Investigation of the behavior of tinnitus patients under varying listening conditions with simultaneous electroencephalography and pupillometry.

OBJECTIVE: This study aims to control all hearing thresholds, including extended high frequencies (EHFs), presents stimuli of varying difficulty levels, and measures electroencephalography (EEG) and pupillometry responses to determine whether listening difficulty in tinnitus patients is effort or fatigue-related. METHODS: Twenty-one chronic tinnitus patients and 26 matched healthy controls having normal pure-tone averages with symmetrical hearing thresholds were included. Subjects were evaluated with 0.125-20 kHz pure-tone audiometry, Montreal Cognitive Assessment Test (MoCA), Tinnitus Handicap Inventory (THI), EEG, and pupillometry. RESULTS: Pupil dilatation and EEG alpha power during the "encoding" phase of the presented sentence in tinnitus patients were less in all listening conditions (p < .05). Also, there was no statistically significant relationship between EEG and pupillometry components for all listening conditions and THI or MoCA (p > .05). CONCLUSION: EEG and pupillometry results under various listening conditions indicate potential listening effort in tinnitus patients even if all frequencies, including EHFs, are controlled. Also, we suggest that pupillometry should be interpreted with caution in autonomic nervous system-related conditions such as tinnitus.

Amygdala structural and functional reorganization as an indicator of affective dysfunction in patients with tinnitus.

The aim of this study was to systematically investigate structural and functional alterations in amygdala subregions using multimodal magnetic resonance imaging (MRI) in patients with tinnitus with or without affective dysfunction. Sixty patients with persistent tinnitus and 40 healthy controls (HCs) were recruited. Based on a questionnaire assessment, 26 and 34 patients were categorized into the tinnitus patients with affective dysfunction (TPAD) and tinnitus patients without affective dysfunction (TPWAD) groups, respectively. MRI-based measurements of gray matter volume, fractional anisotropy (FA), fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC) were conducted within 14 amygdala subregions for intergroup comparisons. Associations between the MRI properties and clinical characteristics were estimated via partial correlation analyses. Compared with that of the HCs, the TPAD and TPWAD groups exhibited significant structural and functional changes, including white matter integrity (WMI), fALFF, ReHo, DC, and FC alterations, with more pronounced WMI changes in the TPAD group, predominantly within the left auxiliary basal or basomedial nucleus (AB/BM), right central nucleus, right lateral nuclei (dorsal portion), and left lateral nuclei (ventral portion containing basolateral portions). Moreover, the TPAD group exhibited decreased FC between the left AB/BM and left middle occipital gyrus and right superior frontal gyrus (SFG), left basal nucleus and right SFG, and right lateral nuclei (intermediate portion) and right SFG. In combination, these amygdalar alterations exhibited a sensitivity of 65.4% and specificity of 96.9% in predicting affective dysfunction in patients with tinnitus. Although similar structural and functional amygdala remodeling were observed in the TPAD and TPWAD groups, the changes were more pronounced in the TPAD group. These changes mainly involved alterations in functionality and white matter microstructure in various amygdala subregions; in combination, these changes could serve as an imaging-based predictor of emotional disorders in patients with tinnitus.

Tinnitus mechanisms and the need for an objective electrophysiological tinnitus test.

Tinnitus, the perception of sound with no external auditory stimulus, is a complex, multifaceted, and potentially devastating disorder. Despite recent advances in our understanding of tinnitus, there are limited options for effective treatment. Tinnitus treatments are made more complicated by the lack of a test for tinnitus based on objectively measured physiological characteristics. Such an objective test would enable a greater understanding of tinnitus mechanisms and may lead to faster treatment development in both animal and human research. This review makes the argument that an objective tinnitus test, such as a non-invasive electrophysiological measure, is desperately needed. We review the current tinnitus assessment methods, the underlying neural correlates of tinnitus, the multiple tinnitus generation theories, and the previously investigated electrophysiological measurements of tinnitus. Finally, we propose an alternate objective test for tinnitus that may be valid in both animal and human subjects.

Impact of Migraine and Vestibular Migraine on Audiometric Profiles and Quality of Life in Patients With Tinnitus.

