Wagner Isabella C, van Buuren Mariët, Bovy Leonore, Morris Richard G, Fernández Guillén
Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Kapittelweg 29, Nijmegen, 6525 EN, The Netherlands.
Centre for Cognitive and Neural Systems, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
Psychopharmacology (Berl). 2017 Feb;234(4):657-669. doi: 10.1007/s00213-016-4502-8. Epub 2016 Dec 24.
Synaptic memory consolidation is thought to rely on catecholaminergic signaling. Eventually, it is followed by systems consolidation, which embeds memories in a neocortical network. Although this sequence was demonstrated in rodents, it is unclear how catecholamines affect memory consolidation in humans.
Here, we tested the effects of catecholaminergic modulation on synaptic and subsequent systems consolidation. We expected enhanced memory performance and increased neocortical engagement during delayed retrieval. Additionally, we tested if this effect was modulated by individual differences in a cognitive proxy measure of baseline catecholamine synthesis capacity.
Fifty-three healthy males underwent a between-subjects, double-blind, placebo-controlled procedure across 2 days. On day 1, subjects studied and retrieved object-location associations and received 20 mg of methylphenidate or placebo. Drug intake was timed so that methylphenidate was expected to affect early consolidation but not encoding or retrieval. Memory was tested again while subjects were scanned three days later.
Methylphenidate did not facilitate memory performance, and there was no significant group difference in activation during delayed retrieval. However, memory representations differed between groups depending on baseline catecholamines. The placebo group showed increased activation in occipito-temporal regions but decreased connectivity with the hippocampus, associated with lower baseline catecholamine synthesis capacity. The methylphenidate group showed stronger activation in the postcentral gyrus, associated with higher baseline catecholamine synthesis capacity.
Altogether, methylphenidate during early consolidation did not foster long-term memory performance, but it affected retrieval-related neural processes depending on individual levels of baseline catecholamines.
突触记忆巩固被认为依赖于儿茶酚胺能信号传导。最终，随之而来的是系统巩固，即将记忆嵌入新皮质网络。尽管这一序列已在啮齿动物中得到证实，但尚不清楚儿茶酚胺如何影响人类的记忆巩固。
在此，我们测试了儿茶酚胺能调节对突触及后续系统巩固的影响。我们预期在延迟检索期间记忆表现会增强，且新皮质参与度会增加。此外，我们测试了这种效应是否受基线儿茶酚胺合成能力的认知替代指标的个体差异调节。
53名健康男性在2天内接受了一项受试者间、双盲、安慰剂对照的实验程序。在第1天，受试者学习并检索物体-位置关联，并接受20毫克哌甲酯或安慰剂。药物摄入时间经过安排，以使哌甲酯预期会影响早期巩固，但不影响编码或检索。三天后对受试者进行扫描时再次测试记忆。
哌甲酯并未促进记忆表现，且在延迟检索期间两组之间的激活无显著差异。然而，根据基线儿茶酚胺水平，两组之间的记忆表征有所不同。安慰剂组在枕颞区的激活增加，但与海马体的连接减少，这与较低的基线儿茶酚胺合成能力相关。哌甲酯组在中央后回的激活更强，这与较高的基线儿茶酚胺合成能力相关。
总体而言，早期巩固期间的哌甲酯并未促进长期记忆表现，但它根据基线儿茶酚胺的个体水平影响与检索相关的神经过程。
