The upside of cumulative conceptual interference on exemplar-level mnemonic discrimination.

Although long-term visual memory (LTVM) has a remarkable capacity, the fidelity of its episodic representations can be influenced by at least two intertwined interference mechanisms during the encoding of objects belonging to the same category: the capacity to hold similar episodic traces (e.g., different birds) and the conceptual similarity of the encoded traces (e.g., a sparrow shares more features with a robin than with a penguin). The precision of episodic traces can be tested by having participants discriminate lures (unseen objects) from targets (seen objects) representing different exemplars of the same concept (e.g., two visually similar penguins), which generates interference at retrieval that can be solved if efficient pattern separation happened during encoding. The present study examines the impact of within-category encoding interference on the fidelity of mnemonic object representations, by manipulating an index of cumulative conceptual interference that represents the concurrent impact of capacity and similarity. The precision of mnemonic discrimination was further assessed by measuring the impact of visual similarity between targets and lures in a recognition task. Our results show a significant decrement in the correct identification of targets for increasing interference. Correct rejections of lures were also negatively impacted by cumulative interference as well as by the visual similarity with the target. Most interestingly though, mnemonic discrimination for targets presented with a visually similar lure was more difficult when objects were encoded under lower, not higher, interference. These findings counter a simply additive impact of interference on the fidelity of object representations providing a finer-grained, multi-factorial, understanding of interference in LTVM.

Computational models can distinguish the contribution from different mechanisms to familiarity recognition.

Familiarity is the strange feeling of knowing that something has already been seen in our past. Over the past decades, several attempts have been made to model familiarity using artificial neural networks. Recently, two learning algorithms successfully reproduced the functioning of the perirhinal cortex, a key structure involved during familiarity: Hebbian and anti-Hebbian learning. However, performance of these learning rules is very different from one to another thus raising the question of their complementarity. In this work, we designed two distinct computational models that combined Deep Learning and a Hebbian learning rule to reproduce familiarity on natural images, the Hebbian model and the anti-Hebbian model, respectively. We compared the performance of both models during different simulations to highlight the inner functioning of both learning rules. We showed that the anti-Hebbian model fits human behavioral data whereas the Hebbian model fails to fit the data under large training set sizes. Besides, we observed that only our Hebbian model is highly sensitive to homogeneity between images. Taken together, we interpreted these results considering the distinction between absolute and relative familiarity. With our framework, we proposed a novel way to distinguish the contribution of these familiarity mechanisms to the overall feeling of familiarity. By viewing them as complementary, our two models allow us to make new testable predictions that could be of interest to shed light on the familiarity phenomenon.

Multimodal imaging of microstructural cerebral alterations and loss of synaptic density in Alzheimer's disease.

Multiple neuropathological events are involved in Alzheimer's disease (AD). The current study investigated the concurrence of neurodegeneration, increased iron content, atrophy, and demyelination in AD. Quantitative multiparameter magnetic resonance imaging (MRI) maps providing neuroimaging biomarkers for myelination and iron content along with synaptic density measurements using [18F] UCB-H PET were acquired in 24 AD and 19 Healthy controls (19 males). The whole brain voxel-wise group comparison revealed demyelination in the right hippocampus, while no significant iron content difference was detected. Bilateral atrophy and synaptic density loss were observed in the hippocampus and amygdala. The multivariate GLM (mGLM) analysis shows a bilateral difference in the hippocampus and amygdala, right pallidum, left fusiform and temporal lobe suggesting that these regions are the most affected despite the diverse differences in brain tissue properties in AD. Demyelination was identified as the most affecting factor in the observed differences. Here, the mGLM is introduced as an alternative for multiple comparisons between different modalities, reducing the risk of false positives while informing about the co-occurrence of neuropathological processes in AD.

Perirhinal cortex is associated with fine-grained discrimination of conceptually confusable objects in Alzheimer's disease.

The perirhinal cortex (PrC) stands among the first brain areas to deteriorate in Alzheimer's disease (AD). This study tests to what extent the PrC is involved in representing and discriminating confusable objects based on the conjunction of their perceptual and conceptual features. To this aim, AD patients and control counterparts performed 3 tasks: a naming, a recognition memory, and a conceptual matching task, where we manipulated conceptual and perceptual confusability. A structural MRI of the antero-lateral parahippocampal subregions was obtained for each participant. We found that the sensitivity to conceptual confusability was associated with the left PrC volume in both AD patients and control participants for the recognition memory task, while it was specifically associated with the volume of the left PrC in AD patients for the conceptual matching task. This suggests that a decreased volume of the PrC is related to the ability to disambiguate conceptually confusable items. Therefore, testing recognition memory or conceptual matching of easily conceptually confusable items can provide a potential cognitive marker of PrC atrophy.

