{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:01:35Z","timestamp":1790701295561,"version":"4.1.0"},"reference-count":46,"publisher":"IMR Press","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Integr. Neurosci."],"abstract":"<jats:p>Migraine is one of the main causes of neurological disability, especially in young adults. Recent developments in preventive migraine therapies have improved outcomes for many patients, while highlighting the need for additional therapeutic options for those who remain refractory to pharmacological prophylaxis. Repetitive Transcranial Magnetic Stimulation (rTMS) has emerged as a promising neuromodulatory tool. We searched published literature for articles describing the efficacy of different rTMS protocols in the treatment of migraine. The literature search was conducted using PubMed and Scopus for articles published up to March 26, 2026. Twenty-four articles were categorized based on cortical targets (primary motor cortex [M1], dorsolateral prefrontal cortex (DLPFC), Vertex, Visual Cortex or Multifocal). High-frequency rTMS (HF-rTMS) targeting either the M1 or the left DLPFC demonstrated potential efficacy for specific goals such as reducing monthly migraine days, pain intensity, and medication intake. According to studies using neurophysiological data (obtained via transcranial magnetic stimulation-electroencephalography (TMS-EEG)), clinical improvement correlates with enhanced frontotemporal network connectivity and restored cortical plasticity. Guided rTMS stimulation through functional connectivity between the DLPFC and the pregenual cingulate cortex (PGC) may increase the precision of pain processing network modulation. Low-frequency rTMS (LF-rTMS) protocols also show potential benefits, including reductions in headache frequency, intensity, disability and medication use, although the supporting evidence is limited and derived primarily from small and uncontrolled studies. Multifocal rTMS paradigms showed promising efficacy in episodic migraine. Considerable heterogeneity in study design, stimulation protocols, and outcome measures limited the ability to draw reliable conclusions. Frequency and localization may be important determinants of clinical success. Future research should focus on network-based, personalized stimulation protocols to potentially increase long-term therapeutic benefit.<\/jats:p>","DOI":"10.31083\/jin52992","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:16:31Z","timestamp":1790698591000},"source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Applications of rTMS in Migraine Prophylaxis"],"prefix":"10.31083","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5536-5013","authenticated-orcid":true,"given":"Vasileios","family":"Siokas","sequence":"first","affiliation":[{"name":"Department of Neurology, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5979-9916","authenticated-orcid":true,"given":"Chrysoula","family":"Marogianni","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2958-5220","authenticated-orcid":true,"given":"Ioannis","family":"Liampas","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1862-7499","authenticated-orcid":true,"given":"Maria","family":"Sokratous","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniil","family":"Tsirelis","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stavroula","family":"Dardioti","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7872-1188","authenticated-orcid":true,"given":"Antonia","family":"Tsika","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0212-5576","authenticated-orcid":true,"given":"Polyxeni","family":"Stamati","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2957-641X","authenticated-orcid":true,"given":"Efthimios","family":"Dardiotis","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Ferrari MD, Goadsby PJ, Burstein R, Kurth T, Ayata C, Charles A, et al. Migraine. Nature Reviews. Disease Primers. 2022; 8: 2.","DOI":"10.1038\/s41572-021-00328-4"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Ashina M. Migraine. The New England Journal of Medicine. 2020; 383: 1866\u20131876.","DOI":"10.1056\/NEJMra1915327"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Tsirelis D, Tsekouras A, Stamati P, Liampas I, Zoupa E, Dastamani M, et al. The impact of genetic factors on the response to migraine therapy. Reviews in the Neurosciences. 2024; 35: 789\u2013812.","DOI":"10.1515\/revneuro-2024-0045"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"GBD 2023 Headache Collaborators. Global, regional, and national burden of headache disorders, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023. The Lancet. Neurology. 2025; 24: 1005\u20131015.","DOI":"10.1016\/S1474-4422(25)00402-8"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Zhang N, Robbins MS. Migraine. Annals of Internal Medicine. 2023; 176: ITC1\u2013ITC16.","DOI":"10.7326\/AITC202301170"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Dong L, Dong W, Jin Y, Jiang Y, Li Z, Yu D. The Global Burden of Migraine: A 30-Year Trend Review and Future Projections by Age, Sex, Country, and Region. Pain and Therapy. 