Neural subtypes of developmental stuttering

项目摘要/摘要 虽然人们很早就认识到口吃的行为异质性，但对此知之甚少。 异质性背后的机制。如果没有这方面的知识，口吃的复杂病因就无法 充分了解，个体化治疗方法的发展将继续是严峻的 受阻了。我们的长期目标是开发以神经科学为基础的治疗方法 口吃。为了追求这一目标，本申请的目的是识别 基于神经解剖异常的口吃(CWS)，并表征每个亚型的行为特征和 在语言产生过程中的大脑活动。中心假设是每种神经亚型都与 行为和脑活动的变化与其主要的神经解剖异常一致。其基本原理是 这项提议的项目是，阐明口吃的神经亚型将有助于我们理解 疾病的异质性和神经学病因，这是开发新的 针对个别神经缺陷的治疗方法。我们将通过以下方式测试我们的中心假设 追求三个具体目标。I)根据神经解剖异常的模式确定CWS的亚型。 为了达到这一目的，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CW包括神经亚型，其特征是 前额叶、基底节、丘脑皮质环路和小脑。二)描述行为特征 与每个神经亚型相关联的档案。基于当代语音运动控制的模型，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部位的功能。III)确定大脑的特征 在每个神经亚型中与语音产生相关的活动。为了实现这一目标，我们将确定 用功能磁学研究显性连续言语时不同神经亚型的脑活动差异 磁共振成像。我们的工作假设是，与对照组相比，CWS的每一种神经亚型 表现出与其主要解剖异常及其共同输入相关的激活减少 区域，左侧运动前区。在成功完成拟议的研究后，我们预计将获得 扩大了对口吃的解剖神经亚型的理解，并首次将行为和 不同亚型在言语产生过程中的脑活动差异。更好地描述神经 口吃的子类型将大大有助于我们对口吃的异质性的理解， 这是阐明这种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.