Muscle Synergies in Parkinson’s Disease

Over the last two decades, experimental studies in humans and other vertebrates have increasingly used muscle synergy analysis as a computational tool to examine the physiological basis of motor control. The theoretical background of muscle synergies is based on the potential ability of the motor system to coordinate muscles groups as a single unit, thus reducing high-dimensional data to low-dimensional elements. Muscle synergy analysis may represent a new framework to examine the pathophysiological basis of specific motor symptoms in Parkinson’s disease (PD), including balance and gait disorders that are often unresponsive to treatment. The precise mechanisms contributing to these motor symptoms in PD remain largely unknown. A better understanding of the pathophysiology of balance and gait disorders in PD is necessary to develop new therapeutic strategies. This narrative review discusses muscle synergies in the evaluation of motor symptoms in PD. We first discuss the theoretical background and computational methods for muscle synergy extraction from physiological data. We then critically examine studies assessing muscle synergies in PD during different motor tasks including balance, gait and upper limb movements. Finally, we speculate about the prospects and challenges of muscle synergy analysis in order to promote future research protocols in PD.

[1]  P. G. Iatridis,et al.  Comprehensive Human Physiology: From Cellular Mechanisms to Integration , 1996 .

[2]  Dario Farina,et al.  Identifying representative synergy matrices for describing muscular activation patterns during multidirectional reaching in the horizontal plane. , 2010, Journal of neurophysiology.

[3]  Surya Ganguli,et al.  Unsupervised Discovery of Demixed, Low-Dimensional Neural Dynamics across Multiple Timescales through Tensor Component Analysis , 2017, Neuron.

[4]  P. Guertin Central Pattern Generator for Locomotion: Anatomical, Physiological, and Pathophysiological Considerations , 2013, Front. Neur..

[5]  Houeto Jean-Luc [Parkinson's disease]. , 2022, La Revue du praticien.

[6]  M. Latash,et al.  Impaired synergic control of posture in Parkinson's patients without postural instability. , 2016, Gait & posture.

[7]  E. Bizzi,et al.  Modulation and vectorial summation of the spinalized frog's hindlimb end-point force produced by intraspinal electrical stimulation of the cord , 2001, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[8]  Christos Strydis,et al.  Cerebellar control of gait and interlimb coordination , 2014, Brain Structure and Function.

[9]  F. Lacquaniti,et al.  Motor patterns in human walking and running. , 2006, Journal of neurophysiology.

[10]  Zaccaria Del Prete,et al.  Yaw Postural Perturbation Through Robotic Platform: Aging Effects on Muscle Synergies , 2018, 2018 7th IEEE International Conference on Biomedical Robotics and Biomechatronics (Biorob).

[11]  F. Lacquaniti,et al.  Five basic muscle activation patterns account for muscle activity during human locomotion , 2004, The Journal of physiology.

[12]  Benjamin J. Fregly,et al.  Persons with Parkinson’s disease exhibit decreased neuromuscular complexity during gait , 2013, Clinical Neurophysiology.

[13]  Yoshihiro Kokubo,et al.  Global, regional, and national burden of Parkinson's disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016 , 2018, The Lancet Neurology.

[14]  Benjamin J. Fregly,et al.  Neuromuscular Complexity During Gait is not Responsive to Medication in Persons with Parkinson’s Disease , 2014, Annals of Biomedical Engineering.

[15]  Silvia Conforto,et al.  Comparison of Initialization Techniques for the Accurate Extraction of Muscle Synergies from Myoelectric Signals via Nonnegative Matrix Factorization , 2018, Applied bionics and biomechanics.

[16]  J. Kalaska,et al.  Sequential activation of muscle synergies during locomotion in the intact cat as revealed by cluster analysis and direct decomposition. , 2006, Journal of neurophysiology.

[17]  E. Bizzi,et al.  Stability of muscle synergies for voluntary actions after cortical stroke in humans , 2009, Proceedings of the National Academy of Sciences.

