Deficient central mechanisms in tinnitus: Exploring the impact on speech comprehension and executive functions.

Many individuals with chronic subjective tinnitus report significant problems in comprehending speech in adverse listening situations. A large body of studies has provided evidence to support the notion that deficits in speech-in-noise (SIN) are prevalent in the tinnitus population, while some studies have challenged these findings. Elemental auditory perception is usually only minimally or not impaired. In addition, deficits in cognitive functions, particularly executive functions, have also been observed in individuals with tinnitus. Given these previous findings, we theorize that deficient central mechanisms may be responsible for the reported speech comprehension problems in tinnitus. 25 participants suffering from chronic subjective tinnitus and 25 control participants, between 23 and 58 years of age, were examined in a cross-sectional design. The groups were case-matched for age, sex, education, and hearing loss. A large audiometric battery was used ranging from threshold and supra-threshold tasks to spoken sentence level speech tasks. Additionally, four cognitive tests were performed, primarily covering the area of executive functions. Tinnitometry and tinnitus-related questionnaires were applied to complement sample description and allow for secondary analyses. We hypothesized that tinnitus participants score lower in complex speech comprehension tasks and executive function tasks compared to healthy controls, while no group differences in elementary audiometric tasks were expected. As expected, individuals with chronic subjective tinnitus scored lower in the SIN and gated speech task, while there were no differences in the basic speech recognition threshold task and the other elementary auditory perception tasks. The cognitive tests revealed clear deficits in interference control in the Stroop task, but not in the Flanker task, in the tinnitus group. There were no differences in inhibition or working memory tasks. Our results clearly delineate differences between tinnitus individuals and control participants in two tests on speech intelligibility under adverse listening conditions. Further, the poorer performance in a task of interference control in individuals with tinnitus points towards an impaired central executive control in individuals with tinnitus. Taken together, our (partly) exploratory study provides novel evidence to the view that deficient central executive system in individuals with tinnitus probably account for impaired speech comprehension.

Neurofeedback for tinnitus treatment: an innovative method with promising potential.

This scientific commentary refers to 'Does it matter what is trained? A randomized controlled trial evaluating the specificity of alpha/delta ratio neurofeedback in reducing tinnitus symptoms 'by Jensen et al. (https://doi.org/10.1093/braincomms/fcad185).

The statistical analysis plan for the unification of treatments and interventions for tinnitus patients randomized clinical trial (UNITI-RCT).

BACKGROUND: Tinnitus is a leading cause of disease burden globally. Several therapeutic strategies are recommended in guidelines for the reduction of tinnitus distress; however, little is known about the potentially increased effectiveness of a combination of treatments and personalized treatments for each tinnitus patient. METHODS: Within the Unification of Treatments and Interventions for Tinnitus Patients project, a multicenter, randomized clinical trial is conducted with the aim to compare the effectiveness of single treatments and combined treatments on tinnitus distress (UNITI-RCT). Five different tinnitus centers across Europe aim to treat chronic tinnitus patients with either cognitive behavioral therapy, sound therapy, structured counseling, or hearing aids alone, or with a combination of two of these treatments, resulting in four treatment arms with single treatment and six treatment arms with combinational treatment. This statistical analysis plan describes the statistical methods to be deployed in the UNITI-RCT. DISCUSSION: The UNITI-RCT trial will provide important evidence about whether a combination of treatments is superior to a single treatment alone in the management of chronic tinnitus patients. This pre-specified statistical analysis plan details the methodology for the analysis of the UNITI trial results. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663828 . The trial is ongoing. Date of registration: December 11, 2020. All patients that finished their treatment before 19 December 2022 are included in the main RCT analysis.

[Functional neuroimaging options for tinnitus]. / Möglichkeiten der funktionellen Bildgebung bei Tinnitus.

BACKGROUND: The pathophysiology behind tinnitus is still not well understood. Different imaging methods help in the understanding of the complex relationships that lead to the perception of tinnitus. OBJECTIVE: Herein, different functional imaging methods that can be used in the study of tinnitus are presented. MATERIALS AND METHODS: Considering the recent literature on the subject, the relevant imaging methods used in tinnitus research are discussed. RESULTS AND CONCLUSION: Functional imaging can reveal correlates of tinnitus. Due to the still limited temporal and spatial resolution of current imaging modalities, a conclusive explanation of tinnitus remains elusive. With increasing use of functional imaging, additional important insights into the explanation of tinnitus will be gained in the future.

