Elisabeth Wallhäusser-Franke

Expression of c-fos in auditory and non-auditory brain regions of the gerbil after manipulations that induce tinnitus

Subjective tinnitus is a phantom sound sensation that does not result from acoustic stimulation and is audible to the affected subject only. Tinnitus-like sensations in animals can be evoked by procedures that also cause tinnitus in humans. In gerbils, we investigated brain activation after systemic application of sodium salicylate or exposure to loud noise, both known to be reliable tinnitus-inductors. Brains were screened for neurons containing the c-fos protein. After salicylate injections, auditory cortex was the only auditory area with consistently increased numbers of immunoreactive neurons compared to controls. Exposure to impulse noise led to prolonged c-fos expression in auditory cortex and dorsal cochlear nucleus. After both manipulations c-fos expression was increased in the amygdala, in thalamic midline, and intralaminar areas, in frontal cortex, as well as in hypothalamic and brainstem regions involved in behavioral and physiological defensive reactions. Activation of these non-auditory areas was attributed to acute stress, to aversive-affective components and autonomous reactions associated with the treatments and a resulting tinnitus. The present findings are in accordance with former results that provided evidence for suppressed activation in auditory midbrain but enhanced activation of the auditory cortex after injecting high doses of salicylate. In addition, our present results provide evidence that acute stress coinciding with a disruption of hearing may evoke activation of the auditory cortex. We interpret these results in favor of our model of central tinnitus generation.

Evidence for tinnitus-related plasticity in the auditory and limbic system, demonstrated by arg3.1 and c-fos immunocytochemistry

Distributions of arg3.1 and c-fos immunoreactive neurons (IRN) in gerbil auditory cortex (AC) and amygdala showed characteristic differences when comparing systemic application of the tinnitus-eliciting drug salicylate with acoustic stimulation or saline injections. In AC, arg3.1 IRN induced by stimulation focused in regions corresponding to the frequency content of the stimulus. Injections of salicylate (350 mg/kg body weight) led to accumulation of arg3.1 IRN in the high frequency domain, while saline injections produced a diffuse distribution. After all treatments, c-fos IRN outnumbered arg3.1 IRN in AC and showed a broad distribution. In subcortical auditory structures arg3.1 IRN were absent in all but one brain. In ventral cochlear nucleus, c-fos IRN were always found after stimulation and often also after saline injections, whereas none were present when injecting salicylate. Similarly, in inferior colliculus, numbers of c-fos IRN were lowest after salicylate injections. In the amygdala, c-fos and arg3.1 IRN were increased substantially after salicylate injections compared to auditory stimulation or saline injections. In particular in its central nucleus, c-fos and arg3.1 IRN were found exclusively after the tinnitus-inducing treatment, suggesting that coactivation of the AC and the amygdala may by an essential feature of tinnitus-related activation.

Salicylate alters 2-DG uptake in the auditory system: a model for tinnitus?

Because salicylate is known to produce tinnitus in humans and animals, the effect of salicylate on the auditory system of gerbils was investigated using [14C]2-deoxyglucose (2-DG). Salicylate treatment reduced activity in the inferior colliculus (IC), particularly in the high frequency part, whereas activation along some isofrequency contours was observed in auditory cortex. In contrast, in saline-treated controls the IC but not the auditory cortex was active. These results suggest that the sensation of subjective tinnitus may be generated within auditory brain structures. The 2-DG method may be used to measure tinnitus objectively in animals and also to evaluate tinnitus treatments.

Salicylate evokes c-fos expression in the brain stem: implications for tinnitus.

SUBJECTIVE tinnitus, a distracting internal noise is experienced by humans and animals. Mongolian gerbils were treated with salicylate as a tinnitus-evoking agent. After salicylate treatment, c-fos expression in auditory brain stem nuclei was as low as after saline treatment (control). Pronounced differences between groups were found, however, in areas susceptible to stress, with many immunoreactive cells in the locus coeruleus, the midbrain periaqueductal grey and the lateral parabrachial nucleus of salicylate-treated animals. These results suggest that salicylate may evoke tinnitus through a combined effect on auditory and non-auditory brain nuclei. While activity in auditory brain stem nuclei is reduced, stress-susceptible areas are activated. It seems possible that the interaction of these effects at particular locations of the brain causes tinnitus.

Tinnitus: distinguishing between subjectively perceived loudness and tinnitus-related distress.