[18]  Eduardo Palermo,et al.  Parkinson’s disease and Levodopa effects on muscle synergies in postural perturbation , 2019, 2019 IEEE International Symposium on Medical Measurements and Applications (MeMeA).

[19]  Emilio Bizzi,et al.  Combinations of muscle synergies in the construction of a natural motor behavior , 2003, Nature Neuroscience.

[20]  M. Hoehn,et al.  Parkinsonism , 1967, Neurology.

[21]  M. Schwartz,et al.  Electromyography Data Processing Impacts Muscle Synergies during Gait for Unimpaired Children and Children with Cerebral Palsy , 2017, Front. Comput. Neurosci..

[22]  E. Bizzi,et al.  Article history: , 2005 .

[23]  L. Miller,et al.  Primary motor cortical neurons encode functional muscle synergies , 2002, Experimental Brain Research.

[24]  Lena H Ting,et al.  Increased neuromuscular consistency in gait and balance after partnered, dance-based rehabilitation in Parkinson's disease. , 2017, Journal of neurophysiology.

[25]  M. Schwartz,et al.  Muscle synergies and complexity of neuromuscular control during gait in cerebral palsy , 2015, Developmental medicine and child neurology.

[26]  Adamantios Arampatzis,et al.  On the Methodological Implications of Extracting Muscle Synergies from Human Locomotion , 2017, Int. J. Neural Syst..

[27]  Michaela Bruton,et al.  Synergies in coordination: a comprehensive overview of neural, computational, and behavioral approaches. , 2018, Journal of neurophysiology.

[28]  Erik Cambria,et al.  Role of Muscle Synergies in Real-Time Classification of Upper Limb Motions using Extreme Learning Machines , 2016, Journal of NeuroEngineering and Rehabilitation.

[29]  Dario Farina,et al.  Motor modules of human locomotion: influence of EMG averaging, concatenation, and number of step cycles , 2014, Front. Hum. Neurosci..

[30]  Matthew C. Tresch,et al.  The number and choice of muscles impact the results of muscle synergy analyses , 2013, Front. Comput. Neurosci..

[31]  S. Micera,et al.  Age-related modifications of muscle synergies and spinal cord activity during locomotion. , 2010, Journal of neurophysiology.

[32]  M. Gelabert-González,et al.  [Deep brain stimulation in Parkinson's disease]. , 2013, Revista de neurologia.

[33]  Ning Lan,et al.  Muscle synergy changes with cutaneous stimulation during resting tremor and reaching task in Parkinson's disease , 2019, 2019 9th International IEEE/EMBS Conference on Neural Engineering (NER).

[34]  Simon A. Overduin,et al.  Modulation of Muscle Synergy Recruitment in Primate Grasping , 2008, The Journal of Neuroscience.

[35]  Stefano Panzeri,et al.  Muscle synergies in neuroscience and robotics: from input-space to task-space perspectives , 2013, Front. Comput. Neurosci..

[36]  Shashank Ghai,et al.  Effect of rhythmic auditory cueing on parkinsonian gait: A systematic review and meta-analysis , 2018, Scientific Reports.

[37]  Mitsuhiro Hayashibe,et al.  Identification of Time-Varying and Time-Scalable Synergies From Continuous Electromyographic Patterns , 2019, IEEE Robotics and Automation Letters.

[38]  F. Lacquaniti Central representations of human limb movement as revealed by studies of drawing and handwriting , 1989, Trends in Neurosciences.

[39]  Eduardo Palermo,et al.  Immediate effects of rhythmic auditory stimulation on gait kinematics in Parkinson’s disease ON/OFF medication , 2019, Clinical Neurophysiology.

[40]  Joel W. Burdick,et al.  Motor Control After Human SCI Through Activation of Muscle Synergies Under Spinal Cord Stimulation , 2019, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[41]  E. Bizzi,et al.  Responses to spinal microstimulation in the chronically spinalized rat and their relationship to spinal systems activated by low threshold cutaneous stimulation , 1999, Experimental Brain Research.

