Brain pathways in social evaluative threat

描述（由申请人提供）：神经影像技术的几项新发展为理解皮质-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。进步来自于两种采集技术，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群体推断的多级路径模型的开发。在这个项目中，这两种技术的新颖组合将用于实现两个目标：首先，确定介导对社会评价威胁的外周反应的皮质-脑干和皮质-下丘脑通路（目标1），其次，检查前额皮质对功能性威胁通路强度的调节（目标2）。识别与威胁有关的大脑通路的能力非常重要，因为大量关于动物和人类的文献表明，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。但对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了解存在重大差距。关于大脑情绪机制的问题以及关于内分泌和自主生理学的问题在很大程度上已经通过不同领域的单独研究得到解决。使用路径分析来检查 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“高级皮层”大脑活动、下丘脑和脑干的皮层下中心以及外周反应之间建立联系。识别大脑通路是一项新的尝试，因为大多数功能磁共振成像研究都检查大脑区域的激活，要么忽略大脑区域的连接方式，要么分析两个区域之间连接性的简单测量。路径分析可用于识别跨越多个区域和测量的路径，为人类大脑与外周通信的新见解提供潜力。选择 SE-CASL 作为一种技术是因为它特别适合研究下丘脑和脑干，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，使其适合检查对社会评价威胁的持续大脑和生理反应。公共卫生相关性：对人身安全和社会地位的威胁会在人类中产生明显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相关，包括抑郁、焦虑、心血管疾病、感染等。尽管已经在非人类动物中仔细研究了威胁反应，但人们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-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，以绘制这些路径，从而深入了解人脑中如何生成和调节威胁反应。

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.