Yana Yunusova

Bulbar and speech motor assessment in ALS: Challenges and future directions

Abstract Bulbar motor deterioration due to amyotrophic lateral sclerosis (ALS) leads to the eventual impairment of speech and swallowing functions. Despite these devastating consequences, no standardized diagnostic procedure for assessing bulbar dysfunction in ALS exists and adequate objective markers of bulbar deterioration have not been identified. In this paper, we consider objective measures of speech motor function, which show promise for forming the basis of a comprehensive, quantitative bulbar motor assessment in ALS. These measures are based on the assessment of four speech subsystems: respiratory, phonatory, articulatory, and resonatory. The goal of this research is to design a non-invasive, comprehensive bulbar motor assessment instrument intended for early detection, monitoring of disease progression, and clinical trial application. Preliminary data from an ongoing study of bulbar motor decline are presented, which demonstrate the potential clinical efficacy of the speech subsystem approach.

Kinematics of disease progression in bulbar ALS

UNLABELLED The goal of this study was to investigate the deterioration of lip and jaw movements during speech longitudinally in three individuals diagnosed with bulbar amyotrophic lateral sclerosis (ALS). The study was motivated by the need to understand the relationship between physiologic changes in speech movements and clinical measures of speech performance such as speaking rate and speech intelligibility. Movements of the lip and jaw were quantified with respect to their size speed, and duration. The data revealed several changes in lip and jaw movement that coincided with ALS progression. In two out of three speakers, the changes in measures of path distance and speed anticipated the drop in speech intelligibility by approximately 3 months. With disease progression, increases in movement duration coincided with declines in speech intelligibility. Overall, the movement measures appeared to be sensitive to disease progression in ALS. LEARNING OUTCOMES By the end of the manuscript, the reader should be able to: (1) describe the changes that occur in articulatory movements of the jaw and lower lip in ALS; (2) understand the relationship between physiologic measures of movement and speech intelligibility and speaking rate; (3) identify critical points in the disease progression and understand which quantitative measures reveal the state of the bulbar system at these time points.

Tongue Movements and Their Acoustic Consequences in Amyotrophic Lateral Sclerosis

Objective: The relations between acoustic measures and their articulatory bases have rarely been tested in dysarthria but are important for diagnostic and treatment purposes. We tested the association between acoustic measures of F2 range and F2 slope with kinematic measures of tongue movement displacement and speed in individuals with amyotrophic lateral sclerosis (ALS) and healthy controls speaking at normal and slow rates. Relations between acoustic and kinematic measures and speech intelligibility were examined. Results: As healthy controls reduced their speaking rate, their F2 slopes and movement speeds decreased. In talkers with ALS, acoustic and kinematic variables were associated with changes in speaking rate, characteristic of disease progression. Participants with slow rate had shallower F2 slopes and slower movement speeds than those with normal rate. Relations between F2 range and tongue displacement were weaker. F2 slope, displacement, and duration were correlated with speech intelligibility most consistently. Conclusion: Findings suggested that F2 slope is a useful marker for tracking disease progression in ALS. F2 slope reflects changes in tongue function with disease progression and is linked to speech intelligibility. Changes in movement speed, however, might be the earliest sign of disease in the tongue.

Predicting Early Bulbar Decline in Amyotrophic Lateral Sclerosis: A Speech Subsystem Approach

Purpose. To develop a predictive model of speech loss in persons with amyotrophic lateral sclerosis (ALS) based on measures of respiratory, phonatory, articulatory, and resonatory functions that were selected using a data-mining approach. Method. Physiologic speech subsystem (respiratory, phonatory, articulatory, and resonatory) functions were evaluated longitudinally in 66 individuals with ALS using multiple instrumentation approaches including acoustic, aerodynamic, nasometeric, and kinematic. The instrumental measures of the subsystem functions were subjected to a principal component analysis and linear mixed effects models to derive a set of comprehensive predictors of bulbar dysfunction. These subsystem predictors were subjected to a Kaplan-Meier analysis to estimate the time until speech loss. Results. For a majority of participants, speech subsystem decline was detectible prior to declines in speech intelligibility and speaking rate. Among all subsystems, the articulatory and phonatory predictors were most responsive to early bulbar deterioration; and the resonatory and respiratory predictors were as responsive to bulbar decline as was speaking rate. Conclusions. The articulatory and phonatory predictors are sensitive indicators of early bulbar decline due to ALS, which has implications for predicting disease onset and progression and clinical management of ALS.

