Are semantic and episodic autobiographical memories influenced by the life period remembered? Comparison of young and older adults

Autobiographical memory consists of a person’s personal history and contributes to building a feeling of identity and continuity. Aging affects episodic autobiographical memory negatively, whereas semantic autobiographical memory is preserved or even enhanced in older adults. The study aim was to analyze whether these hypotheses continue to find support, or if there are differences when these memories are analyzed according to the components of life cycle retrieval. The sample was composed of 151 participants: 78 young and 73 older adults. Subjects were evaluated with the Autobiographical Memory Interview. A mixed ANOVA was performed for semantic memory with two groups and three life periods (childhood, youth–adulthood, and recent life). The main group effect was not significant, but the effects of the life period and the life period × group interaction were significant. When analyzing episodic memory, the main effects of the life period and group were significant, but their interaction was not. Young people have better episodic memory than older adults, and they show a similar episodic memory pattern during the three life periods evaluated. The semantic memory of the older adults is preserved, and the reminiscence bump and recent life scores are similar in both groups.     

Neuronal code for extended time in the hippocampus

The time when an event occurs can become part of autobiographical memories. In brain structures that support such memories, a neural code should exist that represents when or how long ago events occurred. Here we describe a neuronal coding mechanism in hippocampus that can be used to represent the recency of an experience over intervals of hours to days. When the same event is repeated after such time periods, the activity patterns of hippocampal CA1 cell populations progressively differ with increasing temporal distances. Coding for space and context is nonetheless preserved. Compared with CA1, the firing patterns of hippocampal CA3 cell populations are highly reproducible, irrespective of the time interval, and thus provide a stable memory code over time. Therefore, the neuronal activity patterns in CA1 but not CA3 include a code that can be used to distinguish between time intervals on an extended scale, consistent with behavioral studies showing that the CA1 area is selectively required for temporal coding over such periods.     

Role of the hippocampus in remembering the past and imagining the future

It has been proposed that a core network of brain regions, including the hippocampus, supports both past remembering and future imagining. We investigated the importance of the hippocampus for these functions. Five patients with bilateral hippocampal damage and one patient with large medial temporal lobe lesions were tested for their ability to recount autobiographical episodes from the remote past, the recent past, and to imagine plausible episodes in the near future. The patients with hippocampal damage had intact remote autobiographical memory, modestly impaired recent memory, and an intact ability to imagine the future. The patient with large medial temporal lobe lesions had intact remote memory, markedly impaired recent memory, and also had an intact ability to imagine the future. The findings suggest that the capacity for imagining the future, like the capacity for remembering the remote past, is independent of the hippocampus.     

Specific responses of human hippocampal neurons are associated with better memory