OBJECTIVE: To investigate the clinical manifestations and complete auditory function in primary tinnitus patients with and without migraine or vestibular migraine. DESIGN: Retrospective case-control study. SETTING: A tertiary referral center. PARTICIPANTS: This study enrolled 298 patients from the Kaohsiung Veterans General Hospital. All patients were diagnosed with primary tinnitus by a neurotologist between April 2020 and August 2021. Patients were excluded if they had histories of chronic otitis media, idiopathic sudden sensorineural hearing loss, Ménière's disease, skull base neoplasm, or temporal bone trauma. INTERVENTIONS: Twenty-five-item Tinnitus Handicap Inventory (THI), speech audiometry including speech recognition threshold, most comfortable level, uncomfortable loudness levels, dynamic range, and pure-tone audiometry. MAIN OUTCOMES MEASURES: Objective hearing loss is defined as a mean threshold greater than 25 dB. Extremely elevated THI is defined as a score greater than 1 standard deviation above the mean THI. RESULTS: Among the 298 patients with tinnitus, 149 were women and 149 were men, with a mean age of 57.06 (range, 19.22-94.58) years.A total of 125 patients completed the THI questionnaire during their initial visit. The median THI score was 32 (95% confidence interval: 13.98-56.00), and the mean score was 34.99 with a standard deviation of 21.01. The sole contributing factor significantly associated with higher total THI score was the diagnosis of migraine or vestibular migraine (p < 0.001, odds ratio = 19.41).Tinnitus patients with migraine or vestibular migraine exhibited significantly lower mean pure-tone auditory thresholds (right 22.2 versus 29.5, p = 0.002; left 22.5 versus 30.4, p < 0.001), speech recognition threshold (right 20.0 versus 25.2, p = 0.016; left 20.2 versus 25.5, p = 0.019), and most comfortable levels values (right 46.1 versus 51.4, p = 0.007; left 46.9 versus 51.4, p = 0.021) compared with the tinnitus patients without migraine. CONCLUSIONS: In this population-based study, patients with primary tinnitus experienced significantly higher THI scores and exhibited concurrent symptoms, including dizziness/vertigo, cervicalgia, and migraine or vestibular migraine. Among these parameters, the diagnosis of migraine or vestibular migraine was the sole contributor to significant higher THI score.

Perceptual Consequences of Cochlear Deafferentation in Humans.

Cochlear synaptopathy, a form of cochlear deafferentation, has been demonstrated in a number of animal species, including non-human primates. Both age and noise exposure contribute to synaptopathy in animal models, indicating that it may be a common type of auditory dysfunction in humans. Temporal bone and auditory physiological data suggest that age and occupational/military noise exposure also lead to synaptopathy in humans. The predicted perceptual consequences of synaptopathy include tinnitus, hyperacusis, and difficulty with speech-in-noise perception. However, confirming the perceptual impacts of this form of cochlear deafferentation presents a particular challenge because synaptopathy can only be confirmed through post-mortem temporal bone analysis and auditory perception is difficult to evaluate in animals. Animal data suggest that deafferentation leads to increased central gain, signs of tinnitus and abnormal loudness perception, and deficits in temporal processing and signal-in-noise detection. If equivalent changes occur in humans following deafferentation, this would be expected to increase the likelihood of developing tinnitus, hyperacusis, and difficulty with speech-in-noise perception. Physiological data from humans is consistent with the hypothesis that deafferentation is associated with increased central gain and a greater likelihood of tinnitus perception, while human data on the relationship between deafferentation and hyperacusis is extremely limited. Many human studies have investigated the relationship between physiological correlates of deafferentation and difficulty with speech-in-noise perception, with mixed findings. A non-linear relationship between deafferentation and speech perception may have contributed to the mixed results. When differences in sample characteristics and study measurements are considered, the findings may be more consistent.

Investigating sensitivity to multi-domain prediction errors in chronic auditory phantom perception.

