Prestimulus hippocampal activity predicts later recollection

Functional magnetic resonance imaging (fMRI) was used to address the question whether medial temporal lobe (MTL) activity prior to a stimulus event is predictive of whether the event will be successfully encoded in an incidental study task. Participants were scanned while making pleasantness judgments on words presented either in written or spoken form. A cue presented at a variable interval before the onset of each word signaled the modality of the upcoming item. Following the study phase, a surprise recognition memory test was administered that required items to be endorsed as “Remembered,” “Known,” or “New.” Activity in the MTL, including the hippocampus, differed during the cue‐item interval according to whether the item was later endorsed as Remembered rather than judged as Known or New. Thus, the level of hippocampal activity prior to the onset of an event predicts whether the event will be successfully encoded into episodic memory. © 2009 Wiley‐Liss, Inc.     

Executive functioning in psychogeriatric patients: scalability and construct validity of the Behavioral Dyscontrol Scale (BDS)

OBJECTIVES: Item response theory was used to test the scalability of the Behavioral Dyscontrol Scale (BDS). The BDS assesses the control of voluntary movement, working memory and self-monitoring. Construct validity of the BDS was examined with confirmatory factor analysis. METHODS: The BDS was administered to 693 consecutive, community-dwelling visitors of a psychogeriatric day unit (424 women and 269 men between the ages of 50 and 94). Unidimensionality of the BDS was determined using Mokken's scalogram analysis. The BDS total score was correlated with other measures of executive function (Expanded Mental Control Test, category fluency, and alternating graphical sequences) and with episodic memory tests of orientation and delayed picture recognition in order to test a model of distinct latent constructs of executive functioning and episodic memory. RESULTS: Loevinger's scalability coefficient H was 0.58 for the complete item set of the BDS. Subjects can be ordered on the latent dimension of executive ability. The first eight items of the BDS (deleting the insight rating) satisfy the assumption of non-intersecting item characteristic curves (double monotonicity) which means that they comprise a Guttman-ordered scale (H = 0.60). The BDS and three independent measures of executive control strongly correlated with a latent construct of executive functioning (convergent validity). However, discriminant relations with a nonexecutive construct (recognition memory and orientation) could not be demonstrated. CONCLUSIONS: The BDS satisfies criteria for scalability according to item response theory. Its construct validity as an executive-specific measure is as yet unclear.     

Markers of preparatory attention predict visual short-term memory performance

Visual short-term memory (VSTM) is limited in capacity. Therefore, it is important to encode only visual information that is most likely to be relevant to behaviour. Here we asked which aspects of selective biasing of VSTM encoding predict subsequent memory-based performance. We measured EEG during a selective VSTM encoding task, in which we varied parametrically the memory load and the precision of recall required to compare a remembered item to a subsequent probe item. On half the trials, a spatial cue indicated that participants only needed to encode items from one hemifield. We observed a typical sequence of markers of anticipatory spatial attention: early attention directing negativity (EDAN), anterior attention directing negativity (ADAN), late directing attention positivity (LDAP); as well as of VSTM maintenance: contralateral delay activity (CDA). We found that individual differences in preparatory brain activity (EDAN/ADAN) predicted cue-related changes in recall accuracy, indexed by memory-probe discrimination sensitivity (d′). Importantly, our parametric manipulation of memory-probe similarity also allowed us to model the behavioural data for each participant, providing estimates for the quality of the memory representation and the probability that an item could be retrieved. We found that selective encoding primarily increased the probability of accurate memory recall; that ERP markers of preparatory attention predicted the cue-related changes in recall probability.     

