IP Library › Granted Patent US 12,415,071
Granted Patent B2
US 12,415,071 · App. 17/626,319 · Granted Sep 16, 2025

Epidural stimulation and spinal structure locating techniques

Inventors: Peter J. Grahn (Rochester, MN); Igor A. Lavrov (Rochester, MN); Kristin D. Zhao (Rochester, MN); Kendall H. Lee (Rochester, MN); Megan L. Gill (Rochester, MN); Riazul Islam (Rochester, MN)
Assignee: Mayo Foundation for Medical Education and Research
A61N1/36003A61N1/0551
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Quick Facts
Patent No.
US 12,415,071
App. No.
17/626,319
Granted
Sep 16, 2025
Kind
B2
Abstract

Epidural electrical stimulation (EES) systems and techniques for accessing and locating targeted spinal cord segments are disclosed. In some examples, a method includes providing a first set of electrodes of an EES system at a first set of locations on the dura mater of a spine of a mammal, the first set of locations on the dura mater corresponding to a first muscle group of the mammal; providing a second set of electrodes of the epidural electrical stimulation system at a second set of locations on the dura mater of the spine of the mammal, the second set of locations on the dura mater corresponding to a second muscle group of the mammal; and stimulating the first and second sets of locations on the dura mater by electrically energizing the first and second sets of electrodes, respectively, thereby activating the first and second muscle groups in a coordinated manner.

Claims (29)

1. An electrode array for epidural stimulation comprising:

an elongated substrate having a central longitudinal axis;

a first group of inner electrodes arranged on the substrate along a first serpentine path that undulates laterally back and forth across a first inner longitudinal axis from a first end of the substrate to a second end of the substrate thereby conforming the first group of inner electrodes to the locations of a first set of spinal cord rootlets when the electrode array is positioned over the spinal cord, the first inner longitudinal axis parallel to the central longitudinal axis; and

a second group of inner electrodes arranged on the substrate along a second serpentine path that undulates laterally back and forth across a second inner longitudinal axis from the first end of the substrate to the second end of the substrate thereby conforming the second group of inner electrodes to the locations of a second set of spinal cord rootlets when the electrode array is positioned over the spinal cord, the second inner longitudinal axis parallel to the central longitudinal axis.

2. The electrode array of claim 1 , wherein the second group of inner electrodes is symmetrical to the first group of inner electrodes with respect to the central longitudinal axis.

3. The electrode array of claim 1 , further comprising:

a first group of outer electrodes arranged on the substrate along a third serpentine path that undulates laterally back and forth across a first outer longitudinal axis from the first end of the substrate to the second end of the substrate, the first outer longitudinal axis parallel to the first inner longitudinal axis, the first inner longitudinal axis positioned between the central longitudinal axis and the first outer longitudinal axis; and

a second group of outer electrodes arranged on the substrate along a fourth serpentine path that undulates laterally back and forth across a second outer longitudinal axis from the first end of the substrate to the second end of the substrate, the second outer longitudinal axis parallel to the second inner longitudinal axis, the second inner longitudinal axis positioned between the central longitudinal axis and the second outer longitudinal axis.

4. The electrode array of claim 3 , wherein the second group of outer electrodes is symmetrical to the first group of outer electrodes with respect to the central longitudinal axis.

5. The electrode array of claim 3 , comprising a plurality of sections arranged longitudinally along the substrate, each section defining a different respective set of electrodes from the first and second groups of outer electrodes that can be selectively activated independent of the respective sets of electrodes in other sections; and

wherein, in each of the sections, respective set of electrodes in that section are spaced equally along the first and second outer longitudinal axes.

6. The electrode array of claim 3 , comprising a plurality of sections arranged longitudinally along the substrate, each section defining a different respective set of electrodes from the first and second groups of outer electrodes that can be selectively activated independent of the respective sets of electrodes in other sections;

wherein, in each of the sections, at least one pair of adjacent electrodes are spaced at a different distance from at least another pair of adjacent electrodes in that section; and

wherein, in each of the sections, at least one pair of adjacent electrodes are spaced at a different distance from at least another pair of adjacent electrodes in that section.

7. The electrode array of claim 3 , wherein the arrangement of the first group of inner electrodes, the second group of inner electrodes, the first group of outer electrodes, and the second group of outer electrodes along the first, second, third, and fourth serpentine paths, respectively, provides a variable contact density of electrodes along a length of the substrate.

8. The electrode array of claim 7 , wherein the variable contact density is defined at least by a low electrode density region along the length of the substrate, a medium electrode density region along the length of the substrate, and a high electrode density region along the length of the substrate, wherein each of the low, medium, and high density regions comprise multiple electrodes from the first group of inner electrodes, multiple electrodes from the second group of inner electrodes, multiple electrodes from the first group of outer electrodes, and multiple electrodes from the second group of outer electrodes.

