Volitional Walking via Upper Limb Muscle-Controlled Stimulation of the Lumbar Locomotor Center in Man

Gait disturbance in individuals with spinal cord lesion is attributed to the interruption of descending pathways to the spinal locomotor center, whereas neural circuits below and above the lesion maintain their functional capability. An artificial neural connection (ANC), which bridges supraspinal centers and locomotor networks in the lumbar spinal cord beyond the lesion site, may restore the functional impairment. To achieve an ANC that sends descending voluntary commands to the lumbar locomotor center and bypasses the thoracic spinal cord, upper limb muscle activity was converted to magnetic stimuli delivered noninvasively over the lumbar vertebra. Healthy participants were able to initiate and terminate walking-like behavior and to control the step cycle through an ANC controlled by volitional upper limb muscle activity. The walking-like behavior stopped just after the ANC was disconnected from the participants even when the participant continued to swing arms. Furthermore, additional simultaneous peripheral electrical stimulation to the foot via the ANC enhanced this walking-like behavior. Kinematics of the induced behaviors were identical to those observed in voluntary walking. These results demonstrate that the ANC induces volitionally controlled, walking-like behavior of the legs. This paradigm may be able to compensate for the dysfunction of descending pathways by sending commands to the preserved locomotor center at the lumbar spinal cord and may enable individuals with paraplegia to regain volitionally controlled walking.

[1]  E Bizzi,et al.  Motor learning through the combination of primitives. , 2000, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[2]  P. Jacobs,et al.  Involuntary stepping after chronic spinal cord injury. Evidence for a central rhythm generator for locomotion in man. , 1994, Brain : a journal of neurology.

[3]  V. Gurfinkel,et al.  Tonic central and sensory stimuli facilitate involuntary air-stepping in humans. , 2009, Journal of neurophysiology.

[4]  V. Dietz,et al.  Functional electrical stimulation for grasping and walking: indications and limitations , 2001, Spinal Cord.

[5]  Yukio Nishimura,et al.  Restoration of upper limb movement via artificial corticospinal and musculospinal connections in a monkey with spinal cord injury , 2013, Front. Neural Circuits.

[6]  S. Rossignol,et al.  Discharge patterns of reticulospinal and other reticular neurons in chronic, unrestrained cats walking on a treadmill. , 1986, Journal of neurophysiology.

[7]  Yury Gerasimenko,et al.  Novel and Direct Access to the Human Locomotor Spinal Circuitry , 2010, The Journal of Neuroscience.

[8]  E. Roulot,et al.  Re: Attrition rupture of the flexor pollicis longus in rheumatoid arthritis on an interphalangeal sesamoid bone , 2008, The Journal of hand surgery, European volume.

[9]  V. Edgerton,et al.  Hindlimb stepping movements in complete spinal rats induced by epidural spinal cord stimulation , 2005, Neuroscience Letters.

[10]  K W Horch,et al.  Muscle recruitment through electrical stimulation of the lumbo-sacral spinal cord. , 2000, IEEE transactions on rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society.

[11]  Jerald D. Kralik,et al.  Real-time prediction of hand trajectory by ensembles of cortical neurons in primates , 2000, Nature.

[12]  E. Fetz,et al.  Long-term motor cortex plasticity induced by an electronic neural implant , 2006, Nature.

[13]  M. Dimitrijevic,et al.  Evidence for a Spinal Central Pattern Generator in Humans a , 1998, Annals of the New York Academy of Sciences.

[14]  K. Kilgore,et al.  Efficacy of an implanted neuroprosthesis for restoring hand grasp in tetraplegia: a multicenter study. , 2001, Archives of physical medicine and rehabilitation.

[15]  M. Dimitrijevic,et al.  Stepping-like movements in humans with complete spinal cord injury induced by epidural stimulation of the lumbar cord: electromyographic study of compound muscle action potentials , 2004, Spinal Cord.

[16]  Fred H. Gage,et al.  Therapeutic interventions after spinal cord injury , 2006, Nature Reviews Neuroscience.

[17]  Eberhard E. Fetz,et al.  Myo-Cortical Crossed Feedback Reorganizes Primate Motor Cortex Output , 2013, The Journal of Neuroscience.

[18]  Y. Gerasimenko,et al.  The role of cutaneous afferents in controlling locomotion evoked by epidural stimulation of the spinal cord in decerebrate cats , 2008, Neuroscience and Behavioral Physiology.

[19]  E. Fetz,et al.  Direct control of paralyzed muscles by cortical neurons , 2008, Nature.

[20]  Daniel P. Ferris,et al.  Neural coupling between upper and lower limbs during recumbent stepping. , 2004, Journal of applied physiology.

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

[22]  David M. Santucci,et al.  Learning to Control a Brain–Machine Interface for Reaching and Grasping by Primates , 2003, PLoS biology.

[23]  A. Prochazka,et al.  Spinal Cord Microstimulation Generates Functional Limb Movements in Chronically Implanted Cats , 2000, Experimental Neurology.

[24]  S. Solla,et al.  Toward the Restoration of Hand Use to a Paralyzed Monkey: Brain-Controlled Functional Electrical Stimulation of Forearm Muscles , 2009, PloS one.

