{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:13:38Z","timestamp":1793121218562,"version":"4.5.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Upper limb motor impairments after stroke cause patients partial or total loss of the capability of performing daily living, working, and social activities, which significantly affects the quality of life (QoL) of patients and brings a heavy burden to their families and society. As a non-invasive neuromodulation technique, transcranial magnetic stimulation (TMS) can act not only on the cerebral cortex, but also on peripheral nerves, nerve roots, and muscle tissues. Previous studies have shown that magnetic stimulation on the cerebral cortex and peripheral tissues has a positive effect on the recovery of upper limb motor function after stroke, however, few studies have reported the combination of the two.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study was to investigate whether high frequency repetitive transcranial magnetic stimulation (HF-rTMS) combined with cervical nerve root magnetic stimulation more effectively ameliorates upper limb motor function in stroke patients. We hypothesized that the combination of the two can achieve a synergistic effect and further promotes functional recovery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixty patients with stroke were randomly divided into four groups and received real or sham rTMS stimulation and cervical nerve root magnetic stimulation consecutively before other therapies, once daily over five fractions per week for a total of 15 times. We evaluated the upper limb motor function and activities of daily living of the patients at the time of pre-treatment, post-treatment, and 3-month follow up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All patients completed study procedures without any adverse effects. The upper limb motor function and activities of daily living improved in patients of each group were improved after treatment (post 1) and 3 months after treatment (post 2). Combination treatment was significantly better than single treatments alone or sham.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Both rTMS and cervical nerve root magnetic stimulation effectively promoted upper limb motor recovery in patients with stroke. The protocol combining the two is more beneficial for motor improvement and patients can easily tolerate it.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p><jats:ext-link>https:\/\/www.chictr.org.cn\/<\/jats:ext-link>, identifier ChiCTR2100048558.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2023.1100464","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T06:59:57Z","timestamp":1675753197000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["The effects of combined high-frequency repetitive transcranial magnetic stimulation and cervical nerve root magnetic stimulation on upper extremity motor recovery following stroke"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaofang","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qunqiang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhua","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianshe","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiduo","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baolin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2015.00226","article-title":"A review of transcranial magnetic stimulation and multimodal neuroimaging to characterize post-stroke neuroplasticity.","volume":"6","author":"Auriat","year":"2015","journal-title":"Front. Neurol."},{"key":"B2","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.neucli.2015.08.002","article-title":"Repetitive peripheral magnetic stimulation to reduce pain or improve sensorimotor impairments: A literature review on parameters of application and afferents recruitment.","volume":"45","author":"Beaulieu","year":"2015","journal-title":"Neurophysiol. Clin."},{"key":"B3","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.brs.2019.10.019","article-title":"Transcranial direct current stimulation associated with physical-therapy in acute stroke patients - A randomized, triple blind, sham-controlled study.","volume":"13","author":"Bornheim","year":"2020","journal-title":"Brain Stimul."},{"key":"B4","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/j.neuron.2019.05.041","article-title":"Neuromodulation of spike-timing-dependent plasticity: Past, present, and future.","volume":"103","author":"Brzosko","year":"2019","journal-title":"Neuron"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00144","article-title":"Acute and post-acute neuromodulation induces stroke recovery by promoting survival signaling, neurogenesis, and pyramidal tract plasticity.","volume":"13","author":"Caglayan","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"B6","article-title":"Efficacy of functional magnetic stimulation in improving upper extremity function after stroke: A randomized, single-blind, controlled study.","volume":"48","author":"Chen","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"B7","doi-asserted-by":"crossref","first-page":"12913","DOI":"10.1073\/pnas.1404109111","article-title":"Optogenetic neuronal stimulation promotes functional recovery after stroke.","volume":"111","author":"Cheng","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2015.00407","article-title":"Modulation of sensorimotor cortex by repetitive peripheral magnetic stimulation.","volume":"9","author":"Gallasch","year":"2015","journal-title":"Front. Hum. Neurosci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2047","DOI":"10.4103\/1673-5374.282266","article-title":"Paired associated magnetic stimulation promotes neural repair in the rat middle cerebral artery occlusion model of stroke.","volume":"15","author":"Gao","year":"2020","journal-title":"Neural Regen. Res."