Combining cerebral lesions & monkey fMRI for studying cortical network function

描述（由申请人提供）：中风和其他神经系统损伤给个人和社会带来了沉重的负担。表征脑损伤后皮质重塑和恢复的规则是必要的，以便制定新的策略来恢复失去的功能。单个皮质部位的损伤通常会影响与受伤区域在解剖学上或功能上相关的多个区域的功能。这改变了皮层区域之间的正常交流模式，导致全球信息处理混乱。因此，恢复依赖于大规模的皮层网络的适应性重新排列（Payne & Lomber, Nature Reviews 2(12):911-9）。目前，人们对控制系统级恢复的机制知之甚少。与人类生理和行为密切相关的动物模型将使我们能够描述标准化皮质损伤后皮质如何重塑，并更好地理解神经代偿机制。我们的主要目的是开发一种猕猴功能磁共振成像（fMRI）模式，用于在体内、非侵入性和高空间分辨率下研究皮层活动模式在损伤后的变化。后循环梗死、出血或外伤性脑损伤通常会损伤初级视觉皮层（V1），导致部分或完全偏盲，这对依赖视力的日常活动（包括独立行走）造成相当大的破坏（Kerkhoff, Am J Ophth）。, 2000年。130(5): p. 687-8)。视觉运动感知尤其重要，因为它允许受试者通过避免与障碍物的潜在碰撞来导航自然环境。值得注意的是，由V1病变引起的盲半视野内的视觉运动知觉最近被证明可以通过视网膜特异性行为训练得到实质性的恢复（Huxlin K.R., Proceedings of the Vision Sciences Society Meeting, 2007）。然而，目前尚不清楚是什么皮层变化介导了观察到的恢复。在这里，我们将使用随机点运动学图结合功能磁共振成像和电生理学来测量猕猴视觉区域对运动信号强度（相干性）的敏感性，并跟踪它在有和没有训练的情况下V1病变后的时间变化。这将使我们能够对视觉皮层网络功能的变化提出具体的假设，这些变化介导了观察到的恢复。深入了解训练加速康复的机制对设计有效的康复策略具有重要意义。虽然我们专注于视觉，但我们的方法范围更广，并将使我们在未来继续研究包括额叶和感觉-运动皮质网络在内的多个系统的损伤后的分裂、可塑性和重组。为了在某一天提高恢复的机会，获得一种允许侵入性操作以增强适应性重组的动物模型是至关重要的。公共卫生相关性：通常，单个皮质部位的损伤会影响多个解剖或功能相连的大脑区域的功能。目前，在系统水平上，对中风或其他脑损伤后恢复的机制知之甚少。猕猴功能磁共振成像（fMRI）提供了一个无与伦比的机会，可以在体内、无创、高空间分辨率地监测与人类行为和生理密切相关的动物模型损伤后大脑活动模式的变化。在未来，我们计划将该方法广泛应用于猕猴皮层损伤的实验模型，包括视觉、感觉运动和额叶皮质网络系统。了解大脑皮层组织是如何受损伤影响的，这对于将来提高中风患者康复的机会至关重要。

DESCRIPTION (provided by applicant): Stroke and other injuries of the nervous system impose a heavy burden to individuals and to society. Characterizing the rules of cortical remodeling and recovery after brain injury is necessary in order to develop new strategies for restoring lost function. Damage at a single cortical site typically affects the function of multiple areas that are anatomically or functionally connected to the injured region. This alters the normal pattern of communication between cortical areas and leads to disorganized global information processing. As a result, recovery depends on the adaptive re-arrangement of cortical networks on a large scale (Payne & Lomber, Nature Reviews 2(12):911-9). At present, relatively little is known about the mechanisms that govern recovery at the systems level. Animal models closely related to human physiology and behavior will allow us to characterize how cortex remodels after standardized cortical injury and to better understand neural compensatory mechanisms. Our main aim is to develop a macaque functional magnetic resonance imaging (fMRI) paradigm for studying in vivo, non-invasively, and with high spatial resolution, how patterns of cortical activity change following injury. Posterior circulation infarcts, hemorrhages or traumatic brain injury often injure the primary visual cortex (V1) resulting in partial or complete hemianopsias, which are considerably disruptive to vision- dependent daily activities including independent ambulation (Kerkhoff, Am J Ophth., 2000. 130(5): p. 687-8). Visual motion perception is particularly important since it allows subjects to navigate the natural environment by avoiding potential collisions with obstacles. Remarkably, visual motion perception inside the blind hemi-field resulting from V1 lesions was recently shown to recover substantially with retinotopically specific behavioral training (Huxlin K.R., Proceedings of the Vision Sciences Society Meeting, 2007). However, it is not known what cortical changes mediate the observed recovery. Here, we will use random dot kinematograms in conjunction with fMRI and electrophysiology to measure the sensitivity of macaque visual areas to the strength of the motion signal (coherence), and to track how it changes in time following V1 lesions in the presence and absence of training. This will allow us to formulate specific hypotheses about the changes in visual cortical network function that mediate the observed recovery. Obtaining insights into the mechanism by which training accelerates recovery can have important implications for designing effective rehabilitation strategies. Although we focus on vision, our approach is broader in scope and will allow us in the future to pursue the study of diaschisis, plasticity, and reorganization-after-injury in multiple systems, including frontal and sensori-motor cortical networks. Having access to an animal model that permits invasive manipulations designed to enhance adaptive reorganization is vital in order to, some day, improve the chances for recovery. PUBLIC HEALTH RELEVANCE: Typically, injury at a single cortical site affects the function of multiple anatomically or functionally connected brain regions. At present, little is known about the mechanisms that govern recovery after stroke or other brain injury at the systems level. Macaque functional magnetic resonance imaging (fMRI) offers an unparalleled opportunity to monitor in vivo, non-invasively, at high spatial resolution how the patterns of brain activity change after injury in an animal model closely related to human behavior and physiology. In the future, we plan to apply this approach extensively to study macaque experimental models of cortical injury involving the visual, sensorimotor and frontal cortical network systems. Understanding how cortical organization is affected by injury is vital in order to, some day, improve the chances of recovery from stroke.