Brain pathways in social evaluative threat

描述(申请人提供)：神经成像技术的几个新发展为了解皮质-脑干-自主神经和皮质-下丘脑-内分泌通路的进步铺平了道路。进展既来自获取技术，包括自旋-回波连续动脉自旋标记(SE-CASL)功能磁共振成像的开发，也来自分析工具的改进，包括开发能够在大脑路径上定位和进行种群推断的多水平路径模型。在这个项目中，这两种技术的新组合将被用来实现两个目标：第一，识别皮质-脑干和皮质-下丘脑通路，介导对社会评估威胁的外周反应(目标1)，第二，研究前额叶皮质对功能威胁通路强度的调节(目标2)。识别参与威胁的大脑通路的能力很重要，因为动物和人类的大量文献表明，心理威胁和压力可能与许多疾病的不良后果有关，包括心血管健康、哮喘、伤口愈合和免疫功能、抑郁症等。但在将心理威胁与人类外周活动联系起来的具体大脑机制方面，知识存在着严重的缺口。关于情绪的大脑机制以及内分泌和自主神经生理学的问题在很大程度上是通过不同领域的单独研究来解决的。使用通径分析来检查CASL-fMRI和外周反应(皮质醇和自主神经输出的基本测量)，将使我们能够在“较高皮质”的大脑活动、下丘脑和脑干的皮质下中心和外周反应之间建立联系。识别大脑路径是一项新的努力，因为大多数fMRI研究都检查了大脑的区域激活，要么忽略了大脑区域是如何连接的，要么分析了两个区域之间连接的简单衡量标准。路径分析可以用来识别跨越多个区域和测量的路径，为人类大脑与外周交流提供新的见解。SE-CASL被选为一种技术是因为它特别适合于研究下丘脑和脑干，具有更好的空间定位，更可靠的信号和更少的伪影，以及随时间的稳定性，使其适合于检查持续的大脑和对社会评估威胁的生理反应。公共卫生相关性：对身体安全和社会地位的威胁会在人类中产生显著的自主神经和神经内分泌反应，而慢性生理威胁反应与许多疾病有关，包括抑郁、焦虑、心血管疾病、感染和其他。尽管已经对非人类动物的威胁反应进行了仔细的研究，但对于将人类对社会情境的独特认知转化为生理反应的特定皮质-脑干-躯体通路，人们知之甚少。该项目将先进的多变量分析技术与脑干成像的尖端方法相结合，以绘制这些路径，从而深入了解威胁反应是如何在人脑中产生和调节的。

DESCRIPTION (provided by applicant): Several new developments in neuroimaging techniques have paved the way for advances in understanding cortical-brainstem-autonomic and cortical-hypothalamic-endocrine pathways. Advances come from both acquisition techniques, including the development of spin-echo continuous arterial spin labeling (SE-CASL) fMRI, and improvements in analysis tools, including the development of multi-level path models capable of localizing and making population inference on brain pathways. In this project, the novel combination of these two techniques will be used to accomplish two aims: First, to identify cortical-brainstem and cortical- hypothalamic pathways mediating peripheral responses to social evaluative threat (Aim 1), and second, to examine modulation of functional threat-pathway strength by the prefrontal cortex (Aim 2). The ability to identify brain pathways involved in threat is important because a large literature in animals and humans suggests that psychological threat and `stress' are potentially linked to adverse outcomes in many diseases, including cardiovascular health, asthma, wound healing and immune function, depression, and others. But there is a critical gap in knowledge about the specific brain mechanisms that link psychological threat to peripheral activity in humans. Questions about brain mechanisms of emotion and questions about endocrine and autonomic physiology have largely been addressed by separate studies in separate fields. Using path analysis to examine both CASL-fMRI and peripheral responses (cortisol and basic measures of autonomic output) will allow us to forge links between `higher cortical' brain activity, subcortical centers in hypothalamus and brainstem, and peripheral responses. Identifying brain pathways is a new endeavor, as most fMRI studies examine regional brain activation, either ignoring how brain regions are connected or analyzing simple measures of connectivity between two regions. Path analysis can be used to identify pathways that span multiple regions and measures, providing potential for new insights into human brain-peripheral communication. SE-CASL was selected as a technique because it is particularly suited to studying the hypothalamus and brainstem, with improved spatial localization, more reliable signal and reduced artifacts around these regions, and stability over time, making it suitable for examining sustained brain and physiological responses to social evaluative threat. PUBLIC HEALTH RELEVANCE: Threats to both physical safety and social status produce marked autonomic and neuroendocrine responses in humans, and chronic physiological threat responses are associated with a number of disorders, including depression, anxiety, cardiovascular disease, infection, and others. Though threat responses have been carefully studied in nonhuman animals, little is known about the specific cortical-brainstem-body pathways that translate uniquely human cognitions about the social situation into physiological responses. This project combines advanced multivariate analysis techniques with cutting-edge methods for imaging the brainstem to map these pathways, providing insight into how threat responses are generated and regulated in the human brain.