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Motor Neuroprostheses

Arthur Prochazka

10.1002/cphy.c180006

Source: Volume 9, Issue 1, January 2019

Published online: December 2018

Full Article on Wiley Online Library



ABSTRACT

Neuroprostheses (NPs) are electrical stimulators that activate nerves, either to provide sensory input to the central nervous system (sensory NPs), or to activate muscles (motor NPs: MNPs). The first MNPs were belts with inbuilt batteries and electrodes developed in the 1850s to exercise the abdominal muscles. They became enormously popular among the general public, but as a result of exaggerated therapeutic claims they were soon discredited by the medical community. In the 1950s, MNPs reemerged for the serious purpose of activating paralyzed muscles. Neuromuscular electrical stimulation (NMES), when applied in a preset sequence, is called therapeutic electrical stimulation (TES). NMES timed so that it enhances muscle contraction in intended voluntary movements is called functional electrical stimulation (FES) or functional neuromuscular stimulation (FNS). It has been 50 years since the first FES device, a foot‐drop stimulator, was described and 40 years since the first implantable version was tested in humans. A commercial foot‐drop stimulator became available in the 1970s, but for various reasons, it failed to achieve widespread use. With advances in technology, such devices are now more convenient and reliable. Enhancing upper limb function is a more difficult task, but grasp‐release stimulators have been shown to provide significant benefits. This chapter deals with the technical aspects of NMES, the therapeutic and functional benefits of TES and FES, delayed‐onset and carryover effects attributable to “neuromodulation” and the barriers and opportunities in this rapidly developing field. © 2019 American Physiological Society. Compr Physiol 9:127‐148, 2019.

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Figure 1. Figure 1. Basic designs of neural prostheses. (A) A surface stimulator (external pulse generator: EPG) delivers current pulses through the skin via a pair of surface electrodes. In some cases, a wireless controller controls the EPG. (B) An EPG delivers current pulses via one or more conductors, typically insulated wires that pass through the skin and terminate close to or on the nerve. The return current flows through the tissues to a surface (reference) electrode. (C) An EPG delivers current pulses through the skin via a pair of surface electrodes and some of the current is intercepted and “picked up” by a fully implanted lead, which delivers this current to the nerve. (D) An implanted pulse generator (IPG) receives energy and commands wirelessly through the skin and delivers current pulses to the nerve via an electrode. The return current flows through the tissues to a reference electrode on the body of the IPG. (E) An implanted pulse generator (IPG) receives energy and commands wirelessly through the skin and delivers current pulses to the nerve via a pair of electrodes. (F) An injectable microstimulator receives energy and commands wirelessly through the skin and delivers current pulses to the nerve through two conductive terminals on the body of the stimulator.
Figure 2. Figure 2. Four surface foot‐drop stimulators that activate the common peroneal nerve to lift the foot in the swing phase of the locomotor step cycle. (A) The Functional Electrical Peroneal Orthosis (FEPO), commercialized in Europe in the 1970s. (B) The Bioness L300. (C) The Innovative Neurotronics Walkaide. (D) The Bioness L300Go. The FEPO and L300 had underheel switches wirelessly linked to an EPG in a cuff attached below the knee. When the underheel force dropped at the onset of the swing phase, a signal from the switch assembly triggered the EPG to stimulate the nerve via electrodes in the cuff. The Walkaide and Bioness L300Go have a tilt sensor built into the cuff, which is used to trigger stimulation, replacing the underheel switch and allowing users to walk barefoot.
Figure 3. Figure 3. Four surface stimulators that activate muscles in the forearm and hand. (A) The Medtronic Respond physiotherapy stimulator activating the wrist and finger extensors. Preset trains of stimulus pulses were triggered by activating a hand‐held push‐button. Numerous therapeutic stimulators based on this design are commercially available. (B) The EMG‐triggered Neuromove. Weak voluntary contractions are detected via a pair of surface electrodes and this triggers a preset period of stimulation through a pair of electrodes placed orthogonally to the electromyogram electrodes. (C) The Bioness H200. This device comprises a flexible splint with inbuilt electrodes. Trains of stimuli eliciting hand opening and grasp are triggered via a radiofrequency push‐button controller. (D) The Rehabtronics ReGrasp comprises a wristlet garment with inbuilt stimulator/receiver and electrodes. A wireless earpiece detects voluntary head movements and transmits control signals to the wristlet, by which means the user can trigger hand opening or grasp.
Figure 4. Figure 4. Proximal and distal muscle activation in which signals from a microelectrode array implanted in the motor cortex of a tetraplegic man were used to control stimulation through electrodes inserted percutaneously into his upper limb. This enabled him voluntarily to reach out with his weight‐supported arm to drink a mug of coffee and feed himself. Reproduced with permission from (5).
Figure 5. Figure 5. Sacral spinal cord targets (segments S2‐S4) for electrical stimulation to improve bladder function. SNS, sacral nerve stimulation; SARS, sacral anterior root stimulation; ISMS, intraspinal microstimulation; PNS, pudendal nerve stimulation; PTNS, percutaneous tibial nerve stimulation; TENS, transcutaneous electrical nerve stimulation; HFNB, high‐frequency stimulation eliciting nerve block (HFNB); SPN, sacral parasympathetic nucleus (activates bladder contractions); ON, Onuf's nucleus; CSN, cranial sensory neuron; DNP, dorsal nerve of the penis (DNP). Reproduced with permission from (190).


Figure 1. Basic designs of neural prostheses. (A) A surface stimulator (external pulse generator: EPG) delivers current pulses through the skin via a pair of surface electrodes. In some cases, a wireless controller controls the EPG. (B) An EPG delivers current pulses via one or more conductors, typically insulated wires that pass through the skin and terminate close to or on the nerve. The return current flows through the tissues to a surface (reference) electrode. (C) An EPG delivers current pulses through the skin via a pair of surface electrodes and some of the current is intercepted and “picked up” by a fully implanted lead, which delivers this current to the nerve. (D) An implanted pulse generator (IPG) receives energy and commands wirelessly through the skin and delivers current pulses to the nerve via an electrode. The return current flows through the tissues to a reference electrode on the body of the IPG. (E) An implanted pulse generator (IPG) receives energy and commands wirelessly through the skin and delivers current pulses to the nerve via a pair of electrodes. (F) An injectable microstimulator receives energy and commands wirelessly through the skin and delivers current pulses to the nerve through two conductive terminals on the body of the stimulator.


Figure 2. Four surface foot‐drop stimulators that activate the common peroneal nerve to lift the foot in the swing phase of the locomotor step cycle. (A) The Functional Electrical Peroneal Orthosis (FEPO), commercialized in Europe in the 1970s. (B) The Bioness L300. (C) The Innovative Neurotronics Walkaide. (D) The Bioness L300Go. The FEPO and L300 had underheel switches wirelessly linked to an EPG in a cuff attached below the knee. When the underheel force dropped at the onset of the swing phase, a signal from the switch assembly triggered the EPG to stimulate the nerve via electrodes in the cuff. The Walkaide and Bioness L300Go have a tilt sensor built into the cuff, which is used to trigger stimulation, replacing the underheel switch and allowing users to walk barefoot.


Figure 3. Four surface stimulators that activate muscles in the forearm and hand. (A) The Medtronic Respond physiotherapy stimulator activating the wrist and finger extensors. Preset trains of stimulus pulses were triggered by activating a hand‐held push‐button. Numerous therapeutic stimulators based on this design are commercially available. (B) The EMG‐triggered Neuromove. Weak voluntary contractions are detected via a pair of surface electrodes and this triggers a preset period of stimulation through a pair of electrodes placed orthogonally to the electromyogram electrodes. (C) The Bioness H200. This device comprises a flexible splint with inbuilt electrodes. Trains of stimuli eliciting hand opening and grasp are triggered via a radiofrequency push‐button controller. (D) The Rehabtronics ReGrasp comprises a wristlet garment with inbuilt stimulator/receiver and electrodes. A wireless earpiece detects voluntary head movements and transmits control signals to the wristlet, by which means the user can trigger hand opening or grasp.


Figure 4. Proximal and distal muscle activation in which signals from a microelectrode array implanted in the motor cortex of a tetraplegic man were used to control stimulation through electrodes inserted percutaneously into his upper limb. This enabled him voluntarily to reach out with his weight‐supported arm to drink a mug of coffee and feed himself. Reproduced with permission from (5).


