Analysis of stroke-induced changes in connectivity and neural activity

项目摘要 认知障碍是中风常见的功能后遗症，尽管其背后的神经基础 目前还没有确定。白质高强度(WMH)，一种进行性退变形式，也是 小血管疾病是卒中后认知功能障碍的主要危险因素。新出现的研究支持 WMH负荷与关键大脑结构--海马体的体积成反比 为记忆功能，并可能经历二次退化。初步数据显示，海马体 远离皮质卒中，卒中后不会受到严重影响。然而，我们的电生理学数据表明 在慢性中风期间，大脑皮层和海马体之间的网络通讯被破坏， 这与基于连接组的分析一致，该分析表明受损的皮质区域与 涉及空间学习的神经网络。我们假设西医损害易患中风后认知功能障碍 由于学习和记忆区域的连通性丧失和远程退化加剧而造成的损害。 我们的直接目标是从大脑的角度了解中风对海马体功能的影响 连通性。作为一项原则验证的翻译研究，我们将在自发性高血压大鼠中进行这一研究 在检测到自发性西医损害的年龄。确定连接性丢失在卒中后的作用 认知障碍在西医病变的背景下，我们将首先绘制出西医和西医的病变位置和范围 Gm，并量化海马子区体积。然后我们将确定结构连通性的变化 利用基于NeuroVIISAS的Connectome平台构建的轨迹跟踪和DTI简化数据以揭示如何 全球和本地网络都受到影响。与海马体有直接或间接联系的受损区域 将会被确认。中风和西医损害对学习/记忆功能的动态影响将被确定 通过对空间相关的一对受损区域和功能区域之间的共同激活模式进行建模 用Fitzhugh-Nagumo神经元模拟加权和定向连接组进行学习。 将对海马区活动和网络通信的电生理学相关性进行评估 补充神经行为和连接方面的数据。我们预计，对病变范围、位置、 高血压对网络连通性的影响将有助于深入了解西医损害的作用 中风后认知功能下降。它还可能使识别大脑的中继区经历 变化以及可能的连通性丢失的进展。

Project Summary Cognitive impairment is a common functional sequela of stroke, although the neural substrate underlying which is yet to be identified. White matter hyperintensity (WMH), a progressive form of degeneration and a marker of small vessel disease, is a major risk factor for post stroke cognitive impairment. Emerging studies support an inverse relationship between WMH burden and the volume of the hippocampus, which is a key brain structure for memory function and may undergo secondary degeneration. Preliminary data show that the hippocampus is remote from cortical stroke and not affected acutely after stroke. However, our electrophysiology data suggest that network communication between the cortex and hippocampus became disrupted during chronic stroke, which is consistent with connectome-based analysis showing damaged cortical regions are well connected with neural networks involved in spatial learning. We hypothesize that WM lesions predispose to post stroke cognitive impairment due to exacerbated connectivity loss and remote degeneration in the learning and memory region. Our immediate goal is to understand how stroke affects hippocampal function from the perspective of brain connectivity. As a proof-of-principle translational study, we will carry it out in the spontaneously hypertensive rats at an age when spontaneous WM lesion is detected. To determine the role of connectivity loss in post stroke cognitive impairment in the setting of WM lesion, we will first map the lesion location and extent in both WM and GM, and quantify hippocampal subfield volume. We will then determine the changes in structural connectivity with the neuroVIISAS-based connectome platform built with tract tracing and DTI streamline data to reveal how global and local networks are affected. Lesioned regions with direct or indirect connections with the hippocampus will be identified. The dynamic effect of stroke and WM lesion on learning/memory function will be determined by modeling the coactivation pattern between a pair of lesioned region and functional region involved in spatial learning with FitzHugh-Nagumo neuron simulation using the weighted and directed connectome. Electrophysiology correlates of hippocampal activity and network communication will be assessed to complement data in neurobehavior and connectivity. We anticipate that the knowledge of lesion extent, location, and the effect on network connectivity in the setting of hypertension will provide insight into the role of WM lesion in post stroke cognitive decline. It may also enable the identification of relay brain regions undergoing functional changes and possibly the progression of connectivity loss.