Contrasting cortical and subcortical activations produced by attentional-set shifting and reversal learning in humans

Much evidence suggests that lesions of the prefrontal cortex (PFC) produce marked impairments in the ability of subjects to shift cognitive set, as ex emplified by performance of the Wisconsin Card Sorting Test (WCST). However , studies with humans and experimental primates have suggested that damage to different regions of PFC induce dissociable impairments in two forms of shift learning implicit in the WCST (that is, extradimensional (ED) shift l earning and reversal shift learning), with similar deficits also being appa rent after damage to basal ganglia structures, especially the caudate nucle us. In this study, we used the same visual discrimination learning paradigm over multidimensional stimuli, and the (H2O)-O-15 positron emission tomogr aphy (PET) technique, to examine regional cerebral blood flow (rCBF) change s associated with these subcomponent processes of the WCST. In three condit ions, subjects were scanned while acquiring visual discriminations involvin g either (i) the same stimulus dimension as preceding discriminations (intr adimensional (ID) shifts); (ii) different stimulus dimensions from previous discriminations (ED shifts) or (iii) reversed stimulus-reward contingencie s (reversal shifts). Additionally, subjects were scanned while responding t o already learnt discriminations ('performance baseline'). ED shift learnin g, relative to ID shift learning, produced activations in prefrontal region s, including left anterior PFC and right dorsolateral PFC (BA 10 and 946). By contrast, reversal learning, relative to ID shift learning, produced act ivations to the left caudate nucleus. Additionally, compared to reversal an d ID shift learning, ED shift learning was associated with relative deactiv ations in occipito-temporal pathways (for example, BA 17 and 37). These res ults confirm that, in the context of visual discrimination learning over mu ltidimensional stimuli, the control of an acquired attentional bias or 'set ', and the control of previously acquired stimulus reinforcement associatio ns, activate distinct cortical and subcortical neural stations. Moreover, w e propose that the PFC may contribute to the control of attentional-set by modulating attentional processes mediated by occipito-temporal pathways.