Cervical intraspinal microstimulation evokes robust forelimb movements before and after injury

OBJECTIVE Intraspinal microstimulation (ISMS) is a promising method for reanimating paralyzed limbs following neurological injury. ISMS within the cervical and lumbar spinal cord is capable of evoking a variety of highly-functional movements prior to injury, but the ability of ISMS to evoke forelimb movements after cervical spinal cord injury is unknown. Here we examine the forelimb movements and muscles activated by cervical ISMS both before and after contusion injury. APPROACH We documented the forelimb muscles activated and movements evoked via systematic stimulation of the rodent cervical spinal cord both before injury and three, six and nine weeks following a moderate C4/C5 lateralized contusion injury. Animals were anesthetized with isoflurane to permit construction of somatotopic maps of evoked movements and quantify evoked muscle synergies between cervical segments C3 and T1. MAIN RESULTS When ISMS was delivered to the cervical spinal cord, a variety of responses were observed at 68% of locations tested, with a spatial distribution that generally corresponded to the location of motor neuron pools. Stimulus currents required to achieve movement and the number of sites where movements could be evoked were unchanged by spinal cord injury. A transient shift toward extension-dominated movements and restricted muscle synergies were observed at three and six weeks following injury, respectively. By nine weeks after injury, however, ISMS-evoked patterns were similar to spinally-intact animals. SIGNIFICANCE The results demonstrate the potential for cervical ISMS to reanimate hand and arm function following spinal cord injury. Robust forelimb movements can be evoked both before and during the chronic stages of recovery from a clinically relevant and sustained cervical contusion injury.

[1]  E Jankowska,et al.  Direct and indirect activation of nerve cells by electrical pulses applied extracellularly. , 1976, The Journal of physiology.

[2]  J Inukai,et al.  Principles of motor organization of the monkey cervical spinal cord , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[3]  R. Porter,et al.  Corticomotoneuronal synapses in the monkey: Light microscopic localization upon motoneurons of intrinsic muscles of the hand , 1985, The Journal of comparative neurology.

[4]  E. Fetz,et al.  Comparable patterns of muscle facilitation evoked by individual corticomotoneuronal (CM) cells and by single intracortical microstimuli in primates: evidence for functional groups of CM cells. , 1985, Journal of neurophysiology.

[5]  B T Stokes,et al.  An electromechanical spinal injury technique with dynamic sensitivity. , 1992, Journal of neurotrauma.

[6]  F. A. Mussa-lvaldi,et al.  Convergent force fields organized in the frog's spinal cord , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[7]  V. Vanderhorst,et al.  Organization of lumbosacral motoneuronal cell groups innervating hindlimb, pelvic floor, and axial muscles in the cat , 1997, The Journal of comparative neurology.

[8]  V. Mushahwar,et al.  Selective Activation and Graded Recruitment of Functional Muscle Groups through Spinal Cord Stimulation , 1998, Annals of the New York Academy of Sciences.

[9]  Fred H. Gage,et al.  Neurotrophin-3 and Brain-Derived Neurotrophic Factor Induce Oligodendrocyte Proliferation and Myelination of Regenerating Axons in the Contused Adult Rat Spinal Cord , 1998, The Journal of Neuroscience.

[10]  M. Murray,et al.  Transplants of Fibroblasts Genetically Modified to Express BDNF Promote Regeneration of Adult Rat Rubrospinal Axons and Recovery of Forelimb Function , 1999, The Journal of Neuroscience.

[11]  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.

[12]  V. Mushahwar,et al.  Selective activation of muscle groups in the feline hindlimb through electrical microstimulation of the ventral lumbo-sacral spinal cord. , 2000, IEEE transactions on rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society.

[13]  R. Lemon,et al.  Striking differences in transmission of corticospinal excitation to upper limb motoneurons in two primate species. , 2000, Journal of neurophysiology.

[14]  I. Whishaw,et al.  Cervical motoneuron topography reflects the proximodistal organization of muscles and movements of the rat forelimb: A retrograde carbocyanine dye analysis , 2000, The Journal of comparative neurology.

[15]  Ferdinando A. Mussa-Ivaldi,et al.  Repeatable spatial maps of a few force and joint torque patterns elicited by microstimulation applied throughout the lumbar spinal cord of the spinal frog , 2000 .

[16]  T. Schallert,et al.  CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury , 2000, Neuropharmacology.

[17]  S. M. Williams,et al.  Damage to Descending Motor Pathways: The Upper Motor Neuron Syndrome , 2001 .

[18]  A. Prochazka,et al.  Intraspinal micro stimulation generates locomotor-like and feedback-controlled movements , 2002, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[19]  R. N. Lemon,et al.  An electron microscopic examination of the corticospinal projection to the cervical spinal cord in the rat: lack of evidence for cortico-motoneuronal synapses , 2003, Experimental Brain Research.

[20]  R B Stein,et al.  Movements generated by intraspinal microstimulation in the intermediate gray matter of the anesthetized, decerebrate, and spinal cat. , 2004, Canadian journal of physiology and pharmacology.

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

[22]  V. Mushahwar,et al.  Intraspinal microstimulation preferentially recruits fatigue‐resistant muscle fibres and generates gradual force in rat , 2005, The Journal of physiology.

[23]  J. Gensel,et al.  Behavioral and histological characterization of unilateral cervical spinal cord contusion injury in rats. , 2006, Journal of neurotrauma.

[24]  A Prochazka,et al.  Intraspinal microstimulation excites multisegmental sensory afferents at lower stimulus levels than local alpha-motoneuron responses. , 2006, Journal of neurophysiology.

[25]  E. Fetz,et al.  Forelimb movements and muscle responses evoked by microstimulation of cervical spinal cord in sedated monkeys. , 2007, Journal of neurophysiology.

[26]  G. Paxinos,et al.  The Spinal Cord: A Christopher and Dana Reeve Foundation Text and Atlas , 2009 .

[27]  J. E. Collazos-Castro,et al.  Compartmentalization in the triceps brachii motoneuron nucleus and its relation to muscle architecture , 2009, The Journal of comparative neurology.

[28]  Muscle Plasticity in Rat Following Spinal Transection and Chronic Intraspinal Microstimulation , 2011, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[29]  Jonas B. Zimmermann,et al.  Reanimating the arm and hand with intraspinal microstimulation , 2011, Journal of neural engineering.

[30]  R. Morris,et al.  Spatial characterization of the motor neuron columns supplying the rat forelimb , 2012, Neuroscience.

[31]  William J Tyler,et al.  A quantitative overview of biophysical forces impinging on neural function , 2013, Physical biology.