The tinnitus network: comorbidity, plasticity and response to treatment

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Tinnitus, the perception of a phantom sound, ranges from a mere nuisance to a debilitating disorder. As shown by our own research, it is characterized by high comorbidity including affective symptoms, but also attentional and speech comprehension difficulties. On a neuronal level, the disorder is associated with dysfunctions not only in purely auditory processing regions but also including limbic and particularly parietal and prefrontal areas both in spontaneous and evoked measures. Thus, tinnitus is rather a network disorder than a disorder marked by a circumscribed dysfunctional region. In the first funding period of our project, we have characterized pathological changes in the cortical tinnitus network by capitalizing on the excellent temporal and good spatial resolution of Magnetoencephalography (MEG). Here, we propose a project that builds on our earlier research and uses Magnetoencephalography (MEG) to investigate deeper functional connectivity and its changes due to therapeutic tinnitus intervention. Hypothesizing that the thalamus plays a pivotal role in the tinnitus network, we will measure the thalamo-cortical connectivity at rest, in response to musical stimuli and as an interplay of tinnitus with specific stimulated frequencies (study 1). To understand the mechanism for high comorbidity in chronic tinnitus and the impact on functional connectivity, we will further employ experimental paradigms that were used to understand affective disorders. Thus, study 2 will investigate increased fear and diminished safety learning and overgeneralization to conditioned stimuli associated with general threat stimuli in both, the tinnitus-related auditory and the tinnitus-unrelated visual domain. The paradigms of both studies in combination with resting state measures will be used to monitor function connectivity before and after interdisciplinary tinnitus treatment according to current guidelines (study 3). This approach allows us to study to what extent clinical intervention alleviates pathological connectivity changes in tinnitus patients. In addition to these neurophysiological measures, patients will undergo a standard clinical assessment, and will receive a smartphone app measuring depressive symptomatology, tinnitus and activity profiles so that a remote momentary assessment and longitudinal tracking of symptoms becomes possible. As shown by our own and others’ research, prediction of treatment response is still unsatisfactory and we hope to improve this situation by the proposed combination of measures and experimental approaches.Taken together, the proposal aims to further understand the neural correlates and mechanisms underlying tinnitus and its high comorbidity with affective disorders. Following this goal, we will establish novel methods and paradigms to understand the development and treatment of chronic tinnitus.