Transspinal Stimulation Plus Locomotor Training for SCI

Spinal Cord Injuries Clinical Trial

Official title:

Priming With High-Frequency Trans-spinal Stimulation to Augment Locomotor Benefits in Spinal Cord Injury

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04807764
• Other study ID #: R01HD100544
• Status: Recruiting
• Phase: N/A
• Start date: August 1, 2021
• Est. completion date: December 1, 2025

Study information

• Verified date: February 2024
• Source: City University of New York
• Contact: Maria Knikou, PT, PhD
• Phone: 17189823316
• Email: Maria.Knikou[@]csi.cuny.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Locomotor training is often used with the aim to improve corticospinal function and walking ability in individuals with Spinal Cord Injury. Excitingly, the benefits of locomotor training may be augmented by noninvasive electrical stimulation of the spinal cord and enhance motor recovery at SCI. This study will compare the effects of priming locomotor training with high-frequency noninvasive thoracolumbar spinal stimulation. In people with motor-incomplete SCI, a series of clinical and electrical tests of brain and spinal cord function will be performed before and after 40 sessions of locomotor training where spinal stimulation is delivered immediately before either lying down or during standing.

Description:

Spinal cord injury (SCI) greatly impairs standing and walking ability, which severely compromises daily living activities. While these deficits are partially improved by locomotor training, even after multiple training sessions, abnormal muscle activity and coordination still persist. Thus, locomotor training alone cannot fully optimize the neuronal plasticity required to strengthen the synapses connecting the brain, spinal cord, and local circuits. As such, treatment interventions that effectively promote neuromodulation of spinal locomotor networks and strengthen neural connectivity of the injured human spinal cord in combination with physical rehabilitation are greatly needed. It is proposed that transcutaneous spinal cord (transspinal) stimulation as a method to synergistically 'prime' the nervous system to better respond to locomotor training. Transspinal stimulation alters motoneuron excitability over multiple spinal segments, a pre-requisite for functioning descending and local inputs. Importantly, whether concurrent treatment with transspinal stimulation and locomotor training maximizes motor recovery after SCI is unknown. The goal of this clinical trial is to use high frequency (30 Hz) transspinal stimulation to prime locomotor training and ultimately improve standing, walking, and overall function in individuals with chronic incomplete SCI (iSCI). Forty-five individuals with iSCI will undergo 40 sessions of body weight-supported step training primed with high-frequency transspinal stimulation. Participants will be randomized to receive transspinal stimulation during standing (real or sham) or while supine (real). Aim 1 evaluates how priming locomotor training with high-frequency transspinal stimulation in SCI alters corticomotoneuronal connectivity strength, as indicated by motor evoked potentials recorded from the legs.

Aim 2 evaluates how priming locomotor training with high-frequency transspinal stimulation in iSCI affects reorganization and appropriate engagement of spinal neuronal circuits. Finally, Aim 3 evaluates activity-based motor function, ability to stand and walk, and quality of life. These results will support the notion that tonic high-frequency transspinal stimulation strengthens corticomotoneuronal connectivity and improves spinal circuit organization through posture-dependent corticospinal neuroplasticity. It is anticipated that the information gained from this mechanistic clinical trial will greatly impact clinical practice. This is because in real-world clinical settings, noninvasive transspinal stimulation can be more easily and widely implemented than invasive epidural stimulation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: December 1, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Willingness to comply with all study procedures and availability for the duration of the study.

• Ability to understand the consent form, and sign the consent form.

• Male or female, age 18-70 years old.

• In good general health as evidenced by medical history.

• Diagnosed with motor incomplete SCI (AIS C-D).

• Bone mineral density of the hip (proximal femur) T-score <3.5 SD from age- and gender-matched normative data.

• Lesion above thoracic (T) 10 to ensure absent lower motoneuron lesion.

• Presence of tendon reflexes to be able to elicit the soleus H-reflex.

• Absent permanent ankle joint contractures that prevent passive or active ankle movement because corticospinal and spinal excitability is based on the ankle angle. The ankle straps of the Lokomat require also flexible ankle joints.

• A diagnosis of first time SCI due to trauma, vascular, or orthopedic pathology.

• Time after SCI of more than 6 months.

• Stable medical condition without cardiopulmonary disease or cognitive impairment.

Exclusion Criteria:

• Supraspinal lesions.

• Significant neuropathies of the peripheral nervous system.

• Significant degenerative neurological disorders of the spine or spinal cord.

• AIS A or B.

• Presence of pressure sores.

• Advanced urinary tract infection.

• Neoplastic or vascular disorders of the spine or spinal cord.

• Participation in an ongoing research study or new rehabilitation program.

• Pregnant women or women who suspect they may be, or may become pregnant will be excluded from participation because the risks of thoracolumbar stimulation to the fetus are unknown.

• People with cochlear implants, pacemaker, implanted infusion device, and/or implanted stimulators of any type and purpose will be excluded to avoid their malfunction due to stimulation.

• People with history of seizures.

• Medical conditions that increase the possibility of seizures.

• Medications that may change the seizure threshold.

Related Conditions & MeSH terms

• Paraplegia
• Paraplegia, Spastic
• Paraplegia, Spinal
• Quadriplegia
• Spinal Cord Injuries
• Tetraplegia/Tetraparesis

Intervention

Combination Product:
• Standing transspinal stimulation followed by robotic gait training
Fifteen people with spinal cord injury will receive 40 daily sessions of 30 minutes of non-invasive high frequency (e.g. 30 Hz) transcutaneous transspinal stimulation during standing followed by 30 minutes of assisted stepping robotic gait training. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.
• Lying transspinal stimulation followed by robotic gait training
Fifteen people with spinal cord injury will receive 40 daily sessions of 30 minutes of non-invasive high frequency (e.g. 30 Hz) transcutaneous transspinal stimulation while lying supine on a therapy table followed by 30 minutes of assisted stepping robotic gait training. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.

Other:
• Standing sham transspinal stimulation followed by robotic gait training
Fifteen people with spinal cord injury will receive 40 daily sessions of 30 minutes of sham transspinal stimulation during standing at an intensity where sensation is absent followed by 30 minutes of robotic gait training. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.

