Neural Mechanisms of Motion Sickness

描述(申请人提供)：晕动病，被定义为恶心，呕吐，定向障碍和与受试者或周围视觉环境运动相关的症状，可通过受试者绕垂直重力轴旋转(非垂直轴旋转，OVAR)或受试者绕垂直轴高速旋转(RWR)而引起。在这两种刺激下，晕车都会加剧，直到达到无法忍受的恶心程度，最终导致呕吐。受试者在OVAR期间旋转的次数或在RWR期间头部在达到无法忍受的恶心之前的移动次数是衡量晕动病易感性的指标。提出了一个模型，在该模型中，运动病的发展是通过中央前庭系统中称为速度存储的过程的方向和时间特性来调节的。在这个模型中，晕动病是通过响应旋转的速度存储产生的眼睛运动方向和与速度存储相关的方向向量之间的差异来激活的。这个方向向量靠近重力垂线。我们认为，OVAR过程中速度存储矢量和方向矢量(重力直立)之间的长期差异是OVAR过程中绕倾斜轴旋转或RWR过程中头部运动所产生的，从而导致运动病的发生。在这项拟议的研究中，我们将使用OVAR和RWR来表征运动病的空间和时间演变，以在正常受试者中测试该模型，并确定服用巴氯芬是否也降低了运动病的易感性。巴氯芬是一种缩短速度储存反应持续时间的药物。使用OVAR和RWR，我们还将测试小脑结节和悬垂变性患者的运动病敏感性，这些患者在旋转过程中无法再将眼速定向到重力垂直方向。最后，我们将开发治疗干预措施，以缩短前庭反应的持续时间。我们认为，这也将通过非药物手段降低晕动病的易感性。这项研究应该能够更好地了解导致晕动病的机制，并提供新的治疗措施来降低晕动病的易感性，这可能会缓解一系列患有晕动病的对象。

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.