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Attentional set-shifting deficit in Parkinson's disease is associated with prefrontal dysfunction: an FDG-PET study.

Sawada Y, Nishio Y, Suzuki K, Hirayama K, Takeda A, Hosokai Y, Ishioka T, Itoyama Y, Takahashi S, Fukuda H, Mori E - PLoS ONE (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan.

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.

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Related in: MedlinePlus

Results of the whole-brain voxel-based analyses.First row: The brain regions that exhibited regional cerebral glucose metabolic reductions in the 60 PD patients relative to 14 normal volunteers (p<0.05 uncorrected, extent threshold of 100 voxels). Second row and below: The brain regions in which the resting CMRglc was correlated with the RTs in the various psychophysical tasks (Global: second row, Local: third row, Mixed: fourth row) and the shift cost (fifth row) (p<0.001 uncorrected, extent threshold of 100 voxels). PD, Parkinson’s disease; R, right; L, left.
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pone-0038498-g003: Results of the whole-brain voxel-based analyses.First row: The brain regions that exhibited regional cerebral glucose metabolic reductions in the 60 PD patients relative to 14 normal volunteers (p<0.05 uncorrected, extent threshold of 100 voxels). Second row and below: The brain regions in which the resting CMRglc was correlated with the RTs in the various psychophysical tasks (Global: second row, Local: third row, Mixed: fourth row) and the shift cost (fifth row) (p<0.001 uncorrected, extent threshold of 100 voxels). PD, Parkinson’s disease; R, right; L, left.

Mentions: The results of the whole-brain voxel-based multiple regression analyses in which age, sex, MMSE score, and UPDRS-III were included as nuisance variables are shown in Table 2 and Figure 3. For reference purposes, images that depict maps of sites at which there were reductions in CMRglc in the 60 PD patients relative to the 14 healthy controls are presented in Figure 3 and in Supplementary Figure S1. Although the NPI depression scores were only correlated with the Mixed task RTs, previous studies have suggested that depression has a significant impact on cognitive function. We performed supplementary analyses in which the NPI depression score was included as a nuisance variable. The results of these analyses are shown in Supplementary Figure S2.


Attentional set-shifting deficit in Parkinson's disease is associated with prefrontal dysfunction: an FDG-PET study.

Sawada Y, Nishio Y, Suzuki K, Hirayama K, Takeda A, Hosokai Y, Ishioka T, Itoyama Y, Takahashi S, Fukuda H, Mori E - PLoS ONE (2012)

Results of the whole-brain voxel-based analyses.First row: The brain regions that exhibited regional cerebral glucose metabolic reductions in the 60 PD patients relative to 14 normal volunteers (p<0.05 uncorrected, extent threshold of 100 voxels). Second row and below: The brain regions in which the resting CMRglc was correlated with the RTs in the various psychophysical tasks (Global: second row, Local: third row, Mixed: fourth row) and the shift cost (fifth row) (p<0.001 uncorrected, extent threshold of 100 voxels). PD, Parkinson’s disease; R, right; L, left.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369918&req=5

pone-0038498-g003: Results of the whole-brain voxel-based analyses.First row: The brain regions that exhibited regional cerebral glucose metabolic reductions in the 60 PD patients relative to 14 normal volunteers (p<0.05 uncorrected, extent threshold of 100 voxels). Second row and below: The brain regions in which the resting CMRglc was correlated with the RTs in the various psychophysical tasks (Global: second row, Local: third row, Mixed: fourth row) and the shift cost (fifth row) (p<0.001 uncorrected, extent threshold of 100 voxels). PD, Parkinson’s disease; R, right; L, left.
Mentions: The results of the whole-brain voxel-based multiple regression analyses in which age, sex, MMSE score, and UPDRS-III were included as nuisance variables are shown in Table 2 and Figure 3. For reference purposes, images that depict maps of sites at which there were reductions in CMRglc in the 60 PD patients relative to the 14 healthy controls are presented in Figure 3 and in Supplementary Figure S1. Although the NPI depression scores were only correlated with the Mixed task RTs, previous studies have suggested that depression has a significant impact on cognitive function. We performed supplementary analyses in which the NPI depression score was included as a nuisance variable. The results of these analyses are shown in Supplementary Figure S2.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan.

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.

Show MeSH
Related in: MedlinePlus