A calendar savant with episodic memory impairments

Patients with memory disorders have severely restricted learning and memory. For instance, patients with anterograde amnesia can learn motor procedures and retain some restricted ability to learn new words and factual information. However, such learning is inflexible and frequently inaccessible to conscious awareness. Here we present a case of patient AC596, a 25-year-old male with severe episodic memory impairments, presumably due to anoxia during a preterm birth. In contrast to his poor episodic memory, he exhibits savant-like memory for calendar information that can be flexibly accessed by day, month, and year cues. He also has the ability to recollect the exact date of a wide range of personal experiences over the past 20 years. The patient appears to supplement his generally poor episodic memory by using memorized calendar information as a retrieval cue for autobiographical events. These findings indicate that islands of preserved memory functioning, such as a highly developed semantic memory system, can exist in individuals with severely impaired episodic memory systems. In this particular case, our patient's memory for dates far outstripped that of normal individuals and served as a keen retrieval cue, allowing him to access information that was otherwise unavailable.     

Neural correlates of confidence during item recognition and source memory retrieval: evidence for both dual-process and strength memory theories

Although the medial-temporal lobes (MTL), PFC, and parietal cortex are considered primary nodes in the episodic memory network, there is much debate regarding the contributions of MTL, PFC, and parietal subregions to recollection versus familiarity (dual-process theory) and the feasibility of accounts on the basis of a single memory strength process (strength theory). To investigate these issues, the current fMRI study measured activity during retrieval of memories that differed quantitatively in terms of strength (high vs. low-confidence trials) and qualitatively in terms of recollection versus familiarity (source vs. item memory tasks). Support for each theory varied depending on which node of the episodic memory network was considered. Results from MTL best fit a dual-process account, as a dissociation was found between a right hippocampal region showing high-confidence activity during the source memory task and bilateral rhinal regions showing high-confidence activity during the item memory task. Within PFC, several left-lateralized regions showed greater activity for source than item memory, consistent with recollective orienting, whereas a right-lateralized ventrolateral area showed low-confidence activity in both tasks, consistent with monitoring processes. Parietal findings were generally consistent with strength theory, with dorsal areas showing low-confidence activity and ventral areas showing high-confidence activity in both tasks. This dissociation fits with an attentional account of parietal functions during episodic retrieval. The results suggest that both dual-process and strength theories are partly correct, highlighting the need for an integrated model that links to more general cognitive theories to account for observed neural activity during episodic memory retrieval.     

The influence of semantic encoding on recognition memory in Alzheimer''s disease

Within the framework of the distinction between episodic and semantic memory, it has been argued that these two memory systems are organised in a hierarchical way. The hierarchical hypothesis assumes that episodic memory is a specific subsystem of semantic memory and therefore implies that episodic memory cannot exist without semantic memory. If this hypothesis is correct, it should be expected that patients with impaired semantic memory also have impaired episodic memory. In the present study, two experiments investigated the influence of semantic encoding on recognition memory performance in a population of 20 patients with Alzheimer's disease and 18 normal controls. Both experiments assessed recognition memory for semantically-related items. In Experiment 2, but not in Experiment 1, subjects were explicitly instructed to make a semantic association between the items. Alzheimer's disease patients were impaired, compared to the normal controls, on the recognition memory performance of both experiments. The ability to make a semantic association between two items was significantly and positively correlated with the subjects' performance on the recognition tasks. A further analysis showed that patients who were impaired on the semantic association task did significantly worse on the recognition task of Experiment 2 than normal controls and patients who were unimpaired on the semantic association task. These findings are discussed in the context of memory deficits in Alzheimer's disease, and are interpreted as supporting the view that episodic memory for an item is affected by the level of semantic awareness of that same item.     

