{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:46:36Z","timestamp":1782823596342,"version":"3.54.5"},"reference-count":16,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Reynolds Innovative Spinal Electrical Stimulation Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Transcutaneous spinal cord stimulation (tSCS) is a promising neuromodulation approach for motor recovery after spinal cord injury (SCI), yet clinical programming remains largely dependent on subjective parameter selection. This study evaluated high-density surface EMG (HD-sEMG)\u2013derived spatial and temporal features as objective biomarkers for tSCS optimization in three adults with chronic cervical SCI. A 64-channel electrode array recorded stimulation-evoked responses across five cervical stimulation levels, four pulse widths, and graded amplitudes. Features describing activation magnitude, spatial distribution, cluster morphology, and temporal dynamics were extracted from epoch-based activation maps. Of the three enrolled participants, two demonstrated measurable stimulation-evoked responses and contributed to the paired-pulse analyses, whereas pulse-width analyses were limited to a single responsive muscle (left flexor carpi) in one participant. Paired-pulse analysis identified root mean square (RMS) as the most discriminative feature, revealing nonlinear, muscle- and level-specific dose\u2013response relationships in which maximal suppression often occurred at intermediate rather than maximal amplitudes. Increasing pulse width expanded the spatial extent of recruitment (active area: p = 0.006; convex hull area: p = 0.004) without altering response timing. Polarity reversal analysis demonstrated stable innervation zone localization across stimulation levels and amplitudes. These findings establish a spatially resolved HD-sEMG framework that may support individualized tSCS parameter selection in SCI.<\/jats:p>","DOI":"10.3390\/bioengineering13070766","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:01:17Z","timestamp":1782813677000},"page":"766","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Objective Biomarker Development for Parameter Optimization in Neuromodulation Using High-Density EMG Temporal and Spatial Features"],"prefix":"10.3390","volume":"13","author":[{"given":"Shirin","family":"Madarshahian","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Health Data Science, College of Health, Lehigh University, Bethlehem, PA 18015, USA"},{"name":"Good Shepherd Rehabilitation Network, Allentown, PA 18104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1830-7823","authenticated-orcid":false,"given":"Nikoo","family":"Javadpour","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, P. C. Rossin College of Engineering & Applied Science, Lehigh University, Bethlehem, PA 18015, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Trakhtorchuck","sequence":"additional","affiliation":[{"name":"Raphael Center for Neurorestoration, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Guerrero-David","sequence":"additional","affiliation":[{"name":"Jefferson Moss-Magee Rehabilitation Hospital, Philadelphia, PA 19141, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Gustafson","sequence":"additional","affiliation":[{"name":"Physical Medicine and Rehabilitation, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0943-3406","authenticated-orcid":false,"given":"James S.","family":"Harrop","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6101-1158","authenticated-orcid":false,"given":"Caio M.","family":"Matias","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. J.","family":"Mulcahey","sequence":"additional","affiliation":[{"name":"Center for Outcomes and Measurement, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4061-3747","authenticated-orcid":false,"given":"Alessandro","family":"Napoli","sequence":"additional","affiliation":[{"name":"Raphael Center for Neurorestoration, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8073-0796","authenticated-orcid":false,"given":"Alexander","family":"Vaccaro","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Rothman Orthopaedics, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mijail","family":"Serruya","sequence":"additional","affiliation":[{"name":"Raphael Center for Neurorestoration, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Taylor, C., McHugh, C., Mockler, D., Minogue, C., Reilly, R.B., and Fleming, N. (2021). Transcutaneous spinal cord stimulation and motor responses in individuals with spinal cord injury: A methodological review. