Kahnt Thorsten, Tobler Philippe N
Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, and
Department of Economics, Laboratory for Social and Neural Systems Research, University of Zürich, 8006 Zürich, Switzerland.
J Neurosci. 2017 Feb 8;37(6):1493-1504. doi: 10.1523/JNEUROSCI.2827-16.2016. Epub 2017 Jan 9.
Neuromodulators such as dopamine can alter the intrinsic firing properties of neurons and may thereby change the configuration of larger functional circuits. The primate orbitofrontal cortex (OFC) receives dopaminergic input from midbrain nuclei, but the role of dopamine in the OFC is still unclear. Here we tested the idea that dopaminergic activity changes the pattern of connectivity between the OFC and the rest of the brain and thereby reconfigures functional networks in the OFC. To this end, we combined double-blind, placebo-controlled pharmacology [D receptor (D2R) antagonist amisulpride] in humans with resting-state functional magnetic resonance imaging and clustering methods. In the placebo group, we replicated previously observed parcellations of the OFC into two and six subregions based on connectivity patterns with the rest of the brain. Most importantly, while the twofold clustering did not differ significantly between groups, blocking D2Rs significantly changed the composition of the sixfold parcellation, suggesting a dopamine-dependent reconfiguration of functional OFC subregions. Moreover, multivariate decoding analyses revealed that amisulpride changed the whole-brain connectivity patterns of individual OFC subregions. In particular, D2R blockade shifted the balance of OFC connectivity from associative areas in the temporal and parietal lobe toward functional connectivity with the frontal cortex. In summary, our results suggest that dopamine alters the composition of functional OFC circuits, possibly indicating a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks. A key role of any neuromodulator may be the reconfiguration of functional brain circuits. Here we test this idea with regard to dopamine and the organization of functional networks in the orbitofrontal cortex (OFC). We show that blockade of dopamine D receptors has profound effects on the functional connectivity patterns of the OFC, yielding altered connectivity-based subdivisions of this region. Our results suggest that dopamine changes the connectional configuration of the OFC, possibly leading to transitions between different operating modes that favor either sensory input or recurrent processing in the prefrontal cortex. More generally, our findings support a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks and may have clinical implications for understanding the actions of antipsychotic agents.
多巴胺等神经调质可改变神经元的固有放电特性，进而可能改变更大功能回路的结构。灵长类动物的眶额皮质（OFC）从中脑核团接收多巴胺能输入，但其在OFC中的作用仍不清楚。在这里，我们测试了这样一种观点，即多巴胺能活动会改变OFC与大脑其他部分之间的连接模式，从而重新配置OFC中的功能网络。为此，我们将人类的双盲、安慰剂对照药理学[D受体（D2R）拮抗剂氨磺必利]与静息态功能磁共振成像和聚类方法相结合。在安慰剂组中，我们根据与大脑其他部分的连接模式，重现了先前观察到的将OFC划分为两个和六个子区域的结果。最重要的是，虽然两组之间的双重聚类没有显著差异，但阻断D2R显著改变了六重聚类的组成，表明功能性OFC子区域存在多巴胺依赖性的重新配置。此外，多变量解码分析表明，氨磺必利改变了单个OFC子区域的全脑连接模式。特别是，D2R阻断使OFC连接的平衡从颞叶和顶叶的联合区域转向与额叶皮质的功能连接。总之，我们的结果表明多巴胺改变了功能性OFC回路的组成，这可能表明神经调质在功能性脑网络的动态重新配置中具有更广泛的作用。任何神经调质的一个关键作用可能是功能性脑回路的重新配置。在这里，我们针对多巴胺和眶额皮质（OFC）中功能网络的组织来测试这一观点。我们表明，阻断多巴胺D受体会对OFC的功能连接模式产生深远影响，导致该区域基于连接性的细分发生改变。我们的结果表明，多巴胺改变了OFC的连接配置，可能导致不同操作模式之间的转变，这些模式有利于前额叶皮质中的感觉输入或循环处理。更普遍地说，我们的发现支持神经调质在功能性脑网络的动态重新配置中具有更广泛的作用，并且可能对理解抗精神病药物的作用具有临床意义。
