Single and paired TMS pulses engage spatially distinct corticomotor representations in human pericentral cortex

Single-pulse transcranial magnetic stimulation (TMS) of the primary motor hand area can assess corticomotor function in humans by evoking motor-evoked potentials (MEPs). Paired-pulse TMS at peri-threshold intensity elicits short-latency intracortical facilitation (SICF) with early peaks at interpulse intervals of 1.0-1.8 ms (SICF₁) and 2.4-3 ms (SICF₂). The similarity between the periodicity of SICF and indirect (I-)waves in the corticospinal volleys evoked by single-pulse TMS suggests that SICF originates from I-wave generating circuits. This study aimed to explore the mechanisms of MEP generation by mapping the corticomotor representations of single-pulse and paired-pulse TMS targeting SICF₁ and SICF₂ peaks. We performed central sulcus shape-based, robot-assisted and neuro-navigated motor maps in 14 participants (7 females). MEPs were recorded from two hand muscles and the spatial properties of each corticomotor map were analyzed. For both hand muscles, we found a consistent posterior shift of the center of gravity (CoG) for SICF maps compared with single-pulse maps, with a larger shift for SICF₁. CoG displacement in the SICF₁ map correlated with individual SICF₁ latencies. Furthermore, abductor digiti minimi (ADM) maps consistently peaked more medially than first dorsal interosseus (FDI) maps and paired-pulse TMS resulted in larger corticomotor maps than single-pulse TMS. This is the first study to show that circuits responsible for SICF have a more posterior representation in the precentral crown than those generating MEPs via single-pulse TMS. These findings indicate that paired-pulse TMS probing SICF₁, SICF₂, and single-pulse TMS engage overlapping but spatially distinct cortical circuits, adding further insights into the intricate organization of the human motor hand area.<b>NEW & NOTEWORTHY</b> Single- and paired-pulse transcranial magnetic stimulation (TMS) is widely used to study corticomotor physiology in humans, but do they engage the same intracortical circuits? We compared the spatial properties of corticomotor maps elicited by single-pulse TMS to those elicited by paired-pulse short-latency intracortical facilitation (SICF). SICF maps consistently showed a posterior shift in center of gravity compared with single-pulse maps, suggesting that paired-pulse TMS engages cortical circuits that are spatially distinct from single-pulse TMS.