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Background: The Marie-Skłodowska-Curie Actions’ (MSCA) Innovative Training Network (ITN) is a doctoral training programme jointly implemented by academic institutions and industries from countries across Europe and beyond. To our knowledge no study has examined the experience of students participating in MSCA-ITNs. This study aims to evaluate and report MSCA-ITN Early Stage Researcher (ESR) experiences. Methods: The Innovative Training Network - Evaluation Questionnaire (ITN-EQ) was developed to assess supervision, training, collaborations and experiences of ESRs and forwarded to two tinnitus-related ITNs and seven ITNs of other disciplines. Results: Key advantages identified included better career prospects, multidisciplinary research opportunities/collaborations, international exposure, personal/professional development, plus generous salaries and research budgets. However, lack of a common EU framework resulted in the experience being largely dependent on the host institution, country and supervisor. Moreover, managing the dual requirements of ITNs and host institutions while completing a three-year PhD seemed challenging for most ESRs. ESR involvement in workshop and training school planning was desirable. More than 80% of ESRs rated the overall ITN experience favourably and 98.3% would recommend the same to prospective PhD students. Conclusions: This report could provide valuable insights in planning and management of future ITNs and could assist prospective students in their decision of joining an ITN for their PhD.

The continuous auditory perception of an acoustic stimulus without the existence of a corresponding source of sound is termed chronic subjective tinnitus and represents a relative common phenomenon in the global population. On the basis of varieties in phenotype and etiology, there is currently no effective treatment option or cure for tinnitus. Individualization of interventions represents a promising approach to cope with tinnitus heterogeneity. In the present thesis four separate experiments were conducted with a focus on transient changes in tinnitus perception and tinnitus-related electrophysiological brain activity caused either by acoustic stimulation or repetitive transcranial magnetic stimulation (rTMS). In study 1 different noise stimuli were modified according to patients’ tinnitus characteristics and applied to noise- like and tonal tinnitus patients. Besides the ability of each stimulus in brief tinnitus suppression, superior loudness decreases were observed in noise-like tinnitus patients. The main goal of study 2 was to examine the consequences of different individualized sound stimuli on tinnitus- related electrophysiological brain activity and whether potential neural changes can be linked with tinnitus loudness alterations. Results indicate tinnitus-unspecific oscillatory brain activity changes due to sound stimulations plus an absence of behavioral and neural correlations. Contrasts between acoustic stimulation responders and non-responders showed enhanced alpha and diminished gamma band activity in the group of responders according to the current neural models for tinnitus. Additional analyses revealed post stimulation differences between these two subgroups especially in the alpha frequency band in auditory cortical regions. Study 3 and 4 are dedicated to rTMS single sessions in tinnitus. Study 3 was conceptualized as a technical feasibility report using a small sample of tinnitus patients with the aim to investigate the feasibility and reliability of rTMS individualization for tinnitus. Another objective was to ascertain if specific stimulation parameters provoke consistent tinnitus loudness changes. Different auditory cortex positions were stimulated with various frequencies over both hemispheres on two days. Findings indicate consistency of several stimulation parameters e.g., frequency for brief tinnitus suppression. Further, it was feasible to identify an individualized rTMS protocol for reliable placebo-superior tinnitus suppression in each patient. Insights from study 3 were transferred to succeeding study 4. The aim of study 4 was to systematically scrutinize the reliability of rTMS effects as well as the feasibility of rTMS individualization via single sessions using a bigger sample size and only one temporal cortex stimulation position. In addition to behavioral ratings, electrophysiological brain activity was recorded. No reliable rTMS-induced effects neither on tinnitus loudness nor oscillatory brain activity could be detected. Besides rTMS individualization based on behavioral responses, electrophysiological data was used to identify a patient-specific rTMS protocol provoking changes in spontaneous brain activity according to neurophysiological models for