Negative Associations of Stress and Anxiety Levels With Cytotoxic and Regulatory Natural Killer Cell Frequency in Chronic Tinnitus.

Background: Depression and anxiety are known to be associated with stress-induced changes in the immune system. Bothersome tinnitus can be related to stress and often co-occurs with depression and anxiety. This study investigates associations of psychological and audiological tinnitus-related factors with inflammatory parameters and immune cell subsets in chronic tinnitus patients as well as treatment-related effects. Methods: This longitudinal study of inpatients treated with compact multimodal tinnitus-specific cognitive behavioral therapy included four repeated measurement sessions: baseline (N = 41), treatment end, 7.8-week (N = 35), and 13.8-week follow-up (N = 34). Data collection included audiometric testing, blood sampling, and psychometric questionnaires: Tinnitus Handicap Inventory (THI), Perceived Stress Questionnaire (PSQ-20), and Hospital Anxiety Depression Scale (HADS). Flow cytometry was used to analyze immune cell subsets. Statistical analyses comprised correlation and network analysis (cross-sectional), and linear mixed effect models (longitudinal). Results: Bootstrapped network analysis showed negative averaged cross-sectional associations of cytotoxic natural killer (NKc) cell frequency (CD56 + CD16+) and PSQ-20 (-0.21 [-0.48, 0]) and of regulatory natural killer (NKreg) cell frequency (CD56 + CD16dim/-) and HADS anxiety (-0.14 [-0.38, 0]). No significant treatment effects were found. A negative predictive effect of baseline PSQ-20 scores (ß = -6.22 [-12.18, -0.26], p = 0.041) and a positive predictive effect of baseline ferritin levels (ß = 8.90 [2.76, 15.03], p = 0.004) on NKc cell frequency across the repeated measurement sessions were observed. Conclusion: We observed negative relationships between perceived stress levels and NKc cell frequency and between anxiety levels and NKreg cell frequency in chronic tinnitus patients. These exploratory results suggest stress-/anxiety-related immune alterations in bothersome tinnitus but need to be tested in further confirmatory studies with larger sample sizes. The potential of NK cells as biomarkers of emotional distress in chronic tinnitus should be further investigated.

Daily Contributors of Tinnitus Loudness and Distress: An Ecological Momentary Assessment Study.

Background: Tinnitus is a heterogeneous condition which may be associated with moderate to severe disability, but the reasons why only a subset of individuals is burdened by the condition are not fully clear. Ecological momentary assessment (EMA) allows a better understanding of tinnitus by capturing the fluctuations of tinnitus symptoms, such as distress and loudness, and psychological processes, such as emotional arousal, overall stress, mood, and concentration and how these variables interact over time. Whether any of those variables have an influence over the next day, that is, whether any of these variables are auto- or cross-correlated, is still unanswered. Objectives: Assess whether behavioral and symptom-related data from tinnitus users from the TrackYourTinnitus (TYT) mobile app have an impact on tinnitus loudness and distress on subsequent days. Methods: Anonymized data was collected from 278 users of the iOS or Android TYT apps between 2014 and 2020. Tinnitus-related distress, tinnitus loudness, concentration level, mood, emotional arousal, and overall stress level were assessed using either a slider or the Wong-Baker Pain FACES scale via a daily survey. Three modeling strategies were used to investigate whether tinnitus loudness and distress are affected by previous days symptoms or psychological processes: auto- and cross correlations, regressions with elastic net regularization, and subgrouping within group iterative multiple model estimation (S-GIMME). Results: No autocorrelation or cross-correlation was observed at the group level between the variables assessed. However, application of the regression models with elastic net regularization identified individualized predictors of tinnitus loudness and distress for most participants, with the models including contemporaneous and lagged information from the previous day. S-GIMME corroborated these findings by identifying individualized predictors of tinnitus loudness and distress from the previous day. Discussion: We showed that tinnitus loudness and tinnitus distress are affected by the contemporaneous and lagged dynamics of behavioral and emotional processes measured through EMA. These effects were seen at the group, and individual levels. The relevance EMA and the implications of the insights derived from it for tinnitus care are discussed, especially considering current trends toward the individualization of tinnitus care.