},{"key":"B10","doi-asserted-by":"crossref","first-page":"652","DOI":"10.2340\/16501977-2590","article-title":"Intra- and inter-rater reliability of fugl-meyer assessment of upper extremity in stroke.","volume":"51","author":"Hernandez","year":"2019","journal-title":"J. Rehabil. Med."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01747-y","article-title":"High-frequency repetitive transcranial magnetic stimulation improves functional recovery by inhibiting neurotoxic polarization of astrocytes in ischemic rats.","volume":"17","author":"Hong","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-022-00735-7","article-title":"High-frequency repetitive transcranial magnetic stimulation (rTMS) protects against ischemic stroke by inhibiting M1 microglia polarization through let-7b-5p\/HMGA2\/NF-kappaB signaling pathway.","volume":"23","author":"Hong","year":"2022","journal-title":"BMC Neurosci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1161\/STROKEAHA.111.649756","article-title":"Effects of repetitive transcranial magnetic stimulation on motor functions in patients with stroke: A meta-analysis.","volume":"43","author":"Hsu","year":"2012","journal-title":"Stroke"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3473","DOI":"10.1016\/j.jstrokecerebrovasdis.2018.08.007","article-title":"Virtual reality in upper extremity rehabilitation of stroke patients: A randomized controlled trial.","volume":"27","author":"Ikbali Afsar","year":"2018","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"B15","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1177\/02692155211072189","article-title":"A randomized controlled trial of repetitive peripheral magnetic stimulation applied in early subacute stroke: Effects on severe upper-limb impairment.","volume":"36","author":"Jiang","year":"2022","journal-title":"Clin. Rehabil."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2022.106446","article-title":"Effect of high-frequency repetitive peripheral magnetic stimulation on motor performance in intracerebral haemorrhage: A clinical trial.","volume":"31","author":"Ke","year":"2022","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1161\/01.STR.0000221233.55497.51","article-title":"Repetitive transcranial magnetic stimulation-induced corticomotor excitability and associated motor skill acquisition in chronic stroke.","volume":"37","author":"Kim","year":"2006","journal-title":"Stroke"},{"key":"B18","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.rehab.2015.05.005","article-title":"Basic principles of transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS).","volume":"58","author":"Klomjai","year":"2015","journal-title":"Ann. Phys. Rehabil. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.1016\/j.clinph.2017.06.041","article-title":"Modulation of motor cortex excitability by paired peripheral and transcranial magnetic stimulation.","volume":"128","author":"Kumru","year":"2017","journal-title":"Clin. Neurophysiol."},{"key":"B20","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1016\/j.clinph.2014.05.021","article-title":"Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS).","volume":"125","author":"Lefaucheur","year":"2014","journal-title":"Clin. Neurophysiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.4103\/1673-5374.193236","article-title":"Effects of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper limb motor dysfunction in patients with subacute cerebral infarction.","volume":"11","author":"Li","year":"2016","journal-title":"Neural Regen. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2862","DOI":"10.1111\/j.1460-9568.2007.05531.x","article-title":"LTP-like changes induced by paired associative stimulation of the primary somatosensory cortex in humans: Source analysis and associated changes in behaviour.","volume":"25","author":"Litvak","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1109\/TMI.2022.3143133","article-title":"Closed-loop construction and analysis of cortico-muscular-cortical functional network after stroke.","volume":"41","author":"Liu","year":"2022","journal-title":"IEEE Trans. Med. Imaging"},{"key":"B24","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/j.clinph.2012.12.049","article-title":"Magnetic-motor-root stimulation: Review.","volume":"124","author":"Matsumoto","year":"2013","journal-title":"Clin. Neurophysiol."},{"key":"B25","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.neuron.2020.01.039","article-title":"Advanced neurotechnologies for the restoration of motor function.","volume":"105","author":"Micera","year":"2020","journal-title":"Neuron"},{"key":"B26","doi-asserted-by":"publisher","first-page":"175","DOI":"10.31661\/jbpe.v0i0.879","article-title":"The effect of high-frequency repetitive transcranial magnetic stimulation on functional indices of affected upper limb in patients with subacute stroke.","volume":"11","author":"Moslemi Haghighi","year":"2021","journal-title":"J. Biomed. Phys. Eng."