Figure 5. Sacral spinal cord targets (segments S2‐S4) for electrical stimulation to improve bladder function. SNS, sacral nerve stimulation; SARS, sacral anterior root stimulation; ISMS, intraspinal microstimulation; PNS, pudendal nerve stimulation; PTNS, percutaneous tibial nerve stimulation; TENS, transcutaneous electrical nerve stimulation; HFNB, high‐frequency stimulation eliciting nerve block (HFNB); SPN, sacral parasympathetic nucleus (activates bladder contractions); ON, Onuf's nucleus; CSN, cranial sensory neuron; DNP, dorsal nerve of the penis (DNP). Reproduced with permission from (190).
References
 1.Agarwal S, Kobetic R, Nandurkar S, Marsolais EB. Functional electrical stimulation for walking in paraplegia: 17‐year follow‐up of 2 cases. J Spinal Cord Med 26: 86‐91, 2003.
 2.Agnew WF, McCreery DB. Considerations for safety with chronically implanted nerve electrodes. Epilepsia 31(Suppl 2): S27‐S32, 1990.
 3.Agnew WF, McCreery DB, Yuen TGH, Bullara LA. Effects of prolonged electrical stimulation of the central nervous system. In: Agnew WF, McCreery DB, editors. Neural Prostheses Fundamental Studies. Englewood Cliffs, NJ: Prentice Hall, 1990, pp. 225‐252.
 4.Aiyar H, Stellato TA, Onders RP, Mortimer JT. Laparoscopic implant instrument for the placement of intramuscular electrodes in the diaphragm. IEEE Trans Rehabil Eng 7: 360‐371, 1999.
 5.Ajiboye AB, Willett FR, Young DR, Memberg WD, Murphy BA, Miller JP, Walter BL, Sweet JA, Hoyen HA, Keith MW, Peckham PH, Simeral JD, Donoghue JP, Hochberg LR, Kirsch RF. Restoration of reaching and grasping movements through brain‐controlled muscle stimulation in a person with tetraplegia: A proof‐of‐concept demonstration. Lancet 389: 1821‐1830, 2017.
 6.Alam M, Garcia‐Alias G, Jin B, Keyes J, Zhong H, Roy RR, Gerasimenko Y, Lu DC, Edgerton VR. Electrical neuromodulation of the cervical spinal cord facilitates forelimb skilled function recovery in spinal cord injured rats. Exp Neurol 291: 141‐150, 2017.
 7.Albertin G, Hofer C, Zampieri S, Vogelauer M, Lofler S, Ravara B, Guidolin D, Fede C, Incendi D, Porzionato A, De Caro R, Baba A, Marcante A, Piccione F, Gargiulo P, Pond A, Carraro U, Kern H. In complete SCI patients, long‐term functional electrical stimulation of permanent denervated muscles increases epidermis thickness. Neurol Res 40: 277‐282, 2018.
 8.Alon G, Levitt AF, McCarthy PA. Functional electrical stimulation enhancement of upper extremity functional recovery during stroke rehabilitation: A pilot study. Neurorehabil Neural Repair 21: 207‐215, 2007.
 9.Alon G, McBride K. Persons with C5 or C6 tetraplegia achieve selected functional gains using a neuroprosthesis. Arch Phys Med Rehabil 84: 119‐124, 2003.
 10.Alon G, McBride K, Ring H. Improving selected hand functions using a noninvasive neuroprosthesis in persons with chronic stroke. J Stroke Cerebrovasc Dis 11: 99‐106, 2002.
 11.Alon G, Sunnerhagen KS, Geurts AC, Ohry A. A home‐based, self‐administered stimulation program to improve selected hand functions of chronic stroke. NeuroRehabilitation 18: 215‐225, 2003.
 12.Amarenco G, Ismael SS, Even‐Schneider A, Raibaut P, Demaille‐Wlodyka S, Parratte B, Kerdraon J. Urodynamic effect of acute transcutaneous posterior tibial nerve stimulation in overactive bladder. J Urol 169: 2210‐2215, 2003.
 13.Anagnostopoulos CE, Glenn WW. Electronic pacemakers of the heart, gastrointestinal tract, phrenic nerve, bladder, and carotid sinus: Current status. Surgery 60: 480‐494, 1966.
 14.Anderson KD. Targeting recovery: Priorities of the spinal cord‐injured population. J Neurotrauma 21: 1371‐1383, 2004.
 15.Anderson RW, Farokhniaee A, Gunalan K, Howell B, McIntyre CC. Action potential initiation, propagation, and cortical invasion in the hyperdirect pathway during subthalamic deep brain stimulation. Brain Stimul 11: 1140‐1150, 2018.
 16.Andrews BJ, Wheeler GD. Functional and therapeutic benefits of electrical stimulation after spinal injury. Curr Opin Neurol 8: 461‐466, 1995.
 17.Angeli CA, Edgerton VR, Gerasimenko YP, Harkema SJ. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain 137: 1394‐1409, 2014.
 18.Audu ML, Gartman SJ, Nataraj R, Triolo RJ. Posture‐dependent control of stimulation in standing neuroprosthesis: Simulation feasibility study. J Rehabil Res Dev 51: 481‐496, 2014.
 19.Aum DJ, Tierney TS. Deep brain stimulation: Foundations and future trends. Front Biosci (Landmark Ed) 23: 162‐182, 2018.
 20.Baer GA, Talonen PP, Hakkinen V, Exner G, Yrjola H. Phrenic nerve stimulation in tetraplegia. A new regimen to condition the diaphragm for full‐time respiration. Scand J Rehabil Med 22: 107‐111, 1990.
 21.Baigrie B. Electricity and Magnetism: A Historical Perspective. Westport, Connecticut: Greenwood Press, 2007, p. 165.
 22.Baker LL, Yeh C, Wilson D, Waters RL. Electrical stimulation of wrist and fingers for hemiplegic patients. Phys Ther 59: 1495‐1499, 1979.
 23.Banakhar M, Hassouna M. Sacral neuromodulation for genitourinary problems. Prog Neurol Surg 29: 192‐199, 2015.
 24.Bareket‐Keren L, Hanein Y. Novel interfaces for light directed neuronal stimulation: Advances and challenges. Int J Nanomedicine 9(Suppl 1): 65‐83, 2014.
 25.Barker RN, Brauer SG. Upper limb recovery after stroke: The stroke survivors' perspective. Disabil Rehabil 27: 1213‐1223, 2005.
 26.Barker RN, Gill TJ, Brauer SG. Factors contributing to upper limb recovery after stroke: A survey of stroke survivors in Queensland Australia. Disabil Rehabil 29: 981‐989, 2007.
 27.Barrese JC, Rao N, Paroo K, Triebwasser C, Vargas‐Irwin C, Franquemont L, Donoghue JP. Failure mode analysis of silicon‐based intracortical microelectrode arrays in non‐human primates. J Neural Eng 10: 066014, 2013.
 28.Barss TS, Ainsley EN, Claveria‐Gonzalez FC, Luu MJ, Miller DJ, Wiest MJ, Collins DF. Utilizing physiological principles of motor unit recruitment to reduce fatigability of electrically‐evoked contractions: A narrative review. Arch Phys Med Rehabil 99: 779‐791, 2018.
 29.Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J. Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol 50: 344‐346, 1987.
 30.Bennett M, Strother RB, Grill J, Mrva JJ, Zmina T, Thrope GB. Systems and methods for bilateral stimulation of left and right branches of the dorsal genital nerves to treat dysfunctions, such as urinary incontinence. US Patent 7,565,198. Edited by USPTO. USA: Medtrinic Urinary Solutions, 2009, pp. 1‐34.
 31.Bethoux F, Rogers HL, Nolan KJ, Abrams GM, Annaswamy TM, Brandstater M, Browne B, Burnfield JM, Feng W, Freed MJ, Geis C, Greenberg J, Gudesblatt M, Ikramuddin F, Jayaraman A, Kautz SA, Lutsep HL, Madhavan S, Meilahn J, Pease WS, Rao N, Seetharama S, Sethi P, Turk MA, Wallis RA, Kufta C. The effects of peroneal nerve functional electrical stimulation versus ankle‐foot orthosis in patients with chronic stroke: A randomized controlled trial. Neurorehabil Neural Repair 28: 688‐697, 2014.
 32.Bhadra N, Kilgore K, Gustafson KJ. High frequency electrical conduction block of the pudendal nerve. J Neural Eng 3: 180‐187, 2006.
 33.Bioness. Bioness L300 for footdrop https://www.bioness.com/Products/L300_for_Foot_Drop.php.
 34.Bird G. Remarks on the hydro‐electric chain of Dr. Pulvermacher. The Lancet, 58: 388‐389, 1851.
 35.Blok BFM, van Maarseveen JTPW, Holstege G. Electrical stimulation of the sacral dorsal gray commissure evokes relaxation of the external urethral sphincter in the cat. Neurosci Lett 249: 68‐70, 1998.
 36.Boger A, Bhadra N, Gustafson KJ. Bladder voiding by combined high frequency electrical pudendal nerve block and sacral root stimulation. Neurourol Urodyn 27: 435‐439, 2007.
 37.Boggs JW, Wenzel BJ, Gustafson KJ, Grill WM. Bladder emptying by intermittent electrical stimulation of the pudendal nerve. J Neural Eng 3: 43‐51, 2006.
 38.Boggs JW, Wenzel BJ, Gustafson KJ, Grill WM. Frequency‐dependent selection of reflexes by pudendal afferents in the cat. J Physiol 577: 115‐126, 2006.
 39.Bogie KM, Wang X, Triolo RJ. Long‐term prevention of pressure ulcers in high‐risk patients: A single case study of the use of gluteal neuromuscular electric stimulation. Arch Phys Med Rehabil 87: 585‐591, 2006.
 40.Bouton CE, Shaikhouni A, Annetta NV, Bockbrader MA, Friedenberg DA, Nielson DM, Sharma G, Sederberg PB, Glenn BC, Mysiw WJ, Morgan AG, Deogaonkar M, Rezai AR. Restoring cortical control of functional movement in a human with quadriplegia. Nature 533: 247‐250, 2016.
 41.Branco MP, Freudenburg ZV, Aarnoutse EJ, Bleichner MG, Vansteensel MJ, Ramsey NF. Decoding hand gestures from primary somatosensory cortex using high‐density ECoG. Neuroimage 147: 130‐142, 2016.
 42.Brazier AB. A History of Neurophysiology in the 17th and 18th Centuries. New York: Raven, 1984, p. 230.
 43.Brazier MAB. A History of Neurophysiology in the 19th Century. New York: Raven, 1988, p. 265.
 44.Brindley GS. An implant to empty the bladder or close the urethra. J Neurol Neurosurg Psychiatry 40: 358‐369, 1977.
 45.Brindley GS, Lewin WS. The sensations produced by electrical stimulation of the visual cortex. J Physiol 196: 479‐493, 1968.
 46.Brindley GS, Polkey CE, Rushton DN. Sacral anterior root stimulators for bladder control in paraplegia. Paraplegia 20: 365‐381, 1982.
 47.Brissot R, Gallien P, Le Bot MP, Beaubras A, Laisne D, Beillot J, Dassonville J. Clinical experience with functional electrical stimulation‐assisted gait with Parastep in spinal cord‐injured patients. Spine (Phila Pa 1976) 25: 501‐508, 2000.
 48.Brock LG, Coombs JS, Eccles JC. Synaptic excitation and inhibition. J Physiol 117: 8p, 1952.
 49.Buick AR, Kowalczewski J, Carson RG, Prochazka A. Tele‐supervised FES‐assisted exercise for hemiplegic upper limb. IEEE Trans Neural Syst Rehabil Eng 24: 79‐87, 2016.
 50.Bulley C, Shiels J, Wilkie K, Salisbury L. User experiences, preferences and choices relating to functional electrical stimulation and ankle foot orthoses for foot‐drop after stroke. Physiotherapy 97: 226‐233, 2011.
 51.Burke RE. Motor unit properties and selective involvement in movement. [Review]. Ex Sport Sci Rev 3: 31‐81, 1975.
 52.Burridge JH, Haugland M, Larsen B, Pickering RM, Svaneborg N, Iversen HK, Christensen PB, Haase J, Brennum J, Sinkjaer T. Phase II trial to evaluate the ActiGait implanted drop‐foot stimulator in established hemiplegia. J Rehabil Med 39: 212‐218, 2007.
 53.Burridge JH, Haugland M, Larsen B, Svaneborg N, Iversen HK, Christensen PB, Pickering RM, Sinkjaer T. Patients' perceptions of the benefits and problems of using the ActiGait implanted drop‐foot stimulator. J Rehabil Med 40: 873‐875, 2008.
 54.Capogrosso M, Milekovic T, Borton D, Wagner F, Moraud EM, Mignardot JB, Buse N, Gandar J, Barraud Q, Xing D, Rey E, Duis S, Jianzhong Y, Ko WK, Li Q, Detemple P, Denison T, Micera S, Bezard E, Bloch J, Courtine G. A brain‐spine interface alleviating gait deficits after spinal cord injury in primates. Nature 539: 284‐288, 2016.
