COMPUTATIONAL MODELS OF CORTICAL MAP REORGANIZATION

拟议研究的广泛、长期目标是开发、 分析和评价大脑皮质小卒中和卒中后的计算机模型 中风恢复了。在前一个项目期内完成的工作 研究表明，新皮质神经模型中的感觉映射将在 对模拟局灶性病变的反应。这样的地图重组类似于 这在实验中被认为是重要的，并导致了可测试 关于中风后恢复机制的预测。具体的 计划在下一个项目期进行的研究的目标是延长 这项工作的范围包括多区域的初级运动皮质 皮质模型，并结合生化和代谢特征 在缺血性中风中很重要。采取的办法是开发和研究 两个独立的计算模型，然后将它们合并，如下所示。 首先，一个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，结合了 初级运动皮质(4区)和本体感觉皮质(3a区)， 将允许对如下假设进行研究：要素地图类似于 在生理实验中观察到的那些在学习过程中出现的原因是 闭合网络中的突触修饰。电机控制模型 然后将用于研究急性局灶性脑损伤后的运动地图重组 损伤。第二，增强的大脑皮层模型结合了生化和 将实现神经模型中通常不存在的代谢特征 并独立研究以评估这些因素在 弥漫性皮质。一旦损伤对这两个模型的影响是 孤立地理解，它们的功能将组合在一个 统一的模型，以便这些功能之间的交互遵循 可以分析模拟的损伤。通过系统变化的模型 参数以及病变的大小和位置，特定的假设将 对1)产生扩散区的模型特征进行测试 相对神经活动不活跃(“缺血半暗带”)，2)引起或预防 这一区域重新进入永久性脑梗塞，3)导致进化 卒中，以及4)在卒中后导致运动图重组 句号。因此，这项研究将补充传统的临床和 脑血管疾病的动物模型研究方法 有助于我们理解新皮质的动力学 一般信息处理，以及缺血的病理生理学 更具体地说，笔划。

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.