Locations

Country	Name	City	State
United States	Veterans Affairs Medical Center	Bronx	New York
United States	Department of Physical Therapy, Motor Control and NeuroRecovery Laboratory	Staten Island	New York

Sponsors (3)

Lead Sponsor	Collaborator
City University of New York	Bronx Veterans Medical Research Foundation, Inc, Icahn School of Medicine at Mount Sinai

Country where clinical trial is conducted

United States, 

References & Publications (140)

Ackerley SJ, Byblow WD, Barber PA, MacDonald H, McIntyre-Robinson A, Stinear CM. Primed Physical Therapy Enhances Recovery of Upper Limb Function in Chronic Stroke Patients. Neurorehabil Neural Repair. 2016 May;30(4):339-48. doi: 10.1177/1545968315595285. Epub 2015 Jul 15. — View Citation

Alexeeva N, Broton JG, Calancie B. Latency of changes in spinal motoneuron excitability evoked by transcranial magnetic brain stimulation in spinal cord injured individuals. Electroencephalogr Clin Neurophysiol. 1998 Aug;109(4):297-303. doi: 10.1016/s0924-980x(98)00021-6. — View Citation

Anderson KD. Targeting recovery: priorities of the spinal cord-injured population. J Neurotrauma. 2004 Oct;21(10):1371-83. doi: 10.1089/neu.2004.21.1371. — View Citation

Angeli CA, Boakye M, Morton RA, Vogt J, Benton K, Chen Y, Ferreira CK, Harkema SJ. Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Cord Injury. N Engl J Med. 2018 Sep 27;379(13):1244-1250. doi: 10.1056/NEJMoa1803588. Epub 2018 Sep 24. — View Citation

Angeli CA, Edgerton VR, Gerasimenko YP, Harkema SJ. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain. 2014 May;137(Pt 5):1394-409. doi: 10.1093/brain/awu038. Epub 2014 Apr 8. Erratum In: Brain. 2015 Feb;138(Pt 2):e330. — View Citation

Ardestani MM, Henderson CE, Salehi SH, Mahtani GB, Schmit BD, Hornby TG. Kinematic and Neuromuscular Adaptations in Incomplete Spinal Cord Injury after High- versus Low-Intensity Locomotor Training. J Neurotrauma. 2019 Jun 15;36(12):2036-2044. doi: 10.1089/neu.2018.5900. Epub 2019 Feb 1. — View Citation

Arvanian VL, Schnell L, Lou L, Golshani R, Hunanyan A, Ghosh A, Pearse DD, Robinson JK, Schwab ME, Fawcett JW, Mendell LM. Chronic spinal hemisection in rats induces a progressive decline in transmission in uninjured fibers to motoneurons. Exp Neurol. 2009 Apr;216(2):471-80. doi: 10.1016/j.expneurol.2009.01.004. — View Citation

Aymard C, Katz R, Lafitte C, Lo E, Penicaud A, Pradat-Diehl P, Raoul S. Presynaptic inhibition and homosynaptic depression: a comparison between lower and upper limbs in normal human subjects and patients with hemiplegia. Brain. 2000 Aug;123 ( Pt 8):1688-702. doi: 10.1093/brain/123.8.1688. — View Citation

Barthelemy D, Knudsen H, Willerslev-Olsen M, Lundell H, Nielsen JB, Biering-Sorensen F. Functional implications of corticospinal tract impairment on gait after spinal cord injury. Spinal Cord. 2013 Nov;51(11):852-6. doi: 10.1038/sc.2013.84. Epub 2013 Aug 13. — View Citation

Barthelemy D, Willerslev-Olsen M, Lundell H, Biering-Sorensen F, Nielsen JB. Assessment of transmission in specific descending pathways in relation to gait and balance following spinal cord injury. Prog Brain Res. 2015;218:79-101. doi: 10.1016/bs.pbr.2014.12.012. Epub 2015 Mar 29. — View Citation

Barthelemy D, Willerslev-Olsen M, Lundell H, Conway BA, Knudsen H, Biering-Sorensen F, Nielsen JB. Impaired transmission in the corticospinal tract and gait disability in spinal cord injured persons. J Neurophysiol. 2010 Aug;104(2):1167-76. doi: 10.1152/jn.00382.2010. Epub 2010 Jun 16. — View Citation

Baudry S, Penzer F, Duchateau J. Input-output characteristics of soleus homonymous Ia afferents and corticospinal pathways during upright standing differ between young and elderly adults. Acta Physiol (Oxf). 2014 Mar;210(3):667-77. doi: 10.1111/apha.12233. — View Citation

Behrman AL, Ardolino EM, Harkema SJ. Activity-Based Therapy: From Basic Science to Clinical Application for Recovery After Spinal Cord Injury. J Neurol Phys Ther. 2017 Jul;41 Suppl 3(Suppl 3 IV STEP Spec Iss):S39-S45. doi: 10.1097/NPT.0000000000000184. — View Citation

Bennett MR. The concept of long term potentiation of transmission at synapses. Prog Neurobiol. 2000 Feb;60(2):109-37. doi: 10.1016/s0301-0082(99)00006-4. — View Citation

Berg KO, Wood-Dauphinee SL, Williams JI, Maki B. Measuring balance in the elderly: validation of an instrument. Can J Public Health. 1992 Jul-Aug;83 Suppl 2:S7-11. — View Citation

Bethoux F, Bennett S. Evaluating walking in patients with multiple sclerosis: which assessment tools are useful in clinical practice? Int J MS Care. 2011 Spring;13(1):4-14. doi: 10.7224/1537-2073-13.1.4. — View Citation

Calancie B, Broton JG, Klose KJ, Traad M, Difini J, Ayyar DR. Evidence that alterations in presynaptic inhibition contribute to segmental hypo- and hyperexcitability after spinal cord injury in man. Electroencephalogr Clin Neurophysiol. 1993 Jun;89(3):177-86. doi: 10.1016/0168-5597(93)90131-8. — View Citation

Chen R, Tam A, Butefisch C, Corwell B, Ziemann U, Rothwell JC, Cohen LG. Intracortical inhibition and facilitation in different representations of the human motor cortex. J Neurophysiol. 1998 Dec;80(6):2870-81. doi: 10.1152/jn.1998.80.6.2870. — View Citation

Chen YS, Zhou S. Soleus H-reflex and its relation to static postural control. Gait Posture. 2011 Feb;33(2):169-78. doi: 10.1016/j.gaitpost.2010.12.008. Epub 2011 Jan 5. — View Citation

Cirillo J, Calabro FJ, Perez MA. Impaired Organization of Paired-Pulse TMS-Induced I-Waves After Human Spinal Cord Injury. Cereb Cortex. 2016 May;26(5):2167-77. doi: 10.1093/cercor/bhv048. Epub 2015 Mar 25. — View Citation

Cote MP, Murray LM, Knikou M. Spinal Control of Locomotion: Individual Neurons, Their Circuits and Functions. Front Physiol. 2018 Jun 25;9:784. doi: 10.3389/fphys.2018.00784. eCollection 2018. — View Citation

