Cognitive & Behavioural Neuroscience Seminar: Neuroimaging of the catecholaminergic modulation of response inhibition using the stop signal task

Abstract

Response inhibition is a behavioural construct whereby planned or prepotent responses are to be inhibited or countermanded. Research in experimental animals and humans has consistently linked this to an intact catecholamine system with dopaminergic and noradrenergic systems proposed to have a role. In humans, using the stop signal task to assess the neural basis of countermanding behaviour, the inferior frontal gyrus, the (pre-)supplementary motor areas and basal ganglia have been associated with successful stopping, although the network activated by stop signal tasks with fMRI is more widespread. One feature of stop tasks is the infrequent and salient nature of the stop signals. When this confound is accounted for in specific variants of task design the pre-SMA is specifically linked to stopping with important ‘attentional’ roles for other parts of the network. The administration of methylphenidate, a dopamine and noradrenaline reuptake inhibitor, alters behaviour and brain activity during the stop task but the precise effects depend on the inclusion of attentional controls. Similarly, with atomoxetine, a noradrenaline reuptake inhibitor, the modulation of the fMRI contrast during stopping varies depending on whether attentional confounds are included. For methylphenidate error related activity is increased by the drug in the medial prefrontal cortex, whereas atomoxetine increases activity during successful stops in the pre-SMA and supramarginal gyrus. Some of these effects can be predicted by the baseline locus coeruleus integrity indexed on separate scans. Overall, these data suggest differential dopaminergic and noradrenergic modulation of response inhibition and highlight the need for more controlled investigations in patient groups.