI because of its unique advantages, which are considered to have great potential. Here, we review studies on auditory cortex reorganization in deaf patients and CI recipients, and then we try to illustrate the feasibility of fNIRS as a neuroimaging tool in predicting and assessing speech performance in CI recipients. Here, we review research on the cross-modal reorganization of the auditory cortex in deaf patients and CI recipients and seek to demonstrate the viability of using fNIRS as a neuroimaging technique to predict and evaluate speech function in CI recipients. Full article

(1) Background: Vestibular migraine (VM) and Meniere’s disease (MD) share multiple features in terms of clinical presentations and auditory-vestibular dysfunctions, e.g., vertigo, hearing loss, and headache. Therefore, differentiation between VM and MD is of great significance. (2) Methods: We retrospectively analyzed the medical records of 110 patients with VM and 110 patients with MD. We at first established a regression equation by using logistic regression analysis. Furthermore, sensitivity, specificity, accuracy, positive predicted value (PV), and negative PV of screened parameters were assessed and intuitively displayed by receiver operating characteristic curve (ROC curve). Then, two visualization tools, i.e., nomograph and applet, were established for convenience of clinicians. Furthermore, other patients with VM or MD were recruited to validate the power of the equation by ROC curve and the Gruppo Italiano per la Valutazione degli Interventi in Terapia Intensiva (GiViTI) calibration belt. (3) Results: The clinical manifestations and auditory-vestibular functions could help differentiate VM from MD, including attack frequency (X5), phonophobia (X13), electrocochleogram (ECochG) (X18), head-shaking test (HST) (X23), ocular vestibular evoked myogenic potential (o-VEMP) (X27), and horizontal gain of vestibular autorotation test (VAT) (X30). On the basis of statistically significant parameters screened by Chi-square test and multivariable double logistic regression analysis, we established a regression equation: P = 1/[1 + e^{−(−2.269× X5 − 2.395× X13 + 2.141× X18 + 3.949 × X23 + 2.798× X27 − 4.275× X30(1) − 5.811× X30(2) + 0.873)}] (P, predictive value; e, natural logarithm). Nomographs and applets were used to visualize our result. After validation, the prediction model showed good discriminative power and calibrating power. (4) Conclusions: Our study suggested that a diagnostic algorithm based on available clinical features and an auditory-vestibular function regression equation is clinically effective and feasible as a differentiating tool and could improve the differential diagnosis between VM and MD. Full article

Background: Observational studies have suggested that there may be an association between telomere length (TL) and hearing loss (HL). However, inferring causality from observational studies is subject to residual confounding effects, reverse causation, and bias. This study adopted a two-sample Mendelian randomization (MR) approach to evaluate the causal relationship between TL and increased risk of HL. Methods: A total of 16 single nucleotide polymorphisms (SNPs) associated with TL were identified from a genome-wide association study (GWAS) meta-analysis of 78,592 European participants and applied to our modeling as instrumental variables. Summary-level data for hearing loss (HL), age-related hearing loss (ARHL), and noise-induced hearing loss (NIHL) were obtained from the recent largest available GWAS and five MR analyses were used to investigate the potential causal association of genetically predicted TL with increased risk for HL, including the inverse-variance-weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode. In addition, sensitivity analysis, pleiotropy, and heterogeneity tests were also used to evaluate the robustness of our findings. Results: There was no causal association between genetically predicted TL and HL or its subtypes (by the IVW method, HL: odds ratio (OR) = 1.216, p = 0.382; ARHL: OR = 0.934, p = 0.928; NIHL: OR = 1.003, p = 0.776). Although heterogenous sites rs2736176, rs3219104, rs8105767, and rs2302588 were excluded for NIHL, the second MR analysis was consistent with the first analysis (OR = 1.003, p = 0.572). Conclusion: There was no clear causal relationship between shorter TLs and increased risk of HL or its subtypes in this dataset. Full article

