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 (M1-HAND) can assess corticomotor function in humans by evoking motor evoked potentials (MEP). Paired-pulse TMS at peri-threshold intensity elicits short-latency intracortical facilitation (SICF) with early peaks at inter-pulse intervals of 1.0-1.8ms (SICF ₁ ) and 2.4-3ms (SICF ₂ ). 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 SICF ₁ and SICF ₂ peaks in 14 participants (7 female). 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 to single-pulse maps, with a larger shift for SICF ₁ . CoG displacement in the SICF ₁ map correlated with individual SICF ₁ latencies. Further, ADM maps consistently peaked more medially than 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 SICF ₁ , SICF ₂ , and single-pulse TMS engage overlapping but spatially distinct cortical circuits, adding further insights into the intricate organization of the human motor hand area.