From Irritability to Impairment: How Neurodevelopment of Executive Function and Parent-Child Neural Synchrony Influence the Transition from Normal to Abnormal Functioning.

 描述（由申请人提供）：本申请的目标是启动一项创新的多模态神经成像计划，该计划将调查整个学龄前时期易怒神经发育的纵向轨迹。易怒存在于一个维度上， 然而，它也是一个重要的心理健康问题，几乎存在于每一种精神病理学形式中，跨越了内化/外化的鸿沟。区分临床上突出的易怒从发展规范的气质变化已被证明是一项艰巨的任务。在学龄前阶段，这一点更具挑战性，因为此时易怒已经达到了正常水平，测量神经发育受到方法学限制的阻碍。这项最先进的研究计划将：1）通过检查执行功能中的神经成熟作为临床结果的预测因子，确定学龄前精神病理学脆弱性的具体生物标志物; 2）检查养育环境如何调节这种脆弱性，其总体目标是确定从规范的易怒轨迹中异常的行为，作为未来基于大脑的研究的基础。 行为干预我们的跨学科研究团队将招募150名4岁儿童的样本，丰富的高易怒参与纵向项目。在4岁和5岁时，将使用功能性近红外光谱（fNIRS）评估执行功能的神经基础，这是一种无痛，非限制性的光学成像技术，可可靠地用于学龄前儿童前额叶皮层的神经成像研究。在过渡到学龄期（6岁），其中有50%的精神病理学症状已报告在易怒的儿童，第三fNIRS评估将发生沿着同时功能性磁共振成像（fMRI），以探测额叶皮层连接。将采用经过充分验证和对儿童友好的实验范例。在4岁时，我们还将向标准化的基于发育的实验室互动任务引入双人fNIRS成像，以研究亲子神经同步性，这是互动个体的大脑活动信号之间的相关性的测量。主要分析将 1)探讨作为临床结果预测因子的执行功能基础的前额叶激活的增加的斜率和2）检查作为高度易怒儿童的执行功能成熟的预测因子和临床结果的调节因子的父母-孩子神经同步性。一项雄心勃勃的纵向、多模式神经成像计划，结合创新且对发育敏感的行为数据收集，有可能识别执行功能相关神经过程的中断模式，以便针对儿童个体以及儿童和父母进行有针对性的治疗干预。可以开发互动环境，以重建规范的发展轨迹。

 DESCRIPTION (provided by applicant): The goal of this application is to launch an innovative, multi-modal neuroimaging program that will investigate the longitudinal trajectory of the neurodevelopment of irritability across the preschool period. Irritability exists on a dimension in every member of the population, however, it is also a significant mental health concern that is present in nearly every form of psychopathology and spans the internalizing/externalizing gap. Differentiating clinically salient irritability from developmentally-normative temperamental variation has proven to be a difficult task. This is made even more challenging during the preschool period, when irritability has hit its normative peak and measuring neurodevelopment is impeded by methodological constraints. This state-of-the-art program of research will 1) identify specific biomarkers underlying preschool vulnerability for psychopathology by examining neural maturation in executive function as a predictor for clinical outcome and 2) examine how the parenting environment moderates this vulnerability, with the overarching objective of identifying aberrant from normative irritable trajectories as the foundation for future brain-based behavioral intervention. Our transdisciplinary research team will recruit a sample of 150 4 year-old children, enriched for high irritability to participate in a longitudinal project. At age 4, an again at age 5, the neural underpinnings of executive function will be assessed using functional near-infrared spectroscopy (fNIRS), an optical imaging technique that is painless, non-restrictive, and reliably employed in neuroimaging studies of the prefrontal cortex in preschool children. At the transition to school-age (age 6), where a 50% rate of psychopathological symptoms have been reported in irritable children, a third fNIRS assessment will occur along with simultaneous functional magnetic resonance imaging (fMRI) to probe frontal-cortical connectivity. Well- validated and child-friendly experimental paradigms will be employed. At age 4, we will also introduce dual- person fNIRS imaging to a standardized developmentally-based laboratory interaction task in order to investigate parent-child neural synchrony, a measure of the correlation between signals of brain activity of interacting individuals. Primary analyses will 1) probe the slope of increase in prefrontal activation underlying executive function as a predictor of clinical outcome and 2) examine parent-child neural synchrony as a predictor of executive function maturation and as a moderator of clinical outcome in highly irritable children. An ambitious program of longitudinal, multi-modal neuroimaging, combined with innovative and developmentally-sensitive behavioral data collection, has the potential to identify patterns of disruption in neural processes underlying executive function so that targeted therapeutic interventions, aimed at both the child individually, and the child and parent in an interactive context, can be developed to reestablish a normative developmental trajectory.