The neural basis of episodic memory: evidence from functional neuroimaging

We review some of our recent research using functional neuroimaging to investigate neural activity supporting the encoding and retrieval of episodic memories, that is, memories for unique events. Findings from studies of encoding indicate that, at the cortical level, the regions responsible for the effective encoding of a stimulus event as an episodic memory include some of the regions that are also engaged to process the event 'online'. Thus, it appears that there is no single cortical site or circuit responsible for episodic encoding. The results of retrieval studies indicate that successful recollection of episodic information is associated with activation of lateral parietal cortex, along with more variable patterns of activity in dorsolateral and anterior prefrontal cortex. Whereas parietal regions may play a part in the representation of retrieved information, prefrontal areas appear to support processes that act on the products of retrieval to align behaviour with the demands of the retrieval task.     

Continuous Theta Burst Stimulation of Angular Gyrus Reduces Subjective Recollection

The contribution of lateral parietal regions such as the angular gyrus to human episodic memory has been the subject of much debate following widespread observations of left parietal activity in healthy volunteers during functional neuroimaging studies of memory retrieval. Patients with lateral parietal lesions are not amnesic, but recent evidence indicates that their memory abilities may not be entirely preserved. Whereas recollection appears intact when objective measures such as source accuracy are used, patients often exhibit reduced subjective confidence in their accurate recollections. When asked to recall autobiographical memories, they may produce spontaneous narratives that lack richness and specificity, but can remember specific details when prompted. Two distinct theoretical accounts have been proposed to explain these results: that the patients have a deficit in the bottom-up capturing of attention by retrieval output, or that they have an impairment in the subjective experience of recollection. The present study aimed to differentiate between these accounts using continuous theta burst stimulation (cTBS) in healthy participants to disrupt function of specific left parietal subregions, including angular gyrus. Inconsistent with predictions of the attentional theory, angular gyrus cTBS did not result in greater impairment of free recall than cued recall. Supporting predictions of the subjective recollection account, temporary disruption of angular gyrus was associated with highly accurate source recollection accuracy but a selective reduction in participants’ rated source confidence. The findings are consistent with a role for angular gyrus in the integration of memory features into a conscious representation that enables the subjective experience of remembering.     

Autobiographical Thinking Interferes with Episodic Memory Consolidation

New episodic memories are retained better if learning is followed by a few minutes of wakeful rest than by the encoding of novel external information. Novel encoding is said to interfere with the consolidation of recently acquired episodic memories. Here we report four experiments in which we examined whether autobiographical thinking, i.e. an ‘internal’ memory activity, also interferes with episodic memory consolidation. Participants were presented with three wordlists consisting of common nouns; one list was followed by wakeful rest, one by novel picture encoding and one by autobiographical retrieval/future imagination, cued by concrete sounds. Both novel encoding and autobiographical retrieval/future imagination lowered wordlist retention significantly. Follow-up experiments demonstrated that the interference by our cued autobiographical retrieval/future imagination delay condition could not be accounted for by the sound cues alone or by executive retrieval processes. Moreover, our results demonstrated evidence of a temporal gradient of interference across experiments. Thus, we propose that rich autobiographical retrieval/future imagination hampers the consolidation of recently acquired episodic memories and that such interference is particularly likely in the presence of external concrete cues.     

Bridging consciousness and cognition in memory and perception: evidence for both state and strength processes

Subjective experience indicates that mental states are discrete, in the sense that memories and perceptions readily come to mind in some cases, but are entirely unavailable to awareness in others. However, a long history of psychophysical research has indicated that the discrete nature of mental states is largely epiphenomenal and that mental processes vary continuously in strength. We used a novel combination of behavioral methodologies to examine the processes underlying perception of complex images: (1) analysis of receiver operating characteristics (ROCs), (2) a modification of the change-detection flicker paradigm, and (3) subjective reports of conscious experience. These methods yielded converging results showing that perceptual judgments reflect the combined, yet functionally independent, contributions of two processes available to conscious experience: a state process of conscious perception and a strength process of knowing; processes that correspond to recollection and familiarity in long-term memory. In addition, insights from the perception experiments led to the discovery of a new recollection phenomenon in a long-term memory change detection paradigm. The apparent incompatibility between subjective experience and theories of cognition can be understood within a unified state-strength framework that links consciousness to cognition across the domains of perception and memory.     

