Overcoming interference: an fMRI investigation of pattern separation in the medial temporal lobe

The medial temporal lobe (MTL) supports the formation and retrieval of long-term declarative memories, or memories for facts and everyday events. One challenge posed for this type of memory stems from the highly overlapping nature of common episodes. Within cognitive psychology, it is widely accepted that interference between information learned at different times is a major limitation on memory. In spite of several decades of intense research in the fields of interference theory and the neurobiological underpinnings of declarative memory, there is little direct evidence bearing on how the MTL resolves this interference to form accurate memories of everyday facts and events. Computational models of MTL function have proposed a mechanism in which the MTL, specifically the hippocampus, performs pattern separation, whereby overlapping representations are made less similar. However, there is little evidence bearing on how this process is carried out in the intact human MTL. Using high-resolution fMRI, we conducted a set of experiments that taxed behavioral pattern separation by using highly similar, interfering stimuli in a modified continuous recognition task. Regions within the parahippocampal gyrus demonstrated activity consistent with a "recall to reject" strategy. In contrast and critical to performing the task, activity within the hippocampus distinguished between correctly identified true stimulus repetitions, correctly rejected presentations of similar lure stimuli, and false alarms to similar lures. These data support the computational models' assertion that the hippocampus plays a key role in pattern separation.     

Reactivation and Consolidation of Memory During Sleep

ABSTRACT— Recent research has shown compellingly that sleep supports the consolidation of declarative memories for events and facts. During consolidation, memories are stabilized against future interference and undergo qualitative changes with regard to their "explicitness" and underlying neural representation. In this article, we argue that declarative memory consolidation during sleep is based on covert reactivations of newly encoded memory traces in the hippocampus. During slow-wave sleep (SWS), the prominent slow oscillations act to synchronize the repeated reactivation of the newly encoded representations in hippocampal networks with the generation of spindle activity in the thalamus, supporting changes in neocortical networks that contribute to long-term memory storage. In this view, sleep plays an active role in the consolidation of memories, in which the neuronal reactivation of newly acquired memories is critical for the redistribution and integration of these memories into the network of pre-existing long-term memories.     

The contribution of sleep to hippocampus-dependent memory consolidation

There is now compelling evidence that sleep promotes the long-term consolidation of declarative and procedural memories. Behavioral studies suggest that sleep preferentially consolidates explicit aspects of these memories, which during encoding are possibly associated with activation in prefrontal-hippocampal circuitry. Hippocampus-dependent declarative memory benefits particularly from slow-wave sleep (SWS), whereas rapid-eye-movement (REM) sleep seems to benefit procedural aspects of memory. Consolidation of hippocampus-dependent memories relies on a dialog between the neocortex and hippocampus. Crucial features of this dialog are the neuronal reactivation of new memories in the hippocampus during SWS, which stimulates the redistribution of memory representations to neocortical networks; and the neocortical slow (<1Hz) oscillation that synchronizes hippocampal-to-neocortical information transfer to activity in other brain structures.     

人类记忆再巩固研究现状及临床应用

巩固的记忆被提取后,进入不稳定状态,再重新稳定下来,这个过程称为记忆再巩固。本文首先阐述人类记忆再巩固主要研究方法和经典范式,梳理记忆再巩固在人类恐惧记忆和情景记忆两个方面的相关研究,并从认知神经科学角度整理记忆再巩固的加工机制。然后总结记忆再巩固应用于创伤性应激障碍和药物成瘾等心理障碍临床治疗的相关文献。最后本文提出未来研究的方向和建议,希冀对人类记忆再巩固的理论研究和临床应用提供新思路。     

Hippocampal and neocortical contributions to memory: advances in the complementary learning systems framework

The complementary learning systems framework provides a simple set of principles, derived from converging biological, psychological and computational constraints, for understanding the differential contributions of the neocortex and hippocampus to learning and memory. The central principles are that the neocortex has a low learning rate and uses overlapping distributed representations to extract the general statistical structure of the environment, whereas the hippocampus learns rapidly using separated representations to encode the details of specific events while minimizing interference. In recent years, we have instantiated these principles in working computational models, and have used these models to address human and animal learning and memory findings, across a wide range of domains and paradigms. Here, we review a few representative applications of our models, focusing on two domains: recognition memory and animal learning in the fear-conditioning paradigm. In both domains, the models have generated novel predictions that have been tested and confirmed.     