Sex Differences in Comorbidity Combinations in the Swedish Population.

High comorbidity rates, especially mental-physical comorbidity, constitute an increasing health care burden, with women and men being differentially affected. To gain an overview of comorbidity rates stratified by sex across a range of different conditions, this study examines comorbidity patterns within and between cardiovascular, pulmonary, skin, endocrine, digestive, urogenital, musculoskeletal, neurological diseases, and psychiatric conditions. Self-report data from the LifeGene cohort of 31,825 participants from the general Swedish population (62.5% female, 18-84 years) were analyzed. Pairwise comorbidity rates of 54 self-reported conditions in women and men and adjusted odds ratios (ORs) for their comparison were calculated. Overall, the rate of pairwise disease combinations with significant comorbidity was higher in women than men (14.36% vs. 9.40%). Among psychiatric conditions, this rate was considerably high, with 41.76% in women and 39.01% in men. The highest percentages of elevated mental-physical comorbidity in women were found for musculoskeletal diseases (21.43%), digestive diseases (20.71%), and skin diseases (13.39%); in men, for musculoskeletal diseases (14.29%), neurological diseases (11.22%), and digestive diseases (10%). Implications include the need for integrating mental and physical health care services and a shift from a disease-centered to an individualized, patient-centered focus in clinical care.

Transcranial electric and acoustic stimulation for tinnitus: study protocol for a randomized double-blind controlled trial assessing the influence of combined transcranial random noise and acoustic stimulation on tinnitus loudness and distress.

BACKGROUND: Tinnitus is the result of aberrant neuronal activity. As a novel treatment form, neuromodulation is used to modify neuronal activity of brain areas involved in tinnitus generation. Among the different forms of electric stimulation, transcranial random noise stimulation (tRNS) has been shown to be a promising treatment option for tinnitus. In addition, recent studies indicate that the reduction in tinnitus can be more pronounced when different modalities of stimulation techniques are combined ("bimodal stimulation"). TRNS can be used in combination with acoustic stimulation (AS), a further treatment option recognized in the literature. The aim of the proposed study is to investigate whether simultaneous tRNS and AS improve levels of tinnitus loudness and distress. METHODS: The intervention consists of bilateral high-definition tRNS (HD-tRNS) over the auditory cortex combined with the application of AS which is studied in a crossover design. The visits will be performed in 26 sessions. There will be 20 treatment sessions, divided into two blocks: active and sham HD-tRNS. Within the blocks, the interventions are divided into group A: HD-tRNS and AS, and group B: HD-tRNS alone. Furthermore, in addition to the assessments directly following the intervention sessions, there will be six extra sessions performed subsequently at the end of each block, after a period of some days (follow-ups 1 and 2) and a month after the last intervention (C). Primary outcome measures are analog scales for evaluation of subjective tinnitus loudness and distress, and the audiological measurement of minimum masking level (MML). Secondary outcome measures are brain activity as measured by electroencephalography and standardized questionnaires for evaluating tinnitus distress and severity. DISCUSSION: To the best of our knowledge, this is the first study which uses HD-tRNS combined with AS for tinnitus treatment. The crossover design permits the comparison between HD-tRNS active vs. sham and with vs. without AS. Thus, it will be possible to evaluate the efficacy of the combined approach to HD-tRNS alone. In addition, the use of different objective and subjective evaluations for tinnitus enable more reliable and valid results. TRIAL REGISTRATION: Swiss Ethics Committee (BASEC-Nr. 2020-02027); Swiss Federal Complementary Database (kofam.ch: SNCTP000004051 ); and ClinicalTrials.gov (clinicaltrials.gov: NCT04551404 ).

Smartphone-Guided Educational Counseling and Self-Help for Chronic Tinnitus.

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.

