Both differences in encoding processes and monitoring at retrieval reduce false alarms when distinctive information is studied

ABSTRACT

Recent research has provided evidence for memory modifications when a post-reactivation treatment (e.g., drugs, new learning) interferes with the memory re-stabilisation (reconsolidation) process. This finding contradicts the long-standing consolidation theory and has high practical and theoretical implications. With an object-learning paradigm, it was shown that episodic memory is highly susceptible to interfering material presented after its reactivation [Hupbach, A., Gomez, R., Hardt, O., &; Nadel, L. (2007). Reconsolidation of episodic memories: A subtle reminder triggers integration of new information. Learning &; Memory, 14, 47–53. doi:10.1101/lm.365707]. The reactivation of a learned list (List 1) before a second learned list (List 2) led to intrusion errors from List 2 when trying to recall List 1, but not vice-versa. Their work has been widely cited and their findings have been explained according to reconsolidation theory. For the first time, we systematically explored the role of retrieval context as an alternative explanation for Hupbach’s results. Our results showed that the intrusion effect occurs independently of the retrieval context (Experiment 1). Additionally, even when the intrusion rate probability is increased (i.e., List 1 memory test is performed in the List 2 learning context), the groups that did not reactivate the original list did not commit intrusion errors (Experiment 2). In sum, we found that the intrusion effect critically depends on the presence of reactivation, discarding alternative interpretations of the results.     

Human reconsolidation does not always occur when a memory is retrieved: the relevance of the reminder structure

Memory reconsolidation is defined as a process in which the retrieval of a previously consolidated memory returns to a labile state which is then subject to stabilization. The reminder is the event that begins with the presentation of the learned cue and triggers the labilization-reconsolidation process. Since the early formulation of the hypothesis, several controversial items have arisen concerning the conditions that define reconsolidation. It is herein proposed that two diagnostic features characterize reconsolidation, namely: the labilization of the reactivated memory and the specificity of the reminder structure. To study this proposal, subjects received two different training sessions on verbal material on Day 1 and Day 2, respectively. Finally, they were tested for the first and second acquired memories on Day 3. It is demonstrated that the human declarative memory fulfills the two requirements that define the process. First, the reactivated memory is impaired by a new learning only when it is given closely after the reminder, revealing that the memory is labilized. Second, the omission of at least one of the reminder's components prevents labilization. Therefore, results show that the new learning fails to produce an amnesic effect on the target memory either when the reminder omits the learned cue or includes the beginning of the reinforcement.     

Remaking memories: reconsolidation updates positively motivated spatial memory in rats

There is strong evidence that reactivation of a memory returns it to a labile state, initiating a restabilization process termed reconsolidation, which allows for updating of the memory. In this study we investigated reactivation-dependent updating using a new positively motivated spatial task in rodents that was designed specifically to model a human list-learning paradigm. On Day 1, rats were trained to run to three feeders (List 1) for rewards. On Day 2, rats were trained to run to three different feeders (List 2) in either the same (Reminder condition) or a different (No Reminder condition) experimental context than on Day 1. On Day 3, rats were cued to recall List 1. Rats in the Reminder condition made significantly more visits to List 2 feeders (intrusions) during List 1 recall than rats in the No Reminder condition, indicating that the reminder triggered reactivation and allowed integration of List 2 items into List 1. This reminder effect was selective for the reactivated List 1 memory, as no intrusions occurred when List 2 was recalled on Day 3. No intrusions occurred when retrieval took place in a different context from the one used at encoding, indicating that the expression of the updated memory is dependent upon the retrieval context. Finally, the level of intrusions was highest when retrieval took place immediately after List 2 learning, and generally declined when retrieval occurred 1-4 h later, indicating that the List 2 memory competed with short-term retrieval of List 1. These results demonstrate the dynamic nature of memory over time and the impact of environmental context at different stages of memory processing.     

Repetition effects in directed forgetting: evidence for retrieval inhibition

Four experiments were conducted in support of a role for memory retrieval inhibition in directed forgetting. In each experiment, subjects were presented a list of words, some of which they were instructed to remember and some of which they were instructed to forget. After a recall test for all the words, the list was repeated. This time, however, all the words were presented with instructions that they be remembered. The improvement in recall from Trial 1 to Trial 2 was greater for the “forget” (F) words than for the “remember” (R) words. This difference was not due to a memorization-difficulty, item-selection effect (Experiment 2), a differential priority for rehearsal or output position given to the F items on Trial 2 (Experiment 3), or the greater number of F items left to be learned after Trial 1 (Experiment 4). Thus, the differential improvement from List 1 to List 2 for the F items was interpreted as a release of retrieval inhibition owing to the change in cue from forget to remember.     

