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

描述（由申请人提供）：脊椎动物眼动积分器负责通过以与眼睛位置成比例的稳定神经活动速率驱动眼外运动核来稳定所有眼睛位置处的凝视。这个系统的紊乱可以表现为眼球震颤。积分器通过保持精确调谐的神经反馈水平来实现稳定性。这种程度的反馈可以通过实验来操纵--整合器已经被证明在人类的视觉-前庭冲突中表现出短期的可塑性。在金鱼中，可以单独使用视觉反馈，通过实时调整视动刺激的速度作为水平眼睛位置的函数来诱导泄漏或不稳定的神经积分器。本研究的主要目的是将这种方法扩展到人类。本文的初步数据支持这一假设，即人类的眼动力学操纵纯粹的视觉反馈。通过红外眼动跟踪技术测量眼球位置，并控制计算机驱动的视动刺激的水平速度，我们已经能够在一个小样本的正常人受试者中引起泄漏和不稳定。目前的提案旨在扩展这些发现，并广泛描述人类中的这种现象。第一组实验将比较几种不同的视动训练范式在产生所观察到的可塑性方面的功效。在这样做时，将阐明影响和恢复的时间过程。随后的实验将评估效果的可重复性，并确定恢复对稳定视觉反馈的依赖性。最后，我们将对实时视觉反馈参数进行更精细的调整，试图以比简单地诱导泄漏或不稳定更详细的方式来塑造积分器动态。这条研究路线的目的是双重的。在临床上，希望这项研究中揭示的原则可以适用于改变眼震患者的神经整合性能。凝视诱发型和摆动型眼球震颤最初可能是最容易处理的，因为这些形式的眼球位置和漂移速度之间有最可靠的关系。从机制上讲，金鱼积分器研究的人类相关性最近得到了支持，比较高分辨率的眼动测量在2个物种。这些测量揭示了他们的眼神经系统之间高度的定量相似性，这是令人惊讶的，因为他们的视觉系统之间存在巨大差异。在人类身上重复金鱼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，这些研究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.