A potential treatment for paralysis resulting from spinal cord injury is to route control signals from the brain around the injury by artificial connections. Such signals could then control electrical stimulation of muscles, thereby restoring volitional movement to paralysed limbs1,2,3. In previously separate experiments, activity of motor cortex neurons related to actual or imagined movements has been used to control computer cursors and robotic arms4,5,6,7,8,9,10, and paralysed muscles have been activated by functional electrical stimulation11,12,13. Here we show that Macaca nemestrina monkeys can directly control stimulation of muscles using the activity of neurons in the motor cortex, thereby restoring goal-directed movements to a transiently paralysed arm. Moreover, neurons could control functional stimulation equally well regardless of any previous association to movement, a finding that considerably expands the source of control signals for brain-machine interfaces. Monkeys learned to use these artificial connections from cortical cells to muscles to generate bidirectional wrist torques, and controlled multiple neuron–muscle pairs simultaneously. Such direct transforms from cortical activity to muscle stimulation could be implemented by autonomous electronic circuitry, creating a relatively natural neuroprosthesis. These results are the first demonstration that direct artificial connections between cortical cells and muscles can compensate for interrupted physiological pathways and restore volitional control of movement to paralysed limbs.
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Jackson, A., Moritz, C. T., Mavoori, J., Lucas, T. H. & Fetz, E. E. The Neurochip BCI: towards a neural prosthesis for upper limb function. IEEE Trans. Neural Syst. Rehabil. Eng. 14, 187–190 (2006)
Lauer, R. T., Peckham, P. H. & Kilgore, K. L. EEG-based control of a hand grasp neuroprosthesis. Neuroreport 10, 1767–1771 (1999)
Fagg, A. H. et al. Biomimetic brain machine interfaces for the control of movement. J. Neurosci. 27, 11842–11846 (2007)
Carmena, J. M. et al. Learning to control a brain-machine interface for reaching and grasping by primates. PLoS Biol. 1, E42 (2003)
Velliste, M., Perel, S., Spalding, M. C., Whitford, A. S. & Schwartz, A. B. Cortical control of a prosthetic arm for self-feeding. Nature 453, 109–1101 (2008)
Hochberg, L. R. et al. Neuronal ensemble control of prosthetic devices by a human with tetraplegia. Nature 442, 164–171 (2006)
Kennedy, P. R., Bakay, R. A., Moore, M. M., Adams, K. & Goldwaithe, J. Direct control of a computer from the human central nervous system. IEEE Trans. Rehabil. Eng. 8, 198–202 (2000)
Musallam, S., Corneil, B. D., Greger, B., Scherberger, H. & Andersen, R. A. Cognitive control signals for neural prosthetics. Science 305, 258–262 (2004)
Serruya, M. D., Hatsopoulos, N. G., Paninski, L., Fellows, M. R. & Donoghue, J. P. Instant neural control of a movement signal. Nature 416, 141–142 (2002)
Taylor, D. M., Tillery, S. I. & Schwartz, A. B. Direct cortical control of 3D neuroprosthetic devices. Science 296, 1829–1832 (2002)
Nannini, N. & Horch, K. Muscle recruitment with intrafascicular electrodes. IEEE Trans. Biomed. Eng. 38, 769–776 (1991)
Peckham, P. H. et al. An advanced neuroprosthesis for restoration of hand and upper arm control using an implantable controller. J. Hand Surg. 27, 265–276 (2002)
Stein, R. B., Aoyagi, Y., Mushahwar, V. K. & Prochazka, A. Limb movements generated by stimulating muscle, nerve and spinal cord. Arch. Ital. Biol. 140, 273–281 (2002)
Fetz, E. E. & Baker, M. A. Operantly conditioned patterns on precentral unit activity and correlated responses in adjacent cells and contralateral muscles. J. Neurophysiol. 36, 179–204 (1973)
Fetz, E. E. & Finocchio, D. V. Correlations between activity of motor cortex cells and arm muscles during operantly conditioned response patterns. Exp. Brain Res. 23, 217–240 (1975)
