Modulation of fusiform cortex activity by cholinesterase inhibition predicts effects on subsequent memory
Modulation of fusiform cortex activity by cholinesterase inhibition predicts effects on subsequent memory
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DOI：
10.1093/brain/awp176
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发表时间：
2009-09-01
期刊：
影响因子：
14.5
通讯作者：
Dolan, R. J.
中科院分区：
文献类型：
--
作者：
Bentley, P.;Driver, J.;Dolan, R. J.
胆碱能对记忆的影响可能在几个加工阶段表现出来，包括在编码过程中乙酰胆碱对刺激加工的作用。由于先前的研究表明，胆碱酯酶抑制在刺激编码过程中增强了视觉外皮层的活性，特别是在需要注意的任务中，我们测试了这种效应是否与随后的记忆改善有关。在受试者间的毒豆碱对比安慰剂设计中，我们用功能性磁共振成像测量了健康和轻度阿尔茨海默病受试者对面部（和建筑）视觉刺激进行浅层和深层编码任务时的大脑活动。我们探索了在哪些区域，蛇毒碱调制的面孔选择神经反应与蛇毒碱对随后的识别性能的影响相关。在健康的受试者中，褐豆碱可以增强对深度编码和表面编码的面孔的后期识别，这与在深度编码和表面编码任务中褐豆碱诱导的右侧梭状皮质面孔选择反应的增强相关。相比之下，阿尔茨海默病组既没有显示出深度加工效应，也没有显示出蛇毒碱的恢复。相反，病人在服用了毒豆碱后表现出了任务无关的自信记忆的改善，这种效果与双侧梭状皮质的面部选择（但任务无关）反应的增强有关。我们的研究结果表明，胆碱酯酶抑制剂改善记忆的一种机制是通过增强编码时的外皮层刺激选择性，在某种程度上，健康人而不是阿尔茨海默病患者依赖于加工深度。
Cholinergic influences on memory are likely to be expressed at several processing stages, including via well-recognized effects of acetylcholine on stimulus processing during encoding. Since previous studies have shown that cholinesterase inhibition enhances visual extrastriate cortex activity during stimulus encoding, especially under attention-demanding tasks, we tested whether this effect correlates with improved subsequent memory. In a within-subject physostigmine versus placebo design, we measured brain activity with functional magnetic resonance imaging while healthy and mild Alzheimers disease subjects performed superficial and deep encoding tasks on face (and building) visual stimuli. We explored regions in which physostigmine modulation of face-selective neural responses correlated with physostigmine effects on subsequent recognition performance. In healthy subjects physostigmine led to enhanced later recognition for deep- versus superficially-encoded faces, which correlated across subjects with a physostigmine-induced enhancement of face-selective responses in right fusiform cortex during deep- versus superficial-encoding tasks. In contrast, the Alzheimers disease group showed neither a depth of processing effect nor restoration of this with physostigmine. Instead, patients showed a task-independent improvement in confident memory with physostigmine, an effect that correlated with enhancements in face-selective (but task-independent) responses in bilateral fusiform cortices. Our results indicate that one mechanism by which cholinesterase inhibitors can improve memory is by enhancing extrastriate cortex stimulus selectivity at encoding, in a manner that for healthy people but not in Alzheimers disease is dependent upon depth of processing.