A population of human hippocampal neurons has shown responses to individual concepts (e.g., Jennifer Aniston) that generalize to different instances of the concept. However, recordings from the rodent hippocampus suggest an important function of these neurons is their ability to discriminate overlapping representations, or pattern separate, a process that may facilitate discrimination of similar events for successful memory. In the current study, we explored whether human hippocampal neurons can also demonstrate the ability to discriminate between overlapping representations and whether this selectivity could be directly related to memory performance. We show that among medial temporal lobe (MTL) neurons, certain populations of neurons are selective for a previously studied (target) image in that they show a significant decrease in firing rate to very similar (lure) images. We found that a greater proportion of these neurons can be found in the hippocampus compared with other MTL regions, and that memory for individual items is correlated to the degree of selectivity of hippocampal neurons responsive to those items. Moreover, a greater proportion of hippocampal neurons showed selective firing for target images in good compared with poor performers, with overall memory performance correlated with hippocampal selectivity. In contrast, selectivity in other MTL regions was not associated with memory performance. These findings show that a substantial proportion of human hippocampal neurons encode specific memories that support the discrimination of overlapping representations. These results also provide previously unidentified evidence consistent with a unique role of the human hippocampus in orthogonalization of representations in declarative memory.A cornerstone of memory is the ability to discriminate among similar events (e.g., remembering where one parked his/her car today as opposed to yesterday). To discriminate and retrieve similar memories effectively, it is necessary to maintain separation of their neural representations. While the entire medial temporal lobe (MTL) is crucial for the formation of new declarative memories for facts and events (1, 2), focal hippocampal lesions can lead to selective deficits in recognition memory whereby discrimination of previously learned items from novel similar items is impaired (3, 4). Consistent with these findings, the hippocampus is thought to orthogonalize or separate overlapping information to support memory specificity (5). Results supporting this idea come from human fMRI studies showing that the blood-oxygenated level dependent (BOLD) signal in the combined area of CA3 and dentate gyrus (CA3DG) of the hippocampus differentiates between old (targets) and novel similar (lure) images (6, 7). However, because the hippocampal BOLD response does not always reflect underlying single neuron activity (8), intracranial recordings from single neurons in humans can be more directly informative. For example, single neurons within the human hippocampus have been found to significantly increase in firing rate to varying photographs of an individual face (e.g., Jennifer Aniston; refs. 9–12), suggesting that hippocampal neurons may participate in concept representations that are not specific to a single stimulus. It is unknown whether a different population of hippocampal neurons exists that are selective for specific stimuli (i.e., a particular photograph of a face) and whether activity in these neurons supports the role of the hippocampus in discrimination of overlapping memory representations.The current study sought to determine whether the neuronal code reflecting the creation of specific memories could be reflected at the single neuron level in humans. With the rare opportunity to work with patients undergoing clinical evaluation for possible surgical therapy, we were able to record human MTL neurons while subjects were engaged in a hippocampal-dependent memory task requiring the discrimination of studied targets from similar unstudied lures. We hypothesized that firing in a population of hippocampal neurons would reflect memory specificity by firing in a selective manner that discriminates previously learned targets from similar lures. We predicted that firing rate increases that were specific to targets would not generalize to similar lures. Given the suggested role of the hippocampus in pattern separation for memory, we predicted that the specificity of hippocampal firing would be related to the participant’s performance on the discrimination task. We further hypothesized that this relationship would be specific to hippocampal neurons, whereas the firing pattern of neurons in other medial temporal lobe regions which we assessed, including the entorhinal cortex, parahippocompal cortex, and amygdala, would not relate to performance on a test of discrimination ability in memory.     

Detailed recollection of remote autobiographical memory after damage to the medial temporal lobe

Previous findings of intact remote autobiographical memory in patients with medial temporal lobe damage have been questioned on the grounds that the narrative recollections were impoverished and fact-like and that the methods were not sufficiently sensitive to detect an impairment. We adopted a newer method, the Autobiographical Interview [Levine B, Svoboda E, Hay JF, Winocur G, Moscovitch M (2002) Psychol Aging 17:677-689], which uses extensive probing to elicit an average of 50 or more details per memory (in contrast to the approximately 20 details per memory elicited with previous methods). We found that autobiographical recollection was impaired in patients with medial temporal lobe damage when memories were drawn from the recent past but fully intact when memories were drawn from the remote past. Impaired remote autobiographical memory, which has sometimes been reported with this and other tests, is likely caused by significant damage outside the medial temporal lobe.     

Two kinds of memory signals in neurons of the human hippocampus

Prior studies of the neural representation of episodic memory in the human hippocampus have identified generic memory signals representing the categorical status of test items (novel vs. repeated), whereas other studies have identified item specific memory signals representing individual test items. Here, we report that both kinds of memory signals can be detected in hippocampal neurons in the same experiment. We recorded single-unit activity from four brain regions (hippocampus, amygdala, anterior cingulate, and prefrontal cortex) of epilepsy patients as they completed a continuous recognition task. The generic signal was found in all four brain regions, whereas the item-specific memory signal was detected only in the hippocampus and reflected sparse coding. That is, for the item-specific signal, each hippocampal neuron responded strongly to a small fraction of repeated words, and each repeated word elicited strong responding in a small fraction of neurons. The neural code was sparse, pattern-separated, and limited to the hippocampus, consistent with longstanding computational models. We suggest that the item-specific episodic memory signal in the hippocampus is fundamental, whereas the more widespread generic memory signal is derivative and is likely used by different areas of the brain to perform memory-related functions that do not require item-specific information.

