Identification of the neurophysiological basis of central tinnitus

中枢性耳鸣，即在没有任何外部声学刺激的情况下感知声音，是一种发病率越来越高的疾病，影响到高达15%的成年普通人口。在严重的情况下，耳鸣会影响一个人S的正常生活能力，有时还会导致自杀的危险。尽管如此，这种耳鸣仍然没有治愈方法。尽管在世界范围内进行了广泛的研究，但仍然难以捉摸神经元处理的哪些方面实际上是这种现象的基础。目前关于导致耳鸣的神经机制有许多不同的模型，它们都有一个共同点，即耳蜗外周感受器上皮细胞的损伤是导致耳鸣发生的原因，而中枢听觉系统内的不适应神经可塑性变化被认为最终导致听觉皮质内神经元处理的改变，然后被认为是耳鸣。基于我们的初步数据，我们假设反映耳鸣的神经元活动是以听觉皮质内的吸引子样时空活动模式为特征的。为了描述这种吸引子，我们将使用多通道微电极阵列测量清醒行为动物的局部场电位和单位棘波序列，并利用自行开发的新的统计方法来分析这种模式的时空活动模式。根据我们的假设，在主观耳鸣发展的情况下(这是由噪声创伤引起的，并从行为和电生理方面进行了评估)，在安静期间在初级听觉皮质可以测量到的神经元吸引子应该转移到代表具有相同知觉质量的刺激的位置(在抽象的n维状态空间内，其中n等于记录通道的数量)。通过引入一种新的行为测试，在我们的实验动物中检测到耳鸣的可靠性将进一步提高。我们的进一步目标是证明这种吸引子与行为相关。为此，我们进一步假设，两个给定刺激的感知可区分性取决于它们各自的吸引子表示的统计可区分性。为了评估这一假设，我们将记录执行声学辨别范式(穿梭箱训练)的动物的神经元活动，并将行为表现与同时测量的吸引子动态进行统计比较。在后续建议中，基于该项目的发现，我们将开发适当的训练策略，可用于在多维状态空间内系统地移动吸引子，从而改变它们的感知质量。然后，这些技术将被用于开发新的治疗策略，以治疗耳鸣甚至其他幻觉。

Central tinnitus, the perception of sound without any external acoustic stimulus, is a condition with increasing prevalence affecting up to 15% of the adult general population. In severe cases, tinnitus affects a person s ability to lead a normal life, sometimes resulting in the risk of suicide. Still, there is still no cure for such tinnitus. Despite extensive research worldwide it still remains elusive which aspects of neuronal processing actually underlie the phenomenon. A number of different models about the neuronal mechanisms leading to tinnitus are currently discussed, which all have in common that damage to the peripheral receptor epithelium in the cochlea is etiological for the development of the condition, while maladaptive neuroplastic changes within the central auditory system are thought to finally lead to changed neuronal processing within the auditory cortex which then is perceived as tinnitus. Based on our preliminary data, we follow the hypothesis that neuronal activity reflecting tinnitus is characterized by attractor-like spatiotemporal activity patterns within auditory cortex.To describe such attractors, we will measure local field potentials and single-unit spike trains in awake, behaving animals using multichannel microelectrode arrays, and analyze the spatiotemporal activity patterns by means of a self-developed new statistical method for the differentiation of such patterns. According to our hypothesis, in case of subjective tinnitus development (that is induced via noise trauma and evaluated behaviorally and electrophysiologically) the neuronal attractor that can be measured in primary auditory cortex during silence should shift into the location (within an abstract n-dimensional state space, where n equals the number of recording channels) where the stimulus with the same perceptual quality is represented. The reliability of the detection of a tinnitus percept in our experimental animals will be further improved by introducing a new behavioral test.We further aim to demonstrate that such attractors are behaviorally relevant. To this end, we further hypothesize that the perceptual discriminability of two given stimuli depends on the statistical discriminability of their respective attractor representations. To evaluate this hypothesis we will record neuronal activity as described above in animals performing an acoustic discrimination paradigm (shuttle-box training), and statistically compare behavioral performance with simultaneously measured attractor dynamics.In a follow-up proposal, based on the findings of this project, we will develop appropriate training strategies that can be used to systematically shift the attractors within the multi-dimensional state space, thereby changing their perceptual quality. Such techniques will then be used for the development of new therapeutic strategies to treat tinnitus or even other phantom percepts.