 55.Carhart MR, He J, Herman R, D'Luzansky S, Willis WT. Epidural spinal‐cord stimulation facilitates recovery of functional walking following incomplete spinal‐cord injury. IEEE Trans Neural Syst Rehabil Eng 12: 32‐42, 2004.
 56.Cauraugh JH, Kim S. Two coupled motor recovery protocols are better than one: Electromyogram‐triggered neuromuscular stimulation and bilateral movements. Stroke 33: 1589‐1594, 2002.
 57.Cauraugh JH, Kim SB. Stroke motor recovery: Active neuromuscular stimulation and repetitive practice schedules. J Neurol Neurosurg Psychiatry 74: 1562‐1566, 2003.
 58.Cauraugh JH, Kim SB, Duley A. Coupled bilateral movements and active neuromuscular stimulation: Intralimb transfer evidence during bimanual aiming. Neurosci Lett 382: 39‐44, 2005.
 59.Chae J. Neuromuscular electrical stimulation for motor relearning in hemiparesis. Phys Med Rehabil Clin N Am 14: S93‐S109, 2003.
 60.Clark G. Cochlear Implants: Fundamentals and Applications. New York: Springer Verlag, 2003, p. 885.
 61.Clippinger FW, Guilford AW, Radcliffe CW. Clinical Evaluation of Rancho Los Amigos Hospital/Medtronic, Inc. Implanted Neuromuscular Assist Device. Committee on prosthetics research and development, Division of medical sciences, National academy of sciences ‐ National research council. National Academies, 1976, p. 105.
 62.CMS. National Coverage Determination (NCD) for Neuromuscular Electrical Stimulaton (NMES) (160.12). http://www.cms.gov/transmittals/downloads/R55NCD.pdf. edited by Services CfMaM. http://www.cms.gov/medicare‐coverage‐database: Centers for Medicare and Medicaide Services, 2006, p. 2.
 63.Cogan SF. Neural stimulation and recording electrodes. Annu Rev Biomed Eng 10: 275‐309, 2008.
 64.Cogan SF, Ehrlich J, Plante TD, Van Wagenen R. Penetrating microelectrode arrays with low‐impedance sputtered iridium oxide electrode coatings. Conf Proc IEEE Eng Med Biol Soc 2009: 7147‐7150, 2009.
 65.Creasey G, Elefteriades J, DiMarco A, Talonen P, Bijak M, Girsch W, Kantor C. Electrical stimulation to restore respiration. J Rehabil Res Dev 33: 123‐132, 1996.
 66.Dai R, Stein RB, Andrews BJ, James KB, Wieler M. Application of tilt sensors in functional electrical stimulation. IEEE Trans Rehabil Eng 4: 63‐72, 1996.
 67.Davis JA, Jr., Triolo RJ, Uhlir JP, Bhadra N, Lissy DA, Nandurkar S, Marsolais EB. Surgical technique for installing an eight‐channel neuroprosthesis for standing. Clin Orthop Relat Res 237‐252, 2001.
 68.de Kroon JR, Ijzerman MJ, Chae J, Lankhorst GJ, Zilvold G. Relation between stimulation characteristics and clinical outcome in studies using electrical stimulation to improve motor control of the upper extremity in stroke. J Rehabil Med 37: 65‐74, 2005.
 69.de Kroon JR, van der Lee JH, Ijzerman MJ, Lankhorst GJ. Therapeutic electrical stimulation to improve motor control and functional abilities of the upper extremity after stroke: A systematic review. Clin Rehabil 16: 350‐360, 2002.
 70.Deer T, Pope J, Benyamin R, Vallejo R, Friedman A, Caraway D, Staats P, Grigsby E, Porter McRoberts W, McJunkin T, Shubin R, Vahedifar P, Tavanaiepour D, Levy R, Kapural L, Mekhail N. Prospective, multicenter, randomized, double‐blinded, partial crossover study to assess the safety and efficacy of the novel neuromodulation system in the treatment of patients with chronic pain of peripheral nerve origin. Neuromodulation 19: 91‐100, 2016.
 71.Deer TR, Levy RM, Rosenfeld EL. Prospective clinical study of a new implantable peripheral nerve stimulation device to treat chronic pain. Clin J Pain 26: 359‐372, 2010.
 72.Di PWC, Di PSGC, McDermott CJ, Bradburn MJ, Maguire C, Cooper CL, Baird WO, Baxter SK, Bourke SC, Imam I, Bentley A, Ealing J, Elliott M, Hanemann CO, Hughes P, Orrell RW, Shaw PJ, Talbot K, Williams T, Ackroyd R, Berrisford R, Galloway S, Karat D, Maynard N, Sarela A, Simonds AK, Taylor L, Leek R, Darlison R, Leigh N, Dewey M, Radunovic A. Safety and efficacy of diaphragm pacing in patients with respiratory insufficiency due to amyotrophic lateral sclerosis (DiPALS): A multicentre, open‐label, randomised controlled trial. Lancet Neurol 14: 883‐892, 2015.
 73.DiMarco AF, Onders RP, Kowalski KE, Miller ME, Ferek S, Mortimer JT. Phrenic nerve pacing in a tetraplegic patient via intramuscular diaphragm electrodes. Am J Respir Crit Care Med 166: 1604‐1606, 2002.
 74.Dimitrijevic MR, Gerasimenko Y, Pinter MM. Evidence for a spinal central pattern generator in humans. Ann N Y Acad Sci 860: 360‐376, 1998.
 75.Djourno A, Eyries C. [Auditory prosthesis by means of a distant electrical stimulation of the sensory nerve with the use of an indwelt coiling]. Presse Med 65: 1417, 1957.
 76.Djourno A, Eyries C, Vallancien P. [Preliminary attempts of electrical excitation of the auditory nerve in man, by permanently inserted micro‐apparatus]. Bull Acad Natl Med 141: 481‐483, 1957.
 77.Duchenne G‐B. Physiology of Motion Demonstrated by Means of Electrical Stimulation and Clinical Observation and Applied to the Study of Paralysis and Deformities. Philadelphia: W. B. Saunders, 1867, p. 612.
 78.Editorial BMJ. The Medical Battery Company, Limited, and the British Medical Association. In: Br Med J. London: British Medical Association, 1893, p. 1193.
 79.Elefteriades JA, Quin JA, Hogan JF, Holcomb WG, Letsou GV, Chlosta WF, Glenn WW. Long‐term follow‐up of pacing of the conditioned diaphragm in quadriplegia. Pacing Clin Electrophysiol 25: 897‐906, 2002.
 80.Ernst J, Grundey J, Hewitt M, von Lewinski F, Kaus J, Schmalz T, Rohde V, Liebetanz D. Towards physiological ankle movements with the ActiGait implantable drop foot stimulator in chronic stroke. Restor Neurol Neurosci 31: 557‐569, 2013.
 81.Ethier C, Oby ER, Bauman MJ, Miller LE. Restoration of grasp following paralysis through brain‐controlled stimulation of muscles. Nature 485: 368‐371, 2012.
 82.Fang J, Shaw K, George M. Prevalence of Stroke — United States, 2006–2010. In: Morbidity and Mortality Weekly Report (MMWR) Centres for Disease Control and Prevention, 2012, pp. 379‐382.
 83.Fasano A, Lozano AM, Cubo E. New neurosurgical approaches for tremor and Parkinson's disease. Curr Opin Neurol 30: 435‐446, 2017.
 84.Fattahi P, Yang G, Kim G, Abidian MR. A review of organic and inorganic biomaterials for neural interfaces. Adv Mater 26: 1846‐1885, 2014.
 85.Fawcett JW, Curt A, Steeves JD, Coleman WP, Tuszynski MH, Lammertse D, Bartlett PF, Blight AR, Dietz V, Ditunno J, Dobkin BH, Havton LA, Ellaway PH, Fehlings MG, Privat A, Grossman R, Guest JD, Kleitman N, Nakamura M, Gaviria M, Short D. Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: Spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials. Spinal Cord 45: 190‐205, 2007.
 86.Ferrier D. The Functions of the Brain. New York: Putnam's, 1886, p. 498.
 87.Field‐Fote EC. Electrical stimulation modifies spinal and cortical neural circuitry. Exerc Sport Sci Rev 32: 155‐160, 2004.
 88.Finetech. Developments in Functional Electrical Stimulation Systems Finetech Medical. http://finetech-medical.co.uk/en-us/articles/developmentsinfunctionalelectricalstimulation.aspx. [30 January, 2015].
 89.Fjorback MV, van Rey FS, van der Pal F, Rijkhoff NJ, Petersen T, Heesakkers JP. Acute urodynamic effects of posterior tibial nerve stimulation on neurogenic detrusor overactivity in patients with MS. Eur Urol 51: 464‐470; discussion 471‐462, 2007.
 90.Flint RD, Rosenow JM, Tate MC, Slutzky MW. Continuous decoding of human grasp kinematics using epidural and subdural signals. J Neural Eng 14: 016005, 2017.
 91.Foley N, Cotoi A, Serrato J, Mirkowski M, Harris J, Dukelow S, Sequeira K, Knutson J, Chae J, Teasell R. Evidence‐based review of stroke rehabilitation. 10. Upper extremity interventions Toronto: Canadian Stroke Network, 2016.
 92.Forrest GP, Smith TC, Triolo RJ, Gagnon JP, DiRisio D, Miller ME, Murray L, Davis JA, Iqbal A. Energy cost of the case Western reserve standing neuroprosthesis. Arch Phys Med Rehabil 88: 1074‐1076, 2007.
 93.Francisco G, Chae J, Chawla H, Kirshblum S, Zorowitz R, Lewis G, Pang S. Electromyogram‐triggered neuromuscular stimulation for improving the arm function of acute stroke survivors: A randomized pilot study. Arch Phys Med Rehabil 79: 570‐575, 1998.
 94.Friedman H, Nashold BS, Jr., Senechal P. Spinal cord stimulation and bladder function in normal and paraplegic animals. J Neurosurg 36: 430‐437, 1972.
 95.Fritsch G, Hitzig E. Ueber die elektrische Erregbarkeit des Grosshirns (On the Electrical Excitability of the Cerebrum). Arch fuer Anat Physiol und wissenschaftl Mediz, Leipzig 37: 300‐332, 1870.
 96.Gad P, Gerasimenko Y, Zdunowski S, Turner A, Sayenko D, Lu DC, Edgerton VR. Weight bearing over‐ground stepping in an exoskeleton with non‐invasive spinal cord neuromodulation after motor complete paraplegia. Front Neurosci 11: 333, 2017.
 97.Gallien P, Brissot R, Eyssette M, Tell L, Barat M, Wiart L, Petit H. Restoration of gait by functional electrical stimulation for spinal cord injured patients. Paraplegia 33: 660‐664, 1995.
 98.Gan LS, Bornes T, Denington A, Prochazka A. The stimulus router: A novel means of directing current from surface electrodes to nerves. In: 10th Annual Conference of the International FES Society. Montreal, Canada, 2005.
 99.Gan LS, Prochazka A. Properties of the stimulus router system, a novel neural prosthesis. IEEE Trans Biomed Eng 57: 450‐459, 2010.
 100.Gan LS, Prochazka A, Bornes TD, Denington AA, Chan KM. A new means of transcutaneous coupling for neural prostheses. IEEE Trans Biomed Eng 54: 509‐517, 2007.
 101.Gan LS, Ravid E, Kowalczewski JA, Olson JL, Morhart M, Prochazka A. First permanent implant of nerve stimulation leads activated by surface electrodes, enabling hand grasp and release: The stimulus router neuroprosthesis. Neurorehabil Neural Repair 26: 335‐343, 2012.
 102.Gaunt R. Electrical stimulation techniques to restore bladder and sphincter control after spinal cord injury. In: Biomedical Engineering. Edmonton: University of Alberta (Canada), 2008, p. 203.
 103.Gaunt RA, Prochazka A. Control of urinary bladder function with devices: Successes and failures. Prog Brain Res 152: 163‐194, 2006.
 104.Gaunt RA, Prochazka A. Activation and blockade of the pudendal nerve using transcutaneously coupled electrical stimulation. In: Society for Neuroscience Online. San Diego, CA, 2007.
 105.Gaunt RA, Prochazka A. High‐frequency blockade of the pudendal nerve using a transcutaneously coupled stimulator in a chronically implanted cat. In: Proceedings of the 12th Annual Meeting of the International Functional Electrical Stimulation Society, Philadelphia, PA, 2007.
 106.Gaunt RA, Prochazka A, Mushahwar VK, Guevremont L, Ellaway PH. Intraspinal microstimulation excites multisegmental sensory afferents at lower stimulus levels than local alpha‐motoneuron responses. J Neurophysiol 96: 2995‐3005, 2006.
