Using human brain connectivity to identify the causal neuroanatomical substrate of depression symptoms

利用人脑连接来识别抑郁症状的因果神经解剖学基础

• 批准号: 9905135
• 负责人: MICHAEL D FOX
• 金额: $ 16.04万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-19 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9905135
• 关键词: Animal Model; Antidepressive Agents; Area; Biological Markers; Brain; Brain region; Distant; Future; Goals; Grant; Human; Knowledge; Lead; Lesion; Link; Localized Lesion; Location; Magnetic Resonance Imaging; Maps; Mediating; Mental Depression; Neuroanatomy; Patients; Site; Source; Symptoms; Techniques; Testing; Therapeutic Trials; United States National Institutes of Health; base; biomarker identification; connectome; depressive symptoms; disability; insight; neuroimaging; response; therapeutic target

PROJECT SUMMARY Depression is the leading cause of disability worldwide and new treatments are needed. Identifying the brain regions causing depression symptoms can lead to treatment targets and better therapies. However, identifying these regions has been difficult. Neuroimaging of patients identifies brain areas where activity correlates with depression symptoms, but can't determine whether these regions actual cause symptoms. Animal models allow for causal manipulations, but only approximate human symptoms. The goal of this grant is to link depression symptoms to human neuroanatomy in a causal way. Here I focus on two sources of information that can provide theses causal neuroanatomical links. The first is patients with focal brain lesions causing depression symptoms. The second is patients with depression who have received focal brain stimulation for symptomatic relief. In both cases, there is a causal link between symptoms and the site of the lesion or stimulation. However, this causal link can be indirect. Lesion-induced symptoms can come from brain regions connected to the lesion location rather than the lesion location itself. Similarly, benefits of brain stimulation can come from modulation of distant regions connected to the site of stimulation. As such, utilizing these causal sources of information requires a map of human brain connectivity. Due to NIH initiatives like the human connectome project and high powered MRI scanners, such maps are now available. I've recently developed a technique that uses these brain connectivity maps to better localize lesion induced symptoms and identify regions mediating response to focal brain stimulation. Here, I leverage this technique to identify brain regions causing depression symptoms (Aim 1) and brain regions mediating antidepressant response to focal brain stimulation (Aim 2). Successful completion of these aims will lend insight into the causal neuroanatomical substrate of depression symptoms. Such knowledge will facilitate identification of biomarkers for evaluating future therapies, optimal therapeutic targets for invasive and noninvasive brain stimulation, and individualized targets based on patient-specific symptom profiles. These treatment targets can then be empirically tested in future therapeutic trials.

项目总结 抑郁症是全球残疾的主要原因，需要新的治疗方法。辨认大脑 导致抑郁症状的区域可以导致治疗目标和更好的治疗方法。然而，识别 这些地区一直很困难。患者的神经成像确定了与活动相关的大脑区域 抑郁症状，但不能确定这些区域是否真正引起症状。动物模型 允许进行因果操作，但仅允许近似人类症状。这笔赠款的目标是将 抑郁症状与人类神经解剖学有因果关系。在这里，我将重点介绍两个信息来源 可以提供这些因果神经解剖学联系。第一种是脑局灶性病变的患者 抑郁症状。第二个是抑郁症患者，他们接受了局部脑刺激 症状缓解。在这两种情况下，症状与病变部位或 刺激。然而，这种因果联系可能是间接的。病变引起的症状可能来自大脑区域 连接到病变位置而不是病变位置本身。同样，大脑刺激的好处可以 来自与刺激部位相连的远距离区域的调制。因此，利用这些因果关系 信息源需要一张人脑连接图。由于国家卫生研究院的倡议，如人类 Connectome项目和高功率核磁共振扫描仪，这样的地图现在可以使用。我最近开发了一种 使用这些大脑连接图更好地定位病变引起的症状并识别 对局灶性脑刺激的反应进行调节的区域。在这里，我利用这项技术来识别大脑区域 引起抑郁症状(目标1)和局灶性脑内介导抗抑郁药物反应的脑区 刺激(目标2)。这些目标的成功完成将有助于深入了解因果神经解剖学 抑郁症状的底物。这些知识将有助于识别用于评估的生物标记物 未来的治疗，有创和无创脑刺激的最佳治疗靶点，以及个体化 基于患者特定症状特征的目标。然后可以对这些治疗目标进行经验测试 未来的治疗试验。