Impact of different intensities of intermittent theta burst stimulation on the cortical properties during TMS-EEG and working memory performance

Abstract

Introduction: Intermittent theta burst stimulation (iTBS) is a non-invasive brain stimulation technique capable of increasing cortical excitability beyond the stimulation period. Due to the rapid induction of modulatory effects compared to conventional repetitive transcranial magnetic stimulation (rTMS) paradigms, prefrontal application of iTBS is gaining popularity as a therapeutic tool for psychiatric disorders such as depression. In an attempt to increase efficacy, higher than conventional intensities are currently being applied. The assumption that this increases neuromodulatory effect is well established for the standard rTMS paradigms but may be mechanistically false for iTBS. This study examined the influence of intensity on the neurophysiological and behavioural effects of iTBS in the prefrontal cortex. Methods: 16 healthy participants received iTBS over prefrontal cortex (F1 electrode) at either 50, 75 or 100% resting motor threshold (rMT) in separate sessions. Single-pulse TMS and concurrent electroencephalography (EEG) was used to assess changes in cortical reactivity measured as TMS-evoked potentials (TEPs) and TMS-evoked oscillations. The n-back task (2-back and 3-back) were used to assess changes in working memory (accuracy and reaction time). Results: The data can be summarised as an inverse U-shape relationship between intensity and iTBS plastic effects, where 75% iTBS resulted in the largest neurophysiological changes both in TMS-EEG and working memory. Even though 75% iTBS showed significantly decreased reaction time in the 3-back task, between condition comparisons revealed no significant differences. Conclusions: The assumption that higher intensity results in greater neuromodulatory effects is false, at least in healthy individuals, and should be carefully considered for clinical populations. Neurophysiological changes associated with working memory following iTBS suggest functional relevance. However, the effects of different intensities on behavioural performance remain elusive in the present healthy sample.