Caudate nucleus: influence of dopaminergic input on sequence learning and brain activation in Parkinsonism
Caudate nucleus: influence of dopaminergic input on sequence learning and brain activation in Parkinsonism
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DOI：
10.1016/j.neuroimage.2003.12.014
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发表时间：
2004-04-01
期刊：
影响因子：
5.7
通讯作者：
Eidelberg, D
中科院分区：
文献类型：
--
作者：
Carbon, M;Ma, YL;Eidelberg, D
在这项研究中，我们测试了以下假设：（1）序列信息的获取与尾状核多巴胺能输入的完整性有关;（2）尾状核多巴胺能输入的完整性与序列获取过程中的大脑激活显著相关。12名早期帕金森病（PD）患者和6名年龄匹配的健康志愿者使用双示踪剂PET成像设计进行扫描。所有受试者均使用[F-18]氟丙基-betaCIT（FPCIT）进行扫描，以测量纹状体多巴胺转运蛋白（DAT）结合，并使用[O-15]水进行扫描，以评估序列学习任务期间的激活情况，其中对8个目标的重复序列进行运动。PD队列中的尾状核和壳核DAT结合分别降低了15%和43%。在PD中，尾状核DAT结合与靶获得相关（R = 0.57，P < 0.05），而壳核DAT结合与性能无关。在志愿者中，尾状体DAT结合与左侧背外侧和腹侧前额叶皮质、前扣带和运动前区以及右侧小脑的学习相关激活相关（P < 0.05，经多重比较校正）。一个显着的相关性尾状DAT结合，另外检测到右前内侧丘脑，延伸到嘴侧中脑。相比之下，在PD队列中，这些区域关系中的大多数都丢失了：只有腹侧和背外侧前额叶皮层激活与尾状核多巴胺能紧张度相关。我们的研究结果表明，序列学习通常与尾状核和丘脑-皮质功能活动的多巴胺能输入之间的紧密耦合。尽管黑质-尾状核输入的减少很少，但PD患者在疾病早期表现出这种耦合的丧失。(C)2004年爱思唯尔公司All rights reserved.
In this study, we tested the hypotheses that (1) the acquisition of sequential information is related to the integrity of dopaminergic input to the caudate nucleus; and (2) the integrity of dopaminergic input to the caudate nucleus correlates significantly with brain activation during sequence acquisition. Twelve early stage Parkinson's disease (PD) patients and six age-matched healthy volunteers were scanned using a dual tracer PET imaging design. All subjects were scanned with [F-18]fluoropropyl-betaCIT (FPCIT) to measure striatal dopamine transporter (DAT) binding and with [O-15]water to assess activation during a sequence learning task where movements were made to a repeating sequence of eight targets. Caudate and putamen DAT binding in the PD cohort was reduced by 15% and 43%, respectively. In PD, caudate DAT binding correlated with target acquisition (R = 0.57, P < 0.05), while putamen DAT binding did not correlate with performance. In volunteers, caudate DAT binding correlated with learning-related activation (P < 0.05, corrected for multiple comparisons) in the left dorsolateral and ventral prefrontal cortices, the anterior cingulate and premotor regions, and the right cerebellum. A significant correlation with caudate DAT binding was additionally detected in the right anteromedial thalamus, extending into the rostral midbrain. By contrast, in the PD cohort, most of these regional relationships were lost: Only ventral and dorsolateral prefrontal cortex activation correlated with caudate dopaminergic tone. Our findings suggest that sequence learning is normally associated with tight coupling between dopaminergic input to the caudate and thalamo-cortical functional activity. Despite minimal reductions in nigro-caudate input, PD patients demonstrate a loss of this coupling early in the disease. (C) 2004 Elsevier Inc. All rights reserved.