Cote MP, Murray M, Lemay MA. Rehabilitation Strategies after Spinal Cord Injury: Inquiry into the Mechanisms of Success and Failure. J Neurotrauma. 2017 May 15;34(10):1841-1857. doi: 10.1089/neu.2016.4577. Epub 2016 Nov 21. — View Citation

Courtine G, Gerasimenko Y, van den Brand R, Yew A, Musienko P, Zhong H, Song B, Ao Y, Ichiyama RM, Lavrov I, Roy RR, Sofroniew MV, Edgerton VR. Transformation of nonfunctional spinal circuits into functional states after the loss of brain input. Nat Neurosci. 2009 Oct;12(10):1333-42. doi: 10.1038/nn.2401. Epub 2009 Sep 20. — View Citation

Crone C, Hultborn H, Jespersen B, Nielsen J. Reciprocal Ia inhibition between ankle flexors and extensors in man. J Physiol. 1987 Aug;389:163-85. doi: 10.1113/jphysiol.1987.sp016652. — View Citation

Crone C, Johnsen LL, Biering-Sorensen F, Nielsen JB. Appearance of reciprocal facilitation of ankle extensors from ankle flexors in patients with stroke or spinal cord injury. Brain. 2003 Feb;126(Pt 2):495-507. doi: 10.1093/brain/awg036. — View Citation

Crone C, Nielsen J. Methodological implications of the post activation depression of the soleus H-reflex in man. Exp Brain Res. 1989;78(1):28-32. doi: 10.1007/BF00230683. — View Citation

Danner SM, Hofstoetter US, Freundl B, Binder H, Mayr W, Rattay F, Minassian K. Human spinal locomotor control is based on flexibly organized burst generators. Brain. 2015 Mar;138(Pt 3):577-88. doi: 10.1093/brain/awu372. Epub 2015 Jan 12. — View Citation

Deliagina TG, Zelenin PV, Orlovsky GN. Physiological and circuit mechanisms of postural control. Curr Opin Neurobiol. 2012 Aug;22(4):646-52. doi: 10.1016/j.conb.2012.03.002. Epub 2012 Mar 23. — View Citation

Desroches G, Gagnon D, Nadeau S, Popovic M. Magnitude of forward trunk flexion influences upper limb muscular efforts and dynamic postural stability requirements during sitting pivot transfers in individuals with spinal cord injury. J Electromyogr Kinesiol. 2013 Dec;23(6):1325-33. doi: 10.1016/j.jelekin.2013.09.003. Epub 2013 Sep 20. — View Citation

Devanne H, Lavoie BA, Capaday C. Input-output properties and gain changes in the human corticospinal pathway. Exp Brain Res. 1997 Apr;114(2):329-38. doi: 10.1007/pl00005641. — View Citation

Dixon L, Ibrahim MM, Santora D, Knikou M. Paired associative transspinal and transcortical stimulation produces plasticity in human cortical and spinal neuronal circuits. J Neurophysiol. 2016 Aug 1;116(2):904-16. doi: 10.1152/jn.00259.2016. Epub 2016 Jun 8. — View Citation

Dobkin B, Apple D, Barbeau H, Basso M, Behrman A, Deforge D, Ditunno J, Dudley G, Elashoff R, Fugate L, Harkema S, Saulino M, Scott M; Spinal Cord Injury Locomotor Trial Group. Weight-supported treadmill vs over-ground training for walking after acute incomplete SCI. Neurology. 2006 Feb 28;66(4):484-93. doi: 10.1212/01.wnl.0000202600.72018.39. — View Citation

Dobkin BH. Spinal and supraspinal plasticity after incomplete spinal cord injury: correlations between functional magnetic resonance imaging and engaged locomotor networks. Prog Brain Res. 2000;128:99-111. doi: 10.1016/S0079-6123(00)28010-2. No abstract available. — View Citation

Dong Y, Peng CY. Principled missing data methods for researchers. Springerplus. 2013 May 14;2(1):222. doi: 10.1186/2193-1801-2-222. Print 2013 Dec. — View Citation

Donovan J, Kirshblum S. Clinical Trials in Traumatic Spinal Cord Injury. Neurotherapeutics. 2018 Jul;15(3):654-668. doi: 10.1007/s13311-018-0632-5. — View Citation

ECCLES JC, KOSTYUK PG, SCHMIDT RF. The effect of electric polarization of the spinal cord on central afferent fibres and on their excitatory synaptic action. J Physiol. 1962 Jun;162(1):138-50. doi: 10.1113/jphysiol.1962.sp006920. No abstract available. — View Citation

Ellaway PH, Catley M, Davey NJ, Kuppuswamy A, Strutton P, Frankel HL, Jamous A, Savic G. Review of physiological motor outcome measures in spinal cord injury using transcranial magnetic stimulation and spinal reflexes. J Rehabil Res Dev. 2007;44(1):69-76. doi: 10.1682/jrrd.2005.08.0140. — View Citation

Estes SP, Iddings JA, Field-Fote EC. Priming Neural Circuits to Modulate Spinal Reflex Excitability. Front Neurol. 2017 Feb 3;8:17. doi: 10.3389/fneur.2017.00017. eCollection 2017. — View Citation

Field-Fote EC, Yang JF, Basso DM, Gorassini MA. Supraspinal Control Predicts Locomotor Function and Forecasts Responsiveness to Training after Spinal Cord Injury. J Neurotrauma. 2017 May 1;34(9):1813-1825. doi: 10.1089/neu.2016.4565. Epub 2016 Dec 20. — View Citation

Formento E, Minassian K, Wagner F, Mignardot JB, Le Goff-Mignardot CG, Rowald A, Bloch J, Micera S, Capogrosso M, Courtine G. Electrical spinal cord stimulation must preserve proprioception to enable locomotion in humans with spinal cord injury. Nat Neurosci. 2018 Dec;21(12):1728-1741. doi: 10.1038/s41593-018-0262-6. Epub 2018 Oct 31. — View Citation

Geertsen SS, Zuur AT, Nielsen JB. Voluntary activation of ankle muscles is accompanied by subcortical facilitation of their antagonists. J Physiol. 2010 Jul 1;588(Pt 13):2391-402. doi: 10.1113/jphysiol.2010.190678. Epub 2010 May 10. — View Citation

Gerasimenko Y, Gorodnichev R, Moshonkina T, Sayenko D, Gad P, Reggie Edgerton V. Transcutaneous electrical spinal-cord stimulation in humans. Ann Phys Rehabil Med. 2015 Sep;58(4):225-231. doi: 10.1016/j.rehab.2015.05.003. Epub 2015 Jul 20. — View Citation

