A Multi-Method Investigation to Distinguish Sluggish Cognitive Tempo from ADHD

 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，以了解注意力缺陷/多动障碍（ADHD）合并症的病因和发育后果，特别强调认知克里思迟缓（SCT）。作为发展这项研究计划的第一步，我领导了一系列研究，研究ADHD和SCT是否不仅在统计学上不同，而且与青少年的功能有差异或独特的联系。我的试点工作表明，虽然SCT与ADHD注意力不集中，抑郁，焦虑和白天嗜睡的发生率较高相关，但SCT在统计学上与这些领域不同。我还发现，SCT症状与学业和社交障碍有关，即使在控制了ADHD之后。由于SCT症状在统计学上与ADHD不同，并且与一系列损伤唯一相关，因此有人认为SCT可能是与ADHD分离的疾病。此外，SCT结构的临床意义是强调了初步数据显示存在SCT升高，以预测ADHD儿童对精神兴奋剂药物的反应较差。这表明，经常使用的循证ADHD治疗方法对于也显示SCT的ADHD儿童是不够的。这些发现表明了螺旋CT的重要性，以及对螺旋CT的病因、外部相关因素和发育进展进行系统研究的必要性。我目前是辛辛那提儿童医院医疗中心（CCHMC）行为医学和临床心理学部门的研究人员，K23机制将使我能够集中时间和精力发展作为独立临床研究人员的职业生涯。随着我的研究兴趣的发展，我认识到需要获得神经心理学和神经生理学的额外培训，以便对ADHD和SCT进行更全面，多模式的检查。我的培训目标旨在解决我的知识的关键差距，为我的独立研究生涯做好准备。具体来说，我计划（1）获得大脑行为关系的专业知识，特别强调神经心理学，（2）获得神经科学和神经成像方法的知识，特别强调脑磁图（MEG）和脑电图（EEG），（3）获得与儿科人群神经心理学和神经生理学研究相关的统计和编程培训，（4）提高撰写资助申请的技巧，扩大研究传播。我将通过课程作业、在我的培训计划的特定组成部分中具有专业知识的导师和顾问的指导、完成我的研究项目以及参加相关研讨会、讲习班和会议来实现这些培训目标。培训和职业发展计划的完成将使我能够实现我的长期目标，建立一个独立的职业生涯，以患者为导向的研究，显着推进我们对SCT和ADHD并发症的理解。为了分离出SCT的独特相关性，我提出了一个研究项目，这将是第一个直接比较儿童与 使用多方法神经成像和行为方法，将SCT升高（伴或不伴ADHD）应用于典型发育儿童和仅伴ADHD的儿童。我的研究将使用最近验证的SCT措施招募184名儿童（年龄8-12岁）分为四组（每组n = 46）：仅SCT，仅ADHD，SCT+ADHD和典型的发展对照。所有儿童都将完成全面评估，其中包括评估SCT，ADHD和精神病合并症的诊断面试，智力和学业成绩测试以及一系列神经心理测试。一部分参与者将执行一项任务，评估不同的注意力网络，同时接受MEG（与结构MRI共配准），这是一种最佳的成像方法，具有出色的空间和时间分辨率。这个项目将使我能够识别区分SCT和ADHD的潜在功能障碍和损伤，从而与理论，疾病分类学和干预有明确的相关性。辛辛那提儿童医院提供了一个很好的环境，以促进我的发展，作为一个独立的研究者研究大脑行为的关系，在多动症和SCT。一个特殊的指导团队已经组装，以支持我的培训和职业发展。在Jeffery Epstein博士（主要赞助商）的指导下，ADHD中心是世界级的ADHD专业中心。同样在CCHMC，Jing Xiang博士（MEG中心主任;共同导师）和Dean Beebe博士（神经心理学项目主任;共同导师）将分别提供MEG和神经心理学方面的指导。Leanne Tamm和James Peugh博士将分别提供ADHD神经成像和统计方面的现场专业知识。最后，埃里克博士 Willcutt（科罗拉多大学博尔德分校）和Sandra Loo博士（加州大学，洛杉矶）将提供外部专业知识，了解神经心理学和神经生理学方法如何具体告知ADHD合并症模型。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。

 DESCRIPTION (provided by applicant): My long-term career goal is to establish a research program to understand the etiology and developmental consequences of attention-deficit/hyperactivity disorder (ADHD) comorbidities, with a particularly emphasis in sluggish cognitive tempo (SCT). As an initial step in developing this research program, I have led a series of studies examining whether ADHD and SCT are not only distinct statistically but also differentially or uniquely associated with youths' functioning. My pilot work shows that while SCT is associated with higher rates of ADHD inattention, depression, anxiety, and daytime sleepiness, SCT is nonetheless statistically distinct from these domains. I have also found that SCT symptoms are associated with both academic and social impairments, even after controlling for ADHD. Since SCT symptoms are statistically distinct from ADHD and are uniquely associated with a range of impairments, it has been argued that SCT may be disorder separate from ADHD. Moreover, the clinical significance of the SCT construct is underscored by preliminary data showing the presence of elevated SCT to predict a poorer response to psychostimulant medication in children with ADHD. This suggests that frequently-used, evidence-based ADHD treatments are inadequate for children with ADHD who also display SCT. These findings point to the importance of SCT and the need for systematic research investigating the etiology, external correlates, and developmental progression of SCT. I am currently a research faculty member within the Division of Behavioral Medicine and Clinical Psychology at Cincinnati Children's Hospital Medical Center (CCHMC), and the K23 mechanism will enable me to focus my time and effort to develop a career as an independent clinical researcher. As my research interests have evolved, I recognize the need to obtain additional training in neuropsychology and neurophysiology to allow for a more comprehensive, multi-modal examination of ADHD and SCT. 