Tinnitus is an auditory phantom perception in the ears or head in the absence of a corresponding external stimulus. There is currently no effective treatment available that reliably reduces tinnitus. Educational counseling is a treatment approach that aims to educate patients and inform them about possible coping strategies. For this feasibility study, we implemented educational material and self-help advice in a smartphone app. Participants used the educational smartphone app unsupervised during their daily routine over a period of four months. Comparing the tinnitus outcome measures before and after smartphone-guided treatment, we measured changes in tinnitus-related distress, but not in tinnitus loudness. Improvements on the Tinnitus Severity numeric rating scale reached an effect size of 0.408, while the improvements on the Tinnitus Handicap Inventory (THI) were much smaller with an effect size of 0.168. An analysis of user behavior showed that frequent and intensive use of the app is a crucial factor for treatment success: participants that used the app more often and interacted with the app intensively reported a stronger improvement in the tinnitus. Between study allocation and final assessment, 26 of 52 participants dropped out of the study. Reasons for the dropouts and lessons for future studies are discussed in this paper. Full article

This study aimed to evaluate the effectiveness of and satisfaction with hearing aids as a treatment option for tinnitus with hearing loss. Methods: This retrospective study used the tinnitus handicap inventory (THI), the satisfaction with amplification in daily life (SADL) questionnaire, and a medical chart review. A total of 116 patients treated between August 2018 and December 2020 were included. All patients with tinnitus and hearing loss underwent the same counseling sessions. Sixty patients chose to have hearing aids fitted (aided group), whereas 56 patients chose not to (non-aided group). Both the groups had similar audiometric configurations, durations of tinnitus, and ages. Structured interviews were performed, with various measures evaluated using the visual analog scale (VAS) and the THI questionnaire, before and six months after fitting the hearing aids. The SADL questionnaire was administered 6 months after fitting the hearing aids. Results: The patients’ THI scores reduced 6 months after the counseling, but the improvement in the THI scores was only significant in the group that received hearing aids. There were significant differences between the VAS scores of the two groups, and the changes in the VAS scores in the groups were statistically different. Subjective satisfaction with a hearing aid increased with improvements to tinnitus-related discomfort. Conclusion: The study’s results indicated that patients with hearing loss and tinnitus can be treated with hearing aids and counseling. Full article

Background: Tinnitus is a heterogeneous condition. The aim of this study as to compare the online and hospital responses to the Spanish version of European School for Interdisciplinary Tinnitus Research screening-questionnaire (ESIT-SQ) in tinnitus individuals by an unsupervised age clustering. Methods: A cross-sectional study was performed including 434 white Spanish patients with chronic tinnitus to assess the demographic and clinical profile through the ESIT-SQ, with 204 outpatients and 230 individuals from an online survey; a K-means clustering algorithm was used to classify both responses according to age. Results: Online survey showed a high proportion of Meniere’s disease (MD) patients compared to both the general population and the outpatient cohort. The responses showed statistically significant differences between groups regarding education level, tinnitus-related hearing disorders (MD, hyperacusis), sleep difficulties, dyslipidemia, and other tinnitus characteristics, including duration, type of onset, the report of mitigating factors and the use of treatments. However, these differences were partially confirmed after adjusting for age. Conclusions: Self-reported tinnitus surveys are a low confidence source for tinnitus phenotyping. Additional clinical evaluation is needed for tinnitus research to reach the diagnosis. Age-based cluster analysis might help to better define clinical profiles and to compare responses in ESIT-SQ among subgroups of patients with tinnitus. Full article

