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Identification of the neurophysiological basis of central tinnitus

中枢性耳鸣的神经生理学基础的识别

基本信息

批准号：
332767752
负责人：
Professor Dr. Holger Schulze
金额：
--
依托单位：
Hals-Nasen-Ohren-Klinik, Kopf- und Halschirurgie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/332767752?language=en
关键词：
Identification neurophysiological basis central tinnitus

项目摘要

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.

中枢性耳鸣是一种没有任何外部声音刺激的声音感知，是一种患病率越来越高的疾病，影响了高达15%的成年人。严重的情况下，耳鸣会影响人的正常生活，有时甚至会导致自杀的危险。然而，这种耳鸣仍然没有治愈的方法。尽管在世界范围内进行了广泛的研究，但神经元处理的哪些方面实际上是这种现象的基础，仍然是难以捉摸的。关于导致耳鸣的神经元机制，目前讨论了许多不同的模型，这些模型都有一个共同点，即耳蜗外周受体上皮的损伤是耳鸣发展的病因学原因，而中枢听觉系统内的神经可塑性改变被认为最终导致听觉皮层内神经元加工的改变，从而被认为是耳鸣。基于我们的初步数据，我们假设反映耳鸣的神经元活动在听觉皮层内以吸引子样的时空活动模式为特征。为了描述这些吸引子，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单位尖峰序列，并通过自主开发的新的统计方法来分析这些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（由噪音创伤引起并在行为和电生理学上进行评估），在沉默期间可以在初级听觉皮层中测量到的神经元吸引子应该转移到具有相同感知质量的刺激表示的位置（在抽象的n维状态空间中，其中n等于记录通道的数量）。通过引入一种新的行为测试，我们的实验动物耳鸣感知检测的可靠性将进一步提高。我们进一步的目标是证明这些吸引子是行为相关的。为此，我们进一步假设两个给定刺激的知觉可判别性取决于它们各自吸引子表征的统计可判别性。为了评估这一假设，我们将记录上述动物进行声音识别范式（穿梭箱训练）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。在后续的建议中，基于本项目的发现，我们将制定适当的训练策略，可用于系统地改变多维状态空间中的吸引子，从而改变它们的感知质量。这些技术将用于开发新的治疗策略，以治疗耳鸣或甚至其他幻觉。