tinnitus. RTMS individualization via behavioral and electrophysiological responses was feasible, but identification of an individualized protocol via electrophysiological responses seemed superior. The findings of the present thesis not only offer profound insights behind the basic and neurophysiological mechanisms of brief tinnitus suppression, but also provide useful indications and suggestions for prospective research attempts as well as treatment approaches in the fields of acoustic stimulation and rTMS for tinnitus., Die kontinuierliche auditive Wahrnehmung eines akustischen Reizes in Abwesenheit einer entsprechenden Schallquelle wird als chronischer subjektiver Tinnitus bezeichnet und stellt ein global relativ häufig auftretendes Phänomen dar. Aufgrund vielfältiger Phänotypen und Ätiologien gibt es bis dato keine wirksamen Heilverfahren. Die Individualisierung von Interventionen bietet einen vielversprechenden Ansatz, um dieser Heterogenität entgegenzuwirken. Im Rahmen der vorliegenden Dissertation wurden insgesamt vier eigenständige Experimente zu akustischer Stimulation oder repetitiver transkranieller Magnetstimulation (rTMS) bei Tinnitus durchgeführt mit dem Ziel kurzzeitige Veränderungen der Tinnituswahrnehmung als auch elektrophysiologischer Hirnaktivität zu untersuchen. In Studie 1 wurden verschiedene rauschartige Stimuli gemäß den Tinnitus-Charakteristika von Patient*innen mit rauschhaftem oder tonalem Tinnitus modifiziert und für eine kurze akustische Stimulation verwendet. Eine temporäre Suppression des Tinnitus konnte bei allen applizierten Stimuli beobachtet werden. Patient*innen mit rauschhaftem Tinnitus zeigten jedoch eine deutlich stärkere Lautstärkeverminderung. Das Hauptziel von Studie 2 hingegen war es, die Auswirkungen von unterschiedlichen individualisierten rauschhaften Stimuli auf elektrophysiologische Hirnaktivität, assoziiert mit Tinnitus, zu überprüfen. Überdies ging Studie 2 der Frage nach, ob potenzielle neuronale Modulationen mit Veränderungen der Tinnituslautstärke in Zusammenhang stehen. Die Ergebnisse legten Tinnitus-unspezifische elektrophysiologische Veränderungen bedingt durch eine akustische Stimulation nahe, sowie keinen Zusammenhang von neuronalen und Verhaltensdaten. Patient*innen, die auf eine akustische Stimulation respondierten, zeigten erhöhte Alpha sowie verminderte Gamma Aktivität im Einklang mit den aktuellen neuronalen Modellen bei Tinnitus. Weitere Analysen brachten insbesondere Unterschiede im Alpha Frequenzband in auditorischen Bereichen des Kortex im Anschluss an eine Stimulation zum Vorschein. Studie 3 und 4 beschäftigten sich mit sogenannten rTMS Testsitzungen. Studie 3 wurde mit einer kleinen Stichprobe als eine technische Machbarkeitsstudie konzipiert. Das Ziel war es, die Machbarkeit und Zuverlässigkeit einer rTMS Individualisierung mittels Testsitzungen zu evaluieren. Ferner sollte herausgefunden werden, ob bestimmte Stimulationsparameter zuverlässige Veränderungen in der Tinnituslautstärke bewirken. Unterschiedliche Positionen des auditorischen Kortex wurden an zwei Tagen mit verschiedenen Frequenzen über beiden Hemisphären stimuliert. Bestimmte Stimulationsparameter wie etwa Frequenz, waren in der Lage konsistente Veränderungen in der Tinnituswahrnehmung hervorzurufen. Außerdem konnte für jede/n Patient*in ein individuelles rTMS Protokoll identifiziert werden, welches zuverlässig die Tinnituslautstärke verringerte und dabei einer Placebostimulation überlegen war. Die gewonnen Erkenntnisse wurden zur Planung und Durchführung von Studie 4 genutzt. Studie 4 beabsichtigte neben der Reliabilitätsprüfung von rTMS Effekten auch die Möglichkeit der rTMS-Individualisierung anhand einer größeren Stichprobe und einer einzigen temporalen Stimulationsposition systematisch zu untersuchen. Zusätzlich zu Lautstärkebewertungen fanden elektroenzephalographische Aufzeichnungen statt. Es konnten weder reliable V eränderungen der Lautstärke noch reliable elektrophysiologische Hirnaktivitätsveränderungen bedingt durch rTMS nachgewiesen werden. Neben einer Individualisierung anhand von Verhaltensdaten wurden zudem elektrophysiologische Daten herangezogen. Das Ziel war die Identifizierung eines patientenspezifischen rTMS-Protokolls, welches neuronale Veränderungen entsprechend neurophysiologischer Modelle bei Tinnitus verursacht. Beide Individualisierungsansätze waren umsetzbar, wobei eine Individualisierung anhand von elektrophysiologischen Antworten überlegen zu sein scheint. Die vorliegenden Ergebnisse bieten nicht nur einen fundierten Einblick in die grundlegenden und neurophysiologischen Prozesse einer kurzzeitigen Unterdrückung der Tinnituswahrnehmung, sondern liefern auch nützliche Hinweise und Anregungen für zukünftige Forschungsarbeiten und Behandlungsansätze in den Bereichen akustische Stimulation und rTMS bei Tinnitus.

