Brain substrates for cardiovascular stress physiology

心血管应激生理学的脑基质

• 批准号: 10225342
• 负责人: Annie T Ginty
• 金额: $ 13.51万
• 依托单位: BAYLOR UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10225342
• 关键词: Acute; Address; Amygdaloid structure; Area; Atherosclerosis; Base of the Brain; Behavioral Medicine; Biological; Blood Vessels; Brain; Brain Stem; Brain region; Calibration; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Clinical Markers; Data; Development; Disease; Energy Metabolism; Functional Magnetic Resonance Imaging; Goals; Health; Human; Individual; Individual Differences; Insula of Reil; Intervention; Knowledge; Lasers; Limbic System; Link; Machine Learning; Measurable; Measures; Medial; Mentored Research Scientist Development Award; Mentors; Metabolic; Metabolic Pathway; Metabolic stress; Methods; Nature; Neuraxis; Nucleic Acid Regulatory Sequences; Outcome; Oxygen Consumption; Participant; Pathogenicity; Pathway interactions; Pattern; Peripheral; Physiological; Physiology; Play; Positioning Attribute; Prefrontal Cortex; Preparation; Prevention; Professional Competence; Program Development; Psychological Stress; Public Health; Reaction; Regulation; Research; Research Personnel; Risk; Role; Source; Stratification; Stress; System; Techniques; Testing; Time; Training; Translating; Validation; Variant; Work; biological adaptation to stress; cardiovascular disorder risk; cardiovascular risk factor; career; career development; experience; neuroimaging; neurophysiology; neuroregulation; novel; pre-clinical; psychologic; relating to nervous system; research and development; response; risk stratification; skills; stressor; time use

Project Summary/Abstract The candidate’s long-term goal is to become an independent investigator focused on the neurophysiological pathways that link psychological stress with cardiovascular disease (CVD). Individual differences in biological responses to acute psychological stress have been shown to predict risk for subclinical and clinical markers of CVD, indicating that variation in the stress response relates to measurable health outcomes. The proposed research and career development program will position the candidate to definitively address open and mechanistic questions on cardiovascular stress physiology with a multi-dimensional approach. The overall objective of the current project is to identify the ‘brain–cardiovascular’ pathways of metabolically excessive cardiovascular responses to stress. The central hypothesis is that metabolically excessive cardiovascular responses to stress are caused by increased brain activation in areas associated with cardiovascular and autonomic control. In extension, the candidate will test whether altering brain function via neuromodulation will regulate downstream cardiovascular responses. Proposed are two independent studies. In Aim 1, we will newly examine the relationship between metabolically excessive cardiovascular and neural responses using a cross-sectional approach. In Aim 2, we will measure stressor-evoked metabolic and cardiovascular responses before and after neuromodulation in an experimental approach. Participants will engage in a novel, non-invasive neuromodulation technique, transcranial infrared laser stimulation (TILS), known to alter the brain by increasing oxygenation, and will be compared to an established control. This research plan will help the candidate develop essential skills for career development including cardiovascular and metabolic testing, machine learning and cross-validation methods for functional magnetic resonance imaging analyses, and utilizing a neuromodulation technique, TILS. The proposed Mentored Research Scientist Development Award will provide 5 years of training through a combination of research, classroom experiences, and mentoring to further the candidate in preparation for scientific independence. Specifically, the candidate will gain expertise in measuring metabolic activity, advance her computational neuroimaging analysis skills, become proficient in experimentally manipulating brain function, and develop necessary statistical skills. The project brings together a mentoring team of experts in their respective areas to provide the candidate with the necessary skills to continue on the trajectory to make a transformative contribution to the field of Cardiovascular Behavioral Medicine. This project will provide vital information regarding the pathways between psychological stress and CVD risk while at the same time providing training and mentoring for the candidate’s further career.

项目总结/摘要 候选人的长期目标是成为一名独立的研究人员，专注于神经生理学通路， 将心理压力与心血管疾病（CVD）联系起来。急性心肌梗死生物学反应的个体差异 心理压力已被证明可以预测亚临床和临床CVD标志物的风险，这表明， 与可测量的健康结果有关。拟议的研究和职业发展计划将 定位候选人明确解决心血管应激生理学的开放性和机制性问题， 多维度方法。目前项目的总体目标是确定“脑-心血管”通路 对压力的过度心血管反应。核心假设是代谢过度 心血管对压力的反应是由与心血管和心血管疾病相关的区域的大脑激活增加引起的， 自主控制在扩展中，候选人将测试通过神经调节改变大脑功能是否会调节 下游心血管反应。这是两项独立的研究。在目标1中，我们将重新审视 代谢过度的心血管和神经反应之间的关系，使用横截面的方法。在 目的2，我们将测量神经调节前后应激诱发的代谢和心血管反应， 实验方法参与者将从事一种新颖的，非侵入性的神经调节技术，经颅红外 激光刺激（TILS），已知通过增加氧合来改变大脑，并将与已建立的 控制该研究计划将帮助候选人发展职业发展的基本技能，包括 心血管和代谢测试、机器学习和功能磁共振交叉验证方法 成像分析，并利用神经调节技术，TILS。拟议的指导研究科学家 发展奖将提供5年的培训，通过研究，课堂经验， 指导，以进一步候选人在科学独立的准备。具体来说，候选人将获得 测量代谢活动的专业知识，提高她的计算神经成像分析技能，精通 实验性地操纵大脑功能，并发展必要的统计技能。该项目汇集了 由各自领域的专家组成的辅导小组，为候选人提供必要的技能， 致力于为心血管行为医学领域做出变革性贡献。该项目将 提供有关心理压力和CVD风险之间途径的重要信息，同时 为候选人的未来职业生涯提供培训和指导。