Tinnitus is a phantom sound perception in the ears or head and can arise from many different medical disorders. Currently, there is no standard treatment for tinnitus that reliably reduces tinnitus. Individual patients reported that acupressure at various points around the ear can help to reduce tinnitus, which was investigated here. With this longitudinal observational study, we report a systematic evaluation of auricular acupressure on 39 tinnitus sufferers, combined with a self-help smartphone app. The participants were asked to report on tinnitus, stress, mood, neck, and jaw muscle tensions twice a day using an ecological momentary assessment study design for six weeks. On average, 123.6 questionnaires per person were provided and used for statistical analysis. The treatment responses of the participants were heterogeneous. On average, we observed significant negative trends for tinnitus loudness (Cohen’s d effect size: −0.861), tinnitus distress (d = −0.478), stress (d = −0.675), and tensions in the neck muscles (d = −0.356). Comparison with a matched control group revealed significant improvements for tinnitus loudness (p = 0.027) and self-reported stress level (p = 0.003). The positive results of the observational study motivate further research including a randomized clinical trial and long-term assessment of the clinical improvement. Full article

Background: Comorbid occurrence of tinnitus and emotional symptoms of anxiety and depression is highly prevalent. The Ginkgo biloba extract EGb 761^® has been shown to be effective in reducing neuropsychiatric symptoms in patients with dementia and tinnitus. Methods: We performed a mediation analysis to evaluate direct effects of EGb 761^® on tinnitus severity, as well as indirect effects mediated by symptoms of depression and anxiety and by changed cognition. We pooled data from subsets of patients suffering from tinnitus that were enrolled in three double-blind, randomized, placebo-controlled clinical trials, which investigated the efficacy of EGb 761^® (240 mg/day for 22–24 weeks) in dementia with concomitant neuropsychiatric symptoms. Results: In total, 594 patients suffered from tinnitus (EGb 761^®, 289; placebo, 305). Direct effects of EGb 761^® on tinnitus severity (p < 0.001) in patients with mild to moderate dementia were found to represent about 60% of the total effect, whereas the indirect effects (p < 0.001) mediated by improvement of anxiety, depression and cognition represented about 40% of the total effect. Conclusions: EGb 761^® could be considered as a supporting treatment for tinnitus in elderly patients suffering from dementia, with added benefit in those with symptoms of depression or anxiety. Full article

Current evidence on efficacy of hearing aids (HAs) on tinnitus perception and annoyance is considered insufficient due to the heterogeneity of tinnitus characteristics and of methods used in the relevant clinical studies. This is a scoping review focused on the methodological aspects of clinical studies evaluating the value of HA fitting as part of tinnitus management over the past 10 years. Thirty-four studies were included in the review, showing important heterogeneity in almost all aspects of inclusion criteria, comparators, outcome measures, follow-up time and HA fitting procedures. Although all studies show that HA fitting has a positive impact on tinnitus perception in patients with hearing loss, the methodological heterogeneity does not allow robust conclusions. Future studies taking into account the different nature and goals of each tinnitus therapeutic modality and adapting their methods, endpoints and timelines according to them could lay the groundwork for obtaining high-quality evidence on whether and how HA fitting shall be implemented in tinnitus management strategies. Full article

Objective: To investigate the joint impact of tinnitus-related distress (TRD), anxiety, depressive symptoms, and other somatization symptoms on health-related quality of life (HRQoL) in female vs. male patients with chronic tinnitus. Method: Three-hundred-and-fifty-two patients with chronic tinnitus completed audiological testing and a psychological assessment battery that comprised—among other measures—German versions of the Tinnitus Questionnaire, Hospital Anxiety and Depression Scale, Somatic Symptom Scale-8, and Health-Related Quality of Life scale. Descriptive analyses examined associations as well as within- and between-gender differences of the measured variables. Gender-specific serial indirect effects analyses aimed to explain the impact of TRD on HRQoL through psychological processes, notably anxiety, depressive symptoms, and somatization symptoms. Results: Both female and male patients yielded lower mental than physical HRQoL and negative associations between the measured psychological variables and HRQoL. Compared to male patients, female patients reported higher levels of tinnitus-related- and wider psychological distress, other somatization symptoms (e.g., headaches), and impairments in mental and physical HRQoL. For each gender, depressive symptoms, anxiety, and somatization symptoms fully mediated the effect of TRD on mental and physical HRQoL. A double-dissociation revealed an interaction of somatization symptoms and depression on the TRD-HRQoL association in women, and of somatization symptoms and anxiety in men. Conclusions: In patients with chronic tinnitus, psychological constructs account for reported impairments in both mental and physical HRQoL. To improve patients’ HRQoL, treatment conceptualizations should consider gender-specific psychological expressions of low mood or anxiety. Full article

