Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons. Currently, no single test can definitively diagnose ALS. Therefore, identifying noninvasive biomarkers, such as the cortico-muscular coupling index (CMC), is crucial for early diagnosis and prognosis. This study aimed to develop a real-time monitoring system to assess CMC in ALS. This project comprises several studies, but this chapter focuses primarily on the time delay between the cortico-muscular system during motor tasks. For details on other aspects of the study, readers are referred to relevant publications. A real-time system including data acquisition, motor task design device, psychophysics. We acquired simultaneous high-density EEG-sEMG data from 15 healthy subjects during four hand and foot contraction tasks (two static and two dynamic) and from 8 ALS patients performing two tasks (hand static and dynamic). Then calculated the global delay for all tasks and rest conditions. Significant global delays were observed in healthy subjects during static tasks when comparing task and rest conditions (Task 1: Z = −2.970, p = 0.003; and Task 3: Z = −3.215, p = 0.001). Notably, we did not observe any significant differences between task and rest conditions within the ALS patient group (Task 1: Z = −0.305, p = 0.760; Task 2: Z = −0.361, p = 0.718). These findings suggest that the presence of global delay in healthy subjects and its absence in ALS patients may be an important indicator of the disease. Further research with larger and matched sample sizes is needed to confirm these findings and explore the potential of global delay as a biomarker for ALS diagnosis and prognosis.