Support for an auto-associative model of spoken cued recall: evidence from fMRI

Cued recall and item recognition are considered the standard episodic memory retrieval tasks. However, only the neural correlates of the latter have been studied in detail with fMRI. Using an event-related fMRI experimental design that permits spoken responses, we tested hypotheses from an auto-associative model of cued recall and item recognition [Chappell, M., & Humphreys, M. S. (1994). An auto-associative neural network for sparse representations: Analysis and application to models of recognition and cued recall. Psychological Review, 101, 103-128]. In brief, the model assumes that cues elicit a network of phonological short term memory (STM) and semantic long term memory (LTM) representations distributed throughout the neocortex as patterns of sparse activations. This information is transferred to the hippocampus which converges upon the item closest to a stored pattern and outputs a response. Word pairs were learned from a study list, with one member of the pair serving as the cue at test. Unstudied words were also intermingled at test in order to provide an analogue of yes/no recognition tasks. Compared to incorrectly rejected studied items (misses) and correctly rejected (CR) unstudied items, correctly recalled items (hits) elicited increased responses in the left hippocampus and neocortical regions including the left inferior prefrontal cortex (LIPC), left mid lateral temporal cortex and inferior parietal cortex, consistent with predictions from the model. This network was very similar to that observed in yes/no recognition studies, supporting proposals that cued recall and item recognition involve common rather than separate mechanisms.     

The effects of study task on prestimulus subsequent memory effects in the hippocampus

Functional magnetic resonance imaging (fMRI) was employed to examine the effects of a study task manipulation on pre‐stimulus activity in the hippocampus predictive of later successful recollection. Eighteen young participants were scanned while making either animacy or syllable judgments on visually presented study words. Cues presented before each word denoted which judgment should be made. Following the study phase, a surprise recognition memory test was administered in which each test item had to be endorsed as “Remembered,” “Known,” or “New.” As expected, “deep” animacy judgments led to better memory for study items than did “shallow” syllable judgments. In both study tasks, pre‐stimulus subsequent recollection effects were evident in the interval between the cue and the study item in bilateral anterior hippocampus. However, the direction of the effects differed according to the study task: whereas pre‐stimulus hippocampal activity on animacy trials was greater for later recollected items than items judged old on the basis of familiarity (replicating prior findings), these effects reversed for syllable trials. We propose that the direction of pre‐stimulus hippocampal subsequent memory effects depends on whether an optimal pre‐stimulus task set facilitates study processing that is conducive or unconducive to the formation of contextually rich episodic memories. © 2015 Wiley Periodicals, Inc.     

Un nuevo test para la valoración de la memoria episódica. Test episódico y test episódico del cuidador

Introduction and objectives

The purpose of the episodic memory test and the caregiver's episodic memory test is to evaluate episodic memory according to its definition in a way that is feasible for families and achieves high degrees of sensitivity and specificity.

Methods and results

We administered a test consisting of 10 questions about episodic events to 332 subjects, of whom 65 had Alzheimer's disease (AD), 115 had amnestic MCI (aMCI) and 152 showed no cognitive impairment according to Reisberg's global deterioration scale (GDS). We calculated the test's sensitivity and specificity to distinguish AD from episodic aMCI and from normal ageing. The area under the ROC curve for the diagnosis of aMCI was 0.94 and the best cut-off value was 20; for that value, sensitivity was 89% and specificity was 82%. For a diagnosis of AD, the area under the ROC curve was 0.99 and the best cut-off point was 17, with a sensitivity of 98% and a specificity of 91%. A subsequent study using similar methodology yielded similar results when the test was administered directly by the caregiver.

Conclusions

The episodic memory test and the caregiver's episodic memory test are useful as brief screening tools for identifying patients with early-stage AD. It is suitable for use by primary care medical staff and in the home, since it can be administered by a caregiver. The test's limitations are that it must be administered by a reliable caregiver and the fact that it measures episodic memory only.     

