Identification of functional biomarkers for tinnitus and hyperacusis in animals and humans

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Chronic tinnitus (phantom noise) and chronic hyperacusis (decreased tolerance of sound based on loudness) effects 10-20% of the population. Based on acknowledged negative influences of age, stress and noise on probably both entities, the prevalence within the population is expected to increase. For both, tinnitus and hyperacusis, currently no cure exists. Tinnitus and hyperacusis do not imply a higher than normal threshold sensitivity to sound and for both pathologies the neural correlate is unknown or controversial. It is elusive of why probably both entities often co-occur with comorbidities as fear-associated diseases or psychiatric disorders. Almost all tinnitus literature up to now argue for increased spontaneous firing rates following sensory deprivation that convey to the percept of tinnitus through increased central neural gain. In contrast, based on animal studies, we observed that tinnitus is rather associated with a failure to increase central neural gain linked to reduced signal to noise ratio and elevated noise levels. We moreover could establish first a hyperacusis animal model, that based on central auditory responses can be distinguished in its neural central responses from animals with behavioural tinnitus. Using these animal models we could verify in preliminary studies a successful use of functional connectivities in cortical regions using r-fc-BOLD-MRI. To our surprise, first human pilot studies performed in our group, could confirm our observations in animal studies, showing reduced, rather than enhanced, central auditory responsiveness in tinnitus patients. Accordingly, a combination of fine-structure analysis of ABR wave, evoked BOLD fMRI and r-fcMRI pointed to reduced auditory-specific flow in tinnitus patients. Observed changes in BOLD fMRI responses in stress- and attentional-regulating regions, that were also observed by others in previous studies, appeared to be linked to the observed reduced auditory-specific responses. We hypothesize that reduced auditory-specific information flow in tinnitus has until now escaped detection in humans, as low-level auditory brain regions were previously omitted from neuroimaging studies. Based on this previous information the current study aims to use the established procedures to identify and distinguish the neural correlate of tinnitus and hyperacusis in animal models and human patients. The studies will use audiometry, fine-structure analysis of ABR, BOLD fMRI and body fluid analysis in animals and humans with tinnitus and hyperacusis. The study will be performed by a team of specialist in the department of neurology, the ENT clinic and research unit. Coordinated by the primary applicant, this team has already approved a successful cooperation. The results are fundamental for any future tinnitus and hyperacusis therapeutic intervention strategy and are essential for the establishment of objective diagnostic tools to validate therapeutic success.