Hippocampus Is Place of Interaction between Unconscious and Conscious Memories

Recent evidence suggests that humans can form and later retrieve new semantic relations unconsciously by way of hippocampus—the key structure also recruited for conscious relational (episodic) memory. If the hippocampus subserves both conscious and unconscious relational encoding/retrieval, one would expect the hippocampus to be place of unconscious-conscious interactions during memory retrieval. We tested this hypothesis in an fMRI experiment probing the interaction between the unconscious and conscious retrieval of face-associated information. For the establishment of unconscious relational memories, we presented subliminal (masked) combinations of unfamiliar faces and written occupations (“actor” or “politician”). At test, we presented the former subliminal faces, but now supraliminally, as cues for the reactivation of the unconsciously associated occupations. We hypothesized that unconscious reactivation of the associated occupation—actor or politician—would facilitate or inhibit the subsequent conscious retrieval of a celebrity’s occupation, which was also actor or politician. Depending on whether the reactivated unconscious occupation was congruent or incongruent to the celebrity’s occupation, we expected either quicker or delayed conscious retrieval process. Conscious retrieval was quicker in the congruent relative to a neutral baseline condition but not delayed in the incongruent condition. fMRI data collected during subliminal face-occupation encoding confirmed previous evidence that the hippocampus was interacting with neocortical storage sites of semantic knowledge to support relational encoding. fMRI data collected at test revealed that the facilitated conscious retrieval was paralleled by deactivations in the hippocampus and neocortical storage sites of semantic knowledge. We assume that the unconscious reactivation has pre-activated overlapping relational representations in the hippocampus reducing the neural effort for conscious retrieval. This finding supports the notion of synergistic interactions between conscious and unconscious relational memories in a common, cohesive hippocampal-neocortical memory space.     

Memory for events and their spatial context: models and experiments

The computational role of the hippocampus in memory has been characterized as: (i) an index to disparate neocortical storage sites; (ii) a time-limited store supporting neocortical long-term memory; and (iii) a content-addressable associative memory. These ideas are reviewed and related to several general aspects of episodic memory, including the differences between episodic, recognition and semantic memory, and whether hippocampal lesions differentially affect recent or remote memories. Some outstanding questions remain, such as: what characterizes episodic retrieval as opposed to other forms of read-out from memory; what triggers the storage of an event memory; and what are the neural mechanisms involved? To address these questions a neural-level model of the medial temporal and parietal roles in retrieval of the spatial context of an event is presented. This model combines the idea that retrieval of the rich context of real-life events is a central characteristic of episodic memory, and the idea that medial temporal allocentric representations are used in long-term storage while parietal egocentric representations are used to imagine, manipulate and re-experience the products of retrieval. The model is consistent with the known neural representation of spatial information in the brain, and provides an explanation for the involvement of Papez''s circuit in both the representation of heading direction and in the recollection of episodic information. Two experiments relating to the model are briefly described. A functional neuroimaging study of memory for the spatial context of life-like events in virtual reality provides support for the model''s functional localization. A neuropsychological experiment suggests that the hippocampus does store an allocentric representation of spatial locations.     

