Assessing neuromodulation effects of theta burst stimulation to the prefrontal cortex using TMS-evoked potentials

Abstract Theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (TMS), is capable of non-invasively modulating cortical excitability. TBS is gaining popularity as a therapeutic tool for psychiatric disorders such as depression, in which the dorsolateral prefrontal cortex (DLPFC) is the main therapeutic target. However, the neuromodulatory effects of TBS on prefrontal regions remain unclear. An emerging tool to assess neuromodulation in non-motor regions is concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to measure TMS-evoked potentials (TEPs). We assessed twenty-four healthy participants (13 males, mean age 25.2±9.9 years) following intermittent TBS, continuous TBS, and sham applied to the left DLPFC using a double-blinded crossover design. TEPs were obtained at baseline and 2-, 15-, and 30-min post-stimulation. Four TEP components (N40, P60, N100 and P200) were analysed using mixed effects repeated measures models (MRMM). Results indicate no significant effects for any assessed components (all p>.05). The largest effect size (Cohen’s d = −0.5) comparing iTBS and sham was obtained for the N100 component at 15 minutes post-stimulation. This result was in the same direction but smaller than found in previous studies, suggesting that the true effect size may be lower than previously reported. Accurate estimates of the effects sizes and inter-individual heterogeneity will critically inform clinical applications using TEPs to assess the neuromodulatory effects of TBS.