Cochlear Electrical Stimulation to Suppress Tinnitus in Rats

描述（由申请人提供）：许多治疗耳鸣的方法已经尝试过，包括药物，噪音掩蔽，耳鸣再训练疗法，神经和电刺激。通过人工耳蜗植入的耳蜗电刺激（CES）是一种常见的 研究的方法，由于其有前途的结果，在管理患者的耳鸣。耳蜗植入物及其语音处理器主要是为听力恢复而设计的，然而，CES并没有专门设计和用于治疗耳鸣。此外，CES诱导的耳鸣抑制的潜在机制仍不清楚。在这个项目中，我们建议开发一个大鼠模型的CES诱导的耳鸣抑制使用新的薄膜为基础的人工耳蜗装置，并调查潜在的神经机制的诱导耳鸣抑制。具体而言，在目标1中，我们将测试CES是否抑制大鼠耳鸣的行为证据，以及CES是否比听觉皮层或耳蜗核刺激诱导更强大的耳鸣抑制。此外，我们将测试不同的参数，如刺激位置（心尖刺激与基底刺激）、模式（单脉冲刺激与脉冲串刺激）、持续时间、频率和强度，以确定最佳刺激策略。目的2：通过研究脑电刺激对大鼠听觉皮层耳鸣相关神经元的影响，阐明脑电刺激抑制耳鸣的机制。具体来说，我们将确定CES诱导的耳鸣抑制是否是由耳鸣相关的过度活跃、神经同步性、爆发和听觉皮层的音调定位重组的下调引起的。开发这种动物模型将能够广泛测试刺激参数，以确定耳鸣抑制的最佳策略，并将确定外周调制是否比中枢调制更有效，以及自下而上调制是否比自上而下调制更稳健。阐明CES引起耳鸣抑制的潜在机制将提供信息，以帮助改善临床试验和耳鸣管理。我们的新型薄膜人工耳蜗将帮助我们开发针对耳鸣抑制进行优化的新型有效设备。

DESCRIPTION (provided by applicant): Numerous treatment modalities for tinnitus have been attempted, including drugs, noise-masking, Tinnitus Retraining Therapy, Neuromonics, and electrical stimulation. Cochlear electrical stimulation (CES) via cochlear implants is a frequently studied approach due to its promising results in managing patients' tinnitus. Cochlear implants and their speech processors are mainly designed for hearing restoration, however, CES has not been specifically designed and used to manage tinnitus. In addition, the underlying mechanisms of CES-induced tinnitus suppression remain unclear. In this project, we propose to develop a rat model of CES-induced tinnitus suppression using new thin-film based cochlear implant devices and to investigate the underlying neural mechanisms of the induced tinnitus suppression. Specifically, in Aim 1, we will test whether CES suppresses behavioral evidence of tinnitus in rats and whether CES induces more robust tinnitus suppression than auditory cortex or cochlear nucleus stimulation. In addition, we will test different parameters such as stimulation locations (apical vs. basal stimulation), patterns (single pulse vs. pulse train stimulation), duration, rate and intensity in order to identify optimal stimulation strategies. In Aim 2, we will elucidate the underlying mechanisms of CES-induced tinnitus suppression by investigating its induced changes in neural correlates of tinnitus in the rat auditory cortex. Specifically, we will determin whether CES-induced tinnitus suppression results from down-regulation of tinnitus-related hyperactivity, neurosynchrony, bursting, and tonotopic reorganization in the auditory cortex. Developing this animal model will enable extensive testing of stimulation parameters to identify optimal strategies for tinnitus suppression, and will determine whether peripheral modulation is more effective than central modulation and whether bottom-up modulation is more robust than top-down modulation. Elucidation of the mechanisms underlying CES-induced tinnitus suppression will provide information to help improve clinical trials and tinnitus management. Our novel thin-film-based cochlear implants will help us to develop new and effective devices optimized for tinnitus suppression.