Dose-Dependent Effects of Theta Burst rTMS on Cortical Excitability and Resting-State Connectivity of the Human Motor System
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Theta burst stimulation (TBS), a specific protocol of repetitive transcranial magnetic stimulation (rTMS), induces changes in cortical excitability that last beyond stimulation. TBS-induced aftereffects, however, vary between subjects, and the mechanisms underlying these aftereffects to date remain poorly understood. Therefore, the purpose of this study was to investigate whether increasing the number of pulses of intermittent TBS (iTBS) (1) increases cortical excitability as measured by motor-evoked potentials (MEPs) and (2) alters functional connectivity measured using resting-state fMRI, in a dose-dependent manner. Sixteen healthy, human subjects received three serially applied iTBS blocks of 600 pulses over the primary motor cortex (M1 stimulation) and the parieto-occipital vertex (sham stimulation) to test for dose-dependent iTBS effects on cortical excitability and functional connectivity (four sessions in total). iTBS over M1 increased MEP amplitudes compared with sham stimulation after each stimulation block. Although the increase in MEP amplitudes did not differ between the first and second block of M1 stimulation, we observed a significant increase after three blocks (1800 pulses). Furthermore, iTBS enhanced resting-state functional connectivity between the stimulated M1 and premotor regions in both hemispheres. Functional connectivity between M1 and ipsilateral dorsal premotor cortex further increased dose-dependently after 1800 pulses of iTBS over M1. However, no correlation between changes in MEP amplitudes and functional connectivity was detected. In summary, our data show that increasing the number of iTBS stimulation blocks results in dose-dependent effects at the local level (cortical excitability) as well as at a systems level (functional connectivity) with a dose-dependent enhancement of dorsal premotor cortex-M1 connectivity.
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Studies demonstrate that this number of pulses results in an optimal window of cortical excitability, and additional pulses may have an inhibitory effect.
“Studies demonstrate that this number of pulses results in an optimal “window” of cortical excitability, and additional pulses may have an inhibitory effect [59-61].”
From Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial (2024) · cites this paper as [61]
The section on iTBS aftereffects reports that earlier studies observed decreases in cortical excitability after repeated stimulation, supporting the possibility of an inhibitory effect. But this study found no such decrease: a third block, bringing the total to 1800 pulses, further increased excitability. Its Conclusions therefore do not establish the claimed optimal pulse window. (LLM, conf=0.83)
Experimental — accuracy not yet measurediTBS is dose-dependent and repeated application may be of benefit.
“It has also been suggested that iTBS is dose-dependent and repeated application may be of benefit (Nettekoven et al., 2014).”
From Investigation of neurobiological responses to theta burst stimulation during recovery from mild traumatic brain injury (mTBI) (2023) · cites this paper as Nettekoven et al., 2014
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- Authors
- Nettekoven, C., Volz, L. J., Kutscha, M., Pool, E.-M., Rehme, A. K., Eickhoff, S. B., Fink, G. R., & Grefkes, C.
- Affiliations
- Max Planck Institute for Metabolism Research (DE)
- Forschungszentrum Jülich (DE)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-05-14
- Volume
- 34
- Issue
- 20
- Pages
- 6849-6859
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4019799
- OpenAlex
- W2077740203
- Cited by
- 264
- References
- 66
- Citations by year
- 2026: 25 · 2025: 30 · 2024: 27 · 2023: 26 · 2022: 26 · 2021: 29 · 2020: 29 · 2019: 15 · 2018: 16 · 2017: 14 · 2016: 12 · 2015: 9 · 2014: 6
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (LA 3071/3‐1, KFO219-TP8, 816/4-1, 3285/2-1, GR 3285/2‐1, 3071/3-1, KFO-219, EI 816/4–1)
- National Institutes of Health (R01-MH074457-01A1, MH074457)
- National Institute of Mental Health (R01MH074457)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- theta burst stimulation, intermittent theta burst stimulation, repetitive transcranial magnetic stimulation, dose-dependent effects, cortical excitability, motor evoked potentials, resting-state functional connectivity, primary motor cortex, dorsal premotor cortex, motor system, aftereffects
- MeSH terms
- Adult, Female, Humans, Male, Motor Cortex, Nerve Net, Neuronal Plasticity, Theta Rhythm, Single-Blind Method, Cross-Over Studies, Evoked Potentials, Motor, Transcranial Magnetic Stimulation
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