We reviewed the clinical characteristics and treatment outcomes of patients with glomus tympanicum tumors (GTTs) presenting with pulsatile tinnitus (PT). We explored whether transcanal sound recording-spectro-temporal analysis (TSR-STA) usefully evaluated changes in PT. The medical records of 13 patients who underwent surgical removal of GTTs were reviewed retrospectively. Two patients underwent preoperative endovascular embolization. Changes in PT, pre- and postoperative audiometry data, TSR-STA results, and clinical outcomes were evaluated. PT was the chief complaint in eight patients (61.5%) and resolved immediately after surgical intervention in all. Two patients exhibited ipsilateral, pseudo-low-frequency hearing loss (PLFHL); surgical GTT removal elicited postoperative improvements in the ipsilesional low-frequency hearing thresholds. Five patients underwent TSR-STA using previously described methods. TSR-STA revealed definite rise-and-fall patterns; surgical tumor removal abated this pattern in one patient, but, for the other four, the patterns did not change greatly post-intervention. Thus, GTT-related PT can be treated successfully (via surgical GTT removal) without complications. In selected cases, preoperative embolization reduces intraoperative hemorrhage. In PT patients with PLFHL, a detailed otoendoscopic examination of the middle ear is required to rule out a GTT. TSR-STA may usefully (and objectively) assess postoperative improvements in GTT-related PT. Full article

Introduction: Tinnitus is a common and disabling symptom often associated with hearing loss. While clinical practice frequently shows that a certain degree of psychological discomfort often characterizes tinnitus suffers, it has been recently suggested in adults as a determining factor for cognitive decline affecting attention and memory domains. The aim of our systematic review was to provide evidence for a link between tinnitus, psychological distress, and cognitive dysfunction in older patients and to focus on putative mechanisms of this relationship. Methods: We performed a systematic review, finally including 192 articles that were screened. This resulted in 12 manuscripts of which the full texts were included in a qualitative analysis. Results: The association between tinnitus and psychological distress, mainly depression, has been demonstrated in older patients, although only few studies addressed the aged population. Limited studies on cognitive dysfunction in aged patients affected by chronic tinnitus are hardly comparable, as they use different methods to validate cognitive impairment. Actual evidence does not allow us with certainty to establish if tinnitus matters as an independent risk factor for cognitive impairment or evolution to dementia. Conclusion: Tinnitus, which is usually associated with age-related hearing loss, might negatively affect emotional wellbeing and cognitive capacities in older people, but further studies are required to improve the evidence. Full article

Introduction: The most frequent causes of tinnitus associated with hearing loss are noise-induced hearing loss and presbycusis. The mechanism of tinnitus is not yet clear, although several hypotheses have been suggested. Therefore, we aimed to analyze characteristics of chronic tinnitus between noise-induced hearing loss and presbycusis. Materials and Methods: This paper is a retrospective chart review and outpatient clinic-based study of 248 patients with chronic tinnitus from 2015 to 2020 with noise-induced or presbycusis. Pure tone audiometry (PTA), auditory brainstem response (ABR), distortion product otoacoustic emissions (DPOAE), transient evoked otoacoustic emissions (TEOAE), and tinnitograms were conducted. Results: PTA showed that hearing thresholds at all frequencies were higher in patients with noise-induced hearing loss than the presbycusis group. ABR tests showed that patients with presbycusis had longer wave I and III latencies (p < 0.05 each) than patients with noise-induced hearing loss. TEOAE tests showed lower values in patients with noise-induced hearing loss than presbycusis at 1.5, 2, 3, and 4 kHz (p < 0.05 each). DPOAE tests showed that response rates in both ears at 1.5, 2, and 3 kHz were significantly higher in patients with presbycusis than noise-induced hearing loss (p < 0.05 each). Discussion: This study showed that hearing thresholds were higher, the loudness of tinnitus was smaller, and the degree of damage to outer hair cells was lower in patients with presbycusis than with noise-induced hearing loss. Moreover, wave I and III latencies were more prolonged in patients with presbycusis despite their having lower hearing thresholds. These phenomena may reflect the effects of aging or degeneration of the central nervous system with age. Further studies are needed to evaluate the etiologies of tinnitus. Full article

