Diss. Univ. Konstanz, 2009.

Tinnitus is a common and often severely disabling symptom that is characterized by the perceived sensation of sound in the absence of an external stimulus. Traditional treatment approaches have limited efficacy. It is assumed, that tinnitus is connected with dysfunctional activation of neuronal plasticity induced by altered sensory and somatosensory input. Adaptive neuroplastic processes alter the balance between excitatory and inhibitory function of the auditory system at several levels. Functional imaging studies in tinnitus patients have revealed increased neronal activity of primary auditory cortex (PAC). Repetitive transcranial magnetic stimulation (rTMS) induces changes of neuronal activity that outlast the stimulation period. Low-frequency rTMS over the PAC region results in a decrease of cortical activity by inducing long term depression (LTD) and leads to reduced tinnitus perception. The aim of this study was to assess in prospective randomized placebo- controlled study the ability of active low-frequency rTMS guided by frameless stereotaxy to affect symptoms of chronic tinnitus compared to placebo stimulation. Treatment outcome was assessed by subjective specific questionnaires; Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ) and Visual analogue scales (VAS1, VAS2)...

This thesis is an update of the bachelor work entitled "The application of physiotherapeutic tools for some tinnitus types". The original work was complemented with the latest findings in pathogenesis field and in therapy by physiotherapeutic tool. The fundamental of this diploma thesis is a study examining the quality of patients' lives with tinnitus. The study was based upon a research using a modified questionnaire Tinnitus Handicap Inventory by Newman's et. al. (1999). Powered by TCPDF (www.tcpdf.org)

The Tinnitus Functional Index (TFI) was developed in the USA as a standard for assessing the functional impact of tinnitus based on eight tinnitus-related domains. The finalised 25-item version was never formally validated. This PhD seeks to assess the psychometric properties of the questionnaire and evaluate its suitability as the tool of choice for use in the diagnostic and outcome assessment of tinnitus for clinical and research purposes in the UK. The primary objectives were to (i) determine whether the TFI is reliable, (ii) verify its factor structure, and (iii) evaluate its responsiveness to treatment-related change. These objectives were evaluated in two UK studies. The first was a prospective multi-centre longitudinal validation study in which 255 NHS patients were recruited from audiology clinics to complete the TFI over four different time points in a nine-month period. The second was a retrospective analysis of data collected on the TFI and a battery of other health questionnaires from 294 members of the general public who had previously participated in two-centre randomised controlled trial of a novel tinnitus device. Approaches to psychometric analysis included classical and modern test theories, including Rasch measurement theory. Both approaches led to similar conclusions. Seven of the eight subscales were reliable and valid in both studies, although not as sensitive as the original developers proposed. Classical testing showed the auditory subscale to be reasonably reliable, but Rasch modelling indicated that it did not measure the functional impact of tinnitus. The overall factor structure was not confirmed. The sleep and auditory subscales did not relate to the other subscales and did not fit the model. My recommendation is to calculate the composite TFI score using only six subscales. The sleep subscale should be scored separately and the auditory subscale should not be used.

