Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT 06106, USA.
Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1223-8. doi: 10.1073/pnas.0909969107.
The default-mode network, a coherent resting-state brain network, is thought to characterize basal neural activity. Aberrant default-mode connectivity has been reported in a host of neurological and psychiatric illnesses and in persons at genetic risk for such illnesses. Whereas the neurophysiologic mechanisms that regulate default-mode connectivity are unclear, there is growing evidence that genetic factors play a role. In this report, we estimate the importance of genetic effects on the default-mode network by examining covariation patterns in functional connectivity among 333 individuals from 29 randomly selected extended pedigrees. Heritability for default-mode functional connectivity was 0.424 +/- 0.17 (P = 0.0046). Although neuroanatomic variation in this network was also heritable, the genetic factors that influence default-mode functional connectivity and gray-matter density seem to be distinct, suggesting that unique genes influence the structure and function of the network. In contrast, significant genetic correlations between regions within the network provide evidence that the same genetic factors contribute to variation in functional connectivity throughout the default mode. Specifically, the left parahippocampal region was genetically correlated with all other network regions. In addition, the posterior cingulate/precuneus region, medial prefrontal cortex, and right cerebellum seem to form a subnetwork. Default-mode functional connectivity is influenced by genetic factors that cannot be attributed to anatomic variation or a single region within the network. By establishing the heritability of default-mode functional connectivity, this experiment provides the obligatory evidence required before these measures can be considered as endophenotypes for psychiatric or neurological illnesses or to identify genes influencing intrinsic brain function.
默认模式网络是一种连贯的静息状态脑网络，被认为是基底神经活动的特征。在许多神经和精神疾病以及遗传易感性的个体中，都报道了默认模式连接的异常。虽然调节默认模式连接的神经生理机制尚不清楚，但越来越多的证据表明遗传因素起作用。在本报告中，我们通过检查来自 29 个随机选择的扩展家系的 333 个人的功能连接中的协变模式，来估计遗传因素对默认模式网络的重要性。默认模式功能连接的遗传率为 0.424 +/- 0.17（P = 0.0046）。虽然该网络中的神经解剖变异也具有遗传性，但影响默认模式功能连接和灰质密度的遗传因素似乎是不同的，这表明独特的基因影响网络的结构和功能。相反，网络内各区域之间存在显著的遗传相关性，这为相同的遗传因素影响默认模式功能连接的变异性提供了证据。具体来说，左海马旁回与网络中的所有其他区域都具有遗传相关性。此外，后扣带回/楔前叶、内侧前额叶皮层和右侧小脑似乎形成了一个子网。默认模式功能连接受遗传因素的影响，这些遗传因素不能归因于解剖变异或网络内的单个区域。通过建立默认模式功能连接的遗传性，该实验提供了在这些措施被视为精神或神经疾病的内表型或鉴定影响内在大脑功能的基因之前所需的必要证据。