[42]  B. Bloem,et al.  The Emerging Evidence of the Parkinson Pandemic , 2018, Journal of Parkinson's disease.

[43]  Adamantios Arampatzis,et al.  Lower complexity of motor primitives ensures robust control of high-speed human locomotion , 2020, bioRxiv.

[44]  Emilio Bizzi,et al.  The neural origin of muscle synergies , 2013, Front. Comput. Neurosci..

[45]  Elena Moro,et al.  Managing Gait, Balance, and Posture in Parkinson’s Disease , 2018, Current Neurology and Neuroscience Reports.

[46]  Francisco J. Valero Cuevas,et al.  Challenges and New Approaches to Proving the Existence of Muscle Synergies of Neural Origin , 2012, PLoS Comput. Biol..

[47]  T. Drew,et al.  Sequential activation of motor cortical neurons contributes to intralimb coordination during reaching in the cat by modulating muscle synergies. , 2011, Journal of neurophysiology.

[48]  J. M. Brault,et al.  Rhythmic auditory stimulation in gait training for Parkinson's disease patients , 1996, Movement disorders : official journal of the Movement Disorder Society.

[49]  Emilio Bizzi,et al.  Shared and specific muscle synergies in natural motor behaviors. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[50]  W. Rymer,et al.  Abnormal muscle coactivation patterns during isometric torque generation at the elbow and shoulder in hemiparetic subjects. , 1995, Brain : a journal of neurology.

[51]  Alessandro Zampogna,et al.  Abnormal Cerebellar Connectivity Patterns in Patients with Parkinson’s Disease and Freezing of Gait , 2018, The Cerebellum.

[52]  Vincent C. K. Cheung,et al.  On Nonnegative Matrix Factorization Algorithms for Signal-Dependent Noise with Application to Electromyography Data , 2014, Neural Computation.

[53]  N. A. Bernshteĭn The co-ordination and regulation of movements , 1967 .

[54]  Jessica L. Allen,et al.  Neuromechanical Principles Underlying Movement Modularity and Their Implications for Rehabilitation , 2015, Neuron.

[55]  Zaccaria Del Prete,et al.  EMG factorization during walking: does digital filtering influence the accuracy in the evaluation of the muscle synergy number? , 2018, 2018 IEEE International Symposium on Medical Measurements and Applications (MeMeA).

[56]  F Lacquaniti,et al.  Locomotor patterns in cerebellar ataxia. , 2014, Journal of neurophysiology.

[57]  Arnaud Delval,et al.  Auditory cueing of gait initiation in Parkinson’s disease patients with freezing of gait , 2014, Clinical Neurophysiology.

[58]  H. Sebastian Seung,et al.  Learning the parts of objects by non-negative matrix factorization , 1999, Nature.

[59]  Paolo Bonato,et al.  Decomposing time series data by a non-negative matrix factorization algorithm with temporally constrained coefficients , 2015, 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[60]  Diane L. Damiano,et al.  Novel Methods to Enhance Precision and Reliability in Muscle Synergy Identification during Walking , 2016, Front. Hum. Neurosci..

[61]  Adamantios Arampatzis,et al.  Challenging human locomotion: stability and modular organisation in unsteady conditions , 2018, Scientific Reports.

[62]  K. Takakusaki Functional Neuroanatomy for Posture and Gait Control , 2017, Journal of movement disorders.

[63]  Fernanda Irrera,et al.  l-DOPA and Freezing of Gait in Parkinson’s Disease: Objective Assessment through a Wearable Wireless System , 2017, Front. Neurol..

[64]  Fernanda Irrera,et al.  Wearable Sensors System for an Improved Analysis of Freezing of Gait in Parkinson’s Disease Using Electromyography and Inertial Signals , 2019, Sensors.

[65]  Stacie A. Chvatal,et al.  Decomposing Muscle Activity in Motor TasksMethods and Interpretation , 2010 .

[66]  M. Lemay,et al.  Modularity of motor output evoked by intraspinal microstimulation in cats. , 2004, Journal of neurophysiology.

