Neuromotor Modules Revealed by Intraoperative Direct Electrical Stimulation of the Human Primary Motor Cortex

ABSTRACT Muscle synergies extracted from multi-muscle electromyographic (EMG) signals are widely interpreted as fundamental building blocks of motor control which coordinate groups of muscles during movement. Whether EMG-derived muscle synergies represent genuine neurally encoded modules or motor regularities arising from task or biomechanical constraints has been hotly debated, because neurophysiological data that definitively demonstrate the neural basis of muscle synergies in humans has been lacking. Here, we seek to validate the potential neural origin of upper limb muscle synergies by exploiting direct electrical stimulation (DES) of the primary motor cortex (M1) routinely delivered by neurosurgeons during awake craniotomy surgery for glioma excision. Across 13 patients, 69% of the muscle synergies observed during pre-operative voluntary behaviors could be matched to DES-evoked muscle synergies or their combination. Analysis of the synergies’ cortical activity maps further revealed that the cortical representations of the sparser muscle synergies were more anterior and distributed, and those of the non-sparse synergies, more posterior and localized. Our results not only provide direct causal evidence arguing for the neural origin of most behavioral muscle synergies in humans, but also demonstrate the existence of two M1 subdivisions with distinct patterns of muscle synergy organization. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study was funded by Hong Kong Research Grants Council (14114721, 14119022, N_CUHK456/21, R4022-18F), CUHK RSFS (3133184), CUHK Faculty of Medicine Direct Grants (4054652, 4054710). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Research Ethics Committee/Institutional Review Board (Kowloon Central / Kowloon East Clusters) of the Hong Kong Hospital Authority Research Ethics Committee gave ethical approval for this work (KC/KE-21-0012/ER-2). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors.