Neurobehavioral Correlates of Frustration in Children with ADHD

 描述（由申请人提供）：我的长期职业目标是发展一个独立的研究项目，以阐明儿童精神病理学中情绪失调（艾德）的神经生物学机制，从注意力缺陷/多动障碍（ADHD）开始。作为关键的第一步，本研究计划的目标是使用行为任务和多模式神经成像技术来检查ADHD儿童的低挫折耐受性（艾德的一种损害形式）的临床特征和神经相关性。这项研究的目标是为那些患有ADHD的儿童提供预防和干预措施，这些儿童因ED而面临最大的负面后果风险。患有ADHD的儿童在情绪调节方面有困难，包括挫折耐受力差，精神问题增加的风险最大，社会障碍更大，自尊心更差。因此， 为了理解临床特征（例如，症状和损伤）和神经相关性与ADHD儿童的挫折耐受力低。作为一名临床心理学家，我的研究生培训集中在ADHD儿童的循证评估和治疗上，这使我对了解ADHD儿童的艾德感兴趣。在我的论文中，研究情绪调节作为ADHD和抑郁症之间的中介，我意识到需要从神经生物学的角度来理解艾德，这需要使用情感神经科学技术，包括多模态神经成像。因此，我完成了一个简短的博士后奖学金，使我接触到情感神经科学技术在儿童精神病学研究中的应用。然而，这段经历并没有提供我追求长期职业目标所需的全面、正规的神经影像学培训。作为约翰霍普金斯大学（JHU）医学院的助理教授，我有机会获得必要的指导和机构资源，以获得这种全面的培训。因此，K23机制将使我能够投入85%的时间和精力来获得所需的培训，执行拟议的研究计划，并最终成为一名独立的临床研究人员。JHU和Kennedy Krieger Institute（KKI）一起提供了一个世界级的环境，可以在其中进行儿科神经影像学研究的培训。在KKI，神经发育和成像研究中心（CNIR）专注于了解神经发育障碍（包括ADHD）背后的大脑行为相互作用，并拥有独特的设备来支持我的需求。此外，我的导师团队，由斯图尔特莫斯托夫斯基，医学博士，(CNIR主任，主要导师），包括神经科学专家（森博士），儿童精神病理学（特别是挫折和易怒;博士芬德林，Leibenluft），和生物统计学（林德奎斯特博士）谁将为我提供知识 为达到我的培训目标和实施拟议的研究项目所需的资源。在我的培训计划中列出的累积经验将为独立研究计划提供基础，目标是在K23奖项结束之前获得R 01。我的培训目标旨在解决我的知识和培训中的关键差距，为我的独立研究生涯做好准备。具体而言，我计划：（1）获得神经成像技术在儿科精神病人群中的使用/应用的正式培训;（2）获得检查情绪处理和调节背后的大脑行为相互作用的培训;（3）获得神经成像统计和编程的培训;（4）改善研究合作，科学写作（即，补助金和手稿），和演讲技巧;和（5）获得额外的培训，在负责任的研究行为。我将完成这些培训目标，通过课程，指导我的导师/顾问与专业知识，在我的培训计划的特定组成部分，完成我的研究项目，并出席相关的研讨会，讲习班和会议。本申请中提出的研究项目是第一项使用多方法神经影像学和行为方法研究ADHD儿童低挫折耐受性的临床特征和神经相关性的研究。虽然经常观察到ADHD儿童的挫折阈值下降，但还没有研究ADHD儿童低挫折耐受性的神经行为机制，使该项目具有创新性。使用两个令人沮丧的行为任务，包括由应用程序与Mostofsky博士合作开发的任务，本研究将首先通过比较任务表现组和检查任务表现与症状之间的关联（即，ADHD症状、易怒等）。此外，我将采用结构和功能的脑神经成像，以探讨潜在的大脑回路牵连在不良挫折耐受性多动症与TD儿童。这项研究的结果将有助于更好地理解ADHD的行为和情绪失调特征，最终目标是改善ADHD患者的识别和结果。

 DESCRIPTION (provided by applicant): My long-term career goal is to develop an independent research program to elucidate the neurobiological mechanisms underlying emotion dysregulation (ED) in child psychopathology beginning with attention-deficit/hyperactivity disorder (ADHD). As a critical first step, the objectives of this research plan are to examine the clinical characteristics and neural correlates of low frustration tolerance, an impairing form of ED, in children with ADHD using behavioral tasks and multimodal neuroimaging techniques. The goal of this research is to inform prevention and intervention efforts for those children with ADHD at greatest risk for negative outcomes due to ED. Children with ADHD who have difficulty with emotion regulation, including poor frustration tolerance, are at greatest risk for increased psychiatric problems, greater social impairments, and poorer self-esteem. Therefore, it is critical to understand the clinical characteristics (e.g., symptoms and impairments) and neural correlates associated with low frustration tolerance in children with ADHD. As a clinical psychologist, my graduate training focused on the evidence-based assessment and treatment of children with ADHD which led to my interest in understanding ED in children with ADHD. Following my dissertation, which examined emotion regulation as a mediator between ADHD and depression, I realized the need to understand ED from a neurobiological perspective which required the use of affective neuroscience techniques including multi-modal neuroimaging. Therefore, I completed a brief postdoctoral fellowship which exposed me to the application/use of affective neuroscience techniques in child psychiatric research. However, this experience did not provide the comprehensive, formalized training in neuroimaging required to pursue my long-term career goal. As an Assistant Professor at Johns Hopkins University (JHU) School of