Understanding the sources of cortico-cortical paired associative stimulation (ccPAS) variability: Unraveling target-specific and state-dependent influences

Cortico-cortical paired associative stimulation (ccPAS) is a powerful non-invasive brain stimulation technique that involves the repeated paired application of transcranial magnetic stimulation (TMS) to two different brain regions, with precise temporal intervals, to exogenously induce the phenomenon of spike timing-dependent plasticity and modulate the strength of connectivity between the targeted brain areas. In a recent systematic review published in Clinical Neurophysiology, Hernandez-Pavon and colleagues (Hernandez-Pavon et al., 2023) offer an excellent comprehensive synthesis of the literature on ccPAS, exhaustively summarizing findings on the application of ccPAS to multiple domains, reporting both neurophysiological and behavioral outcomes, and highlighting its potential in modulating brain connectivity. Although further second-level evidence is necessary, specifically in the form of meta-analyses to combine data from multiple studies and obtain a precise estimation of effect sizes, the systematic review raises intriguing topics of discussion.