9. The electrode array of claim 1 , comprising a plurality of sections arranged longitudinally along the substrate, each section defining a different respective set of electrodes from the first and second groups of inner electrodes that can be selectively activated independent of the respective sets of electrodes in other sections; and

wherein, in each of the sections, the respective set of electrodes in that section are spaced equally along the first and second inner longitudinal axes.

10. The electrode array of claim 1 , comprising a plurality of sections arranged longitudinally along the substrate, each section defining a different respective set of electrodes from the first and second groups of inner electrodes that can be selectively activated independent of the respective sets of electrodes in other sections;

wherein, in each of the sections, at least one pair of adjacent electrodes are spaced at a different distance from at least another pair of adjacent electrodes in that section; and

wherein, in each of the sections, at least one pair of adjacent electrodes are spaced at a different distance from at least another pair of adjacent electrodes in that section.

11. The electrode array of claim 9 , wherein adjacent electrodes within each section are spaced closer to each other than adjacent electrodes in adjacent sections.

12. The electrode array of claim 1 , further comprising:

a plurality of central electrodes arranged on the substrate along the central longitudinal axis.

13. The electrode array of claim 12 , wherein the plurality of central electrodes includes four central electrodes spaced along a length of the substrate.

14. The electrode array of claim 1 , wherein the arrangement of the first group of inner electrodes and the second group of inner electrodes along the first serpentine path and the second serpentine path, respectively, provides a variable contact density of electrodes along a length of the substrate.

15. The electrode array of claim 14 , wherein the variable contact density is defined at least by a low electrode density region along the length of the substrate, a medium electrode density region along the length of the substrate, and a high electrode density region along the length of the substrate, wherein each of the low, medium, and high density regions comprise multiple electrodes from the first group of inner electrodes and multiple electrodes from the second group of inner electrodes.

16. The electrode array of claim 1 , wherein the substrate is configured to have lateral outlines that follow curved lines defined by an undulating arrangement of electrodes on the substrate.

