Mechanisms of apraxia of speech in primary progressive aphasia

项目总结 言语失用症(AOS)在具有不流利的原发进行性变种的个体中的患病率 失语症(PPA)估计有80%，10，通常被认为是最突出和最衰弱的方面 这一亚组患者的疾病进展。此外，AOS是一项核心诊断纳入标准 PPA的非流利变体，14使得失用言语的检测和特征在临床上至关重要 布景。然而，很大程度上由于失用障碍的原因，仍很难确定该人群中失用言语缺陷的特征。 缺乏对这些缺陷背后的言语运动控制机制的了解。缺乏 机械性的理解也阻碍了行为干预方法的发展 已知潜在的无序的语音控制过程可以作为有效的目标 治疗。因此，有必要研究语音运动控制的机制 这是PPA中AOS的基础。在其他神经受损人群中的先前研究表明，AOS是 由前馈语音运动控制过程受损引起。在拟议的研究中，我们将使用 基于行为和成像的分析以调查前馈语音运动控制的完整性 伴随着PPA和AOS的个体的过程。在目标1中，我们将使用听觉掩蔽范式 评估反馈抑制(即，对前馈控制网络的强制依赖)对语音的影响 一组同时患有PPA和AOS(PPA/+AOS)的个体的运动表现，与一组 仅患有PPA的个体(PPA/-AOS)和一组年龄匹配的健康对照组(HC)。先前对…的研究 中风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按比例更大地降低 PPA/+AOS组与PPA/-AOS或HC组比较。在目标2中，我们将关联 皮层MRI测量反馈抑制引起的言语产生能力的变化 三个假设驱动的感兴趣区(ROI)的厚度。我们的初步数据显示大脑皮质 在与运动语音功能相关的选定区域中，与发音架运动减慢相关的萎缩， 包括腹侧运动前皮质和辅助运动皮质。拟议研究的总体目标是 评估伴有PPA和PPA的个体的前馈语音控制网络的完整性 AOS，通过这种方式，促进了对AOS在PPA中出现的理解。这项研究的结果将 提供计算语音生成模型的进一步实验验证，最重要的是，将 用于为临床环境中的表征和干预方法提供信息。

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.