Psychological Treatment Effects Unrelated to Hair-Cortisol and Hair-BDNF Levels in Chronic Tinnitus.

BACKGROUND: Currently, there are no objective markers to measure treatment efficacy in chronic (distressing) tinnitus. This study explores whether stress-related biomarkers cortisol and brain-derived neurotrophic factor (BDNF) measured in hair samples of chronic tinnitus patients change after compact multimodal tinnitus-specific cognitive behavioral therapy. METHODS: In this longitudinal study, hair-cortisol and hair-BDNF levels, self-reported tinnitus-related distress (Tinnitus Questionnaire; TQ), and perceived stress (Perceived Stress Questionnaire; PSQ-20) were assessed before and 3 months after 5 days of treatment in N = 80 chronic tinnitus patients. Linear mixed-effects models with backward elimination were used to assess treatment-induced changes, and a cross-lagged panel model (structural equation model) was used for additional exploratory analysis of the temporal associations between TQ and hair-BDNF. RESULTS: At follow-up, a reduction in TQ (p < 0.001) and PSQ-20 scores (p = 0.045) was observed, which was not influenced by baseline hair-cortisol or hair-BDNF levels. No changes in biomarker levels were observed after treatment. The exploratory analysis tentatively suggests that a directional effect of baseline TQ scores on hair-BDNF levels at follow-up (trend; p = 0.070) was more likely than the opposite directional effect of baseline hair-BDNF levels on TQ scores at follow-up (n.s.). DISCUSSION: While the treatment effectively reduced tinnitus-related distress and perceived stress in chronic tinnitus patients, this effect was not mirrored in biological changes. However, the lack of changes in hair-cortisol and hair-BDNF levels might have been influenced by the treatment duration, follow-up interval, or confounding medical factors, and therefore must be interpreted with caution. The relationship between tinnitus-related distress and hair-BDNF levels should be explored further to obtain a better understanding of stress-related effects in chronic tinnitus.

Hair-cortisol and hair-BDNF as biomarkers of tinnitus loudness and distress in chronic tinnitus.

The role of stress and its neuroendocrine mediators in tinnitus is unclear. In this study, we measure cortisol as an indicator of hypothalamus-pituitary-adrenal (HPA) axis alterations and brain-derived neurotrophic factor (BDNF) as a marker of adaptive neuroplasticity in hair of chronic tinnitus patients to investigate relationships with tinnitus-related and psychological factors. Cross-sectional data from chronic tinnitus inpatients were analyzed. Data collection included hair sampling, pure tone audiometry, tinnitus pitch and loudness matching, and psychometric questionnaires. Elastic net regressions with n-fold cross-validation were performed for cortisol (N = 91) and BDNF (N = 87). For hair-cortisol (R2 = 0.10), the strongest effects were sampling in autumn and body-mass index (BMI) (positive), followed by tinnitus loudness (positive) and smoking (negative). For hair-BDNF (R2 = 0.28), the strongest effects were hearing aid use, shift work (positive), and tinnitus loudness (negative), followed by smoking, tinnitus-related distress (Tinnitus Questionnaire), number of experienced traumatic events (negative), and physical health-related quality of life (Short Form-12 Health Survey) (positive). These findings suggest that in chronic tinnitus patients, higher perceived tinnitus loudness is associated with higher hair-cortisol and lower hair-BDNF, and higher tinnitus-related distress with lower hair-BDNF. Regarding hair-BDNF, traumatic experiences appear to have additional stress-related effects, whereas hearing aid use and high physical health-related quality of life appear beneficial. Implications include the potential use of hair-cortisol and hair-BDNF as biomarkers of tinnitus loudness or distress and the need for intensive future research into chronic stress-related HPA axis and neuroplasticity alterations in chronic tinnitus.

Deep Learning End-to-End Approach for the Prediction of Tinnitus based on EEG Data.