17. The electrode array of claim 16 , wherein the lateral outlines of the substrate comprise lateral edges of the substrate that follow curved lines defined by an undulating arrangement of outer electrodes on the substrate.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 1, 2022
From: GRAHN, PETER J.; LAVROV, IGOR A.; ZHAO, KRISTIN D.; LEE, KENDALL H.; GILL, MEGAN L.; ISLAM, RIAZUL
To: MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH
Reel/Frame 059129/0393 →
Continuity (2)
Provisional Application 62880050 · Jul 29, 2019
Related Publication 20220241587A1 · Aug 4, 2022
References Cited (163)
US 5002053A · Garcia-Rill et al. · 1991 [cited by applicant]
US 5843142A · Sultan · 1998 [cited by applicant]
US 6662053B2 · Borkan · 2003 [cited by applicant]
US 6839594B2 · Cohen et al. · 2005 [cited by applicant]
US 8352026B2 · DiUbaldi · 2013 [cited by applicant]
US 9101769B2 · Edgerton et al. · 2015 [cited by applicant]
US 9358384B2 · Dubuclet · 2016 [cited by examiner]
US 9409023B2 · Burdick et al. · 2016 [cited by applicant]
US 10265525B2 · Courtine et al. · 2019 [cited by applicant]
US 20060069415A1 · Cameron et al. · 2006 [cited by applicant]
US 20070179579A1 · Feler et al. · 2007 [cited by applicant]
US 20090062883A1 · Meadows et al. · 2009 [cited by applicant]
US 20100057177A1 · Moffitt et al. · 2010 [cited by applicant]
US 20120123293A1 · Shah et al. · 2012 [cited by applicant]
US 20150032187A1 · Ranu et al. · 2015 [cited by applicant]
US 20150231396A1 · Burdick et al. · 2015 [cited by applicant]
US 20160279418A1 · Courtine et al. · 2016 [cited by applicant]
US 20170173326A1 · Bloch et al. · 2017 [cited by applicant]
US 20180229036A1 · Harkema et al. · 2018 [cited by applicant]
US 20200086116A1 · Formento et al. · 2020 [cited by applicant]
US 20210052889A1 · Grahn et al. · 2021 [cited by applicant]
US 20230166105A1 · Grahn et al. · 2023 [cited by applicant]
WO WO2017031306 · 2017 [cited by applicant]
EP Extended Search Report in European Appln. No. 20846513.8, dated Aug. 29, 2022, 12 pages. [cited by applicant]
Andersson et al., “Peripheral feedback mechanisms acting on the central pattern generators for locomotion in fish and cat,” Can. J. Physiol. Pharmacology, 1981, 59(7):713-726. [cited by applicant]
Angeli et al., “Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans,” Brain, May 2014, 137(5):1394-1409. [cited by applicant]
Barolat, “Epidural spinal cord stimulation: anatomical and electrical properties of the intraspinal structures relevant to spinal cord stimulation and clinical correlations,” Neuromodulation, Apr. 1998, 1(2):63-71. [cited by applicant]
Behrman et al., “Neuroplasticity after spinal cord injury and training: an emerging paradigm shift in rehabilitation and walking recovery,” Phys. Therapy, Oct. 2006, 86(10):1406-1425. [cited by applicant]
Bozkus et al., “Comparative anatomy of the porcine and human thoracic spines with reference to thoracoscopic surgical techniques,” Surg. Endoscopy, Dec. 2005, 19(12):1652-1665. [cited by applicant]
Busscher et al., “Comparative anatomical dimensions of the complete human and porcine spine,” Eur. Spine Journal, Jul. 2010, 19(7):1104-1114. [cited by applicant]
Capogrosso et al., “A brain-spinal interface alleviating gait deficits after spinal cord injury in primates,” Nature, Nov. 10, 2016, 539(7628):284-288. [cited by applicant]
Capogrosso et al., “A Computational Model for Epidural Electrical Stimulation of Spinal Sensorimotor Circuits,” J. Neuroscience, Dec. 4, 2013, 33(49):19326-19340. [cited by applicant]
Carhart et al., “Epidural Spinal-Cord Stimulation Facilitates Recovery of Functional Walking Following Incomplete Spinal-Cord Injury,” IEEE Trans. Neural Syst. Rehabil. Engineering, Mar. 2004, 12(1):32-42. [cited by applicant]
Coburn et al., “A theoretical study of epidural electrical stimulation of the spinal cord—Part I: Finite element analysis of stimulus fields,” IEEE Trans. Biomed. Engineering, Nov. 1985, 32(11):971-977. [cited by applicant]
Coburn, “A theoretical study of epidural electrical stimulation of the spinal cord—Part II: Effects on long myelinated fibers,” IEEE Trans. Biomed. Engineering, Nov. 1985, 32(11):978-986. [cited by applicant]
Cotterill et al., “An anatomical comparison of the human and bovine thoracolumbar spine,” J. Orthop. Research, 1986, 4(3):298-303. [cited by applicant]
Courtine et al.,. “Modulation of Multisegmental Monosynaptic Responses (MMR) in a variety of leg muscles during walking and running in humans,” J. Physiology, Apr. 19, 2007, 582(Pt 3):1125-1139. [cited by applicant]
