{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T07:39:38Z","timestamp":1792481978234,"version":"4.5.0"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Spinal Cord"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Structured Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>Methodological review and expert perspective.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To examine the methodological challenges in designing rigorous clinical trials for transcutaneous spinal cord stimulation (tSCS) in chronic spinal cord injury (SCI), with particular focus on challenges of sham control implementation, and to propose alternative trial design approaches that balance scientific rigor with practical feasibility and ethical considerations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>United States.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed the design considerations that influenced the Up-LIFT pivotal trial, examining three critical constraints: the technical limitations of creating safe and convincing sham stimulation for extended protocols; the participant burden associated with traditional sham-controlled designs; and the heightened risks during the COVID-19 pandemic. We reviewed existing literature on placebo effects in neuromodulation, technical challenges of sham tSCS implementation, and ethical considerations specific to the SCI population. Alternative methodological approaches were evaluated, including sequential self-controlled designs, biomarker-guided approaches, and adaptive trial designs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Traditional sham controls for tSCS face serious technical challenges because participants readily detect stimulation parameters, minimal currents produce detectable neuromodulatory effects, and extended protocols amplify these issues through knowledge sharing and functional feedback. Ethical concerns include substantial participant burden, potential for lessebo effects when a sham is suspected, and erosion of therapeutic relationships through prolonged deception. The COVID-19 pandemic added critical safety considerations for the vulnerable SCI population. Alternative designs, such as sequential self-controlled approaches, as implemented in Up-LIFT, can maintain scientific validity while addressing these constraints.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The unique challenges of tSCS clinical trials necessitate innovative methodological approaches beyond traditional placebo-controlled designs. Sequential self-controlled designs, biomarker-guided studies, and adaptive trial methodologies offer scientifically sound alternatives that respect participant welfare while generating robust evidence. Future research should pursue dual paths: developing improved sham paradigms while advancing alternative trial methodologies suitable for neuromodulation-enhanced rehabilitation interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41393-026-01190-5","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T15:15:56Z","timestamp":1772810156000},"page":"352-361","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Study design considerations in clinical trials testing transcutaneous stimulation for spinal cord injury"],"prefix":"10.1038","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0931-0286","authenticated-orcid":false,"given":"James","family":"Guest","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chet","family":"Moritz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"1190_CR1","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1089\/neu.2020.7473","volume":"38","author":"S Kirshblum","year":"2021","unstructured":"Kirshblum S, Snider B, Eren F, Guest J. Characterizing natural recovery after traumatic spinal cord injury. J Neurotrauma. 