Mechanisms of apraxia of speech in primary progressive aphasia

项目摘要 言语失用症（AOS）在原发性进行性失语症非流利型患者中的患病率 失语症（PPA）估计为80%，10，通常被认为是最突出和衰弱的方面， 这部分患者的疾病进展。此外，AOS是一项核心诊断入选标准， PPA的非流利变体，14使得在临床中对失语症言语的检测和表征至关重要。 设置.然而，在这一人群中仍然很难描述失能性言语缺陷的特征，这在很大程度上是由于 缺乏对这些缺陷背后的言语运动控制机制的理解。缺乏 机械的理解也阻碍了行为干预方法的发展， 已知潜在的紊乱的语音控制过程，可以作为有效的目标， 治疗因此，有必要对言语运动控制机制进行研究 这是PPA中AOS的基础。先前在其他神经功能受损人群中的研究表明，AOS是 由受损的前馈语言运动控制过程引起。在研究中，我们将使用 基于行为和成像的分析，以研究前馈语言运动控制的完整性 在伴有PPA和AOS的个体中进行。在目标1中，我们将使用听觉掩蔽范式 为了评估反馈抑制的效果（即，对前馈控制网络的强制依赖）对语音的影响 一组PPA和AOS（PPA/+AOS）患者的运动表现，与一组 仅患有PPA的个体（PPA/-AOS）和一组健康年龄匹配的对照（HC）。以前的研究 在中风诱发的失语症人群中的反馈抑制，以及我们实验室的初步数据表明， 反馈抑制将导致语音产生性能成比例地更大的递减， PPA/+AOS组与PPA/-AOS或HC组相比。在目标2中，我们将关联 用MRI导出的皮层测量结果，由于反馈抑制引起的言语产生性能的变化 三个假设驱动的感兴趣区域（ROI）的厚度。我们的初步数据显示大脑皮层 在与运动语言功能相关的选定区域中与咬合架运动减慢相关的萎缩， 包括腹侧前运动皮层和辅助运动皮层。拟议研究的总体目标是 评估伴随PPA的个体中前馈语音控制网络的完整性， AOS，并以这种方式，推进AOS的理解，因为它发生在PPA。这项研究的结果将 为计算语音产生模型提供进一步的实验验证，最重要的是， 用于告知临床环境中的表征和干预方法。

PROJECT SUMMARY The prevalence of apraxia of speech (AOS) among individuals with a non-fluent variant of primary progressive aphasia (PPA) is estimated to be 80%,10 and is often considered the most salient and debilitating aspect of disease progression for this subset of patients. In addition, AOS is a core diagnostic inclusion criterion for the non-fluent variant of PPA,14 making the detection and characterization of apraxic speech crucial in a clinical setting. However, it remains difficult to characterize apraxic speech deficits in this population, due in large part to a lack of understanding of the mechanisms of speech motor control that underlie these deficits. The lack of mechanistic understanding also handicaps the development of behavioral intervention approaches since little is known about underlying disordered speech control processes that could serve as effective targets of treatment. Therefore, there is a need for research that investigates the mechanisms of speech motor control that underlie AOS in PPA. Prior research in other neurologically impaired populations suggests that AOS is caused by impaired feedforward speech motor control processes. In the proposed research, we will use behavior- and imaging-based analyses to investigate the integrity of feedforward speech motor control processes in individuals with concomitant PPA and AOS. In Aim 1, we will use an auditory masking paradigm to assess the effect of feedback inhibition (i.e., forced reliance on feedforward control networks) on speech motor performance for a group of individuals with both PPA and AOS (PPA/+AOS), as compared to a group of individuals with PPA only (PPA/-AOS), and a group of healthy age-matched controls (HC). Prior research on feedback inhibition in a stroke-induced aphasic population, as well as preliminary data out of our lab, suggest that feedback inhibition will lead to a proportionally greater decrement in speech production performance for the PPA/+AOS group as compared to either the PPA/-AOS or HC groups. In Aim 2, we will correlate the change in speech production performance due to feedback inhibition with MRI-derived measures of cortical thickness in three hypothesis-driven regions of interest (ROIs). Our preliminary data has indicated cortical atrophy associated with slowed articulator movement in select regions related to motor speech function, including the ventral premotor and supplementary motor cortices. The overall goal of the proposed research is to evaluate the integrity of feedforward speech control networks among individuals with concomitant PPA and AOS, and in this way, advance the understanding of AOS as it occurs in PPA. Results of this research will provide further experimental validation of computational speech production models and most importantly, will be used to inform approaches to characterization and intervention in the clinical setting.