Structural and functional cerebellar-cerebral connectivity in children with ADHD

小脑是一种尚未得到充分研究的大脑结构，它与注意力缺陷/多动障碍（ADHD）有关，这是最常见的儿童神经发育障碍。 ADHD 症状已被证明会损害学习能力并破坏生活质量。然而，人们对多动症的神经基础和小脑的作用都还没有完全了解。更好地了解多动症影响的神经系统对于改善患有这种疾病的人的目标治疗选择至关重要。一个主流理论认为，多动症儿童所经历的症状和认知困难是由功能失调的网络组织引起的。到目前为止，这项研究的大部分都集中在皮质网络上。然而，考虑到小脑参与多动症，考虑小脑如何与已知在多动症中发生改变的皮质网络连接是至关重要的。为此，这项拟议的研究旨在调查小脑-大脑网络，以阐明我们对小脑功能障碍与多动症之间关系的理解。该提案的主要目标是研究：（a）在结构和功能网络分析的背景下小脑和大脑之间的连接，以及（b）这些连接如何与工作记忆能力相关。首先，我将测试 ADHD 儿童与典型发育 (TD) 儿童相比，结构性小脑大脑连接的差异（目标 1a），并研究结构连接是否可以预测工作记忆能力（目标 1b）。其次，我将检查 ADHD 儿童与 TD 儿童的功能性小脑-大脑连接（目标 2a），并测试功能连接是否可以预测工作记忆能力（目标 2b）。该提案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之前对感兴趣区域功能连接分析的知识。总体而言，这项研究将阐明小脑与大脑的关系及其与 ADHD 的关系，这也可能适用于伴有小脑功能障碍的其他神经发育障碍。重要的是，这项研究将帮助我们了解多动症的神经基础，并可能最终导致针对多动症中受损的大脑系统的治疗方法的开发。此外，成功完成这项研究计划和培训将使我能够培养过渡到终身独立研究职位所需的技能。

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.