الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Conflicting views on the neural correlates of tinnitus, the widespread disease with devastating effects on the quality of life, are an obvious current obstacle to successful approaches for causative therapies. Hypothesizing that the unnoticed co-occurrence of hyperacusis and differences in the duration of tinnitus may possibly differentially influence the neural correlate of tinnitus, we recruited control subjects, tinnitus patients without hyperacusis (T-group), tinnitus patients with hyperacusis (T+H-group) and hyperacusis patients (H-group). We compared between the groups on the basis of questionnaires, PTA, ABR, cortisol level in saliva and sound-evoked BOLD fMRI in anatomically predefined brain regions (ROI). Then, we subclassified the T-group and the T+H-group into four groups according to the duration of tinnitus < 1 year, 1-5 years, 5-10 years, and >10 years. We compared between the tinnitus duration groups on the basis of questionnaires, PTA, ABR, and cortisol level in saliva.
We found that patients with both tinnitus and hyperacusis (T+H-group) experienced significantly higher distress and annoyance than patients with only tinnitus (T-group), despite there being no group difference in hearing thresholds. Over the years of tinnitus duration, in the T+H-group, the tinnitus complaints (total tinnitus score) were significantly greater from early on and the tinnitus intensity increased over time, while annoyance responses to normal sound (hyperacusis score) remained nearly constant. In contrast, in the T-group tinnitus complaints remained constant, although the tinnitus intensity declined over time. This was explained through a gradually increased annoyance to normal sound over time, shown by a hyperacusis questionnaire (HKI). Parallel a shift from a mainly unilateral- to a bilateral tinnitus percept occurred in the T-group, while bilateral tinnitus dominated in the T+H-group from the start.
For tinnitus only, a reduced and delayed ABR wave V was linked to reduced sound-evoked fMRI BOLD activity in subcortical, cortical, and associated auditory regions. This phenotype was inconclusive when tinnitus co-occurred with hyperacusis through an elevated ABR wave III amplitude, an elevated sound-evoked fMRI BOLD activity in thalamic, cortical, and associated auditory regions, particularly for low-frequency sound. These results suggest that the co-occurrence of hyperacusis leads to a masking of the characteristic lower and delayed central auditory-responsiveness characteristic for tinnitus.
Over time in the T-group, ABR wave V amplitudes and V/I ratios remained reduced and delayed. By contrast, in the T+H group especially the ABR wave III and V and III/I ratio continued to be enhanced and shortened in response to high-level sound stimuli. Interestingly, in line with signs of an increased co-occurrence of hyperacusis in the T-group over time, ABR wave III also slightly increased in the T-group.
On the basis of this finding, we urgently recommend changing medical practice towards a sub-classification of tinnitus with and without hyperacusis with a specific emphasis on tinnitus duration. With the objective tools presented here, mutual efforts and harmonized methods may progress to find urgently needed, personalized therapies for tinnitus in Otolaryngology clinics. The results were submitted in Hofmeier, Wertz et al., and Refat et al.