Targeting the function of the transentorhinal cortex to identify early cognitive markers of Alzheimer's disease.

Initial neuropathology of early Alzheimer's disease accumulates in the transentorhinal cortex. We review empirical data suggesting that tasks assessing cognitive functions supported by the transenthorinal cortex are impaired as early as the preclinical stages of Alzheimer's disease. These tasks span across various domains, including episodic memory, semantic memory, language, and perception. We propose that all tasks sensitive to Alzheimer-related transentorhinal neuropathology commonly rely on representations of entities supporting the processing and discrimination of items having perceptually and conceptually overlapping features. In the future, we suggest a screening tool that is sensitive and specific to very early Alzheimer's disease to probe memory and perceptual discrimination of highly similar entities.

Typicality in the brain during semantic and episodic memory decisions.

Concept typicality is a key semantic dimension supporting the categorical organization of items based on their features, such that typical items share more features with other members of their category than atypical items, which are more distinctive. Typicality effects manifest in better accuracy and faster response times during categorization tasks, but higher performance for atypical items in episodic memory tasks, due to their distinctiveness. At a neural level, typicality has been linked to the anterior temporal lobe (ATL) and the inferior frontal gyrus (IFG) in semantic decision tasks, but patterns of brain activity during episodic memory tasks remain to be understood. We investigated the neural correlates of typicality in semantic and episodic memory to determine the brain regions associated with semantic typicality and uncover effects arising when items are reinstated during retrieval. In an fMRI study, 26 healthy young subjects first performed a category verification task on words representing typical and atypical concepts (encoding), and then completed a recognition memory task (retrieval). In line with previous literature, we observed higher accuracy and faster response times for typical items in the category verification task, while atypical items were better recognized in the episodic memory task. During category verification, univariate analyses revealed a greater involvement of the angular gyrus for typical items and the inferior frontal gyrus for atypical items. During the correct recognition of old items, regions belonging to the core recollection network were activated. We then compared the similarity of the representations from encoding to retrieval (ERS) using Representation Similarity Analyses. Results showed that typical items were reinstated more than atypical ones in several regions including the left precuneus and left anterior temporal lobe (ATL). This suggests that the correct retrieval of typical items requires finer-grained processing, evidenced by greater item-specific reinstatement, which is needed to resolve their confusability with other members of the category due to their higher feature similarity. Our findings confirm the centrality of the ATL in the processing of typicality while extending it to memory retrieval.

Shared vivid remembering: age-related differences in across-participants similarity of neural representations during encoding and retrieval.

Recent advances in multivariate neuroimaging analyses have made possible the examination of the similarity of the neural patterns of activations measured across participants, but it has not been investigated yet whether such measure is age-sensitive. Here, in the scanner, young and older participants viewed scene pictures associated with labels. At test, participants were presented with the labels and were asked to recollect the associated picture. We used Pattern Similarity Analyses by which we compared patterns of neural activation during the encoding or the remembering of each picture of one participant with the averaged pattern of activation across the remaining participants. Results revealed that across-participants neural similarity was higher in young than in older adults in distributed occipital, temporal and parietal areas during encoding and retrieval. These findings demonstrate that an age-related reduction in specificity of neural activation is also evident when the similarity of neural representations is examined across participants.

In vivo exploration of synaptic projections in frontotemporal dementia.

The purpose of this exploratory research is to provide data on synaptopathy in the behavioral variant of frontotemporal dementia (bvFTD). Twelve patients with probable bvFTD were compared to 12 control participants and 12 patients with Alzheimer's disease (AD). Loss of synaptic projections was assessed with [18F]UCBH-PET. Total distribution volume was obtained with Logan method using carotid artery derived input function. Neuroimages were analyzed with SPM12. Verbal fluency, episodic memory and awareness of cognitive impairment were equally impaired in patients groups. Compared to controls, [18F]UCBH uptake tended to decrease in the right anterior parahippocampal gyrus of bvFTD patients. Loss of synaptic projections was observed in the right hippocampus of AD participants, but there was no significant difference in [18F]UCBH brain uptake between patients groups. Anosognosia for clinical disorder was correlated with synaptic density in the caudate nucleus and the anteromedial prefrontal cortex. This study suggests that synaptopathy in bvFTD targets the temporal social brain and self-referential processes.