α/β oscillations indicate inhibition of interfering visual memories

Selective retrieval of a specific target memory often leads to the forgetting of related but irrelevant memories. Current cognitive theory states that such retrieval-induced forgetting arises due to inhibition of competing memory traces. To date, however, direct neural evidence for this claim has not been forthcoming. Studies on selective attention suggest that cortical inhibition is mediated by increased brain oscillatory activity in the alpha/beta frequency band. The present study, testing 18 human subjects, investigated whether these mechanisms can be generalized to selective memory retrieval in which competing memories interfere with the retrieval of a target memory. Our experiment was designed so that each cue used to search memory was associated with a target memory and a competitor memory stored in separate brain hemispheres. Retrieval-induced forgetting was observed in a condition in which the competitor memory interfered with target retrieval. Increased oscillatory alpha/beta power was observed over the hemisphere housing the sensory representation of the competitor memory trace and predicted the amount of retrieval-induced forgetting in the subsequent memory test. These results provide the first direct evidence for inhibition of competing memories during episodic memory retrieval and suggest that competitive retrieval is governed by inhibitory mechanisms similar to those employed in selective attention.     

Improving sensory representations using episodic memory

The medial temporal lobe (MTL) is well known to be essential for declarative memory. However, a growing body of research suggests that MTL structures might be involved in perceptual processes as well. Our previous modeling work suggests that sensory representations in cortex influence the accuracy of episodic memory retrieved from the MTL. We adopt that model here to show that, conversely, episodic memory can also influence the quality of sensory representations. We model the effect of episodic memory as (a) repeatedly replaying episodes from memory and (b) recombining episode fragments to form novel sequences that are more informative for learning sensory representations than the original episodes. We demonstrate that the performance in visual discrimination tasks is superior when episodic memory is present and that this difference is due to episodic memory driving the learning of a more optimized sensory representation. We conclude that the MTL can, even if it has only a purely mnemonic function, influence perceptual discrimination indirectly.     

The role of left ventrolateral prefrontal cortex during episodic decisions: semantic elaboration or resolution of episodic interference?

Context memory retrieval tasks often implicate the left ventrolateral pFC (LVPFC) during functional imaging. Although this region has been linked to controlled semantic processing of materials, it may also play a more general role in selecting among competing episodic representations during demanding retrieval tasks. Thus, the LVPFC response during context memory retrieval may reflect either semantic processing of memoranda or adjudication of interfering episodic memories evoked by memoranda. To distinguish between these hypotheses, we contrasted context and item memory retrieval tasks for meaningful and nonmeaningful memoranda using fMRI. Increased LVPFC activation during context compared with item memory only occurred for meaningful memory probes. In contrast, even demanding context retrieval for nonmeaningful materials failed to engage LVPFC. These data demonstrate that the activation previously seen during episodic tasks likely reflects semantic processing of the probes during episodic retrieval attempt, not the selection among competing elicited episodic representations. Posterior middle temporal gyrus and the body/head of the caudate demonstrated the same selective response as LVPFC, although resting state functional connectivity analyses suggested that these two regions likely shared separate functional relationships with the LVPFC.     

The hippocampal indexing theory and episodic memory: updating the index

A little over 20 years ago, (Teyler and DiScenna,1986; Behav Neurosci 100:147-152) proposed the hippocampal memory index theory. It offered an account of episodic memory based on the intrinsic organization of the hippocampus, its synaptic physiology and its anatomical relationship to other regions of the brain. The essence of their idea was that the hippocampus was functionally designed and anatomically situated to capture information about neocortical activity generated by the individual features of behavioral episode. Moreover, because the hippocampus projects back to these neocortical regions the information it stored could serve as an index to the pattern of neocortical activity produced by the episode. Consequently, a partial cue that activated the index could activate the neocortical patterns and thus retrieve the memory of the episode. In this article we revisit and update indexing theory. Our conclusion is that it has aged very well. Its core ideas can be seen in many contemporary theories and there is a wealth of data that support this conceptual framework.     

