The feeling that physical events are caused by us is tied to our action planning rather than being a mere post hoc deduction.

Transcranial magnetic stimulation (TMS)‐evoked potentials (TEPs) are a promising proxy for measuring effective connectivity, that is, the directed transmission of physiological signals along cortico‐cortical tracts, and for developing connectivity‐based biomarkers. A crucial point is how stimulation parameters may affect TEPs, as they may contribute to the general variability of findings across studies. Here, we manipulated two TMS parameters (i.e. current direction and pulse waveform) while measuring (a) an early TEP component reflecting contralateral inhibition of motor areas, namely, M1‐P15, as an operative model of interhemispheric cortico‐cortical connectivity, and (b) motor‐evoked potentials (MEP) for the corticospinal pathway. Our results showed that these two TMS parameters are crucial to evoke the M1‐P15, influencing its amplitude, latency, and replicability. Specifically, (a) M1‐P15 amplitude was strongly affected by current direction in monophasic stimulation; (b) M1‐P15 latency was significantly modulated by current direction for monophasic and biphasic pulses. The replicability of M1‐P15 was substantial for the same stimulation condition. At the same time, it was poor when stimulation parameters were changed, suggesting that these factors must be controlled to obtain stable single‐subject measures. Finally, MEP latency was modulated by current direction, whereas non‐statistically significant changes were evident for amplitude. Overall, our study highlights the importance of TMS parameters for early TEP responses recording and suggests controlling their impact in developing connectivity biomarkers from TEPs. Moreover, these results point out that the excitability of the corticospinal tract, which is commonly used as a reference to set TMS intensity, may not correspond to the excitability of cortico‐cortical pathways.

Associative plasticity, the neurophysiological bases of Hebbian learning, has been implied in the formation of the association between sensory and motor representations of actions in the Mirror Neuron System; however, such inductor role still needs empirical support. We have assessed whether Paired Associative Stimulation (PAS), known to activate Hebbian associative plasticity, can induce the formation of atypical (absent in normal conditions), visuo-motor associations, reshaping motor resonance. Healthy participants underwent a novel PAS protocol (mirror-PAS, m-PAS), during which they were exposed to repeated pairings of transcranial magnetic stimulation (TMS) applied over the right primary motor cortex (M1), time-locked with the view of index-finger movements of the right (ipsilateral) hand. In a first experiment, the inter-stimulus interval (ISI) between visual-action stimuli and TMS pulses was varied. Before and after each m-PAS session, motor resonance was assessed by recording Motor Evoked Potentials induced by single-pulse TMS applied to the right M1, during the observation of both contralateral (left) and ipsilateral (right) index-finger movements. In the second experiment, the specificity of the m-PAS was assessed by presenting a visual stimulus depicting a non-biological movement. Before m-PAS, the facilitation of corticospinal excitability occurred only during the view of contralateral (with respect to the TMS side) index-finger movements. The m-PAS induced new ipsilateral motor resonance responses, indexed by atypical facilitation of corticospinal excitability by the view of ipsilateral hand movements. This effect occurred only if the associative stimulation followed the chronometry of motor control (ISI of 25 ms) and if the visual stimulus of the m-PAS depicts a biological movement (human hand action). The present findings provide the first empirical evidence that Hebbian learning induced by a PAS protocol shapes the visual-motor matching properties of the human Mirror Neuron System.