No evidence for changes in GABA concentration, functional connectivity, or working memory following continuous theta burst stimulation over dorsolateral prefrontal cortex

Continuous theta burst stimulation (cTBS) is thought to reduce cortical excitability and modulate functional connectivity, possibly by altering cortical inhibition at the site of stimulation. However, most evidence comes from the motor cortex and it remains unclear whether similar effects occur following stimulation over other brain regions. We assessed whether cTBS over left dorsolateral prefrontal cortex altered gamma aminobutyric acid (GABA) concentration, functional connectivity and brain dynamics at rest, and brain activation and memory performance during a working memory task. Seventeen healthy individuals participated in a randomised, sham-controlled, cross-over experiment. Before and after either real or sham cTBS, magnetic resonance spectroscopy was obtained at rest to measure GABA concentrations. Functional magnetic resonance imaging (fMRI) was also recorded at rest and during an n-back working memory task to measure functional connectivity, regional brain activity (low-frequency fluctuations), and task-related patterns of brain activity. We could not find evidence for changes in GABA concentration (P=0.66, Bayes factor [BF10]=0.07), resting-state functional connectivity (P(FWE)>0.05), resting-state low-frequency fluctuations (P=0.88, BF10=0.04), blood-oxygen level dependent activity during the n-back task (P(FWE) >0.05), or working memory performance (P=0.13, BF10=0.05) following real or sham cTBS. Our findings add to a growing body of literature suggesting the effects of cTBS are highly variable between individuals and question the notion that cTBS is a universal ‘inhibitory’ paradigm.