2021;38:1267\u201384.","journal-title":"J Neurotrauma"},{"key":"1190_CR2","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1056\/NEJMoa1803588","volume":"379","author":"CA Angeli","year":"2018","unstructured":"Angeli CA, Boakye M, Morton RA, Vogt J, Benton K, Chen Y, et al. Recovery of over-ground walking after chronic motor complete spinal cord injury. N Engl J Med. 2018;379:1244\u201350.","journal-title":"N Engl J Med"},{"key":"1190_CR3","doi-asserted-by":"publisher","first-page":"2633","DOI":"10.1523\/JNEUROSCI.2374-19.2020","volume":"40","author":"FD Benavides","year":"2020","unstructured":"Benavides FD, Jo HJ, Lundell H, Edgerton VR, Gerasimenko Y, Perez MA. Cortical and subcortical effects of transcutaneous spinal cord stimulation in humans with tetraplegia. J Neurosci. 2020;40:2633\u201343.","journal-title":"J Neurosci"},{"key":"1190_CR4","doi-asserted-by":"publisher","first-page":"2056","DOI":"10.1089\/neu.2023.0438","volume":"41","author":"G Singh","year":"2024","unstructured":"Singh G, Sharma P, Forrest G, Harkema S, Behrman A, Gerasimenko Y. Spinal cord transcutaneous stimulation in cervical spinal cord injury: A review examining upper extremity neuromotor control, recovery mechanisms, and future directions. J Neurotrauma. 2024;41:2056\u201374.","journal-title":"J Neurotrauma"},{"key":"1190_CR5","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1016\/j.neurom.2025.01.005","volume":"28","author":"J Suggitt","year":"2025","unstructured":"Suggitt J, Symonds J, D\u2019Amico JM. Safety and effectiveness of multisite transcutaneous spinal cord stimulation combined with activity-based therapy when delivered in a community rehabilitation setting: A real-world pilot study. Neuromodulation. 2025;28:1144\u201356.","journal-title":"Neuromodulation"},{"key":"1190_CR6","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1038\/s41591-024-02940-9","volume":"30","author":"C Moritz","year":"2024","unstructured":"Moritz C, Field-Fote EC, Tefertiller C, van Nes I, Trumbower R, Kalsi-Ryan S, et al. Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: A safety and efficacy trial. Nat Med. 2024;30:1276\u201383.","journal-title":"Nat Med"},{"key":"1190_CR7","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1111\/ner.13381","volume":"24","author":"M Boakye","year":"2021","unstructured":"Boakye M, Ugiliweneza B, Madrigal F, Mesbah S, Ovechkin A, Angeli C, et al. Clinical trial designs for neuromodulation in chronic spinal cord injury using epidural stimulation. Neuromodulation. 2021;24:405\u201315.","journal-title":"Neuromodulation"},{"key":"1190_CR8","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1093\/brain\/awaf040","volume":"148","author":"JLK Kramer","year":"2025","unstructured":"Kramer JLK, Lam T, Rossi F, Illes J. On the use of sham transcutaneous spinal cord stimulation in spinal cord injury clinical trials. Brain. 2025;148:1456\u201358.","journal-title":"Brain"},{"key":"1190_CR9","first-page":"2015","volume":"ume 6","author":"F Duecker","year":"2015","unstructured":"Duecker F, Sack AT. Rethinking the role of sham TMS. Front Psychol. 2015;ume 6:2015.","journal-title":"Front Psychol"},{"key":"1190_CR10","doi-asserted-by":"publisher","first-page":"3380","DOI":"10.1111\/ejn.14497","volume":"50","author":"R Greinacher","year":"2019","unstructured":"Greinacher R, Buh\u00f4t L, M\u00f6ller L, Learmonth G. The time course of ineffective sham-blinding during low-intensity (1 mA) transcranial direct current stimulation. Eur J Neurosci. 2019;50:3380\u20138.","journal-title":"Eur J Neurosci"},{"key":"1190_CR11","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1038\/s41586-025-09028-5","volume":"643","author":"MP Kilgard","year":"2025","unstructured":"Kilgard MP, Epperson JD, Adehunoluwa EA, Swank C, Porter AL, Pruitt DT, et al. Closed-loop vagus nerve stimulation aids recovery from spinal cord injury. Nature. 