Department of Psychiatry and Psychotherapy, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, 1090 Vienna, Austria.
Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2619-24. doi: 10.1073/pnas.1117104109. Epub 2012 Jan 30.
Reflecting one's mental self is a fundamental process for evaluating the personal relevance of life events and for moral decision making and future envisioning. Although the corresponding network has been receiving growing attention, the driving neurochemical mechanisms of the default mode network (DMN) remain unknown. Here we combined positron emission tomography and functional magnetic resonance imaging to investigate modulations of the DMN via serotonin-1A receptors (5-HT(1A)), separated for 5-HT autoinhibition (dorsal raphe nucleus) and local inhibition (heteroreceptors in projection areas). Using two independent approaches, regional 5-HT(1A) binding consistently predicted DMN activity in the retrosplenial cortex for resting-state functional magnetic resonance imaging and the Tower of London task. On the other hand, both local and autoinhibitory 5-HT(1A) binding inversely modulated the posterior cingulate cortex, the strongest hub in the resting human brain. In the frontal part of the DMN, a negative association was found between the dorsal medial prefrontal cortex and local 5-HT(1A) inhibition. Our results indicate a modulation of key areas involved in self-referential processing by serotonergic neurotransmission, whereas variations in 5-HT(1A) binding explained a considerable amount of the individual variability in the DMN. Moreover, the brain regions associated with distinct introspective functions seem to be specifically regulated by the different 5-HT(1A) binding sites. Together with previously reported modulations of dopamine and GABA, this regional specialization suggests complex interactions of several neurotransmitters driving the default mode network.
反映自我意识是评估生活事件个人相关性以及进行道德决策和未来设想的基本过程。尽管默认模式网络（DMN）的对应网络越来越受到关注，但 DMN 的驱动神经化学机制仍不清楚。在这里，我们结合正电子发射断层扫描和功能磁共振成像来研究通过 5-羟色胺 1A 受体（5-HT1A）对 DMN 的调制，分别针对 5-HT 自动抑制（背侧中缝核）和局部抑制（投射区的异源受体）。使用两种独立的方法，区域 5-HT1A 结合一致预测了静息状态功能磁共振成像和伦敦塔任务中后扣带回皮层的 DMN 活性。另一方面，局部和自动抑制 5-HT1A 结合均反向调节后扣带皮层，这是静息人脑最强的中枢。在 DMN 的额叶部分，背侧内侧前额叶皮层和局部 5-HT1A 抑制之间存在负相关。我们的结果表明，5-羟色胺能神经传递对涉及自我参照处理的关键区域进行了调制，而 5-HT1A 结合的变化解释了 DMN 中个体变异性的相当一部分。此外，与不同内省功能相关的脑区似乎受到不同 5-HT1A 结合部位的特异性调节。与之前报道的多巴胺和 GABA 的调节作用一起，这种区域专业化表明，几种神经递质的复杂相互作用驱动了默认模式网络。
