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
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
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DOI：
10.1523/jneurosci.14-05-02531.1994
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发表时间：
1994-05
期刊：
影响因子：
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通讯作者：
AC Roberts;M. D. De Salvia;L. Wilkinson;P. Collins;J. Muir;B. Everitt;T. Robbins
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作者：
AC Roberts;M. D. De Salvia;L. Wilkinson;P. Collins;J. Muir;B. Everitt;T. Robbins
研究了6-羟多巴胺对猴前额叶皮层损伤后对前额叶功能、空间延迟反应和注意定势转移的影响。后一个测试提供了威斯康星州卡片分类测试的成分分析，这是一种常用的人类额叶功能的临床测试，要求注意力从一个维度转移到另一个维度（额外维度转移），例如，形状到线条，视觉复合辨别的获得显著改善。这种增强是行为特异性的，因为没有影响收购的歧视，需要继续保持对一个特定的维度（intradimensional移位）的注意力设置，也没有任何影响一系列的视觉或空间歧视逆转，涉及重复移位的两个样本之间的反应从同一个维度。相反，空间延迟反应性能受损，与以前的结果一致。神经化学指标显示，仅限于前额叶皮质的多巴胺明显减少，前额叶去甲肾上腺素损失较小。这是伴随着一个长期的适应性变化，在纹状体的细胞外多巴胺在尾状核，在体内微透析测量，升高钾刺激，只要18个月术后。有人提出，注意定势转移是由前额叶和纹状体多巴胺之间的平衡相互作用介导的，并且多巴胺的升高有助于注意定势转移能力的改善。这种解释与帕金森病患者或额叶受损患者的注意定势转移能力受损一致，这些患者的注意定势转移能力受损是使用与这里用于亚人类灵长类动物相同的测试观察到的。
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.