Modanfinil Shifts Human Locus Coeruleus to Low-Tonic, High-Phasic Activity During Functional MRI
Modanfinil Shifts Human Locus Coeruleus to Low-Tonic, High-Phasic Activity During Functional MRI
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DOI：
10.1126/science.1164908
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发表时间：
2008-12-12
期刊：
影响因子：
56.9
通讯作者：
Carter, Cameron S.
中科院分区：
文献类型：
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作者：
Minzenberg, Michael J.;Watrous, Andrew J.;Carter, Cameron S.
认知控制模型对脑桥蓝斑-去甲肾上腺素（LC-NE）系统具有重要的调节作用。在非人类灵长类动物中，阶段性LC-NE活动赋予任务相关脑网络中皮质增益的自适应调整，并在逐个试验的基础上进行性能调整。这个模型还没有在人类身上测试过。我们使用药理学试剂莫达非尼促进健康人在事件相关功能磁共振成像（fMRI）期间执行认知控制任务的低张力/高相位LC-NE活性。莫达法尼给药与任务无关的紧张性LC活动降低、任务相关的LC和前额叶皮层（PFC）活动增加以及LC-PFC功能连接增强相关。这些结果证实了人类LC-NE系统在PFC功能和认知控制中的作用，并提示了促认知去甲肾上腺素能药物的治疗作用机制。
Models of cognitive control posit a key modulatory role for the pontine locus coeruleus- norepinephrine (LC-NE) system. In nonhuman primates, phasic LC- NE activity confers adaptive adjustments in cortical gain in task- relevant brain networks, and in performance, on a trial- by- trial basis. This model has remained untested in humans. We used the pharmacological agent modafinil to promote low- tonic/ high- phasic LC- NE activity in healthy humans performing a cognitive control task during event- related functional magnetic resonance imaging ( fMRI). Modafanil administration was associated with decreased task- independent, tonic LC activity, increased task- related LC and prefrontal cortex ( PFC) activity, and enhanced LC- PFC functional connectivity. These results confirm in humans the role of the LC- NE system in PFC function and cognitive control and suggest a mechanism for therapeutic action of procognitive noradrenergic agents.