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/S0140-6736(17)32152-9","article-title":"Global, regional, and national age-sex specific mortality for 264 causes of death, 1980\u20132016: A systematic analysis for the Global Burden of Disease Study 2016.","volume":"390","author":"Naghavi","year":"2017","journal-title":"Lancet"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-017-0409-2","article-title":"Validity and reliability of a performance evaluation tool based on the modified Barthel Index for stroke patients.","volume":"17","author":"Ohura","year":"2017","journal-title":"BMC Med. Res. Methodol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1136\/jnnp-2016-315030","article-title":"Brain regions important for recovery after severe post-stroke upper limb paresis.","volume":"88","author":"Rondina","year":"2017","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B30","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.clinph.2020.10.003","article-title":"Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines.","volume":"132","author":"Rossi","year":"2021","journal-title":"Clin. Neurophysiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1016\/j.clinph.2015.02.001","article-title":"Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. committee.","volume":"126","author":"Rossini","year":"2015","journal-title":"Clin. Neurophysiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.jstrokecerebrovasdis.2011.10.004","article-title":"Comparison of the effects of high- and low-frequency repetitive transcranial magnetic stimulation on upper limb hemiparesis in the early phase of stroke.","volume":"22","author":"Sasaki","year":"2013","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"B33","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1113\/jphysiol.2002.023317","article-title":"Mechanisms of enhancement of human motor cortex excitability induced by interventional paired associative stimulation.","volume":"543","author":"Stefan","year":"2002","journal-title":"J. Physiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1177\/1545968313510972","article-title":"Corticospinal tract integrity and lesion volume play different roles in chronic hemiparesis and its improvement through motor practice.","volume":"28","author":"Sterr","year":"2014","journal-title":"Neurorehabil. Neural Repair"},{"key":"B35","doi-asserted-by":"publisher","first-page":"T174","DOI":"10.1016\/j.neuroimage.2007.03.033","article-title":"A fronto-parietal network is mediating improvement of motor function related to repetitive peripheral magnetic stimulation: A PET-H2O15 study.","volume":"36","author":"Struppler","year":"2007","journal-title":"Neuroimage"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2459","DOI":"10.4103\/1673-5374.339012","article-title":"Effects of paired associative magnetic stimulation between nerve root and cortex on motor function of lower limbs after spinal cord injury: Study protocol for a randomized controlled trial.","volume":"17","author":"Sun","year":"2022","journal-title":"Neural Regen. Res."},{"key":"B37","doi-asserted-by":"crossref","DOI":"10.3390\/medicina57111215","article-title":"Effects of high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) on upper extremity motor function in stroke patients: A systematic review.","volume":"57","author":"Vabalaite","year":"2021","journal-title":"Medicina"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-020-01936-5","article-title":"Exploring the experiences of stroke patients treated with transcranial magnetic stimulation for upper limb recovery: A qualitative study.","volume":"20","author":"van Lieshout","year":"2020","journal-title":"BMC Neurol."},{"key":"B39","doi-asserted-by":"crossref","first-page":"e98","DOI":"10.1161\/STR.0000000000000098","article-title":"Guidelines for adult stroke rehabilitation and recovery: A guideline for healthcare professionals from the American heart association\/American stroke association.","volume":"47","author":"Winstein","year":"2016","journal-title":"Stroke"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.636184","article-title":"Repetitive transcranial magnetic stimulation on the affected hemisphere enhances hand functional recovery in subacute adult stroke patients: A randomized trial.","volume":"13","author":"Yang","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"B41","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1136\/svn-2019-000321","article-title":"Chinese stroke association guidelines for clinical management of cerebrovascular disorders: Executive summary and 2019 update of clinical management of stroke rehabilitation.","volume":"5","author":"Zhang","year":"2020","journal-title":"Stroke Vasc. Neurol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.4103\/1673-5374.335161","article-title":"Nerve root magnetic stimulation improves locomotor function following spinal cord injury with electrophysiological improvements and cortical synaptic reconstruction.","volume":"17","author":"Zheng","year":"2022","journal-title":"Neural Regen. Res."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2023.1100464\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T14:27:45Z","timestamp":1676039265000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2023.1100464\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,7]]},"references-count":42,"alternative-id":["10.3389\/fnins.2023.1100464"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2023.1100464","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,7]]},"article-number":"1100464"}}