Closed-loop control of spinal cord stimulation to restore hand function after paralysis

As yet, no cure exists for upper-limb paralysis resulting from the damage to motor pathways after spinal cord injury or stroke. Recently, neural activity from the motor cortex of paralyzed individuals has been used to control the movements of a robot arm but restoring function to patients' actual limbs remains a considerable challenge. Previously we have shown that electrical stimulation of the cervical spinal cord in anesthetized monkeys can elicit functional upper-limb movements like reaching and grasping. Here we show that stimulation can be controlled using cortical activity in awake animals to bypass disruption of the corticospinal system, restoring their ability to perform a simple upper-limb task. Monkeys were trained to grasp and pull a spring-loaded handle. After temporary paralysis of the hand was induced by reversible inactivation of primary motor cortex using muscimol, grasp-related single-unit activity from the ventral premotor cortex was converted into stimulation patterns delivered in real-time to the cervical spinal gray matter. During periods of closed-loop stimulation, task-modulated electromyogram, movement amplitude, and task success rate were improved relative to interleaved control periods without stimulation. In some sessions, single motor unit activity from weakly active muscles was also used successfully to control stimulation. These results are the first use of a neural prosthesis to improve the hand function of primates after motor cortex disruption, and demonstrate the potential for closed-loop cortical control of spinal cord stimulation to reanimate paralyzed limbs.

[1]  R. Stein,et al.  Changes in firing rate of human motor units during linearly changing voluntary contractions , 1973, The Journal of physiology.

[2]  M. Craggs Cortical control of motor prostheses: using the cord-transected baboon as the primate model for human paraplegia. , 1975, Advances in neurology.

[3]  T. Sawaguchi,et al.  Behavioral deficits induced by local injection of bicuculline and muscimol into the primate motor and premotor cortex. , 1991, Journal of neurophysiology.

[4]  RP Dum,et al.  The origin of corticospinal projections from the premotor areas in the frontal lobe , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  E. Fetz,et al.  Activity of spinal interneurons and their effects on forearm muscles during voluntary wrist movements in the monkey. , 1998, Journal of neurophysiology.

[6]  M H Schieber,et al.  Partial Inactivation of the Primary Motor Cortex Hand Area: Effects on Individuated Finger Movements , 1998, The Journal of Neuroscience.

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

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

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

[10]  P. Strick,et al.  Motor Areas in the Frontal Lobe: The Anatomical Substrate for the Central Control of Movement , 2004 .

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

[12]  Jon A. Mukand,et al.  Neuronal ensemble control of prosthetic devices by a human with tetraplegia , 2006, Nature.

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

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

[15]  E. Fetz,et al.  Compact movable microwire array for long-term chronic unit recording in cerebral cortex of primates. , 2007, Journal of neurophysiology.

[16]  Marc A. Maier,et al.  Pronounced Reduction of Digit Motor Responses Evoked from Macaque Ventral Premotor Cortex after Reversible Inactivation of the Primary Motor Cortex Hand Area , 2008, The Journal of Neuroscience.

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

[18]  R. Lemon Descending pathways in motor control. , 2008, Annual review of neuroscience.

[19]  Andrew S. Whitford,et al.  Cortical control of a prosthetic arm for self-feeding , 2008, Nature.

[20]  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.

[21]  Michael J. Black,et al.  Decoding Complete Reach and Grasp Actions from Local Primary Motor Cortex Populations , 2010, The Journal of Neuroscience.

[22]  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.

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

[24]  Nicolas Y. Masse,et al.  Reach and grasp by people with tetraplegia using a neurally controlled robotic arm , 2012, Nature.

[25]  Andreas Schulze-Bonhage,et al.  Decoding natural grasp types from human ECoG , 2012, NeuroImage.

[26]  M. Devivo,et al.  Epidemiology of traumatic spinal cord injury: trends and future implications , 2012, Spinal Cord.

[27]  Arjun K. Bansal,et al.  Decoding 3D reach and grasp from hybrid signals in motor and premotor cortices: spikes, multiunit activity, and local field potentials. , 2012, Journal of neurophysiology.

[28]  Jonas B. Zimmermann,et al.  Neural interfaces for the brain and spinal cord—restoring motor function , 2012, Nature Reviews Neurology.

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

[30]  David J. Guggenmos,et al.  Restoration of function after brain damage using a neural prosthesis , 2013, Proceedings of the National Academy of Sciences.

[31]  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.

[32]  A. Schwartz,et al.  High-performance neuroprosthetic control by an individual with tetraplegia , 2013, The Lancet.

[33]  C. Moritz,et al.  Cervical intraspinal microstimulation evokes robust forelimb movements before and after injury , 2013, Journal of neural engineering.

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

[35]  A. Jackson,et al.  Upper-limb muscle responses to epidural, subdural and intraspinal stimulation of the cervical spinal cord , 2014, Journal of neural engineering.