Corrigendum:Multidisciplinary Tinnitus Research: Challenges and Future Directions From the Perspective of Early Stage Researchers (Front. Aging Neurosci., (2021), 13, (647285), 10.3389/fnagi.2021.647285)

In the original article, there was an error. For the sentence “NMDA receptor antagonists (AM-101) have been discontinued in phase III for not meeting endpoints (van de Heyning et al., 2014)” there was a typographical error (phase III should have been phase II). In addition, it was brought to our attention that clinical trials for AM-101 are ongoing. A correction has been made to section 6. Treatment Development, Subsection 6.4. Pharmacology-Based Interventions, paragraph 1. The corrected paragraph is below. A wide variety of therapeutic drugs have been used to relieve tinnitus (Elgoyhen and Langguth, 2010). For acute tinnitus, a dose-dependent reduction in tinnitus intensity was observed with intravenous lidocaine (Trellakis et al., 2006). However, its use is controversial due to its short-lasting response, its potentially life threatening arrhythmogenic side effects, and the low bioavailability of its oral form (Israel et al., 1982; Trellakis et al., 2007; Gil-Gouveia and Goadsby, 2009). A potential goal of pharmacologic tinnitus research could be to identify the mechanism by which lidocaine interferes with tinnitus and mimic this effect using a drug with better tolerance that can be orally administered. For chronic tinnitus, the off-label use of medicines like betahistine (Hall et al., 2018d), anticonvulsants (Hoekstra et al., 2011), and glutamate receptor antagonists have shown little or no effect in clinical trials. Prescription of antidepressants and benzodiazepines is limited to tinnitusassociated comorbidities such as depression, insomnia and anxiety (Langguth et al., 2019). Moreover, three clinical research programs, in the last few years, were discontinued in phase II and III. AMPA antagonist selurampanel (BGG492) has not resulted in a new compound (Cederroth et al., 2018). NMDA receptor antagonists (AM-101) did not meet the primary endpoint of improving minimum masking level in acute tinnitus in a phase II clinical trial but showed improvement for tinnitus loudness, annoyance, sleep difficulties, and tinnitus impact in patients with tinnitus after noise trauma or otitis media (van de Heyning et al., 2014). Many other treatments decreasing tinnitus percept or targeting central auditory processing pathways are at a preclinical phase (Schilder et al., 2019). The modulator of voltage-gated potassium channels (Kv3.1) (AUT00063) was not effective in alleviating tinnitus symptoms (Hall et al., 2019b). The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated

Multidisciplinary Tinnitus Research: Challenges and Future Directions from the Perspective of Early Stage Researchers

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

Multidisciplinary Tinnitus Research: Challenges and Future Directions from the Perspective of Early Stage Researchers

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

Nouveaux outils psychoacoustiques pour l'évaluation et le diagnostic de l'hyperacousie et de la misophonie

L’hyperacousie peut être définie comme une réduction de la tolérance envers le son, où des sons de tous les jours sont perçus comme anormalement fort, inconfortable, ou douloureux, même à des intensités modérées. La misophonie, quant à elle, est caractérisée par des réactions émotionnelles négatives (e.g., rage ou dégout) et/ou des réponses physiologiques (e.g., augmentation du rythme cardiaque et de la sudation) en réponse à des sons spécifiques produits par d’autres humains (e.g., bruits de bouche, de reniflement et/ou de tapotement répétitif). Les méthodes psychoacoustiques actuelles pour évaluer l’hyperacousie utilisent des sons artificiels (bruits ou sons purs) pour estimer la plainte des patients, or cela ne représente pas leur gêne quotidienne. Pour la misophonie, il n’existe pas d’outils psychoacoustiques validés. L’approche entreprise dans cette thèse est d’utiliser des sons de tous les jours pour évaluer la plainte des hyperacousiques et misophoniques. Une première étude sur l’hyperacousie a initié le cadre méthodologique à appliquer dans la seconde étude sur la misophonie. Plusieurs sons de tous les jours ont été évalués sur une échelle agréable-désagréable par des sujets contrôles et hyperacousiques (1ère étude) et par des sujets contrôles et misophoniques (2ème étude). A partir des résultats, nous avons sélectionné des sous-ensembles de sons qui caractérisent efficacement la plainte des hyperacousiques (1ère étude) et des misophoniques (2ème étude). Notre approche a permis de créer un nouvel outil de mesure de l’hyperacousie et de la misophonie qui permet de quantifier l’expérience vécue des sujets avec des sons proches de leur gêne quotidienne.Hyperacusis can be defined as a sound tolerance problem where everyday sounds are perceived as abnormally loud, uncomfortable, or painful, even at moderate levels. On the other hand, misophonia is characterized by intense negative emotional reactions (e.g., anger or disgust) and/or physiological responses (e.g., increased heart rate and sweating) to specific sounds, especially to those produced by people (e.g., eating noises, nasal sounds, and/or repetitive tapping noises). Current psychoacoustic methods to assess hyperacusis use artificial sounds (tones or noises) to estimate subjects’ complaints. However, these sounds do not reflect the day-to-day complaint of hyperacusics. For misophonia, no validated psychoacoustic test exists.The approach undertaken in this thesis was to use everyday sounds to assess the complaints of hyperacusics and misophonics. A first study on hyperacusis set the methodological framework to apply in the second study on misophonia. Everyday sounds were rated on a pleasant to unpleasant scale both by controls and hyperacusics (Study I) and by controls and misophonics (Study II). From these results, we selected a subset of sounds that best characterized the complaints of hyperacusics (Study I) and of misophonics (Study II). Our approach has created a new psychoacoustic tool which can quantify the complaint of hyperacusics and misophonics through an « in situ » task that is close to their daily experience

