Preconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects

Background: Rapid-rate repetitive transcranial magnetic stimulation (rTMS) can produce a lasting increase in cortical excitability in healthy subjects or induce beneficial effects inpatients with neuropsychriatric disorders; however, the conditioning effects of rTMS are often subtle and variable, limiting therapeutic applications. Here we show that magnitude and direction of after-effects induced by rapid-rate rTMS depend on the state of cortical excitability before stimulation and can be tuned by preconditioning with transcranial direct current stimulation (tDCS). Methods: Ten healthy volunteers received a 20-sec train of 5-Hz rTMS given at an intensity of individual active motor threshold to the left primary motor hand area. This interventional protocol was preconditioned by 10 min of anodal, cathodal, or sham tDCS. We used single-pulse TMS to assess corticospinal excitability at rest before, between, and after the two interventions. Results: The 5-Hz rTMS given after sham tDCS failed to produce any after-effect, whereas 5-Hz rTMS led to a marked shift in corticospinal excitability when given after effective tDCS. The direction of rTMS-induced plasticity critically depended on the polarity of tDCS conditioning. Conclusions: Preconditioning with tDCS enhances cortical plasticity induced by rapid-rate rTMS and can shape the direction of rTMS-induced after-effects.