{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T12:02:54Z","timestamp":1792324974546,"version":"4.4.0"},"reference-count":122,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Non-invasive brain stimulation (NIBS) techniques\u2014including repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation (TBS), paired associative stimulation (PAS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS)\u2014have emerged as valuable tools for modulating neural activity and promoting plasticity. Traditionally, their effects have been interpreted within a binary framework of long-term potentiation (LTP)-like and long-term depression (LTD)-like plasticity, largely inferred from changes in motor evoked potentials (MEPs). However, existing models do not fully capture the complexity of the biological processes engaged by these techniques and despite extensive clinical application, the cellular and molecular mechanisms underlying NIBS remain only partially understood. This systematic review, conducted in accordance with the PRISMA 2020 guidelines, synthesizes evidence from in vivo, in vitro, and ex vivo studies to delineate how NIBS influences neurotransmission through intracellular signaling, gene expression, and protein synthesis at the cellular level. Emphasis is placed on the roles of classical synaptic models, grounded in Ca2+-dependent glutamatergic signaling and receptor phosphorylation dynamics, as well as broader forms of plasticity involving BDNF\u2013TrkB signaling, epigenetic modifications, neuroimmune and glial interactions, anti-inflammatory pathways, and apoptosis- and survival-related cascades. By integrating findings in humans with those in animal and cellular models, we identify both shared and technique-specific molecular mechanisms underlying NIBS-induced effects, highlighting emerging evidence for multi-pathway, non-binary plasticity mechanisms. Understanding these convergent pathways provides a mechanistic foundation for refining stimulation paradigms and improving their translational relevance for treatment of neurological and psychiatric disorders.<\/jats:p>","DOI":"10.3390\/cells14241996","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T15:52:59Z","timestamp":1765813979000},"page":"1996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Cellular and Molecular Mechanisms of Non-Invasive Brain Stimulation Techniques: A Systematic Review on the Implications for the Treatment of Neurological Disorders"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3757-8186","authenticated-orcid":false,"given":"Valerio","family":"Sveva","sequence":"first","affiliation":[{"name":"Department of Human Neuroscience, University of Rome \u201cSapienza\u201d, Viale dell\u2019Universit\u00e0 30, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4485-2200","authenticated-orcid":false,"given":"Marco","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Department of Human Neuroscience, University of Rome \u201cSapienza\u201d, Viale dell\u2019Universit\u00e0 30, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2631-4185","authenticated-orcid":false,"given":"Alessandro","family":"Cruciani","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Neurophysiology, Neurobiology, and Psychiatry, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias Paolo","family":"Casula","sequence":"additional","affiliation":[{"name":"Department of System Medicine, University of Tor Vergata, Via Cracovia 50, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6631-6740","authenticated-orcid":false,"given":"Giorgio","family":"Leodori","sequence":"additional","affiliation":[{"name":"Department of Human Neuroscience, University of Rome \u201cSapienza\u201d, Viale dell\u2019Universit\u00e0 30, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Antonella","family":"Selvaggi","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Neurophysiology, Neurobiology, and Psychiatry, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Bologna","sequence":"additional","affiliation":[{"name":"Department of Human Neuroscience, University of Rome \u201cSapienza\u201d, Viale dell\u2019Universit\u00e0 30, 00185 Rome, Italy"},{"name":"IRCCS Neuromed, Via Atinense 18, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9113-5925","authenticated-orcid":false,"given":"Vincenzo","family":"Di Lazzaro","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Neurophysiology, Neurobiology, and Psychiatry, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7103-5209","authenticated-orcid":false,"given":"Anna","family":"Latorre","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3979-156X","authenticated-orcid":false,"given":"Lorenzo","family":"Rocchi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, Cittadella Universitaria di Monserrato, Blocco I S.S. 554 bivio per Sestu, Monserrato, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/s41593-017-0054-4","article-title":"Studying and modifying brain function with non-invasive brain stimulation","volume":"21","author":"Nitsche","year":"2018","journal-title":"Nat. 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