Abstract
OBJECTIVE: This study aims to translate surface electromyography (sEMG) into a clinically applicable, objective tool for assessing bulbar involvement in amyotrophic lateral sclerosis (ALS). METHODS: A clinically grounded sEMG framework was developed, integrating a standardized, repeatable protocol with a novel analytic pipeline, to automatically extract 60 features from six craniofacial muscle groups during a set of motorically demanding but cognitively and linguistically less challenging oral diadochokinetic (DDK) tasks. Using this framework, 104 oral DDK recordings were acquired from 16 individuals with ALS-nine with overt bulbar symptoms (ALS+B) and seven without (ALS-B)-and 10 healthy controls (HCs). The sEMG features were clustered into 10 interpretable composite measures and validated by evaluating their (1) internal consistency using Cronbach's α ; (2) associations with standardized functional outcomes and a biomechanical metric-stiffness-via mediation analysis; (3) discriminatory efficacy in distinguishing ALS+B and ALS-B from HC, as well as from each other, using machine learning classifications; and (4) robustness to common nonmotor confounders, including age, sex, and cognitive-linguistic impairments, through a comparison of discriminatory performance before and after adjustment for these factors. RESULTS: All composite measures exhibited (1) high internal consistency (Cronbach's α = 0.89 ± 0.071 ), (2) significant (or marginally significant) direct or stiffness-mediated indirect associations with the functional outcomes, and (3) consistently high discriminatory accuracy (0.82-0.85), both before and after adjustment for confounders. CONCLUSION: The sEMG framework demonstrates strong potential as a reliable, valid, and robust objective tool to detect subclinical neuromuscular changes throughout the prodromal and symptomatic phases of bulbar involvement in ALS, while remaining resistant against disease-related cognitive-linguistic impairments and disease-unrelated confounders. This tool may augment standard clinical evaluations, enabling earlier detection of bulbar involvement and measurement-based care in ALS.