Functional Neuroimaging and Transcranial Magnetic Stimulation in Mal de Debarquem

描述（由申请人提供）：Mal de debarquement综合征（MdDS）是一种平衡障碍，患者在长时间被动运动暴露后出现持续的内部运动感。这是经典的描述为“landsickness”发生后乘船。患者描述了运动的幻觉，如“摇摆”和“摆动”，即使他们没有身体移动。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这种适应。大多数情况下，maldedebarquement只持续几个小时，但也有许多人谁经历的症状数月或数年，导致显着的发病率。术语MdDS通常保留给出现症状至少一个月的患者。MdDS患者的大型病例系列显示，这些患者中的大多数对视觉运动产生了深刻的敏感性，这种症状仅发生在MdDS发作期间，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脑区可能会揭示MdDS患者与正常对照之间的差异。如果这些区域存在差异，则可以通过重复经颅磁刺激（rTMS）进行外部调制。虽然仍处于实验阶段，但rTMS已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。耳鸣的研究表明，听觉皮层中有一个基线活动增强的区域，这种活动可以用rTMS抑制。这项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差异。在此任务上确定的阈值将被用作fMRI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接收视觉和前庭信息的运动敏感区域MT+/V5。MT+/V5将作为假手术对照1Hz rTMS治疗设计中的目标。我们希望揭示MdDS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。 公共卫生相关性：Mal de Debarquement综合征（MdDS）是一种未被充分认识的平衡控制障碍，发生在被动运动暴露后，例如在游轮，飞机或长途汽车上。它导致严重的发病率，并且仍然没有治愈方法或关于基本病理生理学的知识。由于这种疾病是一种对自我运动的幻肢感知，并且有临床证据表明视觉运动处理可能受到影响，因此我们假设处理视觉和前庭信息的大脑区域可能受到影响。如果在评估视觉运动感知的心理物理任务和功能性神经成像中的大脑激活模式的表现中可以看到差异，那么差异激活的区域可能是经颅磁刺激（TMS）治疗的目标。经颅磁刺激对MdDS的应用被提出作为这种疾病的一种新的治疗方法，其原理与其他适应不良的皮质重组疾病相同。

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.