Abstract

The primary motor cortex (M1) is highly influenced by premotor/motor areas both within and across hemispheres. Dual site transcranial magnetic stimulation (dsTMS) has revealed interhemispheric interactions mainly at early latencies. Here, we used dsTMS to systematically investigate long-latency causal interactions between right-hemisphere motor areas and the left M1 (lM1). We stimulated lM1 using a suprathreshold test stimulus (TS) to elicit motor-evoked potentials (MEPs) in the right hand. Either a suprathreshold or a subthreshold conditioning stimulus (CS) was applied over the right M1 (rM1), the right ventral premotor cortex (rPMv), the right dorsal premotor cortex (rPMd) or the supplementary motor area (SMA) prior to the TS at various CS-TS inter-stimulus intervals (ISIs: 40–150 ms). The CS strongly affected lM1 excitability depending on ISI, CS site and intensity. Inhibitory effects were observed independently of CS intensity when conditioning PMv, rM1 and SMA at a 40-ms ISI, with larger effects after PMv conditioning. Inhibition was observed with suprathreshold PMv and rM1 conditioning at a 150-ms ISI, while site-specific, intensity-dependent facilitation was detected at an 80-ms ISI. Thus, long-latency interhemispheric interactions, likely reflecting indirect cortico-cortical/cortico-subcortical pathways, cannot be reduced to nonspecific activation across motor structures. Instead, they reflect intensity-dependent, connection- and time-specific mechanisms.

Highlights

  • Motor network functioning is based on neural interactions between different premotor and motor areas

  • The conditioning stimulus (CS) site x CS intensity ANOVA performed on the dual-site transcranial magnetic stimulation (dsTMS) modulation index collected at a 40-ms inter-stimulus intervals (ISIs) showed a main effect of CS site (F3,39 = 7.26, P = 0.001; ηp2 = 0.36; Fig. 2a)

  • Post-hoc comparisons suggested that this main effect was accounted for by the more negative dsTMS modulation index values obtained with rPMv conditioning relative to right PMd (rPMd) (−0.01 mV ± 0.02; P = 0.001), right M1 (rM1) (−0.13 mV ± 0.05; P = 0.012) and supplementary motor area (SMA) conditioning (−0.11 mV ± 0.04; P = 0.009)

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Summary

Introduction

Motor network functioning is based on neural interactions between different premotor and motor areas. Mochizuki et al.[21] investigated the influence of a CS administered over right motor-related areas (rM1 and a dorso-lateral premotor site at the border between rPMd and the right PMv, rPMv) on the excitability of lM1 These studies have documented longer-latency premotor-motor interhemispheric interactions, supporting the notion that motor network functioning might rely on interactions at different time-scales. They did not clarify the issue of anatomical specificity, i.e., whether different sectors of premotor cortex (i.e., from ventral to medial areas) exert different effects on contralateral M1 excitability. In those studies, lower (i.e., subthreshold) CS intensities were only used at a single long-latency ISI of 50 ms[22], but not at later ISIs

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