The human dorsal premotor cortex facilitates the excitability of ipsilateral primary motor cortex via a short latency cortico-cortical route

In non-human primates, invasive tracing and electrostimulation studies have identified strong ipsilateral cortico-cortical connections between dorsal premotor- (PMd) and the primary motor cortex (M1HAND). Here, we applied dual-site transcranial magnetic stimulation (dsTMS) to left PMd and M1HAND through specifically designed minicoils to selectively probe ipsilateral PMd-to-M1HAND connectivity in humans. A suprathreshold test stimulus (TS) was applied to M1HAND producing a motor evoked potential (MEP) of about 0.5 mV in the relaxed right first dorsal interosseus muscle (FDI). A subthreshold conditioning stimulus (CS) was given to PMd 2.0–5.2 ms after the TS at intensities of 50-, 70-, or 90% of TS. The CS to PMd facilitated the MEP evoked by TS over M1HAND at interstimulus intervals (ISI) of 2.4 or 2.8 ms. There was a second facilitatory peak at ISI of 4.4 ms. PMd-to-M1HAND facilitation did not change as a function of CS intensity. Even at higher intensities, the CS alone failed to elicit a MEP or a cortical silent period in the pre-activated FDI, excluding a direct spread of excitation from PMd to M1HAND. No MEP facilitation was present while CS was applied rostrally over lateral prefrontal cortex. Together our results indicate that our dsTMS paradigm probes a short-latency facilitatory PMd-to-M1HAND pathway. The temporal pattern of MEP facilitation suggests a PMd-to-M1HAND route that targets intracortical M1HAND circuits involved in the generation of indirect corticospinal volleys. This paradigm opens up new possibilities to study context-dependent intrahemispheric PMd-to-M1HAND interactions in the intact human brain.