Greicius Michael D, Srivastava Gaurav, Reiss Allan L, Menon Vinod
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305-5719, USA.
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4637-42. doi: 10.1073/pnas.0308627101. Epub 2004 Mar 15.
Recent functional imaging studies have revealed coactivation in a distributed network of cortical regions that characterizes the resting state, or default mode, of the human brain. Among the brain regions implicated in this network, several, including the posterior cingulate cortex and inferior parietal lobes, have also shown decreased metabolism early in the course of Alzheimer's disease (AD). We reasoned that default-mode network activity might therefore be abnormal in AD. To test this hypothesis, we used independent component analysis to isolate the network in a group of 13 subjects with mild AD and in a group of 13 age-matched elderly controls as they performed a simple sensory-motor processing task. Three important findings are reported. Prominent coactivation of the hippocampus, detected in all groups, suggests that the default-mode network is closely involved with episodic memory processing. The AD group showed decreased resting-state activity in the posterior cingulate and hippocampus, suggesting that disrupted connectivity between these two regions accounts for the posterior cingulate hypometabolism commonly detected in positron emission tomography studies of early AD. Finally, a goodness-of-fit analysis applied at the individual subject level suggests that activity in the default-mode network may ultimately prove a sensitive and specific biomarker for incipient AD.
最近的功能成像研究揭示了在一组皮质区域的分布式网络中存在共同激活，这一网络表征了人类大脑的静息状态或默认模式。在涉及该网络的脑区中，有几个区域，包括后扣带回皮质和下顶叶，在阿尔茨海默病（AD）病程早期也显示出代谢降低。我们由此推断，AD患者的默认模式网络活动可能存在异常。为了验证这一假设，我们使用独立成分分析在一组13名轻度AD患者和一组13名年龄匹配的老年对照者执行简单感觉运动处理任务时分离出该网络。本文报告了三项重要发现。在所有组中均检测到海马体显著的共同激活，这表明默认模式网络与情景记忆处理密切相关。AD组在后扣带回和海马体的静息状态活动降低，这表明这两个区域之间连接性的破坏导致了在早期AD的正电子发射断层扫描研究中常见的后扣带回代谢减退。最后，在个体受试者水平上进行的拟合优度分析表明，默认模式网络中的活动最终可能被证明是早期AD的一种敏感且特异的生物标志物。
