Structural and Functional Biomarkers of Attention-Deficit/Hyperactivity Disorder

摘要 ADHD是世界范围内最常见的儿童发病性神经发育障碍之一（5-10%）， 估计每年对社会造成数百亿美元的经济负担。从行为上讲，ADHD是 以持续注意力和过度活跃/冲动的问题为特征，这些问题通常会影响学业， 社会和职业能力。社会功能下降的负面后果使儿童 ADHD有更大的行为/情绪问题风险，包括焦虑和抑郁，未经治疗 患有多动症的青少年更容易吸毒、尼古丁依赖和发生车祸。 了解这种疾病的神经相关性对这一人群非常重要， 这种疾病的模型可以反过来为个性化的靶向治疗提供信息， 认知效益 我们最近的研究表明，大脑结构和功能MRI测量的不对称性可能更多 作为定量ADHD大脑发育差异的描述符有价值，而不是偏侧（左/右） 措施单独。在这项工作的基础上，我们现在将研究这些不对称性是如何改变的。 用兴奋剂药物治疗。我们假设大脑半球的不对称性差异可能 在药物治疗成功后一定程度上消退。接下来，我们将跟踪大脑白色 在药物治疗前后使用DTI成像来确定其物质变化（和不对称性）， 预测ADHD受影响青年对药物治疗的有益行为反应的潜力。然后 合理的问题-结构不对称性差异如何与ADHD的功能差异联系起来 大脑？我们将通过将结构和功能MRI特征与临床 评估分数使用创新的方法来数据聚类。我们希望这种综合方法 将提供ADHD的行为特征和定量大脑生物标志物之间的联系。 该项目通过建立在神经影像学的背景优势， 计算神经科学，同时提供转化研究的新培训， 儿童神经发育障碍的现象学和病因学课程，以及 对疑似ADHD儿童的摄入量和评估进行临床跟踪。所提供的增长 使候选人更专注于转化研究和神经发育障碍， 非常适合作为独立调查员取得成功的候选人。

Abstract ADHD is one of the most highly prevalent (5-10%) child-onset neurodevelopmental disorders worldwide with an economic burden to society estimated to be in the tens of billions per year. Behaviorally, ADHD is characterized by problems with sustained attention and hyperactivity/impulsivity that often impair academic, social, and occupational abilities. The negative consequences of diminished social functioning put children with ADHD at greater risk for behavioral/emotional problems including anxiety and depression, and untreated adolescents with ADHD are at greater risk for drug use, nicotine dependency, and automobile accidents. Understanding the neural correlates of this disorder is of high importance for this population, as improved models of the disease could in turn inform individualized targeted therapies for optimal behavioral and cognitive benefit. Our recent work suggests that brain asymmetries in structural and functional MRI measures may be more valuable as descriptors for quantifying developmental differences in the ADHD brain than lateralized (left/right) measures alone. Building on this work, we will now examine how these asymmetries are altered over the course of treatment with stimulant medications. We hypothesize that hemispheric asymmetry differences may resolve to some extent after successful response to pharmaceutical therapy. Next, we will track brain white matter changes (and asymmetries) using DTI imaging before and after medication treatment to determine their potential in predicting a beneficial behavioral response to pharmacotherapy in ADHD-affected youth. It is then reasonable to ask - how are structural asymmetry differences linked to functional differences in the ADHD brain? We will address this question by connecting structural and functional MRI features with clinical assessment scores using an innovative approach to data clustering. We expect that this integrative approach will provide a link between the behavioral traits and quantitative brain biomarkers of ADHD. This project advances the Candidate's training by building on background strengths in neuroimaging and computational neuroscience while providing new training in translational research, data collection in childhood populations, coursework in the phenomenology and etiology of pediatric neurodevelopmental disorders, and clinical shadowing of intake and assessments of children suspected to have ADHD. The growth provided will make the candidate more specialized in translational research and neurodevelopmental disorders, making the candidate well suited for success as an independent investigator.