The hippocampus is essential for the formation of declarative (conscious) memory (1, 2), including both episodic memory (memory for events) and semantic memory (factual knowledge). Episodic memories represent the “what, when, and where” information about remembered events (3). Here, we focus on the neural representation of episodic memory for events, specifically words presented and later repeated in a continuous recognition memory format (4).Bilateral hippocampal lesions result in substantial anterograde amnesia for new events, whether memory is tested by recall or recognition (5). By contrast, bilateral lesions to a more anterior medial temporal lobe structure―the amygdala―have no such effect (6). One might therefore expect to find single-unit activity associated with episodic memory in the hippocampus but not in the amygdala. Yet, the earliest single-neuron studies failed to detect hippocampal neurons that fired differentially to recently presented test items vs. novel items. This was true in studies with humans (7, 8) and monkeys (9–11). One early study with monkeys identified a few such neurons in the hippocampus (12), and other studies found them in areas other than the hippocampus (e.g., inferomedial temporal cortex or inferotemporal temporal cortex) (9–11, 13, 14). Overall, this was not the pattern anticipated from lesion studies.Subsequent studies successfully detected some memory-related neural activity (15–17), observing that ∼10% of hippocampal neurons exhibited differential firing rates based on item status, with some firing more for repeated items and others firing more for novel items. Surprisingly, similar “memory-selective” neurons were also reliably detected in the amygdala at approximately the same frequency. Yet, these memory-selective neurons responded differentially to the generic, categorical status of test items (repeated vs. novel) and thus are not episodic memory signals (i.e., signals representing memory for specific events). According to neurocomputational models dating back to Marr (18), episodic memory representations in the hippocampus are supported by sparse neural codes (19–21). If memories for individual items are sparsely coded in largely nonoverlapping (pattern-separated) neural assemblies, it should be possible to find neurons that respond to particular repeated items, rather than to an item’s generic status. Two recent single-unit studies with humans detected such neurons in the hippocampus, but not in the amygdala (22, 23), apparently reflecting sparsely coded episodic memories. In the present study, we tested 1) whether the generic and the item-specific signals coexist in neural firing patterns recorded during the same memory task, and 2) whether the two kinds of signals are present exclusively in the hippocampus or are also evident in other brain regions.During a continuous recognition memory procedure, neurons were simultaneously recorded from four brain regions: hippocampus, amygdala, anterior cingulate cortex, and prefrontal cortex. Altogether, 55 continuous recognition memory sessions were completed by 34 epilepsy patients who had implanted clinical depth electrodes with microwires measuring single-unit activity (SUA) and multiunit activity bilaterally (24). We limited the present analyses to SUA. Words were presented consecutively and repeated once after varying lags; patients judged each word as either “novel” or “repeated.” Thus, repeated words differed from their earlier presentations as novel words only with respect to their combined “what, when, and where” episodic status (3).     

Sparse and distributed coding of episodic memory in neurons of the human hippocampus

