Structural and functional cerebellar-cerebral connectivity in children with ADHD

小脑是一种研究不足的大脑结构，与注意力缺陷/多动障碍(ADHD)有关，ADHD是儿童最常见的神经发育障碍。ADHD症状已被证明会损害学习能力并扰乱生活质量。然而，ADHD的神经基础和小脑的作用都不完全清楚。更好地了解ADHD影响的神经系统是至关重要的，以改善那些受到ADHD困扰的人的靶向治疗选择。一种主要的理论是，ADHD儿童经历的症状和认知困难是由网络组织功能障碍引起的。到目前为止，这项研究的大部分都集中在皮质网络上。然而，考虑到小脑参与了ADHD，关键是要考虑小脑是如何与ADHD中已知的改变的皮质网络相联系的。为此，这项拟议的研究试图调查小脑-大脑网络，以努力阐明我们对小脑功能障碍与ADHD之间关系的理解。这项建议的主要目标是调查：(A)在结构和功能网络分析的背景下，小脑和大脑之间的联系，以及(B)这些联系如何与工作记忆能力相关联。首先，我将测试ADHD儿童与典型发育(TD)儿童小脑结构连接的差异(目标1a)，并调查结构连接是否可以预测工作记忆能力(目标1b)。其次，我将检测ADHD儿童和TD儿童的小脑-大脑功能连接(目标2a)，并测试功能连接是否能预测工作记忆能力(目标2b)。这项提议将使我有机会通过学习如何使用扩散加权成像数据执行网络级分析和结构数据分析，来扩展我先前对感兴趣区域功能连通性分析的知识。总体而言，本研究将阐明小脑与大脑的关系及其在ADHD中的参与，这可能也适用于其他神经发育障碍的小脑功能障碍。重要的是，这项研究将使我们了解ADHD的神经基础，并最终可能导致针对ADHD大脑系统紊乱的治疗方法的开发。此外，成功完成这项研究计划和培训将使我能够发展必要的技能，以过渡到终身独立研究职位。

The cerebellum is an understudied brain structure that has been implicated in attention-deficit/hyperactivity disorder (ADHD), the most commonly diagnosed neurodevelopmental disorder of childhood. ADHD symptoms have been shown to impair learning ability and disrupt quality of life. However, neither the neural basis of ADHD, nor the cerebellum’s role, is entirely understood. It is critical to better understand the neural systems impacted in ADHD to improve target treatment options for those who are afflicted by the disorder. A leading theory is that symptoms and cognitive difficulties experienced by children with ADHD are caused by dysfunctional network organization. Thus far, the majority of this research has been focused on cortical networks. However, given cerebellar involvement in ADHD, it is crucial to consider how the cerebellum is connected with cortical networks known to be altered in ADHD. To this avail, this proposed research seeks to investigate cerebellar-cerebral networks in an effort to elucidate our understanding of the relationship between cerebellar dysfunction and ADHD. The main goals of this proposal are to investigate: (a) connections between the cerebellum and cerebrum in the context of structural and functional network analyses, and (b) how these connections are associated with working memory ability. First, I will test for differences in structural cerebellarcerebral connectivity in children with ADHD in comparison to typically developing (TD) children (Aim 1a) and investigate whether structural connectivity can predict working memory ability (Aim 1b). Second, I will examine functional cerebellar-cerebral connectivity in children with ADHD in comparison to TD children (Aim 2a) and test whether functional connectivity can predict working memory ability (Aim 2b). This proposal will afford me the opportunity to expand my previous knowledge of region-of-interest functional connectivity analyses by learning how to perform network-level analyses and structural data analysis with diffusion weighted imaging data. Overall, this research will elucidate the cerebellum’s relationship with the cerebrum and its involvement in ADHD, which may be applicable to other neurodevelopmental disorders with cerebellar dysfunction as well. Importantly, this research will inform our understanding of the neural basis of ADHD and may ultimately lead to the development of treatments that target brain systems that are disrupted in ADHD. Moreover, the successful completion of this research proposal and training will allow me to develop the skillsets necessary to transition into a tenured independent research position.