Exploring the validity of articulatory impairment phenotypes in speech motor disorders

项目总结 言语运动障碍对个人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。自从个性化医学出现以来，临床表型已经 成为康复研究中一个日益重要的结构，因为它们有助于识别 针对患者独特的损伤特征个性化的治疗目标3。然而，目前有 没有建立一套客观的措施来表现言语中观察到的发音障碍 机动障碍32。因此，临床医生对截然不同的患者采取了广泛的治疗策略。 关节缺陷，这往往导致不同的治疗结果97。给出了特定的 关节异常和病理生理学1、16、81、90以及关节子系统对 理解力14、53、69、77，迫切需要确定以下人群的发音障碍表型 言语运动障碍的谱系。拟议的研究将全面描述发音的特征 假想运动分化的四个神经科人群(与健康对照相比)的损害 缺陷：(1)非流利变种的原发进行性失语(NfvPPA)或原发进行性失用 语言(PPAOS)，(2)肌萎缩侧索硬化症(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的 电机控制的框架(即协调、一致性、速度、精度和速率)，由 半自动声学功能集。目标1将使用线性判别分析(LDA)来比较 各组在顺序运动期间的发音性能(由声学特征集索引) 速率(SMR)任务。LDA将根据言语严重性进行调整，以确定 声学特征，并确保严重性差异不是导致表型差异的原因。Aim 2将使用 多元回归分析(MRA)以确定与语音清晰度最相关的发音障碍 通过将在每个声学特征上的表现与在 句子可理解性测试(SIT)96.这项拟议研究的总体目标是增进我们对 不同言语运动亚型发音障碍表型的差异性。由此产生的结果 研究将(1)促进基于减损的方法的开发，(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沟通能力下降的影响。这项工程属于 NIDCD在语音、语音和语言研究方面的优先领域3，因为它研究的生物标记物可以 支持语音障碍患者的诊断、治疗和进展监测。此外， 这项工作与行为表型的战略计划密切一致，并总体上与 NIDCD的使命是加深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.