Neurocomputational models hold that sparse distributed coding is the most efficient way for hippocampal neurons to encode episodic memories rapidly. We investigated the representation of episodic memory in hippocampal neurons of nine epilepsy patients undergoing intracranial monitoring as they discriminated between recently studied words (targets) and new words (foils) on a recognition test. On average, single units and multiunits exhibited higher spike counts in response to targets relative to foils, and the size of this effect correlated with behavioral performance. Further analyses of the spike-count distributions revealed that (i) a small percentage of recorded neurons responded to any one target and (ii) a small percentage of targets elicited a strong response in any one neuron. These findings are consistent with the idea that in the human hippocampus episodic memory is supported by a sparse distributed neural code.The hippocampus is known to play a fundamental role in declarative memory (1–4), but it is not known how mnemonic information is coded by the activity of individual hippocampal neurons. At least three different coding schemes have been considered: a localist coding scheme, a fully distributed coding scheme, and a sparse distributed coding scheme (5). In a localist coding scheme, an individual neuron (sometimes referred to as a “grandmother cell”) codes only one memory, and each memory is coded by the activity of only one neuron. In a fully distributed coding scheme, each memory is coded instead by a pattern of activity across many hippocampal neurons. Falling between these two extremes is a sparse distributed coding scheme in which each memory is coded by the activity of a small proportion of hippocampal neurons, and each neuron contributes to the representation of only a few memories. Sparse distributed coding has long been hypothesized to be the most efficient way for hippocampal neurons to encode episodic memories (remembering events) in rapid succession without overwriting previously stored memories (6–8).Most prior work concerned with the coding of declarative memory in the human hippocampus has focused on the neural representation of semantic memories (remembering facts), such as memory for famous people or landmarks (9, 10). The results of these studies suggest that long-established semantic memories may be represented by fewer than 1% of neurons in the hippocampus (11). However, neurocomputational theories are concerned with the representation of episodic memories. The purpose of our study was to test predictions of these neurocomputational theories about how episodic memories are represented by neurons of the hippocampus.The representation of episodic memory in the hippocampus typically has been investigated using recognition procedures. In recognition, the task is to discriminate between familiar items presented earlier in the experimental session (targets) and novel items not previously presented (foils). An episodic memory signal is evident when neurons exhibit different levels of activity for targets (old items) vs. foils (new items). The first recognition studies with humans (12, 13) and monkeys (14–16) failed to detect evidence of episodic memory in neurons of the hippocampus, but more recent studies have identified hippocampal neurons that differentiate targets from foils (17–21). However, these studies did not investigate how the representation of individual targets is distributed across neurons of the hippocampus. Instead, the aim was to find cells that distinguish the class of targets from the class of foils.We investigated the representation of individual targets in neurons of the human hippocampus. The participants were nine patients with pharmaco-resistant epilepsy requiring the implantation of intracranial wire electrodes for clinical evaluation and localization of seizure foci for possible surgical resection. Among them, the patients completed a total of 18 recognition memory tasks in which they first studied 32 words and then attempted to distinguish between the 32 targets that had appeared on the study list and 32 foils that had not. Each of the 64 items on the recognition test was presented only once, a format that differs from many other neurophysiology studies that present individual stimuli multiple times to identify neurons with reliable stimulus-specific firing properties. The multiple-presentation method is well-suited to the study of semantic memory (e.g., a neuron that is found to respond reliably to six presentations of the word “baby” likely is responding to its long-established semantic meaning) but is not well-suited to the study of episodic memory. When targets and foils are presented only once on a recognition test, the targets, but not the foils, are represented by an episodic memory formed earlier at the time of learning. Under these conditions, any difference in neural activity associated with targets and foils would indicate episodic memory. Note that, if the test items were presented again, the targets and foils no longer would be clearly differentiated because even the foils would be represented by a recently formed, context-specific episodic memory. Accordingly, instead of using multiple stimulus presentations during the recognition test, we examined the distribution of activity associated with once-presented targets vs. once-presented foils across all recorded neurons. The different coding schemes under consideration here make distinct predictions about the expected distributions of neural activity.     

Evidence relating human verbal memory to hippocampal N-methyl-D-aspartate receptors.

Studies in rodents and nonhuman primates have linked the activity of N-methyl-D-aspartate (NMDA) receptors within the hippocampus to animals' performance on memory-related tasks. However, whether these receptors are similarly essential for human memory is still an open question. Here we present evidence suggesting that hippocampal NMDA receptors, most likely within the CA1 region, do participate in human verbal memory processes. Words elicit a negative event-related potential (ERP) peaking around 400 ms within the anterior mesial temporal lobe (AMTL-N400). Ketamine, an NMDA-receptor antagonist, reduces the amplitude of the AMTL-N400 (in contrast to other hippocampal potentials) on initial presentation, eliminates the typical AMTL-N400 amplitude reduction with repetition, and leads to significant memory impairment. Of the various hippocampal subfields, only the density of CA1 neurons correlates with the word-related ERPs that are reduced by ketamine. Altogether, our behavioral, anatomical, and electrophysiological results indicate that hippocampal NMDA receptors are involved in human memory.     