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Tinnitus, ringing in the ears, is a phantom sound percept affecting roughly 10-20% of the total world population. Tinnitus severely impacts the quality of life of 10% of tinnitus sufferers, affecting their sleep, concentration, emotion, social enjoyment, and sometimes leading to depression and suicidal tendencies. In humans, most forms of tinnitus are associated with noise-exposure, leading to compensatory maladaptive plasticity of central auditory neurons. Human and animal studies suggest that tinnitus alters normal adult attentional resources. Human studies by McKenna, Hallam and Surlock 1996, suggested tinnitus-related impairment in sustained attention, vigilance, visual conceptualization and visuo-motor memory. Additionally, tinnitus may impact aspects of selective or divided attention as well as working and long-term memory. The involvement of primary auditory cortex and nicotinic signaling in selective attention, working and long-term memory has been well established. Neuronal nicotinic acetylcholine receptors (nAChRs) are present on presynaptic and postsynaptic inputs that innervate neurons across layers of primary auditory cortex (A1). Layer 5 pyramidal neurons (PNs) in the A1 are major output neurons, conveying auditory information to corticocortical and subcortical nuclei. The excitation of PNs is regulated by a complex microcircuitory of inhibitory neurons with vasointestinal peptide positive (VIP) neurons playing a key role in regulating the excitation. The focus of present studies was to: 1) Characterize tinnitus-related changes in the physiology and nAChR signaling of layer 5 PNs and VIP neurons in the A1 and 2) Determine the ability of nAChR partial/desensitizing agonists to ameliorate tinnitus pathology in subcellular studies. Wild-type, ChAT-Cre and VIP-Cre:Rosa26-loxP-stop-loxP-tdTomato (VIP-Cre:Rosa-tdTomato Long-Evans rats were used in the present study. CHAT-Cre rats allowed us to selectively express cre-inducible AAV-EF1a-DIO-hChR2(H134R)-EYFP and stimulate the cholinergic neurons of basal forebrain (BF). VIP-Cre:Rosa-tdTomato express fluorescent tdTomato protein in the VIP positive neurons allowing us to identify them under fluorescence microscopy using 550 nm wavelength. An established noise-exposure (one hour of 116 dB narrowband noise centered at 16 kHz) was used to induce behavioral tinnitus in a rat model. Approximately 50-60% noise-exposed animals (53/92) exhibited behavioral evidence of tinnitus with significant shifts in hearing threshold contiguous to the exposure frequency. Animals were classified as control, exposed tinnitus and non-tinnitus. In vitro whole-cell patch clamp recordings were performed in control and tinnitus animals. Results: Numerous tinnitus-related changes in the physiology of layer 5 PNs and VIP neurons, and changes in the activity of excitatory and inhibitory input neurons were observed. The resting membrane potential of A1 layer 5 PNs from tinnitus animals was significantly depolarized compared to PNs from unexposed controls. PNs from the A1 of animals with behavioral evidence of tinnitus showed increases in the frequency of excitatory and decreases in frequency of inhibitory spontaneous postsynaptic currents, which directly correlated with the rat’s tinnitus score. Optical stimulation of thalamocortical terminals from PNs in tinnitus animals evoked significantly larger excitatory/inward currents than in currents evoked in PNs from controls. A1 layer 5 PNs showed tinnitus-related decreases in postsynaptic gamma-amino butyric acid (GABA) signaling suggestive of GABA-A receptors (GABA-ARs) subunit switches or loss of GABA-ARs. VIP neurons favoring excitation of layer 5 PNs via disinhibition, were depolarized with significantly lower current to evoke action potentials (rheobase current). The excitability of VIP neurons was significantly increased, with this increase being strongly correlated to the rat’s tinnitus score. Tinnitus-related changes in nAChR signaling were then tested in layer 5 PNs and VIP neurons. Both PNs and VIP neurons receive cholinergic input from basal forebrain and were highly sensitive to nicotinic stimulation. Optical stimulation of basal forebrain (BF) terminals evoked a depolarizing current from VIP neurons. In tinnitus animals, layer 5 PNs showed a significant loss of nAChR signaling, while, VIP neurons showed tinnitus-related increase in responses to nicotinic stimulation. Most of the nAChR responses in auditory cortex are believed to be mediated via volume transmission of acetylcholine (ACh). Continuous voltage clamped recordings were used to examine the activity of excitatory and inhibitory neurons impacting PNs in the presence of bath applied ACh. We observed significant tinnitus-related changes in nAChR signaling with layer 5 PNs showing significantly larger GABAergic input after prolonged bath application of ACh. This led us to hypothesize that desensitization of nAChRs could increase/normalize the activity of GABAergic input neurons. To test this hypothesis, nAChR partial desensitizing agonists sazetidine-A and varenicline were used in cellular and behavioral studies. Immediately after bath application of sazetidine-A or varenicline, a dramatic increase in the activity of inhibitory input neurons onto PNs was observed. In a behavioral tinnitus test, both sazetidine-A and varenicline were effective in lowering the tinnitus-like behavior. In conclusion, we identified a significant tinnitus-related disruption in intrinsic physiology of layer 5 PNs and VIP neurons, with strong evidence of dysregulated cholinergic signaling. Partial/desensitizing agonists sazetidine-A and varenicline increased the activity of inhibitory input neurons, showing therapeutic potential in both subcellular and behavioral studies.

