LIAMA Center for Computational Medicine, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
J Neurosci. 2010 Jan 6;30(1):64-9. doi: 10.1523/JNEUROSCI.3941-09.2010.
Previous studies have supported the concept that the default network is an intrinsic brain system that participates in internal modes of cognition. Neural activity and connectivity within the default network, which are correlated with cognitive ability even at rest, may be plausible intermediate phenotypes that will enable us to understand the genetic mechanisms of individuals' cognitive function or the risk for genetic brain diseases. Using resting functional magnetic resonance imaging and imaging genetic paradigms, we investigated whether individual default network connectivity was modulated by COMT val(158)met in 57 healthy young subjects. Compared with COMT heterozygous individuals, homozygous val individuals showed significantly decreased prefrontal-related connectivities, which primarily occurred between prefrontal regions and the posterior cingulate/restrosplenial cortices. Further analyses of the topological characteristics of the default network showed homozygous val individuals had significantly fewer node degrees in the prefrontal regions. This finding may partially elucidate previous reports that the COMT val variant is associated with inefficient prefrontal information processing and poor cognitive performance. Our findings suggest that default network connectivity that involves the prefrontal cortex is modulated by COMT val(158)met through differential effects on prefrontal dopamine levels.
先前的研究支持这样一种概念，即默认网络是一个内在的大脑系统，参与内部认知模式。默认网络中的神经活动和连接性，即使在休息时也与认知能力相关，它们可能是合理的中间表型，使我们能够理解个体认知功能或遗传脑疾病风险的遗传机制。我们使用静息功能磁共振成像和影像遗传学范式，研究了在 57 名健康年轻受试者中，COMT val(158)met 是否调节个体的默认网络连接。与 COMT 杂合子个体相比，纯合子 val 个体表现出前额叶相关连接明显减少，主要发生在前额叶区域和后扣带回/后扣带回皮质之间。对默认网络拓扑特征的进一步分析表明，纯合子 val 个体在前额叶区域的节点度明显减少。这一发现部分解释了先前的报告，即 COMT val 变体与前额叶信息处理效率低下和认知表现不佳有关。我们的研究结果表明，涉及前额叶皮层的默认网络连接受到 COMT val(158)met 的调节，这是通过对前额叶多巴胺水平的不同影响来实现的。
