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

用于海马刺激的交错 TMS-fMRI：模拟遗忘型轻度认知障碍的剂量反应关系

• 批准号: 10429807
• 负责人: Ying-Hui Chou
• 金额: $ 22.38万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10429807
• 关键词: Adult; Alzheimer' s Disease; Animals; Area; Behavior; Behavioral; Brain; Brain imaging; Brain region; Clinical; Collaborations; Data; Development; Disease; Dose; Enrollment; Functional Magnetic Resonance Imaging; Goals; Hippocampus (Brain); Hour; In Vitro; Individual; Learning; Long-Term Potentiation; Magnetic Resonance Imaging; Maps; Measures; Memory; Modeling; Neurophysiology - biologic function; Neuropsychological Tests; Outcome Measure; Participant; Pattern; Performance; Persons; Population; Protocols documentation; Public Health; Randomized; Rattus; Recording of previous events; Research; Research Personnel; Resources; Rest; Risk; Seeds; Site; Slice; Statistical Models; Synapses; Techniques; Therapeutic; Time; Training; amnestic mild cognitive impairment; clinical application; effective therapy; improved; innovation; insight; mild cognitive impairment; neuroregulation; noninvasive brain stimulation; public health relevance; recruit; reduce symptoms; response; tractography; treatment strategy; white matter

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.

项目概要/摘要 Theta burst stimulation（TBS）是一种非侵入性脑刺激技术， 是治疗轻度认知障碍（MCI）和阿尔茨海默病（AD）的一种有前途的疗法。然而，在这方面， 几乎没有进行任何努力来优化TBS对这些人群的应用。先前 体外动物实验发现，TBS可诱导成年大鼠产生长时程增强（LTP 以剂量依赖性方式抑制海马切片。最大的LTP效应是在 TBS课程重复三次，每次课程之间休息60分钟。的 当TBS应用没有足够的间歇时，剂量-反应曲线变平。这 指出了一系列必须适当调整以实现期望的TBS效果的参数。 本研究的目的是探讨在大脑表面区域间隔TBS的影响 在患有遗忘型MCI（aMCI）的个体中与海马体相连。TBS将应用于内部 一台MRI扫描仪与功能性MRI交错，以可视化海马的即时反应， 刺激.本研究的目的1将确定间隔TBS对记忆性能的影响 和海马功能。目标2将确定剂量-反应 TBS效应的关系。将随机分配38名aMCI患者， 两个TBS组之一：活动TBS或假TBS。我们假设1）间隔TBS 协议将增强记忆功能，加强海马功能连接， 与假手术TBS相比，增加海马激活，和2）阳性剂量反应 将观察TBS效应的关系。通过利用最先进的MRI兼容TBS， 我们的创新性研究结果可能提示aMCI中间隔海马TBS的机制。 最终，了解大脑如何对间隔的TBS做出反应将有助于开发一种 优化TBS治疗方案，用于MCI和AD患者。