Reduced hippocampal-cortical connectivity during memory suppression predicts the ability to forget unwanted memories.

The ability to suppress unwelcome memories is important for productivity and well-being. Successful memory suppression is associated with hippocampal deactivations and a concomitant disruption of this region's functionality. Much of the previous neuroimaging literature exploring such suppression-related hippocampal modulations has focused on the region's negative coupling with the prefrontal cortex. Task-based changes in functional connectivity between the hippocampus and other brain regions still need further exploration. In the present study, we utilize psychophysiological interactions and seed connectome-based predictive modeling to investigate the relationship between the hippocampus and the rest of the brain as 134 participants attempted to suppress unwanted memories during the Think/No-Think task. The results show that during retrieval suppression, the right hippocampus exhibited decreased functional connectivity with visual cortical areas (lingual and cuneus gyrus), left nucleus accumbens and the brain-stem that predicted superior forgetting of unwanted memories on later memory tests. Validation tests verified that prediction performance was not an artifact of head motion or prediction method and that the negative features remained consistent across different brain parcellations. These findings suggest that systemic memory suppression involves more than the modulation of hippocampal activity-it alters functional connectivity patterns between the hippocampus and visual cortex, leading to successful forgetting.

Task compliance predicts suppression-induced forgetting in a large sample.

Suppression-induced forgetting (SIF) refers to a memory impairment resulting from repeated attempts to stop the retrieval of unwanted memory associates. SIF has become established in the literature through a growing number of reports built upon the Think/No-Think (TNT) paradigm. Not all individuals and not all reported experiments yield reliable forgetting, however. Given the reliance on task instructions to motivate participants to suppress target memories, such inconsistencies in SIF may reasonably owe to differences in compliance or expectations as to whether they will again need to retrieve those items (on, say, a final test). We tested these possibilities on a large (N = 497) sample of TNT participants. In addition to successfully replicating SIF, we found that the magnitude of the effect was significantly and negatively correlated with participants' reported compliance during the No-Think trials. This pattern held true on both same- and independent-probe measures of forgetting, as well as when the analysis was conditionalized on initial learning. In contrast, test expectancy was not associated with SIF. Supporting previous intuition and more limited post-hoc examinations, this study provides robust evidence that a lack of compliance with No-Think instructions significantly compromises SIF. As such, it suggests that diminished effects in some studies may owe, at least in part, to non-compliance-a factor that should be carefully tracked and/or controlled. Motivated forgetting is possible, provided that one is sufficiently motivated and capable of following the task instructions.

Functional connectivity between right-lateralized ventrolateral prefrontal cortex and insula mediates reappraisal's link to memory control.

BACKGROUND: Memory control (MC) ability is critical for people's mental and physical health. Previous research had conceptually demonstrated that MC ability has close relationship with reappraisal. However, experimental evidence supporting the relationship was limited. Thus, in the present study, we investigated how MC and reappraisal are linked, both in behavior and in the brain. METHODS: The habitual use of reappraisal was assessed by Emotion Regulation Questionnaire, and memory control ability was measured through directed forgetting task. Resting-state functional magnetic resonance imaging was used to test the seed-based functional connectivity in 181 healthy subjects. RESULTS: Behavioral results revealed that more frequent reappraisal was associated with an enhanced ability to control negative memories. Resting-state seed-based functional connectivity showed that habitual use of reappraisal was positively related to the strength of functional connectivity between the right ventrolateral prefrontal cortex (VLPFC) and right insula. Most importantly, this functional connectivity mediated the effect of habitual use of reappraisal on control over negative memories. LIMITATIONS: Present results mainly showed the habitual use of reappraisal was related with MC ability in negative items. Future study could further explore the relationship between MC ability of different categories of negative emotional memories and other kinds of ER strategies. CONCLUSIONS: Our results support the notion that reappraisal provides opportunities for individuals to practice and enhance inhibitory control-a relationship underpinned by connectivity between the right VLPFC and right insula.

Active Forgetting: Adaptation of Memory by Prefrontal Control.