Courtine et al., “Transformation of nonfunctional spinal circuits into functional states after the loss of brain input,” Nat. Neuroscience, Sep. 20, 2009, 12(10):1333-1342. [cited by applicant]
Cuellar et al., “The Role of Functional Neuroanatomy of the Lumbar Spinal Cord in Effect of Epidural Stimulation,” Front. Neuroanatomy, Sep. 2017, 11:82, 17 pages. [cited by applicant]
Danner et al., “Human spinal locomotor control is based on flexibly organized burst generators,” Brain, Mar. 2015, 138(3):577-588. [cited by applicant]
Dath et al., “Anatomical measurements of porcine lumbar vertebrae,” Clin. Biomechanics, Mar. 13, 2007, 22(5):607-613. [cited by applicant]
Dietz et al., “Restoration of sensorimotor functions after spinal cord injury,” Brain, Oct. 7, 2013, 137(Pt 3):654-667. [cited by applicant]
Dimitrijevic et al., “Evidence for a Spinal Central Pattern Generator in Humans,” Ann. N. Y. Acad. Sciences, Nov. 1998, 860:360-376. [cited by applicant]
Dobkin et al., “Weight-supported treadmill vs over-ground training for walking after acute incomplete SCI,” Neurology, Feb. 2006, 66(4):484-493. [cited by applicant]
Dominici et al., “Versatile robotic interface to evaluate, enable and train locomotion and balance after neuromotor disorders,” Nat. Medicine, Jul. 2012, 18(7):1142-1147. [cited by applicant]
Engelke et al., “Radiographic Morphometry of the Lumbar Spine in Munich Miniature Pigs,” J. Am. Assoc. Lab. Anim. Science, May 1, 2016, 55(3):336-345. [cited by applicant]
Fehlings et al., “The evidence for intraoperative neurophysiological monitoring in spine surgery: does it make a difference?,” Spine, Apr. 20, 2010, 35(9S):S37-S46. [cited by applicant]
Field-Fote et al., “Influence of a Locomotor Training Approach on Walking Speed and Distance in People With Chronic Spinal Cord Injury: A Randomized Clinical Trial,” Phys. Therapy, Jan. 2011, 91(1):48-60. [cited by applicant]
Fong et al., “Spinal cord-transected mice learn to step in response to quipazine treatment and robotic training,” J. Neuroscience, Dec. 14, 2005, 25(50):11738-11747. [cited by applicant]
Forrest et al., “Neuromotor and Musculoskeletal Responses to Locomotor Training for an Individual with Chronic Motor Complete AIS-B Spinal Cord Injury,” J. Spinal Cord Medicine, Jan. 2008, 31(5):509-521. [cited by applicant]
Forssberg et al., “The locomotion of the acute spinal cat injected with clonidine i.v.,” Brain Research, Feb. 1973, 50(1):184-186. [cited by applicant]
Gad et al., “Initiation of bladder voiding with epidural stimulation in paralyzed, step trained rats,” PLoS One, Sep. 29, 2014, 9(9):e108184, 9 pages. [cited by applicant]
Gad et al., “Neuromodulation of motor-evoked potentials during stepping in spinal rats,” J. Neurophysiology, Jun. 12, 2013, 110(6):1311-1322. [cited by applicant]
Gad et al., “Neuromodulation of the neural circuits controlling the lower urinary tract,” Exp. Neurology, Jul. 2, 2016, 285(Pt B):182-189. [cited by applicant]
Gad et al., “Weight Bearing Over ground Stepping in an Exoskeleton with Non-invasive Spinal Cord Neuromodulation after Motor Complete Paraplegia,” Front. Neuroscience, Jun. 2017, 11:333, 8 pages. [cited by applicant]
Gerasimenko et al., “Epidural Spinal Cord Stimulation Plus Quipazine Administration Enable Stepping in Complete Spinal Adult Rats,” J. Neurophysiology, Nov. 2007, 98(5):2525-2536. [cited by applicant]
Gerasimenko et al., “Initiation of Locomotor Activity in Spinal Cats by Epidural Stimulation of the Spinal Cord,” Neurosci. Behav. Physiology, Mar. 2003, 33(3):247-254. [cited by applicant]
Gerasimenko et al., “Initiation of locomotor activity in spinalized cats by means of spinal cord epidural stimulation,” Ross Fiziol Zh Im I M Sechenova, Sep. 2001, 87(9):1161-1170 (with English Abstract). [cited by applicant]
Gerasimenko et al., “Noninvasive Reactivation of Motor Descending Control after Paralysis,” J. Neurotrauma, Dec. 2015, 32(24):1968-1980. [cited by applicant]
Gerasimenko et al., “Spinal cord reflexes induced by epidural spinal cord stimulation in normal awake rats,” J. Neurosci. Methods, Oct. 2006, 157(2):253-263. [cited by applicant]
Gill et al., “Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia,” Nat. Medicine, Nov. 2018, 24(11):1677-1682. [cited by applicant]
Grahn et al., “Enabling Task-Specific Volitional Motor Functions via Spinal Cord Neuromodulation in a Human With Paraplegia,” Mayo Clin. Proceedings, Apr. 2017, 92(4):544-554. [cited by applicant]
