Modulatory effects of the supplementary motor area on primary motor cortex outputs

Abstract

Premotor areas of primates are specialized cortical regions that can contribute to hand movements by modulating the outputs of the primary motor cortex (M1). The goal of the present work was to study how the supplementary motor area (SMA) located within the same hemisphere [i.e., ipsilateral SMA (iSMA)] or the opposite hemisphere [i.e., contralateral (cSMA)] modulate the outputs of M1. We used paired-pulse protocols with intracortical stimulations in sedated capuchin monkeys. A conditioning stimulus in iSMA or cSMA was delivered simultaneously or before a test stimulus in M1 with different interstimulus intervals (ISIs) while electromyographic activity was recorded in hand and forearm muscles. The pattern of modulation from iSMA and cSMA shared some clear similarities. In particular, both areas predominantly induced facilitatory effects on M1 outputs with shorter ISIs and inhibitory effects with longer ISIs. However, the incidence and strength of facilitatory effects were greater for iSMA than cSMA. We then compared the pattern of modulatory effects from SMA to the ones from the dorsal and ventral premotor cortexes (PMd and PMv) collected in the same series of experiments. Among premotor areas, the impact of SMA on M1 outputs was always weaker than the one of either PMd or PMv, and this was regardless of the hemisphere, or the ISI, tested. These results show that SMA exerts a unique set of modulations on M1 outputs, which could support its specific function for the production of hand movements. NEW & NOTEWORTHY We unequivocally isolated stimulation to either the ipsilateral or contralateral supplementary motor area (SMA) using invasive techniques and compared their modulatory effects on the outputs of primary motor cortex (M1). Modulations from both SMAs shared many similarities. However, facilitatory effects evoked from ipsilateral SMA were more common and more powerful. This pattern differs from the ones of other premotor areas, which suggests that each premotor area makes unique contributions to the production of motor outputs.

Interhemispheric modulations of motor outputs by the rostral and caudal forelimb areas in rats

“…Based on this analysis, it appears that order in which data was collected across cortical sites within an animal does not affect the pattern of modulation. This finding is in line with the lack of cumulative effects we have previously found when using similar protocols in both rats (Deffeyes et al 2015) and monkeys (Côté et al 2017(Côté et al , 2020Quessy et al 2016).…”

“…To date, studies on interhemispheric interactions in humans or NHPs have focused on the modulatory effects of premotor areas on M1 outputs (Buch et al 2010;Côté et al 2017;Fiori et al 2017;Koch et al 2007;Mochizuki et al 2004aMochizuki et al , 2004bQuessy et al 2016). In NHPs, we have compared the pattern of modulation from various premotor areas on M1 outputs using very similar techniques as the ones in the present study (Côté et al 2017(Côté et al , 2020Quessy et al 2016). Much like RFA in rats, premotor areas induce strong modulations that are affected by the timing of stimulations.…”

“…In addition, considering that RFA has been suggested to be on a higher hierarchical level than CFA , we also studied modulatory effects from RFA on motor outputs of CFA. We discuss how these effects compare with the pattern of interhemispheric modulation between premotor areas and M1 in NHPs (Côté et al 2017(Côté et al , 2020Quessy et al 2016).…”

“…These data would reveal similarities and differences between CFA and RFA and help us understand how these areas can contribute to the production of movements of the ipsilateral arm. Moreover, they would allow us to compare patterns of interhemispheric modulations of RFA to the ones of premotor areas in NHPs (Côté et al 2017(Côté et al , 2020Quessy et al 2016). Therefore, we sought to characterize output properties of CFA and RFA and then studied how these outputs are modulated by conditioning stimulations delivered in forelimb motor areas of the opposite hemisphere.…”

Reduced SMA‐M1 connectivity in older than younger adults measured using dual‐site TMS

“…However, SMA-M1 connectivity ratios at each ISI varied to some extent both between and within individuals, suggesting that a conditioning stimulus to SMA can have both an inhibitory and a facilitatory influence on M1 excitability. A nonhuman primate study using pairedpulse electrical stimulation to investigate connectivity between ipsilateral SMA and M1 showed that stimulating SMA facilitated M1 excitability at short ISIs (1, 2, 2.5 and 5 ms) but inhibited M1 excitability at longer ISIs (10 and 20 ms) (Cote et al, 2020). This finding, suggesting that facilitatory and inhibitory influences of SMA on M1 are time-dependent in nonhuman primates, fits with dualsite TMS studies in humans showing a facilitatory effect of SMA on M1 at short ISIs (6, 7 and 8 ms) but an inhibitory effect of SMA on M1 at a longer ISI (40 ms) in younger adults (Arai et al, 2011(Arai et al, , 2012Fiori et al, 2017;Green et al, 2018).…”