Muscle Synergies for Post-Stroke Motor Assessment and Prediction in a Randomized Acupuncture Trial

Motor rehabilitation after stroke is challenging due to the heterogeneity of stroke presentations. Maximizing recovery hinges on suitable personalization of rehabilitation, which depends on reliable motor assessments and predictions of the subjects’ responses to different interventions using biomarkers of brain impairment. Beyond the previously defined neuroimaging biomarkers, impairment-dependent motor patterns of stroke survivors during voluntary movement are alternatives that potentially offer accurate and precise predictions. Specifically, muscle synergies identified from multi-muscle electromyographic signals (EMG), as neuromotor modules employed by CNS for muscle coordination, have been previously used to evaluate upper limb functions post-stroke in small-to-moderate-sized cohorts. While these initial results appear promising, how muscle synergies should be most profitably used for clinical assessments and whether they predict post-rehabilitation responses remain unexplored. Here, we evaluate the potential of muscle synergies in assessing upper limb motor functions and predicting outcomes from multiple rehabilitative options in a moderately large cohort of subacute stroke survivors (N=88, 55±35 days post-stroke) recruited for a randomized trial of acupuncture as an adjunctive rehabilitative intervention. Subjects (N=59) were randomly assigned to monthlong abdominal acupuncture (Acu), sham acupuncture (ShamAcu), or no acupuncture (NoAcu), alongside basic care. Four clinical scores and EMGs of the stroke-affected upper limb (14 muscles, 8 tasks) were collected before and after intervention. Muscle synergies were extracted from EMGs using factorization. For each subject, features of the synergies and their temporal activations were comprehensively summarized by 12 muscle synergy indexes (MSI). We first demonstrated cross-sectionally that our MSIs correlated significantly with all clinical scores, and thus could capture impairment-related synergy changes. Longitudinally, Acu was differentiated from ShamAcu and NoAcu in having clinical score improvements accompanied by the restorations of more MSIs. For each treatment group, we then built regression models that predict clinical scores’ realized recovery from pre-intervention MSIs and other variables. Model-predicted recovery correlated significantly with observed recovery (R2=0.53-0.70). To test the models’ utility in patient stratification, for every Acu and NoAcu subject we retrospectively identified the intervention option expected to yield greater recovery by comparing the predicted Acu and NoAcu outcomes. Subjects who indeed received the model-assigned intervention showed more realized recovery in Fugl-Meyer Assessment (section A) than those who received incorrectly assigned intervention (p=0.013). Overall, our findings suggest that muscle synergies, when suitably summarized as MSIs, may clarify the intervention’s effects and assist in motor assessment, outcome prediction, and treatment selection. MSIs can be useful recovery biomarkers in future schemes of precision rehabilitation. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT03712085 ### Funding Statement This project was supported by The CUHK School of Biomedical Sciences-Guangdong Provincial Hospital of Traditional Chinese Medicine Translational Collaborative Innovation Scheme (NO.YN2018HK03), sponsored by The Guangdong Provincial Hospital of Traditional Chinese Medicine, to HC and VCKC. ### 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: The study has been approved by Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (Approval No.BF2018-164-01). 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 All data reported in this study as well as the codes developed for the analyses are available to any researcher upon any reasonable request sent to the corresponding authors.