Role of the hippocampus and orbitofrontal cortex during the disambiguation of social cues in working memory

Human social interactions are complex behaviors requiring the concerted effort of multiple neural systems to track and monitor the individuals around us. Cognitively, adjusting our behavior on the basis of changing social cues such as facial expressions relies on working memory and the ability to disambiguate, or separate, the representations of overlapping stimuli resulting from viewing the same individual with different facial expressions. We conducted an fMRI experiment examining the brain regions contributing to the encoding, maintenance, and retrieval of overlapping identity information during working memory using a delayed match-to-sample task. In the overlapping condition, two faces from the same individual with different facial expressions were presented at sample. In the nonoverlapping condition, the two sample faces were from two different individuals with different expressions. fMRI activity was assessed by contrasting the overlapping and nonoverlapping conditions at sample, delay, and test. The lateral orbitofrontal cortex showed increased fMRI signal in the overlapping condition in all three phases of the delayed match-to-sample task and increased functional connectivity with the hippocampus when encoding overlapping stimuli. The hippocampus showed increased fMRI signal at test. These data suggest that lateral orbitofrontal cortex helps encode and maintain representations of overlapping stimuli in working memory, whereas the orbitofrontal cortex and hippocampus contribute to the successful retrieval of overlapping stimuli. We suggest that the lateral orbitofrontal cortex and hippocampus play a role in encoding, maintaining, and retrieving social cues, especially when multiple interactions with an individual need to be disambiguated in a rapidly changing social context in order to make appropriate social responses.     

Episodic recollection in animals: “If it walks like a duck and quacks like a duck…”

In humans, episodic memory is most commonly defined as the subjective experience of recollection, presenting a major challenge to the identification of episodic memory in animals. Here we take the position that episodic memory also has several other distinctive qualities that can be assessed objectively in animals, as well as humans, and the examination of these properties provides insights into underlying mechanisms of episodic memory. We focus on recent evidence accumulated in this laboratory indicating that recognition in rats involves a threshold retrieval process, similar to that observed in human episodic recall. Also, rats can remember the temporal order of unique events, characteristic of the replay of vivid episodic memories in humans. Furthermore, rats combine elements of “when” and “where” events occur, as well as the flow of events within a memory, to distinguish memories that share overlapping features, also characteristic of human episodic memory. Finally, all of these capacities are dependent on the hippocampus, which also plays a critical role in human episodic memory. This combination of findings strongly suggests that animals have the same fundamental information processing functions that underlie episodic recall in humans.     

System consolidation of memory during sleep

Over the past two decades, research has accumulated compelling evidence that sleep supports the formation of long-term memory. The standard two-stage memory model that has been originally elaborated for declarative memory assumes that new memories are transiently encoded into a temporary store (represented by the hippocampus in the declarative memory system) before they are gradually transferred into a long-term store (mainly represented by the neocortex), or are forgotten. Based on this model, we propose that sleep, as an offline mode of brain processing, serves the ‘active system consolidation’ of memory, i.e. the process in which newly encoded memory representations become redistributed to other neuron networks serving as long-term store. System consolidation takes place during slow-wave sleep (SWS) rather than rapid eye movement (REM) sleep. The concept of active system consolidation during sleep implicates that (a) memories are reactivated during sleep to be consolidated, (b) the consolidation process during sleep is selective inasmuch as it does not enhance every memory, and (c) memories, when transferred to the long-term store undergo qualitative changes. Experimental evidence for these three central implications is provided: It has been shown that reactivation of memories during SWS plays a causal role for consolidation, that sleep and specifically SWS consolidates preferentially memories with relevance for future plans, and that sleep produces qualitative changes in memory representations such that the extraction of explicit and conscious knowledge from implicitly learned materials is facilitated.     

Relationship between short- and long-term memory and short- and long-term extinction

Both the acquisition and the extinction of memories leave short- and long-term mnemonic traces. Here, we show that in male Wistar rats, the short-term memory for a step-down inhibitory avoidance task (IA) is resistant to extinction, and that its expression does not influence retrieval or extinction of long-term memory. It has been known for some time that short- and long-term inhibitory avoidance memory involve separate and parallel processes. Here we show that, instead, short-term extinction of IA long-term memory is the first step towards its long-term extinction, and that this link requires functional NMDA receptors and protein synthesis in the CA1 region of the dorsal hippocampus at the time of the first CS-no US presentation.     

The origin of children's implanted false memories: Memory traces or compliance?

A longstanding question in false memory research is whether children's implanted false memories represent actual memory traces or merely result from compliance. The current study examined this question using a response latency based deception task. Forty-five 8-year-old children received narratives about a true (first day at school) and false event (hot air balloon ride). Across two interviews, 58/32% of the participants developed a partial/full false memory. Interestingly, these children also showed higher false recall on an unrelated DRM paradigm compared to children without a false memory. The crucial finding, however, was that the results of the deception task revealed that children with partial and full false memories were faster to confirm than to deny statements relating to the false event. This indicates that children's implanted false memories reflect actual memory traces, and are unlikely to be explained by mere compliance.     

