Researchers from the Chinese University of Hong Kong (CUHK) have resolved a long-standing debate in neuroscience on the neural origin of complex muscle coordination for voluntary movements. Their recent finding that the brain organizes individual muscles into functional "building blocks" (muscle synergies) to coordinate multiple muscle groups simultaneously, rather than by directing each muscle individually, offers transformative insights for paralysis rehabilitation and design of brain-machine interfaces (BMIs) in future.
Everyday activities such as walking or lifting a cup require concurrent, coordinated activation of multiple muscles. For decades, neuroscientists have debated how the central nervous system directs highly complex muscle operations: whether it controls each muscle individually or commands them through combined units known as muscle synergies. It has remained unclear whether electromyography (EMG)-derived muscle synergies represent genuine neurally encoded modules or are mere algorithmic artifacts or epiphenomena of other motor-control principles. [Daedalus 2015;144:83-95; Proc Natl Acad Sci U S A 2020;8135-8142; J Neurophysiol 2021;125:1580-1597]
To decode this mechanism, the researchers compared direct electrical stimulation (DES)–evoked and voluntary behavioural muscle synergies of 10–11 upper limb tasks in 13 patients who underwent awake craniotomy for glioma resection. During awake brain surgery, patients remained conscious while neurosurgeons applied mild DES to the primary motor cortex (M1), and intraoperative real-time EMG data on muscle responses were recorded. Surface EMGs while performing 10–11 upper limb tasks related to activities of daily living were recorded during pre- and postoperative sessions. [Proc Natl Acad Sci U S A 2026;123:e2604933123]
DES of M1 is routinely delivered by neurosurgeons during awake craniotomy to map critical movement areas before brain tumour removal. "This procedure enables neurosurgeons to map the brain more precisely, minimizing any undesired functional impairment after surgery,” explained Dr Peter Vat-Ming Woo of the Department of Surgery, CUHK.
Analyses found that 69 percent of the muscle synergies observed during preoperative voluntary behaviours could be matched to DES-evoked muscle synergies or their combination. Further analysis of the synergies’ cortical activity maps revealed that cortical representations of the sparser muscle synergies were more anterior and distributed, and those of the nonsparse synergies, more posterior and localized.
“This study confirmed that M1 controls the activities of multiple muscles by activating muscle synergies," said the study's first author, Dr Jodie Jingping Xie of the School of Biomedical Sciences, CUHK. “Our results not only provide direct causal evidence arguing for the neural origin of most behavioural muscle synergies in humans, but also demonstrate the potential existence of two M1 subdivisions with distinct patterns of muscle synergy organization.”
Study implications
“By understanding the true functional substrates of the motor cortex, we can build stronger bridges between fundamental neuroscience and patient care," added Woo.
"BMl is an emerging medical technology where electrodes are implanted into the motor cortex of paralyzed patients,” noted Dr Vincent Chi-Kwan Cheung of the School of Biomedical Sciences, CUHK. “By recording the neural signals generated when patients consciously attempt to move their limbs, the system decodes and translates these signals to drive assistive devices that help them communicate or regain mobility. Since M1 is a primary implantation site of BMls for movement control, our findings will help inform the design of more precise and effective BMI systems.”
“The findings also offer valuable insights for designing and improving future motor rehabilitative interventions," Cheung added.