Although a wide range of tinnitus management interventions is currently under research and a variety of therapeutic interventions have already been applied in clinical practice, no optimal and universal tinnitus treatment has been reached yet. This fact is to some extent a consequence of the high heterogeneity of the methodologies used in tinnitus related clinical studies. In this manuscript, we have identified, summarized, and critically appraised tinnitus-related randomized clinical trials since 2010, aiming at systematically mapping the research conducted in this area. The results of our analysis of the 73 included randomized clinical trials provide important insight on the identification of limitations of previous works, methodological pitfalls or gaps in current knowledge, a prerequisite for the adequate interpretation of current literature and execution of future studies. Full article

Repetitive transcranial magnetic stimulation (rTMS) and transcutaneous direct current stimulation (tDCS) are non-invasive treatments for chronic tinnitus based on neuromodulation of cortical activity. Both are considered effective, but with heterogeneous results due to lack of established protocols. Because the target groups for both modalities overlap, it is difficult to recommend one of them. We tried to unify the inclusion criteria and treatment schedules to compare the two modalities. The medical charts of 36 patients who underwent rTMS as part of clinical routine were reviewed and data for 34 patients who underwent tDCS about 7 years later were collected prospectively. Both groups had chronic unilateral tinnitus refractory to medication. Patients were treated for 5 consecutive days, and tinnitus symptoms were evaluated by survey both at the end of the treatment schedule and 1 month after the treatment. The ratio of responders who showed >20% reduction in tinnitus handicap inventory scores were compared. At the end of the treatment, the rTMS group showed a rapid response compared to the tDCS group (rTMS, 30.6%; tDCS, 12.1%; p = 0.054). However, both groups showed a significant and similar reduction in tinnitus symptoms 1 month after the treatment (rTMS, 47.2%; tDCS, 36.4%; p = 0.618). As both groups showed comparable results for tinnitus reduction, tDCS may be superior in terms of cost-effectiveness. Full article

Congenital cytomegalovirus (CMV) infection induces a clinical syndrome usually associated with hearing loss. However, the effect of acquired CVM infection in adults and children has not been clearly defined. The objective of this review is to critically appraise scientific evidence regarding the association of acquired CMV infection with postnatal hearing loss or tinnitus. A systematic review of records reporting sensorineural hearing loss (SNHL) or tinnitus and acquired CMV infection including articles published in English was performed. Search strategy was limited to human studies with acquired CMV infection. After screening and quality assessment, nine studies involving 1528 individuals fulfilled the inclusion criteria. A total of 14% of patients with SNHL showed evidence of previous exposure to CMV, while in individuals without SNHL (controls) the percentage rose up to 19.3%. SNHL was reported as unilateral or bilateral in 15.3%, and not specified in 84.7% of cases. The degree of SNHL ranged from mild to profound for both children and adults. None of the records reported tinnitus. The prevalence of children or adults with acquired SNHL with a confirmed acquired CMV infection by Polymerase Chain Reaction (PCR) or IgM anti-CMV antibodies is low. Phenotyping of patients with acquired CMV infection was limited to hearing loss by pure tone audiometry and no additional audiological testing was performed in most of the studies. Additional symptoms deserve more attention, including episodic vertigo or tinnitus, since some patients with the clinical spectrum of Meniere Disease could result from a CMV latent infection. Full article