 107.Gerasimenko YP, Makarovskii AN, Nikitin OA. Control of locomotor activity in humans and animals in the absence of supraspinal influences. Neurosci Behav Physiol 32: 417‐423, 2002.
 108.Girsch W, Koller R, Holle J, Bijak M, Lanmuller H, Mayr W, Thoma H. Vienna phrenic pacemaker–experience with diaphragm pacing in children. Eur J Pediatr Surg 6: 140‐143, 1996.
 109.Glenn WW, Phelps ML, Elefteriades JA, Dentz B, Hogan JF. Twenty years of experience in phrenic nerve stimulation to pace the diaphragm. Pacing Clin Electrophysiol 9: 780‐784, 1986.
 110.Grandview‐Research. Neurostimulation Devices Market Analysis By Product (Deep Brain Stimulators, Gastric Electric Stimulators, Spinal Cord Stimulators, Sacral Nerve Stimulators, Vagus Nerve Stimulators), By Application (Pain Management, Epilepsy, Essential Tremor, Urinary & Fecal Incontinence, Depression, Dystonia, Gastroparesis, Parkinson's Disease, Other Diseases), And Segment Forecasts To 2024 San Francisco: Grandview Research Inc., 2016.
 111.Graupe D, Kohn KH, Basseas SP. Control of electrically‐stimulated walking of paraplegicsvia above‐ and below‐lesion EMG signature identification. IEEE Trans Automatic Control 34: 130‐138, 1989.
 112.Graupe D, Kohn KH, Kralj A, Basseas S. Patient controlled electrical stimulation via EMG signature discrimination for providing certain paraplegics with primitive walking functions. J Biomed Eng 5: 220‐226, 1983.
 113.Greatbatch W. Medical cardiac pacemaker. Edited by USPTO. USA: Wilson Greatbatch Inc., 1962.
 114.Grill WM, Bhadra N, Wang B. Bladder and urethral pressures evoked by microstimulation of the sacral spinal cord in cats. Brain Research 836: 19‐30, 1999.
 115.Guevremont L, Renzi CG, Norton JA, Kowalczewski J, Saigal R, Mushahwar VK. Locomotor‐related networks in the lumbosacral en-largement of the adult spinal cat: Activation through intraspinal microstimulation. IEEE Trans Neural Syst Rehabil Eng 14: 266‐272, 2006.
 116.Hall SW. Commercializing neuroprostheses: The business of putting the brain back in business. N.J.: Princeton University, 2003, p. 185.
 117.Hansen GvO. EMG‐controlled functional electrical stimulation of the paretic hand. Scand J Rehabil Med 11: 189‐193, 1979.
 118.Hansen M, Haugland M, Sinkjaer T, Donaldson N. Real time foot drop correction using machine learning and natural sensors. Neuromodulation 5: 41‐53, 2002.
 119.Harkema S, Gerasimenko Y, Hodes J, Burdick J, Angeli C, Chen Y, Ferreira C, Willhite A, Rejc E, Grossman RG, Edgerton VR. 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, 2011.
 120.Hassouna MM, Siegel SW, Nyeholt AA, Elhilali MM, van Kerrebroeck PE, Das AK, Gajewski JB, Janknegt RA, Rivas DA, Dijkema H, Milam DF, Oleson KA, Schmidt RA. Sacral neuromodulation in the treatment of urgency‐frequency symptoms: A multicenter study on efficacy and safety. J Urol 163: 1849‐1854, 2000.
 121.Haugland M, Sinkjaer T. Interfacing the body's own sensing receptors into neural prosthesis devices. Technol Health Care 7: 393‐399, 1999.
 122.Heckmann J, Mokrusch T, Kroeckel A, Warnke S, von Stockert T, Neundoerfer B. Electromyogram‐triggered neuromuscular stimulation for improving the arm function of acute stroke survivors: A randomized pilot study. Eur J Phys Med Rehabil 7: 138‐141, 1997.
 123.Heesakkers J, Digesu GA, van Breda J, Van Kerrebroeck P, Elneil S. A novel leadless, miniature implantable Tibial Nerve Neuromodulation System for the management of overactive bladder complaints. Neurourol Urodyn 37: 1060‐1067, 2018.
 124.Heilman BP, Audu ML, Kirsch RF, Triolo RJ. Selection of an optimal muscle set for a 16‐channel standing neuroprosthesis using a human musculoskeletal model. J Rehabil Res Dev 43: 273‐286, 2006.
 125.Heine JP, Schmidt RA, Tanagho EA. Intraspinal sacral root stimulation for controlled micturition. Invest Urol 15: 78‐82, 1977.
 126.Helmholtz HLF. Messungen über den zeitlichen Verlauf der Zuckung animalischer Muskeln und die Fortpflanzungsgeschwindigkeit der Reizung in den Nerven. Archiv für Anatomie, Physiologie und wissenschaftliche Medicin Jahrgang 1850: 276‐364, 1850.
 127.Henneman E. The size‐principle: A deterministic output emerges from a set of probabilistic connections. J Exp Biol 115: 105‐112, 1985.
 128.Henneman E, Clamann HP, Gillies JD, Skinner RD. Rank order of motoneurons within a pool: Law of combination. J Neurophysiol 37: 1338‐1349, 1974.
 129.Herman R, He J, D'Luzansky S, Willis W, Dilli S. Spinal cord stimulation facilitates functional walking in a chronic, incomplete spinal cord injured. Spinal Cord 40: 65‐68, 2002.
 130.Herrington TM, Cheng JJ, Eskandar EN. Mechanisms of deep brain stimulation. J Neurophysiol 115: 19‐38, 2016.
 131.Hincapie JG, Kirsch RF. EMG‐based control for a C5/C6 spinal cord injury upper extremity neuroprosthesis. Conf Proc IEEE Eng Med Biol Soc 2007: 2432‐2435, 2007.
 132.Hodgson JA. Electrode array for muscle stimulation and recording. United States Patent Office, Patent # 4,619,266 1‐5, 1986.
 133.Hoffer JA, Baru M, Bedard S, Calderon E, Desmoulin G, Dhawan P, Jenne G, Kerr J, Whittaker M, Zwimpfer TJ. Initial results with fully implanted NeurostepTM FES system for foot drop. In: 10th Annual Conference of the International FES Society, 2005.
 134.Hoffer JA, Sinkjaer T. A natural ‘force sensor’ suitable for closed‐loop control of functional neuromuscular stimulation. In: Proc 2nd Vienna International Workshop on Functional Electrostimulation, 1986, pp. 47‐50.
 135.Hoffer JA, Stein RB, Haugland MK, Sinkjaer T, Durfee WK, Schwartz AB, Loeb GE, Kantor C. Neural signals for command control and feedback in functional neuromuscular stimulation: A review. J Rehabil Res Dev 33: 145‐157, 1996.
 136.Hoffer JA, Tran BD, Tang JK, Saunders JTW, Francis CA, Sandoval RA, Meyyappan R, Seru S, Wang HDY, Nolette MA, Tanner AC. Diaphragm pacing with endovascular electrodes. In: IFESS 2010 ‐ International Functional Electrical Stimulation Society 15th Annual Conference. Vienna, Austria: 2010, pp. 40‐42.
 137.Hoffmann P. Untersuchungen ueber die Eigenreflexe (Sehnenreflexe) menschlicher Muskeln. Berlin: Springer, 1922.
 138.Hotson G, McMullen DP, Fifer MS, Johannes MS, Katyal KD, Para MP, Armiger R, Anderson WS, Thakor NV, Wester BA, Crone NE. Individual finger control of a modular prosthetic limb using high‐density electrocorticography in a human subject. J Neural Eng 13: 026017, 2016.
 139.Hubscher CH, Herrity AN, Williams CS, Montgomery LR, Willhite AM, Angeli CA, Harkema SJ. Improvements in bladder, bowel and sexual outcomes following task‐specific locomotor training in human spinal cord injury. PLoS One 13: e0190998, 2018.
 140.Hulliger M. The mammalian muscle spindle and its central control. [Review]. Rev Physiol Biochem Pharmacol 101: 1‐110, 1984.
 141.Ininc. Walkaide and Footdrop walkaide.com.
 142.Jaeger RJ. Lower extremity applications of functional neuromuscular stimulation. Assist Technol 4: 19‐30, 1992.
 143.Janssen DA, Farag F, Heesakkers JP. Urgent‐SQ implant in treatment of overactive bladder syndrome: 9‐year follow‐up study. Neurourol Urodyn 32: 472‐475, 2012.
 144.Jeglic A, Vanken E, Benedik M. Implantable muscle/nerve stimulator as part of an electronic brace. In: 3rd International Symposium on External Control of Human Extremities. Nauka: Yugoslav Committee for Electronics and Automation, Belgrade, 1970, pp. 593‐603.
 145.Jilge B, Minassian K, Rattay F, Pinter MM, Gerstenbrand F, Binder H, Dimitrijevic MR. Initiating extension of the lower limbs in subjects with complete spinal cord injury by epidural lumbar cord stimulation. Exp Brain Res 154: 308‐326, 2004.
 146.Johnson V, Eiseman B. Reinforcement of ventilation with electrophrenic pacing of the paralyzed diaphragm. J Thorac Cardiovasc Surg 62: 651‐657, 1971.
 147.Jonas U, Tanagho EA. Studies on the feasibility of urinary bladder evacuation by direct spinal cord stimulation. II. Poststimulus voiding: A way to overcome outflow resistance. Invest Urol 13: 151‐153, 1975.
 148.Jorgenson LA, Newsome WT, Anderson DJ, Bargmann CI, Brown EN, Deisseroth K, Donoghue JP, Hudson KL, Ling GS, MacLeish PR, Marder E, Normann RA, Sanes JR, Schnitzer MJ, Sejnowski TJ, Tank DW, Tsien RY, Ugurbil K, Wingfield JC. The BRAIN Initiative: Developing technology to catalyse neuroscience discovery. Philos Trans R Soc Lond B Biol Sci 370: 2015.
 149.Kapadia N, Zivanovic V, Popovic MR. Restoring voluntary grasping function in individuals with incomplete chronic spinal cord injury: Pilot study. Top Spinal Cord Inj Rehabil 19: 279‐287, 2013.
 150.Kenney L, Bultstra G, Buschman R, Taylor P, Mann G, Hermens H, Holsheimer J, Nene A, Tenniglo M, van der Aa H, Hobby J. An implantable two channel drop foot stimulator: Initial clinical results. Artif Organs 26: 267‐270, 2002.
 151.Kent CW. Electric massage machine. In: USPTO, edited by Office UP. USA: 1919, p. 4.
 152.Kern H, Carraro U. Home‐based functional electrical stimulation for long‐term denervated human muscle: History, basics, results and perspectives of the Vienna Rehabilitation Strategy. Eur J Transl Myol 24: 3296, 2014.
 153.Kern H, Salmons S, Mayr W, Rossini K, Carraro U. Recovery of long‐term denervated human muscles induced by electrical stimulation. Muscle Nerve 31: 98‐101, 2005.
 154.Khaslavskaia S, Klucharev V, Chen AC, Sinkjaer T. The effect of repetitive electrical stimulation on the motor evoked hemodynamic responses. Int J Neurosci 116: 331‐349, 2006.
 155.Khaslavskaia S, Sinkjaer T. Motor cortex excitability following repetitive electrical stimulation of the common peroneal nerve depends on the voluntary drive. Exp Brain Res 162: 497‐502, 2005.
 156.Kilgore KL, Bhadra N. Nerve conduction block utilising high‐frequency alternating current. Med Biol Eng Comput 42: 394‐406, 2004.
 157.Klose KJ, Jacobs PL, Broton JG, Guest RS, Needham‐Shropshire BM, Lebwohl N, Nash MS, Green BA. Evaluation of a training program for persons with SCI paraplegia using the Parastep 1 ambulation system: Part 1. Ambulation performance and anthropometric measures. Arch Phys Med Rehabil 78: 789‐793, 1997.
 158.Kluding PM, Dunning K, O'Dell MW, Wu SS, Ginosian J, Feld J, McBride K. Foot drop stimulation versus ankle foot orthosis after stroke: 30‐week outcomes. Stroke 44: 1660‐1669, 2013.
 159.Knutson JS, Fu MJ, Sheffler LR, Chae J. Neuromuscular electrical stimulation for motor restoration in hemiplegia. Phys Med Rehabil Clin N Am 26: 729‐745, 2015.
 160.Kottink AI, Buschman HP, Kenney LP, Veltink PH, Slycke P, Bultstra G, Hermens HJ. The sensitivity and selectivity of an implantable two‐channel peroneal nerve stimulator system for restoration of dropped foot. Neuromodulation 7: 277‐283, 2004.
 161.Kowalczewski J. Adjustable tissue or nerve cuff and method of use. In: USPTO. USA: 2009, pp. 1‐18.
