Decoding Force Variability at Motor Unit Level in Health and Disease

• Applicant: Dr. Benedict Kleiser
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 584514440

Muscle force, determined by the coordinated activation of motor units (MUs), is impaired in neuromuscular diseases due to changes in motor unit size, recruitment, and firing patterns. However, in clinical practice, muscle force is often assessed using semiquantitative scales, such as INCAT, I-RODS, or the MRC scale. These tools provide only rough estimates and do not capture the fine organization of force control. A more detailed assessment can be achieved using isometric force tasks with visual feedback, where deviations from target force trajectories quantify force variability. Studies show that patients with neuromuscular disorders, e.g. Charcot–Marie–Tooth disease type 1A (CMT1A) and facioscapulohumeral muscular dystrophy (FSHD), often exhibit increased force variability, although the precise relationship between force fluctuations and motor unit activity remains unclear. Conventional invasive EMG (iEMG) allows assessment of MU action potentials and firing rates but is limited to low force levels and few MUs at a time, making it insufficient to study coordinated MU activity underlying force variability. Non-invasive high-density surface EMG (HDsEMG) improves spatial resolution and enables decomposition of multiple MUs simultaneously, providing insights into recruitment patterns, firing rates, and variability. However, initial results with HDsEMG in neuromuscular patients appear to be inconsistent and often do not evaluate their results in relation to force variability. Further, HDsEMG is limited by crosstalk and superficial recordings, particularly in small or atrophied muscles. High-density intramuscular EMG (HDiEMG) overcomes these limitations, allowing multi-channel recordings from deep muscle tissue and complementing HDsEMG to establish a “ground truth” for MU activity and coordination. First own preliminary work combining HDsEMG and force measurements in healthy subjects and patients demonstrated altered force control and possible compensatory MU recruitment in patients. The proposed project aims to elucidate the relationship between MU discharge patterns and force variability in health and disease. Therefore, a force variability paradigm using ramp, sinusoidal, and alternating force tasks will be developed and validated. These protocols will be performed in patients to assess disease-specific alterations in MU coordination and their contribution to the increased force variability. Analyses will include firing rates, recruitment patterns, variability metrics, and modulation of synchronous activity (common drive). The project will provide a mechanistic understanding of how neuromuscular diseases disrupt MU organization, inform the reliability of non-invasive HDsEMG for patient assessment, and lay the groundwork for improved diagnostic and rehabilitation strategies.

• DFG Programme: Fellowship
• International Connection: United Kingdom
• Host: Professor Dr. Dario Farina