The Homeostatic Interaction Between Anodal Transcranial Direct Current Stimulation and Motor Learning in Humans is Related to GABAA Activity.
BACKGROUND
The relative timing of plasticity-induction protocols is known to be crucial. For example, anodal transcranial direct current stimulation (tDCS), which increases cortical excitability and typically enhances plasticity, can impair performance if it is applied before a motor learning task. Such timing-dependent effects have been ascribed to homeostatic plasticity, but the specific synaptic site of this interaction remains unknown.


OBJECTIVE
We wished to investigate the synaptic substrate, and in particular the role of inhibitory signaling, underpinning the behavioral effects of anodal tDCS in homeostatic interactions between anodal tDCS and motor learning.


METHODS
We used transcranial magnetic stimulation (TMS) to investigate cortical excitability and inhibitory signaling following tDCS and motor learning. Each subject participated in four experimental sessions and data were analyzed using repeated measures ANOVAs and post-hoc t-tests as appropriate.


RESULTS
As predicted, we found that anodal tDCS prior to the motor task decreased learning rates. This worsening of learning after tDCS was accompanied by a correlated increase in GABAA activity, as measured by TMS-assessed short interval intra-cortical inhibition (SICI).


CONCLUSIONS
This provides the first direct demonstration in humans that inhibitory synapses are the likely site for the interaction between anodal tDCS and motor learning, and further, that homeostatic plasticity at GABAA synapses has behavioral relevance in humans.
Oxford Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Ugwechi
U
Amadi
Oxford Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Claire
C
Allman
Oxford Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Heidi
H
Johansen-Berg
Oxford Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK; Oxford Centre for Human Brain Activity (OHBA), Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK. Electronic address: charlotte.stagg@ndcn.ox.ac.uk.
Charlotte J
CJ
Stagg
D000328:Adult; D004566:Electrodes; D019054:Evoked Potentials, Motor; D005260:Female; D059330:GABAergic Neurons / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007858:Learning; D008297:Male; D009044:Motor Cortex / Q000166:cytology / Q000502:physiology; D011597:Psychomotor Performance; D065908:Transcranial Direct Current Stimulation; D050781:Transcranial Magnetic Stimulation
GABA; Homeostatic plasticity; Motor learning; Non-invasive brain stimulation (NIBS)