Medicine, I have access to the mentorship and institutional resources necessary to obtain this comprehensive training. As such, the K23 mechanism would allow me to devote 85% of my time and effort to obtain this required training, conduct the proposed research plan, and ultimately become an independent clinical researcher. Together, JHU and Kennedy Krieger Institute (KKI) provide a world-class environment in which to pursue training in pediatric neuroimaging research. At KKI, the Center for Neurodevelopmental and Imaging Research (CNIR) focuses on understanding the brain-behavior interactions underlying neurodevelopmental disorders including ADHD, and is uniquely equipped to support my needs. Further, my mentorship team, led by Stewart Mostofsky, M.D. (CNIR Director, primary mentor), includes experts in neuroscience (Dr. Mori), child psychopathology (particularly frustration and irritability; Drs. Findling, Leibenluft), and bio-statistics (Dr. Lindquist) who will provide me with the intellectual resources required to achieve both my training objectives and implement the proposed research project. The cumulative experiences laid out in my training plan will provide the foundation for an independent research program with the goal of receiving an R01 prior to the end of the K23 award. My training objectives are intended to address critical gaps in my knowledge and training to prepare me for an independent research career. Specifically, I plan to: (1) gain formalized training in the use/application of neuroimaging technologies to pediatric psychiatric populations; (2) obtain training in the examination of the brain-behavior interactions underlying emotional processing and regulation; (3) obtain training in neuroimaging statistics and programming; (4) improve research collaboration, scientific writing (i.e., grant and manuscript), and presentation skills; and (5) obtain additional training in the responsible conduct of research. I will accomplis these training objectives through coursework, guidance from my mentors/consultants with expertise in particular components of my training plan, completion of my research project, and attendance at relevant seminars, workshops, and conferences. The research project proposed in this application is the first study to examine the clinical characteristics and neural correlate of low frustration tolerance in children with ADHD using a multi-method neuroimaging and behavioral approach. While children with ADHD are often observed to have a deceased threshold for frustration, there have been no studies of the neurobehavioral mechanisms underlying low frustration tolerance in children with ADHD making this project innovative. Using two frustrating behavioral tasks, including a task developed by the application in collaboration with Dr. Mostofsky, this study will first characterize low frustration tolerance in children with ADHD compared to typically developing (TD) by comparing groups on task performance and examining the association between task performance and symptoms (i.e., ADHD symptoms, irritability, etc.). Additionally, I will employ structural and functional brain neuroimaging to prbe the underlying brain circuits implicated in poor frustration tolerance in ADHD vs. TD children. The findings from this study will contribute to improved understanding of the behavior and emotional dysregulation which characterizes ADHD, with the ultimate goal of improving the identification of and outcomes for individuals with ADHD.