A psychoacoustic test for diagnosing hyperacusis based on ratings of natural sounds

International audienc

A psychoacoustic test for misophonia assessment

International audienceMisophonia is a condition where a strong arousal response is triggered when hearing specific human generated sounds, like chewing, and/or repetitive tapping noises, like pen clicking. It is diagnosed with clinical interviews and questionnaires since no psychoacoustic tools exist to assess its presence. The present study was aimed at developing and testing a new assessment tool for misophonia. The method was inspired by an approach we have recently developed for hyperacusis. It consisted of presenting subjects (n = 253) with misophonic, pleasant, and unpleasant sounds in an online experiment. The task was to rate them on a pleasant to unpleasant visual analog scale. Subjects were labeled as misophonics (n = 78) or controls (n = 55) by using self-report questions and a misophonia questionnaire, the MisoQuest. There was a significant difference between controls and misophonics in the median global rating of misophonic sounds. On the other hand, median global rating of unpleasant, and pleasant sounds did not differ significantly. We selected a subset of the misophonic sounds to form the core discriminant sounds of misophonia (CDS Miso). A metric: the CDS score, was used to quantitatively measure misophonia, both with a global score and with subscores. The latter could specifically quantify aversion towards different sound sources/events, i.e., mouth, breathing/ nose, throat, and repetitive sounds. A receiver operating characteristic analysis showed that the method accurately classified subjects with and without misophonia (accuracy = 91%). The present study suggests that the psychoacoustic test we have developed can be used to assess misophonia reliably and quickly. Misophonia, literally hatred of sound 1 , is a condition where subjects experience negative emotional reactions (e.g., irritation, anger and/or disgust) 2,3 and a strong autonomic arousal response when hearing specific "trigger" sounds 4,5. These triggers most often contain human generated mouth sounds (e.g., chewing and slurping), breathing and nose sounds (e.g., heavy breathing and sniffing), throat sounds (e.g., swallowing and throat clearing), but also repetitive sounds of objects operated by humans (e.g., pen clicking and keyboard typing) 2-4. In some cases, visual repetitive stimuli, like leg-rocking or finger tapping, can act as misophonic triggers, a phenomenon known as "misokinesia" 2-4. The physical characteristics of sounds (e.g., intensity and frequency) only partially influence the reaction of misophonics to triggers, rather it is their psychological profile, previous experience, and the context in which triggers are experienced that are the most important 1,4,6,7. For instance, experiencing triggers when one cannot escape from the situation (e.g., plane trip) worsens negative reactions 4. Also, eating and chewing sounds are less annoying when originating from babies or animals, as it is "not their fault" if they are generating them 4. Similarly, an individual's own chewing sounds do not trigger a reaction and are often used as a coping mechanism to "cancel out" incoming triggers 3,4. Other coping mechanisms include listening to music, walking away, avoiding social situations, using earplugs/headphones, and asking the originator of the trigger to stop 2-4. Prevalence reports of misophonia show large variability and range from 6% to 49.1% 8-10. These differ considerably due to the different assessment methods and criterion that were used to define misophonia. Besides, misophonia severity varies: Naylor et al. 10 found that 37%, 12% and 0.3% of medical students had mild, moderate, and severe symptoms, respectively. They suggested that misophonia affects many people mildly, but only a few severely. Misophonia can be accompanied by different comorbidities such as obsessive-compulsive personality traits, depression, and anxiety 2,3,8,11. Perfectionism 2 , neuroticism 2,3,12 , difficulties with emotion regulation 12 , and high interoceptive sensibility 5 are also observed. Generally, no audiological problems are detected (e.g., audiogram, loudness discomfort levels, and speech audiometry) 2,3 , and cases of tinnitus and hyperacusis are scarce (2% an