Grahn et al., “Motor-evoked responses via epidural spinal cord stimulation evaluated at intra- and inter-segmental resolution,” Poster, Presented at Proceedings of the NANS2-NIC Joint Meeting, Baltimore, MD, Jun. 25-29,… [cited by applicant]
Grahn et al., “MRI-Guided Stereotactic System for Delivery of Intraspinal Microstimulation,” Spine, Jul. 1, 2016, 41(13):E806-E813. [cited by applicant]
Grillner et al., “Activation of NMDA-receptors elicits “fictive locomotion” in lamprey spinal cord in vitro,” Acta Physiol. Scandinavica, Dec. 1981, 113(4):549-551. [cited by applicant]
Guiho et al., “Impact of direct epispinal stimulation on bladder and bowel functions in pigs: A feasibility study,” Neurourol. Urodynamics, Jun. 12, 2017, 37(1):138-147. [cited by applicant]
Hachmann et al., “Electrical Neuromodulation of the Respiratory System After Spinal Cord Injury,” Mayo Clin. Proceedings, Aug. 3, 2017, 92(9):1401-1414. [cited by applicant]
Hachmann et al., “Large Animal Model for Development of Functional Restoration Paradigms Using Epidural and Intraspinal Stimulation,” PLoS One, Dec. 2013, 8(12):e81443, 7 pages. [cited by applicant]
Hachmann et al., “Review of Epidural Spinal Cord Stimulation for Augmenting Cough after Spinal Cord Injury,” Front. Hum. Neuroscience, Mar. 28, 2017, 11:144, 10 pages. [cited by applicant]
Harkema et al., “Balance and Ambulation Improvements in Individuals With Chronic Incomplete Spinal Cord Injury Using Locomotor Training-Based Rehabilitation,” Arch. Phys. Med. Rehabilitation, Sep. 2012, 93(9):1508-1517. [cited by applicant]
Harkema et al., “Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study,” Lancet, Jun. 4, 2011, 377(9781)1938-1… [cited by applicant]
Harkema et al., “Locomotor Training: As a Treatment of Spinal Cord Injury and in the Progression of Neurologic Rehabilitation,” Arch. Phys. Med. Rehabilitation, Sep. 2012, 93(9):1588-1597. [cited by applicant]
Holsheimer et al., “How do geometric factors influence epidural spinal cord stimulation? A quantitative analysis by computer modeling,” Stereotact. Func. Neurosurgery, 1991, 56(4):234-249. [cited by applicant]
Holsheimer, “Computer modelling of spinal cord stimulation and its contribution to therapeutic efficacy,” Spinal Cord, Aug. 1998, 36(8):531-541. [cited by applicant]
Holsheimer, “Which neuronal elements are activated directly by spinal cord stimulation,” Neuromodulation, Jan. 2002, 5(1):25-31. [cited by applicant]
Ichiyama et al., “Hindlimb stepping movements in complete spinal rats induced by epidural spinal cord stimulation,” Neurosci. Letters, Aug. 2005, 383(3):339-344. [cited by applicant]
Iwahara et al., “Spinal cord stimulation-induced locomotion in the adult cat,” Brain Res. Bulletin, Jan. 1992, 28(1):99-105. [cited by applicant]
Kandziora et al., “Comparison between sheep and human cervical spines: an anatomic, radiographic, bone mineral density, and biomechanical study,” Spine, May 1, 2001, 26(9):1028-1037. [cited by applicant]
Kettler et al., “Are the spines of calf, pig and sheep suitable models for pre-clinical implant tests?,” Eur. Spine Journal, Aug. 25, 2007, 16(12):2186-2192. [cited by applicant]
Kirazli et al., “Anatomy of the spinal dorsal root entry zone: its clinical significance,” Acta Neurochirurgica, Oct. 21, 2014, 156(12):2351-2358. [cited by applicant]
Ko et al., “Gross quantitative measurements of spinal cord segments in human,” Spinal Cord, Jan. 2004, 42(1):35-40. [cited by applicant]
Kowalski et al., “Diaphragm activation via high frequency spinal cord stimulation in a rodent model of spinal cord injury,” Exp. Neurology, Mar. 13, 2013, 247:689-693. [cited by applicant]
Kowalski et al., “High frequency spinal cord stimulation—New method to restore cough,” Respir. Physiol. Neurobiology, Jul. 6, 2016, 232:54-56. [cited by applicant]
Kowalski et al., “Safety assessment of epidural wire electrodes for cough production in a chronic pig model of spinal cord injury,” J. Neurosci. Methods, May 7, 2016, 268:98-105. [cited by applicant]
Ladenbauer et al., “Stimulation of the human lumbar spinal cord with implanted and surface electrodes: A computer simulation study,” IEEE Trans. Neural Sys. Rehabil. Engineering, Dec. 2010, 18(6):637-645. [cited by applicant]
Lavrov et al., “Activation of spinal locomotor circuits in the decerebrated cat by spinal epidural and/or intraspinal electrical stimulation,” Brain Research, Mar. 2015, 1600(C):84-92. [cited by applicant]
