Enhancing Nervous System Recovery through Neurobiologics, Neural Interface Training, and Neurorehabilitation

Max O Krucoff, Shervin Rahimpour, Marc W Slutzky, V Reggie Edgerton, Dennis A Turner, Max O Krucoff, Shervin Rahimpour, Marc W Slutzky, V Reggie Edgerton, Dennis A Turner

Abstract

After an initial period of recovery, human neurological injury has long been thought to be static. In order to improve quality of life for those suffering from stroke, spinal cord injury, or traumatic brain injury, researchers have been working to restore the nervous system and reduce neurological deficits through a number of mechanisms. For example, neurobiologists have been identifying and manipulating components of the intra- and extracellular milieu to alter the regenerative potential of neurons, neuro-engineers have been producing brain-machine and neural interfaces that circumvent lesions to restore functionality, and neurorehabilitation experts have been developing new ways to revitalize the nervous system even in chronic disease. While each of these areas holds promise, their individual paths to clinical relevance remain difficult. Nonetheless, these methods are now able to synergistically enhance recovery of native motor function to levels which were previously believed to be impossible. Furthermore, such recovery can even persist after training, and for the first time there is evidence of functional axonal regrowth and rewiring in the central nervous system of animal models. To attain this type of regeneration, rehabilitation paradigms that pair cortically-based intent with activation of affected circuits and positive neurofeedback appear to be required-a phenomenon which raises new and far reaching questions about the underlying relationship between conscious action and neural repair. For this reason, we argue that multi-modal therapy will be necessary to facilitate a truly robust recovery, and that the success of investigational microscopic techniques may depend on their integration into macroscopic frameworks that include task-based neurorehabilitation. We further identify critical components of future neural repair strategies and explore the most updated knowledge, progress, and challenges in the fields of cellular neuronal repair, neural interfacing, and neurorehabilitation, all with the goal of better understanding neurological injury and how to improve recovery.

Keywords: brain-machine interface (BMI); neural interface; neural regeneration; neural repair; neural stimulation; neuroplasticity; neurorehabilitation; spinal cord stimulation.

Figures

Figure 1
Figure 1
Injury environment timeline. Blue, acute phase; Red, subacute phase; Black, chronic phase. ICP, intracranial pressure.
Figure 2
Figure 2
Intra- and extracellular mechanisms of neuronal growth and inhibition. Blue, associated with neuronal growth; Red, associated with neuronal inhibition; Black, modulates both neuronal growth and inhibition. PTEN, phosphatase and tensin homolog; cAMP, cyclic adenosine monophosphate; GAP43, growth associated protein 43; GDF10, growth differentiation factor 10; CAP23, cytoskeleton-associated protein; ARG1, arginase 1; SPRR1, small proline-rich protein 1; HSPB1, heat shock protein family B (small) member 1; MARCKS, myristoylated alanine-rich C-kinase substrate; SCG10, superior cervical ganglion 10; NgR, nogo receptor; CSPG, chondroitin sulfate proteoglycans; NG2, neural/glial antigen 2; MAG, myelin-associated glycoprotein; OMgp, oligodendrocyte-myelin glycoprotein; CNTF, ciliary neurotrophic factor; OPN, osteopontin; IGF1, insulin-like growth factor 1.
Figure 3
Figure 3
Principal component analysis (PCA). The example reduces 22 joint-position variables of the wrist and fingers to 3 dimensions that represent the state of the hand. (A) Experimental task where the patient is cued to move his hand into one of the three configurations shown. (B) 22 independent variables of hand movement are recorded and reduced to 3 principle components (PCs). Results are plotted as hand position and hand velocity in 3-dimensional PC space. (C) Greater than 80% variance of hand movement is accounted for using only the first three PCs (Krucoff and Slutzky, 2011). MCP, metacarpophalangeal joint; PIP, proximal interphalangeal joint; DIP, distal interphalangeal joint.
Figure 4
Figure 4
Assistive vs. rehabilitative BMIs. The assistive BMI uses brain signals to bypass a neural lesion and generate an intended action. The rehabilitative BMI pairs goal-oriented tasks with positive feedback and works to re-activate lesioned circuits to create plasticity for long-lasting functional improvement.
Figure 5
Figure 5
Recording and stimulating modalities for neural signals. (A) Functional MRI (fMRI), (B) functional Near-Infrared Spectroscopy (fNIRS), (C) scalp electrodes (EEG), (D) epidural electrodes (FP), (E) subdural electrodes (ECoG), (F) intracortical electrodes (AP, or spikes), (G) muscle electrodes (EMG), (H) intraspinal electrodes (AP, or spikes), (I) spinal epidural electrodes (FP). EEG, electroencephalography; FP, field potential; ECoG, electrocorticography; AP, action potential; EMG, electromyography.
Figure 6
Figure 6
Neurorehabilitation strategies. (A) Partial weight-based therapy (PWBT), (B) constraint-induced movement therapy (CIMT) in a patient with a right hemispheric injury, (C) cortical neurostimulation in a patient with a right hemispheric injury, (D) biofeedback in a patient with a left hemispheric injury. CPU, computer processing unit; EEG, electroencephalography; fMRI, functional magnetic resonance imaging.

References

    1. Alilain W. J., Horn K. P., Hu H., Dick T. E., Silver J. (2011). Functional regeneration of respiratory pathways after spinal cord injury. Nature 475, 196–200. 10.1038/nature10199
    1. Allred R. P., Jones T. A. (2008). Maladaptive effects of learning with the less-affected forelimb after focal cortical infarcts in rats. Exp. Neurol. 210, 172–181. 10.1016/j.expneurol.2007.10.010
    1. Allred R. P., Maldonado M. A., Hsu And J. E., Jones T. A. (2005). Training the less-affected forelimb after unilateral cortical infarcts interferes with functional recovery of the impaired forelimb in rats. Restor. Neurol. Neurosci. 23, 297–302.
    1. Alvarez-Buylla A., Lim D. (2004). For the long run: maintaining germinal niches in the adult brain. Neuron 41, 683–686. 10.1016/S0896-6273(04)00111-4
    1. Ang K. K., Guan C., Chua K. S. G., Phua K. S., Wang C., Chin Z. Y., et al. . (2013). A clinical study of motor imagery BCI performance in stroke by including calibration data from passive movement. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2013, 6603–6606. 10.1109/EMBC.2013.6611069
    1. Angeli C. A., Edgerton V. R., Gerasimenko Y. P., Harkema S. J. (2014). Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain 137, 1394–1409. 10.1093/brain/awu038
    1. Arvidsson A., Collin T., Kirik D., Kokaia Z., Lindvall O. (2002). Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat. Med. 8, 963–970. 10.1038/nm747
    1. Baldwin K. T., Carbajal K. S., Segal B. M., Giger R. J. (2015). Neuroinflammation triggered by β-glucan/dectin-1 signaling enables CNS axon regeneration. Proc. Natl. Acad. Sci. U.S.A. 112, 2581–2586. 10.1073/pnas.1423221112
    1. Barbeau H., Rossignol S. (1987). Recovery of locomotion after chronic spinalization in the adult cat. Brain Res. 412, 84–95. 10.1016/0006-8993(87)91442-9
    1. Barrese J. C., Aceros J., Donoghue J. P. (2016). Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates. J. Neural Eng. 13:26003. 10.1088/1741-2560/13/2/026003
    1. Barrese J. C., Rao N., Paroo K., Triebwasser C., Vargas-Irwin C., Franquemont L., et al. . (2013). Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates. J. Neural Eng. 10:66014. 10.1088/1741-2560/10/6/066014
    1. Becker D., Gary D. S., Rosenzweig E. S., Grill W. M., McDonald J. W. (2010). Functional electrical stimulation helps replenish progenitor cells in the injured spinal cord of adult rats. Exp. Neurol. 222, 211–218. 10.1016/j.expneurol.2009.12.029
    1. Bei F., Lee H. H., Liu X., Gunner G., Jin H., Ma L., et al. . (2016). Restoration of visual function by enhancing conduction in regenerated axons. Cell 164, 219–232. 10.1016/j.cell.2015.11.036
    1. Benowitz L. I., Carmichael S. T. (2010). Promoting axonal rewiring to improve outcome after stroke. Neurobiol. Dis. 37, 259–266. 10.1016/j.nbd.2009.11.009
    1. Benowitz L. I., Popovich P. G. (2011). Inflammation and axon regeneration. Curr. Opin. Neurol. 24, 577–583. 10.1097/WCO.0b013e32834c208d
    1. Benowitz L. I., Yin Y. (2007). Combinatorial treatments for promoting axon regeneration in the CNS: strategies for overcoming inhibitory signals and activating neurons' intrinsic growth state. Dev. Neurobiol. 67, 1148–1165. 10.1002/dneu.20515
    1. Benowitz L., Yin Y. (2008). Rewiring the injured CNS: Lessons from the optic nerve. Exp. Neurol. 209, 389–398. 10.1016/j.expneurol.2007.05.025
    1. Bernstein D. R., Stelzner D. J. (1983). Plasticity of the corticospinal tract following midthoracic spinal injury in the postnatal rat. J. Comp. Neurol. 221, 382–400. 10.1002/cne.902210403
    1. Bhullar I. S., Johnson D., Paul J. P., Kerwin A. J., Tepas J. J., Frykberg E. R. (2014). More harm than good: antiseizure prophylaxis after traumatic brain injury does not decrease seizure rates but may inhibit functional recovery. J. Trauma Acute Care Surg. 76, 54–60. 10.1097/TA.0b013e3182aafd15
    1. Bick S. K., Eskandar E. N. (2016). Neuromodulation for restoring memory. Neurosurg. Focus 40:E5. 10.3171/2016.3.FOCUS162
    1. Bienenstock E. L., Cooper L. N., Munro P. W. (1982). Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex. J. Neurosci. 2, 32–48.
