Peri-encoding predictors of memory encoding and consolidation

We review reports of brain activations that occur immediately prior to the onset or following the offset of to-be-remembered information and can predict subsequent mnemonic success. Memory-predictive pre-encoding processes, occurring from fractions of a second to minutes prior to event onset, are mainly associated with activations in the medial temporal lobe (MTL), amygdala and midbrain, and with enhanced theta oscillations. These activations may be considered as the neural correlates of one or more cognitive operations, including contextual processing, attention, and the engagement of distinct computational modes associated with prior encoding or retrieval. Post-encoding activations that correlate with subsequent memory performance are mainly observed in the MTL, sensory cortices and frontal regions. These activations may reflect binding of elements of the encoded information and initiation of memory consolidation. In all, the findings reviewed here illustrate the importance of brain states in the immediate peri-encoding time windows in determining encoding success. Understanding these brain states and their specific effects on memory may lead to optimization of the encoding of desired memories and mitigation of undesired ones.     

Dissociating confidence and accuracy: functional magnetic resonance imaging shows origins of the subjective memory experience

Successful memory typically implies both objective accuracy and subjective confidence, but there are instances when confidence and accuracy diverge. This dissociation suggests that there may be distinct neural patterns of activation related to confidence and accuracy. We used event-related functional magnetic resonance imaging to study the encoding of novel face--name associations, assessed with a postscan memory test that included objective measures of accuracy and subjective measures of confidence. We showed specific neural activity in the left inferior prefrontal cortex associated with trials when subjects expressed high confidence that they had chosen the correct name for the face and made a correct identification. Moreover, we found that this region was also associated with imparting high confidence when subjects chose the incorrect name. However, medial temporal lobe regions showed activity only for high-confidence correct trials. Many functional magnetic resonance imaging studies have shown that the medial temporal lobe and left prefrontal regions are particularly important for the successful formation of memories by using a combination of subjective and objective measures. Our findings suggest that these regions may be differentially involved in the objective and subjective components of memory and that the origins of confidence-accuracy dissociations may be related to incomplete activation of the neural pattern seen in successful encoding. These findings may also aid understanding of eyewitness misidentifications and memory distortions.     

Face memory and its disorders

Face recognition is an essential biologic and social skill. Accurate recognition depends on the ability to encode, store, and retrieve distinct memory representations for the faces of countless individuals encountered in everyday life. In addition, face memory records must be integrated with specific biographic and name information in order to allow the recognition of each person’s unique identity. Converging evidence from functional imaging, cortical electrical recording, and neuropsychologic studies suggests that face memory operations in the human brain are mediated by a distributed neural system. Components of this network include specialized memory storage sites within temporal neocortex that interact with medial temporal lobe and prefrontal cortical areas during face memory encoding and retrieval. Selective damage to these neuroanatomic regions gives rise to face recognition disorders characterized by memory loss or memory distortion.     

Attention-related activity during episodic memory retrieval: a cross-function fMRI study

In functional neuroimaging studies of episodic retrieval (ER), activations in prefrontal, parietal, anterior cingulate, and thalamic regions are typically attributed to episodic retrieval processes. However, these activations are also frequent during visual attention (VA) tasks, suggesting that their role in ER may reflect attentional rather than mnemonic processes. To investigate this possibility, we directly compared brain activity during ER and VA tasks using event-related fMRI. The ER task was a word recognition test with a retrieval mode component, and the VA task was a target detection task with a sustained attention component. The study yielded three main findings. First, a common fronto-parietal-cingulate-thalamic network was found for ER and VA, suggesting that the involvement of these regions during ER reflects general attentional processes. This idea is compatible with some of the interpretations proposed in the ER literature (e.g. postretrieval monitoring), which may be rephrased in terms of attentional processes. Second, several subregions were differentially involved in ER versus VA. For example, the frontopolar cortex and the precuneus were more activated for ER than for VA, possibly reflecting retrieval mode and processing of internally generated stimuli, respectively. Finally, the study yielded an unexpected finding: some medial temporal lobe regions were similarly activated for ER and VA. This finding suggests that the medial temporal lobes may be involved in indexing representations within the focus of consciousness, regardless of whether they are mnemonic or perceptual. Overall, the present results suggest that many of the activations attributed to specific cognitive processes, such as episodic memory, may actually reflect more general cognitive operations.     