Semantic and perceptual encoding lead to decreased fine mnemonic discrimination following multiple presentations.

Competitive trace theory holds that semanticization following reactivation is characterised by a fidelity loss in the memory representation due to the competition between different traces formed after each occurrence of a given stimulus. This is manifested in the Mnemonic Similarity Task as an increase in hits and in false recognition of similar lures. We tested this account across two encoding conditions emphasising the perceptual versus semantic features of the items, which were presented either once or three times. Our results supported the hypothesis that semanticization following repetition occurs regardless of the type of encoding induced.

Interactions with the integrative memory model.

The integrative memory model formalizes a new conceptualization of memory in which interactions between representations and cognitive operations within large-scale cerebral networks generate subjective memory feelings. Such interactions allow to explain the complexity of memory expressions, such as the existence of multiples sources for familiarity and recollection feelings and the fact that expectations determine how one recognizes previously encountered information.

In vivo imaging of synaptic loss in Alzheimer's disease with [18F]UCB-H positron emission tomography.

PURPOSE: Loss of brain synapses is an early pathological feature of Alzheimer's disease. The current study assessed synaptic loss in vivo with positron emission tomography and an 18F-labelled radiotracer of the synaptic vesicle protein 2A, [18F]UCB-H. METHODS: Twenty-four patients with mild cognitive impairment or Alzheimer's disease and positive [18F]Flutemetamol amyloid-PET were compared to 19 healthy controls. [18F]UCB-H brain uptake was quantified with Logan graphical analysis using an image-derived blood input function. SPM12 and regions-of-interest (ROI) analyses were used for group comparisons of regional brain distribution volumes and for correlation with cognitive measures. RESULTS: A significant decrease of [18F]UCB-H uptake was observed in several cortical areas (11 to 18% difference) and in the thalamus (16% difference), with the largest effect size in the hippocampus (31% difference). Reduced hippocampal uptake was related to patients' cognitive decline (ROI analysis) and unawareness of memory problems (SPM and ROI analyses). CONCLUSIONS: The findings thus highlight predominant synaptic loss in the hippocampus, confirming previous autopsy-based studies and a recent PET study with an 11C-labelled SV2A radiotracer. [18F]UCB-H PET allows to image in vivo synaptic changes in Alzheimer's disease and to relate them to patients' cognitive impairment.

Age-related differences in the neural correlates of vivid remembering.

When recollecting events, older adults typically report similar memory vividness levels as young adults, while they actually retrieve fewer episodic details. This suggests that young and older adults use episodic details differently to calibrate their vividness judgements. Capitalizing on the idea that remembering reactivates brain regions that initially processed details at encoding, the current fMRI study sought to examine these age-related changes in the basis of vivid recollection. At encoding, young and older adults saw pictures associated with labels and these labels were then used as retrieval cues for recalling the associated pictures and making memory vividness judgments. Results showed that highly vivid memories were associated with greater activity in the precuneus in young than older adults. Furthermore, the direct comparison between encoding and retrieval patterns of activity using Representational Similarity Analyses revealed stronger item-specific reactivation in the posterior cingulate/retrosplenial cortex in young than older adults. Taken together, these results provide new evidence that aging is associated with reduced reinstatement of activity in brain regions that processed the encoding of complex stimuli, but older individuals judge these impoverished memory representations as subjectively vivid.

The Impact of Semantic Relatedness on Associative Memory in Aging Depending on the Semantic Relationships between the Memoranda.

Background: Aging is characterized by a decline in associative memory. However, under some conditions, such as in the presence of semantic relatedness within the association, the age-related associative decline can be attenuated. In this study, we evaluated whether the nature of the semantic relationship between the memoranda (taxonomic versus thematic) could modulate the impact of semantic relatedness on older adults' associative memory. Methods: We assessed 40 young adults and 40 older adults' associative memory for associations that were either taxonomically-related, thematically-related, or unrelated. Results: While the main results showed age-related differences in all associative memory tasks without attenuation by semantic relatedness, the results after excluding 4 outlier older participants suggest that older adults' associative memory performance did not differ from that of young adults for thematically-related pairs, while there was an age-related difference in associative memory for taxonomically-related pairs as well as for unrelated pairs. Discussion: This could suggest that the nature of the semantic relationship between the memoranda can modulate the impact of semantic relatedness on older adults' associative memory performance, although the reason why this is not the case for all older participants still needs to be understood.

How to induce an age-related benefit of semantic relatedness in associative memory: It's all in the design.