    1. Birbaumer N., Ghanayim N., Hinterberger T., Iversen I., Kotchoubey B., Kübler A., et al. . (1999). A spelling device for the paralysed. Nature 398, 297–298. 10.1038/18581
    1. Bouton C. E., Shaikhouni A., Annetta N. V., Bockbrader M. A., Friedenberg D. A., Nielson D. M., et al. . (2016). Restoring cortical control of functional movement in a human with quadriplegia. Nature 533, 247–250. 10.1038/nature17435
    1. Breakspear M., Stam C. J. (2005). Dynamics of a neural system with a multiscale architecture. Philos. Trans. R. Soc. Lond. B Biol. Sci. 360, 1051–1074. 10.1098/rstb.2005.1643
    1. Breceda E. Y., Dromerick A. W. (2013). Motor rehabilitation in stroke and traumatic brain injury: stimulating and intense. Curr. Opin. Neurol. 26, 595–601. 10.1097/WCO.0000000000000024
    1. Bregman B. S., Kunkel-Bagden E., Schnell L., Dai H. N., Gao D., Schwab M. E. (1995). Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors. Nature 378, 498–501. 10.1038/378498a0
    1. Brogaard B., Gatzia D. E. (2016). What can neuroscience tell us about the hard problem of consciousness? Front. Neurosci. 10:395. 10.3389/fnins.2016.00395
    1. Buch E., Weber C., Cohen L. G., Braun C., Dimyan M. A., Ard T., et al. . (2008). Think to move: a neuromagnetic brain-computer interface (BCI) system for chronic stroke. Stroke 39, 910–917. 10.1161/STROKEAHA.107.505313
    1. Bulinski J. C., Ohm T., Roder H., Spruston N., Turner D. A., Wheal H. V. (1998). Changes in dendritic structure and function following hippocampal lesions: correlations with developmental events? Prog. Neurobiol. 55, 641–650. 10.1016/s0301-0082(98)00023-9
    1. Cai L. L., Fong A. J., Otoshi C. K., Liang Y., Burdick J. W., Roy R. R., et al. . (2006). Implications of assist-as-needed robotic step training after a complete spinal cord injury on intrinsic strategies of motor learning. J. Neurosci. 26, 10564–10568. 10.1523/JNEUROSCI.2266-06.2006
    1. Capogrosso M., Milekovic T., Borton D., Wagner F., Martin Moraud E., Mignardot J.-B., et al. . (2016). A brain-spinal interface alleviating gait deficits after spinal cord injury in primates. Nature 539, 284–288. 10.1038/nature20118
    1. Carhart M. R., He J., Herman R., D'Luzansky S., Willis W. T. (2004). Epidural spinal-cord stimulation facilitates recovery of functional walking following incomplete spinal-cord injury. IEEE Trans. Neural Syst. Rehabil. Eng. 12, 32–42. 10.1109/TNSRE.2003.822763
    1. Carmena J. M., Lebedev M. A., Crist R. E., O'Doherty J. E., Santucci D. M., Dimitrov D. F., et al. . (2003). Learning to control a brain-machine interface for reaching and grasping by primates. PLoS Biol. 1:E42. 10.1371/journal.pbio.0000042
    1. Carmichael S. T., Archibeque I., Luke L., Nolan T., Momiy J., Li S. (2005). Growth-associated gene expression after stroke: evidence for a growth-promoting region in peri-infarct cortex. Exp. Neurol. 193, 291–311. 10.1016/j.expneurol.2005.01.004
    1. Carmichael S. T., Chesselet M.-F. (2002). Synchronous neuronal activity is a signal for axonal sprouting after cortical lesions in the adult. J. Neurosci. 22, 6062–6070.
    1. Carson R. G., Kennedy N. C. (2013). Modulation of human corticospinal excitability by paired associative stimulation. Front. Hum. Neurosci. 7:823. 10.3389/fnhum.2013.00823
    1. Chang C. W., Lo Y. K., Gad P., Edgerton R., Liu W. (2014). Design and fabrication of a multi-electrode array for spinal cord epidural stimulation. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2014, 6834–6837. 10.1109/EMBC.2014.6945198
    1. Chen D. F., Schneider G. E., Martinou J., Tonegawa S. (1997). Bcl-2 promotes regeneration of severed axons in mammalian CNS. Nature 385, 434–439. 10.1038/385434a0
    1. Chen P., Goldberg D. E., Kolb B., Lanser M., Benowitz L. I., Chen P., et al. . (2002). Inosine induces axonal rewiring and behavioral outcome after stroke. Proc. Natl. Acad. Sci. U.S.A. 99, 9031–9036. 10.1073/pnas.132076299
    1. Cherian A., Krucoff M. O., Miller L. E. (2011). Motor cortical prediction of EMG: evidence that a kinetic brain-machine interface may be robust across altered movement dynamics. J. Neurophysiol. 106, 564–575. 10.1152/jn.00553.2010
    1. Collinger J. L., Wodlinger B., Downey J. E., Wang W., Tyler-Kabara E. C., Weber D. J., et al. . (2013). High-performance neuroprosthetic control by an individual with tetraplegia. Lancet 381, 557–564. 10.1016/S0140-6736(12)61816-9
    1. Cook A. W., Weinstein S. P. (1973). Chronic dorsal column stimulation in multiple sclerosis. Preliminary report. N. Y. State J. Med. 73, 2868–2872.
    1. Cooper E. B., Scherder E. J., Cooper J. B. (2006). Electrical treatment of reduced consciousness: experience with coma and Alzheimer's disease. Neuropsychol. Rehabil. 15, 389–405. 10.1080/09602010443000317
    1. Cooper L. N., Bear M. F. (2012). The BCM theory of synapse modification at 30: interaction of theory with experiment. Nat. Rev. Neurosci. 13, 798–810. 10.1038/nrn3353
    1. Cooper S. J. (2005). Donald O. Hebb's synapse and learning rule: a history and commentary. Neurosci. Biobehav. Rev. 28, 851–874. 10.1016/j.neubiorev.2004.09.009
    1. Courtine G., Song B., Roy R. R., Zhong H., Herrmann J. E., Ao Y., et al. . (2008). Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury. Nat. Med. 14, 69–74. 10.1038/nm1682
    1. Crone N. E., Boatman D., Gordon B., Hao L., Adrian E. D., Matthews B. H. C., et al. . (2001). Induced electrocorticographic gamma activity during auditory perception. Clin. Neurophysiol. 112, 565–582. 10.1016/S1388-2457(00)00545-9
    1. Curt A., Van Hedel H. J. A., Klaus D., Dietz V. (2008). Recovery from a spinal cord injury: significance of compensation, neural plasticity, and repair. J. Neurotrauma 25, 677–685. 10.1089/neu.2007.0468
    1. Dachir S., Shabashov D., Trembovler V., Alexandrovich A. G., Benowitz L. I., Shohami E. (2014). Inosine improves functional recovery after experimental traumatic brain injury. Brain Res. 1555, 78–88. 10.1016/j.brainres.2014.01.044
    1. Daly J. J., Roenigk K., Holcomb J., Rogers J. M., Butler K., Gansen J., et al. . (2006). A randomized controlled trial of functional neuromuscular stimulation in chronic stroke subjects. Stroke 37, 172–178. 10.1161/01.STR.0000195129.95220.77
    1. Dancause N. (2005). Extensive cortical rewiring after brain injury. J. Neurosci. 25, 10167–10179. 10.1523/JNEUROSCI.3256-05.2005
    1. Dancause N., Nudo R. (2011). Shaping plasticity to enhance recovery after injury Numa. Prog. Brain Res. 192, 273–295. 10.1016/B978-0-444-53355-5.00015-4
    1. DeFina P. A., Fellus J., Thompson J. W., Eller M., Moser R. S., Frisina P. G., et al. . (2010). Improving outcomes of severe disorders of consciousness. Restor. Neurol. Neurosci. 28, 769–780. 10.3233/RNN-2010-0548
    1. DeFina P., Fellus J., Polito M. Z., Thompson J. W., Moser R. S., DeLuca J. (2009). The new neuroscience frontier: promoting neuroplasticity and brain repair in traumatic brain injury. Clin. Neuropsychol. 23, 1391–1399. 10.1080/13854040903058978
    1. de Lima S., Habboub G., Benowitz L. I. (2012a). Combinatorial therapy stimulates long-distance regeneration, target reinnervation, and partial recovery of vision after optic nerve injury in mice. Int. Rev. Neurobiol. 106, 153–172. 10.1016/B978-0-12-407178-0.00007-7
    1. de Lima S., Koriyama Y., Kurimoto T., Oliveira J. T., Yin Y., Li Y., et al. . (2012b). Full-length axon regeneration in the adult mouse optic nerve and partial recovery of simple visual behaviors. Proc. Natl. Acad. Sci. U.S.A. 109, 9149–9154. 10.1073/pnas.1119449109
    1. Demirtas-Tatlidede A., Vahabzadeh-Hagh A. M., Bernabeu M., Tormos J. M., Pascual-Leone A. (2012). Noninvasive brain stimulation in traumatic brain injury. J. Head Trauma Rehabil. 27, 274–292. 10.1097/HTR.0b013e318217df55
    1. Dickendesher T. L., Baldwin K. T., Mironova Y. A., Koriyama Y., Raiker S. J., Askew K. L., et al. . (2012). NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans. Nat. Neurosci. 15, 703–712. 10.1038/nn.3070
    1. Dimitrijevi,ć M. R., Nathan P. W. (1967). Studies of spasticity in man. I. Some features of spasticity. Brain 90, 1–30.