Over the past century, psychologists have discussed whether forgetting might arise from active mechanisms that promote memory loss to achieve various functions, such as minimizing errors, facilitating learning, or regulating one's emotional state. The past decade has witnessed a great expansion in knowledge about the brain mechanisms underlying active forgetting in its varying forms. A core discovery concerns the role of the prefrontal cortex in exerting top-down control over mnemonic activity in the hippocampus and other brain structures, often via inhibitory control. New findings reveal that such processes not only induce forgetting of specific memories but also can suppress the operation of mnemonic processes more broadly, triggering windows of anterograde and retrograde amnesia in healthy people. Recent work extends active forgetting to nonhuman animals, presaging the development of a multilevel mechanistic account that spans the cognitive, systems, network, and even cellular levels. This work reveals how organisms adapt their memories to their cognitive and emotional goals and has implications for understanding vulnerability to psychiatric disorders.

Does retrieving a memory insulate it against memory inhibition? A retroactive interference study.

Several recent studies suggest that an initial retrieval attempt imbues retrieved memories with special resilience against future interference and other forgetting mechanisms. Here we report two experiments examining whether memories established through initial retrieval remain subject to retrieval-induced forgetting. Using a version of a classical retroactive interference design, we trained participants on a list of A-B pairs via anticipation - constituting a form of retrieval practice. After next training participants on interfering A-C pairs, they performed 0-12 additional A-C anticipation trials. Because these trials required retrieval of A-C pairs, they should function similarly to retrieval practice in paradigms establishing retrieval-induced forgetting. We observed robust evidence that retroactive interference generalises to final memory tests involving novel, independent memory probes. Moreover, in contrast to practising retrieval of A-C items, their extra study failed to induce cue-independent forgetting of the original B items. Together, these findings substantiate the role of retrieval-related inhibitory processes in a traditional retroactive interference design. Importantly, they indicate that an initial retrieval attempt on a competitor does not abolish retrieval-induced forgetting, at least not in the context of this classic design. Although such an attempt may protect against inhibition in some circumstances, the nature of those circumstances remains to be understood.

Reductions in Retrieval Competition Predict the Benefit of Repeated Testing.

Repeated testing leads to improved long-term memory retention compared to repeated study, but the mechanism underlying this improvement remains controversial. In this work, we test the hypothesis that retrieval practice benefits subsequent recall by reducing competition from related memories. This hypothesis implies that the degree of reduction in competition between retrieval practice attempts should predict subsequent memory for practiced items. To test this prediction, we collected electroencephalography (EEG) data across two sessions. In the first session, participants practiced selectively retrieving exemplars from superordinate semantic categories (high competition), as well as retrieving the names of the superordinate categories from exemplars (low competition). In the second session, participants repeatedly studied and were tested on Swahili-English vocabulary. One week after session two, participants were again tested on the vocabulary. We trained a within-subject classifier on the data from session one to distinguish high and low competition states. We then used this classifier to measure the change in competition across multiple successful retrieval practice attempts in the second session. The degree to which competition decreased for a given vocabulary word predicted whether it was subsequently remembered in the third session. These results are consistent with the hypothesis that repeated testing improves retention by reducing competition.

What doesn't kill you makes you stronger: Psychological trauma and its relationship to enhanced memory control.

Control processes engaged in halting the automatic retrieval of unwanted memories have been shown to reduce the later recallability of the targets of suppression. Like other cognitive skills that benefit from practice, we hypothesized that memory control is similarly experience dependent, such that individuals with greater real-life experience at stopping retrieval would exhibit better inhibitory control over unwanted memories. Across two experiments, we found that college students reporting a greater history of trauma exhibited more suppression-induced forgetting of both negative and neutral memories than did those in a matched group who had reported experiencing little to no trauma. The association was especially evident on a test of suppression-induced forgetting involving independent retrieval cues that are designed to better isolate the effects of inhibitory control on memory. Participants reporting more trauma demonstrated greater generalized forgetting of suppressed material. These findings raise the possibility that, given proper training, individuals can learn to better manage intrusive experiences, and are broadly consistent with the view that moderate adversity can foster resilience later in life. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Unintended side effects of a spotless mind: theory and practice.

