Background: Limited information is available on factors that affect the burden tinnitus. The aim of this study is to investigate the association between tinnitus burden and demographic, patient-specific and tinnitus characteristics. Secondly, it was examined which variables could predict a change in tinnitus burden after 12 months. Method: In a prospective Dutch cohort of 383 tinnitus patients seeking medical help, tinnitus complaints, demographics, tinnitus characteristics, psychological wellbeing and quality of life were assessed using an online self-report survey at three timepoints (start, 6 months, 12 months). The main outcome variables for tinnitus burden are the Tinnitus Questionnaire (TQ) and Visual Analog Scale (VAS) for tinnitus burden and loudness. Results: Several variables (time, sex, education level, life events, anxiety and depression, sleep issues, tinnitus loudness, hearing impairment and treatment) were significantly associated with tinnitus burden. Additionally, tinnitus burden after 12 months was associated with anxiety, following treatment, sleep issues, negative life events and hearing impairment (increase) and anxiety, total of life events and environmental quality of life (decrease) predicted the tinnitus burden after 12 months. Conclusions: Several factors, such as education level, life events, psychological factors and sleep quality, are related to tinnitus burden and can predict tinnitus burden over time.

Tinnitus denotes the perception of a non-environmental sound and might result from aberrant auditory prediction. Successful prediction of formal (e.g., type) and temporal sound characteristics facilitates the filtering of irrelevant information, also labelled as 'sensory gating' (SG). Here, we explored if and how parallel manipulations of formal prediction violations and temporal predictability affect SG in persons with and without tinnitus. Age-, education- and sex-matched persons with and without tinnitus (N = 52) participated and listened to paired-tone oddball sequences, varying in formal (standard vs. deviant pitch) and temporal predictability (isochronous vs. random timing). EEG was recorded from 128 channels and data were analyzed by means of temporal spatial principal component analysis (tsPCA). SG was assessed by amplitude suppression for the 2nd tone in a pair and was observed in P50-like activity in both timing conditions and groups. Correspondingly, deviants elicited overall larger amplitudes than standards. However, only persons without tinnitus displayed a larger N100-like deviance response in the isochronous compared to the random timing condition. This result might imply that persons with tinnitus do not benefit similarly as persons without tinnitus from temporal predictability in deviance processing. Thus, persons with tinnitus might display less temporal sensitivity in auditory processing than persons without tinnitus.

Tinnitus is a complex neuro-otologic disorder with a significant global impact, affecting approximately 14% of adults, with 2% experiencing severe forms [...]

BACKGROUND:Chronic tinnitus can have an immense impact on quality of life. Despite recent treatment advances, many tinnitus patients remain refractory to them. Preclinical and clinical evidence suggests that deep brain stimulation (DBS) is a promising treatment to suppress tinnitus. In rats, it has been shown in multiple regions of the auditory pathway that DBS can have an alleviating effect on tinnitus. The thalamic medial geniculate body (MGB) takes a key position in the tinnitus network, shows pathophysiological hallmarks of tinnitus, and is readily accessible using stereotaxy. Here, a protocol is described to evaluate the safety and test the therapeutic effects of DBS in the MGB in severe tinnitus sufferers.METHODS:Bilateral DBS of the MGB will be applied in a future study in six patients with severe and refractory tinnitus. A double-blinded, randomized 2 × 2 crossover design (stimulation ON and OFF) will be applied, followed by a period of six months of open-label follow-up. The primary focus is to assess safety and feasibility (acceptability). Secondary outcomes assess a potential treatment effect and include tinnitus severity measured by the Tinnitus Functional Index (TFI), tinnitus loudness and distress, hearing, cognitive and psychological functions, quality of life, and neurophysiological characteristics.DISCUSSION:This protocol carefully balances risks and benefits and takes ethical considerations into account. This study will explore the safety and feasibility of DBS in severe refractory tinnitus, through extensive assessment of clinical and neurophysiological outcome measures. Additionally, important insights into the underlying mechanism of tinnitus and hearing function might be revealed.TRIAL REGISTRATION:ClinicalTrials.gov NCT03976908 (6 June 2019).

Tinnitus is a common condition with great variability in the intensity of symptomatology. In recent years, more and more insights have been gained into the mechanism of tinnitus and its relationship with hearing loss and other factors such as stress. Depending on the symptoms and clinical findings, a patient may be referred to an ENT specialist or audiologist. For the majority of patients, re-assurance and providing good information is sufficient. For others improving hearing and possibly cognitive behavioral therapy remains the most important pillars for treatment of tinnitus. A number of experimental treatments are currently underway which offer hope for the future.