Tinnitus is attributed by the perception of a sound without any physical source causing the symptom. Symptom profiles of tinnitus patients are characterized by a large heterogeneity, which is a major obstacle in developing general treatments for this chronic disorder. As tinnitus patients often report severe constraints in their daily life, the lack of general treatments constitutes such a challenge that patients crave for any kind of promising method to cope with their tinnitus, even if it is not based on evidence. Another drawback constitutes the lack of objective measurements to determine the individual symptoms of patients. Many data sources are therefore investigated to learn more about the heterogeneity of tinnitus patients in order to develop methods to measure the individual situation of patients more objectively. As research assumes that tinnitus is caused by processes in the brain, electroencephalography (EEG) data are heavily investigated by researchers. Following this, we address the question whether EEG data can be used to classify tinnitus using a deep neural network. For this purpose, we analyzed 16,780 raw EEG samples from 42 subjects (divided into tinnitus patients and control group), with a duration of one second per sample. Four different procedures (with or without noise reduction and down-sampling or up-sampling) for automated preprocessing were used and compared. Subsequently, a neural network was trained to classify whether a sample refers to a tinnitus patient or the control group. We obtain a maximum accuracy in the test set of 75.6% using noise reduction and down-sampling. Our findings highlight the potential of deep learning approaches to detect EEG patterns for tinnitus patients as they are difficult to be recognized by humans.

Unification of Treatments and Interventions for Tinnitus Patients (UNITI): a study protocol for a multi-center randomized clinical trial.

BACKGROUND: Tinnitus represents a relatively common condition in the global population accompanied by various comorbidities and severe burden in many cases. Nevertheless, there is currently no general treatment or cure, presumable due to the heterogeneity of tinnitus with its wide variety of etiologies and tinnitus phenotypes. Hence, most treatment studies merely demonstrated improvement in a subgroup of tinnitus patients. The majority of studies are characterized by small sample sizes, unstandardized treatments and assessments, or applications of interventions targeting only a single organ level. Combinatory treatment approaches, potentially targeting multiple systems as well as treatment personalization, might provide remedy and enhance treatment responses. The aim of the present study is to systematically examine established tinnitus therapies both alone and in combination in a large sample of tinnitus patients. Further, it wants to provide the basis for personalized treatment approaches by evaluating a specific decision support system developed as part of an EU-funded collaborative project (Unification of treatments and interventions for tinnitus patients; UNITI project). METHODS/STUDY DESIGN: This is a multi-center parallel-arm randomized clinical trial conducted at five different clinical sites over the EU. The effect of four different tinnitus therapy approaches (sound therapy, structured counseling, hearing aids, cognitive behavioral therapy) applied over a time period of 12 weeks as a single or rather a combinatory treatment in a total number of 500 chronic tinnitus patients will be investigated. Assessments and interventions are harmonized over the involved clinical sites. The primary outcome measure focuses on the domain tinnitus distress assessed via the Tinnitus Handicap Inventory. DISCUSSION: Results and conclusions from the current study might not only provide an essential contribution to combinatory and personalized treatment approaches in tinnitus but could also provide more profound insights in the heterogeneity of tinnitus, representing an important step towards a cure for tinnitus. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663828 . Registered on 11 December 2020.

Gender differentiates effects of acoustic stimulation in patients with tinnitus.

Gender constitutes a major factor to consider when tailoring subtype-based therapies for tinnitus. Previous reports showed important differences between men and women concerning basic perceptual tinnitus characteristics (i.e., laterality, frequency, tinnitus loudness) as well as psychological reactions linked to this condition. Therapeutic approaches based on acoustic stimulation involve processes beyond a pure masking effect and consist of sound presentation temporarily altering or alleviating tinnitus perception via residual and/or lateral inhibition mechanisms. Presented stimuli may include pure tones, noise, and music adjusted to or modulated to filter out tinnitus pitch and therefore trigger reparative functional and structural changes in the auditory system. Furthermore, recent findings suggest that in tonal tinnitus, the presentation of pitch-adjusted sounds which were altered by a 10Hz modulation of amplitude was more efficient than unmodulated stimulation. In this paper, we investigate sex differences in the outcome of different variants of acoustic stimulation, looking for factors revealing predictive value in the efficiency of tinnitus relief.

Prolonged tinnitus suppression after short-term acoustic stimulation.