Forgetting can be either a source of great frustration or one of great relief, depending on whether the memories in question are relevant to one's immediate goals. Adopting an appropriate strategy or memory mode can help achieve these goals. But do efforts to control memory engender unintended side effects? Presently, we expand on a theoretical perspective of memory control, wherein efforts to suppress episodic encoding or retrieval result in the systemic downregulation of the hippocampal memory system. We review evidence from multiple methodologies, highlighting a non-invasive means of inducing amnesia that casts a shadow over memory for unrelated events. By establishing the causes and consequences of the amnesic side effects associated with memory control, we argue it may be possible to harness hippocampal dynamics to promote more adaptive memory performance in the lab, clinic, and broader context of daily life.

A neural signature of contextually mediated intentional forgetting.

The mental context in which we experience an event plays a fundamental role in how we organize our memories of an event (e.g. in relation to other events) and, in turn, how we retrieve those memories later. Because we use contextual representations to retrieve information pertaining to our past, processes that alter our representations of context can enhance or diminish our capacity to retrieve particular memories. We designed a functional magnetic resonance imaging (fMRI) experiment to test the hypothesis that people can intentionally forget previously experienced events by changing their mental representations of contextual information associated with those events. We had human participants study two lists of words, manipulating whether they were told to forget (or remember) the first list prior to studying the second list. We used pattern classifiers to track neural patterns that reflected contextual information associated with the first list and found that, consistent with the notion of contextual change, the activation of the first-list contextual representation was lower following a forget instruction than a remember instruction. Further, the magnitude of this neural signature of contextual change was negatively correlated with participants' abilities to later recall items from the first list.

Inducing amnesia through systemic suppression.

Hippocampal damage profoundly disrupts the ability to store new memories of life events. Amnesic windows might also occur in healthy people due to disturbed hippocampal function arising during mental processes that systemically reduce hippocampal activity. Intentionally suppressing memory retrieval (retrieval stopping) reduces hippocampal activity via control mechanisms mediated by the lateral prefrontal cortex. Here we show that when people suppress retrieval given a reminder of an unwanted memory, they are considerably more likely to forget unrelated experiences from periods surrounding suppression. This amnesic shadow follows a dose-response function, becomes more pronounced after practice suppressing retrieval, exhibits characteristics indicating disturbed hippocampal function, and is predicted by reduced hippocampal activity. These findings indicate that stopping retrieval engages a suppression mechanism that broadly compromises hippocampal processes and that hippocampal stabilization processes can be interrupted strategically. Cognitively triggered amnesia constitutes an unrecognized forgetting process that may account for otherwise unexplained memory lapses following trauma.

Adaptive top-down suppression of hippocampal activity and the purging of intrusive memories from consciousness.

When reminded of unwanted memories, people often attempt to suppress these experiences from awareness. Prior work indicates that control processes mediated by the dorsolateral prefrontal cortex (DLPFC) modulate hippocampal activity during such retrieval suppression. It remains unknown whether this modulation plays a role in purging an intrusive memory from consciousness. Here, we combined fMRI and effective connectivity analyses with phenomenological reports to scrutinize a role for adaptive top-down suppression of hippocampal retrieval processes in terminating mnemonic awareness of intrusive memories. Participants either suppressed or recalled memories of pictures depicting faces or places. After each trial, they reported their success at regulating awareness of the memory. DLPFC activation was greatest when unwanted memories intruded into consciousness and needed to be purged, and this increased engagement predicted superior control of intrusive memories over time. However, hippocampal activity was decreased during the suppression of place memories only. Importantly, the inhibitory influence of the DLPFC on the hippocampus was linked to the ensuing reduction in intrusions of the suppressed memories. Individuals who exhibited negative top-down coupling during early suppression attempts experienced fewer involuntary memory intrusions later on. Over repeated suppressions, the DLPFC-hippocampus connectivity grew less negative with the degree that they no longer had to purge unwanted memories from awareness. These findings support a role of DLPFC in countermanding the unfolding recollection of an unwanted memory via the suppression of hippocampal processing, a mechanism that may contribute to adaptation in the aftermath of traumatic experiences.

Evidence against associative blocking as a cause of cue-independent retrieval-induced forgetting.