Can zebrafish learn spatial tasks? An empirical analysis of place and single CS-US associative learning

The zebrafish may be an ideal tool with which genes underlying learning and memory can be identified and functionally investigated. From a translational viewpoint, relational learning and episodic memory are particularly important as their impairment is the hallmark of prevalent human neurodegenerative diseases. Recent reports suggest that zebrafish are capable of solving complex relational-type associative learning tasks, namely spatial learning tasks. However, it is not known whether good performance in these tasks was truly based upon relational learning or upon a single CS-US association. Here we study whether zebrafish can find a rewarding stimulus (sight of conspecifics) based upon a single associative cue or/and upon the location of the reward using a method conceptually similar to 'context and cue dependent fear conditioning' employed with rodents. Our results confirm that zebrafish can form an association between a salient visual cue and the rewarding stimulus and at the same time they can also learn where the reward is presented. Although our results do not prove that zebrafish form a dynamic spatial map of their surroundings and use this map to locate their reward, they do show that these fish perform similarly to rodents whose hippocampal function is unimpaired. These results further strengthen the notion that complex cognitive abilities exist in the zebrafish and thus they may be analyzed using the excellent genetic tool set developed for this simple vertebrate.     

Multidimensional measures of person knowledge and spatial associative learning: can these be applied to the differentiation of Alzheimer's disease from frontotemporal and vascular dementia?

Patients with early stage Alzheimer's disease (AD) show deficits in person knowledge and spatial associative memory. The current investigation examined the ability of impairment in these domains to differentiate AD from other overlapping conditions. In experiment 1, 14 AD patients, 21 vascular dementia (VaD) patients, 11 frontal variant frontotemporal dementia (fvFTD) patients and 41 controls were administered a graded faces test. VaD patients demonstrated a level of impairment comparable to the AD group on both the naming and person identification elements of the task. A mild naming deficit was revealed in the fvFTD group. In experiment 2, 22 AD patients, 23 patients with mild cognitive impairment (MCI), 11 fvFTD patients, 13 semantic dementia (SD) patients, and 23 elderly controls were administered the face-place test, a newly developed task that combines naming of famous faces, item recognition and spatial location. The naming component of the face-place test clearly differentiated SD patients from all dementia groups. All patient groups, except those with fvFTD, showed substantial deficits in the item recognition and spatial components. Consistency analyses indicated a fairly robust association between the two episodic components (item recognition and placing), but not between semantic and episodic elements of the FPT. Person knowledge deficits are, therefore, not specific to AD and the employment of face stimuli may influence the performance of SD patients on tasks of episodic memory.     

Episodic and semantic memory in mild cognitive impairment

Little is known about episodic and semantic memory in the early predementia stage of Alzheimer's disease (AD), which is referred to as mild cognitive impairment (MCI). To explore person knowledge, item recognition and spatial associative memory, we designed the Face Place Test (FPT). A total of 75 subjects participated: 22 patients with early AD, 24 with MCI and 29 matched controls. As predicted, AD patients showed significant deficits in person naming, item recognition and recall of spatial location (placing). Surprisingly, subjects with MCI were also impaired on all components. There was no significant difference between AD and MCI except on the placing component. Analysis of the relationship between semantic (naming) and episodic (recognition and placing) components of the FPT revealed a significant association between the two episodic tasks, but not between episodic and semantic performance. Patients with MCI show deficits of episodic and semantic memory. The extent of impairment suggests dysfunction beyond the medial temporal lobe. The FPT might form the basis of a sensitive early indicator of AD.     

Probability effects on event-related potential correlates of recognition memory

A common finding in event-related potential (ERP) studies of recognition memory is that recognised items elicit greater positivity at parietal electrode sites than new items (the 'left parietal old/new effect'). Parietal positivity (the P300 or P3b) is also elicited in detection tasks with no memory demands by items of low probability of occurrence and high 'target value'. It has been argued that correctly recognised items are typically associated with lower probability and higher target value than new items, raising the question of the extent to which the old/new effect receives a contribution from, or interacts with, P300 activity. The present study explored this issue by comparing ERPs associated with correctly classified old and new items across three different ratios of old to new items: 25:75, 50:50 and 75:25. The left parietal old/new effect was not influenced by this manipulation in the latency range in which it is conventionally measured. Probability did influence the parietal ERPs to correctly recognised items post-800 ms; the scalp distribution of this probability effect was however qualitatively distinct from that of the preceding old/new effect. The left parietal old/new effect appears to be a relatively pure reflection of episodic retrieval, uncontaminated by the non-mnemonic factors of probability and target value.     

