Interaction Between Simultaneously Applied Neuromodulatory Interventions in Humans

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Interaction Between Simultaneously Applied Neuromodulatory Interventions in Humans

Siobhan M. Schabrun

a

,

*

, Lucinda S. Chipchase

a

, Natasha Zipf 

a

, Gary W. Thickbroom

b

, Paul W. Hodges

a

a

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

b

The University of Western Australia, Australian Neuro-muscular Research Institute, Nedlands, Perth, Western Australia 6009, Australia

a r t i c l e i n f o

 Article history:

Received 3 May 2012Received in revised form24 September 2012Accepted 24 September 2012Available online xxx

Keywords:

Homeostatic metaplasticityNeuromuscular electrical stimulationPrimary motor cortexTranscranial direct current stimulation

a b s t r a c t

Background:

 Transcranial direct current stimulation (tDCS) is a neuromodulatory technique with thepotential to enhance the ef 

fi

cacy of traditional therapies such as neuromuscular electrical stimulation(NMES). Yet, concurrent application of tDCS/NMES may also activate homeostatic mechanisms that blockor reverse effects on corticomotor excitability. It is unknown how tDCS and NMES interact in the humanprimary motor cortex (M1) and whether effects are summative (increase corticomotor excitabilitybeyond that of tDCS or NMES applied alone) or competitive (block or reduce corticomotor excitabilityeffects 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 beforeand 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 tDCSalone, and iv) sham stimulation.

Results:

 Concurrent application of two protocols that enhance excitability when applied alone (NMES andanodal tDCS) failed to induce summative effects on corticomotor excitability, as predicted by homeostaticplasticity mechanisms. Combined cathodal tDCS and NMES suppressed the enhanced excitation inducedby NMES, an effect that might be explained by calcium dependent anti-gating models.

Conclusions:

 These novel

 fi

ndings highlight the complex mechanisms involved when two neuro-modulatory techniques are combined and suggest that careful testing of combined interventions isnecessary before application in clinical contexts.

Siobhan M. Schabrun
a
,
*
, Lucinda S. Chipchase
a
, Natasha Zipf
a
, Gary W. Thickbroom
b
, Paul W. Hodges
a
a
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
b
The University of Western Australia, Australian Neuro-muscular Research Institute, Nedlands, Perth, Western Australia 6009, Australia
a r t i c l e i n f o
 Article history:
Received 3 May 2012
Received in revised form
24 September 2012
Accepted 24 September 2012
Available online xxx
Keywords:
Homeostatic metaplasticity
Neuromuscular electrical stimulation
Primary motor cortex
Transcranial direct current stimulation

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 neuro-
modulatory techniques are combined and suggest that careful testing of combined interventions is
necessary before application in clinical contexts.