Autobiographical memory in normal aging and primary degenerative dementia (dementia of Alzheimer type)

Autobiographical memory of old people (71-89 years) was studied by a method of free narratives, with normal subjects as well as patients with primary degenerative dementia (SDAT) at three stages of development. The chronological distribution of memories across the life span in both groups showed a peak in adolescence and early adulthood, decrease in mid-life, and increase in recent years. This distribution is different from the results found with the prompt word method among normal old adults, but is similar to the chronological pattern reported for vivid memories. The distribution in the demented group was more flat, which contradicts theories of selective preservation of early memories. With the progression of dementia, autobiographical memory deficits were first evidenced by inaccessibility or loss of memories, and, at a later stage, by loss of details of the retrieved memories and impairment of temporal structure. Events that marked transitions in the lives of the patients ("landmarks") were less subject to forgetting than nontransitional events. The article argues for an approach to autobiographical memory that takes into account sociocultural and developmental determinants of memorability as well as internal mechanisms of the cognitive system.     

Contextual learning requires synaptic AMPA receptor delivery in the hippocampus

The hippocampus plays a central role in learning and memory. Although synaptic delivery of AMPA-type glutamate receptors (AMPARs) contributes to experience-dependent synaptic strengthening, its role in hippocampus-dependent learning remains elusive. By combining viral-mediated in vivo gene delivery with in vitro patch-clamp recordings, we found that the inhibitory avoidance task, a hippocampus-dependent contextual fear-learning paradigm, delivered GluR1-containing AMPARs into CA3-CA1 synapses of the dorsal hippocampus. To block the synaptic delivery of endogenous AMPARs, we expressed a fragment of the GluR1-cytoplasmic tail (the 14-aa GluR1 membrane-proximal region with two serines mutated to phospho-mimicking aspartates: MPR-DD). MPR-DD prevented learning-driven synaptic AMPAR delivery in CA1 neurons. Bilateral expression of MPR-DD in the CA1 region of the rat impaired inhibitory avoidance learning, indicating that synaptic GluR1 trafficking in the CA1 region of the hippocampus is required for encoding contextual fear memories. The fraction of CA1 neurons that underwent synaptic strengthening positively correlated with the performance in the inhibitory avoidance fear memory task. These data suggest that the robustness of a contextual memory depends on the number of hippocampal neurons that participate in the encoding of a memory trace.     

Neural populations in human posteromedial cortex display opposing responses during memory and numerical processing

Our understanding of the human default mode network derives primarily from neuroimaging data but its electrophysiological correlates remain largely unexplored. To address this limitation, we recorded intracranially from the human posteromedial cortex (PMC), a core structure of the default mode network, during various conditions of internally directed (e.g., autobiographical memory) as opposed to externally directed focus (e.g., arithmetic calculation). We observed late-onset (>400 ms) increases in broad high γ-power (70–180 Hz) within PMC subregions during memory retrieval. High γ-power was significantly reduced or absent when subjects retrieved self-referential semantic memories or responded to self-judgment statements, respectively. Conversely, a significant deactivation of high γ-power was observed during arithmetic calculation, the duration of which correlated with reaction time at the signal-trial level. Strikingly, at each recording site, the magnitude of activation during episodic autobiographical memory retrieval predicted the degree of suppression during arithmetic calculation. These findings provide important anatomical and temporal details—at the neural population level—of PMC engagement during autobiographical memory retrieval and address how the same populations are actively suppressed during tasks, such as numerical processing, which require externally directed attention.     