Tinnitus is defined as the phantom perception of sound. To date, there is no curative treatment, and contemporary treatments have failed to show beneficial outcomes. Deep brain stimulation has been suggested as a potential therapy for refractory tinnitus. However, the optimal target and stimulation regimens remain to be defined. Herein, we investigated metabolic and neuronal activity changes using cytochrome C oxidase histochemistry and c-Fos immunohistochemistry in a noise trauma-induced rat model of tinnitus. We also assessed changes in neuronal activity following medial geniculate body (MGB) high-frequency stimulation (HFS). Metabolic activity was reduced in the primary auditory cortex, MGB and CA1 region of the hippocampus in noise-exposed rats. Additionally, c-Fos expression was increased in the primary auditory cortex of those animals. Furthermore, MGB-HFS enhanced c-Fos expression in the thalamic reticular nucleus. We concluded that noise trauma alters tissue activity in multiple brain areas including the auditory and limbic regions. MGB-HFS resulted in higher neuronal activity in the thalamic reticular nucleus. Given the prominent role of the auditory thalamus in tinnitus, these data provide more rationales towards targeting the MGB with HFS as a symptom management tool in tinnitus.

Objectives: Radiofrequency Ablation (RFA) is a widely used technique for treatment of nasal obstruction due to inferior turbinate hypertrophy. This study aims to evaluate short and long-term outcome after RFA. Secondly, predictive factors for this outcome were evaluated. Methods: A prospective clinical study was performed in 65 patients to evaluate short-term outcome and predictive factors (Study A). To evaluate long-term outcome and predictive factors we performed a second clinical study in 124 patients (Study B). Patients scored nasal symptoms on a 1 to 5 points visual analogue scale (VAS) and filled in questionnaires about their comorbidity, previous nasal surgery, and medication use. Results: Study A: There was significant short-term (6-8 weeks after RFA) improvement in nasal obstruction (VAS −1.3, P < .001), trouble exercising (VAS −1.5, P < .001), trouble sleeping (VAS −0.9, P < .001), snoring (VAS −1.1, P< .001), and hyposmia (VAS −0.6, P = .004). Smoking (R2 = .065, P = .047) was a predictor for less optimized and previous use of decongestive nasal spray (R2 = .135, P = .005) for better short-term outcome. Study B: Nasal obstruction significantly decreased in the long term (1-5 years after RFA) compared to VAS before RFA (VAS −1.5, P < .001), but slightly increased compared to VAS 6 to 8 weeks after RFA (VAS +0.3, P = .036). Allergy (R2 = .066, P = .006), asthma (R2 = .068, P = .005), and previous use of corticosteroid nasal spray (R2 = .050, P = .016) were associated with a less optimized and older age (R2 = .217, P < .001) with better long-term outcome. Conclusion: RFA is an efficient treatment for nasal obstruction, and improves sleeping, exercising, snoring, and hyposmia. Predictors for good short-term outcome were previous use of decongestive nasal spray and no smoking. Predictors for a less optimized long-term outcome were allergy, asthma, and previous use of corticosteroid nasal spray. Older age was associated with better long-term outcome.

Deep brain stimulation (DBS) is a neurosurgical treatment with a growing range of indications. The number of clinical studies is expanding because of DBS for new indications and efforts to improve DBS for existing indications. To date, various methods have been used to perform DBS studies. Designing a clinical intervention study with active implantable medical devices has specific challenges while expanding patient treatment. This paper provides an overview of the key aspects that are essential for setting up a DBS study.

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.

Tinnitus is the phantom perception of a sound, often accompanied by increased anxiety and depressive symptoms. Degenerative or inflammatory processes, as well as changes in monoaminergic systems, have been suggested as potential underlying mechanisms. Herein, we conducted the first post-mortem histopathological assessment to reveal detailed structural changes in tinnitus patients' auditory and non-auditory brain regions. Tissue blocks containing the medial geniculate body (MGB), thalamic reticular nucleus (TRN), central part of the inferior colliculus (CIC), and dorsal and obscurus raphe nuclei (DRN and ROb) were obtained from tinnitus patients and matched controls. Cell density and size were assessed in Nissl-stained sections. Astrocytes and microglia were assessed using immunohistochemistry. The DRN was stained using antibodies raised against phenylalanine hydroxylase-8 (PH8) and tyrosine-hydroxylase (TH) to visualize serotonergic and dopaminergic cells, respectively. Cell density in the MGB and CIC of tinnitus patients was reduced, accompanied by a reduction in the number of astrocytes in the CIC only. Quantification of cell surface size did not reveal any significant difference in any of the investigated brain regions between groups. The number of PH8-positive cells was reduced in the DRN and ROb of tinnitus patients compared to controls, while the number of TH-positive cells remained unchanged in the DRN. These findings suggest that both neurodegenerative and inflammatory processes in the MGB and CIC underlie the neuropathology of tinnitus. Moreover, the reduced number of serotonergic cell bodies in tinnitus cases points toward a potential role of the raphe serotonergic system in tinnitus.

