COMPUTATIONAL MODELS OF CORTICAL MAP REORGANIZATION

拟议研究的广泛、长期目标是开发， 分析和评估小皮质中风和中风后的计算机模型， 中风恢复 上一个项目期间完成的工作 新皮层神经模型中的感觉地图将在 对模拟局灶性病变的反应。 这种地图重组类似于 在实验中被发现的重要方面，并导致了可测试的 预测中风后恢复的机制。 具体 计划在下一个项目期间进行的研究的目的是， 这项工作的范围，包括初级运动皮层在多区域 皮质模型，并将生化和代谢特征 在缺血性中风中很重要。 采取的方法是开发和研究 两个独立的计算模型，然后将它们联合收割机组合，如下所示。 第一，指导模拟手臂定位的电机控制模型 在三维空间中将得到发展。 这种模式，结合 初级运动皮层（区域4）和本体感受皮层（区域3a）， 将允许调查的假设，特征图类似 在生理学实验中观察到的现象在学习过程中出现， 闭环网络中的突触修饰。 电机控制模型 然后将用于研究急性局灶性脑缺血后的运动地图重组 病变 第二，一个增强的皮层模型， 将实现通常在神经模型中找不到的代谢特征 并独立研究，以评估这些因素对 病灶周围皮质 一旦病变对这两个模型的影响被 孤立地理解，它们的特征将结合在一个单一的 统一的模型，使这些功能之间的相互作用， 可以分析模拟的损伤。 通过系统地改变模型 参数和病变的大小和位置，具体的假设将 对模型特征进行测试，1）产生 相对的神经不活动（“缺血半暗带”），2）导致或阻止 募集该区域进入永久性梗死，3）导致演变 4）导致中风后运动地图重组 期 因此，这项研究将补充传统的临床和 研究脑血管疾病的动物模型方法， 有助于我们理解大脑皮层 信息处理的一般，和缺血性心脏病的病理生理学 更具体地说。

The broad, long-term objective of the proposed research is to develop, analyze and evaluate computer models of small cortical strokes and post- stroke recovery. Work completed during the previous project period has shown that sensory maps in neural models of neocortex will reorganize in response to simulated focal lesions. Such map reorganization resembles that seen experimentally in important ways, and has led to testable predictions about the mechanisms of post-stoke recovery. The specific aims of the research planned for the next project period are to extend the scope of this work to encompass primary motor cortex in a multiregional cortical model, and to incorporate biochemical and metabolic features important in ischemic stroke. The approach taken is to develop and study two separate computational models, and then to combine them, as follows. First, a motor control model that directs positioning of a simulated arm in three dimensional space will be developed. This model, incorporating both primary motor cortex (area 4) and proprioceptive cortex (area 3a), will permit investigation of the hypothesis that feature maps resembling those observed in physiological experiments emerge during learning due to synaptic modifications in a closed-loop network. The motor control model will then be used to study motor map reorganization following acute focal lesions. Second, an enhanced cortex model incorporating biochemical and metabolic features not usually found in neural models will be implemented and studied independently to assess the effects of these factors in perilesion cortex. Once the effects of lesions on these two models are understood in isolation, their features will be combined in a single unified model so that interactions between these features following simulated lesions can be analyzed. By systematically varying model parameters and the size and location of lesions, specific hypotheses will be tested about model features that 1) produce a perilesion zone of relative neural inactivity ("ischemic penumbra"), 2) cause or prevent recruitment of this zone into the permanent infarct, 3) lead to evolving stroke, and 4) lead to motor map reorganization during the post-stroke period. This research will thus complement traditional clinical and animal model approaches to studying cerebrovascular disease by contributing to our understanding of the dynamics of neocortical information processing generally, and of the pathophysiology of ischemic stroke more specifically.