 162.Kowalczewski J, Chong SL, Galea M, Prochazka A. In‐home tele‐rehabilitation improves tetraplegic hand function. Neurorehabil Neural Repair 25: 412‐422, 2011.
 163.Kowalczewski J, Prochazka A. Technology improves upper extremity rehabilitation. Prog Brain Res 192: 147‐159, 2011.
 164.Kozai TD, Catt K, Du Z, Na K, Srivannavit O, Haque RU, Seymour J, Wise KD, Yoon E, Cui XT. Chronic in vivo evaluation of PEDOT/CNT for stable neural recordings. IEEE Trans Biomed Eng 63: 111‐119, 2016.
 165.Kralj A, Vodovnik L. Functional electrical stimulation of the extremities: Part 1. J Med Eng Technol 1: 12‐15, 1977.
 166.Kralj AR, Bajd T. Functional Electrical Stimulation: Standing and Walking after Spinal Cord Injury. Boca Raton, FL: CRC Press, 1989, p. 198.
 167.Ladenbauer J, Minassian K, Hofstoetter US, Dimitrijevic MR, Rattay F. Stimulation of the human lumbar spinal cord with implanted and surface electrodes: A computer simulation study. IEEE Trans Neural Syst Rehabil Eng 18: 637‐645, 2010.
 168.Lam T, Wolfe DL, Domingo A, Eng JJ, Sproule S. Lower limb rehabilitation following spinal cord injury. In: SCIRE Project (Spinal Cord Injury Rehabilitation Evidence). Vancouver, B.C.: Monkey Hill Health Communications, 2010, pp. 1‐73.
 169.Lau B, Guevremont L, Mushahwar VK. Strategies for generating prolonged functional standing using intramuscular stimulation or intraspinal microstimulation. IEEE Trans Neural Syst Rehabil Eng 15: 273‐285, 2007.
 170.Le Pimpec‐Barthes F, Legras A, Arame A, Pricopi C, Boucherie JC, Badia A, Panzini CM. Diaphragm pacing: The state of the art. J Thorac Dis 8: S376‐S386, 2016.
 171.Lee DJ, Elias GJB, Lozano AM. Neuromodulation for the treatment of eating disorders and obesity. Ther Adv Psychopharmacol 8: 73‐92, 2018.
 172.Lee YH, Creasey GH. Self‐controlled dorsal penile nerve stimulation to inhibit bladder hyperreflexia in incomplete spinal cord injury: A case report. Arch Phys Med Rehabil 83: 273‐277, 2002.
 173.Leuthardt EC, Miller KJ, Schalk G, Rao RP, Ojemann JG. Electrocorticography‐based brain computer interface‐‐‐the Seattle experience. IEEE Trans Neural Syst Rehabil Eng 14: 194‐198, 2006.
 174.Liberson WT, Holmquest HJ, Scot D, Dow M. Functional electrotherapy: Stimulation of the peroneal nerve synchronized with the swing phase of the gait of hemiplegic patients. Arch Phys Med Rehabil 42: 101‐105, 1961.
 175.Licht SH. Electrodiagnosis and Electromyography. New Haven: Licht, E., 1971, p. 533.
 176.Liu J, Li X, Marciniak C, Rymer WZ, Zhou P. Extraction of neural control commands using myoelectric pattern recognition: A novel application in adults with cerebral palsy. Int J Neural Syst 24: 1450022, 2014.
 177.Llewellyn ME, Thompson KR, Deisseroth K, Delp SL. Orderly recruitment of motor units under optical control in vivo. Nat Med 16: 1161‐1165, 2010.
 178.Manella KJ, Field‐Fote EC. Modulatory effects of locomotor training on extensor spasticity in individuals with motor‐incomplete spinal cord injury. Restor Neurol Neurosci 31: 633‐646, 2013.
 179.Marquez‐Chin C, Bagher S, Zivanovic V, Popovic MR. Functional electrical stimulation therapy for severe hemiplegia: Randomized control trial revisited. Can J Occup Ther 84: 87‐97, 2017.
 180.Marsden CD, Meadows JC, Merton PA. “Muscular wisdom” that minimizes fatigue during prolonged effort in man: Peak rates of motoneuron discharge and slowing of discharge during fatigue. Advances in Neurology 39: 169‐211, 1983.
 181.Marsolais EB, Kobetic R. Functional walking in paralyzed patients by means of electrical stimulation. Clin Orthop Relat Res 175: 30‐36, 1983.
 182.Marsolais EB, Kobetic R. Development of a practical electrical stimulation system for restoring gait in the paralyzed patient. Clin Orthop 233: 64‐74, 1988.
 183.Martens FM, den Hollander PP, Snoek GJ, Koldewijn EL, van Kerrebroeck PE, Heesakkers JP. Quality of life in complete spinal cord injury patients with a Brindley bladder stimulator compared to a matched control group. Neurourol Urodyn 30: 551‐555, 2011.
 184.Martin KD, Polanski WH, Schulz AK, Jobges M, Ziemssen T, Schackert G, Pinzer T, Sobottka SB. ActiGait implantable drop foot stimulator in multiple sclerosis: A new indication. J Neurosurg 126: 1685‐1690, 2017.
 185.Matthews PBC. Mammalian Muscle Receptors and Their Central Actions. London: Edward Arnold, 1972, p. 630.
 186.McBride K. Overactive Bladder Treatment Using StimRouter Neuromodulation System: A Prospective Randomized Trial clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT02873312?term=stimrouter&rank=2. [24 January 2017, 2017].
 187.McCreery DB, Agnew WF. Mechanisms of stimulation‐induced neural damage and their relation to guidelines for safe stimulation. In: Agnew WF, McCreery DB, editors. Neural Prostheses Fundamental Studies. Englewood Cliffs, NJ: Prentice Hall, 1990, pp. 297‐317.
 188.McCreery DB, Agnew WF, Yuen TG, Bullara L. Charge density and charge per phase as cofactors in neural injury induced by electrical stimulation. IEEE Trans Biomed Eng 37: 996‐1001, 1990.
 189.McCreery DB, Agnew WF, Yuen TG, Bullara LA. Relationship between stimulus amplitude, stimulus frequency and neural damage during electrical stimulation of sciatic nerve of cat. Med Biol Eng Comput 33: 426‐429, 1995.
 190.McGee MJ, Amundsen CL, Grill WM. Electrical stimulation for the treatment of lower urinary tract dysfunction after spinal cord injury. J Spinal Cord Med 38: 135‐146, 2015.
 191.McNeal D. 2000 years of electrical stimulation. In: Hambrecht FT, Reswick, J.B, editors. Functional Electrical Stimulation. N.Y.: Dekker, 1977, pp. 3‐35.
 192.McNeal DR, Waters R, Reswick J. Experience with implanted electrodes. Neurosurgery 1: 228‐229, 1977.
 193.Mercier LM, Gonzalez‐Rothi EJ, Streeter KA, Posgai SS, Poirier AS, Fuller DD, Reier PJ, Baekey DM. Intraspinal microstimulation and diaphragm activation after cervical spinal cord injury. J Neurophysiol 117: 767‐776, 2017.
 194.Merrill DR, Bikson M, Jefferys JG. Electrical stimulation of excitable tissue: Design of efficacious and safe protocols. J Neurosci Methods 141: 171‐198, 2005.
 195.Midha M, Schmitt JK. Epidural spinal cord stimulation for the control of spasticity in spinal cord injury patients lacks long‐term efficacy and is not cost‐effective. Spinal Cord 36: 190‐192, 1998.
 196.Milosevic L, Kalia SK, Hodaie M, Lozano AM, Fasano A, Popovic MR, Hutchison WD. Neuronal inhibition and synaptic plasticity of basal ganglia neurons in Parkinson's disease. Brain 141: 177‐190, 2018.
 197.Minassian K, Hofstoetter US, Danner SM, Mayr W, Bruce JA, McKay WB, Tansey KE. Spinal rhythm generation by step‐induced feedback and transcutaneous posterior root stimulation in complete spinal cord‐injured individuals. Neurorehabil Neural Repair 30: 233‐243, 2016.
 198.Mogilner AY. Chapter 12 ‐ Neuromodulation and Neuronal Plasticity A2 ‐ Krames, Elliot S. In: Peckham PH, Rezai AR, editors. Neuromodulation. San Diego: Academic Press, 2009, pp. 123‐130.
 199.Moraud EM, von Zitzewitz J, Miehlbradt J, Wurth S, Formento E, DiGiovanna J, Capogrosso M, Courtine G, Micera S. Closed‐loop control of trunk posture improves locomotion through the regulation of leg proprioceptive feedback after spinal cord injury. Sci Rep 8: 76, 2018.
 200.Moritz CT, Lucas TH, Perlmutter SI, Fetz EE. Forelimb movements and muscle responses evoked by microstimulation of cervical spinal cord in sedated monkeys. J Neurophysiol 97: 110‐120, 2007.
 201.Mortimer JT. Motor prostheses. In: Brooks VB, editor. Handbook of Physiology Section 1: The Nervous System. Bethesda, MD: American Physiological Society, 1981, pp. 155‐187.
 202.Mortimer JT. Electrical excitation of nerve. In: Agnew WF, McCreery DB, editors. Neural Prostheses Fundamental Studies. Englewood Cliffs, NJ: Prentice Hall, 1990, pp. 67‐83.
 203.Mortimer JT, Kicher TP, Daroux M. Electrodes for functional neuromuscular stimulation, N01‐NS‐7‐2396 Bethesda, Md.: National Institutes of Health, 1991.
 204.Moya P, Parra P, Arroyo A, Pena E, Benavides J, Calpena R. Sacral nerve stimulation versus percutaneous posterior tibial nerve stimulation in the treatment of severe fecal incontinence in men. Tech Coloproctol 20: 317‐319, 2016.
 205.Mushahwar VK, Aoyagi Y, Stein RB, Prochazka A. Movements generated by intraspinal microstimulation in the intermediate gray matter of the anesthetized, decerebrate, and spinal cat. Can J Physiol Pharmacol 82: 702‐714, 2004.
 206.Mushahwar VK, Collins DF, Prochazka A. Spinal cord microstimulation generates functional limb movements in chronically implanted cats. Exp Neurol 163: 422‐429, 2000.
 207.Mushahwar VK, Gillard DM, Gauthier MJ, Prochazka A. Intraspinal micro stimulation generates locomotor‐like and feedback‐controlled movements. IEEE Trans Neural Syst Rehabil Eng 10: 68‐81, 2002.
 208.Mushahwar VK, Horch KW. Selective activation of functional muscle groups through stimulation of spinal motor pools. In: Proc 15th Ann Intl Conf IEEE Eng Med Biol Soc. San Diego, CA, 1993.
 209.Mushahwar VK, Horch KW. Muscle recruitment through electrical stimulation of the lumbo‐sacral spinal cord. IEEE Trans Rehabil Eng 8: 22‐29, 2000.
 210.Musienko P, Heutschi J, Friedli L, van den Brand R, Courtine G. Multi‐system neurorehabilitative strategies to restore motor functions following severe spinal cord injury. Exp Neurol 235: 100‐109, 2012.
 211.Nashold BS. Dorsal column stimulation for control of pain: A three‐year follow‐up. Surg Neurol 4: 146‐147, 1975.
 212.Nashold BS, Friedman H, Glenn JF, Grimes JH, Barry WF, Avery R. Electromicturition in paraplegia: Implantation of a spinal neuroprosthesis. Proc Veterans Adm Spinal Cord Inj Conf 18: 161‐165, 1971.
 213.Nashold BS, Jr., Friedman H, Boyarsky S. Electrical activation of micturition by spinal cord stimulation. J Surg Res 11: 144‐147, 1971.
 214.Nashold BS, Jr., Friedman H, Glenn JF, Grimes JH, Barry WF, Avery R. Electromicturition in paraplegia. Implantation of a spinal neuroprosthesis. Arch Surg 104: 195‐202, 1972.
 215.Nashold BS, Jr., Friedman H, Grimes J. Electrical stimulation of the conus medullaris to control the bladder in the paraplegic patient. A 10‐year review. Appl Neurophysiol 44: 225‐232, 1981.
 216.Nathan RH. US Patent #5,330,516. Device for generating hand function. US Patent Office 15 claims, 16 drawing sheets, 1994.
 217.Nordhausen CT, Rousche PJ, Normann RA. Optimizing recording capabilities of the Utah Intracortical Electrode Array. Brain Res 637: 27‐36, 1994.
 218.Odstock. http://www.odstockmedical.com/products http://www.odstockmedical.com/products.
 219.Onders RP, Elmo M, Khansarinia S, Bowman B, Yee J, Road J, Bass B, Dunkin B, Ingvarsson PE, Oddsdottir M. Complete worldwide operative experience in laparoscopic diaphragm pacing: Results and differences in spinal cord injured patients and amyotrophic lateral sclerosis patients. Surg Endosc 23: 1433‐1440, 2009.
