Plasticity of the Human Oculomotor Integrator through Real-Time Visual Feedback

描述（由申请人提供）：脊椎动物动眼肌积分器通过以与眼位成比例的稳定神经活动速率驱动眼外运动核，负责在所有眼位稳定凝视。该系统的紊乱可表现为眼球震颤。积分器通过维持精确调谐的神经反馈水平来实现稳定性。这种反馈水平可以在实验中被操纵——在人类视觉与前庭冲突的反应中，积分器显示出短期的可塑性。在金鱼中，一个有漏洞或不稳定的神经积分器可以单独使用视觉反馈来诱导，通过实时调节光动力刺激的速度作为眼睛水平位置的函数。本研究的主要目的是将这种方法推广到人类身上。这里的初步数据支持假设，即人类的动眼力是由纯视觉反馈操纵的。通过红外眼动追踪技术测量眼球位置，并控制计算机驱动的光动力刺激的水平速度，我们已经能够在一小部分正常人类受试者中引起泄漏和不稳定。目前的建议旨在扩展这些发现，并在人类中广泛表征这种现象。第一组实验将比较几种不同的光动力训练模式对产生观察到的可塑性的有效性。在此过程中，将阐明效果和恢复的时间过程。随后的实验将评估效果的可重复性，并确定恢复对稳定的视觉反馈的依赖。最后，我们将对实时视觉反馈参数进行更精细的调整，试图以更详细的方式塑造积分器动力学，而不是简单地诱导泄漏或不稳定。这项研究的目的有两个方面。在临床上，希望本研究揭示的原理可以用于改变眼球震颤患者的神经整合器功能。眼球震颤的凝视诱发型和钟摆型亚型最初可能是最容易控制的，因为这些形式在眼睛位置和漂移速度之间有最可靠的关系。从机制上讲，最近通过比较两种物种的高分辨率眼动测量结果，支持了金鱼积分研究与人类的相关性。这些测量结果揭示了它们的动眼肌系统在数量上的高度相似性，考虑到它们的视觉系统之间的巨大差异，这一点令人惊讶。在人类身上重复金鱼的可塑性实验将有助于评估正在进行的脊椎动物研究的一般相关性，旨在揭示神经整合的细胞和网络机制。

DESCRIPTION (provided by applicant): The vertebrate oculomotor integrator is responsible for stabilizing gaze at all eye positions by driving the extraocular motor nuclei with a steady rate of neural activity proportional to eye position. Disorders of this system can manifest as nystagmus. The integrator performs stability by maintaining a precisely tuned level of neural feedback. This level of feedback can be experimentally manipulated- the integrator has been shown to exhibit short-term plasticity in response to visual-vestibular conflict in humans. In the goldfish, a leaky or unstable neural integrator can be induced using visual feedback alone, by adjusting the velocity of an optokinetic stimulus in real-time as a function of horizontal eye position. The principal aim of the present study is to extend this methodology to humans. The preliminary data herein support the hypothesis that human oculomotor dynamics are manipulated by purely visual feedback. By measuring eye position with infrared eye-tracking technology and controlling the horizontal velocity of a computer-driven optokinetic stimulus, we have been able to elicit leakiness and instability in a small sample of normal human subjects. The current proposal aims to extend these findings and to broadly characterize this phenomenon in humans. The first set of experiments will compare several different optokinetic training paradigms for efficacy in producing the observed plasticity. In doing so, the time course of the effect and of recovery will be elucidated. Subsequent experiments will assess the repeatability of the effect and determine the dependence of recovery on stable visual feedback. Finally, we will make finer adjustments to the real-time visual feedback parameters in an attempt to mold integrator dynamics in a more detailed fashion than simply inducing leak or instability. The purpose of this line of research is 2-fold. Clinically, it is hoped that the principles revealed in this study can be adapted to alter neural integrator performance in patients with nystagmus. The gaze-evoked and pendular subtypes of nystagmus may be most tractable initially, since these forms have the most reliable relationship between eye position and drift velocity. Mechanistically, the human-relevance of goldfish integrator research has been recently supported by comparing high-resolution eye-movement measurements in the 2 species. These measurements reveal a high degree of quantitative similarity between their oculomotor systems, which is surprising in light of the vast differences between their visual systems. Repeating the goldfish plasticity experiments in humans will help in assessing the general relevance of ongoing vertebrate research aimed at revealing the cellular and network mechanisms of neural integration.