Children's Attentional Biases: A Key Component of Negative Valence Systems

描述(由申请人提供)：正如RDoC负价系统领域研讨会所强调的那样，对情感线索的注意偏差在构建对持续威胁和损失的反应中发挥着关键作用。与这两种结构相关的注意偏差背后的神经回路相对较好地被理解，并由自下而上(杏仁核)和自上而下(前额叶皮质区域)过程的组合驱动。尽管它们有共同的神经影响，但与威胁和损失相关的注意偏差被假设在焦点和时间进程上有所不同。例如，对持续威胁的反应被认为是将注意力更快地初始分配到威胁刺激(例如，愤怒)上 脸)。相比之下，对失去的反应被认为是缺乏将注意力从悲伤的脸上转移开的能力。这些注意力偏向被认为是在儿童时期形成的，在青春期稳定下来，并在整个一生中对精神病理学的发展和维持做出贡献。虽然这些理论在成人和儿童中得到越来越多的支持，但在文献中也有一些混合的发现，我们认为这是由于对这一关键结构的评估不足造成的。为了实现RDoC的目标，即开发“基于可观察行为和大脑功能的维度对障碍进行分类的新方法”，我们需要更详细地了解在应对持续的威胁和损失时，注意力的哪些特定组成部分被扰乱。这项研究将包括1000名7-11岁的儿童和他们的母亲。主要目标1是使用行为(眼睛追踪)和生理(事件相关电位；事件相关电位)指数对儿童的注意力偏差进行细粒度检查，以确定儿童注意力的哪些特定组成部分与他们广泛的抑郁和焦虑症状有关，以及更具体的症状领域，如低积极情绪和生理过度唤醒。主要目的2是为了更好地理解遗传和表观遗传对这些偏向的影响。我们将利用电路水平的方法来检查在这个年龄段杏仁核和PFC中已知差异表达的基因之间的总影响水平。从环境影响的差异易感性模型出发，我们还将研究这些遗传和表观遗传影响如何在特定环境影响的背景下运作。最后，考虑到许多母亲对儿童注意力偏向的影响可能混淆了环境和遗传因素，主要目标3是在基于实验室的条件任务的背景下检查注意力的可塑性。我们将考察遗传和表观遗传对儿童注意偏向变化的影响，以及条件效应对注意力分配的新评估的概括性。我们的目标是，这项研究将导致对青少年精神病理学的更详细的理解，强调一种新的基于神经回路中断的心理学分类方法，这表现为在一个人的环境中对情绪线索的偏见处理。 公共卫生相关性：拟议的项目代表着理解RDoC负价系统中的一个关键结构的重要一步--对情绪线索的注意偏差。它将提供有关这些偏见的行为、心理生理、遗传、表观遗传和环境基础的详细信息。因此，它将有助于为更好地描述青年内在化精神病理学的特征铺平道路，并为更有针对性的干预奠定基础。

DESCRIPTION (provided by applicant): As highlighted by the RDoC Negative Valence Systems Domain workshop, attentional biases to affective cues play a key role in the constructs of Responses to sustained threat and Loss. The neural circuitry underlying attentional biases relevant to both constructs is relatively well understood and is driven by a combination of bottom-up (amygdala) and top-down (regions of prefrontal cortex) processes. Despite their common neural influences, attentional biases relevant to threat versus loss are hypothesized to differ in their focus and time course. For example, responses to sustained threat are thought to be characterized by quicker initial allocation of attention toward threatening stimuli (e.g., angry faces). In contrast, responses to loss are thought to be characterized by deficits in the ability t disengage attention from sad faces. These attentional biases are hypothesized to develop during childhood, stabilize in adolescence, and contribute to the development and maintenance of psychopathology across the lifespan. Although there is growing support for these theories among adults and children, there are also a number of mixed findings in the literature, which we believe have resulted from the inadequate assessment of this key construct. To achieve the RDoC goal of developing "new ways of classifying disorders based on dimensions of observable behaviors and brain functions", we need a more detailed understanding of which specific components of attention are disrupted in response to sustained threat and loss. This study will include 1,000 children aged 7-11 years and their mothers. Primary Aim 1 is to conduct a fine-grained examination of children's attentional biases using both behavioral (eyetracking) and physiological (event-related potential; ERP) indices to determine which specific components of children's attention are biased in relation to their broad symptoms of depression and anxiety, as well as the more specific symptom domains of low positive affect and physiological hyperarousal. Primary Aim 2 is to provide a better understanding of the genetic and epigenetic influences on these biases. We will utilize a circuit-level approach to examine aggregate levels of influence among genes known to be differentially expressed in amygdala versus PFC in this age group. Building from models of differential susceptibility to environmental influence, we will also examine how these genetic and epigenetic influences operate within the context of specific environmental influences. Finally, given that many maternal influences on children's attentional biases likely confound environmental and genetic factors, Primary Aim 3 is to examine attentional plasticity in the context of a laboratory-based conditioning task. We will examine genetic and epigenetic influences on changes in children's attentional biases as well as the generalizability of conditioning effects to a novel assessment of attentional allocation. Our goal is that this research will lead to a more detailed understanding of psychopathology in youth, emphasizing a new way of categorizing psychology based on the neural circuits disrupted, which is manifest as biased processing of emotional cues in ones environment. PUBLIC HEALTH RELEVANCE: The proposed project represents an important step in understanding a key construct within the RDoC Negative Valence Systems - attentional biases for emotional cues. It will provide detailed information regarding the behavioral, psychophysiological, genetic, epigenetic, and environmental foundations of these biases. As such, it will help pave the way for better characterizing internalizing psychopathology in youth, and provide the groundwork for more focused interventions.