Mechanisms of apraxia of speech in primary progressive aphasia

原发性进行性失语症言语失用的机制

• 批准号: 9320013
• 负责人: Claire Elizabeth Cordella
• 金额: $ 3.16万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9320013
• 关键词: Acoustics; Address; Age; Anatomy; Apraxias; Area; Articulation; Articulators; Auditory; Behavior; Behavior Therapy; Behavioral; Biological Markers; Biological Neural Networks; Clinical; Control Groups; Data; Detection; Development; Diagnosis; Diagnostic; Disabled Persons; Disease Progression; Feedback; Future; Goals; Image; Impairment; Individual; Inferior frontal gyrus; Intervention; Investigation; Knowledge; Language; Left; Lesion; Linguistics; Location; Magnetic Resonance Imaging; Masks; Measures; Mediating; Mind; Modeling; Motor; Motor Cortex; Movement; Neurologic; Outcome; Patients; Performance; Persons; Population; Prevalence; Primary Progressive Aphasia; Process; Production; Quality of life; Research; Role; Specific qualifier value; Speech; Speech Disorders; Stroke; Theoretical model; Thick; Thinness; Time; Validation; Variant; Voice; aphasic; auditory feedback; base; cerebral atrophy; improved; inclusion criteria; indexing; interest; motor control; neuromechanism; patient subsets; post stroke; sound

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.

项目概要 原发性进行性非流利变体患者言语失用症 (AOS) 的患病率 失语症 (PPA) 估计占 80%，10 通常被认为是失语症最突出和最令人衰弱的方面。 这部分患者的疾病进展。此外，AOS 是以下疾病的核心诊断纳入标准： PPA 的非流畅变体，14 使得失用言语的检测和表征在临床中至关重要 环境。然而，仍然很难描述这一人群中失用性言语缺陷的特征，这在很大程度上是由于 缺乏对造成这些缺陷的言语运动控制机制的理解。缺乏 机械性的理解也阻碍了行为干预方法的发展，因为很少有 众所周知，潜在的无序语音控制过程可以作为有效的目标 治疗。因此，需要研究言语运动控制的机制 这是 PPA 中 AOS 的基础。先前对其他神经受损人群的研究表明，AOS 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来研究前馈语音运动控制的完整性 伴有 PPA 和 AOS 的个体的过程。在目标 1 中，我们将使用听觉掩蔽范例 评估反馈抑制（即强制依赖前馈控制网络）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，与一组患有 PPA 和 AOS 的个体相比 仅患有 PPA 的个体 (PPA/-AOS) 和一组健康年龄匹配的对照 (HC)。先前的研究 中风引起的失语症人群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生成性能成比例更大的下降 PPA/+AOS 组与 PPA/-AOS 或 HC 组相比。在目标 2 中，我们将关联 由于 MRI 衍生的皮质测量的反馈抑制导致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。我们的初步数据表明皮质 与运动言语功能相关的选定区域中与发音器官运动减慢相关的萎缩， 包括腹侧前运动皮质和辅助运动皮质。拟议研究的总体目标是 评估伴随 PPA 的个体之间前馈语音控制网络的完整性 AOS，通过这种方式，可以加深对 PPA 中 AOS 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。