Prefrontal-amygdala interactions in social learning

描述(由申请人提供)：这是针对通知编号：NOT-OD-10-032的申请，申请对我目前的‘父母’R01(MH080716)进行竞争性修订，标题为“NIH宣布通过NIH基本行为和社会科学机会网络(OppNet)为竞争性修订申请(R01、R03、R15、R21、R21/R33和R37)提供恢复法案资金的可用性。”父母R01的目标是阐明前额叶皮质和杏仁核之间的功能相互作用，同时受试者了解其他人的社会价值和他们的面部表情，这方面进展顺利。这项工作对于理解前额叶皮质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。这些数据让我们了解到，在抑郁和焦虑等情绪障碍中，这些系统可能会出现问题。最初的应用程序没有解决的一个问题是，杏仁核和前额叶皮质之间的结构连接如何预测或改变社交学习中的个体差异，特别是在焦虑等结果指标上。在第一年和第二年进行母体R01的一些拟议工作时，我们例行公事地增加测量白质束结构完整性的扫描(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)。本申请旨在扩展这一发现，以确定我们确定的特定结构路径是否依赖于我们使用的功能任务(即被动观看恐惧的面部表情)。在这里，我们提出了额外的任务，需要对受试者进行更大程度的调节，以确定这些调节任务是否与类似途径或可分离途径的结构完整性有关。我们计划资助一个专攻DTI的科学家(物理学家)职位的40%，以及增加一个全职研究助理职位。这些人员将与PI(Whalen)和研究生(Kim)(均由父母R01资助)合作一年，以开展拟议的实验。 与公共健康相关：大脑中一个名为杏仁核的区域对他人的面部表情特别敏感，已被证明对焦虑症患者的面部恐惧表情表现出夸大的反应。这可能在一定程度上导致了对困扰焦虑症患者的潜在威胁的警觉性和高反应性增加的症状。这里提出的研究将进一步加深我们对杏仁核-前额叶连接的结构差异如何预测焦虑症易感性的理解。

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.