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) obtain expertise in brain-behavior relationships with a specific emphasis in neuropsychology, (2) gain knowledge in neuroscience and neuroimaging methods with a specific emphasis in magnetoencephalography (MEG) and electroencephalography (EEG), (3) obtain training in statistics and programming relevant to neuropsychological and neurophysiological research with pediatric populations, and (4) improve grant-writing skills and extend research dissemination. 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. Completion of the training and career development plan will enable me to achieve my long-term goal to establish an independent career in patient-oriented research that significantly advances our understanding of SCT and ADHD comorbidity. In order to separate out the unique correlates of SCT, I propose a research project that will be the first study to directly compare children with elevated SCT (with and without ADHD) to typically developing children and children with ADHD-only using a multi-method neuroimaging and behavioral approach. My study will use recently-validated SCT measures to recruit 184 children (ages 8-12 years) into four groups (n = 46 per group): SCT-only, ADHD-only, SCT+ADHD, and typically developing controls. All children will complete a comprehensive assessment that includes a diagnostic interview assessing SCT, ADHD, and psychiatric comorbidities, intelligence and academic achievement testing, and a battery of neuropsychological tests. A subset of participants will perform a task assessing distinct attentional networks while undergoing MEG (co- registered with structural MRI), an optimal imaging methodology given its excellent spatial and temporal resolution. This project will allow me to identify the underlying dysfunctions and impairments that distinguish SCT from ADHD, in turn having clear relevance for theory, nosology, and intervention. Cincinnati Children's Hospital provides an excellent environment to facilitate my development as an independent investigator studying brain-behavior relationships in ADHD and SCT. An exceptional mentoring team has been assembled to support my training and career development. Under the direction of Dr. Jeffery Epstein (primary sponsor), the Center for ADHD is a world-class ADHD specialty center. Also at CCHMC, Dr. Jing Xiang (Director, MEG Center; co-mentor) and Dr. Dean Beebe (Director, Neuropsychology Program; co- mentor) will provide mentorship in MEG and neuropsychology, respectively. Drs. Leanne Tamm and James Peugh will provide on-site expertise in ADHD neuroimaging and statistics, respectively. Finally, Dr. Erik Willcutt (University of Colorado Boulder) and Dr. Sandra Loo (University of California, Los Angeles) will provide external expertise in how neuropsychological and neurophysiological methods can inform models of ADHD comorbidity specifically. 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.