    1. Dimitrijevic M. R., Danner S. M., Mayr W. (2015). Neurocontrol of movement in humans with spinal cord injury. Artif. Organs 39, 823–833. 10.1111/aor.12614
    1. Dimitrijevic M. R., Dimitrijevic M. M., Sherwood A. M., Faganel J. (1980). Neurophysiological evaluation of chronic spinal cord stimulation in patients with upper motor neuron disorders. Int. Rehabil. Med. 2, 82–85. 10.3109/09638288009163962
    1. Dimitrijevic M. R., Gerasimenko Y., Pinter M. M. (1998). Evidence for a spinal central pattern generator in humans. Ann. N. Y. Acad. Sci. 860, 360–376. 10.1111/j.1749-6632.1998.tb09062.x
    1. Doetsch F., Caillé I., Lim D. A., García-Verdugo J. M., Alvarez-Buylla A. (1999). Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97, 703–716. 10.1016/S0092-8674(00)80783-7
    1. Dominici N., Keller U., Vallery H., Friedli L., van den Brand R., Starkey M., et al. . (2012). Versatile robotic interface to evaluate, enable and train locomotion and balance after neuromotor disorders. Nat. Med. 18, 1142–1149. 10.1038/nm.2845
    1. Donati A. R., Shokur S., Morya E., Campos D. S., Moioli R. C., Gitti C. M., et al. . (2016). Long-term training with a brain-machine interface-based gait protocol induces partial neurological recovery in paraplegic patients. Sci. Rep. 6:30383. 10.1038/srep30383
    1. Donoghue J. P. (2008). Bridging the brain to the world: a perspective on neural interface systems. Neuron 60, 511–521. 10.1016/j.neuron.2008.10.037
    1. Dooley D. M., Sharkey J. (1977–1978). Electrostimulation of the nervous system for patients with demyelinating degenerative diseases of the nervous system vascular diseases of the extremities. Appl. Neurophysiol. 40, 208–217.
    1. Dromerick A. W., Lang C. E., Birkenmeier R. L., Wagner J. M., Miller J. P., Videen T. O., et al. . (2009). Very early constraint-induced movement during stroke rehabilitation (VECTORS): a single-center RCT. Neurology 73, 195–201. 10.1212/WNL.0b013e3181ab2b27
    1. Duncan P. W., Sullivan K. J., Behrman A. L., Azen S. P., Wu S. S., Nadeau S. E., et al. . (2011). Body-weight-supported treadmill rehabilitation after stroke. N. Engl. J. Med. 364, 2026–2036. 10.1056/NEJMoa1010790
    1. Dy C. J., Gerasimenko Y. P., Edgerton V. R., Dyhre-Poulsen P., Courtine G., Harkema S. J. (2010). Phase-dependent modulation of percutaneously elicited multisegmental muscle responses after spinal cord injury. J. Neurophysiol. 103, 2808–2820. 10.1152/jn.00316.2009
    1. Edgerton V. R., Tillakaratne N. J., Bigbee A. J., de Leon R. D., Roy R. R. (2004). Plasticity of the spinal neural circuitry after injury*. Annu. Rev. Neurosci. 27, 145–167. 10.1146/annurev.neuro.27.070203.144308
    1. Eom J.-W., Lee J.-M., Koh J.-Y., Kim Y.-H. (2016). AMP-activated protein kinase contributes to zinc-induced neuronal death via activation by LKB1 and induction of Bim in mouse cortical cultures. Mol. Brain 9, 14. 10.1186/s13041-016-0194-6
    1. Ethier C., Gallego J. A., Miller L. (2015). Brain-controlled neuromuscular stimulation to drive neural plasticity and functional recovery. Curr. Opin. Neurobiol. 33, 95–102. 10.1016/j.conb.2015.03.007
    1. Ethier C., Oby E. R., Bauman M. J., Miller L. E. (2012). Restoration of grasp following paralysis through brain-controlled stimulation of muscles. Nature 485, 368–371. 10.1038/nature10987
    1. Fagg A. H., Hatsopoulos N. G., London B. M., Reimer J., Solla S. A., Wang D., et al. . (2009). Toward a biomimetic, bidirectional, brain machine interface. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2009, 3376–3380. 10.1109/iembs.2009.5332819
    1. Farwell L. A., Donchin E. (1988). Talking off the top of your head: toward a mental prosthesis utilizing event-related brain potentials. Electroencephalogr. Clin. Neurophysiol. 70, 510–523. 10.1016/0013-4694(88)90149-6
    1. Favre I., Zeffiro T. A., Detante O., Krainik A., Hommel M., Jaillard A. (2014). Upper limb recovery after stroke is associated with ipsilesional primary motor cortical activity: a meta-analysis. Stroke 45, 1077–1083. 10.1161/STROKEAHA.113.003168
    1. Feeney D. M., Baron J. C. (1986). Diaschisis. Stroke 17, 817–830. 10.1161/01.STR.17.5.817
    1. Fishman H. M., Bittner G. D. (2003). Vesicle-mediated restoration of a plasmalemmal barrier in severed axons. News Physiol. Sci. 18, 115–118. 10.1152/nips.01429.2002
    1. Fitzsimmons N. A., Lebedev M. A., Peikon I. D., Nicolelis M. A. (2009). Extracting kinematic parameters for monkey bipedal walking from cortical neuronal ensemble activity. Front. Integr. Neurosci. 3:3. 10.3389/neuro.07.003.2009
    1. Flesher S. N., Collinger J. L., Foldes S. T., Weiss J. M., Downey J. E., Tyler-Kabara E. C., et al. . (2016). Intracortical microstimulation of human somatosensory cortex. Sci. Transl. Med. 8:361ra141. 10.1126/scitranslmed.aaf8083
    1. Flint R. D., Rosenow J. M., Tate M. C., Slutzky M. W. (2017). Continuous decoding of human grasp kinematics using epidural and subdural signals. J. Neural Eng. 14:016005. 10.1088/1741-2560/14/1/016005
    1. Flint R. D., Scheid M. R., Wright Z. A., Solla S. A., Slutzky M. W. (2016). Long-term stability of motor cortical activity: implications for brain machine interfaces and optimal feedback control. J. Neurosci. 36, 3623–3632. 10.1523/JNEUROSCI.2339-15.2016
    1. Flint R. D., Wang P. T., Wright Z. A., King C. E., Krucoff M. O., Schuele S. U., et al. . (2014). Extracting kinetic information from human motor cortical signals. Neuroimage 101, 695–703. 10.1016/j.neuroimage.2014.07.049
    1. Flint R. D., Wright Z. A., Scheid M. R., Slutzky M. W. (2013). Long term, stable brain machine interface performance using local field potentials and multiunit spikes. J. Neural Eng. 10:56005. 10.1088/1741-2560/10/5/056005
    1. Flor H., Elbert T., Knecht S., Wienbruch C., Pantev C., Birbaumer N., et al. . (1995). Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature 375, 482–484. 10.1038/375482a0
    1. Fong A. J., Roy R. R., Ichiyama R. M., Lavrov I., Courtine G., Gerasimenko Y., et al. . (2009). Recovery of control of posture and locomotion after a spinal cord injury: solutions staring us in the face. Prog. Brain Res. 175, 393–418. 10.1016/S0079-6123(09)17526-X
    1. Freund P., Schmidlin E., Wannier T., Bloch J., Mir A., Schwab M. E., et al. . (2006). Nogo-A-specific antibody treatment enhances sprouting and functional recovery after cervical lesion in adult primates. Nat. Med. 12, 790–792. 10.1038/nm1436
    1. Friehs G. M., Zerris V. A., Ojakangas C. L., Fellows M. R., Donoghue J. P. (2004). Brain-machine and brain-computer interfaces. Stroke 35, 2702–2705. 10.1161/01.STR.0000143235.93497.03
    1. Furlanetti L. L., Cordeiro J. G., Cordeiro K. K., García J. A., Winkler C., Lepski G. A., et al. . (2015). Continuous high-frequency stimulation of the subthalamic nucleus improves cell survival and functional recovery following dopaminergic cell transplantation in rodents. Neurorehabil. Neural Repair 29, 1001–1012. 10.1177/1545968315581419
    1. Gad P. N., Choe J., Nandra M. S., Zhong H., Roy R. R., Tai Y.-C., et al. . (2013a). Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats. J. Neuroeng. Rehabil. 10:2. 10.1186/1743-0003-10-2
    1. Gad P. N., Choe J., Shah P., Garcia-Alias G., Rath M., Gerasimenko Y., et al. . (2013b). Sub-threshold spinal cord stimulation facilitates spontaneous motor activity in spinal rats. J. Neuroeng. Rehabil. 10:108. 10.1186/1743-0003-10-108
    1. Gad P. N., Gerasimenko Y. P., Zdunowski S., Sayenko D., Haakana P., Turner A., et al. . (2015). Iron “ElectriRx” man: Overground stepping in an exoskeleton combined with noninvasive spinal cord stimulation after paralysis. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2015, 1124–1127. 10.1109/embc.2015.7318563
    1. Gad P. N., Roy R. R., Zhong H., Lu D. C., Gerasimenko Y. P., Edgerton V. R. (2014). Initiation of bladder voiding with epidural stimulation in paralyzed, step trained rats. PLoS ONE 9:e108184. 10.1371/journal.pone.0108184
    1. García-Alías G., Truong K., Shah P. K., Roy R. R., Edgerton V. R. (2015). Plasticity of subcortical pathways promote recovery of skilled hand function in rats after corticospinal and rubrospinal tract injuries. Exp. Neurol. 266, 112–119. 10.1016/j.expneurol.2015.01.009
    1. Gerasimenko Y., Gorodnichev R., Moshonkina T., Sayenko D., Gad P., Reggie Edgerton V. (2015a). Transcutaneous electrical spinal-cord stimulation in humans. Ann. Phys. Rehabil. Med. 58, 225–231. 10.1016/j.rehab.2015.05.003
    1. Gerasimenko Y., Lu D., Modaber M., Zdunowski S., Gad P., Sayenko D., et al. (2015b). Noninvasive reactivation of motor descending control after paralysis. J. Neurotrauma 13, 1–13. 10.1089/neu.2015.4008
    1. Gharabaghi A., Kraus D., Leão M. T., Spüler M., Walter A., Bogdan M., et al. . (2014a). Coupling brain-machine interfaces with cortical stimulation for brain-state dependent stimulation: enhancing motor cortex excitability for neurorehabilitation. Front. Hum. Neurosci. 8:122. 10.3389/fnhum.2014.00122
    1. Gharabaghi A., Naros G., Khademi F., Jesser J., Spüler M., Walter A., et al. . (2014b). Learned self-regulation of the lesioned brain with epidural electrocorticography. Front. Behav. Neurosci. 8:429. 10.3389/fnbeh.2014.00429
    1. Gharabaghi A., Naros G., Walter A., Grimm F., Schuermeyer M., Roth A., et al. . (2014c). From assistance towards restoration with epidural brain-computer interfacing. Restor. Neurol. Neurosci. 32, 517–525. 10.3233/RNN-140387
    1. Goforth P. B., Ellis E. F., Satin L. S. (1999). Enhancement of AMPA-mediated current after traumatic injury in cortical neurons. J. Neurosci. 19, 7367–7374.