2025;643:1030\u20136.","journal-title":"Nature"},{"key":"1190_CR12","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.brainresrev.2007.09.002","volume":"57","author":"VR Edgerton","year":"2008","unstructured":"Edgerton VR, Courtine G, Gerasimenko YP, Lavrov I, Ichiyama RM, Fong AJ, et al. Training locomotor networks. Brain Res Rev. 2008;57:241\u201354.","journal-title":"Brain Res Rev"},{"key":"1190_CR13","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s42234-021-00077-5","volume":"7","author":"I Se\u00e1\u00f1ez","year":"2021","unstructured":"Se\u00e1\u00f1ez I, Capogrosso M. Motor improvements enabled by spinal cord stimulation combined with physical training after spinal cord injury: Review of experimental evidence in animals and humans. Bioelectron Med. 2021;7:16.","journal-title":"Bioelectron Med"},{"key":"1190_CR14","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1002\/ana.26622","volume":"93","author":"HJ Jo","year":"2023","unstructured":"Jo HJ, Kizziar E, Sangari S, Chen D, Kessler A, Kim K, et al. Multisite hebbian plasticity restores function in humans with spinal cord injury. Ann Neurol. 2023;93:1198\u2013213.","journal-title":"Ann Neurol"},{"key":"1190_CR15","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/6751810","volume":"2017","author":"M Knikou","year":"2017","unstructured":"Knikou M. Spinal excitability changes after transspinal and transcortical paired associative stimulation in humans. Neural Plast. 2017;2017:6751810.","journal-title":"Neural Plast"},{"key":"1190_CR16","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.brainres.2007.03.057","volume":"1153","author":"R Bogacz","year":"2007","unstructured":"Bogacz R, McClure SM, Li J, Cohen JD, Montague PR. Short-term memory traces for action bias in human reinforcement learning. Brain Res. 2007;1153:111\u201321.","journal-title":"Brain Res"},{"key":"1190_CR17","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S1350-4533(02)00040-1","volume":"25","author":"DN Rushton","year":"2003","unstructured":"Rushton DN. Functional Electrical Stimulation and rehabilitation\u2014an hypothesis. Med Eng Phys. 2003;25:75\u20138.","journal-title":"Med Eng Phys"},{"key":"1190_CR18","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1002\/ana.24734","volume":"80","author":"CE Lang","year":"2016","unstructured":"Lang CE, Strube MJ, Bland MD, Waddell KJ, Cherry-Allen KM, Nudo RJ, et al. Dose response of task-specific upper limb training in people at least 6 months poststroke: A phase II, single-blind, randomized, controlled trial. Ann Neurol. 2016;80:342\u201354.","journal-title":"Ann Neurol"},{"key":"1190_CR19","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1038\/sj.sc.3102007","volume":"45","author":"J Fawcett","year":"2007","unstructured":"Fawcett J, Curt A, Steeves J, Coleman WP, Tuszynski M, Lammertse D, et al. 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. 2007;45:190\u2013205.","journal-title":"Spinal cord"},{"key":"1190_CR20","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.apmr.2021.09.012","volume":"103","author":"DS Tulsky","year":"2022","unstructured":"Tulsky DS, Boulton AJ, Kisala PA, Heinemann AW, Charlifue S, Kalpakjian CZ, et al. Physical function recovery trajectories after spinal cord injury. Arch Phys Med Rehabil. 2022;103:215\u201323.","journal-title":"Arch Phys Med Rehabil"},{"key":"1190_CR21","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.jphys.2017.08.005","volume":"63","author":"LA Harvey","year":"2017","unstructured":"Harvey LA, Dunlop SA, Churilov L, Galea MP. Spinal Cord Injury Physical Activity Hands On Trial C. Early intensive hand rehabilitation is not more effective than usual care plus one-to-one hand therapy in people with sub-acute spinal cord injury (\u2018Hands On\u2019): a randomised trial. J Physiother. 