AUTHOR=Rong Panying , Heidrick Lindsey , Pattee Gary L. 

TITLE=A multimodal approach to automated hierarchical assessment of bulbar involvement in amyotrophic lateral sclerosis

JOURNAL=Frontiers in Neurology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1396002

DOI=10.3389/fneur.2024.1396002

ISSN=1664-2295

ABSTRACT=As a hallmark feature of amyotrophic lateral sclerosis (ALS), bulbar involvement leads to progressive declines of speech and swallowing functions, significantly impacting social, emotional, and physical health, and quality of life. Standard clinical tools for bulbar assessment focus primarily on clinical symptoms and functional outcomes. However, ALS is known to have a long, clinically silent prodromal stage characterized by complex subclinical changes at various levels of the bulbar motor system. These changes accumulate over time and eventually culminate in clinical symptoms and functional declines. Detection of these subclinical changes is critical, both for mechanistic understanding of bulbar neuromuscular pathology and for optimal clinical management of bulbar dysfunction in ALS. To this end, we developed a novel multimodal measurement tool based on two clinically readily available, noninvasive instruments-facial surface electromyography (sEMG) and acoustic techniques, to hierarchically assess seven constructs of bulbar/speech motor control at the neuromuscular and acoustic levels. These constructs, including prosody, pause, functional connectivity, amplitude, rhythm, complexity, and regularity, are both mechanically and clinically relevant to bulbar involvement. Using a custom-developed, fully automated data analytic algorithm, a variety of features were extracted from the two modalities and then factorized into 10 composite outcome measures. Through validation testing, these outcome measures were demonstrated to (1) be internally consistent and structurally valid in measuring the targeted constructs; (2) hold concurrent validity with the existing clinical and functional criteria for bulbar assessment; and (3) outperform the outcome measures obtained from each constituent modality in differentiating individuals with ALS from neurologically healthy controls. Moreover, the outcome measures combined demonstrated high efficacy for detecting subclinical changes in the targeted constructs, both during the prodromal stage and during the transition from prodromal to symptomatic stages. These findings provided compelling initial evidence for the utility of the multimodal measurement tool in improving early detection and progress monitoring of bulbar involvement in ALS, which have important implications in facilitating timely access to and delivery of optimal clinical care of bulbar dysfunction.