Twin and adoption studies point towards a genetic contribution to tinnitus; however, how the genetic risk applies to different forms of tinnitus is poorly understood. Here, we perform a familial aggregation study and determine the relative recurrence risk for tinnitus in siblings (λs). Four different Swedish studies (N = 186,598) were used to estimate the prevalence of self-reported bilateral, unilateral, constant, and severe tinnitus in the general population and we defined whether these 4 different forms of tinnitus segregate in families from the Swedish Tinnitus Outreach Project (STOP, N = 2305). We implemented a percentile bootstrap approach to provide accurate estimates and confidence intervals for λs. We reveal a significant λs for all types of tinnitus, the highest found being 7.27 (95% CI (5.56–9.07)) for severe tinnitus, with a higher susceptibility in women (10.25; 95% CI (7.14–13.61)) than in men (5.03; 95% CI (3.22–7.01)), suggesting that severity may be the most genetically influenced trait in tinnitus in a sex-dependent manner. Our findings strongly support the notion that genetic factors impact on the development of tinnitus, more so for severe tinnitus. These findings highlight the importance of considering tinnitus severity and sex in the design of large genetic studies to optimize diagnostic approaches and ultimately improve therapeutic interventions. Full article

Tinnitus, the perception of sound in the absence of a corresponding sound, and the distress caused by it, is rarely a static phenomenon. It rather fluctuates over time depending on endogenous and exogenous factors. The COVID-19 pandemic is a potential environmental stressor that might influence the individually perceived tinnitus distress. Since not all people are affected by the pandemic in the same way, the situation allows one to identify environmental factors and personality traits that impact tinnitus distress differently. In our study, 122 tinnitus patients were included at two time points: in the year 2018 and during the German lockdown in April 2020. We assessed tinnitus-related distress, depressive symptoms, personality characteristics and the individual perception of the pandemic situation. On average, there was only a small increase of tinnitus distress with heterogeneous changes during the lockdown. People perceiving the situation as generally stressful with increased grief, frustration, stress and nervousness reported the worsening of tinnitus distress. People with high values in neuroticism also reported the worsening of tinnitus distress, while the personality traits extraversion, conscientiousness and openness seemed to be a protection factor. The study identifies factors that influence tinnitus distress change during a pandemic and spots those patients that need specific help in the pandemic situation. Full article

Many individuals with tinnitus report experiencing hyperacusis (enhanced sensitivity to sounds). However, estimates of the association between hyperacusis and tinnitus is lacking. Here, we investigate this relationship in a Swedish study. A total of 3645 participants (1984 with tinnitus and 1661 without tinnitus) were enrolled via LifeGene, a study from the general Swedish population, aged 18–90 years, and provided information on socio-demographic characteristics, as well as presence of hyperacusis and its severity. Tinnitus presence and severity were self-reported or assessed using the Tinnitus Handicap Inventory (THI). Phenotypes of tinnitus with (n = 1388) or without (n = 1044) hyperacusis were also compared. Of 1661 participants without tinnitus, 1098 (66.1%) were women and 563 were men (33.9%), and the mean (SD) age was 45.1 (12.9). Of 1984 participants with tinnitus, 1034 (52.1%) were women and 950 (47.9%) were men, and the mean (SD) age was 47.7 (14.0) years. Hyperacusis was associated with any tinnitus [Odds ratio (OR) 3.51, 95% confidence interval (CI) 2.99–4.13], self-reported severe tinnitus (OR 7.43, 95% CI 5.06–10.9), and THI ≥ 58 (OR 12.1, 95% CI 7.06–20.6). The association with THI ≥ 58 was greater with increasing severity of hyperacusis, the ORs being 8.15 (95% CI 4.68–14.2) for moderate and 77.4 (95% CI 35.0–171.3) for severe hyperacusis. No difference between sexes was observed in the association between hyperacusis and tinnitus. The occurrence of hyperacusis in severe tinnitus is as high as 80%, showing a very tight relationship. Discriminating the pathophysiological mechanisms between the two conditions in cases of severe tinnitus will be challenging, and optimized study designs are necessary to better understand the mechanisms behind the strong relationship between hyperacusis and tinnitus. Full article