The stop signal task (SST) is widely used to investigate the behavioral and neural processes of motor inhibitory control [1
]. In studies employing fixed stop signal delays (SSD), an inhibitory function could be computed from stop success rate at these SSDs to index individuals' ability of inhibitory control. The inhibitory function or the stop signal reaction time (SSRT) computed from the inhibitory function can then be used in, for example, comparing patients and healthy controls (see [29
] for a review) or tracking the development of inhibitory control through adolescence [30
]. In studies employing a staircase procedure (as in the current study), the SSRT can be computed directly for this purpose. Thus, in behavioral SST studies, there is much consistency as to what represents the outcome measure of inhibitory control.
The imaging literature presents a slightly complicated picture [6
]. For instance, many studies have compared stop and go trials directly in order to identify the neural processes of response inhibition [3
]. The rationale for this contrast perhaps is that the stop but not go process involves response inhibition. Compared to go trials, however, stop trials evoked more perceptual processing. Furthermore, response inhibition is not invariably evoked during stop trials, and subjects succeed or fail in inhibitions depending on whether this capacity is in place. Comparing stop and go trials without distinguishing stop success and error seems to be inconsistent with the underlying rationale of the SST. Other studies contrasted stop success and errors to isolate inhibitory control [4
]. However, successful performance in the SST depends on a number of other cognitive processes in addition to response inhibition. For instance, if participants watch for the stop signal, it is likely that this attention would expedite stop signal processing and facilitate the initiation of motor response inhibition.
We followed the race model by using the SSRT as an index of inhibitory control and identified the anterior pre-supplementary motor area (preSMA) as a brain region mediating response inhibition by comparing individuals with short and long SSRT [9
]. Thus, we replicated here greater activity in the preSMA in association with short SSRT on the basis of a within-subject analysis. In contrast, the inferior frontal cortices did not differentiate between short and long SSRT. These results stood when the order effect of the SSRT sessions was accounted for. We thus confirmed our hypothesis that this medial prefrontal area supports a role of inhibitory control, in keeping with its function in action selection and cognitive control shown in the literature [3
]. In contrast, the IFC is likely to be involved in attentional monitoring and allocation of processing resources, "kicking start" the stop process. Interestingly, consistent with bilateral IFC activation during stop success as compared to stop error [4
], a recent work showed increased no-go errors in patients with left IFC lesions [50
In whole brain analyses, we identified at a moderate threshold three additional structures related to stop signal inhibition, which were not observed in between-subject analyses: right putamen, middle/posterior cingulate cortex (PCC) and part of the vermis in the anterior cerebellum. The finding of right putamen activity in association with short SSRT directly contradicted our previous report which showed greater putamen activity in subjects with long compared to short SSRT [51
]. In fact, a recent study suggested that putamen is a target of prefrontal cortical action of motor inhibition [52
]. On the other hand, putamen lesion is known to cause apraxia, a loss of ability in goal-directed movement [53
]. Putamen is involved in the timing of sequential movements [54
]. In a unilateral motor task, the putamen in the ipsilateral hemisphere coactivated more strongly with the controlling motor cortex (contralateral to movement) than with the noncontrolling cortex, suggesting a complex role of putamen in motor control and its dependence on hemispherity [55
]. Studies also documented activity in the putamen and the cerebellar vermis in movement that requires bimanual coordination [56
]. Both putamen and cerebellum showed greater activation when participants were engaged in spatially incompatible (between hands) drawing than in spatially compatible drawing while the primary motor cortex showed the opposite pattern of response [57
]. Taken together, these studies suggested a role of the putamen in the control rather than simple execution of movement.
The PCC has been implicated in functional neuroimaging in a wide variety of cognitive and affective processes and in the pathogenesis of many neurological conditions [58
]. Although no studies have to our knowledge suggested a specific role of PCC in inhibitory control, a few earlier findings could be discussed with the current result. For instance, a recent magnetoencephalographic study illustrated the importance of enhanced perceptual processing of the stop stimulus in stop signal inhibition [59
]. In particular, the PCC appeared to be a critical site where this enhancement occurs and, via its interconnections with prefrontal structures, greater PCC activity facilitates stop signal inhibition [59
]. Other studies implicated a role of the PCC in motor response inhibition in different behavioral paradigms [60
]. For instance, in an attention cueing task, a spatial cue evoked greater activity in cortical structures including the retrosplenial PCC at a time when premature movement had to be withheld before the target appeared [60
]. Also of note is that the cingulate brain region we identified here did not appear to extend posteriorly to involve the retrosplenial cortex. Further studies were warranted to examine the specific roles of this cingulate region in motor inhibitory control.
We identified in association with short as compared to long SSRT the central lobule of the anterior cerebellum, part of the cerebellar vermis, a structure known to be important for motor control [62
]. In particular, cerebellum activates in response to timed movement which presumably involved a greater extent of inhibitory control, as compared to response to movement guided by external stimulus [63
]. Similarly, non-predictive but not learned, predictable sequence of movement appeared to activate the vermis [67
], potentially because the former required more moment-to-moment control. It has been suggested that cerebellar vermis is important for us to understand the neural processes underlying a number of psychiatric conditions, including attention deficit hyperactivity disorder [68
], schizophrenia [71
], bipolar disorder [74
], and cocaine [76
] and alcohol [77
] use disorders, in which deficits in inhibitory control are implicated. Thus, the finding of greater cerebellar activation in association with response inhibition may also be relevant to studies of these clinical conditions.