Key Features of Human Episodic Recollection in the Cross-Episode Retrieval of Rat Hippocampus Representations of Space

Neurophysiological studies focus on memory retrieval as a reproduction of what was experienced and have established that neural discharge is replayed to express memory. However, cognitive psychology has established that recollection is not a verbatim replay of stored information. Recollection is constructive, the product of memory retrieval cues, the information stored in memory, and the subject''s state of mind. We discovered key features of constructive recollection embedded in the rat CA1 ensemble discharge during an active avoidance task. Rats learned two task variants, one with the arena stable, the other with it rotating; each variant defined a distinct behavioral episode. During the rotating episode, the ensemble discharge of CA1 principal neurons was dynamically organized to concurrently represent space in two distinct codes. The code for spatial reference frame switched rapidly between representing the rat''s current location in either the stationary spatial frame of the room or the rotating frame of the arena. The code for task variant switched less frequently between a representation of the current rotating episode and the stable episode from the rat''s past. The characteristics and interplay of these two hippocampal codes revealed three key properties of constructive recollection. (1) Although the ensemble representations of the stable and rotating episodes were distinct, ensemble discharge during rotation occasionally resembled the stable condition, demonstrating cross-episode retrieval of the representation of the remote, stable episode. (2) This cross-episode retrieval at the level of the code for task variant was more likely when the rotating arena was about to match its orientation in the stable episode. (3) The likelihood of cross-episode retrieval was influenced by preretrieval information that was signaled at the level of the code for spatial reference frame. Thus key features of episodic recollection manifest in rat hippocampal representations of space.     

Elements of episodic-like memory in animal models

Representations of unique events from one’s past constitute the content of episodic memories. A number of studies with non-human animals have revealed that animals remember specific episodes from their past (referred to as episodic-like memory). The development of animal models of memory holds enormous potential for gaining insight into the biological bases of human memory. Specifically, given the extensive knowledge of the rodent brain, the development of rodent models of episodic memory would open new opportunities to explore the neuroanatomical, neurochemical, neurophysiological, and molecular mechanisms of memory. Development of such animal models holds enormous potential for studying functional changes in episodic memory in animal models of Alzheimer’s disease, amnesia, and other human memory pathologies. This article reviews several approaches that have been used to assess episodic-like memory in animals. The approaches reviewed include the discrimination of what, where, and when in a radial arm maze, dissociation of recollection and familiarity, object recognition, binding, unexpected questions, and anticipation of a reproductive state. The diversity of approaches may promote the development of converging lines of evidence on the difficult problem of assessing episodic-like memory in animals.     

Retrieval Intention Modulates the Effects of Directed Forgetting Instructions on Recollection

The neurocognitive basis of memory retrieval is often examined by investigating brain potential old/new effects, which are differences in brain activity between successfully remembered repeated stimuli and correctly rejected new stimuli in a recognition test. In this study, we combined analyses of old/new effects for words with an item-method directed-forgetting manipulation in order to isolate differences between the retrieval processes elicited by words that participants were initially instructed to commit to memory and those that participants were initially instructed to forget. We compared old/new effects elicited by to-be-forgotten (TBF) words with those elicited by to-be-remembered (TBR) words in both an explicit-memory test (a recognition test) and an implicit-memory test (a lexical-decision test). Behavioral results showed clear directed forgetting effects in the recognition test, but not in the lexical decision test. Mirroring the behavioral findings, analyses of brain potentials showed evidence of directed forgetting only in the recognition test. In this test, potentials from 450–650 ms (P600 old/new effects) were more positive for TBR relative to TBF words. By contrast, P600 effects evident during the lexical-decision test did not differ in magnitude between TBR and TBF items. When taken in the context of prior studies that have linked similar parietal old/new effects to the recollection of episodic information, these data suggest that directed-forgetting effects manifest primarily in greater episodic retrieval by TBR than TBF items, and that retrieval intention may be important for these directed-forgetting effects to occur.     

Breast cancer affects both the hippocampus volume and the episodic autobiographical memory retrieval

Background

Neuroimaging studies show the hippocampus is a crucial node in the neural network supporting episodic autobiographical memory retrieval. Stress-related psychiatric disorders, namely Major Depression and Post Traumatic Stress Disorder (PTSD), are related to reduced hippocampus volume. However, this is not the case for remitted breast cancer patients with co-morbid stress-related psychiatric disorders. This exception may be due to the fact that, consequently to the cancer experience as such, this population might already be characterized by a reduced hippocampus with an episodic autobiographical memory deficit.

