Priming the brain to capitalize on metaplasticity in stroke rehabilitation

Repetitive transcranial magnetic stimulation (rTMS) is emerging as a potentially valuable intervention to augment the effects of behavioral therapy for stroke. When used in conjunction with other therapies, rTMS embraces the concept of metaplasticity. Due to homeostatic mechanisms inherent to metaplasticity, interventions known to be in isolation to enhance excitability can interact when applied successively under certain timing conditions and produce enhanced or opposite effects. Similar to "muscular wisdom," with its self-protective mechanisms, there also appears to be "synaptic wisdom" in neural networks with homeostatic processes that prevent over- and under-excitability. These processes have implications for both enhancing and suppressing the excitability effects from behavioral therapy. The purpose of this article is to relate the concept of metaplasticity, as derived from studies in humans who are healthy, to stroke rehabilitation and consider how it can be leveraged to maximize stroke outcomes.