    1. Goldberg J. L., Espinosa J. S., Xu Y., Davidson N., Kovacs G. T. A., Barres B. A. (2002). Retinal ganglion cells do not extend axons by default. Neuron 33, 689–702. 10.1016/S0896-6273(02)00602-5
    1. Grahn P. J., Lee K. H., Kasasbeh A., Mallory G. W., Hachmann J. T., Dube J. R., et al. . (2015). Wireless control of intraspinal microstimulation in a rodent model of paralysis. J. Neurosci. 123, 232–242. 10.3171/2014.10.jns132370
    1. Greenberg B. D., Malone D. A., Friehs G. M., Rezai A. R., Kubu C. S., Malloy P. F., et al. . (2006). Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology 31, 2384–2393. 10.1038/sj.npp.1301165
    1. Grenningloh G., Soehrman S., Bondallaz P., Ruchti E., Cadas H. (2004). Role of the microtubule destabilizing proteins SCG10 and stathmin in neuronal growth. J. Neurobiol. 58, 60–69. 10.1002/neu.10279
    1. Greve M. W., Zink B. J. (2009). Pathophysiology of traumatic brain injury. Mt. Sinai J. Med. 76, 97–104. 10.1002/msj.20104
    1. Grillner S. (1985). Neurobiological bases of rhythmic motor acts in vertebrates. Science 228, 143–149. 10.1126/science.3975635
    1. Guggenmos D. J., Azin M., Barbay S., Mahnken J. D., Dunham C., Mohseni P., et al. . (2013). Restoration of function after brain damage using a neural prosthesis. Proc. Natl. Acad. Sci. U.S.A. 110, 21177–21182. 10.1073/pnas.1316885110
    1. Hackett M. L., Köhler S., O'Brien J. T., Mead G. E. (2014). Neuropsychiatric outcomes of stroke. Lancet Neurol. 13, 525–534. 10.1016/S1474-4422(14)70016-X
    1. Hamani C., McAndrews M. P., Cohn M., Oh M., Zumsteg D., Shapiro C. M., et al. . (2008). Memory enhancement induced by hypothalamic/fornix deep brain stimulation. Ann. Neurol. 63, 119–123. 10.1002/ana.21295
    1. Hanson T. L., Fuller A. M., Lebedev M. A., Turner D. A., Nicolelis M. A. (2012). Subcortical neuronal ensembles: an analysis of motor task association, tremor, oscillations, and synchrony in human patients. J. Neurosci. 32, 8620–8632. 10.1523/JNEUROSCI.0750-12.2012
    1. Harkema S. J., Gerasimenko Y., Hodes J., Burdick J., Angeli C., Chen Y., et al. . (2011). Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study. Lancet 377, 1938–1947. 10.1016/S0140-6736(11)60547-3
    1. Harkema S. J., Schmidt-Read M., Lorenz D. J., Edgerton V. R., Behrman A. L. (2012). Balance and ambulation improvements in individuals with chronic incomplete spinal cord injury using locomotor trainingbased rehabilitation. Arch. Phys. Med. Rehabil. 93, 1508–1517. 10.1016/j.apmr.2011.01.024
    1. Hasan A., Nitsche M. A., Rein B., Schneider-Axmann T., Guse B., Gruber O., et al. . (2011). Dysfunctional long-term potentiation-like plasticity in schizophrenia revealed by transcranial direct current stimulation. Behav. Brain Res. 224, 15–22. 10.1016/j.bbr.2011.05.017
    1. Hatsopoulos N. G., Donoghue J. P. (2009). The science of neural interface systems. Annu. Rev. Neurosci. 32, 249–266. 10.1146/annurev.neuro.051508.135241
    1. Hebb D. O. (1949). The Organization of Behavior: A Neuropsychological Theory. New York, NY: Wiley.
    1. Hergenroeder G. W., Redell J. B., Moore A. N., Dash P. K. (2008). Biomarkers in the clinical diagnosis and management of traumatic brain injury. Mol. Diagn. Ther. 12, 345–358. 10.1007/BF03256301
    1. Hill C. E., Beattie M. S., Bresnahan J. C. (2001). Degeneration and sprouting of identified descending supraspinal axons after contusive spinal cord injury in the rat. Exp. Neurol. 171, 153–169. 10.1006/exnr.2001.7734
    1. Hochberg L. R., Bacher D., Jarosiewicz B., Masse N. Y., Simeral J. D., Vogel J., et al. . (2012). Reach and grasp by people with tetraplegia using a neurally controlled robotic arm. Nature 485, 372–375. 10.1038/nature11076
    1. Hochberg L. R., Serruya M. D., Friehs G. M., Mukand J. A., Saleh M., Caplan A. H., et al. . (2006). Neuronal ensemble control of prosthetic devices by a human with tetraplegia. Nature 442, 164–171. 10.1038/nature04970
    1. Hotson G., McMullen D. P., Fifer M. S., Johannes M. S., Katyal K. D., Para M. P., et al. . (2016). Individual finger control of a modular prosthetic limb using high-density electrocorticography in a human subject. J. Neural Eng. 13:26017. 10.1088/1741-2560/13/2/026017
    1. Houeto J. L., Karachi C., Mallet L., Pillon B., Yelnik J., Mesnage V., et al. . (2005). Tourette's syndrome and deep brain stimulation. J. Neurol. Neurosurg. Psychiatry 76, 992–995. 10.1136/jnnp.2004.043273
    1. Ifft P. J., Shokur S., Li Z., Lebedev M. A., International L. S. (2013). Brain-machine interface enables bimanual arm movements in monkeys. Sci. Transl. Med. 5:210ra154. 10.1126/scitranslmed.3006159
    1. Illis L. S., Oygar A. E., Sedgwick E. M., Awadalla M. A. (1976). Dorsal-column stimulation in the rehabilitation of patients with multiple sclerosis. Lancet 307, 1383–1386. 10.1016/S0140-6736(76)93030-0
    1. Ingram J. N., Körding K. P., Howard I. S., Wolpert D. M. (2008). The statistics of natural hand movements. Exp. Brain Res. 188, 223–236. 10.1007/s00221-008-1355-3
    1. Iwahara T., Atsuta Y., Garcia-Rill E., Skinner R. D. (1992). Spinal cord stimulation-induced locomotion in the adult cat. Brain Res. Bull. 28, 99–105. 10.1016/0361-9230(92)90235-P
    1. Jackson A., Zimmermann J. B. (2012). Neural interfaces for the brain and spinal cord-restoring motor function. Nat. Rev. Neurol. 8, 690–699. 10.1038/nrneurol.2012.219
    1. Jarosiewicz B., Bacher D., Sarma A. A., Masse N. Y., Simeral J. D., Sorice B., et al. (2015). Virtual typing by people with tetraplegia using a stabilized, self-calibrating intracortical brain-computer interface. Sci. Transl. Med. 7, 1–11. 10.1126/scitranslmed.aac7328
    1. Jarvis S., Schultz S. R. (2015). Prospects for optogenetic augmentation of brain function. Front. Syst. Neurosci. 9:157. 10.3389/fnsys.2015.00157
    1. Jennett B., Teasdale G., Braakman R., Minderhoud J., Knill-Jones R. (1976). Predicting outcome in individual patients after severe head injury. Lancet 15, 1031–1034. 10.1016/S0140-6736(76)92215-7
    1. Jones L. (1997). Dextrous hands: human, prosthetic, and robotic. Presence 6, 29–56. 10.1162/pres.1997.6.1.29
    1. Jung R., Belanger A., Kanchiku T., Fairchild M., Abbas J. J. (2009). Neuromuscular stimulation therapy after incomplete spinal cord injury promotes recovery of interlimb coordination during locomotion. J. Neural Eng. 6:55010. 10.1088/1741-2560/6/5/055010
    1. Kafri M., Laufer Y. (2015). Therapeutic effects of functional electrical stimulation on gait in individuals post-stroke. Ann. Biomed. Eng. 43, 451–466. 10.1007/s10439-014-1148-8
    1. Kantak S. S., Stinear J. W., Buch E. R., Cohen L. G. (2012). Rewiring the brain: potential role of the premotor cortex in motor control, learning, and recovery of function following brain injury. Neurorehabil. Neural Repair 26, 282–292. 10.1177/1545968311420845
    1. Kennedy P. R., Bakay R. A. (1998). Restoration of neural output from a paralyzed patient by a direct brain connection. Neuroreport 9, 1707–1711. 10.1097/00001756-199806010-00007
    1. Kern H., McKay W. B., Dimitrijevic M. M., Dimitrijevic M. R. (2005). Motor control in the human spinal cord and the repair of cord function. Curr. Pharm. Des. 11, 1429–1439. 10.2174/1381612053507882
    1. Kim D., Zai L., Liang P., Schaffling C., Ahlborn D., Benowitz L. I. (2013). Inosine enhances axon sprouting and motor recovery after spinal cord injury. PLoS ONE 8:e81948. 10.1371/journal.pone.0081948
    1. King C. E., Wang P. T., McCrimmon C. M., Chou C. C., Do A. H., Nenadic Z. (2015). The feasibility of a brain-computer interface functional electrical stimulation system for the restoration of overground walking after paraplegia. J. Neuroeng. Rehabil. 12:80. 10.1186/s12984-015-0068-7
    1. Kleim J. A., Bruneau R., VandenBerg P., MacDonald E., Mulrooney R., Pocock D. (2003). Motor cortex stimulation enhances motor recovery and reduces peri-infarct dysfunction following ischemic insult. Neurol. Res. 25, 789–793. 10.1179/016164103771953862
    1. Kleim J. A., Jones T. A. (2008). Principles of experience-dependent neural plasticity: implications for rehabilitation after brain damage. J. Speech. Lang. Hear. Res. 51, S225–S239. 10.1044/1092-4388(2008/018)
    1. Kobayashi M., Pascual-Leone A. (2003). Basic principles of magnetic stimulation. Lancet 2, 145–156. 10.1016/S1474-4422(03)00321-1
    1. Koch C., Massimini M., Boly M., Tononi G. (2016). Neural correlates of consciousness: progress and problems. Nat. Rev. Neurosci. 17, 307–321. 10.1038/nrn.2016.22
    1. Kozlowski D. A., James D. C., Schallert T. (1996). Use-dependent exaggeration of neuronal injury after unilateral sensorimotor cortex lesions. J. Neurosci. 16, 4776–4786.