2017;63:197\u2013204.","journal-title":"J Physiother"},{"key":"1190_CR22","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1126\/science.1060937","volume":"293","author":"R de la Fuente-Fernandez","year":"2001","unstructured":"de la Fuente-Fernandez R, Ruth TJ, Sossi V, Schulzer M, Calne DB, Stoessl AJ. Expectation and dopamine release: mechanism of the placebo effect in Parkinson\u2019s disease. Science. 2001;293:1164\u20136.","journal-title":"Science"},{"key":"1190_CR23","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.652552","volume":"15","author":"MA Thomaidou","year":"2021","unstructured":"Thomaidou MA, Peerdeman KJ, Koppeschaar MI, Evers AWM, Veldhuijzen DS. How negative experience influences the brain: A comprehensive review of the neurobiological underpinnings of nocebo hyperalgesia. Front Neurosci. 2021;15:652552.","journal-title":"Front Neurosci"},{"key":"1190_CR24","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1001\/jama.2022.18231","volume":"328","author":"S Hara","year":"2022","unstructured":"Hara S, Andresen H, Solheim O, Carlsen SM, Sundstr\u00f8m T, L\u00f8nne G, et al. Effect of spinal cord burst stimulation vs placebo stimulation on disability in patients with chronic radicular pain after lumbar spine surgery: A randomized clinical trial. JAMA. 2022;328:1506\u201314.","journal-title":"JAMA"},{"key":"1190_CR25","doi-asserted-by":"publisher","first-page":"3915","DOI":"10.1038\/s41380-024-02638-x","volume":"29","author":"NTM Huneke","year":"2024","unstructured":"Huneke NTM, Amin J, Baldwin DS, Bellato A, Brandt V, Chamberlain SR, et al. Placebo effects in randomized trials of pharmacological and neurostimulation interventions for mental disorders: An umbrella review. Molecular Psychiatry. 2024;29:3915\u201325.","journal-title":"Molecular Psychiatry"},{"key":"1190_CR26","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1002\/mds.26500","volume":"31","author":"TA Mestre","year":"2016","unstructured":"Mestre TA, Lang AE, Okun MS. Factors influencing the outcome of deep brain stimulation: Placebo, nocebo, lessebo, and lesion effects. Mov Disord. 2016;31:290\u20136.","journal-title":"Mov Disord"},{"key":"1190_CR27","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/S0033-3182(93)71845-9","volume":"34","author":"TL Bayer","year":"1993","unstructured":"Bayer TL, Chiang E, Coverdale JH, Bangs M, Goodearle H. Anxiety in experimentally induced somatoform symptoms. Psychosomatics. 1993;34:416\u201323.","journal-title":"Psychosomatics"},{"key":"1190_CR28","doi-asserted-by":"publisher","first-page":"e0125223","DOI":"10.1371\/journal.pone.0125223","volume":"10","author":"M Emadi Andani","year":"2015","unstructured":"Emadi Andani M, Tinazzi M, Corsi N, Fiorio M. Modulation of inhibitory corticospinal circuits induced by a nocebo procedure in motor performance. PLoS One. 2015;10:e0125223.","journal-title":"PLoS One"},{"key":"1190_CR29","doi-asserted-by":"publisher","first-page":"e2125531","DOI":"10.1001\/jamanetworkopen.2021.25531","volume":"4","author":"BDM Jones","year":"2021","unstructured":"Jones BDM, Razza LB, Weissman CR, Karbi J, Vine T, Mulsant LS, et al. Magnitude of the placebo response across treatment modalities used for treatment-resistant depression in adults: A systematic review and meta-analysis. JAMA Network Open. 2021;4:e2125531. -e","journal-title":"JAMA Network Open"},{"key":"1190_CR30","doi-asserted-by":"publisher","first-page":"528","DOI":"10.3390\/bioengineering10050528","volume":"10","author":"JM Hope","year":"2023","unstructured":"Hope JM, Field-Fote EC. Assessment of dorsiflexion ability across tasks in persons with subacute SCI after combined locomotor training and transcutaneous spinal stimulation. Bioengineering (Basel). 