Assessment of ipsilateral premotor-to-motor connectivity by highly focal TMS

Introduction: Bifocal transcranial magnetic stimulation (TMS) has been successfully used to examine interhemispheric interactions between motor cortical areas (e.g. transcallosal interhemispheric inhibition). So far, the large size of the transducing coils has precluded bifocal TMS of adjacent motor areas in the same hemisphere. We recently developed highly focal minicoils which enable bifocal TMS of two adjacent cortical areas. Using these minicoils, we studied cortico-cortical connectivity between left dorsal premotor cortex (PMd) and left primary motor hand area (M1-HAND) during movement selection.

Methods: In 18 healthy subjects, we probed the connectivity between left PMd and M1-HAND with two highly focal minicoils (Mag&More, Munich, Germany). The first coil was placed over the motor hot spot of the right first dorsal interosseous (FDI) muscle (i.e. M1 site). The second coil was placed 2cm anterior and 1cm medially to the motor hot spot of the FDI muscle to stimulate the premotor cortex. We first applied a suprathreshold biphasic pulse (S1) to left M1-HAND that induced a MEP amplitude of app. 0.5–1 mV in the right FDI when given alone. The second biphasic stimulus (S2) was applied to the left PMd at different interstimulus intervals (ISIs) after S1, ranging from 2.0 to 5.6ms. The stimulus intensity (SI) of the S2 was set at 70% or 90% of the S1 intensity.

Results: The optimal ISI and S2 intensity that induced the strongest MEP facilitation varied across subjects. The premotor S2 induced short-lasting MEP facilitation which peaked at an early (2.4 to 2.8ms) and late ISIs (3.6 to 4.4ms). This short-latency facilitation pattern resembles conventional I-wave interaction found with double-pulse TMS given through a single coil placed over the M1-HAND. Paired S1-S2 stimulation of left M1-HAND (S1) and PMd (S2) resulted in a facilitation of MEP amplitudes relative to single-pulse TMS of the M1-HAND alone.

Conclusions: Here we introduce a new TMS paradigm which tests the effective connectivity in an ipsilateral premotor-to-motor pathway. This proof-of-principle study shows that highly focal TMS provides an effective means of probing the time course and context dependency of cortico-cortical connectivity between two adjacent cortical areas in the intact human brain.