Methodology

We scanned, with a 3T Siemens TRIO, 16 patients who had lived through a “standard experience of breast cancer” (breast cancer and a standard treatment in remission since 18 month) in the absence of any associated stress-related psychiatric or neurological disorder and 21 matched controls. We then assessed their episodic autobiographical memory retrieval ability.

Principal Findings

Remitted breast cancer patients had both a significantly smaller hippocampus and a significant deficit in episodic autobiographical memory retrieval. The hippocampus atrophy was characterized by a smaller posterior hippocampus. The posterior hippocampus volume was intimately related to the ability to retrieve negative memories and to the past experience of breast cancer or not.

Conclusions/Significance

These results provide two main findings: (1) we identify a new population with a specific reduction in posterior hippocampus volume that is independent of any psychiatric or neurological pathology; (2) we show the intimate relation of the posterior hippocampus to the ability to retrieve episodic autobiographical memories. These are significant findings as it is the first demonstration that indicates considerable long-term effects of living through the experience of breast cancer and shows very specific hippocampal atrophy with a functional deficit without any presence of psychiatric pathology.     

Functional neuroanatomy of the autobiographical memory

Autobiographical memory refers to events and information about personal life and the self. Within autobiographical memory, many authors make a difference between episodic and semantic components. Study of retrograde amnesia gives information about memory consolidation. According to the "standard model" of consolidation, the medial temporal lobe plays a time-limited role in retrieval memory. Functional neuroanatomy studies of autobiographical memory are very few and many are recent. These studies concern which brain regions are involved in the autobiographical retrieval, episodic or semantic autobiographical memory and consolidation process. Results show that autobiographical retrieval depends on specific brain regions like frontal cortex. Concerning memory consolidation, findings are most consistent with the idea that hippocampal complex is involved in both recent and remote memories.     

The Hippocampus Remains Activated over the Long Term for the Retrieval of Truly Episodic Memories

The role of the hippocampus in declarative memory consolidation is a matter of intense debate. We investigated the neural substrates of memory retrieval for recent and remote information using functional magnetic resonance imaging (fMRI). 18 young, healthy participants learned a series of pictures. Then, during two fMRI recognition sessions, 3 days and 3 months later, they had to determine whether they recognized or not each picture using the "Remember/Know" procedure. Presentation of the same learned images at both delays allowed us to track the evolution of memories and distinguish consistently episodic memories from those that were initially episodic and then became familiar or semantic over time and were retrieved without any contextual detail. Hippocampal activation decreased over time for initially episodic, later semantic memories, but remained stable for consistently episodic ones, at least in its posterior part. For both types of memories, neocortical activations were observed at both delays, notably in the ventromedial prefrontal and anterior cingulate cortices. These activations may reflect a gradual reorganization of memory traces within neural networks. Our data indicate maintenance and strengthening of hippocampal and cortico-cortical connections in the consolidation and retrieval of episodic memories over time, in line with the Multiple Trace theory (Nadel and Moscovitch, 1997). At variance, memories becoming semantic over time consolidate through strengthening of cortico-cortical connections and progressive disengagement of the hippocampus.     

Effects of the BDNF Val66Met Polymorphism and Met Allele Load on Declarative Memory Related Neural Networks

It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including an investigation of the effect of met allele load on memory related activation in the medial temporal lobe. In contrast to previous studies, we found no evidence for an effect of BDNF genotype or met load during episodic memory encoding. Met allele carriers showed increased activation during successful retrieval in right hippocampus but this was contrast-specific and unaffected by met allele load. These results suggest that the BDNF Val66Met polymorphism does not, as previously claimed, exert an observable effect on neural systems underlying encoding of new information into episodic memory but may exert a subtle effect on the efficiency with which such information can be retrieved.     