The age-related associative memory deficit can be alleviated, under some conditions, when to-be-remembered associations are semantically related. In this study, we explored the experimental conditions in which older adults benefited from semantic relatedness and those that hindered any associative memory improvement. We did so by manipulating the level of semantic support within the associations presented at encoding and within the recombined pairs (i.e., the lures) at retrieval, such that pairs with high semantic support at encoding were recombined into pairs with equally high or with lower level of semantic support, and vice versa. We predicted that semantic relatedness would benefit older adults' associative memory when there was a decrease in semantic support from encoding to retrieval. Conversely, older adults' associative memory would be hindered when a recombination was equally or more familiar than the studied association. In Experiment 1, we manipulated the presence versus absence of semantic relatedness within associations both at encoding and at retrieval. In Experiment 2, we manipulated the frequency of related associations at encoding and at retrieval. Taken together, the results showed that older adults' associative memory was better in conditions in which associations closely matched semantic knowledge at encoding and were recombined into associations with no or less semantic support at retrieval. In contrast, older adults' performance was worse for semantically poorer associations at encoding that were recombined into associations with greater semantic support at retrieval. This suggests that older adults' associative memory can be improved by semantic support under specific experimental conditions only. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Novelty processing and memory impairment in Alzheimer's disease: A review.

The detection and processing of novelty plays a critical role in memory function. Despite this, relatively little is known about how novelty influences memory in Alzheimer's disease (AD). This review sought to address whether AD patients are still sensitive to novelty; whether novelty triggers memory processes as is observed in healthy subjects; and whether it is possible to promote novelty to enhance memory at the different stages of AD. The studies reviewed showed that novelty processing is mostly impaired in AD patients, whereas it can be preserved under some conditions in MCI, particularly when cognitive demands are otherwise low. We further identify outstanding questions that should be addressed in the near future in order to more robustly establish the fate of novelty processing and detection in the course of AD. Doing so would allow to improve current models of memory impairment in AD, leading to a more comprehensive view of the sources of memory decline and could lead to neuropsychological and/or pharmaceutical rehabilitation programs.

An integrative memory model of recollection and familiarity to understand memory deficits.

Humans can recollect past events in details (recollection) and/or know that an object, person, or place has been encountered before (familiarity). During the last two decades, there has been intense debate about how recollection and familiarity are organized in the brain. Here, we propose an integrative memory model which describes the distributed and interactive neurocognitive architecture of representations and operations underlying recollection and familiarity. In this architecture, the subjective experience of recollection and familiarity arises from the interaction between core systems (storing particular kinds of representations shaped by specific computational mechanisms) and an attribution system. By integrating principles from current theoretical views about memory functioning, we provide a testable framework to refine the prediction of deficient versus preserved mechanisms in memory-impaired populations. The case of Alzheimer's disease (AD) is considered as an example because it entails progressive lesions starting with limited damage to core systems before invading step-by-step most parts of the model-related network. We suggest a chronological scheme of cognitive impairments along the course of AD, where the inaugurating deficit would relate early neurodegeneration of the perirhinal/anterolateral entorhinal cortex to impaired familiarity for items that need to be discriminated as viewpoint-invariant conjunctive entities. The integrative memory model can guide future neuropsychological and neuroimaging studies aiming to understand how such a network allows humans to remember past events, to project into the future, and possibly also to share experiences.

Do Alzheimer's Disease Patients Benefit From Prior-Knowledge in Associative Recognition Memory?

OBJECTIVES: Although the influence of prior knowledge on associative memory in healthy aging has received great attention, it has never been studied in Alzheimer's disease (AD). This study aimed at assessing whether AD patients could benefit from prior knowledge in associative memory and whether such benefit would be related to the integrity of their semantic memory. METHODS: Twenty-one AD patients and 21 healthy older adults took part in an associative memory task using semantically related and unrelated word pairs and were also submitted to an evaluation of their semantic memory. RESULTS: While participants of both groups benefited from semantic relatedness in associative discrimination, related pairs recognition was significantly predicted by semantic memory integrity in healthy older adults only. CONCLUSIONS: We suggest that patients benefitted from semantic knowledge to improve their performance in the associative memory task, but that such performance is not related to semantic knowledge integrity evaluation measures because the two tasks differ in the way semantic information is accessed: in an automatic manner for the associative memory task, with automatic processes thought to be relatively preserved in AD, and in a controlled manner for the semantic knowledge evaluation, with controlled processes thought to be impaired in AD. (JINS, 2019, 25, 443-452).

Impaired perceptual integration and memory for unitized representations are associated with perirhinal cortex atrophy in Alzheimer's disease.