Separate functional classes of MGB neurons might have distinct roles in tinnitus pathophysiology. After noise exposure, fast-responding neurons become less responsive or nonresponsive without change to their spontaneous firing, whereas sustained and suppressed neurons exhibit enhanced spontaneous activity without change to their stimulus-driven activity. Furthermore, results suggest desynchronization of thalamocortical β and γ oscillations as a mechanism of tinnitus suppression by MGB DBS.

Tinnitus is the perception of a 'ringing' sound without an acoustic source. It is generally accepted that tinnitus develops after peripheral hearing loss and is associated with altered auditory processing. The thalamus is a crucial relay in the underlying pathways that actively shapes processing of auditory signals before the respective information reaches the cerebral cortex. Here, we review animal and human evidence to define thalamic function in tinnitus. Overall increased spontaneous firing patterns and altered coherence between the thalamic medial geniculate body (MGB) and auditory cortices is observed in animal models of tinnitus. It is likely that the functional connectivity between the MGB and primary and secondary auditory cortices is reduced in humans. Conversely, there are indications for increased connectivity between the MGB and several areas in the cingulate cortex and posterior cerebellar regions, as well as variability in connectivity between the MGB and frontal areas regarding laterality and orientation in the inferior, medial and superior frontal gyrus. We suggest that these changes affect adaptive sensory gating of temporal and spectral sound features along the auditory pathway, reflecting dysfunction in an extensive thalamo-cortical network implicated in predictive temporal adaptation to the auditory environment. Modulation of temporal characteristics of input signals might hence factor into a thalamo-cortical dysrhythmia profile of tinnitus, but could ultimately also establish new directions for treatment options for persons with tinnitus.

Research in hearing science is accelerating, and a wealth of data concerning auditory brainstem responses (ABR) in various animal models is published in peer-reviewed journals every year. Recently, we reviewed studies using ABR measurements in tinnitus rat models. We found significant discrepancies in the outcomes of these studies, some due to different research approaches and others due to different methodologies. Thus, the present work aimed to collect comprehensive information on all factors influencing ABR recordings in rats and compile recommendations on ABR data reporting. A questionnaire with queries about animal husbandry, transfer, handling, and the exact test conditions before, during, and after ABR recordings was sent to 125 researchers who published the relevant studies between 2015 and 2021. Eighteen researchers provided detailed answers on factors related to ABR measurements. Based on the analysis of the returned questionnaires, we identified three domains reflecting animal-, equipment-, and experiment-dependent factors that might influence the ABR outcome, thus requiring reporting in published research. The analysis of survey results led to the compilation of recommendations for reporting ABR outcomes supported by a literature review. Following these recommendations should facilitate comparative and meta-analyses of ABR results provided by various research groups.

Submucosal laryngeal masses are challenging for ENT specialists as the diagnosis usually remains uncertain until histopathological examination is carried out. We report a case of a 54-year old man complaining of dysphonia and globus sensation. Flexible laryngoscopic examination showed a submucosal swelling in the right anterior laryngeal ventricle. Microlaryngoscopic excision of the submucosal mass was performed. Histological examination revealed salivary gland tissue. We found only a few cases in the literature of ectopic salivary gland tissue situated in the larynx. In these cases, the salivary gland tissue was also located at the anterior portion of the true or false vocal fold. Thus, it is necessary to consider this condition in the differential diagnosis of a submucosal mass in the anterior true or false vocal fold or laryngeal ventricle.

