Effects of rTMS of Pre-Supplementary Motor Area on Fronto Basal Ganglia Network Activity during Stop-Signal Task

Abstract

Stop-signal task (SST) has been a key paradigm for probing human brain mechanisms underlying response inhibition, and the inhibition observed in SST is now considered to largely depend on a fronto basal ganglia network consisting mainly of right inferior frontal cortex, pre-supplementary motor area (pre-SMA), and basal ganglia, including subthalamic nucleus, striatum (STR), and globus pallidus pars interna (GPi). However, causal relationships between these frontal regions and basal ganglia are not fully understood in humans. Here, we partly examined these causal links by measuring human fMRI activity during SST before and after excitatory/inhibitory repetitive transcranial magnetic stimulation (rTMS) of pre-SMA. We first confirmed that the behavioral performance of SST was improved by excitatory rTMS and impaired by inhibitory rTMS. Afterward, we found that these behavioral changes were well predicted by rTMSinduced modulation of brain activity in pre-SMA, STR, and GPi during SST. Moreover, by examining the effects of the rTMS on restingstate functional connectivity between these three regions, we showed that the magnetic stimulation of pre-SMA significantly affected intrinsic connectivity between pre-SMA and STR, and between STR and GPi. Furthermore, the magnitudes of changes in resting-state connectivity were also correlated with the behavioral changes seen in SST. These results suggest a causal relationship between pre-SMA and GPi via STR during response inhibition, and add direct evidence that the fronto basal ganglia network for response inhibition consists of multiple top-down regulation pathways in humans.

Theta burst magnetic stimulation over the pre-supplementary motor area improves motor inhibition

“…This suggests that cTBS had tightened the distribution of SSRTs, effectively reducing the "noise" in withholding a prepared response. This is likely to be mediated via the pre-SMA connections to the striatum, a pathway shown to mediate fast and urgent behaviours [42] and is in line with recent findings showing striatal changes after inhibitory rTMS over the pre-SMA [21]. Thus, our findings support an inhibitory function of the pre-SMA that when perturbed using stimulation paradigms, drives distant and interconnected regions to manifest its behavioural effects.…”

“…Therefore, it is possible that the cTBS used by Verbruggen et al [17] was not as efficient as ours in actually stimulating the pre-SMA, particularly since we stimulated with a cone-shaped coil that reaches deeper structures in the brain. Other rTMS protocols (such as inhibitory quadruple TMS) over the pre-SMA reported worse response inhibition [21], perhaps because of a stronger physiological effect (due to larger pulse trains) as compared to here.…”

“…Amongst the various processes by which the pre-SMA is considered to exert top-down control [34][35][36][37], our results suggest a predominant role in reactive motor inhibition, without a significant contribution to conflict resolution (see next section for interpretation). Previous imaging evidence shows activation of the pre-SMA during performance of the go no-go [38,39], or stop signal tasks [3][4][5]7,9,21]. Greater pre-SMA activation has been associated with: (i) faster SSRTs [6], and (ii) stronger effective connectivity with the right caudate [40] and right IFG [37], related to gray matter densities [41].…”

“…Similarly, the findings with regard to the effects of rTMS over the pre-SMA are also inconsistent, as improved [8,10,11] but also impaired inhibition [21] have been reported, while others noted involvement of the pre-SMA in conflict resolution [13].…”

The Cutting Edge in Brain Science and Sportology

“…When we partake in or watch sports, wider brain areas are incorporated, including subcortical areas such as basal ganglia and cerebellum. Recent advancement of neuroimaging with a high-field MRI scanner at 3T or 7T has just started to make the analysis of the subcortical areas (such as basal ganglia and cerebellum) in humans possible 3) 14) 15) . I believe that the approach that I reviewed in this article would be also applicable to the data obtained from those wider brain areas and thus applicable to sportological analyses of behavioral effects that arise when we play or watch sports.…”