Inhibitory processes and the control of memory retrieval

People are often confronted with reminders of things they would prefer not to think about. When this happens, they often attempt to put the unwanted memories out of awareness. Recent research shows that the capacity to suppress distracting traces is mediated by executive-control processes that are analogous to those involved in overriding prepotent motor responses, and it is these processes that cause persisting memory failures for the suppressed items. There is evidence that memory retrieval and motor tasks that are likely to demand executive control recruit overlapping neural mechanisms, suggesting that a common process mediates control in these domains. Together, these findings indicate that memory failures often arise from the mechanisms that lie at the heart of our capacity to influence the focus of thought.     

What Differentiates Declarative and Procedural Memories: Reply to Cohen,Poldrack, and Eichenbaum (1997)

Cohen, Poldrack, and Eichenbaum (1997; hereafter CPE) offer an account of the nature of individual items in memory and how they relate to one another. They argue that there are two separate memory systems, procedural and declarative (Cohen & Eichenbaum, 1993; Cohen & Squire, 1980). These systems differ in their neuroanatomic substrates, in their operating characteristics, and in the nature of the representations they use. CPE argue that representations in the declarative memory system are compositional, meaning that declarative representations may be composed of other declarative representations. Declarative memories are also flexible, meaning they can be accessed in contexts that differ from those in which they were encoded. Procedural memories, on the other hand, are neither compositional nor flexible. I will argue that there is not sufficient reason to argue that procedural and declarative memories have these distinct characteristics. Both procedural and declarative memories are arguably compositional, and both can appear flexible or inflexible, depending on testing conditions.     

Inverse temporal contributions of the dorsal hippocampus and medial prefrontal cortex to the expression of long-term fear memories

Retrograde amnesia following disruptions of hippocampal function is often temporally graded, with recent memories being more impaired. Evidence supports the existence of one or more neocortical long-term memory storage/retrieval site(s). Neurotoxic lesions of the medial prefrontal cortex (mPFC) or the dorsal hippocampus (DH) were made 1 day or 200 days following trace fear conditioning. Recently encoded trace fear memories were most disrupted by DH lesions, while remotely encoded trace and contextual memories were most disrupted by mPFC lesions. These data strongly support the consolidation theory of hippocampus function and implicate the mPFC as a site of long-term memory storage/retrieval.     

Recognition memory for social and non-social odors: differential effects of neurotoxic lesions to the hippocampus and perirhinal cortex

The contributions of the hippocampus (HC) and perirhinal cortex (PER) to recognition memory are currently topics of debate in neuroscience. Here we used a rapidly-learned (seconds) spontaneous novel odor recognition paradigm to assess the effects of pre-training N-methyl-D-aspartate lesions to the HC or PER on odor recognition memory. We tested memory for both social and non-social odor stimuli. Social odors were acquired from conspecifics, while non-social odors were household spices. Conspecific odor stimuli are ethologically-relevant and have a high degree of overlapping features compared to non-social household spices. Various retention intervals (5 min, 20 min, 1h, 24h, or 48 h) were used between study and test phases, each with a unique odor pair, to assess changes in novelty preference over time. Consistent with findings in other paradigms, modalities, and species, we found that HC lesions yielded no significant recognition memory deficits. In contrast, PER lesions caused significant deficits for social odor recognition memory at long retention intervals, demonstrating a critical role for PER in long-term memory for social odors. PER lesions had no effect on memory for non-social odors. The results are consistent with a general role for PER in long-term recognition memory for stimuli that have a high degree of overlapping features, which must be distinguished by conjunctive representations.     

Affective evidence that inhibition is involved in separating accessory representations from active representations in visual working memory

ABSTRACT

The multiple state theory of working memory suggests that representations are divided into two states: focused-on active representations and accessory memories held for later use. Here we tested two competing hypotheses regarding the neurocognitive mechanisms responsible for this separation: (1) that accessory memories undergo inhibition or (2) that accessory memories are amplified less than active representations. We explored whether accessory memories undergo affective devaluation, a known index of the involvement of inhibition in a visual task. On each trial participants memorized four items, were cued to focus on one, and then completed a visual search or an affective evaluation task. While search distractors matching the colour of an active item slowed search, those matching an accessory memory did not, replicating previous findings that only active items guide search. Also, accessory items were affectively devalued compared to baseline and active items, supporting the hypothesis that accessory memories undergo inhibition.     

