How Different Priming Stimulations Affect the Corticospinal Excitability Induced by Noninvasive Brain Stimulation Techniques: a Systematic Review and Meta-analysis

Noninvasive brain stimulation (NIBS) techniques could induce changes in corticospinal excitability (CSE) and neuroplasticity. These changes could be affected by different factors, including having a session of stimulation called the 'priming' protocol before the main stimulation session called the 'test' protocol. Literature indicates that a priming protocol could affect the activity of postsynaptic neurons, form a neuronal history, and then modify the expected effects of the test protocol on CSE indicated by the amplitude of transcranial magnetic stimulation-induced motor-evoked potentials. This prior history affects a threshold to activate the necessary mechanism stabilizing the neuronal activity within a useful dynamic range. For studying the effects of this history and related metaplasticity mechanisms in the human primary motor cortex (M1), priming-test protocols are successfully employed. Thirty-two studies were included in this review to investigate how different priming protocols could affect the induced effects of a test protocol on CSE in healthy individuals. The results showed that if the history of synaptic activity were high or low enough to displace the threshold, the expected effects of the test protocol would be the reverse. This effect reversal is regulated by homeostatic mechanisms. On the contrary, the effects of the test protocol would not be the reverse, and at most we experience a prolongation of the lasting effects if the aforementioned history is not enough to displace the threshold. This effect prolongation is mediated by nonhomeostatic mechanisms. Therefore, based on the characteristics of priming-test protocols and the interval between them, the expected results of priming-test protocols would be different. Moreover, these findings could shed light on the different mechanisms of metaplasticity involved in NIBS. It helps us understand how we can improve the expected outcomes of these techniques in clinical approaches.