title: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Grossheinrich
authors.forename: Anne
authors.initials: A
authors.lastname: Rau
authors.forename: Oliver
authors.initials: O
authors.lastname: Pogarell
authors.forename: Kristina
authors.initials: K
authors.lastname: Hennig-Fast
authors.forename: Maren
authors.initials: M
authors.lastname: Reinl
authors.forename: Susanne
authors.initials: S
authors.lastname: Karch
authors.forename: Alica
authors.initials: A
authors.lastname: Dieler
authors.forename: Gregor
authors.initials: G
authors.lastname: Leicht
authors.forename: Christoph
authors.initials: C
authors.lastname: Mulert
authors.forename: Andrea
authors.initials: A
authors.lastname: Sterr
authors.forename: Frank
authors.initials: F
authors.lastname: Padberg
mesh_terms: D000328:Adult; D000339:Affect; D003071:Cognition; D018592:Cross-Over Studies; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D010919:Placebos; D017397:Prefrontal Cortex / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D050781:Transcranial Magnetic Stimulation / Q000009:adverse effects* / Q000379:methods*
chemical_list: D010919:Placebos