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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.

中枢性耳鸣是一种在没有任何外部声音刺激的情况下感知声音的疾病，其患病率不断增加，影响高达15%的成年普通人群。在严重的情况下，耳鸣会影响一个人过正常生活的能力，有时会导致自杀的风险。耳鸣的危害有哪些？尽管在世界范围内进行了广泛的研究，但仍然难以理解神经元处理的哪些方面实际上是这种现象的基础。目前讨论了许多关于导致耳鸣的神经元机制的不同模型，这些模型都有一个共同点，即耳蜗外周感受器上皮细胞的损伤是该病症发展的病因，而中枢听觉系统内的适应不良的神经可塑性变化被认为最终导致听觉皮层内的神经元处理发生变化，然后被认为是耳鸣。基于我们的初步数据，我们遵循这样的假设，即反映耳鸣的神经元活动是以听觉皮层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单位锋电位序列，并利用自主开发的新的时空活动模式判别统计方法对时空活动模式进行分析。根据我们的假设，在主观耳鸣发展的情况下（即通过噪声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的神经元吸引子应该转移到表示具有相同感知质量的刺激的位置（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，我们将进一步提高在我们的实验动物中检测耳鸣吸引物的可靠性。我们的进一步目标是证明这种吸引物是行为相关的。为此，我们进一步假设，两个给定的刺激的感知辨别力取决于其各自的吸引子表示的统计辨别力。为了评估这一假设，我们将记录如上所述的动物进行声学辨别范例的神经元活动（穿梭箱训练），并统计比较行为表现与同时测量的吸引子动态。在后续建议中，基于本项目的发现，我们将开发适当的训练策略，可用于系统地转移多维状态空间内的吸引子，从而改变它们的感知质量。这些技术将被用于开发新的治疗策略来治疗耳鸣甚至其他幻觉感知。