2023;10:528.","journal-title":"Bioengineering (Basel)"},{"key":"1190_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-11306-5","volume":"12","author":"R Huang","year":"2022","unstructured":"Huang R, Nikooyan AA, Moore LD, Zdunowski S, Morikawa E, Sierro T, et al. Minimal handgrip force is needed for transcutaneous electrical stimulation to improve hand functions of patients with severe spinal cord injury. Sci Rep. 2022;12:7733.","journal-title":"Sci Rep"},{"key":"1190_CR32","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1016\/j.apmr.2024.06.011","volume":"105","author":"K McKenzie","year":"2024","unstructured":"McKenzie K, Veit N, Aalla S, Yang C, Giffhorn M, Lynott A, et al. Combining neuromodulation strategies in spinal cord injury gait rehabilitation: A proof of concept, randomized, crossover trial. Arch Phys Med Rehabil. 2024;105:1930\u20137.","journal-title":"Arch Phys Med Rehabil"},{"key":"1190_CR33","doi-asserted-by":"publisher","first-page":"7103","DOI":"10.1111\/ejn.16614","volume":"60","author":"G Stepien","year":"2024","unstructured":"Stepien G, Jelonek W, Goodall S, McNeil CJ, Lochynski D. Corticospinal excitability and voluntary activation of the quadriceps muscle is not affected by a single session of anodal transcutaneous spinal direct current stimulation in healthy, young adults. Eur J Neurosci. 2024;60:7103\u201323.","journal-title":"Eur J Neurosci"},{"key":"1190_CR34","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/s41531-024-00792-1","volume":"10","author":"L Wang","year":"2024","unstructured":"Wang L, Sun H, Zhang H, Ji M, Gan C, Shan A, et al. Effect of cerebrospinal dual-site magnetic stimulation on freezing of gait in Parkinson\u2019s disease. NPJ Parkinsons Dis. 2024;10:183.","journal-title":"NPJ Parkinsons Dis"},{"key":"1190_CR35","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1038\/nrn3976","volume":"16","author":"TD Wager","year":"2015","unstructured":"Wager TD, Atlas LY. The neuroscience of placebo effects: connecting context, learning and health. Nat Rev Neurosci. 2015;16:403\u201318.","journal-title":"Nat Rev Neurosci"},{"key":"1190_CR36","doi-asserted-by":"publisher","first-page":"15","DOI":"10.46292\/sci23-00040S","volume":"29","author":"J Oh","year":"2023","unstructured":"Oh J, Scheffler MS, Mahan EE, King ST, Martin CA, Dinh J, et al. Combinatorial effects of transcutaneous spinal stimulation and task-specific training to enhance hand motor output after paralysis. Top Spinal Cord Inj Rehabil. 2023;29:15\u201322.","journal-title":"Top Spinal Cord Inj Rehabil"},{"key":"1190_CR37","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1097\/JU.0000000000004189","volume":"212","author":"A Stampas","year":"2024","unstructured":"Stampas A, Korupolu R, Lee KH, Salazar B, Khavari R. Reduction of overactive bladder medications in spinal cord injury with self-administered neuromodulation: A randomized trial. J Urol. 2024;212:800\u201310.","journal-title":"J Urol"},{"key":"1190_CR38","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41536-020-00114-y","volume":"6","author":"D Cortes","year":"2021","unstructured":"Cortes D, Pera MF. The genetic basis of inter-individual variation in recovery from traumatic brain injury. NPJ Regen Med. 2021;6:5.","journal-title":"NPJ Regen Med"},{"key":"1190_CR39","doi-asserted-by":"publisher","first-page":"S101","DOI":"10.1016\/j.apmr.2011.11.040","volume":"93","author":"J Whyte","year":"2012","unstructured":"Whyte J, Barrett AM. Advancing the evidence base of rehabilitation treatments: a developmental approach. Arch Phys Med Rehabil. 2012;93:S101\u201310.","journal-title":"Arch Phys Med Rehabil"},{"key":"1190_CR40","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.neurom.2024.05.005","volume":"28","author":"K Gelenitis","year":"2025","unstructured":"Gelenitis K, Santamaria A, Pradarelli J, Rieger M, Inanici F, Tefertiller C, et al. Non-invasive transcutaneous spinal cord stimulation programming recommendations for the treatment of upper extremity impairment in tetraplegia. Neuromodulation. 