BACKGROUND: Tinnitus suppression following acoustic stimulation is a well-known phenomenon also termed residual inhibition (RI). Some individuals may experience prolonged RI (PRI), which can last for several hours or even days, after a single short-term acoustic stimulation. Exact mechanisms of this phenomenon are unknown and current evidence anecdotal. OBJECTIVES: The aim of our report is to collect, present, and discuss cases of PRI from our studies on acoustic stimulation in tinnitus with the aim to better understand this phenomenon as well as its implications for individualized treatments. METHODS: We pooled cases of PRI from four of our studies with a total sample size of n = 130. The criterion was set on a PRI duration which is at least sustained twice as long as the acoustic stimulation duration. RESULTS: We report a total number of about 5% of all participants experiencing some form of PRI, with rates of 3%-7% across the individual studies. PRI lasted from 20 min up to several days and was induced by the first stimulus in four out of six cases. Four out of six individuals experiencing PRI were female and PRI mostly occurred when acoustic stimuli were matched to the frequency or type of the tinnitus. CONCLUSION: PTS seems to be elicitable in a small subset of tinnitus patients which could inform future individualized treatment options. Future studies should investigate if and how identified factors like stimulus type, position, sex, and chronification grade uphold experimental scrutiny. We propose that the set of methods is furthermore extended with neurophysiology in particular.

On the relationship between tinnitus distress, cognitive performance and aging.

In this study we analyzed psychometric data of 107 individuals who suffer from chronic subjective tinnitus. In particular, we elucidated the relationship between tinnitus-related distress, psychological comorbidities, age, and hearing, and the performance in cognitive concentration and interference tests. Previous research has provided first evidence that individuals with tinnitus may have deficits in cognitive tasks. The present study aimed at extending former research by investigating the relationship between tinnitus distress and cognition. Statistical analyses comprised correlation and regression approaches. We observed a significant relationship between tinnitus distress (tinnitus score, TQ), age and hearing loss and the performance in tests on selective and sustained attention (d2 test) and cognitive interference (Stroop test). Tinnitus distress was identified as the most important predictor of cognitive performance (additionally age for cognitive interference). For other psychometric variables (perceived stress, PSQ; self-efficacy, optimism and pessimism, SWOP) and hearing loss we could not find any meaningful relationship with cognitive performance. The results clearly point to a (currently non-causal) relationship between cognitive skills and distress of tinnitus-related symptoms. Furthermore, the influence of age is noteworthy as this finding implies that with increasing age an appropriate coping with aversive tinnitus symptoms based on proper cognitive functions and age-related hearing dysfunctions, namely inhibition, may become more difficult. Hence, it is suggested to consider cognitive tests as a supplementary measurement in clinical assessment of tinnitus and to raise awareness for the impairing influence of tinnitus on cognition in daily life.

Tinnitus and tinnitus disorder: Theoretical and operational definitions (an international multidisciplinary proposal).

As for hypertension, chronic pain, epilepsy and other disorders with particular symptoms, a commonly accepted and unambiguous definition provides a common ground for researchers and clinicians to study and treat the problem. The WHO's ICD11 definition only mentions tinnitus as a nonspecific symptom of a hearing disorder, but not as a clinical entity in its own right, and the American Psychiatric Association's DSM-V doesn't mention tinnitus at all. Here we propose that the tinnitus without and with associated suffering should be differentiated by distinct terms: "Tinnitus" for the former and "Tinnitus Disorder" for the latter. The proposed definition then becomes "Tinnitus is the conscious awareness of a tonal or composite noise for which there is no identifiable corresponding external acoustic source, which becomes Tinnitus Disorder "when associated with emotional distress, cognitive dysfunction, and/or autonomic arousal, leading to behavioural changes and functional disability.". In other words "Tinnitus" describes the auditory or sensory component, whereas "Tinnitus Disorder" reflects the auditory component and the associated suffering. Whereas acute tinnitus may be a symptom secondary to a trauma or disease, chronic tinnitus may be considered a primary disorder in its own right. If adopted, this will advance the recognition of tinnitus disorder as a primary health condition in its own right. The capacity to measure the incidence, prevalence, and impact will help in identification of human, financial, and educational needs required to address acute tinnitus as a symptom but chronic tinnitus as a disorder.

