Disrupted neural activity patterns to novelty and effort in young adult APOE-e4 carriers performing a subsequent memory task.
Disrupted neural activity patterns to novelty and effort in young adult APOE-e4 carriers performing a subsequent memory task.
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DOI：
10.1002/brb3.612
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发表时间：
2017-02
影响因子：
3.1
通讯作者：
Rusted JM
中科院分区：
文献类型：
--
作者：
Evans S;Dowell NG;Tabet N;King SL;Hutton SB;Rusted JM
APOE e4等位基因与认知能力较差的衰老和痴呆风险增加有关。先前的成像研究使用了后续记忆范式来探测不同年龄段e4携带者的海马功能，证据表明年轻成年e4携带者的海马过度激活模式。在这项研究中，我们采用了基于单词的fMRI后续记忆任务；瞳孔测量数据也被作为认知努力的指标。参与者（26名非e4携带者和28名e4携带者）执行一个附带的编码任务（表现为单词分类），然后在延迟40分钟后执行一个惊喜的旧/新识别任务。仅在e4携带者中，随后记忆的单词与海马活动的增加有关。在所有参与者中，瞳孔直径的增加区分了随后记忆和遗忘的单词，楔叶和楔前叶的神经活动随瞳孔直径的变化而变化。这些影响在e4携带者中较弱，并且e4携带者在记忆单词时没有表现出更大的瞳孔直径。在识别阶段，基因型状态也会调节海马体的活动：然而，在这里，e4携带者没有表现出对新单词更大的海马体活动的传统模式。总的来说，e4携带者的神经活动变化是不稳定的，不能对新奇事物做出反应，并且与认知努力没有很强的联系，这是由瞳孔直径所指示的。这进一步证明了年轻成年e4携带者的海马募集异常，表现为神经活动的上调和下调，而没有行为表现差异。
The APOE e4 allele has been linked to poorer cognitive aging and enhanced dementia risk. Previous imaging studies have used subsequent memory paradigms to probe hippocampal function in e4 carriers across the age range, and evidence suggests a pattern of hippocampal overactivation in young adult e4 carriers. In this study, we employed a word‐based subsequent memory task under fMRI; pupillometry data were also acquired as an index of cognitive effort. Participants (26 non‐e4 carriers and 28 e4 carriers) performed an incidental encoding task (presented as word categorization), followed by a surprise old/new recognition task after a 40 minute delay. In e4 carriers only, subsequently remembered words were linked to increased hippocampal activity. Across all participants, increased pupil diameter differentiated subsequently remembered from forgotten words, and neural activity covaried with pupil diameter in cuneus and precuneus. These effects were weaker in e4 carriers, and e4 carriers did not show greater pupil diameter to remembered words. In the recognition phase, genotype status also modulated hippocampal activity: here, however, e4 carriers failed to show the conventional pattern of greater hippocampal activity to novel words. Overall, neural activity changes were unstable in e4 carriers, failed to respond to novelty, and did not link strongly to cognitive effort, as indexed by pupil diameter. This provides further evidence of abnormal hippocampal recruitment in young adult e4 carriers, manifesting as both up and downregulation of neural activity, in the absence of behavioral performance differences.