2025;28:162\u201373.","journal-title":"Neuromodulation"},{"key":"1190_CR41","doi-asserted-by":"publisher","first-page":"4175","DOI":"10.3758\/s13428-022-02012-1","volume":"55","author":"S Tueller","year":"2023","unstructured":"Tueller S, Ramirez D, Cance JD, Ye A, Wheeler AC, Fan Z, et al. Power analysis for idiographic (within-subject) clinical trials: Implications for treatments of rare conditions and precision medicine. Behav Res Methods. 2023;55:4175\u201399.","journal-title":"Behav Res Methods"},{"key":"1190_CR42","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/j.1365-2753.2004.00505.x","volume":"11","author":"V Morton","year":"2005","unstructured":"Morton V, Torgerson DJ. Regression to the mean: Treatment effect without the intervention. J Eval Clin Pract. 2005;11:59\u201365.","journal-title":"J Eval Clin Pract"},{"key":"1190_CR43","doi-asserted-by":"publisher","first-page":"e47514","DOI":"10.1371\/journal.pone.0047514","volume":"7","author":"NE O\u2019Connell","year":"2012","unstructured":"O\u2019Connell NE, Cossar J, Marston L, Wand BM, Bunce D, Moseley GL, et al. Rethinking clinical trials of transcranial direct current stimulation: Participant and assessor blinding is inadequate at intensities of 2mA. PLoS One. 2012;7:e47514.","journal-title":"PLoS One"},{"key":"1190_CR44","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.1041932","volume":"16","author":"M Pereira","year":"2022","unstructured":"Pereira M, Fernandes SR, Miranda PC, de Carvalho M. Lumbar trans-spinal direct current stimulation: A modeling-experimental approach to dorsal root ganglia stimulation. Front Neurosci. 2022;16:1041932.","journal-title":"Front Neurosci"},{"key":"1190_CR45","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1152\/jn.00266.2024","volume":"133","author":"HT Finn","year":"2025","unstructured":"Finn HT, Parono M, Bye EA, Taylor JL, Gandevia SC, Heroux ME, et al. Differential effects of stimulation waveform and intensity on the neural structures activated by lumbar transcutaneous spinal cord stimulation. J Neurophysiol. 2025;133:447\u201363.","journal-title":"J Neurophysiol"},{"key":"1190_CR46","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s12984-025-01545-8","volume":"22","author":"N Comino-Suarez","year":"2025","unstructured":"Comino-Suarez N, Moreno JC, Megia-Garcia A, Del-Ama AJ, Serrano-Munoz D, Avendano-Coy J, et al. Transcutaneous spinal cord stimulation combined with robotic-assisted body weight-supported treadmill training enhances motor score and gait recovery in incomplete spinal cord injury: a double-blind randomized controlled clinical trial. J Neuroeng Rehabil. 2025;22:15.","journal-title":"J Neuroeng Rehabil"},{"key":"1190_CR47","doi-asserted-by":"publisher","first-page":"s34","DOI":"10.1017\/cjn.2023.24","volume":"50","author":"A Mollica","year":"2023","unstructured":"Mollica A, Greben R, Cyr M, Olson JA, Burke MJ. Placebo Effects and Neuromodulation: Ethical Considerations and Recommendations. Can J Neurol Sci. 2023;50:s34\u2013s41.","journal-title":"Can J Neurol Sci"},{"key":"1190_CR48","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1080\/23294515.2015.1021494","volume":"7","author":"J Pugh","year":"2016","unstructured":"Pugh J, Kahane G, Maslen H, Savulescu J. Lay attitudes toward deception in medicine: Theoretical considerations and empirical evidence. AJOB Empir Bioeth. 