Impact of personality on acoustic tinnitus suppression and emotional reaction to stimuli sounds.

Background: Acoustic stimulation was shown to be effective in short-term suppression of tinnitus. However, tinnitus cannot be suppressed in all patients. Recent insights from mental health research suggests that personality traits may be important factors in prediction of treatment outcomes or improvement of tinnitus over time. No previous acoustic stimulation study investigated the effects of personality traits on tinnitus suppression and rating of sound stimuli. Objectives: The aim of this study was therefore to examine whether personality is capable to predict tinnitus suppression in chronic tinnitus patients as well as related emotional stimulus evaluation. Methods: Personality data (Big Five Index 2; BFI-2) of two acoustic stimulation experiments were pooled for this analysis. Both experiments were conducted at the University of Regensburg, Germany in the time period between April 2018 and October 2019 and consisted of individual designed noise and amplitude modulated tones matched to the participants' tinnitus pitch. Logistic regressions or linear mixed effect models were performed with tinnitus suppression as well as valence and arousal data as dependent variables and BFI-2 personality dimensions as predictors. Results: 28% of the participants showed pronounced short-term tinnitus suppression after acoustic stimulation (50% reduction in subjective tinnitus loudness). Analyzing BFI-2 data, no significant impact of the big five personality traits (neuroticism, agreeableness, extraversion, conscientiousness, openness) were found, neither on acoustic tinnitus suppression, nor on emotional stimulus evaluation, namely arousal. Conclusion: Personality was not shown to be a predictive factor, neither for acoustic stimulation, nor for emotional reaction to stimuli sounds in our studies. However, since tinnitus cannot be suppressed by acoustic stimulation in all patients, future studies should investigate other explaining factors such as patient-related or (neuro)physiological characteristics.

Towards a unification of treatments and interventions for tinnitus patients: The EU research and innovation action UNITI.

Tinnitus is the perception of a phantom sound and the patient's reaction to it. Although much progress has been made, tinnitus remains a scientific and clinical enigma of high prevalence and high economic burden, with an estimated prevalence of 10%-20% among the adult population. The EU is funding a new collaborative project entitled "Unification of Treatments and Interventions for Tinnitus Patients" (UNITI, grant no. 848261) under its Horizon 2020 framework. The main goal of the UNITI project is to set the ground for a predictive computational model based on existing and longitudinal data attempting to address the question of which treatment or combination of treatments is optimal for a specific patient group based on certain parameters. Clinical, epidemiological, genetic and audiological data, including signals reflecting ear-brain communication, as well as patients' medical history, will be analyzed making use of existing databases. Predictive factors for different patient groups will be extracted and their prognostic relevance validated through a Randomized Clinical Trial (RCT) in which different patient groups will undergo a combination of tinnitus therapies targeting both auditory and central nervous systems. From a scientific point of view, the UNITI project can be summarized into the following research goals: (1) Analysis of existing data: Results of existing clinical studies will be analyzed to identify subgroups of patients with specific treatment responses and to identify systematic differences between the patient groups at the participating clinical centers. (2) Genetic and blood biomarker analysis: High throughput Whole Exome Sequencing (WES) will be performed in well-characterized chronic tinnitus cases, together with Proximity Extension Assays (PEA) for the identification of blood biomarkers for tinnitus. (3) RCT: A total of 500 patients will be recruited at five clinical centers across Europe comparing single treatments against combinational treatments. The four main treatments are Cognitive Behavioral Therapy (CBT), hearing aids, sound stimulation, and structured counseling. The consortium will also make use of e/m-health applications for the treatment and assessment of tinnitus. (4) Decision Support System: An innovative Decision Support System will be implemented, integrating all available parameters (epidemiological, clinical, audiometry, genetics, socioeconomic and medical history) to suggest specific examinations and the optimal intervention strategy based on the collected data. (5) Financial estimation analysis: A cost-effectiveness analysis for the respective interventions will be calculated to investigate the economic effects of the interventions based on quality-adjusted life years. In this paper, we will present the UNITI project, the scientific questions that it aims to address, the research consortium, and the organizational structure.