    1. Krieger D. W. (2013). Therapeutic drug approach to stimulate clinical recovery after brain injury. Front. Neurol. Neurosci. 32:76–87. 10.1159/000346419
    1. Krucoff M. O., Slutzky M. W. (2011). Predicting grasp, kinetic, and kinematic variables of hand movement using epidural and subdural brain signals, in 63rd Annual Meeting of the American Academy of Neurology (Honolulu, HI: ).
    1. Krüger J., Caruana F., Volta R. D., Rizzolatti G. (2010). Seven years of recording from monkey cortex with a chronically implanted multiple microelectrode. Front. Neuroeng. 3:6. 10.3389/fneng.2010.00006
    1. Kuner R. (2010). Central mechanisms of pathological pain. Nat. Med. 16, 1258–1266. 10.1038/nm.2231
    1. Kurimoto T., Yin Y., Habboub G., Gilbert H.-Y., Li Y., Nakao S., et al. . (2013). Neutrophils express oncomodulin and promote optic nerve regeneration. J. Neurosci. 33, 14816–14824. 10.1523/JNEUROSCI.5511-12.2013
    1. Kuznetsova A. Y., Deth R. C. (2008). A model for modulation of neuronal synchronization by D4 dopamine receptor-mediated phospholipid methylation. J. Comput. Neurosci. 24, 314–329. 10.1007/s10827-007-0057-3
    1. Lang C. E., Lohse K. R., Birkenmeier R. L. (2015). Dose and timing in neurorehabilitation: prescribing motor therapy after stroke. Curr. Opin. Neurol. 28, 549–555. 10.1097/WCO.0000000000000256
    1. Langhorne P., Bernhardt J., Kwakkel G. (2011). Stroke rehabilitation. Lancet 377, 1693–1702. 10.1016/S0140-6736(11)60325-5
    1. Laxton A. W., Lipsman N., Lozano A. M. (2013). Deep brain stimulation for cognitive disorders. Handb. Clin. Neurol. 116, 307–311. 10.1016/B978-0-444-53497-2.00025-5
    1. Laxton A. W., Tang-Wai D. F., McAndrews M. P., Zumsteg D., Wennberg R., Keren R., et al. . (2010). A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease. Ann. Neurol. 68, 521–534. 10.1002/ana.22089
    1. Laywell E. D., Rakic P., Kukekov V. G., Holland E. C., Steindler D. A. (2000). Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain. Proc. Natl. Acad. Sci. U.S.A. 97, 13883–13888. 10.1073/pnas.250471697
    1. Lebedev M. A., Tate A. J., Hanson T. L., Li Z., O'Doherty J. E., Winans J. A., et al. . (2011). Future developments in brain-machine interface research. Clinics 66, 25–32. 10.1590/S1807-59322011001300004
    1. Lee J.-K., Kim J.-E., Sivula M., Strittmatter S. M. (2004). Nogo receptor antagonism promotes stroke recovery by enhancing axonal plasticity. J. Neurosci. 24, 6209–6217. 10.1523/JNEUROSCI.1643-04.2004
    1. Leuthardt E. C., Schalk G., Wolpaw J. R., Ojemann J. G., Moran D. W. (2004). A brain-computer interface using electrocorticographic signals in humans. J. Neural Eng. 1, 63–71. 10.1088/1741-2560/1/2/001
    1. Levy R. M., Harvey R. L., Kissela B. M., Winstein C. J., Lutsep H. L., Parrish T. B., et al. . (2016). Epidural electrical stimulation for stroke rehabilitation: results of the prospective, multicenter, randomized, single-blinded everest trial. Neurorehabil. Neural Repair 30, 107–119. 10.1177/1545968315575613
    1. Levy R. M., Ruland S., Weinand M., Lowry D., Dafer R., Bakay R. (2008). Cortical stimulation for the rehabilitation of patients with hemiparetic stroke: a multicenter feasibility study of safety and efficacy. J. Neurosurg. 108, 707–714. 10.3171/JNS/2008/108/4/0707
    1. Li S., Nie E. H., Yin Y., Benowitz L. I., Tung S., Vinters H. V., et al. . (2015). GDF10 is a signal for axonal sprouting and functional recovery after stroke. Nat. Neurosci. 18, 1737–1745. 10.1038/nn.4146
    1. Li Y., Raisman G. (1995). Sprouts from cut corticospinal axons persist in the presence of astrocytic scarring in long-term lesions of the adult rat spinal cord. Exp. Neurol. 134, 102–111. 10.1006/exnr.1995.1041
    1. Liebscher T., Schnell L., Schnell D., Scholl J., Schneider R., Gullo M., et al. . (2005). Nogo-A antibody improves regeneration and locomotion of spinal cord-injured rats. Ann. Neurol. 58, 706–719. 10.1002/ana.20627
    1. Liu G., Gu B., He X. P., Joshi R. B., Wackerle H. D., Rodriguiz R. M., et al. . (2013). Transient inhibition of TrkB kinase after status epilepticus prevents development of temporal lobe epilepsy. Neuron 79, 31–38. 10.1016/j.neuron.2013.04.027
    1. Liu K., Tedeschi A., Park K. K., He Z. (2011). Neuronal intrinsic mechanisms of axon regeneration. Annu. Rev. Neurosci. 34, 131–152. 10.1146/annurev-neuro-061010-113723
    1. Lloyd-Jones D., Adams R. J., Brown T. M., Carnethon M., Dai S., De Simone G., et al. . (2010). Executive summary: heart disease and stroke statistics-2010 update: a report from the american heart association. Circulation 121, e46–e215. 10.1161/CIRCULATIONAHA.109.192667
    1. Lo A. C., Guarino P. D., Richards L. G., Haselkorn J. K., Wittenberg G. F., Federman D. G., et al. . (2010). Robot-assisted therapy for long-term upper-limb impairment after stroke. N. Engl. J. Med. 362, 1772–1783. 10.1056/NEJMoa0911341
    1. Lobel D. A., Lee K. H. (2014). Brain machine interface and limb reanimation technologies: Restoring function after spinal cord injury through development of a bypass system. Mayo Clin. Proc. 89, 708–714. 10.1016/j.mayocp.2014.02.003
    1. London B. M., Jordan L. R., Jackson C. R., Miller L. E. (2008). Electrical stimulation of the proprioceptive cortex (area 3a) used to instruct a behaving monkey. IEEE Trans. neural Syst. Rehabil. Eng. 16, 32–36. 10.1109/TNSRE.2007.907544
    1. Macas J., Nern C., Plate K. H., Momma S. (2006). Increased generation of neuronal progenitors after ischemic injury in the aged adult human forebrain. J. Neurosci. 26, 13114–13119. 10.1523/JNEUROSCI.4667-06.2006
    1. Mackay-Lyons M., McDonald A., Matheson J., Eskes G., Klus M.-A. (2013). Dual effects of body-weight supported treadmill training on cardiovascular fitness and walking ability early after stroke: a randomized controlled trial. Neurorehabil. Neural Repair 27, 644–653. 10.1177/1545968313484809
    1. Magavi S. S., Leavitt B. R., Macklis J. D. (2000). Induction of neurogenesis in the neocortex of adult mice. Nature 405, 951–955. 10.1038/35016083
    1. Maier I. C., Ichiyama R. M., Courtine G., Schnell L., Lavrov I., Edgerton V. R., et al. . (2009). Differential effects of anti-Nogo-A antibody treatment and treadmill training in rats with incomplete spinal cord injury. Brain 132, 1426–1440. 10.1093/brain/awp085
    1. Marmarou A., Signoretti S., Fatouros P. P., Portella G., Aygok G. A., Bullock M. R. (2006). Predominance of cellular edema in traumatic brain swelling in patients with severe head injuries. J. Neurosurg. 104, 720–730. 10.3171/jns.2006.104.5.720
    1. Mayberg H. S., Lozano A. M., Voon V., McNeely H. E., Seminowicz D., Hamani C., et al. . (2005). Deep brain stimulation for treatment-resistant depression. Neuron 45, 651–660. 10.1016/j.neuron.2005.02.014
    1. Mazurek K. A., Holinski B. J., Everaert D. G., Mushahwar V. K., Etienne-Cummings R. (2016). A mixed-signal VLSI system for producing temporally adapting intraspinal microstimulation patterns for locomotion. IEEE Trans. Biomed. Circuits Syst. 10, 902–911. 10.1109/TBCAS.2015.2501419
    1. McFarland D. J., Krusienski D. J., Wolpaw J. R. (2006). Brain-computer interface signal processing at the Wadsworth Center: mu and sensorimotor beta rhythms. Prog. Brain Res. 159, 411–419. 10.1016/S0079-6123(06)59026-0
    1. McFarland D. J., Sarnacki W. A., Wolpaw J. R. (2010). Electroencephalographic (EEG) control of three-dimensional movement. J. Neural Eng. 7:36007. 10.1088/1741-2560/7/3/036007
    1. McGee M. J., Amundsen C. L., Grill W. M. (2015). Electrical stimulation for the treatment of lower urinary tract dysfunction after spinal cord injury. J. Spinal Cord Med. 38, 135–146. 10.1179/2045772314Y.0000000299
    1. McGee M. J., Grill W. M. (2014). Selective co-stimulation of pudendal afferents enhances bladder activation and improves voiding efficiency. Neurourol. Urodyn. 33, 1272–1278. 10.1002/nau.22474
    1. McIntyre A., Viana R., Janzen S., Mehta S., Pereira S., Teasell R. (2012). Systematic review and meta-analysis of constraint-induced movement therapy in the hemiparetic upper extremity more than six months post stroke. Top. Stroke Rehabil. 19, 499–513. 10.1310/tsr1906-499