The perception of a continuous phantom in a sensory domain in the absence of an external stimulus is explained as a maladaptive compensation of aberrant predictive coding, a proposed unified theory of brain functioning. If this were true, these changes would occur not only in the domain of the phantom percept but in other sensory domains as well. We confirm this hypothesis by using tinnitus (continuous phantom sound) as a model and probe the predictive coding mechanism using the established local-global oddball paradigm in both the auditory and visual domains. We observe that tinnitus patients are sensitive to changes in predictive coding not only in the auditory but also in the visual domain. We report changes in well-established components of event-related EEG such as the mismatch negativity. Furthermore, deviations in stimulus characteristics were correlated with the subjective tinnitus distress. These results provide an empirical confirmation that aberrant perceptions are a symptom of a higher-order systemic disorder transcending the domain of the percept.

An Exploratory Study of Bimodal Electro-Aural Stimulation Through the Ear Canals for Tinnitus.

OBJECTIVE: The aim of this study was to explore the potential for bimodal auditory and noninvasive electrical stimulation at the ears to alleviate tonal, somatic tinnitus that was investigated in a small preliminary trial (11 participants). DESIGN: Auditory stimulation took the form of short "notched noise" bursts customized to each participant's tinnitus percept. Simultaneous pulsed electrical stimulation, intended to facilitate neuroplasticity, was delivered via hydrogel electrodes placed in opposite ears. RESULTS: After a 6-week intervention period, average Tinnitus Functional Index (TFI) and Tinnitus Primary Function Questionnaire (TPFQ) scores were consistent with clinically meaningful improvements in the study population. Magnitudes and effect sizes of improvements in TFI and TPFQ are comparable to those reported in other recent bimodal therapy studies using different auditory and electrical stimulation parameters. CONCLUSIONS: Our results should be considered preliminary given the small sample size, lack of crossover data, and small subject pool. When considered alongside other recent bimodal therapy results, we do believe that there are therapeutic benefits of bimodal stimulation for tinnitus sufferers that have the potential to help some with tinnitus, with a variety of stimulation parameters and electrode placements. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25444546.

Comprehensive Characterization of Hearing Loss and Tinnitus in Military-Affiliated and Non-Military-Affiliated Individuals.

PURPOSE: Military-affiliated individuals (MIs) are at a higher risk of developing hearing loss and tinnitus. While these disorders are well-studied in MIs, their impact relative to non-military-affiliated individuals (non-MIs) remains understudied. Our study compared hearing, speech-in-noise (SIN) perception, and tinnitus characteristics between MIs and non-MIs. METHOD: MIs (n = 84) and non-MIs (n = 193) underwent hearing threshold assessment and Quick Speech-in-Noise Test. Participants with tinnitus completed psychoacoustic tinnitus matching, numeric rating scale (NRS) for loudness and annoyance, and Tinnitus Functional Index. Comorbid conditions such as anxiety, depression, and hyperacusis were assessed. We used a linear mixed-effects model to compare hearing thresholds and SIN scores between MIs and non-MIs. A multivariate analysis of variance compared tinnitus characteristics between MIs and non-MIs, and a stepwise regression was performed to identify predictors of tinnitus severity. RESULTS: MIs exhibited better hearing sensitivity than non-MIs; however, their SIN scores were similar. MIs matched their tinnitus loudness to a lower intensity than non-MIs, but their loudness ratings (NRS) were comparable. MIs reported greater tinnitus annoyance and severity on the relaxation subscale, indicating increased difficulty engaging in restful activities. Tinnitus severity was influenced by hyperacusis and depression in both MIs and non-MIs; however, hearing loss uniquely contributed to severity in MIs. CONCLUSIONS: Our findings suggest that while MIs may exhibit better or comparable listening abilities, they were significantly more affected by tinnitus than non-MIs. Furthermore, our study highlights the importance of assessing tinnitus-related distress across multiple dimensions, facilitating customization of management strategies for both MIs and non-MIs.

The Association Between Tinnitus Sensation-Level Loudness and Sleep Quality in Patients With Subjective Consecutive Tinnitus: A Mediation Analysis.

