Neural Mechanisms of Motion Sickness

描述（由申请人提供）：晕动病，定义为恶心、呕吐、定向障碍和与受试者或视觉环境运动相关的相关症状，可通过使受试者绕相对于重力垂直方向倾斜的轴旋转（偏离垂直轴旋转，OVAR）或使受试者在绕垂直轴高速旋转（RWR）时转动其头部引起。在这两种刺激过程中，晕动病会逐渐加重，直到达到无法忍受的恶心程度，最终导致呕吐。受试者在OVAR期间进行的旋转次数或在RWR期间达到无法忍受的恶心之前的头部运动次数是运动病易感性的量度。提出了一个模型，其中晕动病的发展是通过中央前庭系统中称为速度储存的过程的方向和时间特性来介导的。在该模型中，晕动病由通过响应于旋转的速度存储生成的眼睛运动的方向与与速度存储相关联的取向向量之间的差异激活。这个方向矢量接近重力垂线。我们建议，这是延长的速度存储矢量和方向矢量（重力直立）之间的差异产生的旋转绕一个倾斜的轴在OVAR或头部运动在RWR，导致运动病的发展。在拟议的研究中，我们将使用OVAR和RWR来表征晕动病的空间和时间演变，以测试正常受试者的模型，并确定巴氯芬（一种减少速度储存反应持续时间的药物）的给药是否也降低了晕动病的易感性。使用OVAR和RWR，我们还将测试小脑结节和悬雍垂退化的患者的运动病易感性，这些患者在旋转过程中不能再将他们的眼球速度定向到重力垂直方向。最后，我们将开发治疗干预措施，减少前庭反应的持续时间。我们建议，这也将导致减少晕动病的易感性，通过非药物手段。这项研究，这应该导致更好地了解导致晕动病的机制，并提供新的治疗措施，以减少晕动病的易感性，可能会导致缓解广泛的受试者患有晕动病。

DESCRIPTION (provided by applicant): Motion sickness, which is defined as nausea, vomiting, disorientation and related symptoms in association with movement of the subject or the visual surround, can be elicited by rotating subjects about an axis, tilted relative to the gravitational vertical (Off-Vertical Axis Rotation, OVAR) or by having subjects roll their heads while rotating around a vertical axis at a high velocity (RWR). During both stimuli, motion sickness builds until it reaches a level of intolerable nausea, which can culminate in vomiting. The number of rotations subjects make during OVAR or the number of head movements during RWR before reaching intolerable nausea is the measure of motion sickness susceptibility. A model is proposed in which the development of motion sickness is mediated through the orientation and temporal properties of a process in the central vestibular system known as velocity storage. In this model, motion sickness is activated by a difference between the direction of eye movements generated through velocity storage in response to rotation and the orientation vector associated with velocity storage. This orientation vector lies close to the gravitational vertical. We propose that it is the prolonged difference between the velocity storage vector and the orientation vector (gravitational upright) produced by rotation about a tilted axis during OVAR or by head movement during RWR that causes the development of motion sickness. In the proposed study we will characterize the spatial and temporal evolution of motion sickness using OVAR and RWR to test the model in normal subjects and determine whether the administration of baclofen, a drug that reduces the duration of the velocity storage response, also reduces motion sickness susceptibility. Using OVAR and RWR, we will also test the motion sickness susceptibility of cerebellar patients with degeneration of the nodulus and uvula who can no longer orient their eye velocity to the gravitational vertical during rotation. Finally, we will develop therapeutic interventions that will reduce the duration of the vestibular response. We propose that this will also cause a decrease in motion sickness susceptibility by non-pharmacological means. This research, which should lead to a better understanding of the mechanisms that cause motion sickness and provide new therapeutic measures to reduce motion sickness susceptibility, can potentially lead to relief for a wide range of subjects that suffer from motion sickness.