Theta Burst Stimulation of the Prefrontal Cortex: Safety and Impact on Cognition, Mood, and Resting Electroencephalogram

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 sham TBS 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 alpha 2 band after iTBS of the DLPFC, which remained detectable up to SO 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.