Posthypnotic amnesia for recently learned material: Interactions with “episodic” and “semantic” memory

In two experiments, posthypnotic amnesia was suggested for a word list memorized during hypnosis. After an initial test of amnesia the subjects gave word associations (Experiment 1) or category instances (Experiment 2) to stimuli intended to elicit the critical (word list) items covered by the amnesia. The extent of initial amnesia observed was strongly associated with measured hypnotic susceptibility. Even among the most hypnotizable subjects, however, the dense amnesia did not prevent the critical items from being elicited by the semantic memory tasks, nor did it modulate the priming which these associations received by virtue of the prior learning experience. Moreover, production of the critical items did not, in general, remind the amnesic subjects of those items which they had previously learned, but could not now remember. Full memory was restored after the amnesia suggestion was canceled by a prearranged cue. Posthypnotic amnesia appears to represent a temporary dissociation of episodic features from memory traces, so that the subject has difficulty in reconstructing the context in which the target events occurred.     

Human memory reconsolidation can be explained using the temporal context model

Recent work by Hupbach, Gomez, Hardt, and Nadel (Learning & Memory, 14, 47–53, 2007) and Hupbach, Gomez, and Nadel (Memory, 17, 502–510, 2009) suggests that episodic memory for a previously studied list can be updated to include new items, if participants are reminded of the earlier list just prior to learning a new list. The key finding from the Hupbach studies was an asymmetric pattern of intrusions, whereby participants intruded numerous items from the second list when trying to recall the first list, but not viceversa. Hupbach et al. (2007; 2009) explained this pattern in terms of a cellular reconsolidation process, whereby first-list memory is rendered labile by the reminder and the labile memory is then updated to include items from the second list. Here, we show that the temporal context model of memory, which lacks a cellular reconsolidation process, can account for the asymmetric intrusion effect, using well-established principles of contextual reinstatement and item–context binding.     

Testing effects in mixed- versus pure-list designs

In the present study, we investigated the role of list composition in the testing effect. Across three experiments, participants learned items through study and initial testing or study and restudy. List composition was manipulated, such that tested and restudied items appeared either intermixed in the same lists (mixed lists) or in separate lists (pure lists). In Experiment 1, half of the participants received mixed lists and half received pure lists. In Experiment 2, all participants were given both mixed and pure lists. Experiment 3 followed Erlebacher’s (Psychological Bulletin, 84, 212–219, 1977) method, such that mixed lists, pure tested lists, and pure restudied lists were given to independent groups. Across all three experiments, the final recall results revealed significant testing effects for both mixed and pure lists, with no reliable difference in the magnitude of the testing advantage across list designs. This finding suggests that the testing effect is not subject to a key boundary condition—list design—that impacts other memory phenomena, including the generation effect.     

Memory for instances and categories in children and adults

College subjects and 7-year-olds were trained in sorting 16 words into two conceptual categories. Training consisted of either three list presentations (Experiment I) or training to solution (Experiment II). Then either immediately or after a 3 to 4 week delay subjects received a recognition test which assessed memory for the instance vs categorical properties of the task stimuli by embedding words from the original list and from the list categories with confusion items from either the same or different categories as those on the original list. The data indicated that learning and memory were controlled primarily by categorical properties of the task items in adults and by specific instance properties in children. However, there was evidence that children had learned the categorical attributes of the task and may have differed from adults chiefly in their failure to utilize these attributes to assist learning and memory performance. The age differences in learning and memory were independent of the degree of initial training.     

No evidence for a role of reconsolidation in updating of paired associates

Reconsolidation theory states that memories are labilized through reactivation, making them prone to change, before being re-consolidated. When information in memory requires updating, reconsolidation theory therefore predicts that reminders of previously learned information should facilitate updating of that information and should thus improve memory for the updated information. In two experiments, we tested this prediction by investigating memory for word pairs over a short time-scale. Participants studied word pairs (A–B), some of which were subsequently updated with word pairs that shared the first word (A–C). Half of the A–C pairs received a pre-study reminder of the first word in the pair so as to reactivate and labilize A–B memory. In a recognition memory test targeting the A–C list, reminders by and large had no effect on memory. Results thus failed to support the predictions of reconsolidation theory.     