Lavrov et al., “Epidural Stimulation Induced Modulation of Spinal Locomotor Networks in Adult Spinal Rats,” J. Neuroscience, Jun. 2008, 28(23):6022-6029. [cited by applicant]
Lavrov et al., “Facilitation of stepping with epidural stimulation in spinal rats: role of sensory input,” J. Neuroscience, Jul. 30, 2008, 28(31):7774-7780. [cited by applicant]
Lavrov et al., “Integrating multiple sensory systems to modulate neural networks controlling posture,” J. Neurophysiology, Oct. 7, 2015, 114(6):3306-3314. [cited by applicant]
Lavrov et al., “Plasticity of Spinal Cord Reflexes After a Complete Transection in Adult Rats: Relationship to Stepping Ability,” J. Neurophysiology, Oct. 2006, 96(4):1699-1710. [cited by applicant]
Lavrov et al., “The Role of Functional Neuroanatomy of the Lumbar Spinal Cord in Effect of Epidural Stimulation,” Front. Neuroanatomy, Sep. 2017, 11:82, 17 pages. [cited by applicant]
Lee et al., “A novel porcine model of traumatic thoracic spinal cord injury,” J. Neurotrauma, Jan. 14, 2013, 30(3):142-159. [cited by applicant]
Lempka et al., “Computational analysis of kilohertz frequency spinal cord stimulation for chronic pain management,” Anesthesiology, Jun. 2015, 122(6):1362-1376. [cited by applicant]
Lu et al., “Engaging Cervical Spinal Cord Networks to Reenable Volitional Control of Hand Function in Tetraplegic Patients,” Neurorehabil. Neural Repair, Nov. 2016, 30(10):951-962. [cited by applicant]
McLain et al., “Comparative morphometry of L4 vertebrae: comparison of large animal models for the human lumbar spine,” Spine, Apr. 15, 2002, 27(8):200-206. [cited by applicant]
Minassian et al., “Stepping-like movements in humans with complete spinal cord injury induced by epidural stimulation of the lumbar cord: electromyographic study of compound muscle action potentials,” Spinal Cord, Jul. … [cited by applicant]
Minassian et al., “Targeting Lumbar Spinal Neural Circuitry by Epidural Stimulation to Restore Motor Function After Spinal Cord Injury,” Neurotherapeutics, Apr. 2016, 13(2):284-294. [cited by applicant]
Moraud et al., “Mechanisms Underlying the Neuromodulation of Spinal Circuits for Correcting Gait and Balance Deficits after Spinal Cord Injury,” Neuron, Feb. 4, 2016, 89(4):814-828. [cited by applicant]
Murg et al., “Epidural electrical stimulation of posterior structures of the human lumbar spinal cord: 1. Muscle twitches—a functional method to define the site of stimulation,” Spinal Cord, Jul. 2000, 38(7):394-402. [cited by applicant]
Musienko et al., “Multi-system neurorehabilitative strategies to restore motor functions following severe spinal cord injury,” Exp. Neurology, May 2012, 235(1):100-109. [cited by applicant]
Nandra et al., “A Parylene-based microelectrode array implant for spinal cord stimulation in rats,” Conf. Proc. IEEE Eng. Med. Biol. Society, Aug. 11, 2011, 2011:1007-1010. [cited by applicant]
National Spinal Cord Injury Statistical Center, “Spinal cord injury facts and figures at a glance,” J. Spinal Cord Medicine, Sep. 2014, 37(5):659-660. [cited by applicant]
Navarro et al., “Chronic Spinal Compression Model in Minipigs: A Systematic Behavioral, Qualitative, and Quantitative Neuropathological Study,” J. Neurotrauma, Jan. 13, 2012, 29(3):499-513. [cited by applicant]
Ney et al., “Cost-effectiveness of intraoperative neurophysiological monitoring for spinal surgeries: beginning steps,” Clin. Neurophysiology, Mar. 3, 2012, 123(9):1705-1707. [cited by applicant]
PCT International Preliminary Report on Patentability in International Appln. No. PCT/US2019/014757, dated Jul. 28, 2020, 6 pages. [cited by applicant]
PCT International Preliminary Report on Patentability in International Appln. No. PCT/US2020/044003, dated Feb. 1, 2022, 7 pages. [cited by applicant]
PCT International Search Report and Written Opinion in International Appln. No. PCT/US2019/014757, dated Jun. 3, 2019, 9 pages. [cited by applicant]
PCT International Search Report and Written Opinion in International Appln. No. PCT/US2020/044003, dated Jan. 7, 2021, 10 pages. [cited by applicant]
Pettigrew et al., “Epidural Spinal Stimulation to Improve Bladder, Bowel, and Sexual Function in Individuals With Spinal Cord Injuries: A Framework for Clinical Research,” IEEE Trans. Biomed. Engineering, Feb. 2017, 64(… [cited by applicant]
Pleticha et al., “Pig lumbar spine anatomy and imaging-guided lateral lumbar puncture: A new large animal model for intrathecal drug delivery,” J. Neurosci. Methods, Mar. 19, 2013, 216(1):10-15. [cited by applicant]
