Functional Neuroimaging and Transcranial Magnetic Stimulation in Mal de Debarquem

描述（由申请人提供）：失稳综合征（MdDS）是一种平衡障碍，患者在长时间的被动运动暴露后出现持续的内部运动感。这通常被描述为乘船后发生的“晕船”。患者描述了一种运动幻觉，如“摇摆”和“摇摆”，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，因为内耳功能测试和脑结构成像总是正常的。然而，尚不清楚大脑的哪个部分控制这种适应。大多数情况下，精神错乱只持续几个小时，但也有许多人经历了几个月或几年的症状，导致严重的发病率。MdDS一词通常用于出现症状至少一个月的患者。大量MdDS患者的病例系列表明，这些患者中的大多数对视觉运动具有高度敏感性，这一症状仅在MdDS发作期间发生，可能是该综合征的关键组成部分。因此，研究对视觉和前庭刺激均有反应的大脑区域可能会揭示MdDS患者与正常对照之间的差异。如果在这些区域存在差异，活动可以通过重复经颅磁刺激（rTMS）进行外部调节。虽然rTMS仍处于实验阶段，但它已被用于治疗许多以适应不良反应为特征的疾病，最明显的是重度抑郁症、慢性疼痛和耳鸣。对耳鸣的研究表明，听觉皮层中有一个区域的基线活动增强，而这种活动可以通过rTMS来抑制。本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能力的差异。在这项任务中确定的阈值将被用作fMRI范式中的刺激参数，该范式旨在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域MT+/V5，该区域接收视觉和前庭信息。MT+/V5将作为假控1Hz rTMS治疗设计的靶标。我们希望揭示MdDS中大脑活动的功能差异，并能够为这种目前无法治愈的疾病引入一种新的治疗方式。

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.