Central excitability contributes to supramaximal volitional contractions in human incomplete spinal cord injury

Non‐technical summary Individuals with a motor incomplete spinal cord injury (SCI) present clinically with partial control of muscles below the site of the injury, but experience profound weakness which can limit the ability to perform functional tasks such as walking. Interestingly, when individuals with an incomplete SCI are asked to maximally and repeatedly contract their quadriceps muscles, they demonstrate an increase in the peak force generated; individuals without SCI experience a decline in force, or ‘fatigue’. Following these repeated maximal efforts, reflex responses to electrical stimulation over the quadriceps muscle elicited amplified and prolonged, involuntary motor activity. Such responses were not observed prior to the maximal contractions, and were not observed in neurologically intact subjects. This finding suggests that increases in spinal excitability following these maximal efforts may enhance force generating capacity, and provides insight into possible novel therapeutic interventions to restore function following SCI.

[1]  Inge Zijdewind,et al.  Motor unit firing during and after voluntary contractions of human thenar muscles weakened by spinal cord injury. , 2003, Journal of neurophysiology.

[2]  Gary A. Dudley,et al.  Influence of complete spinal cord injury on skeletal muscle cross-sectional area within the first 6 months of injury , 1999, European Journal of Applied Physiology and Occupational Physiology.

[3]  Ming Wu,et al.  Temporal facilitation of spastic stretch reflexes following human spinal cord injury , 2006, The Journal of physiology.

[4]  O. Kiehn,et al.  Firing and Cellular Properties of V2a Interneurons in the Rodent Spinal Cord , 2010, The Journal of Neuroscience.

[5]  Attenuation of myosin light chain phosphorylation and posttetanic potentiation in atrophied skeletal muscle , 1997, Pflügers Archiv.

[6]  M Hallett,et al.  Characterization of postexercise facilitation and depression of motor evoked potentials to transcranial magnetic stimulation , 1996, Neurology.

[7]  S C Gandevia,et al.  Large Involuntary Forces Consistent with Plateau-Like Behavior of Human Motoneurons , 2001, The Journal of Neuroscience.

[8]  W. Rymer,et al.  Windup of flexion reflexes in chronic human spinal cord injury: a marker for neuronal plateau potentials? , 2003, Journal of neurophysiology.

[9]  D. Burke,et al.  Sustained contractions produced by plateau‐like behaviour in human motoneurones , 2002, The Journal of physiology.

[10]  T George Hornby,et al.  Absence of local sign withdrawal in chronic human spinal cord injury. , 2003, Journal of neurophysiology.

[11]  M. Gorassini,et al.  Persistent inward currents in motoneuron dendrites: Implications for motor output , 2005, Muscle & nerve.

[12]  L. Griffin,et al.  Differential fatigue of paralyzed thenar muscles by stimuli of different intensities , 2002, Muscle & nerve.

[13]  D. F. Collins,et al.  Turning on the central contribution to contractions evoked by neuromuscular electrical stimulation. , 2007, Journal of applied physiology.

[14]  Chris M Gregory,et al.  Recruitment patterns in human skeletal muscle during electrical stimulation. , 2005, Physical therapy.

[15]  D. Kernell,et al.  Fatigue‐associated changes in the electromyogram of the human first dorsal interosseous muscle , 1999, Muscle & nerve.

[16]  R. Gorman,et al.  Forces consistent with plateau-like behaviour of spinal neurons evoked in patients with spinal cord injuries. , 2003, Brain : a journal of neurology.

[17]  J Fenton,et al.  M wave potentiation during and after muscle activity. , 1989, Journal of applied physiology.

[18]  A. del Valle,et al.  The role of motor unit rate modulation versus recruitment in repeated submaximal voluntary contractions performed by control and spinal cord injured subjects. , 2001, Journal of electromyography and kinesiology : official journal of the International Society of Electrophysiological Kinesiology.

[19]  X. Li,et al.  5-HT2 receptor activation facilitates a persistent sodium current and repetitive firing in spinal motoneurons of rats with and without chronic spinal cord injury. , 2006, Journal of neurophysiology.

[20]  Jaynie F. Yang,et al.  Intrinsic activation of human motoneurons: reduction of motor unit recruitment thresholds by repeated contractions. , 2002, Journal of neurophysiology.

