Neural subtypes of developmental stuttering

项目总结/摘要 虽然口吃的行为异质性早已被认识到，但人们对口吃的行为异质性知之甚少。 异质性背后的机制。没有这些知识，口吃的复杂病因就不能 充分理解，个性化治疗方法的发展将继续受到严重影响。 受限我们的长期目标是开发基于神经科学的治疗方法， 口吃为了实现这一目标，本申请的目的是鉴定儿童的亚型，其 口吃（CWS）基于神经解剖学异常，并表征每种亚型的行为特征， 大脑在说话过程中的活动。核心假设是，每种神经亚型与 行为和大脑活动的变化与其主要的神经解剖学异常一致。的基本原理 这个被提议的项目是阐明口吃的神经亚型将有助于我们理解 异质性和神经系统病因的疾病，这是一个重要的基础，开发新的 针对个体神经缺陷的治疗方法。我们将测试我们的中心假设， 追求三个具体目标。i）基于神经解剖学异常的模式识别CWS的亚型。 为了实现这一目标，我们将使用聚类方法来分析CWS中的灰质体积模式。我们 假设CWS包括神经亚型，其特征在于在神经元中的初级结构异常。 前额区、基底神经节丘脑皮质回路和小脑。ii）描述行为特征 与每个神经亚型相关的特征。基于当代语言运动控制模型，我们 假设每种神经亚型在口吃行为、语言能力和言语运动方面都不同 表现取决于其主要神经解剖异常位点的功能。iii）表征大脑 与每个神经亚型的言语产生相关的活动。为达致这个目标，我们会 使用功能磁共振技术研究显性连续言语时神经亚型之间的脑活动差异 共振成像我们的工作假设是，与对照组相比，CWS的每种神经亚型都将 表现出与其主要解剖异常及其共同输入相关的激活减少 左前运动区待建议的研究成功完成后，我们预期可 扩展了对口吃的解剖神经亚型的理解，并首次将行为和 不同亚型之间在言语产生过程中的脑活动差异。更好地表征神经 口吃的亚型将大大有助于我们理解口吃的异质性， 这是阐明该疾病复杂病因的重要一步。

Project Summary/Abstract While the behavioral heterogeneity of stuttering has been long recognized, very little is known about mechanisms underlying the heterogeneity. Without this knowledge, the complex etiology of stuttering cannot be fully understood, and the development of individualized treatment approaches will continue to be severely hindered. Our long-term goal is to develop neuroscience-based treatment approaches for developmental stuttering. In pursuit of this goal, the objective of the present application is to identify subtypes of children who stutter (CWS) based on neuroanatomical anomalies and characterize each subtype’s behavioral profiles and brain activity during speech production. The central hypothesis is that each neural subtype is associated with behavioral and brain activity changes consistent with its primary neuroanatomical anomalies. The rationale of this proposed project is that elucidating the neural subtypes of stuttering will help us understand the heterogeneity and neurological etiologies of the disorder, which is an important basis for developing new treatment approaches that target individual neurological deficits. We will test our central hypothesis by pursuing three specific aims. i) Identify subtypes of CWS based upon patterns of neuroanatomical anomalies. To achieve this aim, we will use a clustering method to analyze gray matter volume patterns in CWS. We hypothesize that CWS comprise neural subtypes, characterized by primary structural anomalies in the prefrontal areas, the basal ganglia thalamocortical circuit and the cerebellum. ii) Characterize behavioral profiles associated with each neural subtype. Based on contemporary models of speech motor control, we hypothesize that each neural subtype will differ in both stuttering behaviors, language ability, and speech motor performance depending on the functions of its primary neuroanatomical anomaly loci. iii) Characterize brain activity associated with speech production in each neural subtype. To achieve this aim, we will identify differences in brain activity between neural subtypes during overt continuous speech using functional magnetic resonance imaging. Our working hypothesis is that compared to controls, each neural subtype of CWS will exhibit reduced activation associated with its primary anatomical anomalies as well as their common input region, the left premotor areas. Upon successful completion of the proposed research, we expect to gain an expanded understanding of anatomical neural subtypes of stuttering, and for the first time, link behaviors and brain activity differences during speech production among the different subtypes. Better characterizing neural subtypes of stuttering would substantially contribute to our understanding of the heterogeneity of stuttering, which is an important step in elucidating the disorder’s complex etiology.