Brain changes in tinnitus

耳鸣的大脑变化

基本信息

批准号：
7933869
负责人：
JOSEF P RAUSCHECKER
金额：
$ 33.91万
依托单位：
GEORGETOWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-17 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7933869
关键词：
Acetylcysteine Acoustic Nerve Adult Affect Aging American Animals Area Arousal Attention Auditory Auditory area Auditory system Blindness Brain Brain Injuries Central Hearing Loss Cochlea Cognitive Development Devices Disease Esthesia Face Frequencies Functional Magnetic Resonance Imaging Generations Geniculate body structure Goals Hair Cells Hand Human Image Inferior Colliculus Intervention Lead Lesion Magnetic Resonance Imaging Maps Measurable Measurement Medial Methods Modeling Neurons Noise Nucleus Accumbens Ocular Prosthesis Pathway interactions Patients Perception Peripheral Physiological Population Process Psychophysiology Rehabilitation therapy Research Resolution Role Scanning Self-Help Devices Sensory Sensory Process Signal Transduction Sleep Deprivation Somatosensory Cortex Stimulus Stress Structure System Testing Thalamic Nuclei Thalamic structure Time Tinnitus Touch sensation Ventral Striatum auditory pathway base blind experience gray matter hearing impairment morphometry neuromechanism neuropsychological prevent rehabilitation strategy research study response sensory system somatosensory sound transmission process

项目摘要

DESCRIPTION (provided by applicant): Tinnitus, a mostly whistling, buzzing, or hissing phantom sound perceived in the absence of a corresponding external stimulus, is perceived by about 15% of the adult population, and about 75% of all patients with hearing loss. It can cause severe suffering, and to date, no reliable cure has been found. The causes of tinnitus are still poorly understood. The fact that it persists after section of the auditory nerve indicates that its origin lies within the central auditory system. Based on previous research on tinnitus and somatosensory phantom perception in humans and animals, our hypotheses about tinnitus generation are as follows. Damage to the auditory periphery (e.g. as a consequence of loud-noise exposure or aging), which does not even have to manifest itself in a measurable hearing loss, causes some central auditory neurons to lose their input. It is known from research on somatosensory phantom sensations that brain areas that have lost their input due to peripheral damages start responding to stimuli that are normally processed in adjacent areas. We assume that, just like the area of somatosensory cortex that previously processed sensory input from a now amputated hand, starts responding to touches on the face (which are normally processed in an adjacent area of somatosensory cortex), the areas of auditory cortex affected by hearing loss start responding to hearing-loss edge frequencies. This assumption is corroborated by the fact that psychophysical experiments on patients with hearing loss have shown that sensitivity for edge frequencies increases. The resulting imbalance in neuronal activity is mistakenly interpreted as a sound signal - the tinnitus. As not all patients with hearing loss perceive tinnitus, we assume that activity in extra-auditory structures can regulate neuronal auditory activity and prevent tinnitus perception. A likely candidate for such a structure is the paralimbic nucleus accumbens. This part of the ventral striatum has excitatory connections to the reticular thalamic nucleus (RTN), which in turn can inhibit the medial geniculate nucleus (MGN), the thalamic relay between the inferior colliculus and the auditory cortex assumed to be involved with the direction of attention. In tinnitus patients, NAc gray-matter volume is significantly reduced compared to healthy controls. It seems plausible to assume that the volume- reduced NAc of tinnitus patients cannot exert the inhibition necessary to block the excessive activation that ultimately gives rise to the tinnitus percept. It speaks in favor of the assumption of a connection between tinnitus and the NAc that both tinnitus and activity in the subcallosal area (including the NAc) are modulated by stress, arousal, and sleep deprivation. The aims of the proposed research are 1) to provide direct evidence for reorganization of tonotopic maps in central auditory structures by means of high-resolution functional MRI, both in tinnitus patients and in patients matched for hearing loss who do not perceive tinnitus, and 2) to investigate the role of the NAc in tinnitus by a. comparing NAc volume in tinnitus patients and patients matched for hearing loss who do not perceive tinnitus, using high-resolution structural MRI and voxel-based morphometry, and b. comparing, by means of high-resolution functional MRI, activation in central auditory structures and the NAc of patients with intermittent tinnitus in periods during which they do perceive tinnitus and periods during which they do not. Our predictions are that we will find reorganization of tonotopic maps in all patients with hearing loss, but reduced NAc volume and activity only in patients who do (at the time of measurement) perceive tinnitus. These results would guide tinnitus research into a new direction and open up a new point of intervention by emphasizing the modulatory role of extra-auditory structures responsible for the direction of attention.

