Dopaminergic modulation of cortical function in patients with Parkinson's disease
Dopaminergic modulation of cortical function in patients with Parkinson's disease
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DOI：
10.1002/ana.10078
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发表时间：
2002-02-01
影响因子：
11.2
通讯作者：
Weinberger, DR
中科院分区：
文献类型：
--
作者：
Mattay, VS;Tessitore, A;Weinberger, DR
特发性帕金森氏症患者不仅有典型的运动症状，而且还有认知功能障碍，主要是前额叶皮质的功能障碍。本研究的目的是研究多巴胺能治疗对帕金森病患者工作记忆和运动功能的神经系统的调节作用。对10名I期和II期帕金森病患者在相对低多巴胺状态(即最后一剂多巴胺治疗后12小时)和多巴胺充足状态下进行了功能磁共振成像研究。功能磁共振成像是在三种情况下进行的：工作记忆任务、线索感觉运动任务和休息。与之前的数据一致，在运动任务中激活的皮质运动区在多巴胺充足状态下表现出更大的激活；然而，在低多巴胺能状态下，辅助工作记忆的皮质区域表现出更大的激活。有趣的是，在低多巴胺状态下的工作记忆任务中，大脑皮层激活的增加与任务表现的错误呈正相关，而在多巴胺充足状态下，大脑皮层运动区的激活增加与运动功能的改善呈正相关。这些结果支持来自基础研究的证据，即多巴胺通过两种不同的机制调节服务于工作记忆和运动功能的皮质网络：黑质纹状体投射通过丘脑向运动皮质的投射间接促进运动功能，而中皮质多巴胺能系统通过直接输入前额叶皮质来促进工作记忆功能。这一结果也与前额叶皮质信息处理效率降低有关的证据一致，即低多巴胺状态与前额叶皮质信息处理效率降低有关，而多巴胺能治疗提高了该区域的生理效率。
Patients with idiopathic Parkinson's disease suffer not only from classic motor symptoms, but from deficits in cognitive function, primarily those subserved by the prefrontal cortex as well. The aim of the current study was to investigate the modulatory effects of dopaminergic therapy on neural systems subserving working memory and motor function in patients with Parkinson's disease. Ten patients with stage I and II Parkinson's disease were studied with functional magnetic resonance imaging, during a relatively hypodopaminergic state (ie, 12 hours after a last dose of dopamimetic treatment), and again during a dopamine-replete state. Functional magnetic resonance imaging was performed under three conditions: a working memory task, a cued sensorimotor task and rest. Consistent with prior data, the cortical motor regions activated during the motor task showed greater activation during the dopamine-replete state; however, the cortical regions subserving working memory displayed greater activation during the hypodopaminergic state. Interestingly, the increase in cortical activation during the working memory task in the hypodopaminergic state positively correlated with errors in task performance, and the increased activation in the cortical motor regions during the dopamine-replete state was positively correlated with improvement in motor function. These results support evidence from basic research that dopamine modulates cortical networks subserving working memory and motor function via two distinct mechanisms: nigrostriatal projections facilitate motor function indirectly via thalamic projections to motor cortices, whereas the mesocortical dopaminergic system facilitates working memory function via direct inputs to prefrontal cortex. The results are also consistent with evidence that the hypodopaminergic state is associated with decreased efficiency of prefrontal cortical information processing and that dopaminergic therapy improves the physiological efficiency of this region.