Basal forebrain moderates the magnitude of task-dependent amygdala functional connectivity
Basal forebrain moderates the magnitude of task-dependent amygdala functional connectivity
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DOI：
10.1093/scan/nsu080
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发表时间：
2015-04-01
影响因子：
4.2
通讯作者：
Hariri, Ahmad R.
中科院分区：
文献类型：
--
作者：
Gorka, Adam X.;Knodt, Annchen R.;Hariri, Ahmad R.
动物研究表明，杏仁核促进注意力和情感记忆，部分是通过驱动下游目标区域的活动，包括前额叶皮层（PFC）和海马体。先前的工作已经证明，杏仁核直接影响这些地区通过单突触的神经元信号，并间接驱动活动的胆碱能基底前脑和随后的下游乙酰胆碱释放。然而，迄今为止，没有工作已经解决了胆碱能基底前脑在促进人类杏仁核信号的功能相关性。我们着手确定杏仁核和胆碱能基底前脑内的血氧水平依赖性信号如何相互作用，以预测下游靶点内的神经反应。在这里，我们使用功能连接分析表明，胆碱能基底前脑温和增加杏仁核连接PFC和海马在人类的生物学显着的刺激处理。我们进一步证明，胆碱转运蛋白基因内的功能变化预测这种调节作用的大小。总的来说，我们的研究结果提供了新的证据，胆碱能信号在调节神经通路的重要性，支持人类的觉醒，注意力和记忆。此外，我们的研究结果可能揭示了先前的关联研究，将胆碱转运蛋白基因内的功能变异与重度抑郁症和注意力缺陷多动障碍的诊断联系起来。
Animal studies reveal that the amygdala promotes attention and emotional memory, in part, by driving activity in downstream target regions including the prefrontal cortex (PFC) and hippocampus. Prior work has demonstrated that the amygdala influences these regions directly through monosynaptic glutamatergic signaling, and indirectly by driving activity of the cholinergic basal forebrain and subsequent downstream acetylcholine release. Yet to date, no work has addressed the functional relevance of the cholinergic basal forebrain in facilitating signaling from the amygdala in humans. We set out to determine how blood oxygen level-dependent signal within the amygdala and cholinergic basal forebrain interact to predict neural responses within downstream targets. Here, we use functional connectivity analyses to demonstrate that the cholinergic basal forebrain moderates increased amygdala connectivity with both the PFC and the hippocampus during the processing of biologically salient stimuli in humans. We further demonstrate that functional variation within the choline transporter gene predicts the magnitude of this modulatory effect. Collectively, our results provide novel evidence for the importance of cholinergic signaling in modulating neural pathways supporting arousal, attention and memory in humans. Further, our results may shed light on prior association studies linking functional variation within the choline transporter gene and diagnoses of major depression and attention-deficit hyperactivity disorder.