 220.Onders RP, Markowitz A, Ho VP, Hardacre J, Novitsky Y, Towe C, Elmo M, Kaplan C, Schilz R. Completed FDA feasibility trial of surgically placed temporary diaphragm pacing electrodes: A promising option to prevent and treat respiratory failure. Am J Surg 215: 518‐521, 2017.
 221.Ottobock. Otto Bock MyGait https://www.ottobock.com/en/.
 222.Page SJ, Levin L, Hermann V, Dunning K, Levine P. Longer versus shorter daily durations of electrical stimulation during task‐specific practice in moderately impaired stroke. Arch Phys Med Rehabil 93: 200‐206, 2012.
 223.Pathak AS, Aboseif SR. Overactive bladder: Drug therapy versus nerve stimulation. Nat Clin Pract Urol 2: 310‐311, 2005.
 224.Peckham PH, Creasey GH. Neural prostheses: Clinical applications of functional electrical stimulation in spinal cord injury. Paraplegia 30: 96‐101, 1992.
 225.Peckham PH, Keith MW, Kilgore KL, Grill JH, Wuolle KS, Thrope GB, Gorman P, Hobby J, Mulcahey MJ, Carroll S, Hentz VR, Wiegner A, Implantable Neuroprosthesis Research G. Efficacy of an implanted neuroprosthesis for restoring hand grasp in tetraplegia: A multicenter study. Arch Phys Med Rehabil 82: 1380‐1388, 2001.
 226.Peckham PH, Kilgore KL. Challenges and opportunities in restoring function after paralysis. IEEE Trans Biomed Eng 60: 602‐609, 2013.
 227.Peckham PH, Poon CW, Ko WH, Marsolais EB, Rosen JJ. Multichannel implantable stimulator for control of paralyzed muscle. IEEE Trans Biomed Eng 28: 530‐536, 1981.
 228.Penfield W. Some observations on the cerebral cortex of man. Proc R Soc Lond B Biol Sci 134: 329‐347, 1947.
 229.Perge JA, Homer ML, Malik WQ, Cash S, Eskandar E, Friehs G, Donoghue JP, Hochberg LR. Intra‐day signal instabilities affect decoding performance in an intracortical neural interface system. J Neural Eng 10: 036004, 2013.
 230.Perge JA, Zhang S, Malik WQ, Homer ML, Cash S, Friehs G, Eskandar EN, Donoghue JP, Hochberg LR. Reliability of directional information in unsorted spikes and local field potentials recorded in human motor cortex. J Neural Eng 11: 046007, 2014.
 231.Peters KM, Carrico DJ, Macdiarmid SA, Wooldridge LS, Khan AU, McCoy CE, Franco N, Bennett JB. Sustained therapeutic effects of percutaneous tibial nerve stimulation: 24‐month results of the STEP study. Neurourol Urodyn 2012.
 232.Peters KM, Carrico DJ, Perez‐Marrero RA, Khan AU, Wooldridge LS, Davis GL, Macdiarmid SA. Randomized trial of percutaneous tibial nerve stimulation versus Sham efficacy in the treatment of overactive bladder syndrome: Results from the SUmiT trial. J Urol 183: 1438‐1443, 2010.
 233.Peterson EJ, Tyler DJ. Motor neuron activation in peripheral nerves using infrared neural stimulation. J Neural Eng 11: 016001, 2014.
 234.Petrofsky JS, Heaton H, III, Phillips CA. Outdoor bicycle for exercise in paraplegics and quadriplegics. J Biomed Eng 5: 292‐296, 1983.
 235.Petrofsky JS, Phillips CA. The use of functional electrical stimulation for rehabilitation of spinal cord injured patients. Cent Nerv Syst Trauma 1: 57‐74, 1984.
 236.Pfingst BE. Comparisons of psychophysical and neurophysiological studies of cochlear implants. Hear Res 34: 243‐251, 1988.
 237.Pierrot‐Deseilligny E, Mazevet D. The monosynaptic reflex: A tool to investigate motor control in humans. Interest and limits. Clin Neurophysiol 30: 67‐80, 2000.
 238.Pikov V, Bullara L, McCreery DB. Intraspinal stimulation for bladder voiding in cats before and after chronic spinal cord injury. J Neural Eng 4: 356‐368, 2007.
 239.Pinter MM, Gerstenbrand F, Dimitrijevic MR. Epidural electrical stimulation of posterior structures of the human lumbosacral cord: 3. Control Of spasticity. Spinal Cord 38: 524‐531, 2000.
 240.Polikov VS, Tresco PA, Reichert WM. Response of brain tissue to chronically implanted neural electrodes. J Neurosci Methods 148: 1‐18, 2005.
 241.Popovic D, Gordon T, Rafuse VF, Prochazka A. Properties of implanted electrodes for functional electrical stimulation. Ann Biomed Eng 19: 303‐316, 1991.
 242.Popovic D, Stojanovic A, Pjanovic A, Radosavljevic S, Popovic M, Jovic S, Vulovic D. Clinical evaluation of the bionic glove. Arch Phys Med Rehabil 80: 299‐304, 1999.
 243.Popovic Maneski L, Topalovic I, Jovicic N, Dedijer S, Konstantinovic L, Popovic DB. Stimulation map for control of functional grasp based on multi‐channel EMG recordings. Med Eng Phys 38: 1251‐1259, 2016.
 244.Popovic MR, Kapadia N, Zivanovic V, Furlan JC, Craven BC, McGillivray C. 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, 2011.
 245.Popovic MR, Thrasher TA, Adams ME, Takes V, Zivanovic V, Tonack MI. Functional electrical therapy: Retraining grasping in spinal cord injury. Spinal Cord 44: 143‐151, 2006.
 246.Posluszny JA, Jr., Onders R, Kerwin AJ, Weinstein MS, Stein DM, Knight J, Lottenberg L, Cheatham ML, Khansarinia S, Dayal S, Byers PM, Diebel L. Multicenter review of diaphragm pacing in spinal cord injury: Successful not only in weaning from ventilators but also in bridging to independent respiration. J Trauma Acute Care Surg 76: 303‐309; discussion 309‐310, 2014.
 247.Prochazka A. Proprioceptive feedback and movement regulation. In: Rowell L, Sheperd JT, editors. Handbook of Physiology Section 12 Exercise: Regulation and Integration of Multiple Systems. New York: American Physiological Society, 1996, pp. 89‐127.
 248.Prochazka A. Method and apparatus for controlling a device or process with vibrations generated by tooth clicks. U.S.A: Rehabtronics Inc, 2005, p. 13.
 249.Prochazka A. Method of routing electrical current to bodily tissues via implanted passive conductors. Canada, PCT/CA 2005/000074: Rehabtronics Inc., 2005.
 250.Prochazka A. Neurophysiology and neural engineering: A review. J Neurophysiol 118: 1292‐1309, 2017.
 251.Prochazka A, Gauthier M, Wieler M, Kenwell Z. The bionic glove: An electrical stimulator garment that provides controlled grasp and hand opening in quadriplegia. Arch Phys Med Rehabil 78: 608‐614, 1997.
 252.Prochazka A, Mushahwar V, Yakovenko S. Activation and coordination of spinal motoneuron pools after spinal cord injury. Prog Brain Res 137: 109‐124, 2002.
 253.Prochazka A, Mushahwar VK. Voluntary muscle contractions can be boosted by spinal cord microstimulation. J Physiol 525P: 6S, 2000.
 254.Prochazka A, Wieler M, Kenwell Z. Garment for applying controlled electrical stimulation to restore motor function. US Patent Number 5,562,707, 1996.
 255.Rack PM, Westbury DR. The effects of length and stimulus rate on tension in the isometric cat soleus muscle. J Physiol 204: 443‐460, 1969.
 256.Rattay F, Minassian K, Dimitrijevic MR. Epidural electrical stimulation of posterior structures of the human lumbosacral cord: 2. quantitative analysis by computer modeling. Spinal Cord 38: 473‐489, 2000.
 257.Rattay F, Resatz S, Lutter P, Minassian K, Jilge B, Dimitrijevic MR. Mechanisms of electrical stimulation with neural prostheses. Neuromodulation 6: 42‐56, 2003.
 258.Rebersek S, Vodovnik L. Proportionally controlled functional electrical stimulation of hand. Arch Phys Med Rehabil 54: 378‐382, 1973.
 259.Rejc E, Angeli CA, Atkinson D, Harkema SJ. Motor recovery after activity‐based training with spinal cord epidural stimulation in a chronic motor complete paraplegic. Sci Rep 7: 13476, 2017.
 260.Reynolds S, Ebner A, Meffen T, Thakkar V, Gani M, Taylor K, Clark L, Sadarangani G, Meyyappan R, Sandoval R, Rohrs E, Hoffer JA. Diaphragm activation in ventilated patients using a novel transvenous phrenic nerve pacing catheter. Crit Care Med 45: e691‐e694, 2017.
 261.Rijkhoff NJ. Neuroprostheses to treat neurogenic bladder dysfunction: Current status and future perspectives. Childs Nerv Syst 20: 75‐86, 2004.
 262.Ring H, Treger I, Gruendlinger L, Hausdorff JM. Neuroprosthesis for footdrop compared with an ankle‐foot orthosis: Effects on postural control during walking. J Stroke Cerebrovasc Dis 18: 41‐47, 2009.
 263.Robblee LS, Rose TL. Electrochemical guidelines for selection of protocols and electrode materials for neural stimulation. In: Agnew WF, McCreery DB, editors. Neural Prostheses Fundamental Studies. Englewood Cliffs, NJ: Prentice Hall, 1990, pp. 25‐66.
 264.Scheiner A, Mortimer JT, Roessmann U. Imbalanced biphasic electrical stimulation: Muscle tissue damage. Ann Biomed Eng 18: 407‐425, 1990.
 265.Schiemanck S, Berenpas F, van Swigchem R, van den Munckhof P, de Vries J, Beelen A, Nollet F, Geurts AC. Effects of implantable peroneal nerve stimulation on gait quality, energy expenditure, participation and user satisfaction in patients with post‐stroke drop foot using an ankle‐foot orthosis. Restor Neurol Neurosci 33: 795‐807, 2015.
 266.Schmidt RA, Senn E, Tanagho EA. Functional evaluation of sacral nerve root integrity. Report of a technique. Urology 35: 388‐392, 1990.
 267.Schwen Z, Matsuta Y, Shen B, Wang J, Roppolo JR, de Groat WC, Tai C. Combination of foot stimulation and tolterodine treatment eliminates bladder overactivity in cats. Neurourol Urodyn 33: 1266‐1271, 2013.
 268.Sdrulla A, Chen G. Minimally invasive procedures for neuropathic pain. Pain Manag 6: 103‐109, 2016.
 269.Sharma M, Marsolais EB, Polando G, Triolo RJ, Davis JA, Jr., Bhadra N, Uhlir JP. Implantation of a 16‐channel functional electrical stimulation walking system. Clin Orthop Relat Res 236‐242, 1998.
 270.Sharpe AN, Jackson A. Upper‐limb muscle responses to epidural, subdural and intraspinal stimulation of the cervical spinal cord. J Neural Eng 11: 016005, 2014.
 271.Shealy CN. Dorsal column stimulation: Optimization of application. Surg Neurol 4: 142‐145, 1975.
 272.Shealy CN. The viability of external electrical stimulation as a therapeutic modality. Med Instrum 9: 211‐212, 1975.
 273.Shealy CN, Mortimer JT, Reswick JB. Electrical inhibition of pain by stimulation of the dorsal columns: Preliminary clinical report. Anesth Analg 46: 489‐491, 1967.
 274.Sheffler LR, Hennessey MT, Naples GG, Chae J. Peroneal nerve stimulation versus an ankle foot orthosis for correction of footdrop in stroke: Impact on functional ambulation. Neurorehabil Neural Repair 20: 355‐360, 2006.
 275.Sherrington CS. Flexion‐reflex of the limb, crossed extension‐reflex, and reflex stepping and standing. J Physiol 40: 28‐121, 1910.
 276.Siddiqui NY, Wu JM, Amundsen CL. Efficacy and adverse events of sacral nerve stimulation for overactive bladder: A systematic review. Neurourol Urodyn 29(Suppl 1): S18‐23, 2010.
 277.Siegel S, Noblett K, Mangel J, Griebling TL, Sutherland SE, Bird ET, Comiter C, Culkin D, Bennett J, Zylstra S, Berg KC, Kan F, Irwin CP. Results of a prospective, randomized, multicenter study evaluating sacral neuromodulation with InterStim therapy compared to standard medical therapy at 6‐months in subjects with mild symptoms of overactive bladder. Neurourol Urodyn 34: 224‐230, 2014.
