A longitudinal study of neural network development in children who stutter

我们对口吃的神经生物学和机制基础的理解仍然存在重大差距。

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.