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

Abstract

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.

Differential Contribution of Bilateral Supplementary Motor Area to the Effective Connectivity Networks Induced by Task Conditions Using Dynamic Causal Modeling

“…Thereby, these two areas have been consistently found to be significantly activated during both motor execution and motor imagery tasks (Gao et al, 2011;Gerardin et al, 2000;Guillot et al, 2008;Hanakawa et al, 2003;Jeannerod, 1994;Michelon et al, 2006;Solodkin et al, 2004;Szameitat et al, 2007). These functional results were largely in agreement with the anatomical findings in monkeys and humans, showing that the SMA was densely and reciprocally connected with the hand area of M1 (Arai et al, 2012;Johansen-Berg et al, 2004;Luppino et al, 1993;Muakkassa and Strick, 1979;Rouiller et al, 1994). In addition, the SMA has shown hemispherically asymmetric patterns of activation during both motor execution and motor imagery tasks (Babiloni et al, 2003;Haaland and Harrington, 1996;Jancke et al, 2000;Rogers et al, 2004), demonstrating a left dominant activation of SMA in right-handed subjects.…”

“…The influence of SMA on M1 has been consistently confirmed by many effective connectivity measurements such as Granger causality analysis (Chen et al, 2009;Gao et al, 2008Gao et al, , 2011Sato et al, 2006), structural equation modeling (Solodkin et al, 2004), and dynamic causal modeling (DCM) (Grefkes et al, 2008). These results demonstrated a predominantly facilitatory function of the SMA in the top-down processes during motor execution (Arai et al, 2012;Gao et al, 2011;Grefkes et al, 2008), and implied that ipsilateral and contralateral SMAs played different roles on contralateral M1 (Gao et al, 2011).…”

The dorsal premotor cortex exerts a powerful and specific inhibitory effect on the ipsilateral corticofacial system: a dual-coil transcranial magnetic stimulation study

“…It could be speculated that 72 % of stimulator output is too high an intensity to guarantee focality of stimulation. Indeed other authors have found corticocortical connectivity to M1 from the supplementary motor area (Arai et al 2012), which is not far from the dorsal premotor region over which we applied the condTMS. However, the coils that we used for condTMS were considerably smaller (35 mm of outer diameter) than conventional coils, thereby assuring focality of stimulation (Deng et al 2013).…”

Bilateral supplementary motor area syndrome causing akinetic mutism following parasagittal meningioma resection

“…The dominant SMA-proper is also connected to the inferior frontal gyrus by the frontal aslant tract and plays a role in the production of speech [13,18,[34][35][36]. On the afferent side, the SMA-proper receives input from the globus pallidus, thalamus, cerebellar dentate nucleus, and the primary sensory cortex [1,4,[15][16][17]20,[33][34][35][37][38][39][40][41][42][43][44].…”

“…The efferent connections of the pre-SMA are to the prefrontal cortex, insula, cingulate gyrus, superior frontal gyrus, caudate, anterior thalamus, and anterior putamen [1,21,34,35,37,[39][40][41][42][43]. Functional imaging studies demonstrate a tight coupling between SMA-proper activation and the control and generation of movement, while pre-SMA activation is more tightly coupled to cognitive, non-motor tasks [1,21,45].…”