Tracking Changes in Corticospinal Excitability During Visuomotor Paired Associative Stimulation to Predict Motor Resonance Rewriting.

Background/Objectives. Mirror properties of the action observation network (AON) can be modulated through Hebbian-like associative plasticity using paired associative stimulation (PAS). We recently introduced a visuomotor protocol (mirror-PAS, m-PAS) that pairs transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) with visual stimuli of ipsilateral (to TMS) movements, leading to atypical corticospinal excitability (CSE) facilitation (i.e., motor resonance) during PAS-conditioned action observation. While m-PAS aftereffects are robust, little is known about markers of associative plasticity during its administration and their predictive value for subsequent motor resonance rewriting. The present study aims to fill this gap by investigating CSE modulations during m-PAS and their relationship with the protocol's aftereffects. Methods. We analyzed CSE dynamics in 81 healthy participants undergoing the m-PAS before and after passively observing left- or right-hand index finger movements. Here, typical and PAS-conditioned motor resonance was assessed with TMS over the right M1. We examined CSE changes during the m-PAS and used linear regression models to explore their relationship with motor resonance modulations. Results. m-PAS transiently reshaped both typical and PAS-induced motor resonance. Importantly, we found a gradual increase in CSE during m-PAS, which predicted the loss of typical motor resonance but not the emergence of atypical responses after the protocol's administration. Conclusions. Our results suggest that the motor resonance reshaping induced by the m-PAS is not entirely predictable by CSE online modulations. Likely, this rewriting is the product of a large-scale reorganization of the AON rather than a phenomenon restricted to the PAS-stimulated motor cortex. This study underlines that monitoring CSE during non-invasive brain stimulation protocols could provide valuable insight into some but not all plastic outcomes.