Center for Neurobiology of Learning and Memory, University of California, Irvine, 211 Qureshey Research Laboratory, Irvine, California 92697, USA.
Hippocampus. 2011 Sep;21(9):968-79. doi: 10.1002/hipo.20808. Epub 2010 May 20.
There is widespread evidence that memory deteriorates with aging, however the exact mechanisms that underlie these changes are not well understood. Given the growing size of the aging population, there is an imperative to study age-related neurocognitive changes in order to better parse healthy from pathological aging. Using a behavioral paradigm that taxes pattern separation (the ability to differentiate novel yet similar information from previously learned information and thus avoid interference), we investigated age-related neural changes in the human hippocampus using high-resolution (1.5 mm isotropic) blood-oxygenation level-dependent fMRI. Recent evidence from animal studies suggests that hyperactivity in the CA3 region of the hippocampus may underlie behavioral deficits in pattern separation in aged rats. Here, we report evidence that is consistent with findings from the animal studies. We found a behavioral impairment in pattern separation in a sample of healthy older adults compared with young controls. We also found a related increase in CA3/dentate gyrus activity levels during an fMRI contrast that stresses pattern separation abilities. In a detailed analysis of behavior, we also found that the pattern of impairment was consistent with the predictions of the animal model, where larger changes in the input (greater dissimilarity) were required in order for elderly adults to successfully encode new information as distinct from previously learned information. These findings are also consistent with recent fMRI and behavioral reports in healthy aging, and further suggest that a specific functional deficit in the CA3/dentate network contributes to memory difficulties with aging.
有广泛的证据表明，记忆随着年龄的增长而恶化，然而，这些变化背后的确切机制还不是很清楚。鉴于老龄化人口的不断增长，有必要研究与年龄相关的神经认知变化，以便更好地区分健康和病理性衰老。我们使用一种行为范式来测试模式分离（区分新颖但相似的信息与先前学习的信息的能力，从而避免干扰），使用高分辨率（1.5 毫米各向同性）血氧水平依赖 fMRI 研究人类海马体与年龄相关的神经变化。最近的动物研究证据表明，海马体 CA3 区域的过度活跃可能是老年大鼠在模式分离行为缺陷的基础。在这里，我们报告了与动物研究结果一致的证据。我们发现，与年轻对照组相比，健康的老年成年人在模式分离方面存在行为障碍。我们还发现，在强调模式分离能力的 fMRI 对比中，CA3/齿状回的活动水平相关增加。在对行为的详细分析中，我们还发现，这种损伤模式与动物模型的预测一致，即老年人需要更大的输入变化（更大的差异性）才能成功地将新信息编码为与先前学习的信息不同。这些发现也与健康衰老的最近 fMRI 和行为报告一致，并进一步表明 CA3/齿状回网络中的特定功能缺陷导致与年龄相关的记忆困难。