描述（由申请人提供）：在没有相应的外部刺激的情况下感知的大多数吹口哨，嗡嗡声或嘶嘶的幻影声音，大约有15％的成人人群所感知，所有大约75％的听力损失患者中有75％。它可能会造成严重的痛苦，迄今为止，尚未发现可靠的治愈方法。耳鸣的原因仍然很少了解。它在听觉神经的一部分之后持续存在的事实表明其起源在于中央听觉系统内。基于先前关于人类和动物的耳鸣和体感幻影感知的研究，我们对耳鸣产生的假设如下。对听觉外围的损害（例如，由于响亮的接触或衰老而导致的，甚至不必在可测量的听力损失中表现出来，这会导致一些中央听觉神经元失去输入。从对体感幻象感觉的研究中可以知道，由于周围损伤而失去输入的大脑区域开始对通常在相邻区域进行处理的刺激作出反应。我们假设，就像先前从现在截肢的手中处理的感觉输入的体感皮层区域一样，开始对脸部的触摸（通常在体感皮质的相邻区域进行处理），这是受听觉皮层的区域的影响。听力损失开始响应听力损失的边缘频率。通过对听力损失患者进行心理物理实验的事实证实了这一假设，表明对边缘频率的敏感性增加。神经元活性中产生的不平衡被错误地解释为声音信号 - 耳鸣。并非所有听力损失感知耳鸣的患者，我们假设经常性结构中的活性可以调节神经元的听觉活动并防止耳鸣感知。这种结构的可能候选者是旁皮核伏隔核。腹侧纹状体的这一部分具有与网状丘脑核（RTN）的兴奋性连接，进而可以抑制内侧基因化核（MGN），丘脑下丘和听觉皮层之间的丘脑继电器与假定与听觉的皮质之间的相关性有关注意力。在耳鸣患者中，与健康对照组相比，NAC灰质体积显着减少。假设耳鸣患者的NAC的体积减小似乎不能施加抑制作用，以阻止过度激活最终导致耳鸣感知所必需的抑制作用，这似乎是合理的。它支持假设耳鸣与NAC之间的联系，即在亚易膜区域（包括NAC）中的耳鸣和活动都受到压力，唤醒和睡眠剥夺的调节。拟议的研究的目的是1）通过高分辨率功能性MRI，在中央听觉结构中为中央听觉结构重组的直接证据，无论是在耳鸣患者中，以及与不感知听力损失的患者匹配的患者，以及2个不感染耳鸣的听力损失，）研究NAC在耳鸣中的作用。比较使用高分辨率的结构MRI和基于体素的形态计量学和b，比较了耳鸣患者和与听力损失相匹配的患者的NAC体积。通过高分辨率功能性MRI进行比较，中央听觉结构的激活和间歇性耳鸣患者的NAC在此期间会感知耳鸣和没有的时期。我们的预测是，我们会发现所有听力损失患者的Tonotopic图的重组，但仅在（测量时）感知耳鸣的患者中，NAC的体积和活动降低。这些结果将指导耳鸣研究迈向一个新的方向，并通过强调负责关注方向的外审计结构的调节作用来开辟新的干预点。