Functional Neuroimaging and Transcranial Magnetic Stimulation in Mal de Debarquem

描述(申请人提供)：Mal de Debarquement综合征(MdDS)是一种平衡障碍，患者在长时间的被动运动暴露后会发展出持续的内在运动感。这被经典地描述为在乘船后发生的“晕船”。病人描述了一种幻觉的运动，如“摇摆”和“上下摆动”，即使他们没有身体上的运动。这种疾病被认为是由于大脑适应的主要问题，因为内耳功能和结构脑成像的测试总是正常的。然而，目前还不清楚大脑的哪些部分控制着这种适应。大多数病例只持续几个小时，但也有许多人会经历几个月或几年的症状，导致显著的发病率。术语MDDS通常用于出现症状至少一个月的患者。一大批MDDS患者的病例系列显示，这些患者中的大多数对视觉运动高度敏感，这一症状只在他们的MDDS发作期间发生，可能是这种综合征的关键组成部分。因此，研究对视觉和前庭刺激都有反应的大脑区域可能会发现MDDS患者和正常对照组之间的差异。如果这些区域存在差异，可以通过重复的经颅磁刺激(RTMS)从外部调节活动。虽然仍处于实验阶段，但rTMS已被用于治疗许多以适应不良反应为特征的疾病，最显著的是严重抑郁、慢性疼痛和耳鸣。关于耳鸣的研究表明，在听觉皮质中有一个基线活动增强的区域，这种活动可以被rTMS抑制。这项拨款中建议的研究将首先评估在基于计算机的运动检测任务中检测视觉运动的能力的差异。在这项任务中确定的阈值将被用作功能磁共振成像范例中的刺激参数，该范例试图激活检测视觉运动的大脑区域。将被激活的主要区域是运动敏感区MT+/V5，它同时接收视觉和前庭信息。MT+/V5将作为假控制1赫兹rTMS治疗设计的靶点。我们希望揭示MDDS患者大脑活动的功能差异，并能够引入一种新的治疗方法来治疗这种目前无法治愈的疾病。 与公共卫生相关：Mal de Debarquement综合征(MdDS)是一种在被动运动暴露后(如在邮轮、飞机或长途汽车旅行中)发生的一种未被认识的平衡控制障碍。它会导致严重的发病率，并且仍然没有治愈方法或基本的病理生理学知识。由于这种障碍是一种幻觉的自我运动知觉，而且有临床证据表明视觉运动处理可能会受到影响，我们假设处理视觉和前庭信息的大脑区域可能会受到影响。如果可以看到评估视觉运动知觉的心理物理任务的表现和功能神经成像中大脑激活模式的差异，那么差异激活区域可能是经颅磁刺激(TMS)治疗的靶点。TMS在MDDS中的应用被认为是一种治疗这种疾病的新方法，其原理与其他适应不良的皮质重组障碍相同。

DESCRIPTION (provided by applicant): Mal de debarquement syndrome (MdDS) is a balance disorder in which patients develop a persistent internal sense of movement after a prolonged period of passive motion exposure. This is classically described as "landsickness" occurring after boat rides. Patients describe a hallucination of movement such as "rocking" and "bobbing" even though they are not physically moving. This disorder is thought to be due to a primary problem of brain adaptation as testing of inner ear function and structural brain imaging is always normal. However, it is unknown which parts of the brain control this adaptation. Most cases of mal de debarquement only last a few hours, but there are many people who experience the symptoms for months or years, leading to significant morbidity. The term MdDS is generally reserved for patients who experience symptoms for at least one month. A large case series of patients with MdDS showed that the majority of these patients develop profound sensitivity to visual motion, a symptom which only occurs during their MdDS attacks and may be a key component of this syndrome. Therefore, investigating brain areas that respond to both visual and vestibular stimuli may reveal differences between patients with MdDS and normal controls. If there are differences in such areas, the activity may be modulated externally with repetitive transcranial magnetic stimulation (rTMS). Though still in the experimental phases, rTMS has been used in the treatment of many disorders characterized by maladaptive responses, most notably major depression, chronic pain, and tinnitus. Studies on tinnitus show that there is an area of heightened baseline activity in the auditory cortex and that this activity can be dampened with rTMS. The proposed studies in this grant will first assess differences in the ability to detect visual motion in a computer based motion detection task. The threshold values determined on this task will be used as stimulation parameters in an fMRI paradigm which seeks to activate brain areas that detect visual motion. The main area that will be activated is motion sensitive area MT+/V5 which receives both visual and vestibular information. MT+/V5 will serve as a target in a sham-controlled 1Hz rTMS treatment design. We hope to reveal functional differences in brain activity in MdDS and to be able to introduce a new modality of treatment for this currently incurable disorder. PUBLIC HEALTH RELEVANCE: Mal de Debarquement Syndrome (MdDS) is an under-recognized disorder of balance control occurring after passive motion exposure such as on cruises, airplane or long car rides. It leads to significant morbidity and remains without a cure or knowledge about basic pathophysiology. Because the disorder is one of a phantom perception of self-motion and there is clinical evidence that visual motion processing may be affected, we hypothesize that brain areas that process both visual and vestibular information may be affected. If differences in the performance of psychophysical tasks that assess visual motion perception and in brain activation patterns in functional neuroimaging can be seen, then areas of differential activation may be targets for therapy with transcranial magnetic stimulation (TMS). The application of TMS to MdDS is proposed as a novel therapy for this disorder following the same rationale as other disorders of maladaptive cortical reorganization.