[67]  S. Micera,et al.  How are Muscle Synergies Affected by Electromyography Pre-Processing? , 2018, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[68]  Kamran Iqbal,et al.  A Systematic Review on Muscle Synergies: From Building Blocks of Motor Behavior to a Neurorehabilitation Tool , 2018, Applied bionics and biomechanics.

[69]  Andrea d'Avella,et al.  Modularity in the motor system: decomposition of muscle patterns as combinations of time-varying synergies , 2001, NIPS.

[70]  Tamara G. Kolda,et al.  Tensor Decompositions and Applications , 2009, SIAM Rev..

[71]  Adamantios Arampatzis,et al.  Neuromotor Dynamics of Human Locomotion in Challenging Settings , 2019, iScience.

[72]  Alessandro Zampogna,et al.  Neuroimaging advances in Parkinson's disease with freezing of gait: A systematic review , 2019, NeuroImage: Clinical.

[73]  Francesco Lacquaniti,et al.  Control of Fast-Reaching Movements by Muscle Synergy Combinations , 2006, The Journal of Neuroscience.

[74]  Kimitaka Nakazawa,et al.  Speed-dependent and mode-dependent modulations of spatiotem-poral modules in human locomotion extracted via tensor decom-position , 2020, Scientific Reports.

[75]  L. Ting,et al.  Muscle synergies characterizing human postural responses. , 2007, Journal of neurophysiology.

[76]  Katherine M Steele,et al.  Repeatability of muscle synergies within and between days for typically developing children and children with cerebral palsy. , 2016, Gait & posture.

[77]  P. Strick,et al.  Subdivisions of primary motor cortex based on cortico-motoneuronal cells , 2009, Proceedings of the National Academy of Sciences.

[78]  Dinesh K Pai,et al.  Changes in hand muscle synergies in subjects with spinal cord injury: Characterization and functional implications , 2012, The journal of spinal cord medicine.

[79]  M. Honda,et al.  Enhanced lateral premotor activity during paradoxical gait in Parkinson's disease , 1999, Annals of neurology.

[80]  A. Guével,et al.  Is interindividual variability of EMG patterns in trained cyclists related to different muscle synergies? , 2010, Journal of applied physiology.

[81]  Mark L. Latash,et al.  Towards physics of neural processes and behavior , 2016, Neuroscience & Biobehavioral Reviews.

[82]  Tamar Flash,et al.  Intersegmental coordination patterns are differently affected in Parkinson's disease and cerebellar ataxia. , 2019, Journal of neurophysiology.

[83]  M. Hallett,et al.  Freezing of gait: moving forward on a mysterious clinical phenomenon , 2011, The Lancet Neurology.

[84]  E. Bizzi,et al.  Muscle synergies encoded within the spinal cord: evidence from focal intraspinal NMDA iontophoresis in the frog. , 2001, Journal of neurophysiology.

[85]  M. Okun,et al.  Diagnosis and Treatment of Parkinson Disease: A Review. , 2020, JAMA.

[86]  Lena H Ting,et al.  A limited set of muscle synergies for force control during a postural task. , 2005, Journal of neurophysiology.

[87]  Andrea d'Avella,et al.  Matrix factorization algorithms for the identification of muscle synergies: evaluation on simulated and experimental data sets. , 2006, Journal of neurophysiology.

[88]  Marjan Jahanshahi,et al.  Postural instability and falls in Parkinson’s disease , 2016, Reviews in the neurosciences.

[89]  F A Mussa-Ivaldi,et al.  Computations underlying the execution of movement: a biological perspective. , 1991, Science.

[90]  S. Giszter,et al.  Modular Premotor Drives and Unit Bursts as Primitives for Frog Motor Behaviors , 2004, The Journal of Neuroscience.

[91]  Stacie A. Chvatal,et al.  Common muscle synergies for balance and walking , 2013, Front. Comput. Neurosci..

