Correlation between errors on the Wisconsin Card Sorting Test and the availability of striatal dopamine transporters in healthy volunteers

Hsieh, Pei-Chun; Yeh, Tzung Lieh; Lee, I. Hui; Huang, Hui Chun; Chen, Po See; Yang, Yen Kuang; Chiu, Nan Tsing; Lu, Ru Band; Liao, Mei

doi:10.1503/jpn.090007

Cited by 40 publications

(16 citation statements)

References 34 publications

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“…[40] The DAT has been reported to be associated with cognitive functions in previous studies. [41,42] Spatial working memory is impaired in DAT knockout mice. [43] Selective damage of the dopaminergic neurons in rats can lead to cognitive deficits, particularly when the mesocorticolimbic pathway of the dopaminergic system is involved.…”

Section: Discussionmentioning

confidence: 99%

Incongruent reduction of dopamine transporter availability in different subgroups of alcohol dependence

et al. 2016

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The dopamine transporter (DAT) plays a crucial role in the pathogenesis of alcohol dependence (AD) and major depression (MD), and males have more risk factors for the development of AD. However, imaging studies on brain DAT availability in males with AD comorbid with MD (AD/MD) are limited, and the association of DAT availability with cognitive function and depressive scores in patients with AD/MD has not been analyzed. Hence, this study examined the relationship between brain DAT availability, cognitive function, and depressive symptoms in different subgroups of males with AD.Single-photon emission computed tomography imaging with 99mTc-TRODAT-1 as a ligand was used to measure striatal DAT availability in 49 patients with AD (28 pure AD and 21 AD/MD) and 24 age- and sex-matched healthy volunteers. The Wisconsin Card Sorting Test (WCST) and 17-item Hamilton Depression Rating Scale were used to assess neurocognitive function and depressive scores, respectively. Patients with AD showed a significant reduction of DAT availability in 3 brain regions (P < 0.001), and this reduction was more pronounced in the patients with pure AD compared to healthy controls. The patients with AD showed significantly poorer performance on the WCST, but only in the control group was DAT availability significantly negatively correlated with total errors and perseverative errors (P < 0.001).These preliminary findings suggest that DAT availability is associated with neurocognitive function, and incongruent reduction of DAT may play a pathophysiological role in different subgroups of AD. In addition, decreased DAT availability may be associated with the severity of depressive symptoms in patients with AD/MD.

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Section: Discussionmentioning

confidence: 99%

Incongruent reduction of dopamine transporter availability in different subgroups of alcohol dependence

et al. 2016

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“…After receiving correct feedback for sorting a consecutive series of 10 cards according one category, participants receive correct feedback for sorting the cards in a different manner (but are not otherwise told about the change).Perseveration errors are defined as a failure to shift set to the new sorting criterion. The only dependent variable examined in the current experiment was percentage of perseverative errors, which is the most-commonly used measure of WCST performance (Hsieh et al 2010). …”

Section: Methodsmentioning

confidence: 99%

Factors producing over-selectivity in older individuals

Kelly

Leader

Reed

2016

AGE

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Stimulus over-selectivity describes a phenomenon where only a subset of the relevant stimuli present in the environment, control an individual's behavior. The current experiment explored the degree to which over-selectivity increases in old age. The level of over-selectivity in a visual discrimination task in 60 individuals aged 60-89 years was assessed, as well as the degree to which this reflected attentional control. In addition, the intellectual functioning and cognitive flexibility of the participants were assessed. Results showed that, as age increased, three effects were revealed: levels of stimulus over-selectivity increased, IQ scores decreased, and cognitive flexibility decreased. However, over-selectivity was not related to IQ or cognitive flexibility, and appeared related most to attentional impairments. Thus, ageing is related to significant declines in effective stimulus control. These effects can have a serious impact on the physical and psychological health of old adults, as well as their quality of life, and, therefore, this area of research warrants further exploration. The results are discussed in relation to the attention-deficit and comparator theory of overselectivity.

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“…1 Activity of presynaptic hDAT is strikingly reduced in HIV-1 patients with cocaine abuse. 29, 54 As hDAT availability is correlated with HIV-1 associated neurocognitive deficits, 55, 56 it has been estimated that ~70% of HIV-1 patients are suffering from HAND. 6, 17, 20, 57 The prevalence of HAND and the complicated connection of the HIV-1 infection with cocaine abuse have made a high priority in understanding molecular mechanism of HIV-1 Tat associated neurotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanism of HIV-1 Tat Interacting with Human Dopamine Transporter

Yuan

Huang

Midde

et al. 2015

ACS Chem. Neurosci.

106

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Nearly 70% of HIV-infected individuals suffer from HIV-associated neurocognitive disorders (HAND). HIV-1 transactivator of transcription (Tat) protein is known to synergize with abused drugs and exacerbate the progression of central nervous system (CNS) pathology. Cumulative evidences suggest that the HIV-1 Tat protein exerts the neurotoxicity through interaction with human dopamine transporter (hDAT) in the CNS. Through computational modeling and molecular dynamics (MD) simulations, we develop a three-dimensional (3D) structural model for HIV-1 Tat binding with hDAT. The model provides novel mechanistic insights concerning how HIV-1 Tat interacts with hDAT and inhibits dopamine uptake in hDAT. In particular, according to the computational modeling, Tat binds most favorably with the outward-open state of hDAT. Residues Y88, K92, and Y470 of hDAT are predicted to be key residues involved in the interaction between hDAT and Tat. The roles of these hDAT residues in the interaction with Tat are validated by experimental tests through site-directed mutagensis and DA uptake assays. The agreement between the computational and experimental data suggests that the computationally predicted hDAT-Tat binding mode and mechanistic insights are reasonable and provide a new starting point to design further pharmacological studies on the molecular mechanism of HIV-associated neurocognitive disorders.

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Correlation between errors on the Wisconsin Card Sorting Test and the availability of striatal dopamine transporters in healthy volunteers

Cited by 40 publications

References 34 publications

Incongruent reduction of dopamine transporter availability in different subgroups of alcohol dependence

Incongruent reduction of dopamine transporter availability in different subgroups of alcohol dependence

Factors producing over-selectivity in older individuals

Molecular Mechanism of HIV-1 Tat Interacting with Human Dopamine Transporter

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