Department of Neurology, Parkinson's Disease and Movement Disorders Centre, National Neuroscience Institute, Singapore.
Hum Brain Mapp. 2012 Jan;33(1):27-39. doi: 10.1002/hbm.21187. Epub 2011 Mar 24.
To study the interaction between levodopa and the feedback process on set-shifting in Parkinson's disease (PD).
Functional magnetic resonance imaging (fMRI) studies were performed on 13 PD subjects and 17 age-matched healthy controls while they performed a modified card-sorting task. Experimental time periods were defined based on the types of feedback provided. PD subjects underwent the fMRI experiment twice, once during "off" medication (PDoff) and again after levodopa replacement (PDon).
Compared with normal subjects, the cognitive processing times were prolonged in PDoff but not in PDon subjects during learning through positive outcomes. The ability to set-shift through negative outcomes was not affected in PD subjects, even when "off" medication. Intergroup comparisons showed the lateral prefrontal cortex was deactivated in PDoff subjects during positive feedback learning, especially following internal feedback cues. The cortical activations were increased in the posterior brain regions in PDoff subjects following external feedback learning, especially when negative feedback cues were provided. Levodopa replacement did not completely restore the activation patterns in PD subjects to normal although activations in the corticostriatal loops were restored.
PD subjects showed differential ability to set-shift, depending on the dopamine status as well as the types of feedback cues provided. PD subjects had difficulty performing set-shift tasks through positive outcomes when "off" medication, and showed improvement after levodopa replacement. The ability to set-shift through negative feedback was not affected in PD subjects even when "off" medication, possibly due to compensatory changes outside the nigrostriatal dopaminergic pathway.
研究左旋多巴与帕金森病（PD）中定势转移的反馈过程之间的相互作用。
对 13 名 PD 患者和 17 名年龄匹配的健康对照者进行功能磁共振成像（fMRI）研究，同时进行改良卡片分类任务。实验时间段基于提供的反馈类型进行定义。PD 患者在“停药”（PDoff）和左旋多巴替代治疗（PDon）后两次接受 fMRI 实验。
与正常受试者相比，PDoff 患者在学习过程中通过正反馈的认知处理时间延长，但 PDon 患者则没有。即使停药，PD 患者也无法通过负反馈来进行定势转移。组间比较显示，PDoff 患者在正反馈学习期间外侧前额叶皮层失活，尤其是在内部反馈线索后。在外部反馈学习后，PDoff 患者的大脑后部区域的皮质激活增加，尤其是在提供负反馈线索时。虽然皮质纹状体环路的激活得到了恢复，但左旋多巴替代并不能完全使 PD 患者的激活模式恢复正常。
PD 患者的定势转移能力存在差异，这取决于多巴胺状态以及提供的反馈线索类型。PD 患者在停药时通过正反馈进行定势转移任务存在困难，而在左旋多巴替代治疗后则有所改善。即使停药，PD 患者通过负反馈进行定势转移的能力也不受影响，这可能是由于黑质纹状体多巴胺能通路以外的代偿性变化所致。
