Combining cerebral lesions & monkey fMRI for studying cortical network function

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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.