[21]  G. Herbison,et al.  Spinal cord injury: prognosis for ambulation based on quadriceps recovery , 1992, Paraplegia.

[22]  S. Gandevia.  Spinal and supraspinal factors in human muscle fatigue. , 2001, Physiological reviews.

[23]  O. Kiehn,et al.  Bistability of alpha‐motoneurones in the decerebrate cat and in the acute spinal cat after intravenous 5‐hydroxytryptophan. , 1988, The Journal of physiology.

[24]  D. Downham,et al.  Superimposed single impulse and pulse train electrical stimulation: A quantitative assessment during submaximal isometric knee extension in young, healthy men , 1999, Muscle & nerve.

[25]  W. Rymer,et al.  Restoration of extensor excitability in the acute spinal cat by the 5-HT2 agonist DOI. , 1996, Journal of neurophysiology.

[26]  V. Dietz.  International Encyclopedia of Rehabilitation Spasticity: Spastic Movement Disorder , 2022 .

[27]  D. F. Collins,et al.  Wide-pulse-width, high-frequency neuromuscular stimulation: implications for functional electrical stimulation. , 2006, Journal of applied physiology.

[28]  R. Harris-Warrick,et al.  Electrophysiological Characterization of V2a Interneurons and Their Locomotor-Related Activity in the Neonatal Mouse Spinal Cord , 2010, The Journal of Neuroscience.

[29]  D. Sale,et al.  Interaction of fibre type, potentiation and fatigue in human knee extensor muscles. , 2003, Acta physiologica Scandinavica.

[30]  David A Jones,et al.  Contractile properties of the quadriceps muscle in individuals with spinal cord injury , 1999, Muscle & nerve.

[31]  Kristan A. Leech,et al.  Daily Stepping in Individuals With Motor Incomplete Spinal Cord Injury , 2010, Physical Therapy.

[32]  Henning Andersen,et al.  Post-exercise facilitation of compound muscle action potentials evoked by transcranial magnetic stimulation in healthy subjects , 2000, Experimental Brain Research.

[33]  A. Hicks,et al.  Treadmill training–induced adaptations in muscle phenotype in persons with incomplete spinal cord injury , 2004, Muscle & nerve.

[34]  B. Jacobs,et al.  Response of serotonergic caudal raphe neurons in relation to specific motor activities in freely moving cats , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[35]  A. Sherwood,et al.  Clinical assessment of spasticity in spinal cord injury: a multidimensional problem. , 1996, Archives of physical medicine and rehabilitation.

[36]  A. McComas,et al.  Increased sodium pump activity following repetitive stimulation of rat soleus muscles. , 1989, The Journal of physiology.

[37]  Simon C Gandevia,et al.  Facilitation and inhibition of tibialis anterior responses to corticospinal stimulation after maximal voluntary contractions. , 2010, Journal of neurophysiology.

[38]  J. Wrathall,et al.  Up-regulation of 5-HT2 receptors is involved in the increased H-reflex amplitude after contusive spinal cord injury , 2007, Experimental Neurology.

[39]  Simon C Gandevia,et al.  Depression of Activity in the Corticospinal Pathway during Human Motor Behavior after Strong Voluntary Contractions , 2003, The Journal of Neuroscience.

[40]  J. Hounsgaard,et al.  Ca2+‐Mediated Plateau Potentials in a Subpopulation of Interneurons in the Ventral Horn of the Turtle Spinal Cord , 1992, The European journal of neuroscience.

[41]  R. Waters,et al.  International Standards for Neurological and Functional Classification of Spinal Cord Injury , 1997, Spinal Cord.

[42]  Ian E. Brown,et al.  Post-Activation Potentiation—A Clue for Simplifying Models of Muscle Dynamics' , 1998 .

[43]  O. Kiehn,et al.  Functional role of plateau potentials in vertebrate motor neurons , 1998, Current Opinion in Neurobiology.

[44]  A. McComas,et al.  Twitch potentiation after voluntary contraction , 1983, Experimental Neurology.

[45]  H Hultborn,et al.  Intrinsic membrane properties causing a bistable behaviour of alpha-motoneurones. , 1984, Experimental brain research.