Unitization, the capacity to encode associations as one integrated entity, can enhance associative memory in populations with an associative memory deficit by promoting familiarity-based associative recognition. Patients with Alzheimer's disease (AD) are typically impaired in associative memory compared with healthy controls but do not benefit from unitization strategies. Using fragmented pictures of objects, this study aimed at assessing which of the cognitive processes that compose unitization is actually affected in AD: the retrieval of unitized representations itself, or some earlier stages of processing, such as the integration process at a perceptual or conceptual stage of representation. We also intended to relate patients' object unitization capacity to the integrity of their perirhinal cortex (PrC), as the PrC is thought to underlie unitization and is also one of the first affected regions in AD. We evaluated perceptual integration capacity and subsequent memory for those items that have supposedly been unitized in 23 mild AD patients and 20 controls. We systematically manipulated the level of perceptual integration during encoding by presenting object pictures that were either left intact, separated into 2 fragments, or separated into 4 fragments. Subjects were instructed to unitize the fragments into a single representation. Success of integration was assessed by a question requiring the identification of the object. Participants also underwent a structural magnetic resonance imaging examination, and measures of PrC, posterior cingulate cortex volume and thickness, and hippocampal volume, were extracted. The results showed that patients' perceptual integration performance decreased with the increased fragmentation level and that their memory for unitized representations was impaired whatever the demands in terms of perceptual integration at encoding. Both perceptual integration and memory for unitized representations were related to the integrity of the PrC, and memory for unitized representations was also related to the volume of the hippocampus. We argue that, globally, this supports representational theories of memory that hold that the role of the PrC is not only perceptual nor mnemonic but instead underlies complex object representation.

Associative memory for conceptually unitized word pairs in mild cognitive impairment is related to the volume of the perirhinal cortex.

Unitization, that is, the encoding of an association as one integrated entity, has been shown to improve associative memory in populations presenting with associative memory deficit due to hippocampal dysfunction, such as amnesic patients with focal hippocampal lesions and healthy older adults. One reason for this benefit is that encoding of unitized associations would rely on the perirhinal cortex (PrC) and thus minimize the need for hippocampal recruitment. Mild cognitive impairment (MCI) is accompanied by a deficit in associative memory. However, unitization has never been studied to explore the potential benefit in associative memory in MCI, maybe because MCI is characterized by PrC pathology. However, the PrC may potentially still function sufficiently to allow for the successful adoption of unitization. In this study, we aimed at assessing whether unitization could attenuate MCI patients' associative memory deficit, and whether the ability to remember unitized associations would be modulated by the integrity of the PrC in MCI patients. Unitization was manipulated at a conceptual level, by encouraging participants to encode unrelated word pairs as new compound words. Participants also underwent a structural MRI exam, and measures of PrC were extracted (Brodmann Areas [BA] 35 and 36). Results showed that, contrary to healthy controls, MCI patients did not benefit from unitization. Moreover, their memory performance for unitized associations was related to the measure of PrC integrity (BA35), while it was not the case in controls. This finding thus suggests that unitization does not help to attenuate the associative deficit in MCI patients, and brings support to the literature linking unitization to the PrC function.

The impact of aging on associative memory for preexisting unitized associations.

Aging is accompanied by a decline in associative memory that can, however, be attenuated when associations are unitized at encoding, that is, when they form an integrated entity. Unitization is thought to promote familiarity-based recognition memory, which is preserved in aging. We examined whether preexperimentally unitized associations (compound words (CWs)) do indeed reduce age differences in memory, and whether preexperimental unitization promotes familiarity. In Experiment 1, we assessed the memory of 20 young and 20 older participants for compound versus unrelated word pairs using a yes/no recognition test with Remember/Know/Guess judgments. In Experiment 2, we tested 20 young and 20 older participants using the same procedure, except for the use of a two-alternative forced-choice recognition paradigm, which is thought to enhance the contribution of familiarity. The results of both experiments corroborated the greater contribution of familiarity to recognition of unitized associations. In Experiment 1, however, the use of CWs did not attenuate the age-related associative decline. We suggest that preexisting knowledge associated with recombined compounds induced high absolute familiarity and illusory recollection, leading to high false-recognition rates for the older adults. By contrast, the two groups performed similarly across both conditions in Experiment 2. Thus, the forced-choice procedure facilitates the use of familiarity in such a way that it improves older adults' associative memory to the level of young participants. These results suggest that the modulation of associative memory in aging by preexisting unitization varies according to methodological parameters, such as the nature of the lures and the test format.