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0260166"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e80995","DOI":"10.2196\/80995","article-title":"Effectiveness of Transcutaneous Spinal Cord Stimulation for Lower Limb Rehabilitation in Spinal Cord Injury: Protocol for a Systematic Review and Meta-Analysis","volume":"14","author":"Shankar","year":"2025","journal-title":"JMIR Res. Protoc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12","DOI":"10.46292\/sci25-00028","article-title":"Protocol for Safety, Feasibility, and Efficacy of Using Targeted Transcutaneous Spinal Cord Stimulation to Treat Hypotension During Acute Inpatient Rehabilitation in Individuals With SCI","volume":"32","author":"Chavez","year":"2026","journal-title":"Top. Spinal Cord Inj. Rehabil."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Brihmat, N., Allexandre, D., Saleh, S., Zhong, J., Yue, G.H., and Forrest, G.F. (2022). Stimulation Parameters Used During Repetitive Transcranial Magnetic Stimulation for Motor Recovery and Corticospinal Excitability Modulation in SCI: A Scoping Review. Front. Hum. Neurosci., 16.","DOI":"10.3389\/fnhum.2022.800349"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/ner.13252","article-title":"Biomarker Optimization of Spinal Cord Stimulation Therapies","volume":"24","author":"Nagel","year":"2021","journal-title":"Neuromodulation Technol. Neural Interface"},{"key":"ref_6","first-page":"77","article-title":"Quantitative and sensitive assessment of neurophysiological status after human spinal cord injury","volume":"17","author":"Li","year":"2012","journal-title":"J. Neurosurg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"381","DOI":"10.3390\/traumacare2020031","article-title":"Surface EMG in Subacute and Chronic Care after Traumatic Spinal Cord Injuries","volume":"2","author":"Balbinot","year":"2022","journal-title":"Trauma Care"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Veit, N.C., Yang, C., Aalla, S., Kishta, A., McKenzie, K., Roth, E.J., and Jayaraman, A. (2024). Spinal motor evoked responses elicited by transcutaneous spinal cord stimulation in chronic stroke: Correlation between spinal cord excitability, demographic characteristics, and functional outcomes. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0312183"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Madarshahian, S., Trakhtorchuck, M., Guerrero-David, T., Gustafson, K., Harrop, J.S., Matias, C.M., Mulcahey, M., Napoli, A., Vaccaro, A., and Serruya, M. (2025). Optimizing Transcutaneous Spinal Cord Stimulation: An Exploratory Study on the Role of Electrode Montages and Stimulation Intensity on Reflex Pathway Modulation. Bioengineering, 12.","DOI":"10.3390\/bioengineering12040410"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s12984-020-00786-z","article-title":"Spatial filtering for enhanced high-density surface electromyographic examination of neuromuscular changes and its application to spinal cord injury","volume":"17","author":"Zhang","year":"2020","journal-title":"J. Neuroeng. Rehabil."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s12984-026-01874-2","article-title":"Adaptation of motor unit synergies in the synergetic ankle plantarflexors in ambulatory persons with incomplete spinal cord injury","volume":"23","author":"Duan","year":"2026","journal-title":"J. Neuroeng. Rehabil."},{"key":"ref_12","first-page":"20556683241280242","article-title":"Initial feasibility evaluation of the RISES system: An innovative and activity-based closed-loop framework for spinal cord injury rehabilitation and recovery","volume":"11","author":"Madarshahian","year":"2024","journal-title":"J. Rehabil. Assist. Technol. Eng."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1007\/BF02348439","article-title":"Single motor unit analysis from spatially filtered surface electromyogram signals. Part I: Spatial selectivity","volume":"41","author":"Farina","year":"2003","journal-title":"Med. Biol. Eng. Comput."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.medengphy.2008.05.006","article-title":"Effect of spatial filtering on crosstalk reduction in surface EMG recordings","volume":"31","author":"Mesin","year":"2009","journal-title":"Med. Eng. Phys."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Beausejour, J.P., Rusch, J., Knowles, K.S., Pagan, J.I., Chaput, M., Norte, G.E., DeFreitas, J.M., and Stock, M.S. (2024). A Comparison of Techniques to Determine Active Motor Threshold for Transcranial Magnetic Stimulation Research. bioRxiv.","DOI":"10.1101\/2024.04.19.590327"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"056040","DOI":"10.1088\/1741-2552\/ac7dfc","article-title":"Detection of motor-evoked potentials below the noise floor: Rethinking the motor stimulation threshold","volume":"19","author":"Li","year":"2022","journal-title":"J. Neural Eng."}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/7\/766\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:04:38Z","timestamp":1782821078000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/7\/766"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":16,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["bioengineering13070766"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering13070766","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]}}}