Neuroscience Program, University of Michigan, Ann Arbor, MI 48109, United States.
Behav Brain Res. 2012 Apr 21;230(1):116-24. doi: 10.1016/j.bbr.2012.02.006. Epub 2012 Feb 10.
We previously reported a differential effect of dopaminergic medication across the time course of motor sequence learning in early stage Parkinson's (PD) patients [1]. There was a medication-associated impairment specific to the early phase of learning. In the current study, we investigated the BOLD responses associated with this deleterious medication effect on motor sequence learning. We hypothesized that levodopa (l-DOPA) would negatively affect the recruitment of the ventral striatal circuitry during the early phase of learning. Seventeen early stage PD patients ON and OFF l-DOPA and 21 healthy control participants performed an explicit motor sequence learning task inside the MRI scanner. We observed sequence learning-specific activation during the early phase in the ventral putamen for controls and PD OFF but not for PD ON l-DOPA. A comparison of activation between PD OFF and PD ON showed that activation within the ventral putamen was decreased in PD ON compared to PD OFF. The extent of the l-DOPA associated activation decrease in the ventral putamen showed a small, positive correlation with the degree of sequence learning performance decrease in the early phase of learning (r=0.45-0.54 across measures, p<0.05, one-tailed). These findings provide evidence for the negative effects of l-DOPA in PD patients on the ventral putamen circuitry involved in early motor sequence learning, and provide support for a role of this structure in the sequence learning process.
我们之前报道过，在早期帕金森病（PD）患者的运动序列学习过程中，多巴胺能药物的作用存在差异[1]。在学习的早期阶段存在与药物相关的特定损伤。在当前的研究中，我们研究了与这种对运动序列学习有害的药物作用相关的 BOLD 反应。我们假设左旋多巴（l-DOPA）会在学习的早期阶段对腹侧纹状体回路的募集产生负面影响。17 名处于早期 PD 阶段的患者在服用和不服用 l-DOPA 的情况下，以及 21 名健康对照者在 MRI 扫描仪内进行了明确的运动序列学习任务。我们观察到，对照组和 PD OFF 患者在早期阶段的腹侧壳核出现了与序列学习特异性相关的激活，但 PD ON l-DOPA 患者则没有。PD OFF 和 PD ON 之间的激活比较显示，与 PD OFF 相比，PD ON 患者的腹侧壳核中的激活减少。腹侧壳核中与 l-DOPA 相关的激活减少的程度与早期学习阶段序列学习表现下降的程度呈小的正相关（r=0.45-0.54，各项测量指标均为 p<0.05，单侧）。这些发现为 l-DOPA 在 PD 患者中的负面影响提供了证据，这种负面影响作用于参与早期运动序列学习的腹侧壳核回路，并为该结构在序列学习过程中的作用提供了支持。