Table_4_Reliability of some tinnitus psychoacoustic measures.docx

IntroductionPsychoacoustic measures are used to quantify tinnitus perception in clinical and research settings. Residual inhibition (RI), for instance, is defined as a temporary reduction in tinnitus loudness after the presentation of an acoustic stimulus. A novel approach was developed recently to assess the minimum sound level producing RI, the minimum residual inhibition level (MRIL), after the repeated presentation of short sounds separated by short periods of silence. Two studies were performed: the objective of the study 1 was to assess the reliability and the reproducibility of this measures as well as others, including the minimum masking level (MML). The objective of study 2 was to assess whether a smoother envelope of the sound would produce similar levels of MML and MRIL and improve listening comfort.MethodsThirty participants with chronic tinnitus completed each study. For study 1, MML and MRIL were obtained at the seven standard audiometric frequencies at around 1-month interval. For study 2, MML and MRIL were obtained using triangular and trapezoidal-shaped NBN signals centered at three different frequencies.ResultsThe mean absolute test-retest difference was 3 dB for both MML and MRIL [Intraclass correlation, ICC (2,1) of 0.70 and 0.84, respectively] for the measures obtained in test and retest (86% of cases for MML and 21% of cases for complete MRIL). While the two types of envelopes provided comparable MRIL, the “triangular” envelope provided more listening comfort.DiscussionIn sum, the novel approach provides quick and reliable MML and MRIL measurement, with the potential benefit of subtyping participants.</p

Table_7_Reliability of some tinnitus psychoacoustic measures.docx

IntroductionPsychoacoustic measures are used to quantify tinnitus perception in clinical and research settings. Residual inhibition (RI), for instance, is defined as a temporary reduction in tinnitus loudness after the presentation of an acoustic stimulus. A novel approach was developed recently to assess the minimum sound level producing RI, the minimum residual inhibition level (MRIL), after the repeated presentation of short sounds separated by short periods of silence. Two studies were performed: the objective of the study 1 was to assess the reliability and the reproducibility of this measures as well as others, including the minimum masking level (MML). The objective of study 2 was to assess whether a smoother envelope of the sound would produce similar levels of MML and MRIL and improve listening comfort.MethodsThirty participants with chronic tinnitus completed each study. For study 1, MML and MRIL were obtained at the seven standard audiometric frequencies at around 1-month interval. For study 2, MML and MRIL were obtained using triangular and trapezoidal-shaped NBN signals centered at three different frequencies.ResultsThe mean absolute test-retest difference was 3 dB for both MML and MRIL [Intraclass correlation, ICC (2,1) of 0.70 and 0.84, respectively] for the measures obtained in test and retest (86% of cases for MML and 21% of cases for complete MRIL). While the two types of envelopes provided comparable MRIL, the “triangular” envelope provided more listening comfort.DiscussionIn sum, the novel approach provides quick and reliable MML and MRIL measurement, with the potential benefit of subtyping participants.</p

Table_2_Reliability of some tinnitus psychoacoustic measures.docx

IntroductionPsychoacoustic measures are used to quantify tinnitus perception in clinical and research settings. Residual inhibition (RI), for instance, is defined as a temporary reduction in tinnitus loudness after the presentation of an acoustic stimulus. A novel approach was developed recently to assess the minimum sound level producing RI, the minimum residual inhibition level (MRIL), after the repeated presentation of short sounds separated by short periods of silence. Two studies were performed: the objective of the study 1 was to assess the reliability and the reproducibility of this measures as well as others, including the minimum masking level (MML). The objective of study 2 was to assess whether a smoother envelope of the sound would produce similar levels of MML and MRIL and improve listening comfort.MethodsThirty participants with chronic tinnitus completed each study. For study 1, MML and MRIL were obtained at the seven standard audiometric frequencies at around 1-month interval. For study 2, MML and MRIL were obtained using triangular and trapezoidal-shaped NBN signals centered at three different frequencies.ResultsThe mean absolute test-retest difference was 3 dB for both MML and MRIL [Intraclass correlation, ICC (2,1) of 0.70 and 0.84, respectively] for the measures obtained in test and retest (86% of cases for MML and 21% of cases for complete MRIL). While the two types of envelopes provided comparable MRIL, the “triangular” envelope provided more listening comfort.DiscussionIn sum, the novel approach provides quick and reliable MML and MRIL measurement, with the potential benefit of subtyping participants.</p