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)：该申请的目标是推出一个创新的，多模式的神经成像计划，将调查整个学龄前阶段易怒的神经发展的纵向轨迹。中的维度上存在易怒 然而，人口中的每一个成员也是一个重大的心理健康问题，几乎存在于每一种形式的精神病理学中，并跨越了内化/外化的差距。区分临床显著的易怒和发育正常的气质变异已被证明是一项艰巨的任务。这在学龄前阶段变得更加具有挑战性，那时易怒已经达到了标准的顶峰，测量神经发育受到方法限制的阻碍。这一最先进的研究计划将1)通过检查执行功能的神经成熟度作为临床结果的预测指标，识别学龄前儿童精神病理学易感性的特定生物标志物，以及2)检查父母环境如何缓和这种脆弱性，首要目标是从标准的易怒轨迹中识别异常，作为未来基于大脑的基础 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，这些儿童因易怒而变得丰富，参与一个纵向项目。在4岁时，再次在5岁时，将使用功能性近红外光谱(FNIRS)来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，可靠地应用于学龄前儿童前额叶皮质的神经成像研究。在过渡到学龄儿童(6岁)时，据报道易怒儿童有50%的精神病理症状，第三次fNIRS评估将与同步功能磁共振成像(FMRI)一起进行，以探测额叶-皮质连接。将采用经过充分验证和对儿童友好的实验范例。在4岁时，我们还将在基于发育的标准化实验室互动任务中引入双人fNIRS成像，以研究亲子神经同步性，这是一种衡量互动个体大脑活动信号之间的相关性的指标。初步分析将 1)探讨执行功能的前额叶激活增加的斜率作为临床结果的预测因子；2)考察亲子神经同步性作为高度易怒儿童执行功能成熟的预测因子和临床结果的调节因子。一项雄心勃勃的纵向、多模式神经成像计划，与创新的和对发展敏感的行为数据收集相结合，有可能识别执行功能潜在的神经过程中的干扰模式，从而可以开发针对儿童个体以及互动环境中的儿童和父母的有针对性的治疗干预措施，以重新建立规范的发展轨迹。

 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.