Delay Discounting in Children with ADHD: Neuroimaging and Behavioral Correlates

描述(由申请人提供)：我的长期职业目标是建立一个研究计划，以改进ADHD的治疗，重点是通过提高对ADHD儿童认知和动机变化的了解来实现这一目标。这项研究计划有可能让我们了解ADHD的大脑基础，并改善被诊断为这种慢性疾病的个人的结果。作为一名临床心理学家，我的研究生培训主要集中在研究ADHD有效治疗的认知和行为机制(即行为疗法和兴奋剂药物)。这使我对大脑中认知和动机系统的相互作用产生了兴趣，形成了我的论文的基础，我的论文结合了神经生理学和行为测量来研究自我调节。我目前的博士后职位通过研究大脑-行为关系延长了我之前的训练。随着我的研究兴趣的发展，我认识到有必要接受额外的神经成像培训，以便更全面地检查认知和动机，以及它们之间的相互作用。这最终将使我能够实现我的长期职业目标，即在以患者为导向的研究中建立独立的职业生涯。2013年7月1日，我将被任命为肯尼迪·克里格研究所的教员和约翰·霍普金斯大学医学院精神病学系的讲师。K23机制将使我能够将100%的时间和精力集中在作为一名独立临床研究人员的职业发展上。肯尼迪·克里格研究所和约翰斯·霍普金斯大学拥有世界一流的心理学、神经科学、生物医学工程、生物统计学和临床系，为我作为一名研究ADHD和其他神经发育障碍大脑行为关系的独立研究员提供了良好的发展环境。神经认知和成像研究实验室(INIR)的设备独一无二，可以满足我的需求。在医学博士斯图尔特·莫斯托夫斯基(INIR主任、主要导师)和马克·马宏博士(神经心理学系主任、共同导师)的指导下，以及几位在神经成像、生物统计学和行为心理学方面具有专业知识的顾问，我将拥有非凡的智力资源来实现这些培训目标并实施拟议的研究计划。我在培训计划中积累的经验将为独立研究计划奠定基础，目标是在K23奖项结束之前获得R01。我的培训目标是解决我知识上的重大差距，为我的独立研究生涯做好准备。具体地说，我计划1)获得神经科学和神经成像方法及其在儿科人群中的应用的知识；2)获得大脑-行为关系检查方面的培训；3)获得统计和编程及其在神经成像数据中的应用方面的培训；4)提高研究协作、科学写作和演示技能；以及5)获得负责任的研究实施方面的额外培训。我将通过课程作业、我的导师和顾问的指导，特别是我培训计划中的专业知识，完成我的研究项目，以及参加相关的研讨会、研讨会和会议来实现这些培训目标。我在这项申请中提出的研究项目是第一个使用多种方法的神经成像和行为方法来研究ADHD儿童延迟折扣或冲动选择的认知、神经和行为机制的研究。ADHD模型强调奖赏加工的改变和认知控制功能(如注意调节和工作记忆)的损害，以及这些动机和认知过程之间的相互作用。特别是，包括对延迟的厌恶和对较小的即时奖励的强烈偏好而不是较大的延迟奖励的功能失调的奖励信号，这种偏差被称为延迟折扣，被认为是ADHD的行为调节障碍的原因。然而，ADHD文献一直被不一致的方法所困扰，使结果的解释复杂化。此外，奖赏加工和认知控制的改变对延迟折扣增加的相对贡献，以及这种行为背后的神经机制，还没有被很好地理解，特别是在儿童中。因此，我的研究将使用结构和功能的大脑连接来检验奖励评估和认知控制功能之间的贡献，以延迟ADHD儿童的折扣。这项研究的发现将有助于更好地理解以ADHD为特征的行为失调，以及更普遍的冲动行为，最终目标是改善对这种异质性障碍个体的识别和结果。

DESCRIPTION (provided by applicant): My long-term career goal is to establish a research program to improve treatments for ADHD, with an emphasis on doing so through improved understanding of alterations in cognition and motivation in children with ADHD. This program of research has the potential to inform our understanding of the brain basis of ADHD and to improve outcomes for individuals diagnosed with this chronic disorder. As a clinical psychologist, my graduate training focused primarily on the examination of cognitive and behavioral mechanisms of effective treatments for ADHD (i.e., behavioral therapy and stimulant medication). This led to my interest in the interaction of cognitive and motivational systems in the brain, forming the basis for my dissertation which incorporated neurophysiologic and behavioral measures to study self-regulation. My current position as a postdoctoral fellow has extended my prior training through examination of brain-behavior relationships. As my research interests have developed, I have recognized the need to obtain additional training in neuroimaging to allow for a more comprehensive examination of cognition and motivation, and their interaction. This will ultimately enable me to achieve my long-term career goal to establish an independent career in patient- oriented research. On July 1, 2013, I will be appointed as Faculty at Kennedy Krieger Institute and Instructor in the Department of Psychiatry at Johns Hopkins University School of Medicine. The K23 mechanism will enable me to focus 100% of my time and effort to develop a career as an independent clinical researcher. The Kennedy Krieger Institute and Johns Hopkins University have world-class Psychology, Neuroscience, Biomedical Engineering, Biostatistics, and clinical departments that provide an excellent environment to facilitate my development as an independent investigator studying brain-behavior relationships in ADHD and other neurodevelopmental disorders. The Laboratory for Neurocognitive and Imaging Research (LNIR) is uniquely equipped to support my needs. Under the mentorship of Stewart Mostofsky, M.D. (LNIR Director, primary mentor) and Mark Mahone, Ph.D., ABBP (Department of Neuropsychology, Director, co-mentor), as well as several consultants with expertise in neuroimaging, biostatistics, and behavioral psychology, I will have exceptional intellectual resources to achieve these training objectives and implement the proposed research plan. 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 to prepare me for an independent research career. Specifically, I plan to 1) gain knowledge of neuroscience and neuroimaging methods and applications in pediatric populations; 2) obtain training in the examination of brain-behavior relationships; 3) obtain training in statistics and programming and their application to neuroimaging data; 4) improve research collaboration, scientific writing, and presentation skills; and 5) obtain additional trainng in the responsible conduct of research. I will accomplish these training objectives through coursework, guidance from my mentors and 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 I have proposed in this application is the first study to examine the cognitive, neural, and behavioral mechanisms of delay discounting, or impulsive choice, in children with ADHD using a multi-method neuroimaging and behavioral approach. Models of ADHD have emphasized both alterations in reward processing and impairments in cognitive control functions (e.g., attention regulation and working memory), as well as the interaction between these motivational and cognitive processes. In particular, dysfunctional reward signaling consisting of an aversion to delay and a strong preference for smaller, immediate rewards over larger, delayed rewards, a bias referred to as delay discounting, is thought to contribute to the behavioral dysregulation which characterizes ADHD. However, the ADHD literature has been plagued by inconsistent methods complicating interpretation of results. In addition, the relative contributions of alterations in reward processng and cognitive control to increased delay discounting, as well as the neural mechanisms underlying this behavior, are not well understood, particularly in children. Therefore, my study will employ structural and functional brain connectivity to examine the contributions between reward valuation and cognitive control functions to delay discounting in children with ADHD. The findings from this study will contribute to improved understanding of the behavior dysregulation which characterizes ADHD, and more generally impulsive behavior, with the ultimate goal of improving the identification of and outcomes for individuals with this heterogeneous disorder.