Identical twins with the C9orf72 repeat expansion are discordant for ALS

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease that could co-occur with frontotemporal dementia (FTD), characterized by early behavioral or language changes. Mutations causing ALS and FTD have been found in several often overlapping genes.1 The most common mutation for both syndromes is a noncoding G4C2 expansion in C9orf72,2,3 usually ranging from hundreds to thousands of repeats.4 Currently it is unclear whether expansion alleles with different sizes have the same pathologic consequence, and the lower limit for pathologic repeat number has not been determined.4,5

Profiling Speech and Pausing in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD)

Objective This study examines reading aloud in patients with amyotrophic lateral sclerosis (ALS) and those with frontotemporal dementia (FTD) in order to determine whether differences in patterns of speaking and pausing exist between patients with primary motor vs. primary cognitive-linguistic deficits, and in contrast to healthy controls. Design 136 participants were included in the study: 33 controls, 85 patients with ALS, and 18 patients with either the behavioural variant of FTD (FTD-BV) or progressive nonfluent aphasia (FTD-PNFA). Participants with ALS were further divided into 4 non-overlapping subgroups—mild, respiratory, bulbar (with oral-motor deficit) and bulbar-respiratory—based on the presence and severity of motor bulbar or respiratory signs. All participants read a passage aloud. Custom-made software was used to perform speech and pause analyses, and this provided measures of speaking and articulatory rates, duration of speech, and number and duration of pauses. These measures were statistically compared in different subgroups of patients. Results The results revealed clear differences between patient groups and healthy controls on the passage reading task. A speech-based motor function measure (i.e., articulatory rate) was able to distinguish patients with bulbar ALS or FTD-PNFA from those with respiratory ALS or FTD-BV. Distinguishing the disordered groups proved challenging based on the pausing measures. Conclusions and Relevance This study demonstrated the use of speech measures in the identification of those with an oral-motor deficit, and showed the usefulness of performing a relatively simple reading test to assess speech versus pause behaviors across the ALS—FTD disease continuum. The findings also suggest that motor speech assessment should be performed as part of the diagnostic workup for patients with FTD.

Predicting Speech Intelligibility Decline in Amyotrophic Lateral Sclerosis Based on the Deterioration of Individual Speech Subsystems.

Purpose To determine the mechanisms of speech intelligibility impairment due to neurologic impairments, intelligibility decline was modeled as a function of co-occurring changes in the articulatory, resonatory, phonatory, and respiratory subsystems. Method Sixty-six individuals diagnosed with amyotrophic lateral sclerosis (ALS) were studied longitudinally. The disease-related changes in articulatory, resonatory, phonatory, and respiratory subsystems were quantified using multiple instrumental measures, which were subjected to a principal component analysis and mixed effects models to derive a set of speech subsystem predictors. A stepwise approach was used to select the best set of subsystem predictors to model the overall decline in intelligibility. Results Intelligibility was modeled as a function of five predictors that corresponded to velocities of lip and jaw movements (articulatory), number of syllable repetitions in the alternating motion rate task (articulatory), nasal airflow (resonatory), maximum fundamental frequency (phonatory), and speech pauses (respiratory). The model accounted for 95.6% of the variance in intelligibility, among which the articulatory predictors showed the most substantial independent contribution (57.7%). Conclusion Articulatory impairments characterized by reduced velocities of lip and jaw movements and resonatory impairments characterized by increased nasal airflow served as the subsystem predictors of the longitudinal decline of speech intelligibility in ALS. Declines in maximum performance tasks such as the alternating motion rate preceded declines in intelligibility, thus serving as early predictors of bulbar dysfunction. Following the rapid decline in speech intelligibility, a precipitous decline in maximum performance tasks subsequently occurred.

