Prefrontal-amygdala interactions in social learning

描述（由申请人提供）：这是一份对我目前的“父”R 01进行竞争性修改的申请（MH 080716）响应通知编号：NOT-OD-10-032，标题为“NIH宣布恢复法案资金可用于竞争性修订申请（R 01，R 03，R15，R21，R21/R33和R37）通过NIH基本行为和社会科学机会网络（OppNet）。“R 01的目标是阐明前额叶皮层和杏仁核之间的功能相互作用，同时受试者了解其他个体的社会价值及其面部表情。这项工作对于理解前额叶皮层和杏仁核之间的功能相互作用如何支持精神健康受试者的社会学习具有重要意义。这些数据告诉我们，这些系统在抑郁和焦虑等情绪障碍中可能会出错。最初的申请没有解决的一个问题是杏仁核和前额叶皮层之间的结构联系如何预测或改变社会学习的个体差异，特别是在结果测量中，如焦虑。在第1年和第2年期间进行父R 01的一些拟议工作时，我们常规地增加了测量白色物质束的结构完整性的扫描（即，扩散张量成像（DTI）]。我们刚刚发表了一项令人兴奋的发现，确定了前额叶杏仁核白色物质束，其完整性预测了受试者的焦虑水平（Kim等人，J Neurosci，2009）。本申请旨在扩展该发现以确定我们鉴定的特定结构途径是否依赖于我们使用的功能任务（即，被动地观看恐惧的面部表情）。在这里，我们提出了额外的任务，需要更大程度的监管主体的一部分，以确定这样的监管任务将与结构完整性的类似途径或可分离的途径。我们计划资助40%的工作人员科学家（物理学家）的职位与DTI的专业化，以及增加一个全职的研究助理职位。这些人员将与PI（Whalen）和研究生（Kim）（均由父R 01资助）合作一年，以开展拟议的实验。 公共卫生相关性：大脑中一个叫做杏仁核的区域对他人的面部表情特别敏感，并且已经证明，焦虑症患者对恐惧的面部表情表现出过度的反应。这可能是焦虑症患者对潜在威胁的警惕性和反应过度的症状的部分原因。这里提出的研究将进一步了解杏仁核-前额叶连接的结构差异如何预测焦虑症的脆弱性。

DESCRIPTION (provided by applicant): This is an application for a competitive revision to my current 'parent' R01 (MH080716) in response to Notice Number: NOT-OD-10-032, titled "NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications (R01, R03, R15, R21, R21/R33, and R37) through the NIH Basic Behavioral and Social Science Opportunity Network (OppNet)." The parent R01 is progressing soundly in its aim to elucidate functional interactions between the prefrontal cortex and the amygdala while subjects learn about the social value of other individuals and their facial expressions. This work has significant implications for understanding how functional interactions between the prefrontal cortex and amygdala support social learning in psychiatrically healthy subjects. These data inform our understanding of how these systems might go awry in emotional disorders such as depression and anxiety. A question not addressed by the original application is how structural connections between the amygdala and prefrontal cortex might predict or vary with individual differences in social learning, and specifically in outcome measures such as anxiety. While conducting some of the proposed work of the parent R01 during years 1 and 2, we routinely add a scan that measures the structural integrity of white matter tracts (i.e., diffusion tensor imaging (DTI)]. We just published an exciting finding identifying a prefrontal-amygdala white matter tract, the integrity of which predicted subjects' anxiety levels (Kim et al., J Neurosci, 2009). The present application aims to expand upon this finding to determine if the particular structural pathway we identified is dependent on the functional task we used (i.e., passive viewing of fearful facial expressions). Here we propose additional tasks that require a greater degree of regulation on the part of subjects to determine if such regulatory tasks will be associated with the structural integrity of a similar pathway or separable pathways. We plan to fund 40% of a staff scientist (physicist) position with a specialization in DTI, as well as add one full-time Research Assistant position. These personnel will work with the PI (Whalen) and graduate student (Kim) (both funded under the parent R01) for a one-year period to carry out the proposed experiments. PUBLIC HEALTH RELEVANCE: An area of the brain called the amygdala is particularly responsive to the facial expressions of others and has been shown to exhibit exaggerated reactivity to the facial expression of fear in subjects with anxiety disorders. This may, in part, underlie the symptoms of increased vigilance and hyper-reactivity to potential threat that plague individuals with anxiety disorders. The studies proposed here will further our understanding of how structural differences in amygdala-prefrontal connectivity predict vulnerability to anxiety disorders.