The phenomenon of residual inhibition, whereby the phantom sensation of tinnitus is suppressed following the presentation of a masking stimulus, has significant implications for understanding the neural basis of tinnitus itself. By using novel psychoacoustic techniques and three computer-based tools developed and applied specifically to measure tinnitus sensation and residual inhibition, a pattern emerges in which the depth and duration of tinnitus suppression relates to the center frequency of the band-passed noise masking stimulus. A correspondence between the region of hearing loss, the tinnitus spectrum and the masking stimuli most effective in suppressing tinnitus is revealed. These results suggest that cortical reorganization observed in animal models of tinnitus is not the principal basis of tinnitus, and provide a baseline for optimizing residual inhibition in individual cases and for further experiments. / Note: Pages 17-23 in this thesis were replaced with a citation due to copyright issues. / Thesis / Master of Science (MSc)

Beginner Clinician Self-efficacy in Conducting Tinnitus Management Appointments for Patients with Bothersome Tinnitus Mark Weiner and Dr. Marc Fagelson, Department of Audiology Speech Language Pathology, East Tennessee State University, Johnson City, TN. According to the National Institute on Deafness and Other Communication Disorders, approximately 10% of the U.S. adult population, more than 30 million Americans, experience some form of tinnitus. Roughly 5 million people struggle with bothersome chronic tinnitus, while 2 million report it as debilitating. Clinician self-efficacy is an important driver of the implementation of services that patients require. If clinicians do not have a high self-efficacy, or confidence in their ability to provide for patients, then they are less likely to implement services that the patients require and may not feel comfortable working with the challenging patient populations, such as patients bothered by tinnitus. The purpose of this study was to evaluate audiology student clinicians’ confidence in their ability to conduct tinnitus assessment and management, as well as to determine the skills that audiology student clinicians feel that they need to acquire in order to enhance their clinical self-efficacy. In audiology, tinnitus is one of the more complex issues that patients face, and patients often require extensive counselling in order to help manage their tinnitus. Therefore, high clinician self-efficacy is necessary to meet the varied, and on occasion, profound needs of the tinnitus population. In order to determine the degree to which student clinicians believe they could conduct tinnitus assessment and management appointments, an online RedCap survey was created and sent to students that are currently attending audiology doctoral programs. The survey consisted of eleven questions and measured the confidence of the students in conducting tinnitus assessment and management appointments, determined what the students felt should be included in these appointments, and asked what the students felt they needed to know or to learn in order to provide for patients following their graduation. Fifteen audiology doctoral students from four universities completed the surveys. Responses showed that students felt confident in their ability to conduct tinnitus assessment and management appointments accurately and effectively. However, only eight students reported that they will conduct tinnitus assessment and management appointments when they graduate from their doctoral programs. Students reported that they still felt they needed additional resources such as visual aids and handouts in order to conduct these appointments in the future. These findings show that while students may feel confident in their ability to conduct tinnitus assessment and management appointments, that the knowledge alone will not translate into providing care for patients bothered by tinnitus.