Fetz, E. E. Volitional control of neural activity: implications for brain-computer interfaces. J. Physiol. (Lond.) 579, 571–579 (2007)
Shadmehr, R. & Mussa-Ivaldi, F. A. Adaptive representation of dynamics during learning of a motor task. J. Neurosci. 14, 3208–3224 (1994)
Thach, W. T. Correlation of neural discharge with pattern and force of muscular activity, joint position, and direction of intended next movement in motor cortex and cerebellum. J. Neurophysiol. 41, 654–676 (1978)
Gandolfo, F., Li, C., Benda, B. J., Schioppa, C. P. & Bizzi, E. Cortical correlates of learning in monkeys adapting to a new dynamical environment. Proc. Natl Acad. Sci. USA 97, 2259–2263 (2000)
Nudo, R. J., Milliken, G. W., Jenkins, W. M. & Merzenich, M. M. Use-dependent alterations of movement representations in primary motor cortex of adult squirrel monkeys. J. Neurosci. 16, 785–807 (1996)
Brinkman, C., Porter, R. & Norman, J. Plasticity of motor behavior in monkeys with crossed forelimb nerves. Science 220, 438–440 (1983)
Kuiken, T. A., Dumanian, G. A., Lipschutz, R. D., Miller, L. A. & Stubblefield, K. A. The use of targeted muscle reinnervation for improved myoelectric prosthesis control in a bilateral shoulder disarticulation amputee. Prosthet. Orthot. Int. 28, 245–253 (2004)
Jackson, A., Mavoori, J. & Fetz, E. E. Long-term motor cortex plasticity induced by an electronic neural implant. Nature 444, 56–60 (2006)
Mavoori, J., Jackson, A., Diorio, C. & Fetz, E. An autonomous implantable computer for neural recording and stimulation in unrestrained primates. J. Neurosci. Methods 148, 71–77 (2005)
Lemay, M. A. & Grill, W. M. Modularity of motor output evoked by intraspinal microstimulation in cats. J. Neurophysiol. 91, 502–514 (2004)
Mushahwar, V. K., Gillard, D. M., Gauthier, M. J. & Prochazka, A. Intraspinal micro stimulation generates locomotor-like and feedback-controlled movements. IEEE Trans. Neural Syst. Rehabil. Eng. 10, 68–81 (2002)
Tresch, M. C. & Bizzi, E. Responses to spinal microstimulation in the chronically spinalized rat and their relationship to spinal systems activated by lowthreshold cutaneous stimulation. Exp. Brain Res. 129, 401–416 (1999)
Batschelet, E. Circular Statistics in Biology 3–39 (Academic, 1981)
Evarts, E. V. Relation of pyramidal tract activity to force exerted during voluntary movement. J. Neurophysiol. 31, 14–27 (1968)
Woolsey, C. N. et al. Patterns of localization in precentral and “supplementary” motor areas and their relation to the concept of a premotor area. Res. Publ. Assoc. Res. Nerv. Ment. Dis. 30, 238–264 (1952)
Jackson, A. & Fetz, E. E. A compact moveable microwire array for long-term chronic unit recording in cerebral cortex of primates. J. Neurophysiol. 98, 3109–3118 (2007)
Jackson, A., Mavoori, J. & Fetz, E. E. Correlations between the same motor cortex cells and arm muscles during a trained task, free behavior, and natural sleep in the macaque monkey. J. Neurophysiol. 97, 360–374 (2007)
Loeb, G. E. & Hoffer, J. A. Activity of spindle afferents from cat anterior thigh muscles. II. Effects of fusimotor blockade. J. Neurophysiol. 54, 565–577 (1985)
We thank L. Shupe for programming assistance, C. Kent and L. Miller for advice on nerve block, C. Kirby, A. Price and K. McElwain for animal care, and A. Jackson, Y. Nishimura and A. Richardson for comments on the manuscript. This work was supported by grants from the National Institutes of Health.
Author Contributions C.T.M. and E.E.F. conceived and designed the experiments, C.T.M. and S.I.P. performed the experiments, and C.T.M. and E.E.F. wrote the paper.
This files contains Supplementary Figures S1-S4 with Legends, Supplementary Methods, Supplementary Results, Supplementary Discussion and Supplementary References. (PDF 8992 kb)
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Moritz, C., Perlmutter, S. & Fetz, E. Direct control of paralysed muscles by cortical neurons. Nature 456, 639–642 (2008). https://doi.org/10.1038/nature07418
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