Theta burst stimulation of the prefrontal cortex: Safety and impact on cognition, mood, and resting electroencephalogram
Abstract
Background Because standard repetitive transcranial magnetic stimulation (rTMS) protocols exhibit post-stimulus effects of short duration, novel protocols such as theta burst stimulation (TBS), are promising approaches to enhance the effectiveness of rTMS. However, little is known about the side effect profile of such protocols. Thus, the present study explores whether TBS is safe particularly in terms of effects on cognition, mood, and electroencephalogram (EEG) measures in healthy subjects. Methods Twenty-four healthy volunteers participated in 2 randomized, placebo-controlled, cross-over experiments and underwent continuous TBS (cTBS), intermittent TBS (iTBS), and shamTBS either over the left dorsolateral prefrontal cortex (DLPFC, n = 12) or the medial prefrontal cortices (mPFC, n = 12). Clinical side effects, performance in a neuropsychological battery, mood changes, and resting EEG were recorded. Results Neither a seizure nor epileptiform EEG activity was observed. The most prominent side effect was the occurrence of vagal reactions during TBS; otherwise no serious side effects were found. Standardized low-resolution brain electromagnetic tomography showed current density changes in the alpha2 band after iTBS of the DLPFC, which remained detectable up to 50 min after stimulation. The few changes in neuropsychological performance were concordant with stimulation site. No impact on mood was detected. Conclusions Although TBS protocols of the human prefrontal cortex seem to be safe in healthy subjects, future studies need to address the occurrence of vagal reactions. Excitatory and inhibitory properties of motor cortex TBS might not be transferable to prefrontal sites, and the action of specific TBS protocols needs to be further investigated prior to clinical application.
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Evidence from studies of healthy participants suggests there may be a cognitive enhancing effect of TBS when applied to the prefrontal cortex.
“Notably, evidence from studies of healthy participants suggests there may be a cognitive enhancing effect of TBS when applied to the prefrontal cortex (Debarnot et al., 2015;Grossheinrich et al., 2009;Hoy et al., 2016).”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Grossheinrich et al., 2009
Improvements in working memory, increased synchronisation of task-related theta, and current density changes in resting alpha activity have been reported following iTBS in healthy controls.
“Improvements in working memory and increased synchronisation of task-related theta (Hoy et al., 2015) and current density changes in resting alpha activity (Grossheinrich et al., 2009) have been reported following iTBS in healthy controls.”
From Investigation of neurobiological responses to theta burst stimulation during recovery from mild traumatic brain injury (mTBI) (2023) · cites this paper as Grossheinrich et al., 2009
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- Authors
- Grossheinrich, N., Rau, A., Pogarell, O., Hennig-Fast, K., Reinl, M., Karch, S., Dieler, A., Leicht, G., Mulert, C., Sterr, A., & Padberg, F.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- Corresponding author
- Padberg, Frank
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 65
- Issue
- 9
- Pages
- 778-784
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2066716661
- Cited by
- 168
- References
- 30
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 10 · 2023: 9 · 2022: 12 · 2021: 9 · 2020: 8 · 2019: 11 · 2018: 12 · 2017: 11 · 2016: 9 · 2015: 7 · 2014: 9 · 2013: 6 · 2012: 8
- FWCI
- 6.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- theta burst stimulation, repetitive transcranial magnetic stimulation, prefrontal cortex, dorsolateral prefrontal cortex, medial prefrontal cortex, stimulation safety, adverse effects, resting-state EEG, neuropsychological performance, mood, sham stimulation
- MeSH terms
- Adult, Affect, Cognition, Electroencephalography, Female, Humans, Male, Neuropsychological Tests, Placebos, Psychomotor Performance, Prefrontal Cortex, Cross-Over Studies, Transcranial Magnetic Stimulation
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