Interaction between simultaneously applied neuromodulatory interventions in humans

Background: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique with the potential to enhance the efficacy of traditional therapies such as neuromuscular electrical stimulation (NMES). Yet, concurrent application of tDCS/NMES may also activate homeostatic mechanisms that block or reverse effects on corticomotor excitability. It is unknown how tDCS and NMES interact in the human primary motor cortex (M1) and whether effects are summative (increase corticomotor excitability beyond that of tDCS or NMES applied alone) or competitive (block or reduce corticomotor excitability effects of tDCS or NMES applied alone). Objective: To investigate corticomotor excitability in response to NMES after concurrent application of tDCS protocols that enhance (anodal tDCS) or suppress (cathodal tDCS) excitability of M1. Methods: We used transcranial magnetic stimulation (TMS) to examine corticomotor excitability before and after the concurrent application of: i) NMES with anodal tDCS; and ii) NMES with cathodal tDCS. Effects were contrasted to four control conditions: i) NMES alone, ii) anodal tDCS alone, iii) cathodal tDCS alone, and iv) sham stimulation. Results: Concurrent application of two protocols that enhance excitability when applied alone (NMES and anodal tDCS) failed to induce summative effects on corticomotor excitability, as predicted by homeostatic plasticity mechanisms. Combined cathodal tDCS and NMES suppressed the enhanced excitation induced by NMES, an effect that might be explained by calcium dependent anti-gating models. Conclusions: These novel findings highlight the complex mechanisms involved when two neuromodulatory techniques are combined and suggest that careful testing of combined interventions is necessary before application in clinical contexts.