2016;7:31\u20138.","journal-title":"AJOB Empir Bioeth"},{"key":"1190_CR49","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1001\/jama.2012.115","volume":"307","author":"L Colloca","year":"2012","unstructured":"Colloca L, Finniss D. Nocebo effects, patient-clinician communication, and therapeutic outcomes. JAMA. 2012;307:567\u20138.","journal-title":"JAMA"},{"key":"1190_CR50","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1177\/014107680409701205","volume":"97","author":"FG Miller","year":"2004","unstructured":"Miller FG, Kaptchuk TJ. Sham procedures and the ethics of clinical trials. J R Soc Med. 2004;97:576\u20138.","journal-title":"J R Soc Med"},{"key":"1190_CR51","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1089\/neu.2015.4064","volume":"33","author":"KD Anderson","year":"2015","unstructured":"Anderson KD, Cowan RE, Horsewell J. Facilitators and barriers to spinal cord injury clinical trial participation: Multi-National perspective of people living with spinal cord injury. Journal of Neurotrauma. 2015;33:493\u20139.","journal-title":"Journal of Neurotrauma"},{"key":"1190_CR52","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1038\/s41393-020-00547-8","volume":"58","author":"MJ Mulcahey","year":"2020","unstructured":"Mulcahey MJ, Jones LAT, Rockhold F, Rupp R, Kramer JLK, Kirshblum S, et al. Adaptive trial designs for spinal cord injury clinical trials directed to the central nervous system. Spinal Cord. 2020;58:1235\u201348.","journal-title":"Spinal Cord"},{"key":"1190_CR53","doi-asserted-by":"publisher","first-page":"e2036155","DOI":"10.1001\/jamanetworkopen.2020.36155","volume":"4","author":"RH Perlis","year":"2021","unstructured":"Perlis RH, Haneuse SJPA, Rubenfeld GD, Fihn SD, Rivara FP. Reporting clinical studies affected by the COVID-19 pandemic: Guidelines for authors. JAMA Network Open. 2021;4:e2036155. -e","journal-title":"JAMA Network Open"},{"key":"1190_CR54","doi-asserted-by":"publisher","DOI":"10.3389\/fresc.2022.995244","volume":"3","author":"KD Anderson","year":"2022","unstructured":"Anderson KD, Korupolu R, Musselman KE, Pierce J, Wilson JR, Yozbatiran N, et al. Multi-center, single-blind randomized controlled trial comparing functional electrical stimulation therapy to conventional therapy in incomplete tetraplegia. Front Rehabil Sci. 2022;3:995244.","journal-title":"Front Rehabil Sci"},{"key":"1190_CR55","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1002\/emp2.12282","volume":"1","author":"MK Henzel","year":"2020","unstructured":"Henzel MK, Shultz JM, Dyson-Hudson TA, Svircev JN, DiMarco AF, Gater DR Jr. Initial assessment and management of respiratory infections in persons with spinal cord injuries and disorders in the COVID-19 era. J Am Coll Emerg Physicians Open. 2020;1:1404\u201312.","journal-title":"J Am Coll Emerg Physicians Open"},{"key":"1190_CR56","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1089\/neu.2020.7461","volume":"38","author":"B Hoogenes","year":"2021","unstructured":"Hoogenes B, Queree M, Townson A, Willms R, Eng JJ. COVID-19 and spinal cord injury: Clinical presentation, clinical course, and clinical outcomes: A rapid systematic review. J Neurotrauma. 2021;38:1242\u201350.","journal-title":"J Neurotrauma"},{"key":"1190_CR57","doi-asserted-by":"publisher","first-page":"2002","DOI":"10.3390\/healthcare12192002","volume":"12","author":"A Senthinathan","year":"2024","unstructured":"Senthinathan A, Tadrous M, Hussain S, Ahmad A, Chu C, Craven BC, et al. COVID-19 and mortality in the spinal cord injury population: Examining the impact of sex, mental health, and injury etiology. Healthcare (Basel). 2024;12:2002.","journal-title":"Healthcare (Basel)"},{"key":"1190_CR58","doi-asserted-by":"publisher","first-page":"e67308","DOI":"10.7554\/eLife.67308","volume":"10","author":"CJR Illingworth","year":"2021","unstructured":"Illingworth CJR, Hamilton WL, Warne B, Routledge M, Popay A, Jackson C, et al. Superspreaders drive the largest outbreaks of hospital onset COVID-19 infections. eLife. 