Introdução: o zumbido é uma desordem que acomete 10 a 15% da população mundial e por se tratar de um sintoma subjetivo que apresenta grande repercussão na vida do indivíduo, pesquisas científicas na área são de grande importância. A terapia sonora realizada por meio do aparelho de amplificação sonora individual (AASI) com gerador de som (GS) associado é uma das formas de tratamento do zumbido e vem ganhando espaço nos serviços de saúde auditiva. Proposição: analisar a eficácia de quatro ruídos mascaradores no alívio do zumbido de indivíduos com perda auditiva sensorioneural bilateral de grau leve e moderado e a influência dos mesmos na percepção da fala. Casuística e Métodos: o estudo foi desenvolvido na Clínica de Fonoaudiologia da Faculdade de Odontologia de Bauru (FOB) - USP após a aprovação do Comitê de Ética e anuência do paciente. Participaram 35 indivíduos com zumbido e perda auditiva sensorioneural leve e moderada bilateral, divididos em quatro grupos, sendo três grupos compostos por nove indivíduos e um grupo por oito. Todos os grupos passaram pela adaptação do AASI com GS, sendo regulados no modo combinado (GS + amplificação). No grupo 1 (G1) foi aplicado o estímulo White Noise, no grupo 2 (G2) o Pink Noise, o grupo 3 (G3), o Speech Noise e o grupo 4 (G4) o High Tone Noise. Todos os pacientes passaram pelos seguintes procedimentos: anamnese, diagnóstico audiológico composto por audiometria de alta frequência, imitanciometria e acufenometria. Foram aplicados os questionários Tinnitus Handicap Inventory (THI), a Escala Análoga Visual (EAV) e avaliação da percepção da fala por meio do Hearing in Noise Test (HINT) na situação de fala no silêncio (FS) e ruído frontal (RF). Os procedimentos foram realizados pré e pós-intervenção auditiva, após três meses de uso do AASI. Os resultados foram tabulados e descritos de acordo com a análise estatística descritiva de todas as variáveis estudadas. Resultados: todos os grupos apresentaram diferença estatisticamente significativa para o questionário THI, EAV e HINT na situação de FS, pré e pós-intervenção auditiva. Na situação de RF, somente o G2 apresentou diferença significativa. Porém, na comparação entre grupos não houve diferença significativa. Conclusão: os quatro ruídos mascaradores demonstraram ser igualmente eficazes na melhora do zumbido e na percepção de fala na situação de silêncio, porém no RF, o G2 apresentou melhora significativa. / Introduction: tinnitus is a disorder that affects 10 to 15% of the world\'s population and since it is a subjective symptom which presents great impact on the individual\'s life, all scientific contribution becomes significant and important. The sound therapy performed through the individual sound amplification apparatus (AASI) with associated sound generator (GS) is one of the forms of tinnitus treatment and has been obtaining space in the hearing health services. Proposition: analyzing the effectiveness of four masking noises in relieving tinnitus of individuals with mild and moderate bilateral sensorineural hearing loss and influence thereof on speech perception. Casuistry and Methods: the study was developed at the Speech Therapy Clinic of the Faculty of Dentistry of Bauru (FOB) - USP after approval by the Ethics Committee and patient consent. Participants were 35 individuals with tinnitus and bilateral mild and moderate sensorineural hearing loss, divided into four groups, three groups composed of nine subjects and one group comprising eight subjects. All groups underwent hearing loss adaptation with GS, being regulated in the combined mode (GS + Amplification). In Group 1 (G1) the White Noise stimulus was applied, in group 2 (G2) Pink Noise was applied, in group 3 (G3), Speech Noise and in group 4 (G4) the High Tone Noise was applied. All patients were subjected to the following procedures: anamnesis, audiological diagnosis composed of high frequency audiometry, immittanciometry and acuphenometry. The Tinnitus Handicap Inventory (THI), Visual Analogue Scale (EAV) and Speech Perception Assessment questionnaires were applied through the Hearing in Noise Test (HINT) in the speech silence (FS) and frontal noise (RF) situation. The procedures were performed prior to and after hearing intervention, after three months of use of AASI. The results were tabulated and described according to the descriptive statistical analysis of all variables studied. Results: all groups presented a statistically significant difference for the THI, EAV and HINT questionnaires in the FS, pre- and post-hearing intervention. In the RF situation, only G2 presented a significant difference. However, in the comparison among groups there was no significant difference. Conclusion: the four masking noises proved to be equally effective in improving tinnitus and in speech perception in the silent situation, but in RF situation, G2 presented significant improvement.

