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

描述（由申请人提供）：正如RDoC负价系统域研讨会所强调的那样，对情感线索的注意力偏差在对持续威胁和损失的反应的结构中起着关键作用。与这两种结构相关的注意力偏差背后的神经回路相对较好地理解，并由自下而上（杏仁核）和自上而下（前额叶皮层区域）过程的组合驱动。尽管他们共同的神经影响，有关的威胁与损失的注意力偏差被假设为不同的焦点和时间过程。例如，对持续威胁的反应被认为以更快地将注意力初始分配给威胁刺激为特征（例如，生气 面孔）。相反，对失去的反应被认为是缺乏将注意力从悲伤的面孔上转移开的能力。这些注意力偏差被假设在儿童时期发展，在青春期稳定，并有助于整个生命周期的精神病理学的发展和维持。虽然越来越多的成人和儿童支持这些理论，但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。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疾病进行分类的新方法”，我们需要更详细地了解注意力的哪些特定组成部分在应对持续的威胁和损失时被破坏。这项研究将包括1 000名7至11岁的儿童及其母亲。主要目的1是进行一个细粒度的检查儿童的注意力偏差使用行为（眼动）和生理（事件相关电位; ERP）指标，以确定儿童的注意力的具体组成部分是有偏见的抑郁症和焦虑症的广泛症状，以及更具体的症状域低积极的影响和生理性过度觉醒。主要目的2是提供一个更好的理解这些偏见的遗传和表观遗传的影响。我们将利用电路水平的方法来研究在这个年龄组中已知在杏仁核与PFC中差异表达的基因之间的总影响水平。从对环境影响的不同易感性模型出发，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，鉴于许多母亲对儿童注意力偏差的影响可能混淆环境和遗传因素，主要目的3是在实验室条件反射任务的背景下研究注意力可塑性。我们将研究遗传和表观遗传对儿童注意力偏差变化的影响，以及条件作用对注意力分配的新评估的普遍性。我们的目标是，这项研究将导致更详细地了解青年的精神病理学，强调一种基于神经回路中断的心理学分类的新方法，这表现为对环境中情绪线索的偏见处理。 公共卫生相关性：该项目代表了理解RDoC负价系统中的关键结构-情绪线索的注意力偏差的重要一步。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精神病理学铺平道路，并为更有针对性的干预措施提供基础。

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.