Periodic Reporting for period 2 - TIN-ACT (Research School for TINnitus Assessment, Causes and Treatments)
Periodo di rendicontazione: 2019-11-01 al 2022-04-30
TIN-ACT is a European consortium that investigates tinnitus (“ringing in the ears”). Tinnitus is a very common and potentially devastating condition. People with tinnitus continuously hear a penetrating phantom sound without an acoustic source producing this sound. An estimated 50.8 million EU citizens have tinnitus, of whom 5.1 million are severely bothered by it. Chronic tinnitus can be incredibly debilitating, leading to difficulty concentrating, lack of sleep, anxiety, and depression. Even mild forms of tinnitus reduce productivity due to difficulty hearing and concentrating at work, while also reducing the ability to relax and rest during leisure time. The individual cost of tinnitus is between €2000 and €6200 per year (depending on the severity of the tinnitus), resulting in the total costs related to tinnitus exceeding €140 billion per year in the European Union alone.
The aim of the TIN-AT network is to understand the basic neural mechanisms of tinnitus, to improve the methods to measure tinnitus and ultimately apply this knowledge to improve the treatment of tinnitus. The TIN-ACT network unites world-leading academic groups, research-intensive industrial partners, patient organizations and excellent young researchers. The goal of the network is to provide robust multidisciplinary research and a training-oriented environment that is necessary to overcome the roadblocks that hamper the development of adequate tinnitus treatments.
The aim of the TIN-AT network is to understand the basic neural mechanisms of tinnitus, to improve the methods to measure tinnitus and ultimately apply this knowledge to improve the treatment of tinnitus. The TIN-ACT network unites world-leading academic groups, research-intensive industrial partners, patient organizations and excellent young researchers. The goal of the network is to provide robust multidisciplinary research and a training-oriented environment that is necessary to overcome the roadblocks that hamper the development of adequate tinnitus treatments.
The management and training aspects of TIN-ACT, work package 1, have been satisfactorily implemented in accordance with the grant agreement.
The Fellows involved in work package 2, the assessment of tinnitus, developed new screening tools for tinnitus-related conditions such as synaptopathy, hyperacusis, misophonia, and for measuring outcome domains used in clinical trials. The newly developed tools screening for hyperacusis and misophonia selected sounds based on their pleasantness rating, while presenting those sounds at relatively low stimulation levels, effectively reducing the discomfort to the patient. Furthermore, a new tool was developed to screen for synaptopathy in tinnitus patients, which has the great advantage of being portable and autonomous, and it can therefore be applied easily and in various settings. A new tool developed to assess concentration has improved the measurement of the specific outcome domain ‘concentration’, essential to determining the effectiveness of treatment in clinical trials.
Further work within work package 2 focused on the utility of neural correlates and other biomarkers to assess tinnitus. Transient-induced tinnitus due to earplugging resulted in altered oscillatory dynamics in the auditory cortex of individuals which was present when people reported hearing the phantom sound. Another model of transient tinnitus is the induced Zwicker tone percept, which demonstrated enhanced activity in the auditory cortex. These studies yielded neural correlates that will improve the interpretation of neuronal activity in individuals with tinnitus and highlighted how rapidly the human auditory pathway responds to changes in auditory perception. In addition to neural correlates, specific biomarkers related to tinnitus-related distress were identified. These findings inform research investigating the relationship between stress-related physiological markers and the development and maintenance of tinnitus. Furthermore, gender-specific risk factors and co-morbidities were identified, highlighting the need to take this variable into account when reporting on tinnitus. A meta-analysis conducted within work package 2 highlighted the need for standardization of analysis methods in studies investigating gray matter correlates of tinnitus. The research of work package 2 improved our methods of assessment of tinnitus-related conditions and increased our understanding of tinnitus-related neural correlates and biomarkers in the context of tinnitus assessment.
Tinnitus is a complex symptom, and the causes of tinnitus are not well understood. Understanding the factors that contribute to the development of tinnitus will greatly improve our ability to develop new treatments. The Fellows in work package 3 investigated the causes of tinnitus. The studies in this work package illustrate the usefulness of animal models in tinnitus research, which enables the investigation of the mechanisms underlying observed changes in behaviour or neuronal signatures related to tinnitus at the level of ion channels, something that is not feasible in humans. A novel protein regulating the function of a BK ion channel in the cochlea was identified, which both improves our understanding of how the inner ear functions, and can provide a future therapeutic target. Clinical reports in humans with tinnitus suggest a link between stress and auditory conditions, such as tinnitus. In line with this, emotional stress was shown to alter auditory brainstem responses and outer hair cell motility, thereby affecting the functionality of the auditory system. Similar to the findings on humans in work package 2, research in work package 3 showed that stress hormone-induced changes to the inner ear are gender-dependent. This finding provides an interesting correlate for gender-associated differences in tinnitus symptomatology reported by patients in clinical settings. A comparison of regularly used animal models of tinnitus showed that the different types of tinnitus induction are not based on the same neurophysiological mechanism. The findings of work package 3 are informative to future studies intending to translate findings in animal models of tinnitus to human frameworks.