Gerasimenko Y, Sayenko D, Gad P, Kozesnik J, Moshonkina T, Grishin A, Pukhov A, Moiseev S, Gorodnichev R, Selionov V, Kozlovskaya I, Edgerton VR. Electrical Spinal Stimulation, and Imagining of Lower Limb Movements to Modulate Brain-Spinal Connectomes That Control Locomotor-Like Behavior. Front Physiol. 2018 Sep 19;9:1196. doi: 10.3389/fphys.2018.01196. eCollection 2018. — View Citation

Gerasimenko YP, Lu DC, Modaber M, Zdunowski S, Gad P, Sayenko DG, Morikawa E, Haakana P, Ferguson AR, Roy RR, Edgerton VR. Noninvasive Reactivation of Motor Descending Control after Paralysis. J Neurotrauma. 2015 Dec 15;32(24):1968-80. doi: 10.1089/neu.2015.4008. Epub 2015 Aug 20. — View Citation

Gill ML, Grahn PJ, Calvert JS, Linde MB, Lavrov IA, Strommen JA, Beck LA, Sayenko DG, Van Straaten MG, Drubach DI, Veith DD, Thoreson AR, Lopez C, Gerasimenko YP, Edgerton VR, Lee KH, Zhao KD. Publisher Correction: Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia. Nat Med. 2018 Dec;24(12):1942. doi: 10.1038/s41591-018-0248-7. — View Citation

Gorodnichev RM, Pivovarova EA, Pukhov A, Moiseev SA, Savokhin AA, Moshonkina TR, Shcherbakova NA, Kilimnik VA, Selionov VA, Kozlovskaia IB, Edgerton VR, Gerasimenko IuP. [Transcutaneous electrical stimulation of the spinal cord: non-invasive tool for activation of locomotor circuitry in human]. Fiziol Cheloveka. 2012 Mar-Apr;38(2):46-56. Russian. — View Citation

Grey MJ, Klinge K, Crone C, Lorentzen J, Biering-Sorensen F, Ravnborg M, Nielsen JB. Post-activation depression of soleus stretch reflexes in healthy and spastic humans. Exp Brain Res. 2008 Feb;185(2):189-97. doi: 10.1007/s00221-007-1142-6. Epub 2007 Oct 12. — View Citation

Hanna-Boutros B, Sangari S, Giboin LS, El Mendili MM, Lackmy-Vallee A, Marchand-Pauvert V, Knikou M. Corticospinal and reciprocal inhibition actions on human soleus motoneuron activity during standing and walking. Physiol Rep. 2015 Feb 25;3(2):e12276. doi: 10.14814/phy2.12276. — View Citation

Hannah R, Cavanagh SE, Tremblay S, Simeoni S, Rothwell JC. Selective Suppression of Local Interneuron Circuits in Human Motor Cortex Contributes to Movement Preparation. J Neurosci. 2018 Jan 31;38(5):1264-1276. doi: 10.1523/JNEUROSCI.2869-17.2017. Epub 2017 Dec 20. — View Citation

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. 2011 Jun 4;377(9781):1938-47. doi: 10.1016/S0140-6736(11)60547-3. Epub 2011 May 19. — View Citation

Harkema SJ, Hurley SL, Patel UK, Requejo PS, Dobkin BH, Edgerton VR. Human lumbosacral spinal cord interprets loading during stepping. J Neurophysiol. 1997 Feb;77(2):797-811. doi: 10.1152/jn.1997.77.2.797. — View Citation

Hofstoetter US, Knikou M, Guertin PA, Minassian K. Probing the Human Spinal Locomotor Circuits by Phasic Step-Induced Feedback and by Tonic Electrical and Pharmacological Neuromodulation. Curr Pharm Des. 2017;23(12):1805-1820. doi: 10.2174/1381612822666161214144655. — View Citation

Hofstoetter US, Krenn M, Danner SM, Hofer C, Kern H, McKay WB, Mayr W, Minassian K. Augmentation of Voluntary Locomotor Activity by Transcutaneous Spinal Cord Stimulation in Motor-Incomplete Spinal Cord-Injured Individuals. Artif Organs. 2015 Oct;39(10):E176-86. doi: 10.1111/aor.12615. Epub 2015 Oct 6. — View Citation

Hofstoetter US, McKay WB, Tansey KE, Mayr W, Kern H, Minassian K. Modification of spasticity by transcutaneous spinal cord stimulation in individuals with incomplete spinal cord injury. J Spinal Cord Med. 2014 Mar;37(2):202-11. doi: 10.1179/2045772313Y.0000000149. Epub 2013 Nov 26. — View Citation

Horak FB, Nashner LM. Central programming of postural movements: adaptation to altered support-surface configurations. J Neurophysiol. 1986 Jun;55(6):1369-81. doi: 10.1152/jn.1986.55.6.1369. — View Citation

Hounsgaard J, Hultborn H, Jespersen B, Kiehn O. Bistability of alpha-motoneurones in the decerebrate cat and in the acute spinal cat after intravenous 5-hydroxytryptophan. J Physiol. 1988 Nov;405:345-67. doi: 10.1113/jphysiol.1988.sp017336. — View Citation

Ichiyama RM, Broman J, Roy RR, Zhong H, Edgerton VR, Havton LA. Locomotor training maintains normal inhibitory influence on both alpha- and gamma-motoneurons after neonatal spinal cord transection. J Neurosci. 2011 Jan 5;31(1):26-33. doi: 10.1523/JNEUROSCI.6433-09.2011. — View Citation

Ilha J, Centenaro LA, Broetto Cunha N, de Souza DF, Jaeger M, do Nascimento PS, Kolling J, Ben J, Marcuzzo S, Wyse AT, Gottfried C, Achaval M. The beneficial effects of treadmill step training on activity-dependent synaptic and cellular plasticity markers after complete spinal cord injury. Neurochem Res. 2011 Jun;36(6):1046-55. doi: 10.1007/s11064-011-0446-x. Epub 2011 Mar 22. — View Citation

James ND, Bartus K, Grist J, Bennett DL, McMahon SB, Bradbury EJ. Conduction failure following spinal cord injury: functional and anatomical changes from acute to chronic stages. J Neurosci. 2011 Dec 14;31(50):18543-55. doi: 10.1523/JNEUROSCI.4306-11.2011. — View Citation

James ND, McMahon SB, Field-Fote EC, Bradbury EJ. Neuromodulation in the restoration of function after spinal cord injury. Lancet Neurol. 2018 Oct;17(10):905-917. doi: 10.1016/S1474-4422(18)30287-4. Epub 2018 Sep 18. — View Citation

