Imaging Biomarkers for TMS treatment of Depression

用于 TMS 治疗抑郁症的成像生物标志物

基本信息

批准号：
8666819
负责人：
Stephan F Taylor
金额：
$ 19.44万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8666819
关键词：
Antidepressive Agents Asses Biological Markers Blinded Blood flow Brain Brain region Cerebrovascular Circulation Clinical Development Dorsal Electroconvulsive Therapy Emotions Exhibits FDA approved Frequencies Functional Magnetic Resonance Imaging Image Intervention Left Link Location Magnetic Resonance Magnetic Resonance Imaging Major Depressive Disorder Maps Measurement Measures Medial Mediating Mediator of activation protein Mental Depression Mental disorders Metabolism Methods Modality National Institute of Mental Health Nature Neuronal Plasticity Patients Performance Perfusion Pharmaceutical Preparations Pharmacotherapy Placebo Control Effect Placebos Plastics Prefrontal Cortex Probability Publishing Randomized Relative (related person)Research Rest Scanning Short-Term Memory Signal Transduction Spin Labels Symptoms Techniques Testing Therapeutic Effect Time Transcranial magnetic stimulation Treatment Efficacy United States United States Food and Drug Administration Work active method blood oxygen level dependent depressive symptoms design emotion regulation executive function expectation frontal lobe improved innovation neuroimaging public health relevance relating to nervous system repetitive transcranial magnetic stimulation response theories treatment response

项目摘要

DESCRIPTION (provided by applicant): Recently, the Food and Drug Administration has approved a technique called repetitive transcranial magnetic stimulation (rTMS), a noninvasive method for stimulating the brain, for the treatment of Major depressive disorder (MDD). While rTMS is an important alternative for patients who cannot tolerate medications or fail to respond to standard pharmacotherapy, like any single antidepressant treatment, rTMS fails to fully alleviate symptoms in 50- 65% of patients. One of the major stumbling blocks in improving the efficacy of rTMS efficacy is our limited understanding of how rTMS works on the brain to alleviate depression. rTMS changes neural excitability, and a typical treatment course consists of 25 rTMS sessions (1 session per day). Fifteen or more sessions are generally required before symptom changes become evident, and very little information exists about the nature and extent of induced changes (i.e., neural plasticity). The current proposal will use functional magnetic resonance imaging (fMRI) to investigate changes in neural activation in MDD patients after multiple rTMS treatments to left dorsolateral prefrontal cortex (dlPFC), targeting functional networks of the dlPFC. Forty patients with MDD will be scanned while performing a working memory task, as working memory (WM) is impaired in MDD and working memory performance reliably activates left dlPFC. Patients will be randomized to receive 20 active or 20 sham rTMS sessions, followed by fMRI scans. Using arterial spin labeling (ASL) fMRI, we will quantitate cerebral blood flow (CBF) during WM performance and during rest. As patients with MDD often overactivate left dlPFC relative to healthy control subjects, left dlPFC activation is predicted to decrease in the active rTMS group compared to the sham group, reflecting improved cortical efficiency as a specific result of the rTMS treatments. Comparison to stimulation with a sham coil should establish that observed changes are not due to placebo or time effects. Networks functionally connected to left dlPFC will also be assessed for changes as a result of active rTMS. Neural activity pre-treatment and changing with treatment will be explored as biomarkers which may moderate and mediate treatment response. The study will fill an important gap by providing information about neural changes associated with rTMS therapy, improving our understanding of the mechanism of rTMS. Impact of the proposed research: MDD is one of the most common mental disorders in the United States, and current pharmacologic treatments leave at least 1/3 of patients with persistent symptoms of depression, highlighting the need to develop and refine therapy. Improved understanding of regions and networks altered by rTMS in MDD will begin the development of a biomarker for treatment response and may identify new targets, both critical steps necessary to refine rTMS methods and improve treatment efficacy.

描述（由申请人提供）：最近，食品药品监督管理局批准了一种称为重复经颅磁刺激（RTMS）的技术，这是一种刺激大脑的无创方法，用于治疗主要抑郁症（MDD）。尽管RTMS是无法忍受药物或无法对标准药物治疗反应的患者的重要替代方法，例如任何抗抑郁药治疗，但RTMS无法完全缓解50-65％的患者的症状。我们对RTM在大脑中如何减轻抑郁症的方式的理解有限，这是提高RTMS功效的主要绊脚石之一。 RTMS改变了神经兴奋性，典型的治疗课程包括25个RTMS会议（每天1次）。在症状变化变得明显之前，通常需要15次或更多会议，并且关于诱发变化的性质和程度（即神经可塑性）的信息很少。当前的建议将使用功能性磁共振成像（fMRI）来研究多种RTMS治疗后MDD患者对左侧外侧前额叶皮层（DLPFC）的神经激活的变化，以DLPFC的功能网络为目标。执行工作记忆任务时将扫描40例MDD患者，因为工作记忆（WM）在MDD中受损，并且工作记忆性能可靠地激活左DLPFC。患者将随机接受20个活动或20个假RTMS会议，然后进行fMRI扫描。使用动脉自旋标记（ASL）fMRI，我们将在WM性能和休息期间定量脑血流（CBF）。由于MDD患者通常相对于健康对照受试者过度活化左DLPFC，因此左DLPFC激活被预计为与假手术组相比，活性RTMS组的减小，反映了RTMS处理的特定结果的皮质效率提高。与假线圈刺激相比，应确定观察到的变化不是由于安慰剂或时间效应所致。由于活动RTMS的结果，还将评估与左DLPFC功能连接到左DLPFC的网络。神经活动预处理和治疗的变化将被探讨为生物标志物，可能中度和介导治疗反应。这项研究将通过提供有关与RTMS治疗相关的神经变化的信息来填补重要空白，从而提高我们对RTMS机制的理解。拟议的研究的影响：MDD是美国最常见的精神障碍之一，当前的药物治疗至少使1/3患有抑郁症状症状的患者，强调需要开发和完善治疗。对MDD中RTMS改变的区域和网络的了解，将开始开发生物标志物以进行治疗反应，并可能确定新的目标，这是完善RTMS方法所必需的关键步骤并提高治疗效果。