定向遗忘中提取抑制的机制：成功提取引起抑制

两个实验采用无关材料考察了字表方式下提取诱发遗忘解释定向遗忘中提取抑制的可能性。在实验中,学习完两个字表后,对字表2 进行不同次数（0、1、3次）的提取练习以考察是否会增强定向遗忘效应以及定向遗忘效应是否随着提取练习次数的增加而增强。实验一中,字表2提取练习是要求被试回忆字表2项目,不给予线索提示。在实验二中,采用词干补笔测验的形式对字表2进行提取练习,词干补笔测验保证了对字表2项目的成功提取。研究结果发现,只有在实验二中对字表2的成功提取练习增强了定向遗忘效应,从而表明成功提取可以解释定向遗忘中的提取抑制     

Retroactive interference as a function of degree of interpolated study without overt retrieval practice

In two experiments, retroactive interference (RI) was examined under conditions designed to minimize retrieval-induced inhibition and output interference. In Experiment 1, the participants first learned a list of 10 person-location pairs, after which they viewed an interpolated list with the same person terms and different locations for one, four, or eight cycles. Learning was via a study-only method, so that the experimental participants did not perform instructed retrieval of the second list before a cued recall test that asked for List 1 locations only. The experimental participants in Experiment 2 received incidental learning instructions and then viewed a list of 20 unrelated words followed by another list presented either one or four times; the first two letters of each List 1 word were provided on the critical recall test. In both experiments, RI occurred and increased with degree of interpolation. The results suggest that RI does not require retrieval-induced inhibition.     

Enhancing retention through reconsolidation: negative emotional arousal following retrieval enhances later recall

When information is retrieved from memory, it enters a labile state rendering it amenable to change. This process of reconsolidation may explain, in part, the benefits that are observed in later retention following retrieval of information on an initial test. We examined whether the benefits of retrieval could be modulated by an emotional event occurring after retrieval. Participants studied Swahili-English vocabulary pairs. On a subsequent cued-recall test, each retrieval was followed by a blank screen, a neutral picture, or a picture inducing negative affect. Performance on a final cued-recall test was best for items whose initial retrieval was followed by negative pictures. This outcome occurred when a negative picture was presented immediately after (Experiment 1) or 2 s after (Experiment 2) successful retrieval, but not when it was presented after restudy of the vocabulary pair (Experiment 3). Postretrieval reconsolidation via emotional processing may enhance the usual positive effects of retrieval.     

Short-term memory in autism spectrum disorder

Three experiments examined verbal short-term memory in comparison and autism spectrum disorder (ASD) participants. Experiment 1 involved forward and backward digit recall. Experiment 2 used a standard immediate serial recall task where, contrary to the digit-span task, items (words) were not repeated from list to list. Hence, this task called more heavily on item memory. Experiment 3 tested short-term order memory with an order recognition test: Each word list was repeated with or without the position of 2 adjacent items swapped. The ASD group showed poorer performance in all 3 experiments. Experiments 1 and 2 showed that group differences were due to memory for the order of the items, not to memory for the items themselves. Confirming these findings, the results of Experiment 3 showed that the ASD group had more difficulty detecting a change in the temporal sequence of the items.     

The simultaneous learning effect: why does simultaneous task learning improve retention?

Despite the prevalence of encoding variables that have been shown to influence the rate of learning, very few affect the rate of forgetting of verbal material. However, when a list of words is learned simultaneously with other lists, the rate of forgetting is markedly lower than that of single-task learning. Although the magnitude of this simultaneous learning effect is large compared with typical list learning effects, it has received little empirical attention. Experiments 1 and 2 tested the hypothesis that the simultaneous learning effect is the result of a differential contribution of short-term memory during encoding. The results showed that the advantage for simultaneous task learning was obtained even under conditions that minimized the potential effects of short-term memory. Experiment 3 revealed that the simultaneous learning effect was larger when the specific items learned simultaneously were the same on each learning trial than when they were different. This finding supported a cuing explanation of the effect: the items from the other lists act as retrieval cues during delayed recall.     

A primacy effect in monkeys when list position is relevant

In Experiment 1 (1a and 1b), Rhesus monkeys (Macaca mulatta) learned lists of two-choice visual discriminations in which list position was relevant to discrimination performance. For example, Stimulus A was the rewarded stimulus if it was presented at List Position 1, but was not rewarded if it was presented at any other position in the list; similarly, Stimulus B was rewarded only at List Position 2, and so on. In learning these lists, all animals showed a marked primacy effect. In Experiment 2 (2a and 2b), Rhesus monkeys and Cynomolgus monkeys (M. fascicularis) learned lists of visual discriminations in which each visual stimulus occupied a fixed position in a list, but list position was not relevant to discrimination performance. For example, Stimulus E was always rewarded, and was always presented at List Position 1. To increase the salience of list beginning as a distinctive event, successive presentations of the list were separated by 24-hr intervals. In Experiment 2 there was no primacy effect, however. These results show for the first time that a primacy effect can be obtained in visual discrimination learning by monkeys. Furthermore, they suggest that it is obtained only when list position is relevant to the discrimination learning task.     

