title: Interaction between simultaneously applied neuromodulatory interventions in humans.
abstract: 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.
authors.affiliation: The University of Queensland, NHMRC Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation Science, St Lucia, Brisbane, Queensland 4072, Australia. s.schabrun@uq.edu.au
authors.forename: Siobhan M
authors.initials: SM
authors.lastname: Schabrun
authors.forename: Lucinda S
authors.initials: LS
authors.lastname: Chipchase
authors.forename: Natasha
authors.initials: N
authors.lastname: Zipf
authors.forename: Gary W
authors.initials: GW
authors.lastname: Thickbroom
authors.forename: Paul W
authors.initials: PW
authors.lastname: Hodges
mesh_terms: D004558:Electric Stimulation; D004599:Electric Stimulation Therapy / Q000379:methods*; D019054:Evoked Potentials, Motor / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D055815:Young Adult
keywords: Homeostatic metaplasticity; Neuromuscular electrical stimulation; Primary motor cortex; Transcranial direct current stimulation