低频重复经颅磁刺激增强AD工作记忆功能的脑网络连接机制研究

Alzheimer’s disease (AD) is a neurodegenerative disorder that endangers people's physical and mental health seriously. Working memory dysfunction is typically observed in AD. The repetitive Transcranial Magnetic Stimulation (rTMS) is en effective technology for the treatments of diseases in nervous system..Selecting AD rats as the research object, this project aims to explore the dysfunction of LFPs functional connectivity in AD rat prefrontal cortex (PFC) and the mechanism of low-frequency rTMS strengthens brain functional connectivity in working memory dysfunction. .Research contents: 1) Preparation and identification of AD rats (Aβ1-42-induced toxicity rat model). Animals and groups: SD rats are divided into four groups: Control、Control +rTMS、AD、AD +rTMS groups. 2) LFPs are simultaneously recorded from multiple electrodes placed in PFC while the grouped rats perform a Y-maze working memory task. 3) Spectral analysis is used to assess the dominant frequencies in the LFPs and the featured frequencies are extracted. 4) Causality analysis in frequency domain is applied to calculate the DTF, which can directly describe the functional connectivity in LFPs. 5) Causal networks are built based on the DTF matrics and the global efficiency E of the networks is further estimated. 6) Combined with the behavior results、DTF and E, we make research on the dysfunction of LFPs functional connectivity in AD rat prefrontal cortex (PFC) and the mechanism of low-frequency rTMS strengthens brain functional connectivity in working memory dysfunction. .Significance: Studies of this project are expected to provide support for the mechanism research and clinical application of low-frequency rTMS in working memory dysfunction. .

老年性痴呆（AD）严重危害人类健康，主要临床表现为工作记忆障碍。重复经颅磁刺激（rTMS）是近年发展治疗神经系统疾病的新技术。.研究目的：以AD模型大鼠为研究对象，从神经信息功能性连接角度，研究低频rTMS增强AD工作记忆局部场电位LFPs功能性连接机制。.研究内容：1）制备和认定AD模型大鼠，实验动物分4组：正常、正常+rTMS、AD、AD+rTMS组。2）应用在体多通道微电极记录技术，记录并获取大鼠Y迷宫工作记忆行为学参数与前额叶皮层16通道LFPs。3）时频分析：获取LFPs特征频段。4）频域因果分析：计算定量描述LFPs功能性连接参数DTF。5）构建LFPs因果网络，计算网络信息传递效率E。6）基于工作记忆行为学、DTF、E，研究AD工作记忆脑功能连接缺陷，以及低频rTMS增强AD工作记忆功能连接的机制。.研究意义：为低频rTMS干预AD工作记忆障碍机制研究和临床应用提供支持。

1.项目研究背景与科学问题.研究背景：.老年性痴呆（AD）严重危害人类健康，主要临床表现为工作记忆障碍。重复经颅磁刺激（rTMS）是近年发展治疗神经系统疾病的新技术。本项目以AD模型大鼠为研究对象，从神经信息功能性连接角度，研究低频rTMS增强AD工作记忆局部场电位LFPs功能性连接机制。为研究老年性痴呆工作记忆障碍的神经环路信息编码与脑网络缺陷机制提供支持。.科学问题：.（1）AD模型大鼠在工作记忆中责任脑区（前额叶皮层）多通道LFPs的功能性连接是否存在缺陷？（2）从神经信息功能性连接角度，低频rTMS能否及如何增强AD大鼠工作记忆功能？ .2. 项目完成情况.项目研究计划按预期目标完成。.3. 项目成果.（1）项目标注成果.在国际学术期刊发表本项目标注SCI 论文5 篇，累计影响因子17.14。.（2）项目研究成果.1）研究AD大鼠在工作记忆中LFPs功能性连接的缺陷；.① AD工作记忆障碍LFPs振荡缺损.② AD工作记忆障碍LFPs功能性连接缺损.③ AD工作记忆障碍LFPs因果网络全局效率降低.2）研究低频rTMS增强AD大鼠工作记忆LFPs功能性连接的机制.① 低频rTMS增强AD工作记忆LFPs振荡.② 低频rTMS增强AD工作记忆LFPs功能性连接.③ 低频rTMS提高AD工作记忆LFPs因果网络全局效率