Neural Mechanisms of Motion Sickness

描述（由申请人提供）：晕动病，定义为与受试者运动或视觉环境相关的恶心、呕吐、定向障碍和相关症状，可通过使受试者绕轴旋转、相对于重力垂直方向倾斜（离垂直轴旋转，OVAR）或使受试者在绕垂直轴高速旋转时转动头部（RWR）引起。在这两种刺激下，晕动病会不断积累，直到达到无法忍受的恶心程度，最终会导致呕吐。在达到难以忍受的恶心之前，受试者在OVAR期间旋转的次数或在RWR期间头部运动的次数是衡量晕动病易感性的标准。本文提出了一种模型，其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介导的。在这个模型中，晕车是由响应旋转的速度存储和与速度存储相关的方向矢量产生的眼球运动方向之间的差异引起的。这个方向矢量靠近重力垂线。我们认为，在OVAR期间，速度存储矢量和方向矢量（重力垂直）之间的长时间差异是由围绕倾斜轴旋转或在RWR期间头部运动产生的，这导致了晕动病的发展。在本研究中，我们将使用OVAR和RWR来表征晕动病的时空演变，并在正常受试者中测试该模型，并确定服用巴氯芬（一种减少速度储存反应持续时间的药物）是否也会降低晕动病的易感性。使用OVAR和RWR，我们还将测试小脑结节和小舌变性患者在旋转过程中不能再将他们的眼球速度定位于重力垂直方向的晕动病易感性。最后，我们将开发治疗干预措施，将减少前庭反应的持续时间。我们认为这也会通过非药物手段减少晕动病的易感性。这项研究将有助于我们更好地理解晕动病的机制，并提供新的治疗措施来减少晕动病的易感性，这可能会为广大的晕动病患者带来潜在的缓解。

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.