Delay Discounting in Children with ADHD: Neuroimaging and Behavioral Correlates

多动症儿童的延迟折扣：神经影像学和行为相关性

• 批准号: 8733755
• 负责人: Keri Shiels Rosch
• 金额: $ 14.85万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-13 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8733755
• 关键词: Accounting; Adaptive Behaviors; Address; Anatomy; Anterior; Attention; Attention deficit hyperactivity disorder; Base of the Brain; Behavior; Behavior Control; Behavior Therapy; Behavioral; Behavioral Mechanisms; Biomedical Engineering; Biometry; Brain; Brain region; Child; Childhood; Chronic Disease; Clinical; Cognition; Cognitive; Collaborations; Complex; Data; Decision Making; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Disease; Doctor of Medicine; Doctor of Philosophy; Educational workshop; Emotional; Environment; Faculty; Failure; Foundations; Functional Magnetic Resonance Imaging; Gambling; Goals; Image; Impairment; Impulsive Behavior; Impulsivity; Individual; Individual Differences; Informal Social Control; Institutes; Knowledge; Laboratories; Literature; MRI Scans; Measures; Medial; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodology; Methods; Modeling; Motivation; Neurocognitive; Neurodevelopmental Disorder; Neuropsychology; Neurosciences; Obesity; Outcome; Participant; Pattern; Performance; Pharmaceutical Preparations; Plague; Play; Population; Positioning Attribute; Postdoctoral Fellow; Process; Psychiatry; Psychologist; Psychology; Reaction Time; Regulation; Relative (related person); Research; Research Personnel; Research Project Grants; Resolution; Resources; Rest; Rewards; Scanning; Short-Term Memory; Signal Transduction; Social Development; Substance abuse problem; System; Therapeutic Intervention; Time; Training; Universities; Ventral Striatum; Visuospatial; Writing; base; behavior measurement; brain behavior; brain morphology; career; cognitive control; discounting; disorder control; effective therapy; experience; improved; instructor; interest; medical schools; neuroimaging; neuromechanism; patient oriented research; peer; preference; programs; public health relevance; relating to nervous system; response; responsible research conduct; reward processing; skills; statistics; symposium

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.

描述（由申请人提供）：我的长期职业目标是建立一个研究项目，以改善多动症的治疗方法，重点是通过提高对多动症儿童认知和动机变化的理解来实现这一目标。这个研究项目有可能让我们了解多动症的大脑基础，并改善被诊断患有这种慢性疾病的个体的预后。作为一名临床心理学家，我的研究生培训主要集中在对多动症有效治疗的认知和行为机制的研究（即行为治疗和兴奋剂药物）。这使我对大脑中认知系统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，该论文结合了神经生理学和行为测量来研究自我调节。我现在的博士后职位通过研究大脑-行为关系扩展了我之前的训练。随着我的研究兴趣的发展，我认识到需要在神经影像学方面获得额外的培训，以便对认知和动机及其相互作用进行更全面的检查。这将最终使我能够实现我的长期职业目标，建立一个独立的职业生涯，以病人为导向的研究。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机制将使我能够集中100%的时间和精力发展独立临床研究人员的职业生涯。肯尼迪克里格研究所和约翰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、生物统计学和临床部门，这些部门为我作为一名独立研究者研究多动症和其他神经发育障碍的大脑-行为关系提供了良好的环境。神经认知和成像研究实验室（LNIR）有独特的设备来支持我的需求。在Stewart Mostofsky， M.D. （LNIR主任，主要导师）和Mark Mahone， Ph.D， ABBP（神经心理学系主任，共同导师）的指导下，以及几位在神经影像学，生物统计学和行为心理学方面具有专业知识的顾问，我将拥有特殊的智力资源来实现这些培训目标并实施拟议的研究计划。在我的训练计划中积累的经验将为一个独立的研究项目提供基础，目标是在K23奖结束之前获得R01。我的培训目标是为了解决我在知识上的关键空白，为我独立的研究生涯做好准备。具体来说，我计划1)学习神经科学和神经成像方法及其在儿科人群中的应用；2)接受脑-行为关系检验方面的训练；3)接受统计学和编程方面的培训，并将其应用于神经影像学数据；4)提高科研合作、科学写作和演讲技巧；5)在负责任的研究行为方面获得额外的培训。我将通过课程学习、导师和顾问在我的培训计划的特定组成部分的专业知识的指导、完成我的研究项目、参加相关的研讨会、讲习班和会议来实现这些培训目标。我在本申请中提出的研究项目是第一个使用多方法神经成像和行为方法研究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模型强调了奖励处理的改变和认知控制功能（例如，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，功能失调的奖励信号，包括对延迟的厌恶和对小的、即时的奖励的强烈偏好，而不是大的、延迟的奖励，这种偏见被称为延迟折扣，被认为是导致ADHD特征的行为失调的原因。然而，ADHD文献一直受到不一致的方法的困扰，使结果的解释复杂化。此外，奖励处理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，还没有得到很好的理解，特别是在儿童中。因此，我的研究将采用结构和功能脑连接来检验奖励评估和认知控制功能之间对ADHD儿童延迟折扣的贡献。这项研究的发现将有助于提高对ADHD特征的行为失调的理解，以及更广泛的冲动行为，最终目标是提高对患有这种异质性疾病的个体的识别和治疗效果。