Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation

新的证据表明，海马区突触可塑性功能障碍 阿尔茨海默病(AD)进展过程中的神经元变性是其标志 认知障碍。虽然目前还没有有效的疾病修正疗法来治疗 AD，最近在AD动物模型中的临床前研究表明，重复的经颅 磁刺激(RTMS)促进海马区突触可塑性，并最终改善 学习和记忆能力。在这个应用程序中，我们将利用基于MRI的神经元连接 以MAP为向导精确传播浅层rTMS引起的神经元兴奋 脉搏进入海马体。这种以图像为导向的方法的前提得到了 之前发表的对健康成年人的研究和我们在轻度遗忘症患者中的试点数据 认知障碍(AMCI)。我们的初步研究结果表明，应用单剂量的 在结构上与海马体相连的大脑浅层区域上的rTMS可以 短暂调节海马区活动，增强联想记忆功能。具体的 本项目的目的是1)确定海马区rTMS对记忆的行为影响 功能，2)验证MRI引导的rTMS对海马区功能连接的影响；以及3) 开发个性化的、图像引导的海马区rTMS方案。60例急性心肌梗死患者 将参加双盲、随机、假对照、交叉研究 RTMS条件：兴奋性刺激、抑制性刺激和假刺激。每个人 参与者将针对每种情况完成10次刺激会议，间隔4周 避免潜在结转效应的条件。在初步数据的基础上，这里我们将 严格测试我们的假设，即活动的rTMS协议对 记忆功能和海马区功能连接性与假rTMS的比较 患有急性心肌梗死的个体。此外，从目标1和目标2获得的数据将用于开发 预测rTMS干预反应的统计模型。拟议的研究使用 以精准医学为基础的干预措施提供集成MRI的创新平台 (包括功能磁共振和扩散张量成像)和rTMS改善记忆功能 患有急性心肌梗死的个体。该项目代表了开发非侵入性 对阿尔茨海默病患者大有裨益的海马区刺激方案。

Emerging evidence indicates that dysfunction of hippocampal synaptic plasticity, which precedes neuronal degeneration during the progression of Alzheimer's disease (AD), underlies the hallmark cognitive impairment. Although there are currently no effective disease modifying treatments for AD, recent preclinical studies in animal models of AD have suggested that repetitive transcranial magnetic stimulation (rTMS) promotes hippocampal synaptic plasticity and, ultimately, improves learning and memory abilities. In this application, we will utilize MRI-based neuronal connectivity maps as a guide to precisely propagate the neuronal excitation elicited by the superficial rTMS pulse to the hippocampus. The premise of this image-guided approach is supported by both previously published research in healthy adults and our pilot data in individuals with amnestic mild cognitive impairment (aMCI). Our preliminary findings demonstrate that applying a single dose of rTMS over a superficial brain region that is structurally connected to the hippocampus can transiently modulate hippocampal activity and enhance associative memory function. The specific aims of this project are to 1) determine the behavioral effect of hippocampal rTMS on memory function, 2) verify MRI-guided rTMS effects on hippocampal functional connectivity; and 3) develop a personalized, image-guided hippocampal rTMS protocol. Sixty individuals with aMCI will be enrolled in the double-blind, randomized, sham-controlled, crossover study with three rTMS conditions: excitatory stimulation, inhibitory stimulation, and sham stimulation. Each participant will complete 10 stimulation sessions for each condition with a 4-week interval between conditions to avoid potential carry-over effects. Building on preliminary data, here we will rigorously test our hypothesis that active rTMS protocols have a stronger modulation effect on both memory function and hippocampal functional connectivity, compared with sham rTMS in individuals with aMCI. Furthermore, data acquired from aims 1 and 2 will be used to develop statistical models to predict responses to rTMS intervention. The proposed research uses interventions grounded in precision medicine to provide an innovative platform that integrates MRI (including functional MRI and diffusion-tensor imaging) and rTMS to improve memory function in individuals with aMCI. This project represents a critical step in developing a non-invasive hippocampal stimulation protocol that should greatly benefit patients with Alzheimer's disease.