 278.Simeral JD, Kim SP, Black MJ, Donoghue JP, Hochberg LR. Neural control of cursor trajectory and click by a human with tetraplegia 1000 days after implant of an intracortical microelectrode array. J Neural Eng 8: 025027, 2011.
 279.Snoek GJ, MJ IJ, in ’t Groen FA, Stoffers TS, Zilvold G. Use of the NESS handmaster to restore handfunction in tetraplegia: Clinical experiences in ten patients. Spinal Cord 38: 244‐249, 2000.
 280.Spadone R, Merati G, Bertocchi E, Mevio E, Veicsteinas A, Pedotti A, Ferrarin M. Energy consumption of locomotion with orthosis versus Parastep‐assisted gait: A single case study. Spinal Cord 41: 97‐104, 2003.
 281.Spensley J. STIMuGRIP(R); a new Hand Control Implant. Conf Proc IEEE Eng Med Biol Soc 1: 513, 2007.
 282.Stein RB. Assembly for functional electrical stimulation during movement. US Patent Number 5,643,332, 1997.
 283.Stein RB, Gordon T, Jefferson J, Sharfenberger A, Yang JF, de Zepetnek JT, Belanger M. Optimal stimulation of paralyzed muscle after human spinal cord injury. J Appl Physiol 72: 1393‐1400, 1992.
 284.Stewart CC. On the course of impulses to and from the cat's bladder. Am J Physiol 2: 182‐202, 1899.
 285.Strojnik P, Acimovic R, Vavken E, Simic V, Stanic U. Treatment of drop foot using an implantable peroneal underknee stimulator. Scand J Rehabil Med 19: 37‐43, 1987.
 286.Synapse‐biomedical. Synapse biomedical www.synapsebiomedical.com.
 287.Tai C, Wang J, Wang X, de Groat WC, Roppolo JR. Bladder inhibition or voiding induced by pudendal nerve stimulation in chronic spinal cord injured cats. Neurourol Urodyn 26: 570‐577, 2007.
 288.Tai C, Wang J, Wang X, Roppolo JR, de Groat WC. Voiding reflex in chronic spinal cord injured cats induced by stimulating and blocking pudendal nerves. Neurourol Urodyn 26: 879‐886, 2007.
 289.Talonen PP, Baer GA, Hakkinen V, Ojala JK. Neurophysiological and technical considerations for the design of an implantable phrenic nerve stimulator. Med Biol Eng Comput 28: 31‐37, 1990.
 290.Tanagho EA. Neural stimulation for bladder control. Semin Neurol 8: 170‐173, 1988.
 291.Tanagho EA, Schmidt RA. Electrical stimulation in the clinical management of the neurogenic bladder. J Urol 140: 1331‐1339, 1988.
 292.Tanagho EA, Schmidt RA, Orvis BR. Neural stimulation for control of voiding dysfunction: A preliminary report in 22 patients with serious neuropathic voiding disorders. J Urol 142: 340‐345, 1989.
 293.Tanagho EA, Schmidt RA, Orvis BR. Neural stimulation for control of voiding dysfunction: A preliminary report in 22 patients with serious neuropathic voiding disorders. J Urol 142: 340‐345, 1989.
 294.Taylor P, Burridge J, Dunkerley A, Wood D, Norton J, Singleton C, Swain I. Clinical audit of 5 years provision of the Odstock dropped foot stimulator. Artif Organs 23: 440‐442, 1999.
 295.Taylor PN, Burridge JH, Dunkerley AL, Wood DE, Norton JA, Singleton C, Swain IC. Clinical use of the Odstock dropped foot stimulator. Its effect on the speed and effort of walking. Arch Phys Med Rehabil 80: 1577‐1583, 1999.
 296.Terson de Paleville DGL, Harkema SJ, Angeli CA. Epidural stimulation with locomotor training improves body composition in individuals with cervical or upper thoracic motor complete spinal cord injury: A series of case studies. J Spinal Cord Med 1‐7, 2018.
 297.Thoma H, Gerner H, Holle J, Kluger P, Mayr W, Meister B, Schwanda G, Stohr H. The phrenic pacemaker. Substitution of paralyzed functions in tetraplegia. ASAIO Trans 33: 472‐479, 1987.
 298.Thorsen R, Spadone R, Ferrarin M. A pilot study of myoelectrically controlled FES of upper extremity. IEEE Trans Neural Syst Rehabil Eng 9: 161‐168, 2001.
 299.Triolo RJ, Bieri C, Uhlir J, Kobetic R, Scheiner A, Marsolais EB. Implanted Functional Neuromuscular Stimulation systems for individuals with cervical spinal cord injuries: Clinical case reports. Arch Phys Med Rehabil 77: 1119‐1128, 1996.
 300.Tsoucalas G, Karamanou M, Lymperi M, Gennimata V, Androutsos G. The “torpedo” effect in medicine. Int Marit Health 65: 65‐67, 2014.
 301.Tutolo M, Ammirati E, Heesakkers J, Kessler TM, Peters KM, Rashid T, Sievert KD, Spinelli M, Novara G, Van der Aa F, De Ridder D. Efficacy and safety of sacral and percutaneous tibial neuromodulation in non‐neurogenic lower urinary tract dysfunction and chronic pelvic pain: A systematic review of the literature. Eur Urol 73: 406‐418, 2018.
 302.Van Balken MR. Percutaneous tibial nerve stimulation in lower urinary tract disorders. Amsterdam: Vrijes Universiteit 2007, p. 220.
 303.van Balken MR. Percutaneous tibial nerve stimulation: The Urgent PC device. Expert Rev Med Devices 4: 693‐698, 2007.
 304.van Breda HMK, Martens FMJ, Tromp J, Heesakkers J. A new implanted posterior tibial nerve stimulator for the treatment of overactive bladder syndrome: 3‐month results of a novel therapy at a single center. J Urol 198: 205‐210, 2017.
 305.van der Lee JH, Beckerman H, Lankhorst GJ, Bouter LM. Constraint‐induced movement therapy [letter; comment]. Arch Phys Med Rehabil 80: 1606‐1607, 1999.
 306.van der Pal F, van Balken MR, Heesakkers JP, Debruyne FM, Bemelmans BL. Implant‐driven tibial nerve stimulation in the treatment of refractory overactive bladder syndrome: 12‐month follow‐up. Neuromodulation 9: 163‐171, 2006.
 307.Van Heeckeren DW, Glenn WW. Electrophrenic respiration by radiofrequency induction. J Thorac Cardiovasc Surg 52: 655‐665, 1966.
 308.Van Kerrebroeck PE, Koldewijn EL, Debruyne FM. Worldwide experience with the Finetech‐Brindley sacral anterior root stimulator. Neurourol Urodyn 12: 497‐503, 1993.
 309.van Swigchem R, Vloothuis J, den Boer J, Weerdesteyn V, Geurts AC. Is transcutaneous peroneal stimulation beneficial to patients with chronic stroke using an ankle‐foot orthosis? A within‐subjects study of patients' satisfaction, walking speed and physical activity level. J Rehabil Med 42: 117‐121, 2010.
 310.Vansteensel MJ, Pels EG, Bleichner MG, Branco MP, Denison T, Freudenburg ZV, Gosselaar P, Leinders S, Ottens TH, Van Den Boom MA, Van Rijen PC, Aarnoutse EJ, Ramsey NF. Fully implanted brain‐computer interface in a locked‐in patient with ALS. N Engl J Med 375: 2060‐2066, 2016.
 311.Venugopalan L, Taylor PN, Cobb JE, Swain ID. Upper limb functional electrical stimulation devices and their man‐machine interfaces. J Med Eng Technol 39: 471‐479, 2015.
 312.Vinjamuri R, Weber DJ, Degenhart AD, Collinger JL, Sudre GP, Adelson PD, Holder DL, Boninger ML, Schwartz AB, Crammond DJ, Tyler‐Kabara EC, Wang W. A fuzzy logic model for hand posture control using human cortical activity recorded by micro‐ECog electrodes. Conf Proc IEEE Eng Med Biol Soc 2009: 4339‐4342, 2009.
 313.Vodovnik L. Therapeutic effects of functional electrical stimulation of extremities. Med Biol Eng Comput 19: 470‐478, 1981.
 314.Vodovnik L, Crochetiere WJ, Reswick JB. Control of a skeletal joint by electrical stimulation of antagonists. Med Biol Eng 5: 97‐109, 1967.
 315.Vodovnik L, Long C, 2nd, Reswick JB, Lippay A, Starbuck D. Myo‐electric control of paralyzed muscles. IEEE Trans Biomed Eng 12: 169‐172, 1965.
 316.Wagner F, Mignardot J‐B, Mignardot C, Capogrosso M, Komi S, Demesmaeker R, Seáñez‐González I, Vat M, Caban M, Watrin A, Rowald A, Avanthay M, Fodor I, Tschopp M, Van Den Keybus K, Eberle G, Schurch B, Carda S, Pralong E, Bolliger M, von Zitzewitz J, Bak M, Buschman R, Buse N, Delattre V, Denison T, Lambert H, Curt A, Minassian K, Bloch J, Courtine G. Targeted neurostimulation of the spinal cord enables walking in humans with spinal cord injury. In: Society for Neuroscience AGM. San Diego, California, 2018.
 317.Wang W, Degenhart AD, Collinger JL, Vinjamuri R, Sudre GP, Adelson PD, Holder DL, Leuthardt EC, Moran DW, Boninger ML, Schwartz AB, Crammond DJ, Tyler‐Kabara EC, Weber DJ. Human motor cortical activity recorded with Micro‐ECoG electrodes, during individual finger movements. Conf Proc IEEE Eng Med Biol Soc 2009: 586‐589, 2009.
 318.Waters R, Bowman B, Baker L, Benton L, Meadows P. Treatment of hemiplegic upper extremity using electrical stimulation and biofeedback training. In: Popovic DJ, editor. Advances in External Control of Human Extremities. Belgrade: Yugoslav Committee for Electronics and Automation, 1981, pp. 251‐266.
 319.Waters RL, McNeal DR, Faloon W, Clifford B. Functional electrical stimulation of the peroneal nerve for hemiplegia. Long‐term clinical follow‐up. J Bone Joint Surg Am 67: 792‐793, 1985.
 320.Wenger N, Moraud EM, Gandar J, Musienko P, Capogrosso M, Baud L, Le Goff CG, Barraud Q, Pavlova N, Dominici N, Minev IR, Asboth L, Hirsch A, Duis S, Kreider J, Mortera A, Haverbeck O, Kraus S, Schmitz F, DiGiovanna J, van den Brand R, Bloch J, Detemple P, Lacour SP, Bezard E, Micera S, Courtine G. Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury. Nat Med 22: 138‐145, 2016.
 321.WHO. International Classification of Functioning, Disability and Health (ICF) World Health Organization. http://www.who.int/classifications/icf/en/.
 322.Wichmann T, DeLong MR. Deep brain stimulation for movement disorders of basal ganglia origin: Restoring function or functionality? Neurotherapeutics 13: 264‐283, 2016.
 323.Wilkenfeld AJ, Audu ML, Triolo RJ. Feasibility of functional electrical stimulation for control of seated posture after spinal cord injury: A simulation study. J Rehabil Res Dev 43: 139‐152, 2006.
 324.Williams MR, Kirsch RF. Evaluation of head orientation and neck muscle EMG signals as three‐dimensional command sources. J Neuroeng Rehabil 12: 25, 2015.
 325.Wodlinger B, Downey JE, Tyler‐Kabara EC, Schwartz AB, Boninger ML, Collinger JL. Ten‐dimensional anthropomorphic arm control in a human brain‐machine interface: Difficulties, solutions, and limitations. J Neural Eng 12: 016011, 2015.
 326.Yakovenko S, Mushahwar V, VanderHorst V, Holstege G, Prochazka A. Spatiotemporal activation of lumbosacral motoneurons in the locomotor step cycle. J Neurophysiol 87: 1542‐1553, 2002.
 327.Yoo PB, Grill WM. Minimally‐invasive electrical stimulation of the pudendal nerve: A pre‐clinical study for neural control of the lower urinary tract. Neurourol Urodyn 26: 562‐569, 2007.
 328.Yoo PB, Klein SM, Grafstein NH, Horvath EE, Amundsen CL, Webster GD, Grill WM. Pudendal nerve stimulation evokes reflex bladder contractions in persons with chronic spinal cord injury. Neurourol Urodyn 26: 1020‐1023, 2007.
 329.Yuen TGH, Agnew WF, Bullara LA, McCreery DB. Biocompatibility of electrodes and materials in the central nervous system. In: Agnew WF, McCreery DB, editors. Neural Prostheses Fundamental Studies. Englewood Cliffs, NJ: Prentice Hall, 1990, pp. 198‐223.
 330.Zhang X, Roppolo JR, de Groat WC, Tai C. Mechanism of nerve conduction block induced by high‐frequency biphasic electrical currents. IEEE Trans Biomed Eng 53: 2445‐2454, 2006.
 331.Zimmermann JB, Jackson A. Closed‐loop control of spinal cord stimulation to restore hand function after paralysis. Front Neurosci 8: 87, 2014.

