Neuroimaging and lesion studies have shown that the right IFC participates in a network sensitive to the detection of low-frequency, unpredictable events requiring attention (see for review Corbetta and Shulman 2002). It is possible that part of the signal in the inferior frontal region depends on noradrenergic modulation from the brainstem locus coeruleus (LC). The LC receives input (in particular) from the lateral PFC (Arnsten and Goldman-Rakic 1984), fires more to behaviorally relevant stimuli (targets) than to irrelevant distractors, and is needed especially during attentional tasks that are made difficult by temporal unpredictability or distractor interference (see for review Aston-Jones et al 1999). The PFC, in turn, receives noradrenergic input in response to sudden changes in task demands (Dalley et al 2001).
Although this pattern of results mainly concerns vigilance tasks in monkeys and tests of spatial and temporal orienting of attention in humans, it is plausible that there are underlying functions in common with Stop-signal and NoGo response inhibition. In particular, it is clear that these tasks also entail stimulus-driven (‘target’) attention, unpredictability, and vigilance (or “sustained attention”). Such considerations lead to the prediction that drugs that alter noradrenergic tone should affect response inhibition. In fact, it has already been shown that the noradrenergic antagonist yohimbine disrupted NoGo (and not Go) trials in monkeys (Ma et al 2003) and that the noradrenaline reuptake inhibitor, desipramine, speeds SSRT in children with ADHD (Overtoom et al 2003). Moreover, another selective noradrenaline reuptake inhibitor, atomoxetine, has clinical efficacy in ADHD (Michelson et al 2003). Given the role of the NA system in attention, perhaps partly mediated by an LC/right IFC circuit, and the importance of right IFC pathology for ADHD, this system should be investigated with respect to component functions such as vigilance and stimulus-driven attention, which are constituents of response inhibition tasks.
n summary, multiple component functions may contribute to the speed with which a subject cancels a planned/prepotent response (Figure 2). Such functions may include: 1) maintaining and successfully executing the task rules; (2) maintaining alertness/vigilance for the unpredictable occurrence of the Stop-signal; 3) processing the Stop-signal, which requires detecting it as the target for a different action/nonaction and which may require shifting attention from the visual to the auditory domain (although most neuroimaging studies present both Go stimuli and Stop-signal stimuli within the visual domain); and 4) the inhibition itself, which constitutes the executive control and which may require suppression, at the neural-systems level, by PFC of the motor system (cf. Aron et al 2004b). Different functions such as these may be related to different neurotransmitter systems or to different modes (i.e., tonic vs. phasic) of those systems. Right IFC pathology could affect the capacity to maintain alertness, perhaps by reducing efferent input to the LC, or the reverse could be the case: LC input to right IFC could be rendered less effective. Right IFC pathology could also affect the detection of the Stop-signal, the shifting of attention from visual to auditory domains (or cross-modal integration).
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