Kawaishi Y, Domen K. The relationship between dynamic balancing ability and posture-related modulation of the soleus H-reflex. J Electromyogr Kinesiol. 2016 Feb;26:120-4. doi: 10.1016/j.jelekin.2015.11.010. Epub 2015 Dec 12. — View Citation

Kirshblum SC, Burns SP, Biering-Sorensen F, Donovan W, Graves DE, Jha A, Johansen M, Jones L, Krassioukov A, Mulcahey MJ, Schmidt-Read M, Waring W. International standards for neurological classification of spinal cord injury (revised 2011). J Spinal Cord Med. 2011 Nov;34(6):535-46. doi: 10.1179/204577211X13207446293695. No abstract available. — View Citation

Knikou M, Angeli CA, Ferreira CK, Harkema SJ. Soleus H-reflex gain, threshold, and amplitude as function of body posture and load in spinal cord intact and injured subjects. Int J Neurosci. 2009;119(11):2056-73. doi: 10.1080/00207450903139747. — View Citation

Knikou M, Angeli CA, Ferreira CK, Harkema SJ. Soleus H-reflex modulation during body weight support treadmill walking in spinal cord intact and injured subjects. Exp Brain Res. 2009 Mar;193(3):397-407. doi: 10.1007/s00221-008-1636-x. Epub 2008 Nov 15. — View Citation

Knikou M, Conway BA. Modulation of soleus H-reflex following ipsilateral mechanical loading of the sole of the foot in normal and complete spinal cord injured humans. Neurosci Lett. 2001 May 4;303(2):107-10. doi: 10.1016/s0304-3940(01)01718-9. — View Citation

Knikou M, Dixon L, Santora D, Ibrahim MM. Transspinal constant-current long-lasting stimulation: a new method to induce cortical and corticospinal plasticity. J Neurophysiol. 2015 Sep;114(3):1486-99. doi: 10.1152/jn.00449.2015. Epub 2015 Jun 24. — View Citation

Knikou M, Hajela N, Mummidisetty CK, Xiao M, Smith AC. Soleus H-reflex phase-dependent modulation is preserved during stepping within a robotic exoskeleton. Clin Neurophysiol. 2011 Jul;122(7):1396-404. doi: 10.1016/j.clinph.2010.12.044. Epub 2011 Jan 14. — View Citation

Knikou M, Hajela N, Mummidisetty CK. Corticospinal excitability during walking in humans with absent and partial body weight support. Clin Neurophysiol. 2013 Dec;124(12):2431-8. doi: 10.1016/j.clinph.2013.06.004. Epub 2013 Jun 28. — View Citation

Knikou M, Mummidisetty CK. Locomotor training improves premotoneuronal control after chronic spinal cord injury. J Neurophysiol. 2014 Jun 1;111(11):2264-75. doi: 10.1152/jn.00871.2013. Epub 2014 Mar 5. — View Citation

Knikou M, Murray LM. Neural interactions between transspinal evoked potentials and muscle spindle afferents in humans. J Electromyogr Kinesiol. 2018 Dec;43:174-183. doi: 10.1016/j.jelekin.2018.10.005. Epub 2018 Oct 9. — View Citation

Knikou M, Murray LM. Repeated transspinal stimulation decreases soleus H-reflex excitability and restores spinal inhibition in human spinal cord injury. PLoS One. 2019 Sep 26;14(9):e0223135. doi: 10.1371/journal.pone.0223135. eCollection 2019. — View Citation

Knikou M, Smith AC, Mummidisetty CK. Locomotor training improves reciprocal and nonreciprocal inhibitory control of soleus motoneurons in human spinal cord injury. J Neurophysiol. 2015 Apr 1;113(7):2447-60. doi: 10.1152/jn.00872.2014. Epub 2015 Jan 21. — View Citation

Knikou M. Function of group IB inhibition during assisted stepping in human spinal cord injury. J Clin Neurophysiol. 2012 Jun;29(3):271-7. doi: 10.1097/WNP.0b013e318257c2b7. — View Citation

Knikou M. Functional reorganization of soleus H-reflex modulation during stepping after robotic-assisted step training in people with complete and incomplete spinal cord injury. Exp Brain Res. 2013 Jul;228(3):279-96. doi: 10.1007/s00221-013-3560-y. Epub 2013 May 25. — View Citation

Knikou M. Neural control of locomotion and training-induced plasticity after spinal and cerebral lesions. Clin Neurophysiol. 2010 Oct;121(10):1655-68. doi: 10.1016/j.clinph.2010.01.039. Epub 2010 Apr 27. — View Citation

Knikou M. Neurophysiological characterization of transpinal evoked potentials in human leg muscles. Bioelectromagnetics. 2013 Dec;34(8):630-40. doi: 10.1002/bem.21808. Epub 2013 Sep 20. — View Citation

Knikou M. Plantar cutaneous input modulates differently spinal reflexes in subjects with intact and injured spinal cord. Spinal Cord. 2007 Jan;45(1):69-77. doi: 10.1038/sj.sc.3101917. Epub 2006 Mar 14. — View Citation

Knikou M. The H-reflex as a probe: pathways and pitfalls. J Neurosci Methods. 2008 Jun 15;171(1):1-12. doi: 10.1016/j.jneumeth.2008.02.012. Epub 2008 Mar 4. — View Citation

Knikou M. Transpinal and transcortical stimulation alter corticospinal excitability and increase spinal output. PLoS One. 2014 Jul 9;9(7):e102313. doi: 10.1371/journal.pone.0102313. eCollection 2014. — View Citation

Kobayashi M, Pascual-Leone A. Transcranial magnetic stimulation in neurology. Lancet Neurol. 2003 Mar;2(3):145-56. doi: 10.1016/s1474-4422(03)00321-1. — View Citation

Kraemer HC. A Source of False Findings in Published Research Studies: Adjusting for Covariates. JAMA Psychiatry. 2015 Oct;72(10):961-2. doi: 10.1001/jamapsychiatry.2015.1178. No abstract available. — View Citation

Kumru H, Benito-Penalva J, Valls-Sole J, Murillo N, Tormos JM, Flores C, Vidal J. Placebo-controlled study of rTMS combined with Lokomat(R) gait training for treatment in subjects with motor incomplete spinal cord injury. Exp Brain Res. 2016 Dec;234(12):3447-3455. doi: 10.1007/s00221-016-4739-9. Epub 2016 Jul 28. — View Citation