[46]  M. Gorassini,et al.  Spasticity in rats with sacral spinal cord injury. , 1999, Journal of neurotrauma.

[47]  S. Gandevia,et al.  High-frequency submaximal stimulation over muscle evokes centrally generated forces in human upper limb skeletal muscles. , 2009, Journal of applied physiology.

[48]  Graham H. Creasey,et al.  International Standards for Neurological and Functional Classification of Spinal Cord Injury. American Spinal Injury Association. , 1997 .

[49]  Reductions in recruitment force thresholds in human single motor units by successive voluntary contractions , 2004, Experimental Brain Research.

[50]  J. Hounsgaard,et al.  Intrinsic membrane properties causing a bistable behaviour of α-motoneurones , 2004, Experimental Brain Research.

[51]  M. Gorassini,et al.  Evidence for plateau potentials in tail motoneurons of awake chronic spinal rats with spasticity. , 2001, Journal of neurophysiology.

[52]  Arun Jayaraman,et al.  Lower-extremity muscle cross-sectional area after incomplete spinal cord injury. , 2006, Archives of physical medicine and rehabilitation.

[53]  U. V. von Euler,et al.  The after effects of a tetanus on mammalian muscle , 1938, The Journal of physiology.

[54]  B. Bigland-ritchie,et al.  Fatigue of intermittent submaximal voluntary contractions: central and peripheral factors. , 1986, Journal of applied physiology.

[55]  R. Shields,et al.  Muscle and bone plasticity after spinal cord injury: review of adaptations to disuse and to electrical muscle stimulation. , 2008, Journal of rehabilitation research and development.

[56]  A. Privat,et al.  Direct evidence for the link between monoaminergic descending pathways and motor activity. I. A study with microdialysis probes implanted in the ventral funiculus of the spinal cord , 1995, Brain Research.

[57]  C. Heckman,et al.  Extra Forces Evoked during Electrical Stimulation of the Muscle or Its Nerve Are Generated and Modulated by a Length-Dependent Intrinsic Property of Muscle in Humans and Cats , 2011, The Journal of Neuroscience.

[58]  T George Hornby,et al.  Motoneurons: A preferred firing range across vertebrate species? , 2002, Muscle & nerve.

[59]  C. Heckman,et al.  Motoneuron excitability: The importance of neuromodulatory inputs , 2009, Clinical Neurophysiology.

[60]  P. Hodges,et al.  A comparison of computer-based methods for the determination of onset of muscle contraction using electromyography. , 1996, Electroencephalography and clinical neurophysiology.

[61]  R. Gorman,et al.  Decline in spindle support to alpha‐motoneurones during sustained voluntary contractions. , 1991, The Journal of physiology.

[62]  K. Magleby,et al.  Augmentation Increases Vesicular Release Probability in the Presence of Masking Depression at the Frog Neuromuscular Junction , 2004, The Journal of Neuroscience.

[63]  Richard W. Bohannon,et al.  Interrater reliability of a modified Ashworth scale of muscle spasticity. , 1987, Physical therapy.

[64]  Jaynie F. Yang,et al.  Role of motoneurons in the generation of muscle spasms after spinal cord injury. , 2004, Brain : a journal of neurology.

[65]  Robert Heitz,et al.  Repeated Maximal Volitional Effort Contractions in Human Spinal Cord Injury: Initial Torque Increases and Reduced Fatigue , 2009, Neurorehabilitation and neural repair.

[66]  R. Marino,et al.  Metric properties of the ASIA motor score: subscales improve correlation with functional activities. , 2004, Archives of physical medicine and rehabilitation.

[67]  Jaynie F. Yang,et al.  Intrinsic activation of human motoneurons: possible contribution to motor unit excitation. , 2002, Journal of neurophysiology.

[68]  J. Rothwell,et al.  Direct demonstration of reduction of the output of the human motor cortex induced by a fatiguing muscle contraction , 2003, Experimental Brain Research.

[69]  J. Hounsgaard,et al.  Depolarization-induced facilitation of a plateau-generating current in ventral horn neurons in the turtle spinal cord. , 1997, Journal of neurophysiology.

[70]  K. Hainaut,et al.  Nonlinear summation of contractions in striated muscle. I. Twitch potentiation in human muscle , 1986, Journal of Muscle Research & Cell Motility.