 

Teaching Material

A. Prochazka. Motor Neuroprostheses. Compr Physiol 9: 2019, 127-148.

Didactic Synopsis

Major Teaching Points:

  1. Brief history of electrical stimulation of the nervous system. Electrical stimulation of human peripheral nerves with the use of electrostatic machines for clinical purposes began in the 17th century but only began to be properly understood and applied in the 20th century.
  2. Basic mechanisms and methods of electrical stimulation with neural prostheses (NPs). Methods: Trains of current pulses are applied either with stimulators external to the body connected through pad electrodes applied to the skin, or via implanted stimulators and wire electrodes terminating near or on peripheral nerves or within the central nervous system. Mechanisms: control of the recruitment of nerve axons depends on the amount of charge delivered per current pulse.
  3. Tissue interfaces (surface or implanted electrodes), corrosion, tissue reactions. Electrode corrosion and inflammatory reactions of bodily tissues can occur, depending on the type of electrode, the current and duration of pulses delivered and whether the pulses are monophasic or biphasic.
  4. Types of motor NPs. MNPs either deliver fixed sequences of stimulation for exercise and retraining purposes (therapeutic electrical stimulation: TES), or stimulation triggered by biomechanical events or the user's own electromyographic activity to augment muscle contractions in exercise training, or in functional tasks (functional electrical stimulation: FES).
  5. Lower and upper limb MNPs. Various designs of surface and implanted MNPs have been developed and commercialized to stimulate paralyzed muscles. Influential metastudies have concluded that FES may improve walking, balance and range of motion in hemiplegic people and those with spinal cord injury.
  6. Respiratory MNPs, MNPs for bladder control. There is a surprisingly long history of attempts to stimulate the phrenic nerve for respiration, and various nerves innervating or reflexly affecting the bladder and external urethral sphincter to restore control over micturition. Implanted stimulators for respiration and bladder control are available commercially.
  7. Epidural and intraspinal stimulators. Epidural stimulation of the spinal cord via electrode arrays placed on the dorsal dura mater, originally developed to treat chronic pain, is increasingly being used to restore upper and lower limb movements. Intraspinal stimulation targeting motoneuron pools activating limb muscles or spinal cord nuclei controlling micturition is still in the experimental stages.
  8. Carry-over therapeutic effects and mechanisms. Beneficial carry-over effects lasting up to a few hours are commonly observed after sessions of TES or FES. In some NP applications, long-lasting beneficial effects develop slowly, over days or weeks, and may become permanent.
  9. Barriers to MNP technology transfer. TES stimulators have become inexpensive consumer products, and are widely used. FES devices are much more expensive, because they incorporate sensors and control logic, they are designed to be wearable in daily life, and they are subjected to more stringent regulatory testing. Reimbursement of FES devices is a major barrier to their widespread use.

Didactic Legends

The figures—in a freely downloadable PowerPoint format—can be found on the Images tab along with the formal legends published in the article. The following legends to the same figures are written to be useful for teaching.

Figure 1 Teaching points: Basic designs of neural prostheses. (A) A surface stimulator (also known as an external pulse generator: EPG) delivers current pulses through the skin via a pair of surface electrodes. In some cases, a wireless controller controls the EPG. (B) An EPG delivers current pulses via one or more conductors, typically insulated wires that pass through the skin and terminate close to or on the nerve. The return current flows through the tissues to a surface (reference) electrode. (C) An EPG delivers current pulses through the skin via a pair of surface electrodes and some of the current is intercepted and “picked up” by a fully implanted lead, which delivers this current to the nerve. (D) An implanted pulse generator (IPG) receives energy and commands wirelessly through the skin and delivers current pulses to the nerve via an electrode. The return current flows through the tissues to a reference electrode on the body of the IPG. (E) An implanted pulse generator (IPG) receives energy and commands wirelessly through the skin and delivers current pulses to the nerve via a pair of electrodes. (F) An injectable microstimulator receives energy and commands wirelessly through the skin and delivers current pulses to the nerve through two conductive terminals on the body of the stimulator.

Figure 2 Teaching points: The figure shows four surface foot-drop stimulators that activate the common peroneal nerve to lift the foot in the swing phase of the locomotor step cycle. (A) The Functional Electrical Peroneal Orthosis (FEPO), commercialized in Europe in the 1970s. (B) The Bioness L300. (C) The Innovative Neurotronics Walkaide. (D) The Bioness L300Go. The FEPO and L300 had underheel switches wirelessly linked to an EPG in a cuff attached below the knee. When the under-heel force dropped at the onset of the swing phase, a signal from the switch assembly triggered the EPG to stimulate the nerve via electrodes in the cuff. The Walkaide and Bioness L300Go have a tilt sensor built into the cuff, which is used to trigger stimulation, replacing the under-heel switch and allowing users to walk barefoot.

Figure 3 Teaching points: The figure shows four surface stimulators that activate muscles in the forearm and hand. (A) The Medtronic Respond physiotherapy stimulator activating the wrist and finger extensors. Preset trains of stimulus pulses were triggered by activating a hand-held push-button. Numerous therapeutic stimulators based on this design are commercially available. (B) The Neuromove. In this device, weak voluntary contractions are detected via an electromyogram amplifier connected to a pair of surface electromyogram electrodes and this triggers a pre-set period of stimulation through a pair of electrodes placed orthogonally to the electromyogram electrodes. (C) The Bioness H200. This device comprises a flexible splint with inbuilt electrodes. Trains of stimuli eliciting hand opening and grasp are triggered via a wireless push-button controller. (D) The Rehabtronics ReGrasp comprises a wristlet garment with inbuilt stimulator/receiver and electrodes. A wireless earpiece detects voluntary head movements and transmits control signals to the wristlet, by which means the user can trigger hand opening or grasp.

Figure 4 Teaching points: The figure shows a system in which brain signals recorded from a microelectrode array implanted in the motor cortex of a tetraplegic man were used to control stimulation through electrodes implanted through the skin into muscles in his arm. This enabled him voluntarily to reach out with his weight-supported arm to drink a mug of coffee and feed himself.

Figure 5 Teaching points: The figure shows a variety of sites in the sacral spinal cord and peripheral nerves which have been stimulated electrically to improve bladder function. SNS, sacral nerve stimulation; SARS, sacral anterior root stimulation; ISMS, intraspinal microstimulation; PNS, pudendal nerve stimulation; PTNS, percutaneous tibial nerve stimulation; TENS, transcutaneous electrical nerve stimulation; HFNB, high-frequency stimulation eliciting nerve block (HFNB). The following abbreviations refer to anatomical areas in the central and peripheral nervous system: SPN, sacral parasympathetic nucleus (activates bladder contractions); ON, Onuf's nucleus; CSN, cranial sensory neuron; DNP, dorsal nerve of the penis (DNP).

 


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Article Title: Motor Neuroprostheses
 

How to Cite

Arthur Prochazka. Motor Neuroprostheses. Compr Physiol 2018, 9: 127-148. doi: 10.1002/cphy.c180006