PURPOSE: So far, there have been no in-depth analyses of the connection between tinnitus sensation-level loudness and sleep quality. Accordingly, the present study was formulated as a mediation analysis focused on exploring this relationship. METHOD: Overall, 1,255 adults with consecutive subjective tinnitus who had sought outpatient treatment were enrolled in the present study. RESULTS: Direct effects of tinnitus sensation-level loudness on sleep quality were not statistically significant (95% confidence intervals [CI] include zero), as measured by the point estimate, -0.016. However, the 95% CI for indirect effects did not include zero when assessing the Self-Rating Anxiety Scale (SAS) scores, the Self-Rating Depression Scale (SDS) scores, the visual analogue scale (VAS) scores, and self-reported tinnitus annoyance. CONCLUSIONS: These results suggest that tinnitus sensation-level loudness does not directly have an effect on sleep quality. However, it indirectly impacts sleep quality, mediated by SAS scores, SDS scores, the impact of tinnitus on life measured using the VAS, and self-reported tinnitus annoyance. As such, alleviating anxiety and depression in patients with tinnitus may result in reductions in their insomnia even if there is no reduction in tinnitus loudness. Importantly, otolaryngologists and other clinicians treating tinnitus should refer patients with tinnitus suffering from insomnia with comorbid depression or anxiety for appropriate psychological and/or psychiatric treatment.

Investigation of the Effectiveness of Kinesio Tape Treatment in Adult Individuals with Subjective Tinnitus.

Objective: Tinnitus is one of the most common otologic symptoms and has a serious effect on the quality of life. The pathophysiology of tinnitus is not fully understood and no consensus has been reached on an effective treatment method for tinnitus. To evaluate the effectiveness of the kinesiotape (KT) method in subjective tinnitus treatment. Material and Method: KT is a method used for sensory simulation. It is a method that aims to increase muscle function, positively affect lymphatic fluid and blood circulation, and stimulate the neurological system. In this study, KT method was applied and the study was prospective. 34 individuals with subjective tinnitus, and normal hearing were included. The study group (n = 17) was informed about tinnitus and KT was applied for 4 weeks, the control group (n = 17) was only informed about tinnitus. The information about tinnitus given to both groups included verbal information about what tinnitus is, how to deal with tinnitus and basic recommendations. All individuals were initially administered tinnitus measurements (pitch, loudness, minimal masking level, residual inhibition), Tinnitus Handicap Inventory (THI), Visual Analogue Scale (VAS), SF-36, and Beck Depression Inventory (BDI). All evaluations were repeated after 4 weeks. Results: Tinnitus loudness and pitch decreased in the KT group (P < .05). In both groups, there was a significant difference between the first and last measurements of the severity of tinnitus, the degree of discomfort from tinnitus with VAS, and the catastrophic and total scores of THI (P < .05). KT group, the emotional sub-score of THI improved significantly with KT (P < .05), and significant improvement was achieved in the BDI scores (P < .05). There was a significant difference in the SF-36 after the application of KT (P < .05). Conclusion: In subjective tinnitus, the pathophysiology of which is unknown and there is no consensus on an effective treatment method, improvement in tinnitus severity, quality of life and depression perception in both audiologic and perceptual evaluations were obtained as a result of KT application. We believe that KT, which has no side effects and is easy to apply, is a method that can be easily used in individuals with subjective tinnitus.

Tinnitus: Clinical Insights in Its Pathophysiology-A Perspective.

Tinnitus, the perception of sound without a corresponding external sound source, and tinnitus disorder, which is tinnitus with associated suffering, present a multifaceted clinical challenge due to its heterogeneity and its incompletely understood pathophysiology and especially due to the limited therapeutic options. In this narrative review, we give an overview on various clinical aspects of tinnitus including its heterogeneity, contributing factors, comorbidities and therapeutic pathways with a specific emphasis on the implications for its pathophysiology and future research directions. Tinnitus exhibits high perceptual variability between affected individuals (heterogeneity) and within affected individuals (temporal variability). Hearing loss emerges as predominant risk factor and the perceived pitch corresponds to areas of hearing loss, supporting the compensatory response theory. Whereas most people who have tinnitus can live a normal life, in 10-20% tinnitus interferes severely with quality of life. These patients suffer frequently from comorbidities such as anxiety, depression or insomnia, acting as both risk factors and consequences. Accordingly, neuroimaging studies demonstrate shared brain networks between tinnitus and stress-related disorders shedding light on the intricate interplay of mental health and tinnitus. The challenge lies in deciphering causative relationships and shared pathophysiological mechanisms. Stress, external sounds, time of day, head movements, distraction, and sleep quality can impact tinnitus perception. Understanding these factors provides insights into the interplay with autonomic, sensory, motor, and cognitive processes. Counselling and cognitive-behavioural therapy demonstrate efficacy in reducing suffering, supporting the involvement of stress and anxiety-related networks. Hearing improvement, especially through cochlear implants, reduces tinnitus and thus indirectly validates the compensatory nature of tinnitus. Brain stimulation techniques can modulate the suffering of tinnitus, presumably by alteration of stress-related brain networks. Continued research is crucial for unravelling the complexities of tinnitus. Progress in management hinges on decoding diverse manifestations, identifying treatment-responsive subtypes, and advancing targeted therapeutic approaches.

