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: 9190796
• 负责人: Claire Elizabeth Cordella
• 金额: $ 3.62万
• 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/9190796
• 关键词: Acoustics; Address; Age; Anatomy; Apraxias; Area; Articulators; Auditory; Behavior; Behavior Therapy; Biological Markers; Clinical; Data; Detection; Development; Diagnosis; Diagnostic; Disabled Persons; Disease Progression; Feedback; Future; Goals; Image; Impairment; Individual; Inferior frontal gyrus; Intervention; Investigation; Joints; Knowledge; Language; Lead; Left; Lesion; Linguistics; Location; Magnetic Resonance Imaging; Masks; Measures; Mediating; Mind; Modeling; Motor; Motor Cortex; Movement; 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; Time; Validation; Variant; Voice; Work; aphasic; auditory feedback; base; cerebral atrophy; handicapping condition; improved; inclusion criteria; indexing; interest; motor control; neuromechanism; patient subsets; post stroke; relating to nervous system; 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.

项目摘要 具有非浮力变体的个体中语音（AOS）的流行率（AOS）的流行率 失语症（PPA）估计为80％，10，通常被认为是最显着，最令人衰弱的方面 这一子集的疾病进展。此外，AOS是核心诊断纳入标准 PPA的非氟变体，14使临床中的失毒语音检测和表征至关重要 环境。但是，很难表征该人群中的失毒语音缺陷，这在很大程度上是由于 由于缺乏对这些缺陷的言语运动控制机制的理解。缺乏 机械理解还障碍了行为干预方法的发展，因为很少 关于潜在无序的语音控制过程的了解，该过程可以作为有效目标 治疗。因此，需要研究调查语音运动控制机制 这是PPA中的AOS。对其他神经学障碍人群的事先研究表明，AOS是 由馈电语音电机控制过程受损而导致。在拟议的研究中，我们将使用 基于行为和成像的分析，以研究馈电语音电机控制的完整性 伴随PPA和AOS的个体的过程。在AIM 1中，我们将使用听觉掩蔽范式 评估反馈抑制的影响（即强迫依赖馈电控制网络）对语音的影响 与一组一组PPA和AOS（PPA/+AOS）的个体的运动性能相比 只有PPA（PPA/-AOS）和一组健康年龄匹配的对照（HC）的个体。先前的研究 中风引起的失语症的反馈抑制以及我们实验室的初步数据 反馈的抑制作用将导致语音生产绩效的比例更大 与PPA/-AOS或HC组相比，PPA/+AOS组。在AIM 2中，我们将使 通过MRI衍生的皮质测量，由于反馈抑制而导致的语音生产性能变化 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 与运动语音功能相关的某些区域中的枢轴运动减慢相关的萎缩， 包括腹侧和补充运动皮层。拟议研究的总体目标是 评估伴随PPA和 AOS，并以这种方式提高对AOS在PPA中的理解。这项研究的结果将 提供计算语音生产模型的进一步实验验证，最重要的是，将 用于在临床环境中为表征和干预的方法提供信息。