    1. Memberg W. D., Polasek K. H., Hart R. L., Bryden A. M., Kilgore K. L., Nemunaitis G. A., et al. . (2014). Implanted neuroprosthesis for restoring arm and hand function in people with high level tetraplegia. Arch. Phys. Med. Rehabil. 95, 1201–1211.e1. 10.1016/j.apmr.2014.01.028
    1. Menzer D. L., Rao N. G., Bondy A., Truccolo W., Donoghue J. P. (2014). Population interactions between parietal and primary motor cortices during reach. J. Neurophysiol. 112, 2959–2984. 10.1152/jn.00851.2012
    1. Mestais C. S., Charvet G., Sauter-starace F., Foerster M., Ratel D. (2015). WIMAGINE: wireless 64-channel ECoG recording implant for long term clinical applications. IEEE Trans. Neural Syst. Rehabil. Eng. 23, 10–21. 10.1109/TNSRE.2014.2333541
    1. Meunier D., Lambiotte R., Bullmore E. T. (2010). Modular and hierarchically modular organization of brain networks. Front. Neurosci. 4:200. 10.3389/fnins.2010.00200
    1. Mihara M., Hattori N., Hatakenaka M., Yagura H., Kawano T., Hino T., et al. . (2013). Near-infrared spectroscopy-mediated neurofeedback enhances efficacy of motor imagery-based training in poststroke victims: a pilot study. Stroke 44, 1091–1098. 10.1161/STROKEAHA.111.674507
    1. Milot M.-H., Spencer S. J., Chan V., Allington J. P., Klein J., Chou C., et al. . (2013). A crossover pilot study evaluating the functional outcomes of two different types of robotic movement training in chronic stroke survivors using the arm exoskeleton BONES. J. Neuroeng. Rehabil. 10:112. 10.1186/1743-0003-10-112
    1. Minassian K., Jilge B., Rattay F., Pinter M. M., Binder H., Gerstenbrand F., et al. . (2004). 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. Spinal Cord 42, 401–416. 10.1038/sj.sc.3101615
    1. Minassian K., Persy I., Rattay F., Pinter M. M., Kern H., Dimitrijevic M. R. (2007). Human lumbar cord circuitries can be activated by extrinsic tonic input to generate locomotor-like activity. Hum. Mov. Sci. 26, 275–295. 10.1016/j.humov.2007.01.005
    1. Minev I. R., Musienko P., Hirsch A., Barraud Q., Wenger N., Moraud E. M., et al. . (2015). Electronic dura mater for long term multimodal neural interfaces. Science 347, 159–163. 10.1126/science.1260318
    1. Monfils M.-H., VandenBerg P. M., Kleim J. A., Teskey G. C. (2004). Long-term potentiation induces expanded movement representations and dendritic hypertrophy in layer V of rat sensorimotor neocortex. Cereb. Cortex 14, 586–593. 10.1093/cercor/bhh020
    1. Moritz C. T., Perlmutter S. I., Fetz E. E. (2008). Direct control of paralysed muscles by cortical neurons. Nature 456, 639–642. 10.1038/nature07418
    1. Morrow M. M., Jordan L. R., Miller L. E. (2007). Direct comparison of the task-dependent discharge of M1 in hand space and muscle space. J. Neurophysiol. 97, 1786–1798. 10.1152/jn.00150.2006
    1. Mothe A. J., Tator C. H. (2012). Advances in stem cell therapy for spinal cord injury. Thew J. Clin. Investig. 122, 3824–3834. 10.1172/JCI64124
    1. Nahmani M., Turrigiano G. G. (2014). Adult cortical plasticity following injury: recapitulation of critical period mechanisms? Neuroscience 283, 4–16. 10.1016/j.neuroscience.2014.04.029
    1. Napieralski J. A., Butler A. K., Chesselet M. F. (1996). Anatomical and functional evidence for lesion-specific sprouting of corticostriatal input in the adult rat. J. Comp. Neurol. 373, 484–497.
    1. Nicolelis M. A., Lebedev M. A. (2009). Principles of neural ensemble physiology underlying the operation of brain-machine interfaces. Nat. Rev. Neurosci. 10, 530–540. 10.1038/nrn2653
    1. Nudo R. J. (2013). Recovery after brain injury: mechanisms and principles. Front. Hum. Neurosci. 7:887. 10.3389/fnhum.2013.00887
    1. Nudo R. J., Jenkins W. M., Merzenich M. M. (1990). Repetitive microstimulation alters the cortical representation of movements in adult rats. Somatosens. Mot. Res. 7, 463–483. 10.3109/08990229009144720
    1. Nudo R. J., Milliken G. W. (1996). Reorganization of movement representations in primary motor cortex following focal ischemic infarcts in adult squirrel monkeys. J. Neurophysiol. 75, 2144–2149.
    1. Nuyujukian B. P., Ieee M., Kao J. C., Ieee S. M., Ryu S. I., Ieee M., et al. . (2016). Brain – computer typing Interface. Proc. IEEE 1–7. 10.1109/JPROC.2016.2586967
    1. O'Doherty J. E., Lebedev M. A., Hanson T. L., Fitzsimmons N. A., Nicolelis M. A. L. (2009). A brain-machine interface instructed by direct intracortical microstimulation. Front. Integr. Neurosci. 3:20. 10.3389/neuro.07.020.2009
    1. Ohab J. J., Carmichael S. T. (2008). Poststroke neurogenesis: emerging principles of migration and localization of immature neurons. Neuroscience 14, 369–380. 10.1177/1073858407309545
    1. Omura T., Omura K., Tedeschi A., Riva P., Painter M. W., Rojas L., et al. . (2015). Robust axonal regeneration occurs in the injured CAST/Ei mouse CNS. Neuron 86, 1215–1227. 10.1016/j.neuron.2015.05.005
    1. Oxley T. J., Opie N. L., John S. E., Rind G. S., Ronayne S. M., Wheeler T. L., et al. . (2016). Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity. Nat. Biotechnol. 34, 320–327. 10.1038/nbt.3428
    1. Pais-Vieira M., Chiuffa G., Lebedev M., Yadav A., Nicolelis M. A. L. (2015). Building an organic computing device with multiple interconnected brains. Sci. Rep. 5:11869. 10.1038/srep11869
    1. Park C. K., Nehls D. G., Teasdale G. M., McCulloch J. (1989). Effect of the NMDA antagonist MK-801 on local cerebral blood flow in focal cerebral ischaemia in the rat. J. Cereb. Blood Flow Metab. 9, 617–622. 10.1038/jcbfm.1989.88
    1. Park K. K., Liu K., Hu Y., Smith P. D., Wang C., Cai B., et al. . (2008). Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 322, 963–966. 10.1126/science.1161566
    1. Patil P. G., Carmena J. M., Nicolelis M. A., Turner D. A. (2004). Ensemble recordings of human subcortical neurons as a source of motor control signals for a brain-machine interface. Neurosurgery 55, 27–35. 10.1227/01.neu.0000126872.23715.e5
    1. Patil P. G., Turner D. A. (2008). The development of brain-machine interface neuroprosthetic devices. Neurotherapeutics 5, 137–146. 10.1016/j.nurt.2007.11.002
    1. Pekna M., Pekny M., Nilsson M. (2012). Modulation of neural plasticity as a basis for stroke rehabilitation. Stroke 43, 2819–2828. 10.1161/STROKEAHA.112.654228
    1. Perel P., Arango M., Clayton T., Edwards P., Komolafe E., Poccock S., et al. . (2008). Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients. BMJ 336, 425–429. 10.1136/bmj.39461.643438.25
    1. Pfurtscheller G., Brunner C., Schlögl A., Lopes da Silva F. H. (2006). Mu rhythm (de)synchronization and EEG single-trial classification of different motor imagery tasks. Neuroimage 31, 153–159. 10.1016/j.neuroimage.2005.12.003
    1. Pfurtscheller G., Flotzinger D., Mohl W., Peltoranta M. (1992). Prediction of the side of hand movements from single-trial multi-channel EEG data using neural networks. Electroencephalogr. Clin. Neurophysiol. 82, 313–315. 10.1016/0013-4694(92)90112-U
    1. Plautz E. J., Barbay S., Frost S. B., Friel K. M., Dancause N., Zoubina E. V., et al. . (2003). Post-infarct cortical plasticity and behavioral recovery using concurrent cortical stimulation and rehabilitative training: a feasibility study in primates. Neurol. Res. 25, 801–810. 10.1179/016164103771953880
    1. Popovic M. R., Kapadia N., Zivanovic V., Furlan J. C., Craven B. C., McGillivray C. (2011). Functional electrical stimulation therapy of voluntary grasping versus only conventional rehabilitation for patients with subacute incomplete tetraplegia: a randomized clinical trial. Neurorehabil. Neural Repair 25, 433–442. 10.1177/1545968310392924
    1. Prochazka A. (2016). Targeted stimulation of the spinal cord to restore locomotor activity. Nat. Med. 22, 125–126. 10.1038/nm.4043
    1. Protas E. J., Holmes S. A., Qureshy H., Johnson A., Lee D., Sherwood A. M. (2001). Supported treadmill ambulation training after spinal cord injury: a pilot study. Arch. Phys. Med. Rehabil. 82, 825–831. 10.1053/apmr.2001.23198
    1. Quartarone A., Rizzo V., Morgante F. (2008). Clinical features of dystonia: a pathophysiological revisitation. Curr. Opin. Neurol. 21, 484–490. 10.1097/WCO.0b013e328307bf07
    1. Rajangam S., Tseng P.-H., Yin A., Lehew G., Schwarz D., Lebedev M. A., et al. . (2016). Wireless cortical brain-machine interface for whole-body navigation in primates. Sci. Rep. 6:22170. 10.1038/srep22170
