The mechanism for stable gaze-holding requires a neural integrator that converts pulse of neural discharge to steady firing rate. The integrator is feedback-dependent, impaired feedback manifests as either “unstable” integration when it is too much or “leaky” when it is too little. The “unstable” integrator is known to cause sinusoidal oscillations of the eyes called pendular nystagmus, whereas the “leaky” integrator causes jerky eye oscillations called gaze-evoked nystagmus. We hypothesized that integrator can be simultaneously leaky and unstable. Mechanistically, some parts of network are served by increased feedback gain (unstable network), while other part would be decreased feedback gain (leaky). Both leaky and unstable, the network converges on the ocular motor plant, leading to simultaneously present gaze-evoked jerk and sinusoidal nystagmus. We tested our hypothesis by measuring eye movements with search coil technique in 7 multiple sclerosis patients. Five of these patients had gaze-evoked nystagmus and superimposed pendular nystagmus. The gaze-evoked nystagmus depicted all the features of “leaky” integrator, that is, the drifts were always toward the null that was located at the central eye-in-orbit orientation, there were no drifts at null, and the drift velocity increased as the eyes moved farther away from the null. The pendular nystagmus had all the features of “unstable” integrator, that is, constant 4- to 6-Hz frequency, eye-in-orbit position dependence of the oscillation amplitude, and the voluntary saccade causing an oscillatory phase reset. These features were then simulated in a computational model conceptualizing our hypothesis of simultaneously leaky and unstable neural integrator.

保持稳定注视的机制需要一个神经积分器，该积分器将神经放电的脉冲转换为稳定的发射速率。积分器是依赖于反馈的，反馈过多会表现为“不稳定”的积分，而积分过多则“泄漏”。众所周知，“不稳定”积分器会引起称为正弦眼眼震颤的正弦振动，而“漏气”积分器会导致称为凝视诱发眼球震颤的眼神抖动。我们假设积分器可能同时泄漏和不稳定。从机械上讲，网络的某些部分通过增加的反馈增益（不稳定的网络）服务，而其他部分则通过减少的反馈增益（泄漏）。网络既泄漏又不稳定，网络汇聚在眼动植物上，导致同时出现凝视诱发的抽搐和正弦性眼球震颤。我们通过使用搜索线圈技术测量7名多发性硬化症患者的眼球运动来检验我们的假设。这些患者中有五名患有凝视诱发的眼球震颤和重叠的摆动眼球震颤。凝视的眼球震颤描绘了“泄漏”积分器的所有特征，即，漂移始终朝着位于中心在轨方向的零点，零点处没有漂移，并且漂移速度增加了当眼睛从零距离移开时。摆动性眼球震颤具有“不稳定”积分器的所有特征，即恒定的4至6 Hz频率，振荡幅度在眼内位置的依赖性以及导致振荡相位复位的自发扫视。