Selectively retrieving an item from long-term memory reduces the accessibility of competing traces, a phenomenon known as retrieval-induced forgetting (RIF). RIF exhibits cue independence, or the tendency for forgetting to generalize to novel test cues, suggesting an inhibitory basis for this phenomenon. An alternative view (Camp, Pecher, & Schmidt, 2007; Camp et al., 2009; Perfect et al., 2004) suggests that using novel test cues to measure cue independence actually engenders associative interference when participants covertly supplement retrieval with practiced cues that then associatively block retrieval. Accordingly, the covert-cueing hypothesis assumes that the relative strength of the practiced items at final test ­ and not the inhibition levied on the unpracticed items during retrieval practice ­ underlies cue-independent forgetting. As such, this perspective predicts that strengthening practiced items by any means, even if not via retrieval practice, should induce forgetting. Contrary to these predictions, however, we present clear evidence that cue-independent forgetting is induced by retrieval practice and not by repeated study exposures. This dissociation occurred despite significant, comparable levels of strengthening of practiced items in each case, and despite the use of Anderson and Spellman's original (1995) independent probe method criticized by covert-cueing theorists as being especially conducive to associative blocking. These results demonstrate that cue-independent RIF is unrelated to the strengthening of practiced items, and thereby fail to support a key prediction of the covert-cueing hypothesis. The results, instead, favor a role of inhibition in resolving retrieval interference.

The sleeping brain's influence on verbal memory: boosting resistance to interference.

Memories evolve. After learning something new, the brain initiates a complex set of post-learning processing that facilitates recall (i.e., consolidation). Evidence points to sleep as one of the determinants of that change. But whenever a behavioral study of episodic memory shows a benefit of sleep, critics assert that sleep only leads to a temporary shelter from the damaging effects of interference that would otherwise accrue during wakefulness. To evaluate the potentially active role of sleep for verbal memory, we compared memory recall after sleep, with and without interference before testing. We demonstrated that recall performance for verbal memory was greater after sleep than after wakefulness. And when using interference testing, that difference was even more pronounced. By introducing interference after sleep, this study confirms an experimental paradigm that demonstrates the active role of sleep in consolidating memory, and unmasks the large magnitude of that benefit.

Understanding words in context: the role of Broca's area in word comprehension.

What role does meaning selection play in word comprehension, and what neural systems support this selection process? Most words have multiple meanings and are therefore ambiguous. This is true of both homonymous words (words that have multiple unrelated meanings) and polysemous words (words that have multiple related meanings). The extant evidence indicates that meaning selection is an integral part of homonym comprehension. However, it is not known whether meaning selection extends to polysemous words, or what neural systems support meaning selection during comprehension. Prior neuroimaging and neuropsychological evidence suggest that the left inferior frontal gyrus (LIFG) may play a role in resolving competition during language processing. We therefore sought to test the hypotheses that meaning selection is part of polysemous word comprehension, and that the LIFG resolves meaning competition during word comprehension. We tested healthy participants on a version of the triplet lexical decision task, with polysemous and homonymous stimuli. Results suggest that the meanings of polysemous words, like the meanings of homonyms, are selected based on context. However, homonymous and polysemous words differed in how meaning frequency affected meaning selection. We then administered the triplet lexical decision task to patients with LIFG damage to examine whether this region plays a role in context-dependent meaning selection. Results support the hypothesis that the LIFG serves as a top-down biasing mechanism that facilitates rapid meaning selection during word comprehension. We conclude that context-dependent meaning selection is an integral part of word comprehension for both homonyms and polysemous words, and that the LIFG facilitates this selection process.

Interfering with theories of sleep and memory: sleep, declarative memory, and associative interference.

Mounting behavioral evidence in humans supports the claim that sleep leads to improvements in recently acquired, nondeclarative memories. Examples include motor-sequence learning; visual-discrimination learning; and perceptual learning of a synthetic language. In contrast, there are limited human data supporting a benefit of sleep for declarative (hippocampus-mediated) memory in humans (for review, see). This is particularly surprising given that animal models (e.g.,) and neuroimaging studies (e.g.,) predict that sleep facilitates hippocampus-based memory consolidation. We hypothesized that we could unmask the benefits of sleep by challenging the declarative memory system with competing information (interference). This is the first study to demonstrate that sleep protects declarative memories from subsequent associative interference, and it has important implications for understanding the neurobiology of memory consolidation.