Fig. 1.

Paired-associative stimulation (PAS) protocols. A Schematic detailing of the transspinal-TMS (left) and TMS-transspinal (right). In both protocols, transspinal stimulation produces orthodromic and antidromic excitation of large muscle afferents, orthodromic excitation of motor axons via depolarization of motoneurons, and excitation of ascending dorsal column fibers. The interstimulus interval (ISI) between TMS and transspinal stimulation was estimated based on Eq. 1. For both protocols, the ISI was used to set the order of triggering pulses to the Magstim or constant current stimulator. The ISI allowed transspinal induced excitation of dorsal columns to interact with TMS-evoked descending motor volleys at their site of origin within the primary motor cortex (transspinal-TMS PAS protocol), and TMS-evoked motor volleys to arrive at corticospinal presynaptic terminals of spinal motoneurons before transspinal stimulation transynaptically activated spinal motoneurons (TMS-transspinal PAS protocol). B Rectified EMG tracing of early and late TA flexion reflex from a single participant. The analysis window for the early TA flexion reflex started 60 ms after the first pulse in the stimulation train with 40 ms duration. The analysis window for the late TA flexion reflex started 130 ms after the first pulse with a duration of 130 ms