    1. Ramakrishnan A., Ifft P. J., Pais-Vieira M., Byun Y. W., Zhuang K. Z., Lebedev M. A., et al. . (2015). Computing arm movements with a monkey brainet. Sci. Rep. 5:10767. 10.1038/srep10767
    1. Ramos-Murguialday A., Broetz D., Rea M., Läer L., Yilmaz O., Brasil F. L., et al. . (2013). Brain-machine interface in chronic stroke rehabilitation: a controlled study. Ann. Neurol. 74, 100–108. 10.1002/ana.23879
    1. Ramos-Murguialday A., Schürholz M., Caggiano V., Wildgruber M., Caria A., Hammer E. M., et al. . (2012). Proprioceptive feedback and brain computer interface (BCI) based neuroprostheses. PLoS ONE 7:e47048. 10.1371/journal.pone.0047048
    1. Rattay F., Minassian K., Dimitrijevic M. R. (2000). Epidural electrical stimulation of posterior structures of the human lumbosacral cord: 2. quantitative analysis by computer modeling. Spinal Cord 38, 473–489. 10.1038/sj.sc.3101039
    1. Rea M., Rana M., Lugato N., Terekhin P., Gizzi L., Brötz D., et al. . (2014). Lower limb movement preparation in chronic stroke: a pilot study toward an fNIRS-BCI for gait rehabilitation. Neurorehabil. Neural Repair 28, 564–575. 10.1177/1545968313520410
    1. Rebesco J. M., Miller L. E. (2011). Enhanced detection threshold for in vivo cortical stimulation produced by Hebbian conditioning. J. Neural Eng. 8:16011. 10.1088/1741-2560/8/1/016011
    1. Reinkensmeyer D. J., Aoyagi D., Emken J. L., Galvez J. A., Ichinose W., Kerdanyan G., et al. . (2006). Tools for understanding and optimizing robotic gait training. J. Rehabil. Res. Dev. 43, 657–670. 10.1682/JRRD.2005.04.0073
    1. Reinkensmeyer D. J., Emken J. L., Cramer S. C. (2004). Robotics, motor learning, and neurologic recovery. Annu. Rev. Biomed. Eng. 6, 497–525. 10.1146/annurev.bioeng.6.040803.140223
    1. Rigosa J., Panarese A., Dominici N., Friedli L., van den Brand R., Carpaneto J., et al. . (2015). Decoding bipedal locomotion from the rat sensorimotor cortex. J. Neural Eng. 12:56014. 10.1088/1741-2560/12/5/056014
    1. Roy R. R., Harkema S. J., Edgerton V. R. (2012). Basic concepts of activity-based interventions for improved recovery of motor function after spinal cord injury. Arch. Phys. Med. Rehabil. 93, 1487–1497. 10.1016/j.apmr.2012.04.034
    1. Ryapolova-Webb E., Afshar P., Stanslaski S., Denison T., de Hemptinne C., Bankiewicz K., et al. . (2014). Chronic cortical and electromyographic recordings from a fully implantable device: preclinical experience in a nonhuman primate. J. Neural Eng. 11:16009. 10.1088/1741-2560/11/1/016009
    1. Sakurada T., Kawase T., Takano K., Komatsu T., Kansaku K. (2013). A BMI-based occupational therapy assist suit: asynchronous control by SSVEP. Front. Neurosci. 7:172. 10.3389/fnins.2013.00172
    1. Sandberg K., Frässle S., Pitts M. (2016). Future directions for identifying the neural correlates of consciousness. Nat. Rev. Neurosci. 10.1038/nrn.2016.104. [Epub ahead of print].
    1. Sayenko D. G., Angeli C., Harkema S. J., Edgerton V. R., Gerasimenko Y. P. (2014). Neuromodulation of evoked muscle potentials induced by epidural spinal-cord stimulation in paralyzed individuals. J. Neurophysiol. 111, 1088–1099. 10.1152/jn.00489.2013
    1. Schaechter J. D., Moore C. I., Connell B. D., Rosen B. R., Dijkhuizen R. M. (2006). Structural and functional plasticity in the somatosensory cortex of chronic stroke patients. Brain 129, 2722–2733. 10.1093/brain/awl214
    1. Schlaepfer W. W., Bunge R. P. (1973). Effects of calcium ion concentration on the degeneration of amputated axons in tissue culture. J. Cell Biol. 59, 456–470. 10.1083/jcb.59.2.456
    1. Schwarz D. A., Lebedev M. A., Hanson T. L., Dimitrov D. F., Lehew G., Meloy J., et al. . (2014). Chronic, wireless recordings of large-scale brain activity in freely moving rhesus monkeys. Nat. Methods 11, 670–676. 10.1038/nmeth.2936
    1. Serences J. T., Yantis S. (2006). Selective visual attention and perceptual coherence. Trends Cogn. Sci. 10, 38–45. 10.1016/j.tics.2005.11.008
    1. Seri B., García-Verdugo J. M., McEwen B. S., Alvarez-Buylla A. (2001). Astrocytes give rise to new neurons in the adult mammalian hippocampus. J. Neurosci. 21, 7153–7160.
    1. Sherwood A. M., Dimitrijevic M. R., Barry McKay W. (1992). Evidence of subclinical brain influence in clinically complete spinal cord injury: discomplete SCI. J. Neurol Sci. 110, 90–98. 10.1016/0022-510X(92)90014-C
    1. Shetty A. K., Turner D. A. (1995). Enhanced cell survival in fetal hippocampal suspension transplants grafted to adult rat hippocampus following kainate lesions: a three-dimensional graft reconstruction study. Neuroscience 67, 561–582. 10.1016/0306-4522(95)00025-E
    1. Shetty A. K., Turner D. A. (1999). Aging impairs axonal sprouting response of dentate granule cells following target loss and partial deafferentation. J. Comp. Neurol. 414, 238–254.
    1. Shetty P. K., Galeffi F., Turner D. A. (2014). Nicotinamide pre-treatment ameliorates NAD(H) hyperoxidation and improves neuronal function after severe hypoxia. Neurobiol. Dis. 62, 469–478. 10.1016/j.nbd.2013.10.025
    1. Shik M. L., Orlovsky G. N. (1976). Neurophysiology of locomotor automatism. Physiol. Rev. 56, 465–501.
    1. Shin S., Dixon E., Okonkwo D., Richardson M. (2014). Neurostimulation for traumatic brain injury. J. Neurosurg. 121, 1219–1231. 10.3171/2014.7.JNS131826
    1. Sitaram R., Caria A., Birbaumer N. (2009). Hemodynamic brain-computer interfaces for communication and rehabilitation. Neural Netw. 22, 1320–1328. 10.1016/j.neunet.2009.05.009
    1. Smith P. D., Sun F., Park K. K., Cai B., Wang C., Kuwako K., et al. . (2009). SOCS3 deletion promotes optic nerve regeneration in vivo. Neuron 64, 617–623. 10.1016/j.neuron.2009.11.021
    1. Soekadar S. R., Birbaumer N., Slutzky M. W., Cohen L. G. (2015). Brain-machine interfaces in neurorehabilitation of stroke. Neurobiol. Dis. 83, 172–179. 10.1016/j.nbd.2014.11.025
    1. Stefan K., Kunesch E., Cohen L. G., Benecke R., Classen J. (2000). Induction of plasticity in the human motor cortex by paired associative stimulation. Brain 123(Pt 3), 572–584. 10.1093/brain/123.3.572
    1. Stevenson I. H., London B. M., Oby E. R., Sachs N. A., Reimer J., Englitz B., et al. . (2012). Functional connectivity and tuning curves in populations of simultaneously recorded neurons. PLoS Comput. Biol. 8:e1002775. 10.1371/journal.pcbi.1002775
    1. Steyerberg E. W., Mushkudiani N., Perel P., Butcher I., Lu J., McHugh G. S., et al. . (2008). Predicting outcome after traumatic brain injury: development and international validation of prognostic scores based on admission characteristics. PLoS Med. 5:e165. 10.1371/journal.pmed.0050165
    1. Stockwell R. A. (1981). Joints, in Cunningham's Textbook of Anatomy, ed Romanes G. J.(Oxford: Oxford Medical Publications; ), 211–264.
    1. Stroemer R. P., Kent T. A., Hulsebosch C. E. (1995). Neocortical neural sprouting, synaptogenesis, and behavioral recovery after neocortical infarction in rats. Stroke 26, 2135–2144. 10.1161/01.STR.26.11.2135
    1. Suh S. W., Chen J. W., Motamedi M., Bell B., Listiak K., Pons N. F., et al. . (2000). Evidence that synaptically-released zinc contributes to neuronal injury after traumatic brain injury. Brain Res. 852, 268–273. 10.1016/S0006-8993(99)02095-8
    1. Sun F., He Z. (2010). Neuronal intrinsic barriers for axon regeneration in the adult CNS. Curr. Opin. Neurobiol. 20, 510–518. 10.1016/j.conb.2010.03.013
    1. Suthana N., Haneef Z., Stern J., Mukamel R., Behnke E., Knowlton B., et al. . (2012). Memory enhancement and deep-brain stimulation of the entorhinal area. N. Engl. J. Med. 366, 502–510. 10.1056/NEJMoa1107212
    1. Sweet J. A., Eakin K. C., Munyon C. N., Miller J. P. (2014). Improved learning and memory with theta-burst stimulation of the fornix in rat model of traumatic brain injury. Hippocampus 24, 1592–1600. 10.1002/hipo.22338
    1. Tator C. H. (1995). Update on the pathophysiology and pathology of acute spinal cord injury. Brain Pathol. 5, 407–413. 10.1111/j.1750-3639.1995.tb00619.x
    1. Tator C. H., Edmonds V. E. (1979). Acute spinal cord injury: analysis of epidemiologic factors. Can. J. Surg. 22, 575–578.