Competition among multiple memory systems: converging evidence from animal and human brain studies

Research of the neurobiological bases of learning and memory suggest that these processes are not unitary in nature, but rather that relatively independent neural systems appear to mediate different types of memory. Neurobiological studies, for instance, have identified separable cognitive or "declarative" and stimulus-response "habit" memory systems that rely upon the medial temporal lobe (e.g. hippocampus) and basal ganglia (e.g. caudate-putamen), respectively. Evidence indicates that multiple memory systems are activated simultaneously and in parallel in various learning tasks, and recent findings suggest that these systems may interact. One form of interaction between medial temporal lobe and basal ganglia memory systems appears competitive in nature, and has been revealed in non-human animal studies in which damage to a given memory system results in enhanced learning. Recent human neuroimaging research has also provided evidence in favor of competition between memory systems. Thus, converging evidence across species supports the hypothesis of interactive multiple memory systems in the mammalian brain. Potential neurobiological mechanisms mediating such interactions include direct anatomical projections between the medial temporal lobe and basal ganglia, indirect neuromodulatory influences of other brain structures (e.g. basolateral amygdala) and activity of neocortical brain regions involved in top-down response selection.     

Multiple anatomical systems embedded within the primate medial temporal lobe: implications for hippocampal function

A review of medial temporal lobe connections reveals three distinct groupings of hippocampal efferents. These efferent systems and their putative memory functions are: (1) The 'extended-hippocampal system' for episodic memory, which involves the anterior thalamic nuclei, mammillary bodies and retrosplenial cortex, originates in the subicular cortices, and has a largely laminar organisation; (2) The 'rostral hippocampal system' for affective and social learning, which involves prefrontal cortex, amygdala and nucleus accumbens, has a columnar organisation, and originates from rostral CA1 and subiculum; (3) The 'reciprocal hippocampal-parahippocampal system' for sensory processing and integration, which originates from the length of CA1 and the subiculum, and is characterised by columnar, connections with reciprocal topographies. A fourth system, the 'parahippocampal-prefrontal system' that supports familiarity signalling and retrieval processing, has more widespread prefrontal connections than those of the hippocampus, along with different thalamic inputs. Despite many interactions between these four systems, they may retain different roles in memory which when combined explain the importance of the medial temporal lobe for the formation of declarative memories.     

Activity in human medial temporal lobe associated with encoding process in spatial working memory revealed by magnetoencephalography

Animal studies have suggested that working memory may be affected after lesions in the medial temporal lobe, although this assumption has not been corroborated by neuropsychological studies in humans. However, very recently, several functional neuroimaging studies in humans have successfully observed activation of the medial temporal lobe during working memory tasks. The main aim of this study was to investigate the contribution of the medial temporal lobe to the encoding process in spatial working memory. To address this issue we registered the neuromagnetic brain patterns of eight adult volunteers while they performed a spatial working memory task and more perceptual task using identical stimuli. After a initial phase (between 200 and 400 ms) without differences in activation, the medial temporal lobe showed a sustained activity, more evident in the right hemisphere, lasting up to 800 ms during the encoding stage of the spatial working memory task, while the activation in the perceptual task terminated earlier (approximately 400 ms after stimulus onset). The finding of a continued activation of the medial temporal lobe strongly suggests the contribution of this brain region to encoding operations in working memory.     