A Neural Network Model for K(λ) Retrieval and Application to Global K par Monitoring

Accurate estimation of diffuse attenuation coefficients in the visible wavelengths K _d(λ) from remotely sensed data is particularly challenging in global oceanic and coastal waters. The objectives of the present study are to evaluate the applicability of a semi-analytical K _d(λ) retrieval model (SAKM) and Jamet’s neural network model (JNNM), and then develop a new neural network K _d(λ) retrieval model (NNKM). Based on the comparison of K _d(λ) predicted by these models with in situ measurements taken from the global oceanic and coastal waters, all of the NNKM, SAKM, and JNNM models work well in K _d(λ) retrievals, but the NNKM model works more stable and accurate than both SAKM and JNNM models. The near-infrared band-based and shortwave infrared band-based combined model is used to remove the atmospheric effects on MODIS data. The K _d(λ) data was determined from the atmospheric corrected MODIS data using the NNKM, JNNM, and SAKM models. The results show that the NNKM model produces <30% uncertainty in deriving K _d(λ) from global oceanic and coastal waters, which is 4.88-17.18% more accurate than SAKM and JNNM models. Furthermore, we employ an empirical approach to calculate K _par from the NNKM model-derived diffuse attenuation coefficient at visible bands (443, 488, 555, and 667 nm). The results show that our model presents a satisfactory performance in deriving K _par from the global oceanic and coastal waters with 20.2% uncertainty. The K _par are quantified from MODIS data atmospheric correction using our model. Comparing with field measurements, our model produces ~31.0% uncertainty in deriving K _par from Bohai Sea. Finally, the applicability of our model for general oceanographic studies is briefly illuminated by applying it to climatological monthly mean remote sensing reflectance for time ranging from July, 2002- July 2014 at the global scale. The results indicate that the high K _d(λ) and K _par values are usually found around the coastal zones in the high latitude regions, while low K _d(λ) and K _par values are usually found in the open oceans around the low-latitude regions. These results could improve our knowledge about the light field under waters at either the global or basin scales, and be potentially used into general circulation models to estimate the heat flux between atmosphere and ocean.     

The cognitive neuroscience of remote episodic, semantic and spatial memory

The processes and mechanisms implicated in retention and retrieval of memories as they age is an enduring problem in cognitive neuroscience. Research from lesion and functional neuroimaging studies on remote episodic, semantic and spatial memory in humans is crucial for evaluating three theories of hippocampal and/or medial temporal lobe-neocortical interaction in memory retention and retrieval: cognitive map theory, standard consolidation theory and multiple trace theory. Each theory makes different predictions regarding first, the severity and extent of retrograde amnesia following lesions to some or all of the structures mentioned; second, the extent of activation of these structures to retrieval of memory across time; and third, the type of memory being retrieved. Each of these theories has strengths and weaknesses, and there are various unresolved issues. We propose a unified account based on multiple trace theory. This theory states that the hippocampus is needed for re-experiencing detailed episodic and spatial memories no matter how old they are, and that it contributes to the formation and assimilation of semantic memories and schematic spatial maps.     

Episodic memory and autonoetic consciousness: a first-person approach

Episodic memory is identified with autonoetic consciousness, which gives rise to remembering in the sense of self-recollection in the mental re-enactment of previous events at which one was present. Autonoetic consciousness is distinguished from noetic consciousness, which gives rise to awareness of the past that is limited to feelings of familiarity or knowing. Noetic consciousness is identified not with episodic but with semantic memory, which involves general knowledge. A recently developed approach to episodic memory makes use of 'first-person' reports of remembering and knowing. Studies using this approach have revealed many independent variables that selectively affect remembering and others that selectively affect knowing. These studies can also be interpreted in terms of distinctiveness and fluency of processing. Remembering and knowing do not correspond with degrees of confidence in memory. Nor does remembering always control the memory response. There is evidence that remembering is selectively impaired in various populations, including not only amnesic patients and older adults but also adults with Asperger's syndrome. This first-person approach to episodic memory represents one way in which that most elusive aspect of consciousness, its subjectivity, can be investigated scientifically. The two kinds of conscious experiences can be manipulated experimentally in ways that are systematic, replicable and intelligible theoretically.     

