Paired associative stimulations: Novel tools for interacting with sensory and motor cortical plasticity

In the early 2000s, a novel non-invasive brain stimulation protocol, the paired associative stimulation (PAS), was introduced, allowing to induce and investigate Hebbian associative plasticity within the humans’ motor system, with patterns resembling spike-timing-dependent plasticity properties found in cellular models. Since this evidence, PAS efficacy has been proved in healthy, and to a lesser extent, in clinical populations. Recently, novel ‘modified’ protocols targeting sensorimotor and crossmodal networks appeared in the literature. In the present work, we have reviewed recent advances using these ‘modified’ PAS protocols targeting sensory and motor cortical networks. To better categorize them, we propose a novel classification according to the nature of the peripheral and cortical stimulations (i.e., within-system, cross-systems, and cortico-cortical PAS). For each protocol of the categories mentioned above, we describe and discuss their main features, how they have been used to study and promote brain plasticity, and their advantages and disadvantages. Overall, current evidence suggests that these novel non-invasive brain stimulation protocols represent very promising tools to study the plastic properties of humans’ sensorimotor and crossmodal networks, both in the healthy and in the damaged central nervous system.