Glucocorticoid-induced impairment of declarative memory retrieval is associated with reduced blood flow in the medial temporal lobe

Previous work indicates that stress levels of circulating glucocorticoids can impair retrieval of declarative memory in human subjects. Several studies have reported that declarative memory retrieval relies on the medial temporal lobe. The present study used H(2)(15)O-positron emission tomography to investigate whether acutely elevated glucocorticoid levels affect regional cerebral blood flow in the medial temporal lobe, as well as in other brain regions, during declarative memory retrieval in healthy male human subjects. When measured over four different declarative memory retrieval tasks, a single, stress-level dose of cortisone (25 mg) administered orally 1 h before retention testing, induced a large decrease in regional cerebral blood flow in the right posterior medial temporal lobe, the left visual cortex and the cerebellum. The decrease in the right posterior medial temporal lobe was maximal in the parahippocampal gyrus, a region associated with successful verbal memory retrieval. Cortisone administration also significantly impaired cued recall of word pairs learned 24 h earlier, while drug effects on performance in the other tasks (verbal recognition, semantic generation and categorization) were not significant. The present results provide further evidence that acutely elevated glucocorticoid levels can impair declarative memory retrieval processes and suggest that such impairments may be related to a disturbance of medial temporal lobe function.     

Neural bases of learning and memory: functional neuroimaging evidence

Positron emission tomography and functional magnetic resonance imaging studies have identified brain regions associated with different forms of memory. Working memory has been associated primarily with the bilateral prefrontal and parietal regions; semantic memory with the left prefrontal and temporal regions; episodic memory encoding with the left prefrontal and medial temporal regions; episodic memory retrieval with the right prefrontal, posterior midline and medial temporal regions; and skill learning with the motor, parietal, and subcortical regions. Recent studies have provided higher specificity, by dissociating the neural correlates of different subcomponents of complex memory tasks, and the cognitive roles of different subregions of larger brain areas.     

The neural mechanism of declarative memory consolidation and retrieval: a hypothesis

This paper proposes a new theory addressing the neural mechanism of declarative memory consolidation and retrieval. The premise of the theory is that the cortex is responsible for the storage of declarative memory while the medial temporal lobe is responsible for the consolidation and retrieval of declarative memory. The theory suggests that the medial temporal lobe can only accomplish its functions related to memory by hierarchically and cooperatively regulating the descending limbic system, including the hypothalamus, epithalamus, septum, mammillary bodies and the bed nucleus of the stria terminalis. These descending limbic structures, together with the amygdala, further send efferents to the four ascending NA, 5-HT, DA and ACh systems. It is these four ascending extrathalamic regulatory systems that provide the feedback neural pathways to the cortex and regulate the processes of memory consolidation and retrieval in the cortex. Therefore, the coupling of these descending limbic structures to the ascending NA, 5-HT, DA and ACh systems completes the neural circuits responsible for the consolidation and retrieval of new declarative memories. This neural mechanism of declarative memory consolidation and retrieval is universal to all species in higher mammals.     

Associations evoked during memory encoding recruit the context-network

An extensive cortical network consisting of structures in the medial temporal lobe (hippocampus and parahippocampal cortex), lateral parietal cortex, retrosplenial cortex, and medial prefrontal cortex has recently attracted attention in cognitive neuroscience research, linking the network to both episodic memory and spatial processing. It has been suggested that its function may be best characterized as supporting the processing of contextual associations (context network). In this study, we explored whether the role of this network in contextual processing extends to associations that are evoked in a spontaneous manner. In a novel memory encoding task, participants indicated whether they encoded pictures (objects and novel faces) based on an evoked association or based on a perceptual feature. Memory encoding with subjective associations enhanced memory formation relative to feature-based encoding, and this effect was more pronounced for rapidly evoked associations. Functional magnetic resonance imaging during encoding yielded significant activations in all regions of the context network, i.e., medial prefrontal cortex, lateral parietal cortex, retrosplenial cortex, and posterior medial temporal lobe for the associative vs. feature-based comparisons. The low number of misses did not permit the analysis of a subsequent memory contrast. Our data suggest that the context network, which includes the posterior hippocampus and parahippocampal cortex, might support the linkage of external stimuli to long-term memory representations.     

