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: 10290232
• 负责人: MICHAEL D FOX
• 金额: $ 70.28万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 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/10290232
• 关键词: Age; Animal Model; Antidepressive Agents; Area; Biological Markers; Blood Vessels; Brain; Brain region; Data; Data Set; Databases; Deep Brain Stimulation; Diffusion; Distant; Dorsal; Future; Gender; Goals; Grant; Human; Knowledge; Lateral; Lead; Left; Lesion; Link; Localized Lesion; Location; Magnetic Resonance Imaging; Maps; Measures; Mediating; Mental Depression; Modality; Neuroanatomy; Patient imaging; Patients; Penetrating Head Injuries; Pharmaceutical Preparations; Play; Prefrontal Cortex; Refractory; Rest; Role; Severities; Site; Source; Stroke; Symptoms; Techniques; Testing; Therapeutic Trials; Time; Transcranial magnetic stimulation; United States National Institutes of Health; base; biomarker identification; connectome; depressive symptoms; disability; insight; neuroimaging; neuropsychiatric symptom; physically handicapped; post stroke; prospective; response; symptomatic improvement; therapeutic target; tractography

PROJECT SUMMARY: Using human brain connectivity to identify the causal neuroanatomical substrate of depression symptoms 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. Because this technique utilizes existing connectivity data, it does not require connectivity imaging of the patients themselves. As such, the technique can be applied to any lesion or stimulation dataset and has already lent insight into a variety of neuropsychiatric symptoms. Here, I leverage this technique to identify brain regions causing depression symptoms (Aim 1) and brain regions mediating anti-depressant 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.

项目概述：利用人脑连通性识别因果神经解剖学