Learmonth YC, Paul L, McFadyen AK, Mattison P, Miller L. Reliability and clinical significance of mobility and balance assessments in multiple sclerosis. Int J Rehabil Res. 2012 Mar;35(1):69-74. doi: 10.1097/MRR.0b013e328350b65f. — View Citation

Lee JK, Emch GS, Johnson CS, Wrathall JR. Effect of spinal cord injury severity on alterations of the H-reflex. Exp Neurol. 2005 Dec;196(2):430-40. doi: 10.1016/j.expneurol.2005.08.018. Epub 2005 Sep 26. — View Citation

Lemay JF, Duclos C, Nadeau S, Gagnon DH. Postural control during gait initiation and termination of adults with incomplete spinal cord injury. Hum Mov Sci. 2015 Jun;41:20-31. doi: 10.1016/j.humov.2015.02.003. Epub 2015 Feb 26. — View Citation

Martinez SA, Nguyen ND, Bailey E, Doyle-Green D, Hauser HA, Handrakis JP, Knezevic S, Marett C, Weinman J, Romero AF, Santiago TM, Yang AH, Yung L, Asselin PK, Weir JP, Kornfeld SD, Bauman WA, Spungen AM, Harel NY. Multimodal cortical and subcortical exercise compared with treadmill training for spinal cord injury. PLoS One. 2018 Aug 9;13(8):e0202130. doi: 10.1371/journal.pone.0202130. eCollection 2018. — View Citation

Milosevic M, Gagnon DH, Gourdou P, Nakazawa K. Postural regulatory strategies during quiet sitting are affected in individuals with thoracic spinal cord injury. Gait Posture. 2017 Oct;58:446-452. doi: 10.1016/j.gaitpost.2017.08.032. Epub 2017 Aug 31. — View Citation

Milosevic M, Masani K, Kuipers MJ, Rahouni H, Verrier MC, McConville KM, Popovic MR. Trunk control impairment is responsible for postural instability during quiet sitting in individuals with cervical spinal cord injury. Clin Biomech (Bristol, Avon). 2015 Jun;30(5):507-12. doi: 10.1016/j.clinbiomech.2015.03.002. Epub 2015 Mar 14. — View Citation

Milosevic M, Yokoyama H, Grangeon M, Masani K, Popovic MR, Nakazawa K, Gagnon DH. Muscle synergies reveal impaired trunk muscle coordination strategies in individuals with thoracic spinal cord injury. J Electromyogr Kinesiol. 2017 Oct;36:40-48. doi: 10.1016/j.jelekin.2017.06.007. Epub 2017 Jul 1. — View Citation

Minassian K, Hofstoetter US, Dzeladini F, Guertin PA, Ijspeert A. The Human Central Pattern Generator for Locomotion: Does It Exist and Contribute to Walking? Neuroscientist. 2017 Dec;23(6):649-663. doi: 10.1177/1073858417699790. Epub 2017 Mar 28. — View Citation

Minassian K, Hofstoetter US. Spinal Cord Stimulation and Augmentative Control Strategies for Leg Movement after Spinal Paralysis in Humans. CNS Neurosci Ther. 2016 Apr;22(4):262-70. doi: 10.1111/cns.12530. Epub 2016 Feb 18. — View Citation

Molnar E. Long-term potentiation in cultured hippocampal neurons. Semin Cell Dev Biol. 2011 Jul;22(5):506-13. doi: 10.1016/j.semcdb.2011.07.017. Epub 2011 Jul 22. — View Citation

Morrison SA, Lorenz D, Eskay CP, Forrest GF, Basso DM. Longitudinal Recovery and Reduced Costs After 120 Sessions of Locomotor Training for Motor Incomplete Spinal Cord Injury. Arch Phys Med Rehabil. 2018 Mar;99(3):555-562. doi: 10.1016/j.apmr.2017.10.003. Epub 2017 Oct 26. — View Citation

Mummidisetty CK, Smith AC, Knikou M. Modulation of reciprocal and presynaptic inhibition during robotic-assisted stepping in humans. Clin Neurophysiol. 2013 Mar;124(3):557-64. doi: 10.1016/j.clinph.2012.09.007. Epub 2012 Oct 6. — View Citation

Murray LM, Knikou M. Remodeling Brain Activity by Repetitive Cervicothoracic Transspinal Stimulation after Human Spinal Cord Injury. Front Neurol. 2017 Feb 20;8:50. doi: 10.3389/fneur.2017.00050. eCollection 2017. — View Citation

Murray LM, Knikou M. Repeated cathodal transspinal pulse and direct current stimulation modulate cortical and corticospinal excitability differently in healthy humans. Exp Brain Res. 2019 Jul;237(7):1841-1852. doi: 10.1007/s00221-019-05559-2. Epub 2019 May 11. — View Citation

Murray LM, Knikou M. Transspinal stimulation increases motoneuron output of multiple segments in human spinal cord injury. PLoS One. 2019 Mar 7;14(3):e0213696. doi: 10.1371/journal.pone.0213696. eCollection 2019. — View Citation

Nielsen JB, Crone C, Hultborn H. The spinal pathophysiology of spasticity--from a basic science point of view. Acta Physiol (Oxf). 2007 Feb;189(2):171-80. doi: 10.1111/j.1748-1716.2006.01652.x. — View Citation

Nielsen JB. Human Spinal Motor Control. Annu Rev Neurosci. 2016 Jul 8;39:81-101. doi: 10.1146/annurev-neuro-070815-013913. Epub 2016 Mar 25. — View Citation

Norton JA, Gorassini MA. Changes in cortically related intermuscular coherence accompanying improvements in locomotor skills in incomplete spinal cord injury. J Neurophysiol. 2006 Apr;95(4):2580-9. doi: 10.1152/jn.01289.2005. Epub 2006 Jan 11. — View Citation

Papegaaij S, Baudry S, Negyesi J, Taube W, Hortobagyi T. Intracortical inhibition in the soleus muscle is reduced during the control of upright standing in both young and old adults. Eur J Appl Physiol. 2016 May;116(5):959-67. doi: 10.1007/s00421-016-3354-6. Epub 2016 Mar 22. — View Citation

Petersen JA, Spiess M, Curt A, Dietz V, Schubert M; EM-SCI Study Group. Spinal cord injury: one-year evolution of motor-evoked potentials and recovery of leg motor function in 255 patients. Neurorehabil Neural Repair. 2012 Oct;26(8):939-48. doi: 10.1177/1545968312438437. Epub 2012 Mar 28. — View Citation

