Collaborative Tinnitus Research at Washington University

描述(申请人提供)：慢性失能主观性耳鸣是一个严重的问题，对许多美国人。神经成像研究表明，这种耳鸣与各种皮质区域的过度活动有关，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，以诱导大脑皮质区的电活动。在低频(1赫兹)刺激下，rTMS被认为导致中枢谷氨酸能纤维抑制活性增加。RTMS似乎是一种新的、有前景的耳鸣治疗方法，因为它可能能够使最近通过神经成像发现的导致耳鸣的过度活跃的皮质区域安静下来。研究人员的初步研究包括对6名受试者进行PET扫描和rTMS。在6名受试者中，有3人报告耳鸣失调量表(THI)下降了20分或更多。当被问及是否会向朋友推荐rTMS治疗时，4名患者给予了肯定的回答(“可能会”或“肯定会”)。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可以预测结果。我们还将评估与rTMS治疗相关的患者、临床、神经认知和神经影像方面的变化。本项目有三个具体目标：1)评价rTMS治疗主观性特发性难治性耳鸣的疗效。我们将采用单盲交叉随机试验设计，比较主动和假rTMS。登记将由55名受试者组成；样本大小将确保有足够的能力检测治疗之间有临床意义的差异，定义为THI分数的20分变化。治疗前后的各种神经认知功能测试将包括在内，以评估rTMS对认知和执行功能是否有任何显著的不利影响。2)明确重度耳鸣患者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、听力测量、临床特征、神经认知特征和PET扫描结果，以及rTMS治疗后这些因素的某些变化，这些因素可以预测rTMS的反应。3)为了确定耳鸣患者更有可能对rTMS有反应的独特表型，假设我们将能够识别某些患者因素、听力测量、临床特征和神经认知因素，这些因素可以用来识别更有可能从rTMS受益的患者。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、假手术后和积极治疗后进行彻底的神经认知测试和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.