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Transcranial magnetic stimulation of the brain: What is stimulated? - A consensus and critical position paper
Open accessAbstract
Transcranial (electro)magnetic stimulation (TMS) is currently the method of choice to non-invasively induce neural activity in the human brain. A single transcranial stimulus induces a time-varying electric field in the brain that may evoke action potentials in cortical neurons. The spatial relationship between the locally induced electric field and the stimulated neurons determines axonal depolarization. The induced electric field is influenced by the conductive properties of the tissue compartments and is strongest in the superficial parts of the targeted cortical gyri and underlying white matter. TMS likely targets axons of both excitatory and inhibitory neurons. The propensity of individual axons to fire an action potential in response to TMS depends on their geometry, myelination and spatial relation to the imposed electric field and the physiological state of the neuron. The latter is determined by its transsynaptic dendritic and somatic inputs, intrinsic membrane potential and firing rate. Modeling work suggests that the primary target of TMS is axonal terminals in the crown top and lip regions of cortical gyri. The induced electric field may additionally excite bends of myelinated axons in the juxtacortical white matter below the gyral crown. Neuronal excitation spreads ortho- and antidromically along the stimulated axons and causes secondary excitation of connected neuronal populations within local intracortical microcircuits in the target area. Axonal and transsynaptic spread of excitation also occurs along cortico-cortical and cortico-subcortical connections, impacting on neuronal activity in the targeted network. Both local and remote neural excitation depend critically on the functional state of the stimulated target area and network. TMS also causes substantial direct co-stimulation of the peripheral nervous system. Peripheral co-excitation propagates centrally in auditory and somatosensory networks, but also produces brain responses in other networks subserving multisensory integration, orienting or arousal. The complexity of the response to TMS warrants cautious interpretation of its physiological and behavioural consequences, and a deeper understanding of the mechanistic underpinnings of TMS will be critical for advancing it as a scientific and therapeutic tool.
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“studies suggest that cerebellar modulation is possible with TMS (Hardwick et al., 2014; Siebner et al., 2022)”
From A double-blind, randomized, sham-controlled clinical trial of cerebellar intermittent theta burst stimulation for bipolar disorder: Safety, tolerability, mood and cognitive effects (2025) · cites this paper as Siebner et al., 2022
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Self-citationRepetitive transcranial magnetic stimulation in primary sleep disorders
Lanza, G., Fisicaro, F., Cantone, M., Pennisi, M., Cosentino, F., Lanuzza, B., Tripodi, M., Bella, R., Paulus, W., & Ferri, R. (2022) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2022.101735 · Cited by 133
Self-citationSpampinato, D. A., Ibáñez, J., Rocchi, L., & Rothwell, J. C. (2023) · The Journal of Physiology · doi:10.1113/jp281885 · Cited by 147
Self-citation
Metadata
- Authors
- Siebner, H. R., Funke, K., Aberra, A. S., Antal, A., Bestmann, S., Chen, R., Classen, J., Davare, M., Di Lazzaro, V., Fox, P. T., Hallett, M., Karabanov, A. N., Kesselheim, J., Beck, M. M., Koch, G., Liebetanz, D., Meunier, S., Miniussi, C., Paulus, W., Peterchev, A. V., Popa, T., Ridding, M. C., Thielscher, A., Ziemann, U., Rothwell, J. C., & Ugawa, Y.
- Affiliations
- University of Copenhagen (DK)
- Ruhr University Bochum (DE)
- Duke University (US)
- Universitätsmedizin Göttingen (DE)
- Wellcome Centre for Human Neuroimaging (GB)
- University Health Network (CA)
- Leipzig University (DE)
- King's College London (GB)
- The University of Texas at San Antonio Health Science Center (US)
- National Institutes of Health (US)
- Hvidovre Hospital (DK)
- University of Ferrara (IT)
- Centre National de la Recherche Scientifique (FR)
- University of Trento (IT)
- Fukushima Medical University (JP)
- University of South Australia (AU)
- Hertie Institute for Clinical Brain Research (DE)
- UCL Queen Square Institute of Neurology (GB)
- Corresponding author
- Siebner, Hartwig R.
- ORCID
- Siebner, Hartwig R.
- Funke, Klaus
- Aberra, Aman S.
- Antal, Andrea
- Bestmann, Sven
- Chen, Robert
- Classen, Joseph
- Davare, Marco
- Fox, Peter T.
- Hallett, Mark
- Karabanov, Anke N.
- Kesselheim, Janine
- Beck, Mikkel M.
- Koch, Giacomo
- Liebetanz, David
- Meunier, Sabine
- Miniussi, Carlo
- Paulus, Walter
- Peterchev, Angel V.
- Popa, Traian
- Ridding, Michael C.
- Thielscher, Axel
- Ziemann, Ulf
- Rothwell, John C.
- Ugawa, Yoshikazu
- Venue
- Clinical Neurophysiology
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 140
- Pages
- 59-97
- ISSN
- 1388-2457 (ISSN-L)
- PMC
- PMC9753778
- OpenAlex
- W4280629063
- Cited by
- 566
- References
- 439
- Citations by year
- 2026: 138 · 2025: 179 · 2024: 138 · 2023: 90 · 2022: 20
- FWCI
- 37.47
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical Neurophysiology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- PubMed Central (acceptedVersion, cc-by)
- UniSA Research Outputs Repository (University of South Australia) (submittedVersion, other-oa)
- Brunel University Research Archive (BURA) (Brunel University London) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Trento) (submittedVersion, cc-by-nc-nd)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion, cc-by)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, cc-by)
- Funders
- National Science Foundation (1106401)
- Niedersächsische Ministerium für Wissenschaft und Kultur
- Deutsche Forschungsgemeinschaft (FU256/3-2, SFB 874, 122679504)
- Institut National de la Santé et de la Recherche Médicale
- Ministry of Education, Culture, Sports, Science and Technology (16H05322, 20K07866, 19H01091, 15H05881)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Bundesministerium für Bildung und Forschung (01EE1403B, 01GP2124B)
- Lundbeckfonden (R118‐A11308, R186-2015-2138, R244‐2017‐196, R313–2019–622, R186-2015)
- Novo Nordisk
- Fondazione Cassa Di Risparmio Di Trento E Rovereto
- Novo Nordisk Fonden (NNF14OC001)
- H. Lundbeck A/S (R244-2017-196, R186-2015-2138)
- Fondation Defitech
- National Institutes of Health (1106401, H2020)
- Horizon 2020 Framework Programme (101017716)
- Biotechnology and Biological Sciences Research Council
- National Institute of Mental Health (R01MH111865, RF1MH114268, R01MH127104)
- National Institute of Neurological Disorders and Stroke (R01NS117405, R01NS088674)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- transcranial magnetic stimulation, induced electric field, axonal depolarization, cortical gyri, myelinated axons, multisensory integration
- MeSH terms
- Action Potentials, Brain, Humans, Neurons, Evoked Potentials, Motor, Consensus, Transcranial Magnetic Stimulation
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