Imaging Biomarkers for TMS treatment of Depression

用于 TMS 治疗抑郁症的成像生物标志物

• 批准号: 8507377
• 负责人: Stephan F Taylor
• 金额: $ 23.33万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8507377
• 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

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，美国食品和药物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，用于治疗重度抑郁症（MDD）。虽然 rTMS 对于无法耐受药物或对标准药物治疗无反应的患者来说是一种重要的替代方案，但与任何单一抗抑郁治疗一样，rTMS 无法完全缓解 50-65% 患者的症状。提高 rTMS 疗效的主要障碍之一是我们对 rTMS 如何作用于大脑以缓解抑郁症的了解有限。 rTMS 改变神经兴奋性，典型的治疗疗程包括 25 次 rTMS 疗程（每天 1 次）。在症状变化变得明显之前，通常需要十五次或更多疗程，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。目前的提案将使用功能磁共振成像 (fMRI) 来研究 MDD 患者在对左背外侧前额叶皮层 (dlPFC) 进行多次 rTMS 治疗后神经激活的变化，以 dlPFC 的功能网络为目标。四十名 MDD 患者将在执行工作记忆任务时接受扫描，因为 MDD 患者的工作记忆 (WM) 受损，而工作记忆性能会可靠地激活左侧 dlPFC。患者将被随机分配接受 20 次主动 rTMS 治疗或 20 次假 rTMS 治疗，然后进行功能磁共振成像扫描。使用动脉自旋标记 (ASL) fMRI，我们将定量 WM 表现和休息期间的脑血流量 (CBF)。由于与健康对照受试者相比，MDD 患者经常过度激活左侧 dlPFC，因此预计左侧 dlPFC 激活会 与假手术组相比，活性 rTMS 组的皮质效率降低，反映出 rTMS 治疗的具体结果是皮质效率提高。与假线圈刺激的比较应该确定观察到的变化不是由于安慰剂或时间效应造成的。功能性连接至左 dlPFC 的网络也将被评估是否因活跃的 rTMS 而发生变化。将探索治疗前的神经活动和治疗后的变化作为可以调节和介导治疗反应的生物标志物。该研究将通过提供与 rTMS 治疗相关的神经变化信息来填补一个重要的空白，提高我们对 rTMS 机制的理解。 拟议研究的影响：抑郁症是美国最常见的精神障碍之一，目前的药物治疗使至少 1/3 的患者患有持续性抑郁症状，这凸显了开发和完善治疗方法的必要性。更好地了解 rTMS 在 MDD 中改变的区域和网络将开始开发治疗反应的生物标志物，并可能确定新的靶点，这都是完善 rTMS 方法和提高治疗效果所必需的关键步骤。