Gotham A M, Brown R G, Marsden C D
University Department of Neurology, Institute of Psychiatry, London, UK.
Brain. 1988 Apr;111 ( Pt 2):299-321. doi: 10.1093/brain/111.2.299.
A wide range of cognitive impairments can be observed in patients with Parkinson's disease. A close parallel exists between these deficits and those found following damage to prefrontal cortex. Anatomical evidence is reviewed which reveals a complex pattern of neuronal circuits connecting the frontal cortex and basal ganglia. All these circuits are in some way dependent upon dopamine, suggesting that changes in the levels of dopamine stimulation may alter performance on 'frontal' tests. To test this hypothesis, a group of patients with Parkinson's disease were assessed both on and off levodopa treatment, on a range of tests selected from the human and animal experimental literature as being sensitive to disruption of prefrontal cortex. A variable pattern of results was obtained. On one test, a measure of verbal fluency, patients were impaired, compared with normal controls, only when off levodopa. On two measures, associative conditional learning and subject-ordered pointing, patients were impaired only when on levodopa, while on the final measures, the Wisconsin Card Sorting Test, patients were impaired both on and off levodopa. Two mechanisms are discussed to explain these results, one based on the effects of dopamine depletion, and the other based on the adverse effects of dopamine overstimulation. The results suggest that different areas of prefrontal cortex are involved in the tasks employed, and that functional levels of dopamine in separate areas of cortex and caudate may differ crucially in Parkinson's disease.
帕金森病患者可观察到广泛的认知障碍。这些缺陷与前额叶皮质受损后出现的缺陷极为相似。本文回顾了相关解剖学证据，这些证据揭示了连接额叶皮质和基底神经节的复杂神经元回路模式。所有这些回路在某种程度上都依赖多巴胺，这表明多巴胺刺激水平的变化可能会改变 “额叶” 测试的表现。为了验证这一假设，一组帕金森病患者在服用左旋多巴和未服用左旋多巴的情况下，接受了一系列从人类和动物实验文献中挑选出来的、对前额叶皮质破坏敏感的测试。结果呈现出一种多变的模式。在一项语言流畅性测试中，与正常对照组相比，患者仅在未服用左旋多巴时表现受损。在两项测试中，即联想条件学习和按主题顺序指向测试中，患者仅在服用左旋多巴时表现受损，而在最后一项测试，即威斯康星卡片分类测试中，患者在服用和未服用左旋多巴时均表现受损。文中讨论了两种机制来解释这些结果，一种基于多巴胺耗竭的影响，另一种基于多巴胺过度刺激的不良影响。结果表明，前额叶皮质的不同区域参与了所采用的任务，并且在帕金森病中，皮质和尾状核不同区域的多巴胺功能水平可能存在显著差异。
