Modulation of associative plasticity by general network excitability in the human motor cortex

Introduction: Associative neuroplasticity encompasses the modification of synaptic strength by co-activation of two synaptic inputs to a common target neuron. It is a candidate to represent the neurophysiological basis of learning. Since unlimited neuroplastic network modifications would have dysfunctional effects on neuronal networks, homeostatic mechanisms are suggested to control for stability. Accordingly in human experiments the history of general/background cortical excitability determines the direction of its subsequent modulation: an identical neuroplasticity-inducing stimulation protocol can accomplish neuroplastic excitability diminution or enhancement, in each case counteracting the previous level of excitability. However, the impact of background excitability on associative plasticity, which encompasses a focal modification of synaptic strength, has not been studied so far.

Methods: Paired associative stimulation (PAS), a paradigm suited to induce associative synapse-specific neuroplasticity, and transcranial direct current stimulation (tDCS), which enhances or reduces excitability of the motor cortex polarity-dependently, but whose effects are not restricted to specific synaptic connections, were applied in healthy humans. tDCS was administered before or simultaneously with PAS.

Results: When applied before PAS, excitability-enhancing anodal tDCS boosted the excitability-enhancing efficacy of the PAS protocol, while excitability-diminishing cathodal tDCS turned it to inhibition. This result argues against a relevant homeostatic impact of previous background activity on associative plasticity. However, in accordance with homeostatic rules of neuroplasticity, cathodal tDCS resulted in a prolonged excitability enhancement, while anodal tDCS reduced it, when tDCS and PAS were applied simultaneously.

Conclusion: We conclude that background network excitability influence associative plasticity. However, the relationship might be more complex than previously thought: Whereas enhanced or diminished background activity established before the induction of plasticity has no homeostatic effect, the results accomplished by simultaneous modulation of both parameters are in accordance with homeostatic rules.