Collaborative Tinnitus Research at Washington University

描述（由申请人提供）：慢性失能性主观耳鸣是一个重要的问题，为大量的美国人。神经影像学研究表明，耳鸣与各种皮质区域的过度活跃有关，特别是听觉皮质和中颞区。重复经颅磁刺激（rTMS）涉及对颅骨施加频繁、重复的磁刺激，以诱导大脑底层皮层区域的电活动。在低频（1 Hz）刺激下，据信rTMS导致CNS中多巴胺能纤维的抑制活性增加。rTMS似乎是一种新的和有前途的治疗耳鸣的方式，因为它可能能够安静的过度活跃的皮质区最近通过神经成像，有助于耳鸣确定。研究者的初步研究包括6名受试者的PET扫描和rTMS。在6例受试者中，3例报告耳鸣障碍量表（THI）降低20分或以上。当被问及他们是否会向朋友推荐rTMS治疗时，4名患者的回答是肯定的（“可能是”或“肯定是”）。这个合作研究项目的总体目标是评估rTMS在大量耳鸣患者中的有效性，并彻底评估是否有患者和临床因素是结果的预测因素。我们还将评估是否存在与rTMS治疗相关的患者、临床、神经认知和神经影像学变化。本课题的具体目的有三：1）评价rTMS治疗主观性特发性耳鸣的疗效。我们将采用活性与假rTMS的单盲交叉随机试验设计。入组将包括55例受试者;样本量将确保有足够的把握度检测治疗之间有临床意义的差异，定义为THI评分变化20分。将纳入治疗前后的各种神经认知功能测试，以评估rTMS对认知和执行功能是否有任何显著的不良影响。2)确定重度耳鸣患者对rTMS治疗反应的预测因素和相关因素。假设存在某些患者因素、听力学测量、临床特征、神经认知特征和基线时的PET扫描结果以及rTMS治疗后这些因素的某些变化，这些因素是rTMS反应的预测因子。3)为了确定一个独特的耳鸣患者表型，更有可能响应rTMS的假设是，我们将能够确定某些患者因素，听力学措施，临床特征和神经认知因素，可用于确定患者更有可能受益于rTMS。这项合作研究项目完成后，将获得有关rTMS治疗耳鸣疗效的新知识。这项研究是独一无二的，因为所有受试者都将在基线、假手术后和活性治疗后进行全面的神经认知测试和PET扫描成像。

DESCRIPTION (provided by applicant): Chronic incapacitating subjective tinnitus is a significant problem for a large number of Americans. Neuroimaging studies have shown such tinnitus to be associated with hyperactivity of a variety of cortical regions, especially the auditory cortices and middle temporal regions. Repetitive transcranial magnetic stimulation (rTMS) involves the application of frequent, repeated magnetic stimuli to the skull to induce electrical activity in the underlying cortical areas of the brain. At low-frequency (1 Hz) stimulation, it is believed that rTMS leads to an increase in the inhibitory activity of glutaminergic fibers in the CNS. rTMS seems to be a novel and promising treatment modality for tinnitus as it may be able to quiet the hyperactive cortical areas recently identified through neuroimaging that contribute to tinnitus. Preliminary research by the investigators included PET scan and rTMS for 6 subjects. Of the 6 subjects, 3 reported a 20-point reduction or greater in the Tinnitus Handicap Inventory (THI). When asked if they would recommend rTMS treatment to a friend, 4 patients responded favorably ("maybe yes" or "definitely yes"). The Overall Goal in this collaborative research project is to assess the effectiveness of rTMS in a large number of tinnitus patients and to thoroughly assess whether there are patient and clinical factors that are predictors of outcome. We will also assess whether there are patient, clinical, neurocognitive, and neuroimaging changes associated with rTMS treatment. There are three Specific Aims to this project: 1) To assess the therapeutic benefit of rTMS for subjective idiopathic troublesome tinnitus. We will employ a single-blind cross-over randomized trial design of active vs. sham rTMS. Enrollment will consist of 55 subjects; the sample size will ensure sufficient power to detect a clinically meaningful difference between treatments, defined as 20-point change in the THI score. A variety of neurocognitive function tests, before and after treatment, will be included to assess whether there are any significant adverse effects of rTMS on cognition and executive function. 2) To identify predictors and correlates of response to rTMS therapy for patients with severe tinnitus. The hypothesis is that there are certain patient factors, audiological measures, clinical features, neurocognitive features, and PET scan findings at baseline and certain changes in these factors after rTMS treatment that are predictors of response to rTMS. 3) To identify a unique tinnitus patient phenotype that is more likely to respond to rTMS The hypothesis is that we will be able to identify certain patient factors, audiological measures, clinical features, and neurocognitive factors that can be used to identify patients more likely to benefit from rTMS. Upon completion of this collaborative research project, new knowledge will be gained about the efficacy of rTMS for tinnitus. This study is unique since all subjects will have thorough neurocognitive testing and PET scan imaging at baseline, after sham, and after active treatment.