2025; 14: 297\u2013315.","DOI":"10.1007\/s40122-024-00690-7"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Song X, Zhu Q, Su L, Shi L, Chi H, Yan Y, et al. New perspectives on migraine treatment: a review of the mechanisms and effects of complementary and alternative therapies. Frontiers in Neurology. 2024; 15: 1372509.","DOI":"10.3389\/fneur.2024.1372509"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Khan J, Asoom LIA, Sunni AA, Rafique N, Latif R, Saif SA, et al. Genetics, pathophysiology, diagnosis, treatment, management, and prevention of migraine. Biomedicine & Pharmacotherapy. 2021; 139: 111557.","DOI":"10.1016\/j.biopha.2021.111557"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Karsan N. Pathophysiology of Migraine. Continuum (Minneapolis, Minn.). 2024; 30: 325\u2013343.","DOI":"10.1212\/CON.0000000000001412"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018). Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology. 2020; 131: 474\u2013528.","DOI":"10.1016\/j.clinph.2019.11.002"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Zhou J, Wang Y, Luo X, Fitzgerald PB, Cash RFH, Fitzgibbon BM, et al. Revisiting the effects of rTMS over the dorsolateral prefrontal cortex on pain: An updated systematic review and meta-analysis. 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Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology. 2025; 173: 166\u2013172.","DOI":"10.1016\/j.clinph.2025.03.019"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Cocores AN, Smirnoff L, Greco G, Herrera R, Monteith TS. Update on Neuromodulation for Migraine and Other Primary Headache Disorders: Recent Advances and New Indications. Current pain and headache reports. 2025; 29: 47.","DOI":"10.1007\/s11916-024-01314-7"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Starling AJ, Tepper SJ, Marmura MJ, Shamim EA, Robbins MS, Hindiyeh N, et al. A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE Study). Cephalalgia: an International Journal of Headache. 2018; 38: 1038\u20131048.","DOI":"10.1177\/0333102418762525"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Yuan H, Orr SL, Al-Karagholi MAM, Ashina M, Cohen F, Diener HC, et al. International Headache society evidence-based guidelines on the use of non-invasive neuromodulation devices for the acute and preventive treatment of migraine. Cephalalgia: an International Journal of Headache. 2025; 45: 3331024251388377.","DOI":"10.1177\/03331024251388377"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Naji F, Sharbafchi MR, Khorvash F, Maracy MR, Ghasemi Mobarak Abadi N. The Efficacy of Repetitive Transcranial Magnetic Stimulation (rTMS) versus Transcranial Direct-Current Stimulation (tDCS) on Migraine Headaches: A Randomized Clinical Trial. Advanced Biomedical Research. 2024; 13: 7.","DOI":"10.4103\/abr.abr_142_23"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Kumar A, Mattoo B, Bhatia R, Kumaran S, Bhatia R. Neuronavigation based 10 sessions of repetitive transcranial magnetic stimulation therapy in chronic migraine: an exploratory study. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2021; 42: 131\u2013139.","DOI":"10.1007\/s10072-020-04505-3"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Misra UK, Kalita J, Bhoi SK. High frequency repetitive transcranial magnetic stimulation (rTMS) is effective in migraine prophylaxis: an open labeled study. Neurological Research. 2012; 34: 547\u2013551.","DOI":"10.1179\/1743132812Y.0000000045"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Misra UK, Kalita J, Tripathi G, Bhoi SK. Role of \u03b2 endorphin in pain relief following high rate repetitive transcranial magnetic stimulation in migraine. Brain Stimulation. 2017; 10: 618\u2013623.","DOI":"10.1016\/j.brs.2017.02.006"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Kalita J, Kumar S, Singh VK, Misra UK. A Randomized Controlled Trial of High Rate rTMS Versus rTMS and Amitriptyline in Chronic Migraine. 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Journal of the Neurological Sciences. 2004; 227: 67\u201371.","DOI":"10.1016\/j.jns.2004.08.008"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Sahu AK, Sinha VK, Goyal N. Effect of adjunctive intermittent theta-burst repetitive transcranial magnetic stimulation as a prophylactic treatment in migraine patients: A double-blind sham-controlled study. Indian Journal of Psychiatry. 2019; 61: 139\u2013145.","DOI":"10.4103\/psychiatry.IndianJPsychiatry_472_18"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Amin R, Emara T, Ashour S, Hemeda M, Salah Eldin N, Hamed S, et al. The role of left prefrontal transcranial magnetic stimulation in episodic migraine prophylaxis. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery. 2020; 56: 19.","DOI":"10.1186\/s41983-019-0140-5"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Clemente L, Paparella G, Scannicchio S, Abbatantuono C, Tancredi G, Ladisa E, et al. Dorso lateral prefrontal cortex stimulation with TMS in chronic migraine individuals refractory to anti-CGRP monoclonal antibodies: Clinical, neuropsychological and neurophysiological effects. Cephalalgia: an International Journal of Headache. 2025; 45: 3331024251364843.","DOI":"10.1177\/03331024251364843"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Granato A, Fantini J, Monti F, Furlanis G, Musho Ilbeh S, Semenic M, et al. Dramatic placebo effect of high frequency repetitive TMS in treatment of chronic migraine and medication overuse headache. Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia. 2019; 60: 96\u2013100.","DOI":"10.1016\/j.jocn.2018.09.021"},{"key":"ref30","unstructured":"Khairkar P, Khoiwal R, Bamal I, Khivsara A, Gupta NK, Pateriya A, et al. High-Frequency Repetitive Transcranial Magnetic Stimulation at 20 Hz: A Case Series Evaluating Efficacy in Treatment-Resistant Migraine After 10 Hz Repetitive Transcranial Magnetic Stimulation Failure. Pain Medicine Case Reports. 2025; 9: 243\u2013247."},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Shah J, Dhull P, Somasekharan M, Soni R, Gupta S. Repetitive transcranial magnetic stimulation for prophylactive treatment of chronic migraine: A randomised, single-blind, parallel-group, sham-controlled trial. Neurology Asia. 2022; 27: 137.","DOI":"10.54029\/2022mau"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Leahu P, Bange M, Ciolac D, Scheiter S, Matei A, Gonzalez-Escamilla G, et al. Increased migraine-free intervals with multifocal repetitive transcranial magnetic stimulation. Brain Stimulation. 2021; 14: 1544\u20131552.","DOI":"10.1016\/j.brs.2021.10.383"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Teepker M, H\u00f6tzel J, Timmesfeld N, Reis J, Mylius V, Haag A, et al. Low-frequency rTMS of the vertex in the prophylactic treatment of migraine. Cephalalgia: an International Journal of Headache. 2010; 30: 137\u2013144.","DOI":"10.1111\/j.1468-2982.2009.01911.x"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Todorov V, Bogdanova D, Tonchev P, Milanov I. REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION OVER TWO TARGET AREAS, SHAM STIMULATION AND TOPIRAMATE IN THE TREATMENT OF CHRONIC MIGRAINE. Comptes rendus de l\u2019Acade\u2019mie bulgare des Sciences. 2020; 73: 1298\u20131305.","DOI":"10.7546\/CRABS.2020.09.15"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Zhu J, Fan H, Ma X, Fan Y, Mao Q, Xiao J, et al. Repetitive transcranial magnetic stimulation for vestibular migraine in women of reproductive age: a retrospective propensity score-matched study. Frontiers in Neurology. 2026; 16: 1735437.","DOI":"10.3389\/fneur.2025.1735437"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Zhen Z, Li Y, Zhou J, Li H, Zalesky A, Cash R, et al. Prospective open-label trial of personalised connectivity-guided transcranial magnetic stimulation therapy for migraine. The Journal of Headache and Pain. 2026; 27: 44.","DOI":"10.1186\/s10194-026-02273-7"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Zardouz S, Shi L, Leung A. A feasible repetitive transcranial magnetic stimulation clinical protocol in migraine prevention. SAGE Open Medical Case Reports. 2016; 4: 2050313X16675257.","DOI":"10.1177\/2050313X16675257"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Hammad AB, Elsharkawy RE, Abdel Azim GS. Repetitive transcranial magnetic stimulation as a prophylactic treatment in migraine. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery. 2021; 57: 5.","DOI":"10.1186\/s41983-020-00254-4"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Fregni F, Pascual-Leone A. Technology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS. Nature Clinical Practice. Neurology. 2007; 3: 383\u2013393.","DOI":"10.1038\/ncpneuro0530"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Zgarbura RC, Rizea LC, Dinca M, Pavel A, Parliteanu OA, Sabri J, et al. Repetitive Transcranial Magnetic Stimulation in Migraine: Clinical Outcomes and Neurobiological Mechanisms-A Systematic Review. Neurology International. 2026; 18: 80.","DOI":"10.3390\/neurolint18050080"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Almaraz AC, Dilli E, Dodick DW. The effect of prophylactic medications on TMS for migraine aura. 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Clinical utility and prospective of TMS-EEG: Updated review from an international expert group. Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology. 2026; 184: 2111487.","DOI":"10.1016\/j.clinph.2025.2111487"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Feng Y, Zhang B, Zhang J, Yin Y. Effects of Non-invasive Brain Stimulation on Headache Intensity and Frequency of Headache Attacks in Patients With Migraine: A Systematic Review and Meta-Analysis. Headache. 2019; 59: 1436\u20131447.","DOI":"10.1111\/head.13645"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Zrenner C, Ziemann U. Closed-Loop Brain Stimulation. Biological Psychiatry. 2024; 95: 545\u2013552.","DOI":"10.1016\/j.biopsych.2023.09.014"}],"container-title":["Journal of Integrative Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/25\/9\/10.31083\/JIN52992","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:17:09Z","timestamp":1790698629000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/25\/9\/10.31083\/JIN52992"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":46,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026]]}},"alternative-id":["S0219-6352(26)01190-3"],"URL":"https:\/\/doi.org\/10.31083\/jin52992","relation":{},"ISSN":["0219-6352","1757-448X"],"issn-type":[{"value":"0219-6352","type":"print"},{"value":"1757-448X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"article-number":"52992"}}