Interhemispheric interaction between human dorsal premotor and contralateral primary motor cortex

Abstract

We used transcranial magnetic stimulation (TMS) in a paired pulse protocol to investigate interhemispheric interactions between the right dorsal premotor (dPM) and left primary motor cortex (M1) using interstimulus intervals of 4, 6, 8, 10, 12, 16 and 20 ms in ten healthy subjects. A conditioning stimulus over right dPM at an intensity of either 90 or 110% resting motor threshold (RMT) suppressed motor-evoked potentials (MEPs) evoked in the first dorsal interosseous (FDI) muscle by stimulation of left M1. Maximum effects occurred for interstimulus intervals (ISIs) of 8-10 ms. There was no effect if the conditioning stimulus was applied 2.5 cm lateral, anterior or medial to dPM. The effect differed from previously described M1 interhemispheric inhibition in that the threshold for the latter was greater than 90% RMT, whereas stimulation of the dPM at the same intensity led to significant inhibition. In addition, voluntary contraction of the left FDI (i.e. contralateral to the conditioning TMS) enhanced interhemispheric inhibition from right M1 but had no effect on the inhibition from right dPM. Finally, conditioning to right dPM at 90% RMT reduced short-interval intracortical inhibition (SICI; at ISI = 2 ms) in left M1 whilst there was no effect if the conditioning stimulus was applied to right M1. We conclude that conditioning TMS over dPM has effects that differ from the previous pattern of interhemispheric inhibition described between bilateral M1s. This may reflect the existence of commissural fibres between dPM and contralateral M1 that may play a role in bimanual coordination.

Figure 1. Time course of the effects of conditioning TMS pulses applied to right dPM (A, 90% RMT; B, 110% RMT) on responses evoked in the right FDI from left M1

n = 10. Significant inhibitory points are indicated by * (P < 0.05).

Figure 2. Comparisons of the effect of conditioning TMS over dPM, M1 and DLPFC at an intensity of 90% RMT (A, n = 10) or 110% RMT (B, n = 10) and a comparison of the effects of right–left conditioning TMS over dPM on the contralateral M1 (C, n = 8)

Significant differences are indicated by * (P < 0.05) or ** (P < 0.01).

Figure 3. Comparisons of four orthogonal directions of conditioning TMS (110% RMT) over dPM (A) or M1 (B)

n = 8. Current in the brain was directed in four directions: anteriorly (An), posteriorly (P), medially (M) and laterally (L). A two-factor ANOVA (with main factors of direction and ISI) showed no significant main effect.

Figure 4. A comparison of the effects of conditioning TMS (110% RMT) given to dorsal PM, and to sites 2.5 cm medial (medial PM) or lateral (lateral PM) to that point

n = 8. A two-factor ANOVA (with main factors of site and ISI) and post hoc analysis showed that dorsal PM produced larger suppression than conditioning at either of the other two sites.

Figure 5. Comparisons of the effects of tonic contraction of the left FDI versus rest on the effectiveness of conditioning stimuli (110% RMT) applied over right dPM (A) or M1 (B)

n = 8. A three-factor ANOVA and post hoc analyses disclosed that conditioning TMS over right M1 had a larger suppressive effect if it was applied during contraction of left FDI, whereas the level of contraction had no effect on the conditioning effect of dPM stimulation.

Figure 6

A–D, traces show average MEPs from right FDI muscle in a single subject for analysis of the conditioning TMS effect (dPM, 90% RMT) on short-interval intracortical inhibition (SICI). A, a response to the test TMS pulse over left M1 (control wave). B, a preceding conditioning TMS over left M1 at 2 ms before test stimulus leads to inhibition of the test pulse (16% of control wave, usual SICI; trace B/A). C, a conditioning TMS over right dPM 10 ms before the test stimulus leads to a small inhibition of the test pulse (conditioned control wave). D, a response in the presence of conditioning TMS over right dPM 8 ms before a conditioning TMS over left M1; the conditioned SICI (trace D/C) was decreased (48% of conditioned control wave). E, comparisons of the effect on SICI of conditioning stimuli applied over right dPM or M1. Filled bars are usual SICI and open bars are conditioned SICI. Conditioning stimuli over right M1 had no effect on SICI in left M1 (P = 0.7), whereas conditioning stimuli over right dPM reduced SICI in left M1 (*P = 0.006).