Exploring the validity of articulatory impairment phenotypes in speech motor disorders

项目摘要 言语运动障碍对个体的沟通能力有深远的影响，通常会导致 生活质量显著下降35，49.自个性化医疗出现以来，临床表型 成为康复研究中越来越重要的结构，因为它们有助于识别 针对患者独特的损伤情况制定个性化的治疗目标3。然而，目前 没有建立一套客观的措施，以表型在言语中观察到的发音障碍 运动障碍32.因此，临床医生采用广泛的治疗策略， 发音缺陷，这往往会导致可变的治疗结果97。考虑到特定的 发音异常和病理生理学1，16，81，90和发音子系统的影响， 可理解性14，53，69，77，有一个关键的需要，以确定整个发音障碍表型 一系列的言语运动障碍拟议的研究将全面表征发音 四个神经系统人群（与健康对照组相比）的假设发散运动障碍 缺陷：（1）原发性进行性失语症（nfvPPA）的非流利变体或原发性进行性失用症， 言语障碍（PPAOS），（2）肌萎缩侧索硬化（ALS），（3）帕金森病（PD），和（4） 脊髓小脑性共济失调（SCA）。发音障碍的特征将基于假设驱动 运动控制的框架（即，协调性、一致性、速度、精度和速率）， 半自动化的声学特征集。目标1将使用线性判别分析（LDA）来比较 在顺序运动期间各组的发音性能（如由声学特征集索引的 速率（SMR）任务。LDA将根据言语严重程度进行调整，以确定 声学特征，并确保严重性差异不会导致表型差异。Aim 2将使用 多元回归分析（MRA），以确定与可懂度最相关的发音缺陷， 通过将每个声学特征的性能与 96.第96章我的天拟议研究的总体目标是提高我们对以下问题的认识： 不同言语运动亚型的构音障碍表型的多样性。结果从这个 研究将（1）促进基于损伤的方法的发展，（2）产生更细粒度的结果 评估行为或药物治疗效果的措施，以及（3）阐明 不同的发音机制对功能性沟通下降的贡献。这个项目属于福尔斯 NIDCD的优先领域3在声音，言语和语言研究，因为它调查生物标志物， 支持言语障碍患者的诊断、治疗和进展监测。此外，委员会还认为， 这项工作与行为表型分析的战略计划密切相关， NIDCD的使命是增进我们对沟通障碍的认识和理解。

PROJECT SUMMARY Speech motor disorders have profound impacts on an individual’s ability to communicate, often leading to a significant reduction in quality of life35,49. Since the advent of personalized medicine, clinical phenotypes have become an increasingly important construct in rehabilitation research, as they facilitate the identification of treatment targets that are individualized to a patient’s unique impairment profile3. There is, however, currently no established set of objective measures that to phenotype the articulation impairments observed in speech motor disorders32. Consequently, clinicians employ broad treatment strategies for patients with distinct articulatory deficits, which often result in variable therapy outcomes97. Given the links between specific articulatory abnormalities and pathophysiologies1,16,81,90 and the impact of the articulatory subsystem on intelligibility14,53,69,77, there is a critical need to determine the articulatory impairment phenotypes across the spectrum of speech motor disorders. The proposed study will comprehensively characterize articulatory impairments in four neurologic populations (compared to healthy controls) with hypothetically divergent motor deficits: (1) the nonfluent variant of primary progressive aphasia (nfvPPA) or primary progressive apraxia of speech (PPAOS), (2) amyotrophic lateral sclerosis (ALS), (3) Parkinson’s disease (PD), and (4) spinocerebellar ataxia (SCA). Articulatory impairments will be characterized based on a hypothesis-driven framework of motor control (i.e., Coordination, Consistency, Speed, Precision, and Rate) composed of a semi-automated acoustic feature set. Aim 1 will use a linear discriminant analysis (LDA) to compare the articulatory performance (as indexed by the acoustic feature set) of the groups during the sequential motion rate (SMR) task. The LDA will be adjusted for speech severity to determine the true discriminatory power of the acoustic features and ensure that severity differences are not driving phenotype differences. Aim 2 will use a multiple regression analysis (MRA) to determine the articulatory deficits most associated with intelligibility in the four neurologic populations by correlating performance on each acoustic feature with performance on the Sentence Intelligibility Test (SIT)96. The overall goal of the proposed research is to advance our knowledge of the diversity of articulatory impairment phenotypes in different speech motor subtypes. Results from this research will (1) facilitate the development of impairment-based approaches, (2) yield more granular outcome measures for evaluating the efficacy of behavioral or pharmaceutical treatments, and (3) elucidate the contribution of distinct articulatory mechanisms to declines in functional communication. This project falls under NIDCD’s Priority Area 3 in Voice, Speech, and Language Research, as it investigates biomarkers that could support diagnosis, treatment, and progress monitoring in individuals with speech impairments. Furthermore, this work is closely aligned with the strategic plan for behavioral phenotyping and is overall consistent with the mission of NIDCD to further our knowledge and understanding of communication disorders.