Introdução: o zumbido é uma desordem que acomete 10 a 15% da população mundial e por se tratar de um sintoma subjetivo que apresenta grande repercussão na vida do indivíduo, pesquisas científicas na área são de grande importância. A terapia sonora realizada por meio do aparelho de amplificação sonora individual (AASI) com gerador de som (GS) associado é uma das formas de tratamento do zumbido e vem ganhando espaço nos serviços de saúde auditiva. Proposição: analisar a eficácia de quatro ruídos mascaradores no alívio do zumbido de indivíduos com perda auditiva sensorioneural bilateral de grau leve e moderado e a influência dos mesmos na percepção da fala. Casuística e Métodos: o estudo foi desenvolvido na Clínica de Fonoaudiologia da Faculdade de Odontologia de Bauru (FOB) - USP após a aprovação do Comitê de Ética e anuência do paciente. Participaram 35 indivíduos com zumbido e perda auditiva sensorioneural leve e moderada bilateral, divididos em quatro grupos, sendo três grupos compostos por nove indivíduos e um grupo por oito. Todos os grupos passaram pela adaptação do AASI com GS, sendo regulados no modo combinado (GS + amplificação). No grupo 1 (G1) foi aplicado o estímulo White Noise, no grupo 2 (G2) o Pink Noise, o grupo 3 (G3), o Speech Noise e o grupo 4 (G4) o High Tone Noise. Todos os pacientes passaram pelos seguintes procedimentos: anamnese, diagnóstico audiológico composto por audiometria de alta frequência, imitanciometria e acufenometria. Foram aplicados os questionários Tinnitus Handicap Inventory (THI), a Escala Análoga Visual (EAV) e avaliação da percepção da fala por meio do Hearing in Noise Test (HINT) na situação de fala no silêncio (FS) e ruído frontal (RF). Os procedimentos foram realizados pré e pós-intervenção auditiva, após três meses de uso do AASI. Os resultados foram tabulados e descritos de acordo com a análise estatística descritiva de todas as variáveis estudadas. Resultados: todos os grupos apresentaram diferença estatisticamente significativa para o questionário THI, EAV e HINT na situação de FS, pré e pós-intervenção auditiva. Na situação de RF, somente o G2 apresentou diferença significativa. Porém, na comparação entre grupos não houve diferença significativa. Conclusão: os quatro ruídos mascaradores demonstraram ser igualmente eficazes na melhora do zumbido e na percepção de fala na situação de silêncio, porém no RF, o G2 apresentou melhora significativa. / Introduction: tinnitus is a disorder that affects 10 to 15% of the world\'s population and since it is a subjective symptom which presents great impact on the individual\'s life, all scientific contribution becomes significant and important. The sound therapy performed through the individual sound amplification apparatus (AASI) with associated sound generator (GS) is one of the forms of tinnitus treatment and has been obtaining space in the hearing health services. Proposition: analyzing the effectiveness of four masking noises in relieving tinnitus of individuals with mild and moderate bilateral sensorineural hearing loss and influence thereof on speech perception. Casuistry and Methods: the study was developed at the Speech Therapy Clinic of the Faculty of Dentistry of Bauru (FOB) - USP after approval by the Ethics Committee and patient consent. Participants were 35 individuals with tinnitus and bilateral mild and moderate sensorineural hearing loss, divided into four groups, three groups composed of nine subjects and one group comprising eight subjects. All groups underwent hearing loss adaptation with GS, being regulated in the combined mode (GS + Amplification). In Group 1 (G1) the White Noise stimulus was applied, in group 2 (G2) Pink Noise was applied, in group 3 (G3), Speech Noise and in group 4 (G4) the High Tone Noise was applied. All patients were subjected to the following procedures: anamnesis, audiological diagnosis composed of high frequency audiometry, immittanciometry and acuphenometry. The Tinnitus Handicap Inventory (THI), Visual Analogue Scale (EAV) and Speech Perception Assessment questionnaires were applied through the Hearing in Noise Test (HINT) in the speech silence (FS) and frontal noise (RF) situation. The procedures were performed prior to and after hearing intervention, after three months of use of AASI. The results were tabulated and described according to the descriptive statistical analysis of all variables studied. Results: all groups presented a statistically significant difference for the THI, EAV and HINT questionnaires in the FS, pre- and post-hearing intervention. In the RF situation, only G2 presented a significant difference. However, in the comparison among groups there was no significant difference. Conclusion: the four masking noises proved to be equally effective in improving tinnitus and in speech perception in the silent situation, but in RF situation, G2 presented significant improvement.