Department of Radiology, Tianjin Medical University General Hospital, Tianjin, China, Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China, Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China, and Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4072, Australia.
J Neurosci. 2013 Oct 30;33(44):17519-26. doi: 10.1523/JNEUROSCI.2163-13.2013.
The dopamine system is known to modulate brain function in an inverted U-shaped manner. Recently, the functional networks of the brain were categorized into two systems, a "control system" and a "processing system." However, it remains unclear whether the inverted U-shaped model of dopaminergic modulation could be applied to both of these functional systems. The catechol-O-methyltransferase (COMT) and dopamine D2 receptor (DRD2) were genotyped in 258 healthy young human subjects. The local and long-range functional connectivity densities (FCDs) of each voxel were calculated and compared in a voxel-wise manner using a two-way (COMT and DRD2 genotypes) analysis of covariance. The resting-state functional connectivity analysis was performed to determine the functional networks to which brain regions with significant FCD differences belonged. Significant COMT × DRD2 interaction effects were found in the local FCDs of the superior portion of the right temporal pole (sTP) and left lingual gyrus (LG) and in the long-range FCDs of the right putamen and left medial prefrontal cortex (MPFC). Post hoc tests showed nonlinear relationships between the genotypic subgroups and FCD. In the control system, the sTP and putamen, components of the salience network, showed a U-shaped modulation by dopamine signaling. In the processing system, however, the MPFC of the default-mode network and the LG of the visual network showed an inverted U-shaped modulation by the dopamine system. Our findings suggest an interaction between COMT and DRD2 genotypes and show a functional system-dependent modulation of dopamine signaling.
多巴胺系统被认为以倒 U 型方式调节大脑功能。最近，大脑的功能网络被分为两个系统，一个是“控制系统”，另一个是“处理系统”。然而，多巴胺调节的倒 U 型模型是否适用于这两个功能系统尚不清楚。在 258 名健康年轻的人类受试者中，对儿茶酚-O-甲基转移酶（COMT）和多巴胺 D2 受体（DRD2）进行了基因分型。以 COMT 和 DRD2 基因型为双因素协方差分析，以体素为单位计算并比较每个体素的局部和长程功能连接密度（FCD）。进行静息态功能连接分析，以确定具有显著 FCD 差异的脑区所属的功能网络。在右侧颞极（sTP）和左侧舌回（LG）的局部 FCD 以及右侧壳核和左侧内侧前额叶皮层（MPFC）的长程 FCD 中，均发现 COMT×DRD2 交互作用显著。事后检验显示，基因型亚组与 FCD 之间存在非线性关系。在控制系统中，突显网络的组成部分 sTP 和壳核的多巴胺信号呈现出 U 型调制。然而，在处理系统中，默认模式网络的 MPFC 和视觉网络的 LG 则表现出多巴胺系统的倒 U 型调制。我们的研究结果表明 COMT 和 DRD2 基因型之间存在相互作用，并显示多巴胺信号的功能系统依赖性调制。