Objectives Overall success of current tinnitus therapies is low, which may be due to the heterogeneity of tinnitus patients. Therefore, subclassification of tinnitus patients is expected to improve therapeutic allocation, which, in turn, is hoped to improve therapeutic success for the individual patient. The present study aims to define factors that differentially influence subjectively perceived tinnitus loudness and tinnitus-related distress. Methods In a questionnaire-based cross-sectional survey, the data of 4705 individuals with tinnitus were analyzed. The self-report questionnaire contained items about subjective tinnitus loudness, type of onset, awareness and localization of the tinnitus, hearing impairment, chronic comorbidities, sleep quality, and psychometrically validated questionnaires addressing tinnitus-related distress, depressivity, anxiety, and somatic symptom severity. In a binary step-wise logistic regression model, we tested the predictive power of these variables on subjective tinnitus loudness and tinnitus-related distress. Results The present data contribute to the distinction between subjective tinnitus loudness and tinnitus-related distress. Whereas subjective loudness was associated with permanent awareness and binaural localization of the tinnitus, tinnitus-related distress was associated with depressivity, anxiety, and somatic symptom severity. Conclusions Subjective tinnitus loudness and the potential presence of severe depressivity, anxiety, and somatic symptom severity should be assessed separately from tinnitus-related distress. If loud tinnitus is the major complaint together with mild or moderate tinnitus-related distress, therapies should focus on auditory perception. If levels of depressivity, anxiety or somatic symptom severity are severe, therapies and further diagnosis should focus on these symptoms at first.

Tinnitus and insomnia: Is hyperarousal the common denominator?

Tinnitus is an auditory sensation that is generated by aberrant activation within the auditory system. Sleep disturbances are a frequent problem in the tinnitus population. They are known to worsen the distress caused by the tinnitus which in turn worsens sleep quality. Beyond that, disturbed sleep is a risk factor for mental health problems and distressing tinnitus is often associated with enhanced depressivity, anxiety, and somatic symptom severity. Moreover there is evidence that therapies which alleviate tinnitus-related distress have a positive influence on sleep quality and help interrupt this vicious cycle. This suggests that distressing tinnitus and insomnia may both be promoted by similar physiological mechanisms. One candidate mechanism is hyperarousal caused by enhanced activation of the sympathetic nervous system. There is increasing evidence for hyperarousal in insomnia patients, and animal models of tinnitus and insomnia show conspicuous similarities in the activation pattern of limbic and autonomous brain regions. In this article we review the evidence for this hypothesis which may have implications for therapeutic intervention in tinnitus patients with comorbid insomnia.

Psychoacoustic tinnitus loudness and tinnitus-related distress show different associations with oscillatory brain activity.

Background The phantom auditory perception of subjective tinnitus is associated with aberrant brain activity as evidenced by magneto- and electroencephalographic studies. We tested the hypotheses (1) that psychoacoustically measured tinnitus loudness is related to gamma oscillatory band power, and (2) that tinnitus loudness and tinnitus-related distress are related to distinct brain activity patterns as suggested by the distinction between loudness and distress experienced by tinnitus patients. Furthermore, we explored (3) how hearing impairment, minimum masking level, and (4) psychological comorbidities are related to spontaneous oscillatory brain activity in tinnitus patients. Methods and Findings Resting state oscillatory brain activity recorded electroencephalographically from 46 male tinnitus patients showed a positive correlation between gamma band oscillations and psychoacoustic tinnitus loudness determined with the reconstructed tinnitus sound, but not with the other psychoacoustic loudness measures that were used. Tinnitus-related distress did also correlate with delta band activity, but at electrode positions different from those associated with tinnitus loudness. Furthermore, highly distressed tinnitus patients exhibited a higher level of theta band activity. Moreover, mean hearing loss between 0.125 kHz and 16 kHz was associated with a decrease in gamma activity, whereas minimum masking levels correlated positively with delta band power. In contrast, psychological comorbidities did not express significant correlations with oscillatory brain activity. Conclusion Different clinically relevant tinnitus characteristics show distinctive associations with spontaneous brain oscillatory power. Results support hypothesis (1), but exclusively for the tinnitus loudness derived from matching to the reconstructed tinnitus sound. This suggests to preferably use the reconstructed tinnitus spectrum to determine psychoacoustic tinnitus loudness. Results also support hypothesis (2). Moreover, hearing loss and minimum masking level correlate with oscillatory power in distinctive frequency bands. The lack of an association between psychological comorbidities and oscillatory power may be attributed to the overall low level of mental health problems in the present sample.

