Doctoral Studies as part of an Innovative Training Network (ITN): Early Stage Researcher (ESR) experiences [version 2; peer review: 2 approved]

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

Doctoral Studies as part of an Innovative Training Network (ITN):Early Stage Researcher (ESR) experiences [version 2; peer review: 2 approved]

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

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

A Combined Image- and Coordinate-Based Meta-Analysis of Whole-Brain Voxel-Based Morphometry Studies Investigating Subjective Tinnitus

Previous voxel-based morphometry (VBM) studies investigating tinnitus have reported structural differences in a variety of spatially distinct gray matter regions. However, the results have been highly inconsistent and sometimes contradictory. In the current study, we conducted a combined image- and coordinate-based meta-analysis of VBM studies investigating tinnitus to identify robust gray matter differences associated with tinnitus, as well as examine the possible effects of hearing loss on the outcome of the meta-analysis. The PubMed and Web of Science databases were searched for studies published up to August 2021. Additional manual searches were conducted for studies published up to December 2021. A whole-brain meta-analysis was performed using Seed-Based d Mapping with Permutation of Subject Images (SDM-PSI). Fifteen studies comprising 423 individuals with tinnitus and either normal hearing or hearing loss (mean age 50.94 years; 173 females) and 508 individuals without tinnitus and either normal hearing or hearing loss (mean age 51.59 years; 234 females) met the inclusion criteria. We found a small but significant reduction in gray matter in the left inferior temporal gyrus for groups of normal hearing individuals with tinnitus compared to groups of hearing-matched individuals without tinnitus. In sharp contrast, in groups with hearing loss, tinnitus was associated with increased gray matter levels in the bilateral lingual gyrus and the bilateral precuneus. Those results were dependent upon matching the hearing levels between the groups with or without tinnitus. The current investigation suggests that hearing loss is the driving force of changes in cortical gray matter across individuals with and without tinnitus. Future studies should carefully account for confounders, including hearing loss, hyperacusis, anxiety, and depression, to identify gray matter changes specifically related to tinnitus. Ultimately, the aggregation of standardized individual datasets with both anatomical and useful phenotypical information will permit a better understanding of tinnitus-related gray matter differences, the effects of potential comorbidities, and their interactions with tinnitus

A Combined Image- and Coordinate-Based Meta-Analysis of Whole-Brain Voxel-Based Morphometry Studies Investigating Subjective Tinnitus

Previous voxel-based morphometry (VBM) studies investigating tinnitus have reported structural differences in a variety of spatially distinct gray matter regions. However, the results have been highly inconsistent and sometimes contradictory. In the current study, we conducted a combined image- and coordinate-based meta-analysis of VBM studies investigating tinnitus to identify robust gray matter differences associated with tinnitus, as well as examine the possible effects of hearing loss on the outcome of the meta-analysis. The PubMed and Web of Science databases were searched for studies published up to August 2021. Additional manual searches were conducted for studies published up to December 2021. A whole-brain meta-analysis was performed using Seed-Based d Mapping with Permutation of Subject Images (SDM-PSI). Fifteen studies comprising 423 individuals with tinnitus and either normal hearing or hearing loss (mean age 50.94 years; 173 females) and 508 individuals without tinnitus and either normal hearing or hearing loss (mean age 51.59 years; 234 females) met the inclusion criteria. We found a small but significant reduction in gray matter in the left inferior temporal gyrus for groups of normal hearing individuals with tinnitus compared to groups of hearing-matched individuals without tinnitus. In sharp contrast, in groups with hearing loss, tinnitus was associated with increased gray matter levels in the bilateral lingual gyrus and the bilateral precuneus. Those results were dependent upon matching the hearing levels between the groups with or without tinnitus. The current investigation suggests that hearing loss is the driving force of changes in cortical gray matter across individuals with and without tinnitus. Future studies should carefully account for confounders, including hearing loss, hyperacusis, anxiety, and depression, to identify gray matter changes specifically related to tinnitus. Ultimately, the aggregation of standardized individual datasets with both anatomical and useful phenotypical information will permit a better understanding of tinnitus-related gray matter differences, the effects of potential comorbidities, and their interactions with tinnitus

Hyperacusis is associated with smaller gray matter volumes in the supplementary motor area

Hyperacusis is a disorder in loudness perception characterized by increased sensitivity to ordinary environmental sounds and associated with otologic conditions, including hearing loss and tinnitus (the phantom perception of sound) as well as neurologic and neuropsychiatric conditions. Hyperacusis is believed to arise centrally in the brain; however, the underlying causes are unknown. To gain insight into differences in brain morphology associated with hyperacusis, we undertook a retrospective case-control study comparing whole-brain gray matter morphology in participants with sensorineural hearing loss and tinnitus who either scored above or below the threshold for hyperacusis based on a standard questionnaire. We found that participants reporting hyperacusis had smaller gray matter volumes and cortical sheet thicknesses in the right supplementary motor area (SMA), independent of anxiety, depression, tinnitus burden, or sex. In fact, the right SMA volumes extracted from an independently defined volume of interest could accurately classify participants. Finally, in a subset of participants where functional data were also available, we found that individuals with hyperacusis showed increased sound-evoked responses in the right SMA compared to individuals without hyperacusis. Given the role of the SMA in initiating motion, these results suggest that in hyperacusis the SMA is involved in a motor response to sounds

Doctoral Studies as part of an Innovative Training Network (ITN): Early Stage Researcher (ESR) experiences [version 2; peer review: 2 approved with reservations]

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