The role of retrieval practice in directed forgetting

Three experiments tested the possibility that retrieval-induced forgetting is responsible for directed forgetting with the list method. In Experiments 1 and 2, additional List 2 retrieval practice was given to determine whether this would increase directed forgetting. In Experiment 1 all items came from a single category, and in Experiment 2 unrelated words were used. In Experiment 3 additional List 2 study accompanied List 2 retrieval practice. There was no evidence that List 2 retrieval practice, with or without additional List 2 study, affected the magnitude of directed forgetting. It was argued that retrieval-induced forgetting could not account for these results. Accounts with greater viability include retrieval strategy disruption and a modified version of the dissociation hypothesis.     

Reconsolidation in humans opens up declarative memory to the entrance of new information

A consolidated memory recalled by a reminder enters a vulnerability phase (labilization), followed by a process of stabilization (reconsolidation). Several authors have suggested that the labilization of the consolidated memory makes the incorporation of new information possible. Here, we demonstrate updating in the framework of memory declarative reconsolidation in humans by giving an opportune verbal instruction. Volunteers learn an association between five cue-syllables (L1) and their respective response-syllables. Twenty-four hours later, the paired-associate verbal memory is labilized by exposing the subjects to the reminder, and then they receive the verbal Instruction of adding three new cue-response syllables (INFO) with their respective responses to the former list of five. The new information is incorporated into the single former L1-memory and both INFO and L1 are successfully retrieved on the third day. However, when the Instruction is not preceded by a proper reminder, or when the instruction omits the order of adding the INFO into the former L1-memory, we observed interference in retrieval of both the original and the new information, suggesting that they are encoded independently and coexist as separate memories.     

Inhibition of mTOR by rapamycin in the amygdala or hippocampus impairs formation and reconsolidation of inhibitory avoidance memory

Mammalian target of rapamycin (mTOR), a central regulator of protein synthesis in neurons, has been implicated in synaptic plasticity and memory. Here we show that mTOR inhibition by rapamycin in the basolateral amygdala (BLA) or dorsal hippocampus (DH) impairs both formation and reconsolidation of memory for inhibitory avoidance (IA) in rats. Male Wistar rats received bilateral infusions of vehicle or rapamycin into the BLA or DH before or after IA training or retrieval. Memory retention was tested at different time points after drug infusion. Rapamycin impaired long-term IA retention when given before or immediately after training or retrieval into the BLA. When infused into the DH, rapamycin produced memory impairment when given before training or immediately after retrieval. The impairing effects of post-retrieval rapamycin required memory retrieval and were not reversed by a reminder shock. The results provide the first evidence that mTOR in the BLA and DH might play a role in IA memory reconsolidation.     

The effects of the dopamine D1 receptor antagonist SCH23390 on memory reconsolidation following reminder-activated retrieval in day-old chicks

This series of experiments examined the involvement of the dopamine D1 receptor antagonist, SCH23390, on memory reconsolidation following reminder-activated retrieval. Day-old male New HampshirexWhite Leghorn chicks were trained on a single trial passive avoidance task. A dose of 0.5 mg/kg of SCH23390 was administered subcutaneously 5 min before reminder trials, which were presented at 30, 60, and 90 min following training. Memory deficits were observed when reminder trials were presented at 30 and 60 min following training, but not when a reminder was presented at 90 min. No effect on memory retention was observed when reminder trials were not presented, suggesting that reconsolidation mechanisms were both contingent on the presentation of the reminder and independent of the consolidation process. Following a reminder presented at 60 min post-training, deficits in memory retention emerged between 45 and 60 min. The deficit was prolonged, lasting for up until 48 h after reminder presentation. The results indicate an important role for the D1 receptor in reconsolidation processes.     

Facilitation and impairment of event memory produced by photograph review

Selectively reviewing some items from a larger set of previously learned items increases memory for the items that are reviewed but may also be accompanied by a cost: Memory for the nonreviewed items may be impaired relative to cases where no review occurs at all. This cost to nonreviewed items has primarily been shown in contexts of verbal list learning and in situations where the reviewed and nonreviewed items are categorically or semantically related. Using a more naturalistic impetus to selective review--photographs relating to previously experienced events--we assessed whether the memory of older and younger adults for unrelated complex activities that they themselves had performed was also impaired due to nonreview. Both younger and older adults showed impaired memory for nonreviewed activities when tested with free recall (Experiment 1), but not when tested with recognition or cued recall (Experiment 2). If mitigating retrieval cues are unavailable, selective review may impair memory for nonreviewed everyday events.