L-dopa modulates functional connectivity in striatal cognitive and motor networks: a double-blind placebo-controlled study.
L-dopa modulates functional connectivity in striatal cognitive and motor networks: a double-blind placebo-controlled study.
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DOI：
10.1523/jneurosci.0810-09.2009
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发表时间：
2009-06-03
期刊：
影响因子：
--
通讯作者：
McMahon K
中科院分区：
文献类型：
--
作者：
Kelly C;de Zubicaray G;Di Martino A;Copland DA;Reiss PT;Klein DF;Castellanos FX;Milham MP;McMahon K
静息状态fMRI数据的功能连接（FC）分析允许大规模功能网络的映射，并提供了一种检查多巴胺能挑战影响的新方法。本研究采用双盲、安慰剂对照设计，研究了多巴胺前体左旋多巴对19名健康年轻人纹状体静息状态FC的影响。我们检查了6个纹状体感兴趣区域的FC，这些区域之前被证明可以引发与尾状核和壳核的动机、认知和运动分支相关的网络。除了复制先前证明的纹状体FC模式外，我们还观察到左旋多巴的强大作用。具体来说，左旋多巴增加了连接壳核roi与小脑和脑干的运动通路中的FC。左旋多巴增加了下腹侧纹状体和腹外侧前额叶皮层之间的FC，但破坏了腹侧纹状体和尾状背侧的FC和默认模式网络。这些FC的改变与健康参与者认知和运动纹状体网络中多巴胺能调节的研究是一致的。最近的研究表明，在一些被认为以多巴胺能神经传递异常为特征的情况下，静息状态FC发生了改变。我们的研究结果表明，在这些人群中应用类似的实验药理学操作可能会进一步加深我们对多巴胺能神经传递在这些条件下的作用的理解。
Functional connectivity (FC) analyses of resting-state fMRI data allow for the mapping of large-scale functional networks, and provide a novel means of examining the impact of dopaminergic challenge. Here, using a double-blind, placebo-controlled design, we examined the effect of L-dopa, a dopamine precursor, on striatal resting-state FC in 19 healthy young adults. We examined the FC of 6 striatal regions-of-interest previously shown to elicit networks known to be associated with motivational, cognitive and motor subdivisions of the caudate and putamen. In addition to replicating the previously demonstrated patterns of striatal FC, we observed robust effects of L-dopa. Specifically, L-dopa increased FC in motor pathways connecting the putamen ROIs with the cerebellum and brainstem. While L-dopa also increased FC between the inferior ventral striatum and ventrolateral prefrontal cortex, it disrupted ventral striatal and dorsal caudate FC with the default mode network. These alterations in FC are consistent with studies that have demonstrated dopaminergic modulation of cognitive and motor striatal networks in healthy participants. Recent studies have demonstrated altered resting state FC in several conditions believed to be characterized by abnormal dopaminergic neurotransmission. Our findings suggest that the application of similar experimental pharmacological manipulations in such populations may further our understanding of the role of dopaminergic neurotransmission in those conditions.