Human declarative memory formation: segregating rhinal and hippocampal contributions

The medial temporal lobe (MTL) is the core structure of the declarative memory system, but which specific operation is performed by anatomically defined MTL substructures? One hypothesis proposes that the hippocampus carries out an exclusively mnemonic operation during declarative memory formation that is insensitive to content, whereas the rhinal cortex carries out an operation supporting memory formation indirectly. To explore the interaction between a salient item feature and memory formation, we contrasted neural correlates of memory formation of high‐ and low‐frequency words. Event‐related potentials (ERPs) were recorded via depth electrodes from within the MTL in nine epilepsy patients while they memorized single words. To assess memory formation, ERPs to words subsequently recalled in a free recall test were contrasted with ERPs to forgotten words. More high‐ than low‐frequency words were remembered. High‐frequency words led to distinct ERP subsequent memory effects in rhinal cortex and hippocampus. Low‐frequency words, however, were only associated with the hippocampal ERP effect. The anatomically restricted interaction between word frequency and memory formation might indicate a semantically affected operation in the parahippocampal region supporting memory formation indirectly. By contrast, the missing interaction in hippocampal recordings might suggest a direct correlate of declarative memory formation that is insensitive to item properties. Hippocampus 2002;12:514–519. © 2002 Wiley‐Liss, Inc.     

Prefrontal-temporal circuitry for episodic encoding and subsequent memory.

Humans encounter and form memories for multiple types of experiences that differ in content, novelty, and memorability. Critical for understanding memory is determining (1) how the brain supports the encoding of events with differing content and (2) whether neural regions that are sensitive to novelty also influence whether stimuli will be subsequently remembered. This event-related functional magnetic resonance imaging (fMRI) study crossed content (picture/word), novelty (novel/repeated), and subsequent memory (remembered/forgotten) to examine prefrontal and temporal lobe contributions to encoding. Results revealed three patterns of encoding-related activation in anatomically connected inferior prefrontal and lateral temporal structures that appeared to vary depending on whether visuospatial/visuo-object, phonological/lexical, or semantic attributes were processed. Event content also modulated medial temporal lobe activity; word encoding predominantly activated the left hemisphere, whereas picture encoding activated both hemispheres. Critically, in prefrontal and temporal regions that were modulated by novelty, the magnitude of encoding activation also predicted whether an event would be subsequently remembered. These results suggest that (1) regions that demonstrate a sensitivity to novelty may actively support encoding processes that impact subsequent explicit memory and (2) multiple content-dependent prefrontal-temporal circuits support event encoding. The similarities between prefrontal and lateral temporal encoding responses raise the possibility that prefrontal modulation of posterior cortical representations is central to encoding.     

Intrinsic functional connectivity in the default mode network predicts mnemonic discrimination: A connectome-based modeling approach

The ability to distinguish existing memories from similar perceptual experiences is a core feature of episodic memory. This ability is often examined using the mnemonic similarity task in which people discriminate memories of studied objects from perceptually similar lures. Studies of the neural basis of such mnemonic discrimination have mostly focused on hippocampal function and connectivity. However, default mode network (DMN) connectivity may also support such discrimination, given that the DMN includes the hippocampus, and its connectivity supports many aspects of episodic memory. Here, we used connectome-based predictive modeling to identify associations between intrinsic DMN connectivity and mnemonic discrimination. We leveraged a wide range of abilities across healthy younger and older adults to facilitate this predictive approach. Resting-state functional connectivity in the DMN predicted mnemonic discrimination outside the MRI scanner, especially among prefrontal and temporal regions and including several hippocampal regions. This predictive relationship was stronger for younger than older adults, primarily for temporal–prefrontal connectivity. The novel associations established here are consistent with mounting evidence that broader cortical networks including the hippocampus support mnemonic discrimination. They also suggest that age-related network disruptions undermine the extent that the DMN supports this ability. This study provides the first indication of how intrinsic functional properties of the DMN support mnemonic discrimination.     

