一种基于机制的分层时间言语组织框架，用于神经退行性疾病中运动性言语障碍的客观鉴别评估。

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中文摘要

引言： 言语按照潜在的语言结构、时间协调、韵律组织和呼吸需求，被组织成离散的话语和停顿。时间性言语特征，包括节律和停顿模式，受多种神经生理机制调控，并为运动性言语障碍的评估和管理提供了有价值的见解。本研究采用一种基于机制的分层时间言语组织分析框架，以得出可解释的客观指标，用于评估神经退行性疾病中的节律和停顿障碍。
方法： 在段落朗读任务中，从两个神经退行性疾病组——肌萎缩侧索硬化（ALS）和帕金森病（PD）——以及神经健康对照组（HC）获取了口面部运动学和声学记录。使用自动化分析程序，得出运动学节律指标（基于运动）和声学节律指标（基于声音），以表征在韵律、音节和亚音节水平上构音运动和临界频带声学调制包络的分层节律调制。得出停顿指标，以表征句内和句间停顿模式。比较各组之间的节律和停顿模式。随后对声学得出的节律和停顿指标进行（1）判别分析，用于ALS、PD和HC组之间的多类分类，以及（2）正则化回归模型，以评估其与功能结局的关联。
结果： 两个神经退行性疾病队列均表现出分层节律调制的重组，其特征为韵律水平调制减少和音节水平调制增加。然而，这些变化在ALS中主要由构音障碍驱动，在PD中主要由呼吸-喉部障碍驱动。此外，两个队列均表现出音节内时间组织规律性降低和句内停顿模式改变，而ALS队列还表现出句间停顿的额外变化。捕捉这些节律和停顿障碍的指标表现出有希望的分类性能（平均准确率 = 0.77；平均曲线下面积[AUC] = 0.84），并与跨疾病的功能性言语衰退具有有意义的关联。
讨论： 节律和停顿指标捕捉到了ALS和PD中节律和停顿障碍背后生理基质的疾病特异性亚临床变化，显示出作为临床适用的客观标志物的潜力，以实现更准确的鉴别诊断、靶向干预和基于测量的神经退行性运动性言语障碍护理。

英文摘要

INTRODUCTION: Speech is organized into discrete utterances and pauses in accordance with underlying linguistic structure, temporal coordination, prosodic organization, and respiratory demands. Temporal speech characteristics, including rhythmic and pausing patterns, are governed by multiple neurophysiological mechanisms and provide valuable insights for the assessment and management of motor speech disorders. This study employed a mechanistically informed analytic framework of hierarchical temporal speech organization to derive interpretable, objective measures for assessing rhythmic and pausing disturbances in neurodegenerative diseases.
METHODS: Orofacial kinematic and acoustic recordings were obtained from two neurodegenerative disease groups-amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD)-along with a neurologically healthy control (HC) group, during a passage reading task. Using automated analytic procedures, kinematic rhythm measures (movement-based) and acoustic rhythm measures (sound-based) were derived to characterize hierarchical rhythmic modulation of articulatory movements and critical-band acoustic modulation envelopes at prosodic, syllabic, and sub-syllabic levels. Pause measures were derived to characterize within- and between-sentence pausing patterns. Rhythmic and pausing patterns were compared across groups. The acoustically derived rhythm and pause measures were subsequently subjected to (1) discriminant analyses for multiclass classification among the ALS, PD, and HC groups, and (2) regularized regression models to evaluate their associations with functional outcomes.
RESULTS: Both neurodegenerative disease cohorts exhibited a reorganization of hierarchical rhythmic modulation characterized by reduced prosodic-level modulation and increased syllabic-level modulation. Such changes were, however, driven primarily by articulatory impairment in ALS and by respiratory-laryngeal impairment in PD. In addition, both cohorts showed reduced regularity of intra-syllabic temporal organization and altered within-sentence pausing patterns, whereas the ALS cohort exhibited additional changes in between-sentence pausing. Measures capturing these rhythmic and pausing disturbances demonstrated promising classification performance (mean accuracy = 0.77; mean area under the curve [AUC] = 0.84) and meaningful associations with functional speech decline across diseases.
DISCUSSION: The rhythm and pause measures captured disease-specific subclinical changes in the physiological substrates underlying rhythmic and pausing disturbances in ALS and PD, demonstrating potential as clinically applicable, objective markers to enable more accurate differential diagnosis, targeted intervention, and measurement-based care for neurodegenerative motor speech disorders.