Evaluation of tinnitus in patients with Temporomandibular Disorders through Axis II of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and the Tinnitus Handicap Inventory (THI).

BACKGROUND: Tinnitus is a quite common and bothersome disorder that results in a perceived sound or noise, without an external origin, often causing notable psychological distress. Some interconnections between tinnitus, bodily pain perception, and psychological well-being were previously reported, thus the relationships between tinnitus and temporomandibular joint (TMJ)-related muscle issues, resulting in somatosensory tinnitus, must be deeply investigated. This study aims to assess the prevalence of tinnitus in patients with temporomandibular disorders (TMD) and to examine the correlation between tinnitus and scales assessing the severity of TMD as well as psychological-related parameters. MATERIALS AND METHODS: In this cross-sectional study, a total of 37 adults with TMD symptoms were enrolled. Diagnostic data were collected using the Axis II of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and the Tinnitus Handicap Inventory (THI) questionnaire. Statistical analysis included descriptive assessments and significance was set at p < .05. RESULTS: Individuals with tinnitus and TMD reported a significantly higher number of body pain areas, indicating a link between tinnitus and increased bodily pain perception. Tinnitus did not significantly impact TMJ-related functions. Significantly higher levels of psychological distress were observed in individuals with tinnitus, as evidenced by elevated scores in depression, generalised anxiety and somatic symptoms. CONCLUSION: Tinnitus is a complex condition with significant effects on health and well-being, requiring an interdisciplinary approach for effective evaluation and care. The study provides deep insights into the prevalence of tinnitus in TMD patients, underscoring the need for comprehensive treatment strategies addressing both TMD and tinnitus.

Active TriCROS: A Simultaneous Stimulation With a (Bi)CROS System and a Hearing Aid in the Worst Ear for Severely Asymmetrical Hearing Loss.

OBJECTIVE: Severely asymmetrical hearing loss (SAHL) is characterized by a moderately severe or severe hearing loss in one side and normal or mildly impaired controlateral hearing in the other. The Active tri-CROS combines the Contralateral Routing-of-Signal System (CROS, or BiCROS if the best ear is stimulated) and the stimulation of the worst ear by an in-the-canal hearing aid. This study aims to evaluate the benefit of the Active tri-CROS for SAHL patients. STUDY DESIGN: This retrospective study was conducted from September 2019 to December 2020. SETTING: Ambulatory, tertiary care. PATIENTS: Patients were retrospectively included if they had received the Active tri-CROS system after having used a CROS or BiCROS system for SAHL for at least 3 years. MAIN OUTCOME MEASURES: Audiometric gain, signal-to-noise ratio, spatial localization, and the Abbreviated Profile of Hearing Aid Benefit and Tinnitus Handicap Inventory questionnaires were performed before equipment and after a month with the system. RESULTS: Twenty patients (mean, 62 yr old) with a mean of 74.3 ± 8.7 dB HL on the worst ear were included. The mean tonal hearing gain on the worst ear was 20 ± 6 dB. Signal-to-noise ratio significantly rose from 1.43 ± 3.9 to 0.16 ± 3.4 dB ( p = 0.0001). Spatial localization was not significantly improved. The mean Tinnitus Handicap Inventory test score of the eight patients suffering from tinnitus rose from 45.5 ± 18.5 to 31 ± 25.2 ( p = 0.016). CONCLUSIONS: The Active tri-CROS system is a promising new therapeutically solution for SAHL.