The medial and lateral entorhinal cortex both contribute to contextual and item recognition memory: A test of the binding ofitems and context model

It has been suggested that the role of the hippocampus for episodic memory is to selectively bind together item and contextual information. One such model, the Binding of Items and Context (BIC) model, proposed that the perirhinal cortex provides item and the postrhinal/parahippocampal cortex provides context to the hippocampus via the medial (MEC) and lateral entorhinal cortices (LEC) to be bound into an episodic representation. This model proposes that item and context information are stored and processed independently and in parallel before hippocampal processing. To evaluate this model, the present experiment evaluated the role of the MEC and LEC for item and contextual novelty detection. The present results suggest that excitotoxic lesions to the LEC primarily disrupt item novelty detection, whereas lesions to the MEC primarily disrupt contextual novelty detection. These data provide a functional double dissociation between the MEC and LEC across item and contextual processing. Despite this dissociation, the present results suggest that item and contextual information are not represented independently before hippocampal processing. These data support the basic assumptions of the BIC model, but suggest that item and context information may interact in the entorhinal cortex. © 2013 Wiley Periodicals, Inc.     

Role of the medial temporal lobes in relational memory: neuropsychological evidence from a cued recognition paradigm

In this study, we examined the role of the hippocampus in relational memory by comparing item recognition performance in amnesic patients with medial temporal lobe (MTL) damage and their matched controls. Specifically, we investigated the contribution of associative memory to item recognition using a cued recognition paradigm. Control subjects studied cue-target pairs once, whereas amnesic patients studied cue-target pairs six times. Following study, subjects made recognition judgments about targets that were presented either alone (no cue), with the originally presented cue (same cue), or with a cue that had been presented with a different target (recombined cue). Controls had higher recognition scores in the same cue than in the recombined cue condition, indicating that they benefited from the associative information provided by the same cue. By contrast, amnesic patients did not. This was true even for a subgroup of patients whose recognition performance in the no cue condition was matched to that of the controls. These data provide further support for the idea that the hippocampus plays a critical role in relational memory, even when associative information need not be retrieved intentionally.     

The effect of retrieval cues on post-retrieval monitoring in episodic memory: an electrophysiological study

The aim of the present experiment was to examine whether episodic retrieval and 'post-retrieval' monitoring are affected by the nature of the cue that guides a search of memory. We recorded event-related brain potentials (ERPs) from young healthy adult participants while they tried to recall studied words (e.g. 'MOTHER') with the aid of word-stem (e.g. 'MOT') and word-fragment (e.g. 'M-TH--') retrieval cues. Analyses of the behavioural data showed that while it was far more difficult to generate completions per se for the fragments, the levels of conscious, or 'explicit', recall obtained with each type of cue were statistically identical. ERP analyses focussed upon differences in neural activity evoked by each type of cue (termed 'old/new' ERP effects) during successful versus unsuccessful retrieval. The stem and fragment old/new ERP effects were remarkably similar in their time course and magnitude, and also in their scalp distribution, which changed over time as multiple neuronal populations, and hence multiple cognitive operations, became activated. These behavioural and ERP findings suggest that the cognitive operations reflected by old/new effects in cued recall tasks may be insensitive to changes in the retrieval strategy, or effort, that participants apply to monitor the episodic status of retrieved information. The findings are discussed in relation to previous ERP and functional imaging studies that have investigated task-specific features of retrieval and post-retrieval processing in episodic memory.