Tinnitus-Related Distress and the Personality Characteristic Resilience

It has been suggested that personality traits may be prognostic for the severity of suffering from tinnitus. Resilience as measured with the Wagnild and Young resilience scale represents a positive personality characteristic that promotes adaptation to adverse life conditions including chronic health conditions. Aim of the study was to explore the relation between resilience and tinnitus severity. In a cross-sectional study with a self-report questionnaire, information on tinnitus-related distress and subjective tinnitus loudness was recorded together with the personality characteristic resilience and emotional health, a measure generated from depression, anxiety, and somatic symptom severity scales. Data from 4705 individuals with tinnitus indicate that tinnitus-related distress and to a lesser extent the experienced loudness of the tinnitus show an inverse correlation with resilience. A mediation analysis revealed that the relationship between resilience and tinnitus-related distress is mediated by emotional health. This indirect effect indicates that high resilience is associated with better emotional health or less depression, anxiety, and somatic symptom severity, which in turn is associated with a less distressing tinnitus. Validity of resilience as a predictor for tinnitus-related distress is supported but needs to be explored further in longitudinal studies including acute tinnitus patients.

Unilateral Cochlear Implantation Reduces Tinnitus Loudness in Bimodal Hearing: A Prospective Study

Perceptive and receptive aspects of subjective tinnitus like loudness and tinnitus-related distress are partly independent. The high percentage of hearing loss in individuals with tinnitus suggests causality of hearing impairment particularly for the tinnitus percept, leading to the hypothesis that restoration of auditory input has a larger effect on tinnitus loudness than on tinnitus-related distress. Furthermore, it is assumed that high levels of depression or anxiety prevent reductions of tinnitus loudness and distress following restoration of activity in the cochlea. This prospective study investigated the influence of unilateral cochlear implant (CI) on tinnitus in 19 postlingually deafened adults during 6 months following implantation. All had bimodal provision with the other ear being continuously supported by a hearing aid. On the day before CI implantation (T1, T2), and at about 3 and 6 months postsurgery (T3, T4), participants were questioned about their current tinnitus. Loudness was rated on a Numeric Rating Scale, distress was assessed by the TQ12 Tinnitus Questionnaire, and depression and anxiety were recorded with the Hospital Anxiety and Depression Scale. At T2, 79% experienced tinnitus, one participant developed tinnitus after implantation. Following implantation, tinnitus loudness was reduced significantly by 42%, while reductions in tinnitus-related distress (−24%), depression (−20%), and anxiety (−20%) did not attain statistical significance. Significant correlations existed between tinnitus measures, and between postimplantation tinnitus-related distress and anxiety and depression scores. Moreover, improvement of hearing in the CI ear was significantly correlated with reduction in tinnitus loudness. A new aspect of this study is the particular influence of CI provision on perceptive aspects of preexisting tinnitus (hypothesis 1), with the effect size regarding postimplant reduction of perceived tinnitus loudness (1.40) being much larger than effect sizes on the reduction of tinnitus-related distress (0.38), depression (0.53), and anxiety (0.53). Contrary to expectation both tinnitus measures reduce even in the majority of CI recipients with increased levels of anxiety or depression. This suggests that reduction of the tinnitus signal by restoring activity in the cochlea cannot be entirely compensated for by central tinnitus mechanisms and results in a reduction of perceptive and less so of reactive aspects of subjective tinnitus.

Langzeit-Entwicklung von akutem Tinnitus

BACKGROUND Aim was to assess correlations between hearing threshold and mental health measures at tinnitus onset and tinnitus severity after 6 months. Short self-report questionnaires were used to permit later use in ENT-practices. METHOD 28 patients with tinnitus of no longer than 4 weeks filled out questionnaires at inclusion (T1), and at 6 weeks (T2), 3 (T3) and 6 months (T4) after tinnitus onset. An audiogram was recorded at T1. Tinnitus loudness and sound sensitivity were assessed by numeric rating scales, tinnitus-distress was recorded with the short form of the tinnitus questionnaire. Mental health and personality factors were measured by the depressivity, anxiety and somatic severity scales of the Patient Health Questionnaire, and the resilience scale. RESULTS Tinnitus loudness and distress were stable throughout the investigation period whereas sound sensitivity decreased. Resilience did not represent a predictor for tinnitus severity after 6 months. Depressivity and hearing loss at T1 had an effect on later tinnitus loudness, while depressivity and age at T1 showed an effect on sound sensitivity and tinnitus-related distress at T4. CONCLUSION Stability of tinnitus severity during the 6 months after onset supports the hypothesis of early manifestation. RESULTS also support the hypothesis that later tinnitus severity is related to psychological distress and hearing impairment at onset. RESULTS suggest to use hearing aids to alleviate tinnitus loudness, and to include tools for the identification of depressive disorders at an early stage to identify patients that might benefit from psychotherapeutic interventions.