Episodic memory in nonhumans: what, and where, is when?

Episodic memory is defined as the recollection of specific events in one's past, accompanied by the experience of having been there personally. This definition presents high hurdles to the investigation of episodic memory in nonhumans. Recent studies operationalize episodic memory as memory for when and where an event occurred, for the order in which events occurred, or for an animal's own behavior. None of these approaches has yet generalized across species, and each fails to capture features of human episodic memory. Nonetheless, the study of episodic memory in nonhumans seems less daunting than it did five years ago. To demonstrate a correspondence between human episodic memory and nonhuman memory, progress is needed in three areas. Putative episodic memories in nonhumans should be shown to be; first, represented in long-term memory, rather than short-term or working memory; second, explicit, or accessible to introspection; and third, distinct from semantic memory, or general knowledge about the world.     

Stimulation of the left dorsolateral prefrontal cortex with slow rTMS enhances verbal memory formation

Encoding of episodic memories relies on stimulus-specific information processing and involves the left prefrontal cortex. We here present an incidental finding from a simultaneous EEG-TMS experiment as well as a replication of this unexpected effect. Our results reveal that stimulating the left dorsolateral prefrontal cortex (DLPFC) with slow repetitive transcranial magnetic stimulation (rTMS) leads to enhanced word memory performance. A total of 40 healthy human participants engaged in a list learning paradigm. Half of the participants (N = 20) received 1 Hz rTMS to the left DLPFC, while the other half (N = 20) received 1 Hz rTMS to the vertex and served as a control group. Participants receiving left DLPFC stimulation demonstrated enhanced memory performance compared to the control group. This effect was replicated in a within-subjects experiment where 24 participants received 1 Hz rTMS to the left DLPFC and vertex. In this second experiment, DLPFC stimulation also induced better memory performance compared to vertex stimulation. In addition to these behavioural effects, we found that 1 Hz rTMS to DLPFC induced stronger beta power modulation in posterior areas, a state that is known to be beneficial for memory encoding. Further analysis indicated that beta modulations did not have an oscillatory origin. Instead, the observed beta modulations were a result of a spectral tilt, suggesting inhibition of these parietal regions. These results show that applying 1 Hz rTMS to DLPFC, an area involved in episodic memory formation, improves memory performance via modulating neural activity in parietal regions.

Encoding of episodic memories relies on stimulus-specific information processing and involves the left prefrontal cortex. An incidental finding from a simultaneous EEG-TMS experiment reveals that applying 1-Hz repetitive transcranial magnetic stimulation to this area of the brain improves memory performance by modulating neural activity in parietal regions.     

PRKCA Polymorphism Changes the Neural Basis of Episodic Remembering in Healthy Individuals

Everyday functioning relies on episodic memory, the conscious retrieval of past experiences, but this crucial cognitive ability declines severely with aging and disease. Vulnerability to memory decline varies across individuals however, producing differences in the time course and severity of memory problems that complicate attempts at diagnosis and treatment. Here we identify a key source of variability, by examining gene dependent changes in the neural basis of episodic remembering in healthy adults, targeting seven polymorphisms previously linked to memory. Scalp recorded Event-Related Potentials (ERPs) were measured while participants remembered words, using an item recognition task that requires discrimination between studied and unstudied stimuli. Significant differences were found as a consequence of a Single Nucleotide Polymorphism (SNP) in just one of the tested genes, PRKCA (rs8074995). Participants with the common G/G variant exhibited left parietal old/new effects, which are typically seen in word recognition studies, reflecting recollection-based remembering. During the same stage of memory retrieval participants carrying a rarer A variant exhibited an atypical pattern of brain activity, a topographically dissociable frontally-distributed old/new effect, even though behavioural performance did not differ between groups. Results replicated in a second independent sample of participants. These findings demonstrate that the PRKCA genotype is important in determining how episodic memories are retrieved, opening a new route towards understanding individual differences in memory.