Ketamine effects on memory reconsolidation favor a learning model of delusions.
Ketamine effects on memory reconsolidation favor a learning model of delusions.
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DOI：
10.1371/journal.pone.0065088
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fletcher PC
中科院分区：
文献类型：
--
作者：
Corlett PR;Cambridge V;Gardner JM;Piggot JS;Turner DC;Everitt JC;Arana FS;Morgan HL;Milton AL;Lee JL;Aitken MR;Dickinson A;Everitt BJ;Absalom AR;Adapa R;Subramanian N;Taylor JR;Krystal JH;Fletcher PC
妄想是一种持续的、常常是奇怪的信念，是精神病的特征。先前的研究表明，它们的出现可能是由于预测错误依赖学习中的干扰。在这里，我们建立了补充研究，以检验这种干扰是否也调节记忆再巩固，从而解释其显著的持久性。首先，我们量化了18名人类受试者（8名女性）在因果学习任务中对预测误差的个体大脑反应。接下来，对同样的人进行氯胺酮影响的安慰剂对照研究。我们确定了这种NMDA受体拮抗剂（先前显示可诱导异常预测误差信号并导致感知和信念的短暂改变）在72小时内对恐惧记忆进化的影响：他们最初接受巴甫洛夫恐惧条件反射；24小时后，在给予氯胺酮或安慰剂期间，条件刺激（CS）出现一次，无强化；24小时后再次测试记忆强度。氯胺酮组的CS重现导致了比安慰剂组更强的后续记忆。此外，强化程度与个体对氯胺酮的心理影响的易感性和预测误差脑信号有关。这一发现在一个具有食欲学习过程的独立样本（8名人类受试者，4名女性）中得到了部分重复。这些结果表明，预测误差、记忆强度和精神病之间存在联系。他们指出，一种核心的破坏不仅可以解释妄想信念的出现，还可以解释妄想信念的持续存在。
Delusions are the persistent and often bizarre beliefs that characterise psychosis. Previous studies have suggested that their emergence may be explained by disturbances in prediction error-dependent learning. Here we set up complementary studies in order to examine whether such a disturbance also modulates memory reconsolidation and hence explains their remarkable persistence. First, we quantified individual brain responses to prediction error in a causal learning task in 18 human subjects (8 female). Next, a placebo-controlled within-subjects study of the impact of ketamine was set up on the same individuals. We determined the influence of this NMDA receptor antagonist (previously shown to induce aberrant prediction error signal and lead to transient alterations in perception and belief) on the evolution of a fear memory over a 72 hour period: they initially underwent Pavlovian fear conditioning; 24 hours later, during ketamine or placebo administration, the conditioned stimulus (CS) was presented once, without reinforcement; memory strength was then tested again 24 hours later. Re-presentation of the CS under ketamine led to a stronger subsequent memory than under placebo. Moreover, the degree of strengthening correlated with individual vulnerability to ketamine's psychotogenic effects and with prediction error brain signal. This finding was partially replicated in an independent sample with an appetitive learning procedure (in 8 human subjects, 4 female). These results suggest a link between altered prediction error, memory strength and psychosis. They point to a core disruption that may explain not only the emergence of delusional beliefs but also their persistence.
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影响因子：
16.2
作者：
Daw ND;Gershman SJ;Seymour B;Dayan P;Dolan RJ
通讯作者：
Dolan RJ
影响因子：
11.3
作者：
Bhatt, Reena;Laws, Keith R.;McKenna, Peter J.
通讯作者：
McKenna, Peter J.
影响因子：
16.2
作者：
Corlett, PR;Aitken, MRF;Fletcher, PC
通讯作者：
Fletcher, PC
影响因子：
2.6
作者：
Corlett PR;Fletcher PC
通讯作者：
Fletcher PC
DOI：
10.1080/02724990042000010
发表时间：
2001-02-01
期刊：
QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION B-COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
Dickinson, A
通讯作者：
Dickinson, A