Rattay et al., “Epidural electrical stimulation of posterior structures of the human lumbosacral cord: 2. Quantitative analysis by computer modeling,” Spinal Cord, Aug. 2000, 38(8):473-489. [cited by applicant]
Rattay et al., “Finite Element Modeling for Extracellular Stimulation,” In: Encyclopedia of Computational Neuroscience, Jaeger et al. (eds.), Mar. 4, 2014, 12 pages. [cited by applicant]
Rejc et al., “Effects of Lumbosacral Spinal Cord Epidural Stimulation for Standing after Chronic Complete Paralysis in Humans,” PLoS One, Jul. 2015, 10(7):e0133998, 20 pages. [cited by applicant]
Rejc et al., “Effects of Stand and Step Training with Epidural Stimulation on Motor Function for Standing in Chronic Complete Paraplegics,” J. Neurotrauma, May 2017, 34(9):1787-1802. [cited by applicant]
Sayenko et al., “Effects of paired transcutaneous electrical stimulation delivered at single and dual sites over lumbosacral spinal cord,” Neurosci. Letters, Nov. 2015, 609(C):229-234. [cited by applicant]
Sayenko et al., “Neuromodulation of evoked muscle potentials induced by epidural spinal-cord stimulation in paralyzed individuals,” J. Neurophysiology, Mar. 2014, 111(5):1088-1099. [cited by applicant]
Sayenko et al., “Spinal segment-specific transcutaneous stimulation differentially shapes activation pattern among motor pools in humans,” J. Appl. Physiology, Jun. 2015, 118(11):1364-1374. [cited by applicant]
Schomberg et al., “Translational relevance of Swine Model of Spinal Cord Injury,” J. Neurotrauma, Aug. 25, 2016, 34(3):541-551. [cited by applicant]
Shah et al., “Spinal epidural stimulation strategies: clinical implications of locomotor studies in spinal rat,” Neuroscientist, Mar. 26, 2017, 23(6):664-680. [cited by applicant]
Shah et al., “Unique Spatiotemporal Neuromodulation of the Lumbosacral Circuitry Shapes Locomotor Success after Spinal Cord Injury,” J. Neurotrauma, Sep. 2016, 33(18):1709-1723. [cited by applicant]
Sheng et al., “Anatomy of large animal spines and its comparison to the human spine: A systematic review,” Eur. Spine Journal, Oct. 30, 2009, 19(1):46-56. [cited by applicant]
Sheng et al., “Comparison of cervical spine anatomy in calves, pigs and humans,” PLoS One, Feb. 11, 2016, 11(2):e0148610, 10 pages. [cited by applicant]
Stecker, “A review of intraoperative monitoring for spinal surgery,” Surg. Neurol. International, Jul. 17, 2012, 3(Suppl 3):S174-S187. [cited by applicant]
Struijk et al., “Excitation of Dorsal Root Fibers in Spinal Cord Stimulation: A Theoretical Study,” IEEE Trans. Biomed. Engineering, Jul. 1993, 40(7):632-639. [cited by applicant]
Toossi et al., “Mechanically Stable Intraspinal Microstimulation Implants for Human Translation,” Ann. Biomed. Engineering, Aug. 25, 2016, 45(3):681-694. [cited by applicant]
van den Brand et al., “Restoring Voluntary Control of Locomotion after Paralyzing Spinal Cord Injury,” Science, Jun. 2012, 336(6085):1182-1185. [cited by applicant]
Wenger et al., “Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury,” Nat. Medicine, Feb. 2016, 22(2):138-145. [cited by applicant]
Wilke et al., “Anatomy of the sheep spine and its comparison to the human spine,” Anat. Record, Apr. 1997, 247(4):542-555. [cited by applicant]
Yingling et al., “The porcine cervical spine as a model of the human lumbar spine: an anatomical, geometric, and functional comparison,” J. Spinal Disorders, Oct. 1999, 12(5):415-423. [cited by applicant]
Yushkevich et al., “User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability,” NeuroImage, Mar. 20, 2006, 31(3):1116-1128. [cited by applicant]
Zurita et al., “The pig model of chronic paraplegia: A challenge for experimental studies in spinal cord injury,” Prog. Neurobiology, May 5, 2012, 97(3):288-303. [cited by applicant]
Behrman et al., “Locomotor training after human spinal cord injury: a series of case studies, ” Phys. Ther., Jul. 2000, 80(7):688-700. [cited by applicant]
ClinicalTrials.gov [online], “Spinal Cord Injury Epidural Stimulation,” NCT02592668, Jan. 2016, last updated Apr. 2020, retrieved from URL<https://www.clinicaltrials.gov/study/NCT02592668>, 11 pages. [cited by applicant]
Courtine et al., “Defining ecological strategies in neuroprosthetics,” Neuron, Apr. 2015, 86(1):29-33. [cited by applicant]
Dimitrijevic et al., “EMG evidence of suprasegmental infuence on motor unit activity in paralyzed muscles,” Clin. Neurophysiol., 1983, 56:S68. [cited by applicant]
Dimitrijevic et al., “Human Spinal Cord Motor Control That is Partially or Completely Disconnected from the Brain,” Am. J. Neuroprot. Neuroregen., Oct. 2016, 8(1):12-26. [cited by applicant]