2021;10:e67308.","journal-title":"eLife"},{"key":"1190_CR59","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1001\/jama.2020.4689","volume":"323","author":"MM McDermott","year":"2020","unstructured":"McDermott MM, Newman AB. Preserving clinical trial integrity during the coronavirus pandemic. JAMA. 2020;323:2135\u20136.","journal-title":"JAMA"},{"key":"1190_CR60","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1152\/japplphysiol.01128.2014","volume":"118","author":"DG Sayenko","year":"2015","unstructured":"Sayenko DG, Atkinson DA, Dy CJ, Gurley KM, Smith VL, Angeli C, et al. Spinal segment-specific transcutaneous stimulation differentially shapes activation pattern among motor pools in humans. J Appl Physiol (1985). 2015;118:1364\u201374.","journal-title":"J Appl Physiol (1985)"},{"key":"1190_CR61","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2020.135052","volume":"732","author":"MA Islam","year":"2020","unstructured":"Islam MA, Zaaya M, Comiskey E, Demetrio J, O\u2019Keefe A, Palazzo N, et al. Modulation of soleus H-reflex excitability following cervical transspinal conditioning stimulation in humans. Neuroscience Letters. 2020;732:135052.","journal-title":"Neuroscience Letters"},{"key":"1190_CR62","doi-asserted-by":"crossref","unstructured":"Steele AG, Manson GA, Horner PJ, Sayenko DG, Contreras-Vidal JL. Effects of transcutaneous spinal stimulation on spatiotemporal cortical activation patterns: a proof-of-concept EEG study. J Neural Eng. 2022;19.","DOI":"10.1088\/1741-2552\/ac7b4b"},{"key":"1190_CR63","doi-asserted-by":"publisher","unstructured":"Dalrymple AN, Hooper CA, Kuriakose MG, Capogrosso M, Weber DJ. Using a high-frequency carrier does not improve comfort of transcutaneous spinal cord stimulation. J Neural Eng. 2023;20. https:\/\/doi.org\/10.1088\/1741-2552\/acabe8.","DOI":"10.1088\/1741-2552\/acabe8"},{"key":"1190_CR64","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1093\/ptj\/pzz005","volume":"99","author":"E Ariel","year":"2019","unstructured":"Ariel E, Ratmansky M, Levkovitz Y, Goor-Aryeh I. Efficiency of tissue penetration by currents induced by 3 electrotherapeutic techniques: A comparative study using a novel deep-tissue measuring technique. Phys Ther. 2019;99:540\u20138.","journal-title":"Phys Ther"},{"key":"1190_CR65","doi-asserted-by":"publisher","first-page":"3993","DOI":"10.1523\/JNEUROSCI.3931-13.2014","volume":"34","author":"M Fiorio","year":"2014","unstructured":"Fiorio M, Emadi Andani M, Marotta A, Classen J, Tinazzi M. Placebo-induced changes in excitatory and inhibitory corticospinal circuits during motor performance. J Neurosci. 2014;34:3993\u20134005.","journal-title":"J Neurosci"}],"container-title":["Spinal Cord"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41393-026-01190-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41393-026-01190-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41393-026-01190-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T07:02:15Z","timestamp":1792479735000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41393-026-01190-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,6]]},"references-count":65,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["1190"],"URL":"https:\/\/doi.org\/10.1038\/s41393-026-01190-5","relation":{},"ISSN":["1362-4393","1476-5624"],"issn-type":[{"value":"1362-4393","type":"print"},{"value":"1476-5624","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,6]]},"assertion":[{"value":"12 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Both authors (J.G. and C.M.) served as investigators in the Up-LIFT clinical trial discussed in this manuscript. Neither author has any equity interest, or other commercial relationship with Onward Medical, the sponsor of the Up-LIFT trial. The authors declare no other conflicts of interest related to this work.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}