Gender differences in the functional neuroanatomy of emotional episodic autobiographical memory

Autobiographical memory is based on interactions between episodic memory contents, associated emotions, and a sense of self-continuity along the time axis of one's life. The functional neuroanatomy subserving autobiographical memory is known to include prefrontal, medial and lateral temporal, as well as retrosplenial brain areas; however, whether gender differences exist in neural correlates of autobiographical memory remains to be clarified. We reanalyzed data from a previous functional magnetic resonance imaging (fMRI) experiment to investigate gender-related differences in the neural bases of autobiographical memories with differential remoteness and emotional valence. On the behavioral level, there were no significant gender differences in memory performance or emotional intensity of memories. Activations common to males and females during autobiographical memory retrieval were observed in a bilateral network of brain areas comprising medial and lateral temporal regions, including hippocampal and parahippocampal structures, posterior cingulate, as well as prefrontal cortex. In males (relative to females), all types of autobiographical memories investigated were associated with differential activation of the left parahippocampal gyrus. By contrast, right dorsolateral prefrontal cortex was activated differentially by females. In addition, the right insula was activated differentially in females during remote and negative memory retrieval. The data show gender-related differential neural activations within the network subserving autobiographical memory in both genders. We suggest that the differential activations may reflect gender-specific cognitive strategies during access to autobiographical memories that do not necessarily affect the behavioral level of memory performance and emotionality.     

The contribution of different prefrontal cortex regions to recollection and familiarity: a review of fMRI data

Dual-process theories of recognition memory sustain that recollection and familiarity reflect different mnemonic processes and rely on separate neural substrates that are located primarily in the medial temporal lobe (MTL). Aggleton and Brown’s model (1999) assumes that this distinction extends to other brain regions, including the thalamus, and that both recognition memory processes interact with the prefrontal cortex (PFC). Nevertheless, it is still unclear whether recollection and familiarity are subtended by separate prefrontal regions. Here we provided a review of the literature that first focused on functional magnetic resonance imaging studies that adopted the Remember/Know method and reported recollection- and familiarity-based activity in the PFC. There is evidence that functional activations are differently located within the lateral (i.e., along the dorso-ventral axis), medial (i.e., along the rostro-caudal axis) and anterior (i.e., along the medio-lateral axis) prefrontal surfaces according to whether they are recollection- or familiarity-related. Overall, the findings we summarise suggest that recollection and familiarity are qualitatively different processes and rely on distinct neural pathways even outside the MTL.     

Differential neural activity during search of specific and general autobiographical memories elicited by musical cues

Previous neuroimaging studies that have examined autobiographical memory specificity have utilized retrieval cues associated with prior searches of the event, potentially changing the retrieval processes being investigated. In the current study, musical cues were used to naturally elicit memories from multiple levels of specificity (i.e., lifetime period, general event, and event-specific). Sixteen young adults participated in a neuroimaging study in which they retrieved autobiographical memories associated with musical cues. These musical cues led to the retrieval of highly emotional memories that had low levels of prior retrieval. Retrieval of all autobiographical memory levels was associated with activity in regions in the autobiographical memory network, specifically the ventromedial prefrontal cortex, posterior cingulate, and right medial temporal lobe. Owing to the use of music, memories from varying levels of specificity were retrieved, allowing for comparison of event memory and abstract personal knowledge, as well as comparison of specific and general event memory. Dorsolateral and dorsomedial prefrontal regions were engaged during event retrieval relative to personal knowledge retrieval, and retrieval of specific event memories was associated with increased activity in the bilateral medial temporal lobe and dorsomedial prefrontal cortex relative to retrieval of general event memories. These results suggest that the initial search processes for memories of different specificity levels preferentially engage different components of the autobiographical memory network. The potential underlying causes of these neural differences are discussed.     

Medial temporal and prefrontal contributions to working memory tasks with novel and familiar stimuli.

