Concussion and Attention-Deficit/Hyperactivity Disorder: Investigating the relationship between cognitive outcome, prescription stimulants, and functional MRI biomarkers in the ABCD study.

项目摘要/摘要 创伤性脑损伤(TBI)是导致儿童后天性神经功能障碍的最常见原因。轻度颅脑损伤，或 脑震荡在青春期非常普遍，与短期和长期的认知缺陷有关，主要是 注意力不集中。注意力缺陷多动障碍(ADHD)在儿童中同样普遍，代表着一种 注意力不集中的主要形式，即使没有头部损伤的病史也会发生。它们之间的表型相似性 原发性ADHD与脑震荡后注意力不集中的长期症状都是一个诊断难题 和临床机会之窗，了解脑损伤影响认知的机制。与此相一致 这个K23奖项的目标是为申请者提供必要的培训，以识别不同的 原发性ADHD儿童与有脑震荡病史的ADHD儿童的脑活动特征，这将 激发针对这些注意力不集中症状的特定机制治疗。拟议的研究利用了 青少年大脑认知发展研究，这是有史以来规模最大的脑震荡儿童队列研究 配合详细的认知和功能磁共振数据，以实现这一目标。它充分利用了最棒的 申请人的导师和合作者的认知神经科学和成像专业知识，以实现 申请者的短期培训目标：认知评估(博士)、脑损伤研究(博士)、多动症 研究(Dr.Fair)、基于任务(Stop Signal，n-Back)的fMRI(Dr.BARCH)、静息状态fMRI(Dr.Dosenbach)，以及 多变量成像统计学(汤普森博士)。拟议的培训将有助于申请者的长期 目标是成为认知神经成像领域的独立内科医生和科学家。这些培训 目标将通过拟议的研究来推进。首先，申请者将使用多变量功能磁共振成像方法 检测儿童与任务相关的大脑激活(目标1a)和静息状态连接(1b)的不同模式 有ADHD和脑震荡病史的患者，与对照组和单独情况下的任何一种情况相比。然后申请者 我将使用任务相关和静息状态来研究自上次脑震荡(目标2)以来的时间与功能磁共振的相关性 功能磁共振成像。最后，申请人将对处方兴奋剂的效果进行探索性分析 这些组的大脑活动(目标3)。值得注意的是，建议的方法和技术可以扩展到 回答许多关于神经性和认知障碍之间的交集的悬而未决的问题 在ABCD和未来的成像研究中。拥有采用多种融合技术的研究计划 为了审问与脑震荡及其认知后遗症有关的神经特征，申请人将继续 在他的独立职业生涯中，解决与NINDS相关的研究问题。

Project Summary/Abstract Traumatic brain injury (TBI) is the most common cause of acquired neurological deficits in children. Mild TBI, or concussion, is highly prevalent in adolescence, and is linked with short- and long-term cognitive deficits, chiefly inattention. Attention-deficit hyperactivity disorder (ADHD) is similarly prevalent in children and represents a primary form of inattention that occurs even without a history of head injury. The phenotypic similarity between primary ADHD vs long-term symptoms of inattention subsequent to concussion is both a diagnostic dilemma and clinical window of opportunity into the mechanisms by which brain injury affects cognition. In line with this framework, the goal of this K23 award is to provide the applicant with training necessary to identify distinct signatures of brain activity in children with primary ADHD vs ADHD with a history of concussion, which will motivate mechanism-specific treatments for these inattention symptoms. The proposed research leverages the Adolescent Brain Cognitive Development study, which is the largest ever cohort of children with concussion paired with detailed cognitive and functional MRI data, to achieve this goal. It capitalizes on the the superb cognitive neuroscience and imaging expertise of the applicant's mentors and collaborators to achieve the applicant’s short-term goals of training in cognitive assessment (Dr. Barch), TBI research (Dr. Brody), ADHD research (Dr. Fair), task-based (stop signal, n-back) fMRI (Dr. Barch), resting state fMRI (Dr. Dosenbach), and multivariate imaging statistics (Dr. Thompson). The proposed training will facilitate the applicant’s long-term goal of becoming an independent physician-scientist in the field of cognitive neuroimaging. These training goals will be advanced through the proposed research. First, the applicant will use multivariate fMRI methods to detect distinct patterns of task-related brain activation (Aim 1a) and resting-state connectivity (1b) in children with ADHD and a history of concussion, compared to controls and either condition alone. Then the applicant will investigate the fMRI correlates of time since last concussion (Aim 2) using task-related and resting-state fMRI. Finally, the applicant will perform exploratory analysis on the effects of prescription stimulant medications on brain activity in these groups (Aim 3). Notably, the proposed methods and techniques can be extended to answer many other outstanding questions about the intersection between neurological and cognitive disorders in the ABCD and future imaging studies. With a research program that employs multiple converging techiques to interrogate neural signatures related to concussion and its cognitive sequelae, the applicant will continue to address research questions relevant to the NINDS throughout his independent career.