Discussion
The current study aimed at taking advantage of a single-pulse TMS technique to assess whether and how PMCd and SMA may play a distinctive role in a specific feature of action inhibition, namely being able to perform a short-term inhibition of a due movement just begun or about to begin. Single-pulse TMS was applied to the PMCd and SMA regions during the pre-movement or early response phase of a SST. Accuracy in the performance during effective stimulation was compared to accuracy in the sham stimulation. There were two main findings.
First, the real stimulation of PMCd produced a much stronger and highly replicable increase in error rates than the placebo stimulation. Importantly, this effect concerned the STOP trials only. Indeed, participants had no any impairment in initiating and completing the mouth movements in the NO-STOP trials.
Second,
Taken together, these findings suggest a differential contribution of PMCD and SMA in action inhibition during a SST.
As far as the first finding is concerned, it is worth mentioning that our results are in line, partially at least, with previous studies investigating the inhibitory role of PMCD in both non-human primates and humans. Indeed, a single cell study recorded from PMCD neurons of two monkeys (Macaca mulatta) when performing both NO-STOP and STOP trials in a countermanding task (Mirabella et al. 2011). In the NO-STOP trials, the monkeys should execute a speeded reaching movement at the appearance of a suitable target. In the Stop trials, after a variable delay, a stop signal appeared, instructing the monkeys to inhibit the movement initiation. The results showed that more than one third of recorded PMCD neurons involved in motor planning exhibit a countermanding modulation. These neurons changed their pattern of discharge when a reaching movement were executed with respect to when it was inhibited, and this change preceded the end of the stop-signal reaction time.
An early model for SST proposed two neural units racing towards a threshold in STOP trials: The idea of a neural decision unit accumulating activity towards threshold is well established in decision theory, with the accumulation itself representing sensory information providing evidence for a particular decision. In the case of countermanding, the first unit represents the ‘Go’ decision, and the second one (the Stop unit) starts accumulating after the Stop signal delay if the Stop signal is presented. Failed Stop trials can then be explained by the Go unit reaching threshold before the Stop unit and therefore escaping inhibition, whereas successfully cancelled trials are due to the Stop unit winning the race. A feature of this model is that the two units in this model move towards threshold independently from one another (Logan GD, Cowan WB, Davis KA. 1984)
A distinctive inhibitory role of PMCd over movement production seems to be also suggested by GO/NOGO studies. For instance, Kalaska and Crammond (1995) showed that neural activity of PMCd neurons changed when a movement should be suppressed with respect to when it should be executed. Similar results have been also reported by Ledberg et al., (2007), who showed that cortical activity in PMCd allowed to predict the monkey’s choice after 150 ms.
Although the GO/NOGO and stop-signal paradigms are different, being the latter (but not the former) concerned with an ongoing motor response, nevertheless there are reasons to assume that these different kinds of action restraining may have a cortical overlap (Battaglia-Mayer et al., 2014). This seems to be also consistent with lesion data. Indeed, the injection of GABA-A antagonists within PMCd reduces the ability of monkeys to withhold movements (Sawaguchi et al., 1996). Similarly, lesions PMCd may result in increased frequency of impulsive and uncontrolled reaching movements (Moll & Kuypers, 1977).
A similar inhibitory role of PMCd have been reported also in a human lesion study. Indeed, patients with focal lesions, especially in the left superior portion of BA6 (putative PMCd and SMA), have been demonstrated to succumb to an increased number of false alarms, thus revealing a clear deficit in inhibiting responses to a NOGO stimulus (Picton et al., 2007).
This study allows us to introduce our second finding, that is, the substantial difference between PMCd and SMA involvement in action inhibition during the SST. Cases of epileptic negative myoclonus related to paroxysmal activities
located over the frontal regions have been reported, suggesting the possible involvement of both mesial frontal areas, specifically SMA, and of the premotor regions over the dorsolateral surface of the frontal lobe [8-10]. (MELETTI)
Il nostro studio mette in luce l’importanza di pmcd in questo tipo di compito, rispetto a sma, ma primo è chiaramente confinato alle risorse necessarie per performare questo tipo di SST, secondo il comparison tra dati comportamentali e di stimolazione su soggetti sani e i dati nei pazienti o relativi a lesioni è sempre da fare con particolare cautela.
Our results do not rule out a contribution of SMA to action inhibition, of course. But they suggest that, differently from PMCd, SMA seems to be not selectively related to stopping an ongoing motor response
SMA has been typically considered to be critically involved in action preparation, being also concerned with the suppression of a potential action, but not selectively with the inhibition of an ongoing actual action. Indeed, SMA has been shown to be active even when people merely view graspable objects, without any intention to act upon them (Grézes & Decety, 2002). Such an activity has been interpreted in terms of an automatic inhibitory process concerning actions, which might be afforded by the viewed object but are in fact not required to be performed (see Nachev, Kennard, & Husain, 2008). This interpretation is consistent with lesion data indicating that patients with microlesion of SMA, differently from healthy people and control patients with pre-SMA damage, are impaired in automatic suppression of evoked motor plans (Sumner et al., 2007). Furthermore, it is worth noting that single cell recordings from pre-SMA and proper-SMA neurons in monkeys showed that only a very small percentage of recorded neurons (2.4%) were involved in action inhibition (Scangos & Stuphorn, 2010). Even though the presence of a recording bias or other factors that might have influenced the total number of identified neurons could not be excluded, it is also plausible to hypothesize that SMA (and pre-SMA to a certain extent) are not the main actors in cancelling a movement after the appearance of an imperative stop-signal. This interpretation is not in contrast with the finding of Chen et al. (2010) who showed that local field potential (LFP) power spectra obtained from data recorded over SMA display changes in the low-frequency range (10–50 Hz) early enough to suggest that this region is causally involved in movement inhibition. Indeed, changes in LFPs could be caused not by the local activity but by inputs coming from other brain regions (Logothetis, 2003; Mattia et al., 2013).
(PMCd è un possibile nodo di overlap tra motor inhibition for action preparation (Parmigiani et al., submitted) and action stopping. Our study aimed at investigating whether and how PMCd and SMA are part of the neural underpinnings that enables appropriate stop and go behaviours required in performing a SST.
In conclusion, although further research is needed, our findings seem to indicate a distinctive role for PMCd in action control, suggesting that PMCd can be selectively involved in promptly interrupting an ongoing action. This does not rule out the possibility that SMA might contribute to this function. However, this contribution does not seem to be necessarily related to the prompt inhibition of a just started action.