Collaborative Tinnitus Research at Washington University

描述（由申请人提供）：慢性失能性主观性耳鸣是大量美国人的一个重要问题。神经影像学研究表明，这种耳鸣与多种皮层区域的过度活跃有关，特别是听觉皮层和中颞叶区域。重复经颅磁刺激（rTMS）是指对颅骨进行频繁、重复的磁刺激，以诱发大脑皮层底层的电活动。在低频（1hz）刺激下，rTMS导致中枢神经系统中谷氨酰胺能纤维抑制活性的增加。rTMS似乎是一种新颖而有前途的耳鸣治疗方式，因为它可能能够平息最近通过神经影像学发现的导致耳鸣的过度活跃的皮层区域。研究者对6名受试者进行了PET扫描和rTMS的初步研究。在6名受试者中，3名报告耳鸣障碍量表（THI）降低20分或更高。当被问及他们是否会向朋友推荐rTMS治疗时，4名患者的反应是积极的（“可能会”或“肯定会”）。本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，并全面评估是否存在患者和临床因素可以预测结果。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改变。本项目有三个具体目的：1)评估rTMS治疗主观性特发性麻烦性耳鸣的疗效。我们将采用单盲交叉随机试验设计，对主动与假性rTMS进行比较。入组55名受试者；样本量将确保足够的力量来检测治疗之间的临床有意义的差异，定义为THI评分20分的变化。在治疗前后，将包括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)探讨重度耳鸣患者对rTMS治疗反应的预测因素及相关因素。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PET扫描结果以及rTMS治疗后这些因素的某些变化是rTMS反应的预测因子。3)确定一种更可能对rTMS有反应的独特耳鸣患者表型。假设我们将能够确定某些患者因素、听力学测量、临床特征和神经认知因素，这些因素可以用来确定更可能从rTMS中获益的患者。本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，因为所有受试者在基线、假手术后和积极治疗后都将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.