Dits Joyce, Houben Mark M J, van der Steen Johannes
Department of Neuroscience, Erasmus MC.
J Vis Exp. 2013 May 23(75):e4144. doi: 10.3791/4144.
The vestibular organ is a sensor that measures angular and linear accelerations with six degrees of freedom (6DF). Complete or partial defects in the vestibular organ results in mild to severe equilibrium problems, such as vertigo, dizziness, oscillopsia, gait unsteadiness nausea and/or vomiting. A good and frequently used measure to quantify gaze stabilization is the gain, which is defined as the magnitude of compensatory eye movements with respect to imposed head movements. To test vestibular function more fully one has to realize that 3D VOR ideally generates compensatory ocular rotations not only with a magnitude (gain) equal and opposite to the head rotation but also about an axis that is co-linear with the head rotation axis (alignment). Abnormal vestibular function thus results in changes in gain and changes in alignment of the 3D VOR response. Here we describe a method to measure 3D VOR using whole body rotation on a 6DF motion platform. Although the method also allows testing translation VOR responses (1), we limit ourselves to a discussion of the method to measure 3D angular VOR. In addition, we restrict ourselves here to description of data collected in healthy subjects in response to angular sinusoidal and impulse stimulation. Subjects are sitting upright and receive whole-body small amplitude sinusoidal and constant acceleration impulses. Sinusoidal stimuli (f = 1 Hz, A = 4°) were delivered about the vertical axis and about axes in the horizontal plane varying between roll and pitch at increments of 22.5° in azimuth. Impulses were delivered in yaw, roll and pitch and in the vertical canal planes. Eye movements were measured using the scleral search coil technique (2). Search coil signals were sampled at a frequency of 1 kHz. The input-output ratio (gain) and misalignment (co-linearity) of the 3D VOR were calculated from the eye coil signals (3). Gain and co-linearity of 3D VOR depended on the orientation of the stimulus axis. Systematic deviations were found in particular during horizontal axis stimulation. In the light the eye rotation axis was properly aligned with the stimulus axis at orientations 0° and 90° azimuth, but gradually deviated more and more towards 45° azimuth. The systematic deviations in misalignment for intermediate axes can be explained by a low gain for torsion (X-axis or roll-axis rotation) and a high gain for vertical eye movements (Y-axis or pitch-axis rotation (see Figure 2). Because intermediate axis stimulation leads a compensatory response based on vector summation of the individual eye rotation components, the net response axis will deviate because the gain for X- and Y-axis are different. In darkness the gain of all eye rotation components had lower values. The result was that the misalignment in darkness and for impulses had different peaks and troughs than in the light: its minimum value was reached for pitch axis stimulation and its maximum for roll axis stimulation.
Nine subjects participated in the experiment. All subjects gave their informed consent. The experimental procedure was approved by the Medical Ethics Committee of Erasmus University Medical Center and adhered to the Declaration of Helsinki for research involving human subjects. Six subjects served as controls. Three subjects had a unilateral vestibular impairment due to a vestibular schwannoma. The age of control subjects (six males and three females) ranged from 22 to 55 years. None of the controls had visual or vestibular complaints due to neurological, cardio vascular and ophthalmic disorders. The age of the patients with schwannoma varied between 44 and 64 years (two males and one female). All schwannoma subjects were under medical surveillance and/or had received treatment by a multidisciplinary team consisting of an othorhinolaryngologist and a neurosurgeon of the Erasmus University Medical Center. Tested patients all had a right side vestibular schwannoma and underwent a wait and watch policy (Table 1; subjects N1-N3) after being diagnosed with vestibular schwannoma. Their tumors had been stabile for over 8-10 years on magnetic resonance imaging.
前庭器官是一种能测量六个自由度（6DF）角加速度和线加速度的传感器。前庭器官的完全或部分缺陷会导致轻度至重度的平衡问题，如眩晕、头晕、视振荡、步态不稳、恶心和/或呕吐。一种常用且有效的量化注视稳定的方法是增益，它被定义为补偿性眼动相对于施加的头部运动的幅度。为了更全面地测试前庭功能，必须认识到三维前庭眼反射（3D VOR）理想情况下不仅会产生幅度（增益）与头部旋转相等且相反的补偿性眼球旋转，而且旋转轴与头部旋转轴共线（对齐）。因此，异常的前庭功能会导致3D VOR反应的增益变化和对齐变化。在这里，我们描述一种使用六自由度运动平台上的全身旋转来测量3D VOR的方法。尽管该方法也允许测试平移VOR反应（1），但我们仅限于讨论测量3D角VOR的方法。此外，我们在此仅限于描述健康受试者在角正弦和脉冲刺激下收集的数据。受试者直立坐着，接受全身小幅度正弦和恒定加速度脉冲。正弦刺激（f = 1 Hz，A = 4°）围绕垂直轴以及在水平面内围绕从横滚到俯仰以22.5°方位角增量变化的轴进行。脉冲在偏航、横滚和俯仰以及垂直半规管平面中施加。使用巩膜搜索线圈技术（2）测量眼动。搜索线圈信号以1 kHz的频率采样。根据眼线圈信号计算3D VOR的输入输出比（增益）和未对准（共线性）（3）。3D VOR的增益和共线性取决于刺激轴的方向。特别是在水平轴刺激期间发现了系统偏差。在明视觉下，眼旋转轴在方位角0°和90°时与刺激轴正确对齐，但逐渐越来越偏向45°方位角。中间轴未对准的系统偏差可以通过扭转（X轴或横滚轴旋转）增益低和垂直眼动（Y轴或俯仰轴旋转）增益高来解释（见图2）。因为中间轴刺激会导致基于各个眼旋转分量矢量求和的补偿反应，由于X轴和Y轴的增益不同，净反应轴会发生偏差。在暗视觉下，所有眼旋转分量的增益值较低。结果是，暗视觉下和脉冲刺激时的未对准与明视觉下有不同的峰值和谷值：俯仰轴刺激时达到最小值，横滚轴刺激时达到最大值。
九名受试者参与了该实验。所有受试者均已签署知情同意书。实验程序经伊拉斯姆斯大学医学中心医学伦理委员会批准，并遵循涉及人类受试者研究的《赫尔辛基宣言》。六名受试者作为对照。三名受试者因前庭神经鞘瘤导致单侧前庭功能障碍。对照受试者（六名男性和三名女性）的年龄在22至55岁之间。所有对照受试者均无因神经、心血管和眼科疾病引起的视觉或前庭主诉。患有神经鞘瘤的患者年龄在44至64岁之间（两名男性和一名女性）。所有患有神经鞘瘤的受试者均在医学监测之下和/或已接受由伊拉斯姆斯大学医学中心的耳鼻喉科医生和神经外科医生组成的多学科团队的治疗。受试患者均患有右侧前庭神经鞘瘤，在被诊断为前庭神经鞘瘤后采取了观察等待策略（表1；受试者N1 - N3）。他们的肿瘤在磁共振成像上已稳定8 - 10年以上。
