Brain pathways in social evaluative threat

描述（由申请人提供）：神经成像技术的几项新进展为理解皮质-脑干-自主神经和皮质-下丘脑-内分泌通路的进展铺平了道路。这些进展来自两种采集技术，包括自旋回波连续动脉自旋标记（SE-CASL）功能磁共振成像的发展，以及分析工具的改进，包括能够对大脑通路进行定位和人口推断的多级路径模型的发展。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，确定皮层-脑干和皮层-下丘脑通路介导的外周反应的社会评价威胁（目标1），第二，检查调制功能威胁通路强度的前额叶皮层（目标2）。识别与威胁有关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。但是，关于将心理威胁与人类外周活动联系起来的特定大脑机制的知识存在重大差距。关于情绪的大脑机制问题以及关于内分泌和自主神经生理学的问题，在很大程度上已经通过不同领域的独立研究得到了解决。使用路径分析来检查CASL-fMRI和外周反应（皮质醇和自主输出的基本措施）将使我们能够建立“高级皮质”大脑活动，下丘脑和脑干的皮质下中心和外周反应之间的联系。识别大脑通路是一项新的奋进，因为大多数功能性磁共振成像研究都是检查区域性大脑激活，要么忽略大脑区域是如何连接的，要么分析两个区域之间连接的简单测量。路径分析可用于识别跨越多个区域和措施的路径，为人类大脑-外周通信提供新的见解。选择SE-CASL作为一种技术，因为它特别适合于研究下丘脑和脑干，具有改进的空间定位，更可靠的信号和减少这些区域周围的伪影，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价威胁的生理反应。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，慢性生理威胁反应与许多疾病有关，包括抑郁症、焦虑症、心血管疾病、感染等。虽然已经在非人类动物中仔细研究了威胁反应，但对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-身体通路知之甚少。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，以绘制这些通路，从而深入了解威胁反应如何在人脑中产生和调节。

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.