[92]  Mohammad Sharif Shourijeh,et al.  An approach for improving repeatability and reliability of non-negative matrix factorization for muscle synergy analysis. , 2016, Journal of electromyography and kinesiology : official journal of the International Society of Electrophysiological Kinesiology.

[93]  Mark L. Latash,et al.  Motor equivalence and structure of variance: multi-muscle postural synergies in Parkinson’s disease , 2017, Experimental Brain Research.

[94]  N. Lan,et al.  The impact of evoked cutaneous afferents on voluntary reaching movement in patients with Parkinson’s disease , 2019, Journal of neural engineering.

[95]  Simon A. Overduin,et al.  Microstimulation Activates a Handful of Muscle Synergies , 2012, Neuron.

[96]  G. Deuschl,et al.  MDS clinical diagnostic criteria for Parkinson's disease , 2015, Movement disorders : official journal of the Movement Disorder Society.

[97]  E. Bizzi,et al.  Central and Sensory Contributions to the Activation and Organization of Muscle Synergies during Natural Motor Behaviors , 2005, The Journal of Neuroscience.

[98]  Adamantios Arampatzis,et al.  Modular organization of murine locomotor pattern in the presence and absence of sensory feedback from muscle spindles , 2019, The Journal of physiology.

[99]  Alfredo Berardelli,et al.  The effect of L-dopa in Parkinson’s disease as revealed by neurophysiological studies of motor and sensory functions , 2017, Expert review of neurotherapeutics.

[100]  Valentina Agostini,et al.  Feasibility of Muscle Synergy Outcomes in Clinics, Robotics, and Sports: A Systematic Review , 2018, Applied bionics and biomechanics.

[101]  Eduardo Palermo,et al.  Factorization of EMG via muscle synergies in walking task: Evaluation of intra-subject and inter-subject variability , 2017, 2017 IEEE International Instrumentation and Measurement Technology Conference (I2MTC).

[102]  M. Latash,et al.  Dopaminergic modulation of multi-muscle synergies in postural tasks performed by patients with Parkinson's disease. , 2017, Journal of electromyography and kinesiology : official journal of the International Society of Electrophysiological Kinesiology.

[103]  Martin A. Giese,et al.  Model selection for the extraction of movement primitives , 2013, Front. Comput. Neurosci..

[104]  Loukianos Spyrou,et al.  Evaluation of matrix factorisation approaches for muscle synergy extraction. , 2018, Medical engineering & physics.

[105]  Turgay Akay,et al.  Fractal analysis of muscle activity patterns during locomotion: pitfalls and how to avoid them , 2020, bioRxiv.

[106]  Jinsook Roh,et al.  Evidence for altered upper extremity muscle synergies in chronic stroke survivors with mild and moderate impairment , 2015, Front. Hum. Neurosci..

[107]  Jeffrey M. Hausdorff,et al.  Rhythmic auditory stimulation modulates gait variability in Parkinson's disease , 2007, The European journal of neuroscience.

[108]  Andrea d'Avella,et al.  Modularity for Motor Control and Motor Learning. , 2016, Advances in experimental medicine and biology.

[109]  M. Latash,et al.  Systemic effects of deep brain stimulation on synergic control in Parkinson’s disease , 2018, Clinical Neurophysiology.

[110]  Eduardo Palermo,et al.  On the Reliability and Repeatability of Surface Electromyography Factorization by Muscle Synergies in Daily Life Activities , 2018, Applied bionics and biomechanics.

[111]  Richard R Neptune,et al.  Merging of healthy motor modules predicts reduced locomotor performance and muscle coordination complexity post-stroke. , 2010, Journal of neurophysiology.

[112]  Wynne A. Lee,et al.  Neuromotor synergies as a basis for coordinated intentional action. , 1984, Journal of motor behavior.

[113]  E. Bizzi,et al.  The construction of movement by the spinal cord , 1999, Nature Neuroscience.

[114]  E. Bizzi,et al.  Modules in the brain stem and spinal cord underlying motor behaviors. , 2011, Journal of neurophysiology.