6-HYDROXYDOPAMINE LESIONS OF THE PREFRONTAL CORTEX IN MONKEYS ENHANCEPERFORMANCE ON AN ANALOG OF THE WISCONSIN CARD SORT TEST - POSSIBLE INTERACTIONS WITH SUBCORTICAL DOPAMINE

The effects of 6-hydroxydopamine lesions of the prefrontal cortex in m onkeys were investigated on two cognitive tests of prefrontal function , spatial delayed response, and attentional set shifting. The latter t est provided a componential analysis of the Wisconsin Card Sort Test, a commonly used clinical test of frontal lobe function in man. Acquisi tion of a visual compound discrimination requiring a shift of attentio n from one dimension to another (extradimensional shift), for example, shapes to lines, was significantly improved. This enhancement was beh aviorally specific in that there were no effects on acquisition of a d iscrimination that required the continued maintenance of an attentiona l set toward one particular dimension (intradimensional shift), nor an y effects on a series of visual or spatial discrimination reversals th at involved the repeated shifting of responding between two exemplars from the same dimension. In contrast, spatial delayed response perform ance was impaired, in agreement with previous results. Neurochemical m easures showed a marked depletion of dopamine limited to the prefronta l cortex and a smaller loss of prefrontal noradrenaline. This was acco mpanied by a long-term adaptive change in the striatum such that extra cellular dopamine in the caudate nucleus, as measured by in vivo micro dialysis, was elevated in response to potassium stimulation as long as 18 months postsurgery. It is proposed that attentional set shifting i s mediated by a balanced interaction between prefrontal and striatal d opamine, and that elevated dopamine contributes to the improvement in attentional set-shifting ability. This interpretation is consistent wi th the impairment in attentional set-shifting ability observed in pati ents with Parkinson's disease or with damage to the frontal lobes usin g the same test as used here for infrahuman primates.