Lesions of parahippocampal structures impair performance of delayed matching tasks in nonhuman primates, suggesting a role for these structures in the maintenance of items in working memory and short-term stimulus matching. However, most human functional imaging studies have not shown medial temporal activation during working memory tasks and have primarily focused on functional magnetic resonance imaging (fMRI) signal intensity changes in the prefrontal and posterior parietal cortex. The goal of this study was to test the hypothesis that the difference between the human and nonhuman primate data results from the use of highly familiar stimuli in human working memory studies and trial-unique stimuli in nonhuman primate studies. We used fMRI to examine prefrontal and temporal lobe activation during performance of a working memory (two-back) task, using blocks of novel and highly familiar complex pictures. Performance of the working memory task with novel complex pictures resulted in greater signal change within medial temporal lobe structures than performance of the task with familiar complex pictures. In contrast, the working memory task with highly familiar stimuli resulted in greater prefrontal activation. These results are consistent without hypothesis that the medial temporal lobe is recruited for the short-term maintenance of information that has no prior representation in the brain, whereas the prefrontal cortex is important for monitoring familiar stimuli that have a high degree of interference. A second set of tasks examined stimulus matching. Subjects performed a target-matching task, during which they identified a single target presented in blocks of novel or familiar stimuli. The results provide evidence of hippocampal and parahippocampal recruitment in the target-matching task with familiar stimuli. These results are consistent with prior animal studies and suggest that prefrontal regions may be important for the monitoring and matching of familiar stimuli which have a high potential for interference, whereas medial temporal regions may become proportionally more important for matching and maintenance of novel stimuli.     

Intersection of reward and memory in monkey rhinal cortex

In humans and other animals, the vigor with which a reward is pursued depends on its desirability, that is, on the reward's predicted value. Predicted value is generally context-dependent, varying according to the value of rewards obtained in the recent and distant past. Signals related to reward prediction and valuation are believed to be encoded in a circuit centered around midbrain dopamine neurons and their targets in the prefrontal cortex and basal ganglia. Notably absent from this hypothesized reward pathway are dopaminergic targets in the medial temporal lobe. Here we show that a key part of the medial temporal lobe memory system previously reported to be important for sensory mnemonic and perceptual processing, the rhinal cortex (Rh), is required for using memories of previous reward values to predict the value of forthcoming rewards. We tested monkeys with bilateral Rh lesions on a task in which reward size varied across blocks of uncued trials. In this experiment, the only cues for predicting current reward value are the sizes of rewards delivered in previous blocks. Unexpectedly, monkeys with Rh ablations, but not intact controls, were insensitive to differences in predicted reward, responding as if they expected all rewards to be of equal magnitude. Thus, it appears that Rh is critical for using memory of previous rewards to predict the value of forthcoming rewards. These results are in agreement with accumulating evidence that Rh is critical for establishing the relationships between temporally interleaved events, which is a key element of episodic memory.     

fMRI studies of successful emotional memory encoding: A quantitative meta-analysis

Over the past decade, fMRI techniques have been increasingly used to interrogate the neural correlates of successful emotional memory encoding. These investigations have typically aimed to either characterize the contributions of the amygdala and medial temporal lobe (MTL) memory system, replicating results in animals, or delineate the neural correlates of specific behavioral phenomena. It has remained difficult, however, to synthesize these findings into a systems neuroscience account of how networks across the whole-brain support the enhancing effects of emotion on memory encoding. To this end, the present study employed a meta-analytic approach using activation likelihood estimates to assess the anatomical specificity and reliability of event-related fMRI activations related to successful memory encoding for emotional versus neutral information. The meta-analysis revealed consistent clusters within bilateral amygdala, anterior hippocampus, anterior and posterior parahippocampal gyrus, the ventral visual stream, left lateral prefrontal cortex and right ventral parietal cortex. The results within the amygdala and MTL support a wealth of findings from the animal literature linking these regions to arousal-mediated memory effects. The consistency of findings in cortical targets, including the visual, prefrontal, and parietal cortices, underscores the importance of generating hypotheses regarding their participation in emotional memory formation. In particular, we propose that the amygdala interacts with these structures to promote enhancements in perceptual processing, semantic elaboration, and attention, which serve to benefit subsequent memory for emotional material. These findings may motivate future research on emotional modulation of widespread neural systems and the implications of this modulation for cognition.