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

Abstract

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 (CP(80%AMT) and CP(60%AMT), respectively) was followed by a test pulse (TP) over right M1 induced by anterior-posterior- or posterior-anterior- (TP(AP), TP(PA)) 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 CP(80%AMT) over left M1 and TPAP at ISIs of 6 and 8 ms. The same CP(80%AMT) produced IHF at an ISI of 8 ms when applied over left dPM but only with TP(PA). In addition, when CP(60%AMT) was given to M1, IHF was present at an ISI of 6 ms (but not 8 ms) when followed by TP(PA), 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 ofinterneurons in the receiving M1. These may correspond to elements involved in the generation of I3 and I1 waves, respectively.

Figure 1

A, experimental set-up and position of custom-made 70 mm figure-of-eight TMS coils on subject's head. TMS test pulses were applied over right M1 (filled coil) inducing AP- or PA-directed current flows. Conditioning pulses were given over left primary motor cortex (M1) or dorsal premotor cortex (dPM) (open coil). MEPs were recorded from left first dorsal interosseus muscle (FDI). EMG was also recorded from right FDI to control for complete relaxation in the main experiment. B, custom-made ‘baby coils’ with handles perpendicular to the coil windings (‘branding iron style’).

Figure 2

Mean relative MEP amplitudes of conditioned MEPs at interstimulus intervals (ISIs) of 3–10 ms in the different experimental conditions in the main experiment. Mean values (± s.e.m.) are shown.

Figure 3

Conditioned relative MEP amplitudes (mean values ± s.e.m.) at ISIs of 6 ms (A) and 8 ms (B) in all stimulation conditions. Conditions producing IHF are marked with an asterisk. Brackets signify comparisons between experimental conditions. *P < 0.05. AMT, active motor threshold. AP, anterior–posterior current flow of the TMS test pulse; PA, posterior–anterior current flow of the TMS test pulse.

Figure 4

Interhemispheric facilitation induced by conditioning M1 or dPM at rest or under pre-activation of the target muscle (mean values ± s.e.m.). Brackets signify comparisons between experimental conditions. *P < 0.05.