Research Lab

Systems Motor Neuroscience: What are the Fundamental Building Blocks of Movement Generation?    

How the central nervous system (CNS) specifies coordinated activities for hundreds of muscles to generate diverse motor behaviors is an unsolved “hard” problem in neuroscience. The CNS may simplify the daunting task of muscle coordination by computing muscle commands through the combination of pre-organized modules known as muscle synergies, each of which activates a group of muscles as a unit (Cheung and Seki, J. Neurophysiol., 2021). How the muscle synergies are organized and recruited by the CNS, however, remains elusive and controversial. Our lack of understanding of the synergies’ neuronal underpinnings has become a roadblock in the development of neural-machine interfaces for the motor system.

For this question, we have pursued the hypothesis that behavioral muscle synergies are encoded by spinal interneuronal and motoneuronal circuits. We have employed optogenetics to elicit spinal circuit activities, multi-channel electrode arrays and carbon nanotube fiber electrodes to record activities of neuronal populations, and computational tools (e.g., Guo et al., IEEE JBHI, 2025) to decode muscle synergies from neuronal and muscle activities. Our recent data suggest that many spinal interneurons exhibit state-dependent encoding of locomotor muscle synergies (He et al., in revision).

Motor Learning and Development: How do Forces of Nature and Nurture Interact During Motor Skill Acquisition?

Neuromotor commands for different behaviors are generated by the combination of modules called muscle synergies. Recent data have argued that muscle synergies are inborn or determined early in life, but neuromusculoskeletal development and subsequent acquisition of new motor skills may demand reshaping of the early synergies. In our previous study (Cheung et al., Nat. Comm., 2020), we ask how locomotor synergies change during development and training by studying running in preschoolers and diverse adults from sedentary subjects to marathoners. During development, synergies are fractionated into units with fewer muscles. As adults train to run, specific synergies coalesce to become merged synergies. Fractionation and merging of muscle synergies may be a mechanism for modifying early motor modules (Nature) to accommodate the changing limb biomechanics and influences from sensorimotor training (Nurture).

More recently, by analyzing the muscle patterns of children with spinal muscular atrophy, we demonstrated that early sensorimotor experiences play a critical role in the development of locomotor muscle synergies (Cheung et al., J. Neurophysiol., 2024). We have continued to study movement patterns of infants before and after walking onset to better understand the trajectory of neuromotor development.

Neuro-rehabilitation: Can We Develop Effective, Personalized Stroke Rehabilitation Grounded on Neuroscientific Principles?

Stroke remains a leading cause of long-term adult disability. There is still an urgent need for novel and efficacious motor rehabilitative strategies that can provide better functional outcomes for diverse stroke survivors. There is increasing recognition that rehabilitation paradigms should promote restitution of the patient’s abnormal muscle coordination (Cheung et al., PNAS, 2012) towards the normal pattern during training, and that multi-muscle functional electrical stimulation (FES) may be a viable strategy for achieving this goal. Multi-muscle FES, when applied to a large functional set of muscles and driven by the muscles’ natural coordination pattern, can guide muscle activations towards the normal pattern through neuroplasticity, thus restoring impairment at the level of muscle-activation deficit.

Recently, we have utilized the theory of muscle synergy from motor neuroscience to guide our personalized multi-muscle FES training for gait rehabilitation. The FES pattern for each stroke survivor is constructed based on the normative muscle synergies that are absent in the stroke survivor’s muscle pattern. Since muscle synergies are the natural motor-control units, reinforcement of their activations through FES should lead to restoration of normal neuromuscular coordination, thus more natural post-training gait.

1. Guo X, Huang S, He B, Lan C, Xie JJ, Lau KYS, Takei T, Mak ADP, Cheung RTH, Seki K, Cheung VCK*, Chan RHM* (2025) Inhibitory components in muscle synergies factorized by the rectified latent variable model from electromyographic data. IEEE Journal of Biomedical and Health Informatics. DOI: 10.1109/JBHI.2024.3453603.
2. Cheung VCK*, Ha SC, Zhang-Lea JH, Chan ZY, Teng Y, Yeung G, Wu L*, Liang D, Cheung RTH* (2024) Motor patterns of patients with spinal muscular atrophy suggestive of sensory and corticospinal contributions to the development of locomotor muscle synergies. Journal of Neurophysiology. 131(2): 338-59.
3. Cheung VCK*, Seki K* (2021) Approaches to revealing the neural basis of muscle synergies: A review and a critique. Journal of Neurophysiology. 125: 1580-1597. [Invited in-depth review, for acknowledging the career of Emilio Bizzi, Institute Professor of MIT]
4. Cheung VCK*, Cheung BMF, Zhang JH, Chan ZYS, Ha SCW, Chen C-Y, Cheung RTH* (2020) Plasticity of muscle synergies through fractionation and merging during development and training of human runners. Nature Communications. 11: 4356.
5. Cheung VCK, Turolla A, Agostini M, Silvoni S, Bennis C, Kasi P, Paganoni S, Bonato P, Bizzi E* (2012) Muscle synergy patterns as physiological markers of motor cortical damage. Proceedings of the National Academy of Sciences, USA. 109(36): 14652-14656.[Recommended by Faculty of 1000]