Background: Chronic tinnitus can have an immense impact on quality of life. Despite recent treatment advances, many tinnitus patients remain refractory to them. Preclinical and clinical evidence suggest that deep brain stimulation (DBS) is as a promising treatment to suppress tinnitus. The thalamic medial geniculate body (MGB) takes a key position in the tinnitus network, shows pathophysiological hallmarks of tinnitus, and is readily accessible using stereotaxy. This study will evaluate the safety and therapeutic effects of DBS in the MGB in severe tinnitus sufferers. Methods: Bilateral DBS of the MGB will be applied in six patients with severe and refractory tinnitus. A double-blinded, randomized 2x2 crossover design (stimulation ON and OFF) will be applied, followed by a period of six months open label follow-up. The primary focus is to assess safety and feasibility (acceptability). Secondary outcomes assess a potential treatment effect and include tinnitus severity measured by the Tinnitus Functional Index (TFI), tinnitus loudness and distress, hearing, cognitive and psychological functions, quality of life, and neurophysiological characteristics. Discussion: Whilst carefully balancing risks and benefits and taking ethical considerations into account, this study explores the safety and feasibility of DBS in severe refractory tinnitus, by extensive assessment of clinical and neurophysiological outcome measures. Additionally, important insights in the underlying mechanism of tinnitus and hearing function might be revealed. Trial registration: ClinicalTrials.gov NCT03976908 (June 6, 2019)

Tinnitus is a clinical condition defined by hearing a sound in the absence of an objective source. Early experiments in animal models have suggested that tinnitus stems from an alteration of processing in the auditory system. However, translating these results to humans has proven challenging. One limiting factor has been the insufficient spatial resolution of non-invasive measurement techniques to investigate responses in subcortical auditory nuclei, like the inferior colliculus and the medial geniculate body (MGB). Here we employed ultra-high field functional magnetic resonance imaging (UHF-fMRI) at 7 Tesla to investigate the frequency-specific processing in sub-cortical and cortical regions in a cohort of six tinnitus patients and six hearing loss matched controls. We used task-based fMRI to perform tonotopic mapping and compared the magnitude and tuning of frequency-specific responses between the two groups. Additionally, we used resting-state fMRI to investigate the functional connectivity. Our results indicate frequency-unspecific reductions in the selectivity of frequency tuning that start at the level of the MGB and continue in the auditory cortex, as well as reduced thalamocortical and cortico-cortical connectivity with tinnitus. These findings suggest that tinnitus may be associated with reduced inhibition in the auditory pathway, potentially leading to increased neural noise and reduced functional connectivity. Moreover, these results indicate the relevance of high spatial resolution UHF-fMRI for the investigation of the role of sub-cortical auditory regions in tinnitus.

Deep brain stimulation of the central auditory pathway is emerging as a promising treatment modality for tinnitus. Within this pathway, the dorsal cochlear nucleus (DCN) plays a key role in the pathophysiology of tinnitus and is believed to be a tinnitus generator. We hypothesized that high-frequency stimulation (HFS) of the DCN would influence tinnitus-related abnormal neuronal activity within the auditory pathway and hereby suppress tinnitus. To this end, we assessed the effect of HFS of the DCN in a noise-induced rat model of tinnitus. The presence of tinnitus was verified using the gap prepulse inhibition of the acoustic startle response paradigm. Hearing thresholds were determined before and after noise trauma by measuring the auditory brainstem responses. In addition, changes in neuronal activity induced by noise trauma and HFS were assessed using c-Fos immunohistochemistry in related structures. Results showed tinnitus development after noise trauma and hearing loss ipsilateral to the side exposed to noise trauma. During HFS of the DCN, tinnitus was suppressed. There was no change in c-Fos expression within the central auditory pathway after HFS. These findings suggest that DCN-HFS changes patterns of activity and results in information lesioning within the network and hereby blocking the relay of abnormal tinnitus-related neuronal activity.

BACKGROUND:Neuromodulation is a promising treatment modality for tinnitus, especially in chronic and severe cases. The auditory thalamus plays a key role in the pathophysiology of tinnitus, as it integrates and processes auditory and limbic information.OBJECTIVE:The effect of high frequency stimulation and low frequency stimulation of the medial geniculate bodies on tinnitus in a noise-induced tinnitus rat model is assessed.MATERIALS AND METHODS:Presence of tinnitus was verified using the gap-induced prepulse inhibition of the acoustic startle response paradigm. Hearing thresholds were determined before and after noise trauma with auditory brainstem responses. Anxiety-related side-effects were evaluated in the elevated zero maze and open field.RESULTS:Results show tinnitus development after noise exposure and preserved hearing thresholds of the ear that was protected from noise trauma. We found that high frequency stimulation of the medial geniculate bodies suppressed tinnitus. This effect maintained directly after stimulation when the stimulator was turned off. Low frequency stimulation did not have any effects on the gap:no-gap ratio of the acoustic startle response.CONCLUSION:High frequency stimulation of the MGB has a direct and residual suppressing effect on tinnitus in this animal model. Low frequency stimulation of the MGB did not inhibit tinnitus.