title: Brain Connectivity Associated with Muscle Synergies in Humans.
abstract: The human brain is believed to simplify the control of the large number of muscles in the body by flexibly combining muscle coordination patterns, termed muscle synergies. However, the neural connectivity allowing the human brain to access and coordinate muscle synergies to accomplish functional tasks remains unknown. Here, we use a surprising pair of synergists in humans, the flexor hallucis longus (FHL, a toe flexor) and the anal sphincter, as a model that we show to be well suited in elucidating the neural connectivity underlying muscle synergy control. First, using electromyographic recordings, we demonstrate that voluntary FHL contraction is associated with synergistic anal sphincter contraction, but voluntary anal sphincter contraction occurs without FHL contraction. Second, using fMRI, we show that two important medial wall motor cortical regions emerge in relation to these tasks: one located more posteriorly that preferentially activates during voluntary FHL contraction and one located more anteriorly that activates during both voluntary FHL contraction as well as voluntary anal sphincter contraction. Third, using transcranial magnetic stimulation, we demonstrate that the anterior region is more likely to generate anal sphincter contraction than FHL contraction. Finally, using a repository resting-state fMRI dataset, we demonstrate that the anterior and posterior motor cortical regions have significantly different functional connectivity with distinct and distant brain regions. We conclude that specific motor cortical regions in humans provide access to different muscle synergies, which may allow distinct brain networks to coordinate muscle synergies during functional tasks.
  
  
  CONCLUSIONS
  How the human nervous system coordinates activity in a large number of muscles is a fundamental question. The brain and spinal cord are believed to simplify the control of muscles by grouping them into functional units called muscle synergies. Motor cortex is involved in activating muscle synergies; however, the motor cortical connections that regulate muscle synergy activation are unknown. Here, we studied pelvic floor muscle synergies to elucidate these connections in humans. Our experiments confirmed that distinct motor cortical regions activate different muscle synergies. These regions have different connectivity to distinct brain networks. Our results are an important step forward in understanding the cortical control of human muscles synergies, and may also have important clinical implications for understanding movement dysfunction.
authors.affiliation: Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, California 90033.
authors.forename: Manku
authors.identifier: http://orcid.org/0000-0002-3645-312X
authors.initials: M
authors.lastname: Rana
authors.affiliation: Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, California 90033.
authors.forename: Moheb S
authors.identifier: http://orcid.org/0000-0001-8939-7339
authors.initials: MS
authors.lastname: Yani
authors.affiliation: Physical Therapy Department, Loma Linda University, Loma Linda, California 92350, and.
authors.forename: Skulpan
authors.initials: S
authors.lastname: Asavasopon
authors.affiliation: Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, California 90033, Department of Neurology, University of Southern California, Los Angeles, California 90033.
authors.forename: Beth E
authors.initials: BE
authors.lastname: Fisher
authors.affiliation: Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, California 90033, kutch@usc.edu.
authors.forename: Jason J
authors.identifier: http://orcid.org/0000-0002-2417-4879
authors.initials: JJ
authors.lastname: Kutch
mesh_terms: D000328:Adult; D001921:Brain / Q000502:physiology; D004576:Electromyography / Q000379:methods; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D017773:Pelvic Floor / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods; D055815:Young Adult
keywords: EMG; TMS; fMRI; functional connectivity; motor cortex; pelvic floor