Even with an incomplete understanding of the causes of tinnitus, there are treatments that can reduce the tinnitus burden by attenuation of the tinnitus percept, improving mental resilience to reduce the negative impact of tinnitus, and restoring the auditory input signals. Fellows in work package 4 developed and tested tinnitus treatments. Broadband amplification reduced tinnitus-related distress and annoyance, and this amplification led to changes in neuronal activity. Short-term reduction in tinnitus loudness and annoyance was accomplished with a novel method combining auditory and biotherapy while measuring minimum residual inhibition levels with a novel stimulus that provides better listening comfort. In individuals with more severe hearing loss, cochlear implantation (CI) is performed to improve hearing thresholds and it appears that this procedure can reduce tinnitus in a proportion of CI recipients. These findings provide useful indications that personalised hearing aid fitting, and tailored electrical stimulation in CI recipients, can benefit patients by decreasing their tinnitus, and these methods may be able to induce changes at central levels of auditory processing.
The Fellows involved in work package 2, the assessment of tinnitus, developed new screening tools for tinnitus-related conditions such as synaptopathy, hyperacusis, misophonia, and for measuring outcome domains used in clinical trials. The newly developed tools screening for hyperacusis and misophonia selected sounds based on their pleasantness rating, while presenting those sounds at relatively low stimulation levels, effectively reducing the discomfort to the patient. Furthermore, a new tool was developed to screen for synaptopathy in tinnitus patients, which has the great advantage of being portable and autonomous, and it can therefore be applied easily and in various settings. A new tool developed to assess concentration has improved the measurement of the specific outcome domain ‘concentration’, essential to determining the effectiveness of treatment in clinical trials.
Further work within work package 2 focused on the utility of neural correlates and other biomarkers to assess tinnitus. Transient-induced tinnitus due to earplugging resulted in altered oscillatory dynamics in the auditory cortex of individuals which was present when people reported hearing the phantom sound. Another model of transient tinnitus is the induced Zwicker tone percept, which demonstrated enhanced activity in the auditory cortex. These studies yielded neural correlates that will improve the interpretation of neuronal activity in individuals with tinnitus and highlighted how rapidly the human auditory pathway responds to changes in auditory perception. In addition to neural correlates, specific biomarkers related to tinnitus-related distress were identified. These findings inform research investigating the relationship between stress-related physiological markers and the development and maintenance of tinnitus. Furthermore, gender-specific risk factors and co-morbidities were identified, highlighting the need to take this variable into account when reporting on tinnitus. A meta-analysis conducted within work package 2 highlighted the need for standardization of analysis methods in studies investigating gray matter correlates of tinnitus. The research of work package 2 improved our methods of assessment of tinnitus-related conditions and increased our understanding of tinnitus-related neural correlates and biomarkers in the context of tinnitus assessment.
Tinnitus is a complex symptom, and the causes of tinnitus are not well understood. Understanding the factors that contribute to the development of tinnitus will greatly improve our ability to develop new treatments. The Fellows in work package 3 investigated the causes of tinnitus. The studies in this work package illustrate the usefulness of animal models in tinnitus research, which enables the investigation of the mechanisms underlying observed changes in behaviour or neuronal signatures related to tinnitus at the level of ion channels, something that is not feasible in humans. A novel protein regulating the function of a BK ion channel in the cochlea was identified, which both improves our understanding of how the inner ear functions, and can provide a future therapeutic target. Clinical reports in humans with tinnitus suggest a link between stress and auditory conditions, such as tinnitus. In line with this, emotional stress was shown to alter auditory brainstem responses and outer hair cell motility, thereby affecting the functionality of the auditory system. Similar to the findings on humans in work package 2, research in work package 3 showed that stress hormone-induced changes to the inner ear are gender-dependent. This finding provides an interesting correlate for gender-associated differences in tinnitus symptomatology reported by patients in clinical settings. A comparison of regularly used animal models of tinnitus showed that the different types of tinnitus induction are not based on the same neurophysiological mechanism. The findings of work package 3 are informative to future studies intending to translate findings in animal models of tinnitus to human frameworks.
Even with an incomplete understanding of the causes of tinnitus, there are treatments that can reduce the tinnitus burden by attenuation of the tinnitus percept, improving mental resilience to reduce the negative impact of tinnitus, and restoring the auditory input signals. Fellows in work package 4 developed and tested tinnitus treatments. Broadband amplification reduced tinnitus-related distress and annoyance, and this amplification led to changes in neuronal activity. Short-term reduction in tinnitus loudness and annoyance was accomplished with a novel method combining auditory and biotherapy while measuring minimum residual inhibition levels with a novel stimulus that provides better listening comfort. In individuals with more severe hearing loss, cochlear implantation (CI) is performed to improve hearing thresholds and it appears that this procedure can reduce tinnitus in a proportion of CI recipients. These findings provide useful indications that personalised hearing aid fitting, and tailored electrical stimulation in CI recipients, can benefit patients by decreasing their tinnitus, and these methods may be able to induce changes at central levels of auditory processing.
The impact of TIN-ACT will extend beyond the academic world and help patients and society by improving the understanding of tinnitus biology, developing and implementing novel diagnostic and treatment strategies, and raising awareness of the importance of tinnitus research through dissemination and outreach activities. Both the ESRs and the Principal Investigators of TIN-ACT are reaching out to the public by taking the opportunity to present their projects in the local or national media, at patient organization meetings, general science fairs and via our educational video series.