Abstract
The attentional set-shifting deficit that has been observed in Parkinson’s disease (PD) has long been considered neuropsychological evidence of the involvement of meso-prefrontal and prefrontal-striatal circuits in cognitive flexibility. However, recent studies have suggested that non-dopaminergic, posterior cortical pathologies may also contribute to this deficit. Although several neuroimaging studies have addressed this issue, the results of these studies were confounded by the use of tasks that required other cognitive processes in addition to set-shifting, such as rule learning and working memory. In this study, we attempted to identify the neural correlates of the attentional set-shifting deficit in PD using a compound letter task and 18F-fluoro-deoxy-glucose (FDG) positron emission tomography during rest. Shift cost, which is a measure of attentional set-shifting ability, was significantly correlated with hypometabolism in the right dorsolateral prefrontal cortex, including the putative human frontal eye field. Our results provide direct evidence that dysfunction in the dorsolateral prefrontal cortex makes a primary contribution to the attentional set-shifting deficit that has been observed in PD patients.
Highlights
Cognitive inflexibility is a primary neuropsychological feature of Parkinson’s disease (PD) [1,2]
Ravizza and colleagues demonstrated that interference from competing stimuli, or stimulus ‘cross-talk,’ resulted in poorer attentional set-shifting performance on the modified Odd-Man-Out task in PD patients [10]
We found one outlier PD patient whose mean RT on the Global task was longer than the mean RT of all of the PD patients +3 SDs
Summary
Cognitive inflexibility is a primary neuropsychological feature of Parkinson’s disease (PD) [1,2]. Neuropsychological tests of ‘frontal lobe’ function, such as the Wisconsin Card Sorting Test (WCST), the Intra-Dimensional/Extra-Dimensional (ID/ED) set-shifting paradigm, the Odd-Man-Out task and variants of these tests, have been used to measure cognitive flexibility [3,4,5,6] In these tasks, subjects are shown a successive series of visual stimuli that have multiple perceptual dimensions, and they are asked to flexibly switch their behavioral responses from one particular perceptual dimension to another dimension on the basis of a prelearned rule. Both letter and digit identification are governed by wellestablished stimulus-response rules, require no new learning and require little working memory, whereas the manipulation of multidimensional geometric figures demands rather high capacities for both learning and working memory Another problem in investigating set-shifting is that there are two critical components of any given cognitive set: the stimulus set and the response set [7,9]. The current evidence suggests that in situations in which competitive stimuli are present, early stage PD patients have impaired attentional set-shifting abilities, but not impaired task-set switching abilities [1]
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