Electrical impedance myography in the evaluation of the tongue musculature in amyotrophic lateral sclerosis

Introduction: Electrical impedance myography (EIM) quantifies muscle health and is used as a biomarker of muscle abnormalities in neurogenic and myopathic diseases. EIM has yet to be evaluated in the tongue musculature in patients with amyotrophic lateral sclerosis (ALS), who often show clinical bulbar signs. Methods: The lingual musculature of 19 subjects with motor neuron disease and 21 normal participants was assessed using EIM, strength and endurance testing, and clinical assessment. Results: Tongue musculature in the ALS group was characterized by significantly smaller phase (Ph) and greater resistance (R) when compared with the healthy cohort. Ph and tongue endurance were correlated in the ALS group. Conclusions: EIM of tongue musculature could distinguish those with ALS from healthy controls. The demonstrated relationship between tongue function and Ph supports further testing of EIM of the tongue as a potential biomarker in ALS. Muscle Nerve 52: 584–591, 2015

A protocol for comprehensive assessment of bulbar dysfunction in amyotrophic lateral sclerosis (ALS)

Improved methods for assessing bulbar impairment are necessary for expediting diagnosis of bulbar dysfunction in ALS, for predicting disease progression across speech subsystems, and for addressing the critical need for sensitive outcome measures for ongoing experimental treatment trials. To address this need, we are obtaining longitudinal profiles of bulbar impairment in 100 individuals based on a comprehensive instrumentation-based assessment that yield objective measures. Using instrumental approaches to quantify speech-related behaviors is very important in a field that has primarily relied on subjective, auditory-perceptual forms of speech assessment1. Our assessment protocol measures performance across all of the speech subsystems, which include respiratory, phonatory (laryngeal), resonatory (velopharyngeal), and articulatory. The articulatory subsystem is divided into the facial components (jaw and lip), and the tongue. Prior research has suggested that each speech subsystem responds differently to neurological diseases such as ALS. The current protocol is designed to test the performance of each speech subsystem as independently from other subsystems as possible. The speech subsystems are evaluated in the context of more global changes to speech performance. These speech system level variables include speaking rate and intelligibility of speech. The protocol requires specialized instrumentation, and commercial and custom software. The respiratory, phonatory, and resonatory subsystems are evaluated using pressure-flow (aerodynamic) and acoustic methods. The articulatory subsystem is assessed using 3D motion tracking techniques. The objective measures that are used to quantify bulbar impairment have been well established in the speech literature and show sensitivity to changes in bulbar function with disease progression. The result of the assessment is a comprehensive, across-subsystem performance profile for each participant. The profile, when compared to the same measures obtained from healthy controls, is used for diagnostic purposes. Currently, we are testing the sensitivity and specificity of these measures for diagnosis of ALS and for predicting the rate of disease progression. In the long term, the more refined endophenotype of bulbar ALS derived from this work is expected to strengthen future efforts to identify the genetic loci of ALS and improve diagnostic and treatment specificity of the disease as a whole. The objective assessment that is demonstrated in this video may be used to assess a broad range of speech motor impairments, including those related to stroke, traumatic brain injury, multiple sclerosis, and Parkinson disease.

The Effect of Speaking Rate on Velopharyngeal Function in Healthy Speakers

The purpose of this study was to assess the effect of speaking rate variation on aerodynamic and acoustic measures of velopharyngeal (VP) function. Twenty-seven healthy adult speakers (14 males, 13 females) participated in the study. The modified pressure-flow method was used to collect aerodynamic data of /m/ and /p/ segments in the word ‘hamper’ and the utterances ‘Mama made some lemon jam’ (MMJ) and ‘Buy Bobby a puppy’ (BBP). SPL was collected simultaneously with aerodynamic data for all utterances. A Nasometer was used to obtain nasalance scores and nasalance distance for MMJ and BBP. Sentences were produced at normal, fast, slow, and slowest speaking rates. The results showed that nasal airflow and VP orifice area were unaffected by speaking rate variations in males and females, whereas intra-oral pressure appeared to decrease as speaking rate slowed for both speaker groups. However, this effect was removed by statistically controlling SPL. Nasalance and nasalance distance (MMJ – BBP) did not change with speaking rate variation. There was a statistical difference between nasalance scores produced by male and female speakers. The results suggested that aerodynamic and acoustic measures of velopharyngeal function are not affected by variation in speaking rate in healthy males and females.