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Journal of Neuroscience, Vol 14, 2531-2544, Copyright © 1994 by Society for Neuroscience
6-Hydroxydopamine lesions of the prefrontal cortex in monkeys enhance performance on an analog of the Wisconsin Card Sort Test: possible interactions with subcortical dopamine
AC Roberts, MA De Salvia, LS Wilkinson, P Collins, JL Muir, BJ Everitt and TW Robbins
Department of Experimental Psychology, University of Cambridge, United Kingdom.
The effects of 6-hydroxydopamine lesions of the prefrontal cortex in
monkeys were investigated on two cognitive tests of prefrontal function,
spatial delayed response, and attentional set shifting. The latter test
provided a componential analysis of the Wisconsin Card Sort Test, a
commonly used clinical test of frontal lobe function in man. Acquisition of
a visual compound discrimination requiring a shift of attention from one
dimension to another (extradimensional shift), for example, shapes to
lines, was significantly improved. This enhancement was behaviorally
specific in that there were no effects on acquisition of a discrimination
that required the continued maintenance of an attentional set toward one
particular dimension (intradimensional shift), nor any effects on a series
of visual or spatial discrimination reversals that involved the repeated
shifting of responding between two exemplars from the same dimension. In
contrast, spatial delayed response performance was impaired, in agreement
with previous results. Neurochemical measures showed a marked depletion of
dopamine limited to the prefrontal cortex and a smaller loss of prefrontal
noradrenaline. This was accompanied by a long-term adaptive change in the
striatum such that extracellular dopamine in the caudate nucleus, as
measured by in vivo microdialysis, was elevated in response to potassium
stimulation as long as 18 months postsurgery. It is proposed that
attentional set shifting is mediated by a balanced interaction between
prefrontal and striatal dopamine, and that elevated dopamine contributes to
the improvement in attentional set-shifting ability. This interpretation is
consistent with the impairment in attentional set-shifting ability observed
in patients with Parkinson's disease or with damage to the frontal lobes
using the same test as used here for infrahuman primates.
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