[25]  V. Mushahwar,et al.  Afferent inputs to mid‐ and lower‐lumbar spinal segments are necessary for stepping in spinal cats , 2010, Annals of the New York Academy of Sciences.

[26]  S. Ueno,et al.  Magnetic stimulation of the sacral roots for the treatment of stress incontinence: an investigational study and placebo controlled trial. , 2000, The Journal of urology.

[27]  S. Grillner,et al.  On the central generation of locomotion in the low spinal cat , 1979, Experimental Brain Research.

[28]  B. Day,et al.  Magnetic stimulation over the spinal enlargements. , 1989, Journal of neurology, neurosurgery, and psychiatry.

[29]  K Matsuyama,et al.  Vestibulospinal and reticulospinal neuronal activity during locomotion in the intact cat. II. Walking on an inclined plane. , 2000, Journal of neurophysiology.

[30]  L. Miller,et al.  Restoration of grasp following paralysis through brain-controlled stimulation of muscles , 2012, Nature.

[31]  L. Shupe,et al.  The Neurochip-2: An Autonomous Head-Fixed Computer for Recording and Stimulating in Freely Behaving Monkeys , 2011, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[32]  V. Edgerton,et al.  Epidural stimulation: Comparison of the spinal circuits that generate and control locomotion in rats, cats and humans , 2008, Experimental Neurology.

[33]  Yukio Nishimura,et al.  Spike-Timing-Dependent Plasticity in Primate Corticospinal Connections Induced during Free Behavior , 2013, Neuron.

[34]  V. Gurfinkel,et al.  Locomotor‐like movements evoked by leg muscle vibration in humans , 1998, The European journal of neuroscience.

[35]  K. Kilgore,et al.  An implanted upper-extremity neuroprosthesis using myoelectric control. , 2008, The Journal of hand surgery.

[36]  E. Zehr,et al.  Cutaneous reflexes during human gait: electromyographic and kinematic responses to electrical stimulation. , 1997, Journal of neurophysiology.

[37]  S. Grillner,et al.  The locomotion of the acute spinal cat injected with clonidine i.v. , 1973, Brain research.

[38]  M. E. Goldberger.  Partial and complete deafferentation of cat hindlimb: the contribution of behavioral substitution to recovery of motor function , 2004, Experimental Brain Research.

[39]  O. A. Nikitin,et al.  Initiation of Locomotor Activity in Spinal Cats by Epidural Stimulation of the Spinal Cord , 2003, Neuroscience and Behavioral Physiology.

[40]  E. Fetz,et al.  The neurochip BCI: towards a neural prosthesis for upper limb function , 2006, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[41]  T. Sinkjaer,et al.  Therapy of paretic arm in hemiplegic subjects augmented with a neural prosthesis: a cross-over study. , 2004, Canadian journal of physiology and pharmacology.

[42]  S. Micera,et al.  Restoring Voluntary Control of Locomotion after Paralyzing Spinal Cord Injury , 2012, Science.

[43]  Noritaka Kawashima,et al.  Shaping appropriate locomotive motor output through interlimb neural pathway within spinal cord in humans. , 2008, Journal of neurophysiology.

[44]  V. Mushahwar,et al.  Intraspinal microstimulation generates functional movements after spinal-cord injury , 2004, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[45]  S. Rossignol,et al.  Dynamic sensorimotor interactions in locomotion. , 2006, Physiological reviews.

[46]  Andrew Jackson,et al.  An autonomous implantable computer for neural recording and stimulation in unrestrained primates , 2005, Journal of Neuroscience Methods.

[47]  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.

[48]  S. Rossignol,et al.  Activity of medullary reticulospinal neurons during fictive locomotion. , 1993, Journal of neurophysiology.

[49]  Christie K. Ferreira,et al.  Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study , 2011, The Lancet.

[50]  Yasuo Terao,et al.  Magnetic-motor-root stimulation: Review , 2013, Clinical Neurophysiology.

[51]  C. Moritz,et al.  Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury , 2013, Journal of neural engineering.

[52]  S. Meagher.  Instant neural control of a movement signal , 2002 .

[53]  S. Rossignol,et al.  Nonlocomotor and locomotor hindlimb responses evoked by electrical microstimulation of the lumbar cord in spinalized cats. , 2006, Journal of neurophysiology.

[54]  Ann M. Stowe,et al.  Post-infarct cortical plasticity and behavioral recovery using concurrent cortical stimulation and rehabilitative training: A feasibility study in primates , 2003, Neurological research.

[55]  Hui Zhong,et al.  Facilitation of Stepping with Epidural Stimulation in Spinal Rats: Role of Sensory Input , 2008, The Journal of Neuroscience.

[56]  S. Rossignol,et al.  Contribution of cutaneous inputs from the hindpaw to the control of locomotion. II. Spinal cats. , 2003, Journal of neurophysiology.

[57]  S. Rossignol,et al.  Characteristics and mechanisms of locomotion induced by intraspinal microstimulation and dorsal root stimulation in spinal cats. , 2007, Journal of neurophysiology.