Effective connectivity between human supplementary motor area and primary motor cortex: a paired-coil TMS study.

The supplementary motor area (SMA) is important for preparation and execution of voluntary movements and densely anatomically connected with the hand area of primary motor cortex (M1). However, little is known about the effective connectivity between SMA and ipsilateral M1 (SMA → M1). Here, we used paired-coil transcranial magnetic stimulation (pcTMS) to study the SMA → M1 effective connectivity in healthy human subjects. In Experiment 1, we tested the effects of different induced current directions in the SMA and M1, and different intensities of conditioning SMA stimulation. Coil placement over the SMA-proper was verified by MRI-navigation. We found a SMA → M1 facilitatory effect on motor evoked potential (MEP) amplitude that occurred very specifically only with an induced conditioning current directed from the midline towards the targeted SMA, an induced test current in M1 directed antero-medially and sufficient intensity of conditioning SMA stimulation. In Experiment 2, we selected these effective parameters to explore the effects of SMA → M1 on the active MEP amplitude, cortical silent period (CSP) duration, and using a triple-pulse protocol, on short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). None of these measures was affected by conditioning SMA stimulation. Our findings demonstrate that pcTMS identifies predominantly facilitatory connections from SMA-proper to the hand area of the ipsilateral M1. The successful activation of this connection depends on effective SMA-proper stimulation, is state dependent and likely mediated via excitatory interneurons in M1.