The tinnitus network: comorbidity, plasticity and response to treatment

耳鸣是对幻觉声音的感觉，范围从纯粹的滋扰到令人衰弱的紊乱。我们自己的研究表明，它的特点是高共病，包括情感症状，但也有注意力和言语理解困难。在神经元水平上，这种障碍不仅与纯听觉处理区域的功能障碍有关，还包括边缘区域，特别是在自发和诱发测量中的顶叶和前额叶区域。因此，耳鸣与其说是一种以受限的功能障碍区域为标志的障碍，不如说是一种网络障碍。在我们项目的第一个资助期，我们利用脑磁图(MEG)良好的时间和空间分辨率，表征了皮质耳鸣网络的病理变化。在这里，我们提出了一个项目，该项目建立在我们早期研究的基础上，并使用脑磁图(MEG)来研究更深层次的功能连接及其由于治疗性耳鸣干预而发生的变化。假设丘脑在耳鸣网络中起关键作用，我们将测量静息状态下丘脑-皮质的连通性，对音乐刺激作出反应，并将其作为耳鸣与特定刺激频率的相互作用(研究1)。为了了解慢性耳鸣高共病的机制及其对功能连通性的影响，我们将进一步使用用于理解情感障碍的实验范式。因此，研究2将在耳鸣相关的听觉和非耳鸣相关的视觉领域调查恐惧增加、安全学习减少以及对与一般威胁刺激相关的条件性刺激的过度概括。根据目前的指南，这两项研究的范例结合静息状态措施将用于监测跨学科耳鸣治疗前后的功能连通性(研究3)。这种方法使我们能够研究临床干预在多大程度上缓解了耳鸣患者的病理连接性变化。除了这些神经生理指标外，患者还将接受标准的临床评估，并将收到一款智能手机应用程序，用于测量抑郁症状、耳鸣和活动情况，从而实现对症状的远程瞬时评估和纵向跟踪。正如我们自己和其他人的研究表明，治疗反应的预测仍然不令人满意，我们希望通过提出的措施和实验方法的结合来改善这种情况。综上所述，该建议旨在进一步了解耳鸣及其与情感障碍的高共患率的神经相关性和机制。遵循这一目标，我们将建立新的方法和范例来了解慢性耳鸣的发展和治疗。

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.