BackgroundThe heterogeneity of tinnitus is substantial. Its numerous pathophysiological mechanisms and clinical manifestations have hampered fundamental and treatment research significantly. A decade ago, the Tinnitus Research Initiative introduced the Tinnitus Sample Case History Questionnaire, a case history instrument for standardised collection of information about the characteristics of the tinnitus patient. Since then, a number of studies have been published which characterise individuals and groups using data collected with this questionnaire. However, its use has been restricted to a clinical setting and to the evaluation of people with tinnitus only. In addition, it is limited in the ability to capture relevant comorbidities and evaluate their temporal relationship with tinnitus.MethodHere we present a new case history instrument which is comprehensive in scope and can be answered by people with and without tinnitus alike. This ‘European School for Interdisciplinary Tinnitus Research Screening Questionnaire’ (ESIT-SQ) was developed with specific attention to questions about potential risk factors for tinnitus (including demographics, lifestyle, general medical and otological histories), and tinnitus characteristics (including perceptual characteristics, modulating factors, and associations with co-existing conditions). It was first developed in English, then translated into Dutch, German, Italian, Polish, Spanish, and Swedish, thus having broad applicability and supporting international collaboration.ConclusionsWith respect to better understanding tinnitus profiles, we anticipate the ESIT-SQ to be a starting point for comprehensive multi-variate analyses of tinnitus. Data collected with the ESIT-SQ can allow establishment of patterns that distinguish tinnitus from non-tinnitus, and definition of common sets of tinnitus characteristics which might be indicated by the presence of otological or comorbid systemic diseases for which tinnitus is a known symptom.

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.

Tinnitus can be a burdensome condition on both individual and societal levels. Many aspects of this condition remain elusive, including its underlying mechanisms, ultimately hindering the development of a cure. Interdisciplinary approaches are required to overcome long-established research challenges. This review summarizes current knowledge in various tinnitus-relevant research fields including tinnitus generating mechanisms, heterogeneity, epidemiology, assessment, and treatment development, in an effort to highlight the main challenges and provide suggestions for future research to overcome them. Four common themes across different areas were identified as future research direction: (1) Further establishment of multicenter and multidisciplinary collaborations; (2) Systematic reviews and syntheses of existing knowledge; (3) Standardization of research methods including tinnitus assessment, data acquisition, and data analysis protocols; (4) The design of studies with large sample sizes and the creation of large tinnitus-specific databases that would allow in-depth exploration of tinnitus heterogeneity., publishedVersion

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. publishedVersion

Background: Past research highlighted the benefits of personalized repetitive transcranial magnetic stimulation (rTMS) for the treatment of chronic subjective tinnitus. Objective/Hypothesis: The objective was to investigate the feasibility of rTMS personalization by identifying individually optimal stimulation parameters in test sessions. Particularly, effectiveness and retest-reliability of different stimulation parameters were examined. Methods: Via electric-field guided rTMS, five patients were stimulated with different frequencies on three positions of the left and right superior temporal gyrus on 2 separate days. After each stimulation, the patients had to evaluate tinnitus loudness and discomfort of the used protocol. Results: Individualization of rTMS was possible in all five patients. Significant lower tinnitus loudness was found for 1 Hz stimulation. Positive correlations between 2 days were observed for hemisphere (left, right), position (mSTG, pSTG), and frequency (1, 10, 20 Hz). High-frequency stimulation produced high discomfort. Conclusion: Personalization of rTMS is considered as feasible. Consistency of parameter-specific tinnitus suppression is demonstrated.