A stable hippocampal representation of a space requires its direct experience

In humans and other mammals, the hippocampus is critical for episodic memory, the autobiographical record of events, including where and when they happen. When one records from hippocampal pyramidal neurons in awake, behaving rodents, their most obvious firing correlate is the animal's position within a particular environment, earning them the name "place cells." When an animal explores a novel environment, its pyramidal neurons form their spatial receptive fields over a matter of minutes and are generally stable thereafter. This experience-dependent stabilization of place fields is therefore an attractive candidate neural correlate of the formation of hippocampal memory. However, precisely how the animal's experience of a context translates into stable place fields remains largely unclear. For instance, we still do not know whether observation of a space is sufficient to generate a stable hippocampal representation of that space because the animal must physically visit a spot to demonstrate which cells fire there. We circumvented this problem by comparing the relative stability of place fields of directly experienced space from merely observed space following blockade of NMDA receptors, which preferentially destabilizes newly generated place fields. This allowed us to determine whether place cells stably represent parts of the environment the animal sees, but does not actually occupy. We found that the formation of stable place fields clearly requires direct experience with a space. This suggests that place cells are part of an autobiographical record of events and their spatial context, consistent with providing the "where" information in episodic memory.     

Gamma oscillations dynamically couple hippocampal CA3 and CA1 regions during memory task performance

The hippocampal formation is believed to be critical for the encoding, consolidation, and retrieval of episodic memories. Yet, how these processes are supported by the anatomically diverse hippocampal networks is still unknown. To examine this issue, we tested rats in a hippocampus-dependent delayed spatial alternation task on a modified T maze while simultaneously recording local field potentials from dendritic and somatic layers of the dentate gyrus, CA3, and CA1 regions by using high-density, 96-site silicon probes. Both the power and coherence of gamma oscillations exhibited layer-specific changes during task performance. Peak increases in the gamma power and coherence were found in the CA3-CA1 interface on the maze segment approaching the T junction, independent of motor aspects of task performance. These results show that hippocampal networks can be dynamically coupled by gamma oscillations according to specific behavioral demands. Based on these findings, we propose that gamma oscillations may serve as a physiological mechanism by which CA3 output can coordinate CA1 activity to support retrieval of hippocampus-dependent memories.     

Activity of human hippocampal and amygdala neurons during retrieval of declarative memories

Episodic memories allow us to remember not only that we have seen an item before but also where and when we have seen it (context). Sometimes, we can confidently report that we have seen something (familiarity) but cannot recollect where or when it was seen. Thus, the two components of episodic recall, familiarity and recollection, can be behaviorally dissociated. It is not clear, however, whether these two components of memory are represented separately by distinct brain structures or different populations of neurons in a single anatomical structure. Here, we report that the spiking activity of single neurons in the human hippocampus and amygdala [the medial temporal lobe (MTL)] contain information about both components of memory. We analyzed a class of neurons that changed its firing rate to the second presentation of a previously novel stimulus. We found that the neuronal activity evoked by the presentation of a familiar stimulus (during retrieval) distinguishes stimuli that will be successfully recollected from stimuli that will not be recollected. Importantly, the ability to predict whether a stimulus is familiar is not influenced by whether the stimulus will later be recollected. We thus conclude that human MTL neurons contain information about both components of memory. These data support a continuous strength of memory model of MTL function: the stronger the neuronal response, the better the memory.     

Human hippocampus represents space and time during retrieval of real-world memories