Petruska JC, Ichiyama RM, Jindrich DL, Crown ED, Tansey KE, Roy RR, Edgerton VR, Mendell LM. Changes in motoneuron properties and synaptic inputs related to step training after spinal cord transection in rats. J Neurosci. 2007 Apr 18;27(16):4460-71. doi: 10.1523/JNEUROSCI.2302-06.2007. — View Citation

Platz T, Adler-Wiebe M, Roschka S, Lotze M. Enhancement of motor learning by focal intermittent theta burst stimulation (iTBS) of either the primary motor (M1) or somatosensory area (S1) in healthy human subjects. Restor Neurol Neurosci. 2018;36(1):117-130. doi: 10.3233/RNN-170774. — View Citation

Pulverenti TS, Islam MA, Alsalman O, Murray LM, Harel NY, Knikou M. Transspinal stimulation decreases corticospinal excitability and alters the function of spinal locomotor networks. J Neurophysiol. 2019 Dec 1;122(6):2331-2343. doi: 10.1152/jn.00554.2019. Epub 2019 Oct 2. — View Citation

Raithatha R, Carrico C, Powell ES, Westgate PM, Chelette Ii KC, Lee K, Dunsmore L, Salles S, Sawaki L. Non-invasive brain stimulation and robot-assisted gait training after incomplete spinal cord injury: A randomized pilot study. NeuroRehabilitation. 2016;38(1):15-25. doi: 10.3233/NRE-151291. — View Citation

Ramer LM, Ramer MS, Bradbury EJ. Restoring function after spinal cord injury: towards clinical translation of experimental strategies. Lancet Neurol. 2014 Dec;13(12):1241-56. doi: 10.1016/S1474-4422(14)70144-9. Epub 2014 Nov 10. — View Citation

Rath M, Vette AH, Ramasubramaniam S, Li K, Burdick J, Edgerton VR, Gerasimenko YP, Sayenko DG. Trunk Stability Enabled by Noninvasive Spinal Electrical Stimulation after Spinal Cord Injury. J Neurotrauma. 2018 Nov 1;35(21):2540-2553. doi: 10.1089/neu.2017.5584. Epub 2018 Jul 5. — View Citation

Rejc E, Angeli C, Harkema S. Effects of Lumbosacral Spinal Cord Epidural Stimulation for Standing after Chronic Complete Paralysis in Humans. PLoS One. 2015 Jul 24;10(7):e0133998. doi: 10.1371/journal.pone.0133998. eCollection 2015. — View Citation

Rejc E, Angeli CA, Bryant N, Harkema SJ. Effects of Stand and Step Training with Epidural Stimulation on Motor Function for Standing in Chronic Complete Paraplegics. J Neurotrauma. 2017 May 1;34(9):1787-1802. doi: 10.1089/neu.2016.4516. Epub 2016 Oct 5. — View Citation

Roby-Brami A, Bussel B. Long-latency spinal reflex in man after flexor reflex afferent stimulation. Brain. 1987 Jun;110 ( Pt 3):707-25. doi: 10.1093/brain/110.3.707. — View Citation

Rossignol S, Dubuc R, Gossard JP. Dynamic sensorimotor interactions in locomotion. Physiol Rev. 2006 Jan;86(1):89-154. doi: 10.1152/physrev.00028.2005. — View Citation

Rossignol S, Frigon A. Recovery of locomotion after spinal cord injury: some facts and mechanisms. Annu Rev Neurosci. 2011;34:413-40. doi: 10.1146/annurev-neuro-061010-113746. — View Citation

Sadlaoud K, Tazerart S, Brocard C, Jean-Xavier C, Portalier P, Brocard F, Vinay L, Bras H. Differential plasticity of the GABAergic and glycinergic synaptic transmission to rat lumbar motoneurons after spinal cord injury. J Neurosci. 2010 Mar 3;30(9):3358-69. doi: 10.1523/JNEUROSCI.6310-09.2010. — View Citation

Sasagawa S, Ushiyama J, Masani K, Kouzaki M, Kanehisa H. Balance control under different passive contributions of the ankle extensors: quiet standing on inclined surfaces. Exp Brain Res. 2009 Jul;196(4):537-44. doi: 10.1007/s00221-009-1876-4. Epub 2009 Jun 9. — View Citation

Sayenko DG, Rath M, Ferguson AR, Burdick JW, Havton LA, Edgerton VR, Gerasimenko YP. Self-Assisted Standing Enabled by Non-Invasive Spinal Stimulation after Spinal Cord Injury. J Neurotrauma. 2019 May 1;36(9):1435-1450. doi: 10.1089/neu.2018.5956. Epub 2018 Dec 15. — View Citation

Schindler-Ivens S, Shields RK. Low frequency depression of H-reflexes in humans with acute and chronic spinal-cord injury. Exp Brain Res. 2000 Jul;133(2):233-41. doi: 10.1007/s002210000377. — View Citation

Schubert M, Curt A, Jensen L, Dietz V. Corticospinal input in human gait: modulation of magnetically evoked motor responses. Exp Brain Res. 1997 Jun;115(2):234-46. doi: 10.1007/pl00005693. — View Citation

Shapkova EY, Schomburg ED. Two types of motor modulation underlying human stepping evoked by spinal cord electrical stimulation (SCES). Acta Physiol Pharmacol Bulg. 2001;26(3):155-7. — View Citation

Simonsen EB, Dyhre-Poulsen P. Amplitude of the human soleus H reflex during walking and running. J Physiol. 1999 Mar 15;515 ( Pt 3)(Pt 3):929-39. doi: 10.1111/j.1469-7793.1999.929ab.x. — View Citation

Slawinska U, Majczynski H, Dai Y, Jordan LM. The upright posture improves plantar stepping and alters responses to serotonergic drugs in spinal rats. J Physiol. 2012 Apr 1;590(7):1721-36. doi: 10.1113/jphysiol.2011.224931. Epub 2012 Feb 20. — View Citation

Smith AC, Knikou M. A Review on Locomotor Training after Spinal Cord Injury: Reorganization of Spinal Neuronal Circuits and Recovery of Motor Function. Neural Plast. 2016;2016:1216258. doi: 10.1155/2016/1216258. Epub 2016 May 11. — View Citation

Smith AC, Mummidisetty CK, Rymer WZ, Knikou M. Locomotor training alters the behavior of flexor reflexes during walking in human spinal cord injury. J Neurophysiol. 2014 Nov 1;112(9):2164-75. doi: 10.1152/jn.00308.2014. Epub 2014 Aug 13. — View Citation

Smith AC, Rymer WZ, Knikou M. Locomotor training modifies soleus monosynaptic motoneuron responses in human spinal cord injury. Exp Brain Res. 2015 Jan;233(1):89-103. doi: 10.1007/s00221-014-4094-7. Epub 2014 Sep 10. — View Citation

