Magnetic stimulation of human premotor or motor cortex produces interhemispheric facilitation through distinct pathways

We explored interhemispheric facilitation (IHF) between (a) left and right primary motor cortex (M1) and (b) left dorsal premotor (dPM) and right M1 in 20 right-handed healthy human subjects using a paired pulse transcranial magnetic stimulation (TMS) protocol. A conditioning TMS pulse (CP) applied to left M1 or dPM with an intensity of 80% and 60% active motor threshold (CP80%AMT and CP60%AMT, respectively) was followed by a test pulse (TP) over right M1 induced by anterior–posterior- or posterior–anterior- (TPAP, TPPA) directed currents in the brain at interstimulus intervals (ISIs) of 3–8 and 10 ms. EMG was recorded from left first dorsal interosseous muscle. In the main experimental condition IHF was evoked by CP80%AMT over left M1 and TPAP at ISIs of 6 and 8 ms. The same CP80%AMT produced IHF at an ISI of 8 ms when applied over left dPM but only with TPPA. In addition, when CP60%AMT was given to M1, IHF was present at an ISI of 6 ms (but not 8 ms) when followed by TPPA, indicating that IHF elicited over dPM was not caused by current spread of the conditioning pulse to M1. We conclude that IHF can be induced differentially by conditioning M1 and dPM using subthreshold CP. These facilitatory interactions depended on the intensity and ISI of the CP as well as the current flow direction of the TP. We suggest that not only do the CPs activate separate anatomical pathways but also that these pathways project to different populations of interneurons in the receiving M1. These may correspond to elements involved in the generation of I3 and I1 waves, respectively.