Aproximaciones psicoterapéuticas para el manejo del tinnitus crónico no pulsátil / Psychotherapy approaches for the management of non-pulsatile chronic tinnitus

Resumen La fisiopatología del tinnitus crónico no pulsátil es poco clara, pero se reconoce un componente psicológico relevante, por tanto, existen distintas aproximaciones psicoterapéuticas que han sido estudiadas. La terapia cognitivo conductual es la que cuenta con mayor evidencia. Ella contempla la reestructuración de las cogniciones disfuncionales que favorecen la presencia del tinnitus. Se ha verificado su eficacia en los niveles de distrés, calidad de vida, severidad, sintomatología depresiva e insomnio asociados. La desensibilización y reprocesamiento por movimientos oculares recoge algunos presupuestos de la terapia cognitivo conductual, pero considera técnicas como la estimulación bilateral. Sus resultados en patologías crónicas somáticas han sugerido la aplicación en tinnitus, corroborando su eficacia en calidad de vida, distrés y sintomatología depresiva. Dos psicoterapias basadas en mindfulness aplicadas en tinnitus son la reducción del estrés basado en el mindfulness y la terapia cognitiva basada en mindfulness. La primera ha demostrado eficacia en la calidad de vida y en la disminución y el refuerzo de cogniciones negativas y positivas, respectivamente. La segunda, es eficaz en la severidad, intensidad, distrés, ansiedad, depresión y discapacidad asociadas a tinnitus. Finalmente, la terapia de aceptación y compromiso promueve la aceptación como componente central del tratamiento de condiciones crónicas, considerando el control que ejerce el contexto sobre la vivencia de estas condiciones y el compromiso terapéutico. Esta terapia es eficaz en calidad de vida. Se promueve la investigación en aproximaciones psicoterapéuticas para el tinnitus, lo que posibilitará la aplicación de terapias más específicas y la clarificación de su fisiopatología.

Abstract The pathophysiology of non-pulsatile chronic tinnitus is unclear, but it is recognized a relevant psychological component. In this sense, different psychotherapeutic approaches have been studied. Cognitive behavioral therapy is the psychotherapy with the most evidence. It considers the restructuring of dysfunctional cognitions that favor the presence of tinnitus. Its efficacy has been verified on distress, quality of life, severity, associated depressive symptoms and insomnia. Eye movement desensitization and reprocessing includes some conceptions of cognitive behavioral therapy and considers techniques such as bilateral stimulation. Its results in chronic somatic pathologies have suggested its application in tinnitus, corroborating its efficacy in quality of life, distress, and depressive symptoms. Two mindfulness-based psychotherapies applied in tinnitus are mindfulness-based stress reduction and mindfulness-based cognitive therapy. The first has shown efficacy on quality of life and reduction and reinforcement of negative and positive cognitions, respectively. The second is effective on severity, loudness, distress, anxiety, depression and disability associated with tinnitus. Finally, acceptance and commitment therapy promote acceptance as a central component of the treatment of chronic conditions, considering the control exerted by the context over the experience of these conditions and the therapeutic commitment. This therapy is effective on quality of life. We foster the research on psychotherapeutic approaches to tinnitus, which will make it possible the application of more specific interventions and, at the same time, elucidate its pathophysiology.

Hair-cortisol and hair-BDNF as biomarkers of tinnitus loudness and distress in chronic tinnitus.