Soto O, Valls-Sole J, Shanahan P, Rothwell J. Reduction of intracortical inhibition in soleus muscle during postural activity. J Neurophysiol. 2006 Oct;96(4):1711-7. doi: 10.1152/jn.00133.2006. Epub 2006 Jun 21. — View Citation

Tansey KE, McKay WB, Kakulas BA. Restorative neurology: consideration of the new anatomy and physiology of the injured nervous system. Clin Neurol Neurosurg. 2012 Jun;114(5):436-40. doi: 10.1016/j.clineuro.2012.01.010. Epub 2012 Feb 1. — View Citation

Thomas SL, Gorassini MA. Increases in corticospinal tract function by treadmill training after incomplete spinal cord injury. J Neurophysiol. 2005 Oct;94(4):2844-55. doi: 10.1152/jn.00532.2005. Epub 2005 Jul 6. — View Citation

Thompson AK, Pomerantz FR, Wolpaw JR. Operant conditioning of a spinal reflex can improve locomotion after spinal cord injury in humans. J Neurosci. 2013 Feb 6;33(6):2365-75. doi: 10.1523/JNEUROSCI.3968-12.2013. — View Citation

Thompson AK, Wolpaw JR. Operant conditioning of spinal reflexes: from basic science to clinical therapy. Front Integr Neurosci. 2014 Mar 18;8:25. doi: 10.3389/fnint.2014.00025. eCollection 2014. — View Citation

Thompson AK, Wolpaw JR. Restoring walking after spinal cord injury: operant conditioning of spinal reflexes can help. Neuroscientist. 2015 Apr;21(2):203-15. doi: 10.1177/1073858414527541. Epub 2014 Mar 17. — View Citation

Tokuno CD, Taube W, Cresswell AG. An enhanced level of motor cortical excitability during the control of human standing. Acta Physiol (Oxf). 2009 Mar;195(3):385-95. doi: 10.1111/j.1748-1716.2008.01898.x. Epub 2008 Sep 4. — View Citation

van Middendorp JJ, Hosman AJ, Donders AR, Pouw MH, Ditunno JF Jr, Curt A, Geurts AC, Van de Meent H; EM-SCI Study Group. A clinical prediction rule for ambulation outcomes after traumatic spinal cord injury: a longitudinal cohort study. Lancet. 2011 Mar 19;377(9770):1004-10. doi: 10.1016/S0140-6736(10)62276-3. Epub 2011 Mar 4. — View Citation

van Middendorp JJ, Hosman AJ, Pouw MH; EM-SCI Study Group; Van de Meent H. ASIA impairment scale conversion in traumatic SCI: is it related with the ability to walk? A descriptive comparison with functional ambulation outcome measures in 273 patients. Spinal Cord. 2009 Jul;47(7):555-60. doi: 10.1038/sc.2008.162. Epub 2008 Dec 23. — View Citation

Wagner FB, Mignardot JB, Le Goff-Mignardot CG, Demesmaeker R, Komi S, Capogrosso M, Rowald A, Seanez I, Caban M, Pirondini E, Vat M, McCracken LA, Heimgartner R, Fodor I, Watrin A, Seguin P, Paoles E, Van Den Keybus K, Eberle G, Schurch B, Pralong E, Becce F, Prior J, Buse N, Buschman R, Neufeld E, Kuster N, Carda S, von Zitzewitz J, Delattre V, Denison T, Lambert H, Minassian K, Bloch J, Courtine G. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. 2018 Nov;563(7729):65-71. doi: 10.1038/s41586-018-0649-2. Epub 2018 Oct 31. — View Citation

Wernig A, Muller S, Nanassy A, Cagol E. Laufband therapy based on 'rules of spinal locomotion' is effective in spinal cord injured persons. Eur J Neurosci. 1995 Apr 1;7(4):823-9. doi: 10.1111/j.1460-9568.1995.tb00686.x. Erratum In: Eur J Neurosci 1995 Jun 1;7(6):1429. — View Citation

Winter DA, Patla AE, Prince F, Ishac M, Gielo-Perczak K. Stiffness control of balance in quiet standing. J Neurophysiol. 1998 Sep;80(3):1211-21. doi: 10.1152/jn.1998.80.3.1211. — View Citation

Wirth B, van Hedel HJ, Curt A. Ankle paresis in incomplete spinal cord injury: relation to corticospinal conductivity and ambulatory capacity. J Clin Neurophysiol. 2008 Aug;25(4):210-7. doi: 10.1097/WNP.0b013e318183f4e3. — View Citation

Yang F, Xu Q, Cheong YK, Shechter R, Sdrulla A, He SQ, Tiwari V, Dong X, Wacnik PW, Meyer R, Raja SN, Guan Y. Comparison of intensity-dependent inhibition of spinal wide-dynamic range neurons by dorsal column and peripheral nerve stimulation in a rat model of neuropathic pain. Eur J Pain. 2014 Aug;18(7):978-88. doi: 10.1002/j.1532-2149.2013.00443.x. Epub 2014 Jan 6. — View Citation

Zewdie ET, Roy FD, Yang JF, Gorassini MA. Facilitation of descending excitatory and spinal inhibitory networks from training of endurance and precision walking in participants with incomplete spinal cord injury. Prog Brain Res. 2015;218:127-55. doi: 10.1016/bs.pbr.2014.12.005. Epub 2015 Mar 29. — View Citation

Zorner B, Blanckenhorn WU, Dietz V; EM-SCI Study Group; Curt A. Clinical algorithm for improved prediction of ambulation and patient stratification after incomplete spinal cord injury. J Neurotrauma. 2010 Jan;27(1):241-52. doi: 10.1089/neu.2009.0901. — View Citation

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Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasticity of spinal neuronal networks	Neurophysiological assessments probing changes in excitatory and inhibitory spinal reflex excitability from interventions by recording amplitude modulation of the soleus H-reflex following posterior tibial and common peroneal nerves stimulation both at rest and during robotic-assisted stepping.	4 years
Primary	Plasticity of corticospinal networks	Neurophysiological measurements assessing changes in corticospinal excitability from the interventions by recording responses to single-pulse transcranial magnetic stimulation (TMS) at rest and during robotic-assisted stepping.	4 years
Secondary	Ambulatory function	Change in two-minute walk and 10-meter timed test.	4 years
Secondary	Balance	Changes in BESTtest clinical assessments.	4 years
Secondary	Autonomic function	Questionnaire assessing participants perceived changes in bowel, bladder, and sexual function	4 years