Dimitrijevic, “Residual motor functions in spinal cord injury,” Adv. Neurol., 1988, 47:138-155. [cited by applicant]
Huang et al., “Modulation effects of epidural spinal cord stimulation on muscle activities during walking, ” IEEE Trans. Neural. Syst. Rehabil. Eng., Mar. 2006, 14(1):14-23. [cited by applicant]
Kakulas, “Pathology of spinal injuries,” Cent. Nerv. Syst. Trauma, Jan. 1984, 1(2):117-129. [cited by applicant]
Minassian et al., “Spinal Cord Stimulation and Augmentative Control Strategies for Leg Movement after Spinal Paralysis in Humans,” CNS Neurosci. Ther., Apr. 2016, 22(4):262-270. [cited by applicant]
Moritz, “Now is the Critical Time for Engineered Neuroplasticity,” Neurotherapeutics, Jul. 2018, 15(3):628-634. [cited by applicant]
Shah et al., “Variability in step training enhances locomotor recovery after a spinal cord injury, ” Eur. J. Neurosci., Jul. 2012, 36(1):2054-2062. [cited by applicant]
Sherwood et al., “Evidence of subclinical brain influence in clinically complete spinal cord injury: discomplete Sci,” J. Neurol. Sci., Jul. 1992, 110(1-2):90-98. [cited by applicant]
Taccola et al., “And yet it moves: Recovery of volitional control after spinal cord injury,” Prog. Neurobiol., Jan. 2018, 160:64-81. [cited by applicant]
Wenger et al., “Closed-loop neuromodulation of spinal sensorimotor circuits controls refined locomotion after complete spinal cord injury,” Sci. Transl. Med., Sep. 2014, 6(255):255ra133. [cited by applicant]
Anderson et al., “Astrocyte scar formation aids central nervous system axon regeneration,” Nature, Apr. 2016, 532(7598):195-200. [cited by applicant]
Angeli et al., “Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Cord Injury,” N. Engl. J. Med., Sep. 2018, 379(13):1244-1250. [cited by applicant]
Bydon et al., “The current role of steroids in acute spinal cord injury,” World Neurosurg., Nov. 2014, 82(5):848-854. [cited by applicant]
Calvert et al., “Electrophysiological Guidance of Epidural Electrode Array Implantation over the Human Lumbosacral Spinal Cord to Enable Motor Function after Chronic Paralysis,” J. Neurotrauma, May 2019, 36(9):1451-1460. [cited by applicant]
Chen et al., “GDNF Schwann cells in hydrogel scaffolds promote regional axon regeneration, remyelination and functional improvement after spinal cord transection in rats,” J. Tissue Eng. Regen. Med., Jan. 2018, 12(1):e3… [cited by applicant]
Collinger et al., “High-performance neuroprosthetic control by an individual with tetraplegia,” Lancet, Feb. 2013, 381(9866):557-564. [cited by applicant]
Flesher et al., “Intracortical microstimulation of human somatosensory cortex,” Sci. Transl. Med., Oct. 2016, 8(361):361ra141. [cited by applicant]
Gerasimenko et al., “Transcutaneous electrical spinal-cord stimulation in humans,” Ann. Phys. Rehabil. Med., Sep. 2015, 58(4):225-231. [cited by applicant]
Harkema et al., “Normalization of Blood Pressure With Spinal Cord Epidural Stimulation After Severe Spinal Cord Injury,” Front. Hum. Neurosci., Mar. 2018, 12:83. [cited by applicant]
Harvey, “Physiotherapy rehabilitation for people with spinal cord injuries,” J. Physiother., Jan. 2016, 62(1):4-11. [cited by applicant]
Ichiyama et al., “Step training reinforces specific spinal locomotor circuitry in adult spinal rats,” J. Neurosci., Jul. 2008, 28(29):7370-7375. [cited by applicant]
Kirshblum et al., “Reference for the 2011 revision of the international standards for neurological classification of spinal cord injury,” J. Spinal Cord Med., Nov. 2011, 34(6):547-554. [cited by applicant]
Lang et al., “Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury,” Naure, Feb. 2015, 518(7539):404-408. [cited by applicant]
Minassian et al., “Human lumbar cord circuitries can be activated by extrinsic tonic input to generate locomotor-like activity,” Hum. Mov. Sci., Apr. 2007, 26(2):275-295. [cited by applicant]
Rejc et al., “Motor recovery after activity-based training with spinal cord epidural stimulation in a chronic motor complete paraplegic,” Sci. Rep., Oct. 2017, 7(1):13476. [cited by applicant]
Sekhon et al., “Epidemiology, demographics, and pathophysiology of acute spinal cord injury,” Spine, Dec. 2001, 26(24 Suppl):S2-S12. [cited by applicant]
Terson de Paleville et al., “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 … [cited by applicant]
West et al., “Association of Epidural Stimulation With Cardiovascular Function in an Individual With Spinal Cord Injury,” JAMA Neurol., May 2018, 75(5):630-632. [cited by applicant]