The role of stress and its neuroendocrine mediators in tinnitus is unclear. In this study, we measure cortisol as an indicator of hypothalamus-pituitary-adrenal (HPA) axis alterations and brain-derived neurotrophic factor (BDNF) as a marker of adaptive neuroplasticity in hair of chronic tinnitus patients to investigate relationships with tinnitus-related and psychological factors. Cross-sectional data from chronic tinnitus inpatients were analyzed. Data collection included hair sampling, pure tone audiometry, tinnitus pitch and loudness matching, and psychometric questionnaires. Elastic net regressions with n-fold cross-validation were performed for cortisol (N = 91) and BDNF (N = 87). For hair-cortisol (R2 = 0.10), the strongest effects were sampling in autumn and body-mass index (BMI) (positive), followed by tinnitus loudness (positive) and smoking (negative). For hair-BDNF (R2 = 0.28), the strongest effects were hearing aid use, shift work (positive), and tinnitus loudness (negative), followed by smoking, tinnitus-related distress (Tinnitus Questionnaire), number of experienced traumatic events (negative), and physical health-related quality of life (Short Form-12 Health Survey) (positive). These findings suggest that in chronic tinnitus patients, higher perceived tinnitus loudness is associated with higher hair-cortisol and lower hair-BDNF, and higher tinnitus-related distress with lower hair-BDNF. Regarding hair-BDNF, traumatic experiences appear to have additional stress-related effects, whereas hearing aid use and high physical health-related quality of life appear beneficial. Implications include the potential use of hair-cortisol and hair-BDNF as biomarkers of tinnitus loudness or distress and the need for intensive future research into chronic stress-related HPA axis and neuroplasticity alterations in chronic tinnitus.

The role of the medial geniculate body of the thalamus in the pathophysiology of tinnitus and implications for treatment.

Tinnitus is an auditory sensation in the absence of actual external stimulation. Different clinical interventions are used in tinnitus treatment, but only few patients respond to available options. The lack of successful tinnitus treatment is partly due to the limited knowledge about the mechanisms underlying tinnitus. Recently, the auditory part of the thalamus has gained attention as a central structure in the neuropathophysiology of tinnitus. Increased thalamic spontaneous firing rate, bursting activity and oscillations, alongside an increase of GABAergic tonic inhibition have been shown in the auditory thalamus in animal models of tinnitus. In addition, clinical neuroimaging studies have shown structural and functional thalamic changes with tinnitus. This review provides a systematic overview and discussion of these observations that support a central role of the auditory thalamus in tinnitus. Based on this approach, a neuromodulative treatment option for tinnitus is proposed.

Effects of sound source localization of masking sound on perception level of simulated tinnitus.

Tinnitus therapies have been combined with the use of varieties of sound/noise. For masking external sounds, location of the masker in space is important; however, effects of the spatial location of the masker on tinnitus are less understood. We aimed to test whether a masking sound location would affect the perception level of simulated tinnitus. The 4 kHz simulated tinnitus was induced in the right ear of healthy volunteers through an open-type earphone. White noise was presented to the right ear using a single-sided headphone or a speaker positioned on the right side at a distance of 1.8 m for masking the simulated tinnitus. In other sessions, monaurally recorded noise localized within the head (inside-head noise) or binaurally recorded noise localized outside the head (outside-head noise) was separately presented from a dual-sided headphone. The noise presented from a distant speaker and the outside-head noise masked the simulated tinnitus in 71.1% and 77.1% of measurements at a lower intensity compared to the noise beside the ear and the inside-head noise, respectively. In conclusion, spatial information regarding the masking noise may play a role in reducing the perception level of simulated tinnitus. Binaurally recorded sounds may be beneficial for an acoustic therapy of tinnitus.

Striatal networks for tinnitus treatment targeting.

Neuromodulation treatment effect size for bothersome tinnitus may be larger and more predictable by adopting a target selection approach guided by personalized striatal networks or functional connectivity maps. Several corticostriatal mechanisms are likely to play a role in tinnitus, including the dorsal/ventral striatum and the putamen. We examined whether significant tinnitus treatment response by deep brain stimulation (DBS) of the caudate nucleus may be related to striatal network increased functional connectivity with tinnitus networks that involve the auditory cortex or ventral cerebellum. The first study was a cross-sectional 2-by-2 factorial design (tinnitus, no tinnitus; hearing loss, normal hearing, n = 68) to define cohort level abnormal functional connectivity maps using high-field 7.0 T resting-state fMRI. The second study was a pilot case-control series (n = 2) to examine whether tinnitus modulation response to caudate tail subdivision stimulation would be contingent on individual level striatal connectivity map relationships with tinnitus networks. Resting-state fMRI identified five caudate subdivisions with abnormal cohort level functional connectivity maps. Of those, two connectivity maps exhibited increased connectivity with tinnitus networks-dorsal caudate head with Heschl's gyrus and caudate tail with the ventral cerebellum. DBS of the caudate tail in the case-series responder resulted in dramatic reductions in tinnitus severity and loudness, in contrast to the nonresponder who showed no tinnitus modulation. The individual level connectivity map of the responder was in alignment with the cohort expectation connectivity map, where the caudate tail exhibited increased connectivity with tinnitus networks, whereas the nonresponder individual level connectivity map did not.

The effectiveness of the combined transcranial direct current stimulation (tDCS) and tailor-made notched music training (TMNMT) on psychoacoustic, psychometric, and cognitive indices of tinnitus patients.

PURPOSE: Tinnitus network(s) consists of pathways in the auditory cortex, frontal cortex, and the limbic system. The cortical hyperactivity caused by tinnitus may be suppressed by neuromodulation techniques. Due to the lack of definitive treatment for tinnitus and limited usefulness of the individual methods, in this study, a combination of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) and tailor-made notched music training (TMNMT) was used. MATERIAL AND METHODS: In this descriptive-analytic study, 26 patients with chronic unilateral tinnitus of the right ear were randomly divided into the clinical trial group (CTG) and the control group (CG). In both groups, six sessions of tDCS with 2 mA intensity for 20 min, with anode on F4 and cathode on F3, were conducted. Simultaneous with tDCS sessions, and based on TMNMT, the participant was asked to listen passively for 120 min/day, to a CD containing her/his favorite music with a proper notch applied in its spectrum according to the individual's tinnitus The treatment outcome was measured by, psychoacoustic (loudness-matching), psychometric (awareness, loudness and annoyance Visual Analogue Scale (VAS) scores, and Tinnitus Handicap Inventory (THI)) scores, and cognitive assessments (randomized dichotic digits test (RDDT) and dichotic auditory-verbal memory test (DAVMT)). Repeated measurement test was used for statistical analyses. RESULTS: In the CTG, the tinnitus loudness and annoyance VAS scores, and THI were reduced significantly (p = 0.001). In addition, the DAVMT and RDDT scores were enhanced (p = 0.001). Such changes were not observed in the CG (p > 0.05). CONCLUSION: The combination of tDCS and TMNMT led to a reduction in the loudness, awareness, annoyance, and also disability induced by tinnitus in CTG. Furthermore, this method showed an improvement of cognitive functions (auditory divided attention, selective attention and working memory) in the CTG.

A Prospective Study of the Effect of Tinnitus Sound Matching Degree on the Efficacy of Customized Sound Therapy in Patients with Chronic Tinnitus.

OBJECTIVES: The aim of this study was to explore and compare the customized sound therapy effect between tinnitus sound matching and nonmatching patients in tinnitus customized sound therapy and therapy-related influencing factors. METHODS: This prospective study investigated a total of 100 patients with unilateral chronic tinnitus who received customized sound therapy. The participants were dichotomously divided into matching (group A) and nonmatching (group B) groups after 4 stages of tinnitus matching via the tinnitus assistant app (provided by Sound Ocean Company, SuZhou, China). Each group consists of 50 participants. Before and 6 months after the treatment, Hospital Anxiety and Depression Scale (HADS), tinnitus handicap inventory (THI), and tinnitus loudness Visual Analog Scale (VAS) were used to evaluate the customized sound therapy effect and explore other related influencing factors. RESULTS: (1) The HADS-A, HADS-D, THI, and VAS scores of 2 groups were both significantly decreased after treatment. (2) The HADS-A and THI scores improved markedly in group A than that in group B, which could be related to the hearing loss of the tinnitus side ear before treatment; the lighter the degree of hearing loss, the better the improvement. No statistically significant differences were detected in HADS-D and VAS scores between the 2 groups, and also, these were not related to the degree of hearing loss. The differences in age, gender, and tinnitus duration did not show any statistically significant effect on the improvement of the 2 groups. CONCLUSIONS: Both tinnitus sound matching and nonmatching of the customized sound therapy brought a significant effect to tinnitus participants. Our study also suggests that THI and HADS-A scores of those with tinnitus matching participants improved markedly as compared to those of nonmatching participants, and the customized sound therapy effect is negatively correlated with the severity of hearing loss.