    1. Tator C. H., Fehlings M. G. (1991). Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J. Neurosurg. 75, 15–26. 10.3171/jns.1991.75.1.0015
    1. Taub E., Morris D. M. (2001). Constraint-induced movement therapy to enhance recovery after stroke. Curr. Atheroscler. Rep. 3, 279–286. 10.1007/s11883-001-0020-0
    1. Taub E., Uswatte G., Elbert T. (2002). New treatments in neurorehabilitation founded on basic research. Nat. Rev. Neurosci. 3, 228–236. 10.1038/nrn754
    1. Teasell R. W., Murie Fernandez M., McIntyre A., Mehta S. (2014). Rethinking the continuum of stroke rehabilitation. Arch. Phys. Med. Rehabil. 95, 595–596. 10.1016/j.apmr.2013.11.014
    1. Tedeschi A. (2011). Tuning the orchestra: transcriptional pathways controlling axon regeneration. Front. Mol. Neurosci. 4:60. 10.3389/fnmol.2011.00060
    1. Terroni L., Amaro E., Iosifescu D. V., Tinone G., Sato J. R., Leite C. C., et al. . (2011). Stroke lesion in cortical neural circuits and post-stroke incidence of major depressive episode: a 4-month prospective study. World J. Biol. Psychiatry 12, 539–548. 10.3109/15622975.2011.562242
    1. Teyler T. J., Morgan S. L., Russell R. N., Woodside B. L. (2001). Synaptic plasticity and secondary epileptogenesis. Int. Rev. Neurobiol. 45, 253–267. 10.1016/S0074-7742(01)45014-8
    1. Thickbroom G. W., Mastaglia F. L. (2009). Plasticity in neurological disorders and challenges for noninvasive brain stimulation (NBS). J. Neuroeng. Rehabil. 6:4. 10.1186/1743-0003-6-4
    1. Thompson K., Pohlmann-Eden B., Campbell L. A., Abel H. (2015). Pharmacological treatments for preventing epilepsy following traumatic head injury. Cochrane Database Syst. Rev. 8:CD009900 10.1002/14651858.CD009900.pub2
    1. Thored P., Arvidsson A., Cacci E., Ahlenius H., Kallur T., Darsalia V., et al. . (2006). Persistent production of neurons from adult brain stem cells during recovery after stroke. Stem Cells 24, 739–747. 10.1634/stemcells.2005-0281
    1. Troyk P. R., Mushahwar V. K., Stein R. B., Suh S., Everaert D., Holinski B., et al. . (2012). An implantable neural stimulator for intraspinal microstimulation. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2012, 900–903. 10.1109/embc.2012.6346077
    1. Turner D. A., Patil P. G., Nicolelis M. A. L. (2008). Conceptual and technical approaches to human neural ensemble recordings, in Methods Neural Ensemble Rec. 2nd Edn., ed Nicolelis M. A. L.(Boca Raton, FL: CRC Press; Taylor & Francis; ), 1–17.
    1. van den Brand R., Heutschi J., Barraud Q., DiGiovanna J., Bartholdi K., Huerlimann M., et al. . (2012). Restoring voluntary control of locomotion after paralyzing spinal cord injury. Science 336, 1182–1185. 10.1126/science.1217416
    1. van den Brand R., Mignardot J. B., von Zitzewitz J., Le Goff C., Fumeaux N., Wagner F., et al. . (2015). Neuroprosthetic technologies to augment the impact of neurorehabilitation after spinal cord injury. Ann. Phys. Rehabil. Med. 58, 232–237. 10.1016/j.rehab.2015.04.003
    1. Vansteensel M. J., Pels E. G. M., Bleichner M. G., Branco M. P., Denison T., Freudenburg Z. V., et al. . (2016). Fully implanted brain–computer interface in a locked-in patient with ALS. N. Engl. J. Med. 375, 2060–2066. 10.1056/nejmoa1608085
    1. Vargas-Irwin C. E., Shakhnarovich G., Yadollahpour P., Mislow J. M. K., Black M. J., Donoghue J. P. (2010). Decoding complete reach and grasp actions from local primary motor cortex populations. J. Neurosci. 30, 9659–9669. 10.1523/JNEUROSCI.5443-09.2010
    1. Vidaurre C., Klauer C., Schauer T., Ramos-Murguialday A., Müller K.-R. (2016). EEG-based BCI for the linear control of an upper-limb neuroprosthesis. Med. Eng. Phys. 38, 1195–1204. 10.1016/j.medengphy.2016.06.010
    1. Villamar M. F., Santos Portilla A., Fregni F., Zafonte R. (2012). Noninvasive brain stimulation to modulate neuroplasticity in traumatic brain injury. Neuromodulation 15, 326–337. 10.1111/j.1525-1403.2012.00474.x
    1. Wahl A. S., Omlor W., Rubio J. C., Chen J. L., Zheng H., Schröter A., et al. . (2014). Asynchronous therapy restores motor control by rewiring of the rat corticospinal tract after stroke. Science 344, 1250–1255. 10.1126/science.1253050
    1. Warren Olanow C., Bartus R. T., Baumann T. L., Factor S., Boulis N., Stacy M., et al. . (2015). Gene delivery of neurturin to putamen and substantia nigra in Parkinson disease: a double-blind, randomized, controlled trial. Ann. Neurol. 78, 248–257. 10.1002/ana.24436
    1. Waters R. L., Adkins R. H., Yakura J. S., Sie I. (1996). Effect of surgery on motor recovery following traumatic spinal cord injury. Spinal Cord 34, 188–192. 10.1038/sc.1996.37
    1. Waters R. L., Yakura J. S., Adkins R. H., Sie I. (1992). Recovery following complete paraplegia. Arch. Phys. Med. Rehabil. 73, 784–789.
    1. Weiskopf N., Veit R., Erb M., Mathiak K., Grodd W., Goebel R., et al. . (2003). Physiological self-regulation of regional brain activity using real-time functional magnetic resonance imaging (fMRI): methodology and exemplary data. Neuroimage 19, 577–586. 10.1016/S1053-8119(03)00145-9
    1. Wernig A., Müller S. (1992). Laufband locomotion with body weight support improved walking in persons with severe spinal cord injuries. Paraplegia 30, 229–238. 10.1038/sc.1992.61
    1. Wernig A., Nanassy A., Müller S. (1998). Maintenance of locomotor abilities following Laufband (treadmill) therapy in para- and tetraplegic persons: follow-up studies. Spinal Cord 36, 744–749. 10.1038/sj.sc.3100670
    1. Wessberg J., Stambaugh C. R., Kralik J. D., Beck P. D., Laubach M., Chapin J. K., et al. . (2000). Real-time prediction of hand trajectory by ensembles of cortical neurons in primates. Nature 408, 361–365. 10.1038/35042582
    1. Wolf S. L., Winstein C. J., Miller J. P., Taub E., Uswatte G., Morris D., et al. . (2006). Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE randomized clinical trial. JAMA 296, 2095–2104. 10.1001/jama.296.17.2095
    1. Wolman L. (1965). The disturbance of circulation in traumatic paraplegia in acute and late stages: a pathological study. Paraplegia 2, 213–226. 10.1038/sc.1964.39
    1. Wolpaw J. R., McFarland D. J. (1994). Multichannel EEG-based brain-computer communication. Electroencephalogr. Clin. Neurophysiol. 90, 444–449. 10.1016/0013-4694(94)90135-X
    1. Wolpaw J. R., Tennissen A. M. (2001). Activity-dependent spinal cord plasticity in health and disease. Annu. Rev. Neurosci. 24, 807–843. 10.1146/annurev.neuro.24.1.807
    1. Womelsdorf T., Schoffelen J.-M., Oostenveld R., Singer W., Desimone R., Engel A. K., et al. . (2007). Modulation of neuronal interactions through neuronal synchronization. Science 316, 1609–1612. 10.1126/science.1139597
    1. Xi G., Keep R., Hoff J. (2006). Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 5, 53–63. 10.1016/S1474-4422(05)70283-0
    1. Yin Y., Cui Q., Gilbert H.-Y., Yang Y., Yang Z., Berlinicke C., et al. . (2009). Oncomodulin links inflammation to optic nerve regeneration. Proc. Natl. Acad. Sci. U.S.A. 106, 19587–19592. 10.1073/pnas.0907085106
    1. Yin Y., Cui Q., Li Y., Irwin N., Fischer D., Harvey A. R., et al. . (2003). Macrophage-derived factors stimulate optic nerve regeneration. J. Neurosci. 23, 2284–2293.
    1. Yin Y., Henzl M. T., Lorber B., Nakazawa T., Thomas T. T., Jiang F., et al. . (2006). Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nat. Neurosci. 9, 843–852. 10.1038/nn1701
    1. Yurkewicz L., Weaver J., Bullock M. R., Marshall L. L. (2005). The effect of the selective NMDA receptor antagonist traxoprodil in the treatment of traumatic brain injury. J. Neurotrauma 22, 1428–1443. 10.1089/neu.2005.22.1428
    1. Zai L., Ferrari C., Dice C., Subbaiah S., Havton L. A., Coppola G., et al. . (2011). Inosine augments the effects of a Nogo receptor blocker and of environmental enrichment to restore skilled forelimb use after stroke. J. Neurosci. 31, 5977–5988. 10.1523/JNEUROSCI.4498-10.2011
    1. Zai L., Ferrari C., Subbaiah S., Havton L. A., Coppola G., Strittmatter S., et al. . (2009). Inosine alters gene expression and axonal projections in neurons contralateral to a cortical infarct and improves skilled use of the impaired limb. J. Neurosci. 29, 8187–8197. 10.1523/JNEUROSCI.0414-09.2009
    1. Zetterberg H., Smith D. H., Blennow K. (2013). Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood. Nat. Rev. Neurol. 9, 201–210. 10.1038/nrneurol.2013.9
    1. Zhang R. L., Zhang Z. G., Zhang L., Chopp M. (2001). Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia. Neuroscience 105, 33–41. 10.1016/S0306-4522(01)00117-8
    1. Zimmermann J. B., Jackson A. (2014). Closed-loop control of spinal cord stimulation to restore hand function after paralysis. Front. Neurosci. 8:87. 10.3389/fnins.2014.00087
    1. Zink B. J., Szmydynger-Chodobska J., Chodobski A. (2010). Emerging concepts in the pathophysiology of traumatic brain injury. Psychiatr. Clin. North Am. 33, 741–756. 10.1016/j.psc.2010.08.005

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner