Figure 2. Elements that contribute to the MEP signal.

Applying a suprathreshold transcranial magnetic stimulation (TMS) pulse over the primary motor cortex (M1) leads to a trans‐synaptic activation of pyramidal cells, evoking descending volleys in the pyramidal axons projecting on spinal motoneurons (i.e. pyramidal tract). Motoneuron activation then leads to a contraction of the targeted muscle evoking a motor‐evoked potential (MEP). The effect of cortical volleys on spinal cord circuitry can be evaluated by conditioning the Hoffman (H)‐reflex (e.g. via peripheral nerve stimulation) with TMS. It is also critical to consider the direction of the TMS current, as this can change the cortical elements recruited with stimulation. When TMS is applied with lateral‐to‐medial (LM) currents, pyramidal cells are activated directly (D‐wave). However, other current directions recruit pyramidal cells indirectly (I‐waves) through the activation of excitatory interneurons. For instance, low‐intensity TMS applied with a poster‐to‐anterior (PA) current preferentially recruits early I‐waves (blue circle), whereas anterior‐to‐posterior currents tend to recruit late arriving excitatory inputs (late I‐waves; red circle) that are different from ones sensitive to PA. Of note, MEPs can be elicited in hand, arm, leg and face muscles, albeit with different stimulation parameters. For instance, hand muscle MEPs are triggered most effectively with PA currents with relatively low stimulus intensities, whereas leg and face MEPs are more easily produced with lateral–medial currents. The threshold to elicit hand MEPs is low primarily due to hand muscles having the most extensive cortical representation that is located most superficially to the hemispherical surface. Importantly, while hand, arm and leg responses involve the corticospinal pathway, face muscle responses involve pyramidal neurons synapsing with motoneurons in the brainstem via the corticobulbar pathway.