A longitudinal study of neural network development in children who stutter

我们对口吃的神经生物学和机械基础的理解仍然存在重大差距。 越来越多的证据表明，基底节-丘脑皮质（BGTC）和小脑（CE）可能发挥作用， 网络在口吃的持续和恢复。迄今为止，很少有人试图研究BGTC如何 CE网络结构和功能与言语内在时序的行为差异有关， 非语言手势，以及这些过程如何与口吃的持续和恢复联系起来。远景目标 是利用并显著扩展我们目前对儿童口吃的大规模调查， 描述发展性口吃背后的神经网络大脑机制。整体 本申请的目的是检查儿童和青少年中BG和CE网络的连接性， 与听觉、运动和感觉运动计时有关的口吃。核心假设是， 能力是持续卡顿的基础，这反映在BGTC和CE网络连接模式中。的 提出该项目的理由是，更好地了解皮质- 支持时间处理的皮层下网络在口吃的孩子中存在差异，这应该会导致更清晰的 解释口吃持续和恢复的机制。我们计划测试我们的中央 假设，从而通过追求以下具体目标实现我们的总体目标： 1.沿着BGTC和CE网络检查详细的大脑功能和结构连接差异沿着 与口吃的持续和恢复有关; 2.检查节奏感知的性能差异 和生产任务，因为它们涉及口吃的持久性和恢复; 3.建立一个全面的， 发展数据集，直到青春期，阐明BG和CE网络连接和多因素 影响口吃的持续和恢复。根据目标1，我们将应用先进的功能磁共振成像技术， 多位点发育神经成像联盟使用的DTI采集协议（即，ABCD）比较 儿童和青少年中BGTC和CE网络的功能和结构连接变化， 口吃在aim 2下，我们将研究皮层-皮层下网络连接和表现之间的联系 时间处理任务，税收内在的时间能力。根据目标3，我们将大大扩大我们的 儿童口吃到青少年的研究不足和动态时期的调查，利用一个 ABCD联盟的大型发展数据集。这种方法是创新的，因为它将是 第一个提供了一个详细的说明皮层下连接相关的异常时间处理功能 在口吃。这项拟议中的研究意义重大，因为它将导致对特质与 与口吃持续和恢复相关的补偿性神经网络发展。最后， 这些知识有可能为开发更好的预后工具和干预措施提供信息， 童年时口吃

Significant gaps remain in our understanding of the neurobiological, mechanistic bases of stuttering. Accumulating evidence points to the possible role of basal ganglia-thalamocortical (BGTC) and cerebellar (CE) networks in stuttering persistence and recovery. To date there have been few attempts to examine how BGTC and CE network structure and function relate to behavioral differences in intrinsic timing of speech and nonspeech gestures, and how these processes link to stuttering persistence and recovery. The long-term goal is to leverage and significantly expand our current large-scale investigation of childhood stuttering to more fully characterize the neural network-based brain mechanisms that underlie developmental stuttering. The overall objective of this application is to examine connectivity of BG and CE networks in children and adolescents who stutter relevant to auditory, motor, and sensorimotor timing. The central hypothesis is that deficient intrinsic timing ability underlies persistent stuttering, which is reflected in BGTC and CE network connectivity patterns. The rationale for the proposed project is that a better understanding of how maturational patterns of cortical- subcortical networks supporting temporal processing differ in children who stutter should lead to a clearer account of the mechanisms underlying persistence and recovery of stuttering. We plan to test our central hypothesis and, thereby, accomplish our overall objective for this project by pursuing the following specific aims: 1. Examine detailed brain functional and structural connectivity differences along the BGTC and CE networks associated with stuttering persistence and recovery; 2. Examine performance differences on rhythm perception and production tasks as they relate to stuttering persistence and recovery; 3. Establish a comprehensive, developmental dataset up to adolescence that elucidates BG and CE network connectivity and multifactorial influences associated with stuttering persistence and recovery. Under aim 1, we will apply advanced fMRI and DTI acquisition protocols used by a multi-site developmental neuroimaging consortium (i.e., ABCD) to compare functional and structural connectivity changes in the BGTC and CE networks in children and adolescents who stutter. Under aim 2, we will examine the links between cortical-subcortical network connectivity and performance on temporal processing tasks that tax intrinsic timing abilities. Under aim 3, we will significantly expand our investigations of childhood stuttering into the understudied and dynamic period of adolescence by leveraging a large developmental dataset through the ABCD consortium. This approach is innovative, because it will be the first to provide a detailed account of subcortical connectivities relevant to aberrant temporal processing function in stuttering. The proposed research is significant, because it will lead to mechanistic insights into trait versus compensatory neural network development associated with persistence and recovery of stuttering. Ultimately, such knowledge has the potential to inform the development of better prognostic tools and interventions for stuttering during childhood.