Cognitive-Emotional Interactions in the Brain

Abstract

Emotion and cognition are mediated by separate but interacting systems of the brain. The core of the emotional system is a network that evaluates (computes) the biological significance of stimuli, including stimuli from the external or internal environment or from within the brain (thoughts, images, memories). The computation of stimulus significance takes place prior to and independent of conscious awareness, with only the computational products reaching awareness, and only in some instances. The amygdala may be a focal structure in the affective network. By way of neural interactions between the amygdala and brain areas involved in cognition (particularly the neocortex and hippocampus), affect can influence cognition and cognition can influence affect. Emotional experiences, it is proposed, result when stimulus representations, affect representations, and self representations coincide in working memory.     

Aging memories: differential decay of episodic memory components

Some memories about events can persist for decades, even a lifetime. However, recent memories incorporate rich sensory information, including knowledge on the spatial and temporal ordering of event features, while old memories typically lack this "filmic" quality. We suggest that this apparent change in the nature of memories may reflect a preferential loss of hippocampus-dependent, configurational information over more cortically based memory components, including memory for individual objects. The current study systematically tests this hypothesis, using a new paradigm that allows the contemporaneous assessment of memory for objects, object pairings, and object-position conjunctions. Retention of each memory component was tested, at multiple intervals, up to 3 mo following encoding. The three memory subtasks adopted the same retrieval paradigm and were matched for initial difficulty. Results show differential decay of the tested episodic memory components, whereby memory for configurational aspects of a scene (objects' co-occurrence and object position) decays faster than memory for featured objects. Interestingly, memory requiring a visually detailed object representation decays at a similar rate as global object recognition, arguing against interpretations based on task difficulty and against the notion that (visual) detail is forgotten preferentially. These findings show that memories undergo qualitative changes as they age. More specifically, event memories become less configurational over time, preferentially losing some of the higher order associations that are dependent on the hippocampus for initial fast encoding. Implications for theories of long-term memory are discussed.     

Neural correlates underlying true and false associative memories

Despite the fact that associative memory studies produce a large number of false memories, neuroimaging analyses utilizing this paradigm typically focus only on neural activity mediating successful retrieval. The current study sought to expand on this prior research by examining the neural basis of both true and false associative memories. Though associative false memories are substantially different than those found in semantic or perceptual false memory paradigms, results suggest that associative false memories are mediated by similar neural mechanisms. Specifically, we found increased frontal activity that likely represents enhanced monitoring and evaluation compared to that needed for true memories and correct rejections. Results also indicated that true, and not false associative memories, are mediated by neural activity in the MTL, specifically the hippocampus. Finally, while activity in early visual cortex distinguished true from false memories, a lack of neural differences between hits and correct rejections failed to support previous findings suggesting that activity in early visual cortex represents sensory reactivation of encoding-related processing.     

How intention to retrieve a memory and expectation that a memory will come to mind influence the retrieval of autobiographical memories

While involuntary memories are retrieved with no intention and are usually unexpected (when one is not waiting for a memory to arise), voluntary memories are intended and expected (when one is searching and waiting for a memory to arise). The present study aimed to investigate the effects of retrieval intentionality (i.e. wanting to retrieve a memory) and monitoring processes (i.e. waiting for a memory to appear) during autobiographical memory retrieval. In addition, we introduced two novel laboratory conditions that have not been used in previous research on voluntary memories: in the first, participants were asked to report anything they could think of in response to each cue word; in the second, they could skip a word if nothing came to mind. These novel manipulations allowed us to differentiate between voluntary memories retrieved in response to experimenter-generated cues (when participants were forced to provide a memory or a thought for each cue) and self-selected cues (when participants were free to not answer a cue if they found it too difficult). We found that highly accessible memories were mostly experienced when retrieval was involuntary and unexpected, while memories with low accessibility were accessed through intentional retrieval and monitoring processes. Response times for memories recalled in the experimenter-generated cue conditions were longer compared to the self-selected cue conditions. This novel finding shows that experimenter-generated recall favours memories with low accessibility; it further supports the idea that, in a substantial number of trials, voluntary memories are directly rather than effortfully retrieved. The idea that the driving force behind differences between involuntary and voluntary memories is not the intention per se is further discussed.     

Gamma oscillations distinguish true from false memories

ABSTRACT— To test whether distinct patterns of electrophysiological activity prior to a response can distinguish true from false memories, we analyzed intracranial electroencephalographic recordings while 52 patients undergoing treatment for epilepsy performed a verbal free-recall task. These analyses revealed that the same pattern of gamma-band (28–100 Hz) oscillatory activity that predicts successful memory formation at item encoding—increased gamma power in the hippocampus, prefrontal cortex, and left temporal lobe—reemerges at retrieval to distinguish correct from incorrect responses. The timing of these oscillatory effects suggests that self-cued memory retrieval begins in the hippocampus and then spreads to the cortex. Thus, retrieval of true, as compared with false, memories induces a distinct pattern of gamma oscillations, possibly reflecting recollection of contextual information associated with past experience.