Effects of online repetitive transcranial magnetic stimulation (rTMS) on cognitive processing: A meta-analysis and recommendations for future studies

Abstract

Online repetitive transcranial magnetic stimulation (rTMS), applied while subjects are performing a task, is widely used to disrupt brain regions underlying cognition. However, online rTMS has also induced "paradoxical enhancement". Given the rapid proliferation of this approach, it is crucial to develop a better understanding of how online stimulation influences cognition, and the optimal parameters to achieve desired effects. To accomplish this goal, a quantitative meta-analysis was performed with random-effects models fitted to reaction time (RT) and accuracy data. The final dataset included 126 studies published between 1998 and 2016, with 244 total effects for reaction times, and 202 for accuracy. Meta-analytically, rTMS at 10 Hz and 20 Hz disrupted accuracy for attention, executive, language, memory, motor, and perception domains, while no effects were found with 1 Hz or 5 Hz. Stimulation applied at and 10 and 20 Hz slowed down RTs in attention and perception tasks. No performance enhancement was found. Meta-regression analysis showed that fMRI-guided targeting and short inter-trial intervals are associated with increased disruptive effects with rTMS.

Keywords: Cognition; Meta-analysis; Online rTMS.

Figure 1:

Consort diagram.

Figure 2:

Studies summary. Percentage experiments addressing: A) cognitive domains, B) a priori directionality of effect, C) histogram of sample size included across studies (adjusted for number of experiments), D) targeting approach, E) stimulated brain target, F) use of neuronavigation, G) amplitude dosing approach, H) stimulation frequency, I) inter-trial interval (ITI), J) number of pulses per trial, and K) stimulation timing relative to the cognitive process.

Figure 3:

Summary of the standardized mean differences and 95% confidence intervals between active and sham rTMS obtained on A) accuracy, and B) reaction times, stratified by cognitive domains and frequency of stimulation. Negative values (blue) represent lower accuracy or slower reaction time associated with active rTMS, while positive values (red) represent higher accuracy or faster reaction time. Light grey indicates that no data were found, while dark grey indicates that the rTMS effect did not reach significance. These tables are summarizing the forest plots that can be found in the supplementary material.

Figure 4:

Assessment of risk of bias, presented as percentages across all included studies.

Figure 5:

Funnel plot assessing potential publication bias in the A) accuracy and B) reaction time outcomes. The outer dashed lines indicate the triangular region within which 95% of studies are expected to lie in the absence of biases and heterogeneity.