Memory stretches over a lifetime. In controlled laboratory settings, the hippocampus and other medial temporal lobe brain structures have been shown to represent space and time on the scale of meters and seconds. It remains unclear whether the hippocampus also represents space and time over the longer scales necessary for human episodic memory. We recorded neural activity while participants relived their own experiences, cued by photographs taken with a custom lifelogging device. We found that the left anterior hippocampus represents space and time for a month of remembered events occurring over distances of up to 30 km. Although previous studies have identified similar drifts in representational similarity across space or time over the relatively brief time scales (seconds to minutes) that characterize individual episodic memories, our results provide compelling evidence that a similar pattern of spatiotemporal organization also exists for organizing distinct memories that are distant in space and time. These results further support the emerging view that the anterior, as opposed to posterior, hippocampus integrates distinct experiences, thereby providing a scaffold for encoding and retrieval of autobiographical memories on the scale of our lives.The hippocampus plays a critical role in remembering the events of our lives (1). Direct evidence from single-neuron recordings in rats indicates that cells in the hippocampus fire in specific spatial locations (2–6) or at specific times during a temporal delay (7, 8). Single-neuron and functional MRI (fMRI) studies in individuals navigating virtual environments have confirmed that cells coding for spatial location are also present in the human hippocampus (9–11). Similarly, place-responsive cell activity recorded in the hippocampus of patients with epilepsy during navigation of a virtual town was shown to reinstate during episodic memory retrieval of the previous virtual navigation (12). Together, these studies provide evidence that the same neurons in the medial temporal lobe (MTL) that are active during an experience also help represent the memory for that experience. These results, however, are limited to simple events in laboratory settings that occur on the scale of minutes and meters, thereby leaving unanswered whether we harness similar mechanisms in more natural settings and over larger temporal and spatial scales.Recent studies have used more naturalistic designs with incidentally acquired memories recorded via lifelogging devices that automatically capture photographs from the participants’ lives (13, 14). The typical finding is increased hippocampal activation when participants view images from their cameras as opposed to images from other participants’ cameras (15–17), and this activation decays over the course of months (14). Still, there is no evidence to date that the hippocampus or other MTL structures actually represent space or time of autobiographical experiences. We addressed this question by having participants relive their own real-life experiences in the fMRI scanner. We then used multivariate pattern analysis (18) to identify regions of the MTL that represent space and time of these remembered experiences. If a brain region represented either space or time of personal experiences, the distances between neural activity patterns would correlate with the spatial or temporal proximity of the original experiences.     

Verbal novelty detection within the human hippocampus proper

Animal studies and neuropsychological tests of patients with temporal lobe epilepsy have demonstrated the importance of human medial temporal lobes for memory formation. In addition, more recent studies have shown that the human hippocampal region is also involved in novelty detection. However, the exact contribution of the hippocampus proper to these processes is still unknown. To examine further its role we compared event-related potentials recorded within the medial temporal lobes in 29 temporal lobe epilepsy patients with and 21 without hippocampal sclerosis. While in patients with extrahippocampal lesions but without hippocampal sclerosis event-related potentials to first presentations and repetitions of words were reduced on the side of the epileptogenic focus, in patients with hippocampal sclerosis only those to first presentations but not to repetitions were affected. Because sclerosis of the hippocampus proper selectively reduced event-related potentials to new but not old verbal stimuli, it can be concluded that the human hippocampus proper contributes to verbal novelty detection.     

Genuine episodic memory deficits and executive dysfunctions in alcoholic subjects early in abstinence

BACKGROUND: Chronic alcoholism is known to impair episodic memory function, but the specific nature of this impairment is still unclear. Moreover, it has never been established whether episodic memory deficit in alcoholism is an intrinsic memory deficit or whether it has an executive origin. Thus, the objectives are to specify which episodic memory processes are impaired early in abstinence from alcohol and to determine whether they should be regarded as genuine memory deficits or rather as the indirect consequences of executive impairments. METHODS: Forty recently detoxified alcoholic inpatients at alcohol entry treatment and 55 group-matched controls underwent a neuropsychological assessment of episodic memory and executive functions. The episodic memory evaluation consisted of 3 tasks complementing each other designed to measure the different episodic memory components (learning, storage, encoding and retrieval, contextual memory, and autonoetic consciousness) and 5 executive tasks testing capacities of organization, inhibition, flexibility, updating, and integration. RESULTS: Compared with control subjects, alcoholic patients presented impaired learning abilities, encoding processes, retrieval processes, contextual memory and autonoetic consciousness. However, there was no difference between the 2 groups regarding the storage capacities assessed by the rate of forgetting. Concerning executive functions, alcoholic subjects displayed deficits in each executive task used. Nevertheless, stepwise regression analyses showed that only performances on fluency tasks were significantly predictive of some of the episodic memory disorders (learning abilities for 40%, encoding processes for 20%, temporal memory for 21%, and state of consciousness associated with memories for 26%) in the alcoholic group. DISCUSSION: At alcohol treatment entry, alcoholic patients present genuine episodic memory deficits that cannot be regarded solely as the consequences of executive dysfunctions. These results are in accordance with neuroimaging findings showing hippocampal atrophy. Moreover, given the involvement of episodic memory and executive functions in alcohol treatment, these data could have clinical implications.     

