Interleaved TMS-fMRI for Hippocampal Stimulation: Modeling Dose-Response Relationship in Amnestic Mild Cognitive Impairment

项目摘要/摘要 Theta Burst刺激术(TBS)是一种非侵入性脑刺激技术，现已成为 一种治疗轻度认知障碍(MCI)和阿尔茨海默病(AD)的有前途的疗法。然而， 几乎没有作出努力来优化TBS在这些人群中的应用。上一首 动物体外研究发现TBS可诱导成年大鼠的长时程增强(LTP) 以剂量依赖的方式在海马区切片。观察到最大LTP效应是在 TBS课程重复三次，每次课程之间有60分钟的休息时间。这个 当TBS应用没有足够的间隔时，剂量-反应曲线变得平坦。这 指向必须正确调整才能实现所需TBS效果的参数数组。 本研究的目的是研究间隔TBS对大脑浅层区域的影响。 与遗忘性MCI(AMCI)患者的海马区相连。TBS将在内部应用 核磁共振扫描仪与功能磁共振成像相互交错，以可视化对海马区的即时反应 刺激。这项研究的目标1将确定间隔TBS对记忆性能的影响 以及AMCI患者的海马区功能。目标2将建立剂量反应 间隔TBS效应的关系。38名患有急性心肌梗死的患者将被随机分配 到两个TBS组之一：活动TBS或假TBS。我们假设1)间隔的TBS 协议将增强记忆功能，加强海马区功能连接，并 与假TBS组相比，增加了海马区的激活，并且2)呈阳性剂量反应 将观察TBS效应之间的关系。通过利用与MRI兼容的尖端TBS， 我们的创新性研究结果可能提示了aMCI中间隔的海马TBS的机制。 最终，了解大脑如何对间隔的TBS做出反应将使 优化了MCI和AD患者的TBS治疗方案。

Project Summery/Abstract Theta burst stimulation (TBS) is a non-invasive brain stimulation technique that has emerged as a promising therapy for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, little effort has been undertaken to optimize the application of TBS for these populations. Previous animal in vitro studies have found that TBS could induce long-term potentiation (LTP) in adult rat hippocampal slices in a dose-dependent manner. The maximum LTP effect was observed after TBS sessions were repeated three times, with a 60-minute break between each session. The dose-response curve was flattened when TBS applications did not have adequate interludes. This points to an array of parameters that must be properly tuned to achieve the desired TBS effects. The purpose of the study is to investigate the effects of spaced TBS at a superficial brain region connected to the hippocampus in individuals with amnestic MCI (aMCI). TBS will be applied inside an MRI scanner interleaved with fMRI to visualize the immediate response to the hippocampal stimulation. Aim 1 of the study will determine the effects of spaced TBS on memory performance and hippocampal function in individuals with aMCI. Aim 2 will establish dose-response relationship of the spaced TBS effect. Thirty-eight individuals with aMCI will be randomly assigned to one of the two TBS groups: active TBS or sham TBS. We hypothesize that 1) the spaced TBS protocol will enhance memory function, strengthen hippocampal functional connectivity, and increase hippocampal activation compared to the sham TBS, and 2) a positive dose-response relationship of the TBS effect will be observed. By leveraging cutting edge MRI-compatible TBS, findings of our innovative study may suggest mechanisms of spaced hippocampal TBS in aMCI. Ultimately, understanding how brain responds to the spaced TBS will enable development of an optimized TBS therapeutic protocol for individuals with MCI and AD.