CA3 size predicts the precision of memory recall

There is enduring interest in why some of us have clearer memories than others, given the substantial individual variation that exists in retrieval ability and the precision with which we can differentiate past experiences. Here we report novel evidence showing that variation in the size of human hippocampal subfield CA3 predicted the amount of neural interference between episodic memories within CA3, which in turn predicted how much retrieval confusion occurred between past memories. This effect was not apparent in other hippocampal subfields. This shows that subtle individual differences in subjective mnemonic experience can be accurately gauged from measurable variations in the anatomy and neural coding of hippocampal region CA3. Moreover, this mechanism may be relevant for understanding memory muddles in aging and pathological states.Our memories often contain overlapping elements, because they tend to feature the same people and places that form the cornerstones of our lives. Nevertheless, we are generally able to recall many of these past experiences as distinct episodes, although we are not all equally adept at doing so. There is substantial individual variation in retrieval ability and the precision with which we can differentiate past events (1, 2). This is most acute as we age and in conditions such as dementia, where confusion about the past is often evident (2). There is keen interest, therefore, in elucidating the neural mechanisms that allow us to recollect numerous life experiences despite a high degree of intermemory similarity.We know little about how this is achieved in humans, but theoretical models propose that computations within hippocampal subfields facilitate the efficient storage and retrieval of similar memories (3–7). When we experience an event, pattern separation leads to the formation of a distinct neural representation within region CA3 (8–11). At retrieval, a previously stored memory representation within CA3 can be reactivated through the process of pattern completion (12, 13). However, when episodes are highly similar, the CA3 neuronal representations may not be completely distinct, leading to partial overlap (14). It is therefore not clear precisely what the limits of CA3 pattern separation might be. Here we directly tested the capacity of human CA3 to maintain distinct episodic representations in the presence of overlapping elements. We further investigated whether variation in this ability provides an explanatory account of individual differences in the precision of episodic memory retrieval.     

Spatial memory, recognition memory, and the hippocampus

There is wide agreement that spatial memory is dependent on the integrity of the hippocampus, but the importance of the hippocampus for nonspatial tasks, including tasks of object recognition memory is not as clear. We examined the relationship between hippocampal lesion size and both spatial memory and object recognition memory in rats. Spatial memory was impaired after bilateral dorsal hippocampal lesions that encompassed 30-50% total volume, and as lesion size increased from 50% to approximately 100% of total hippocampal volume, performance was similarly impaired. In contrast, object recognition was intact after dorsal hippocampal lesions that damaged 50-75% of total hippocampal volume and was impaired only after larger lesions that encompassed 75-100% of hippocampal volume. Last, ventral hippocampal lesions that encompassed approximately 50% of total hippocampal volume impaired spatial memory but did not affect object recognition memory. These findings show that the hippocampus is important for both spatial memory and recognition memory. However, spatial memory performance requires more hippocampal tissue than does recognition memory.     

Segregating the functions of human hippocampus

It is now accepted that hippocampal lesions impair episodic memory. However, the precise functional role of the hippocampus in episodic memory remains elusive. Recent functional imaging data implicate the hippocampus in processing novelty, a finding supported by human in vivo recordings and event-related potential studies. Here we measure hippocampal responses to novelty, using functional MRI (fMRI), during an item-learning paradigm generated from an artificial grammar system. During learning, two distinct types of novelty were periodically introduced: perceptual novelty, pertaining to the physical characteristics of stimuli (in this case visual characteristics), and exemplar novelty, reflecting semantic characteristics of stimuli (in this case grammatical status within a rule system). We demonstrate a left anterior hippocampal response to both types of novelty and adaptation of these responses with stimulus familiarity. By contrast to these novelty effects, we also show bilateral posterior hippocampal responses with increasing exemplar familiarity. These results suggest a functional dissociation within the hippocampus with respect to the relative familiarity of study items. Neural responses in anterior hippocampus index generic novelty, whereas posterior hippocampal responses index familiarity to stimuli that have behavioral relevance (i.e., only exemplar familiarity). These findings add to recent evidence for functional segregation within the human hippocampus during learning.