An extension of the novelty-seeking model: Considering the plurality of novelty types and their differential interactions with memory.

The novelty-seeking model suggests that curiosity and creativity originate from novelty processes. However, different types of novelty exist, each with distinctive relationships with memory, which potentially influence curiosity and creativity in distinct ways. We thus propose expanding the NSM model to consider these different novelty types and their specific involvement in creativity.

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.

A day that America will remember: flashbulb memory, collective memory, and future thinking for the capitol riots.

ABSTRACTThis study explores the topics of flashbulb memory, collective identity, future thinking, and shared representations for a public event. We assessed the memories of the Capitol Riots, which happened in Washington DC, on 6 January 2021. Seventy Belgian and seventy-nine American citizens participated in an online study, in which they freely recalled the unfolding of Capitol Riots and answered questions regarding their memory. Inter-subjects similarity of recalled details was analysed using a schematic narrative template (i.e., the event, the causes and the consequences). Results revealed that representations of the event, and its causes were more similar among Belgians compared to Americans, whereas Americans' representations of the consequences showed more similarity than Belgians'. Also, as expected, Americans reported more flashbulb memories (FBMs) than Belgians. The analysis underlined the importance of rehearsal through media and communication in FBM formation. This research revealed a novel relation between FBM and future representations. Regardless of national identity, participants who formed an FBM were more likely to think that the event would be remembered in the future, that the government should memorialise the event, and that a similar attack on the Capitol could happen in the future compared to participants who did not form FBM.

Hippocampal metabolic subregions and networks: Behavioral, molecular, and pathological aging profiles.

INTRODUCTION: Hippocampal local and network dysfunction is the hallmark of Alzheimer's disease (AD). METHODS: We characterized the spatial patterns of hippocampus differentiation based on brain co-metabolism in healthy elderly participants and demonstrated their relevance to study local metabolic changes and associated dysfunction in pathological aging. RESULTS: The hippocampus can be differentiated into anterior/posterior and dorsal cornu ammonis (CA)/ventral (subiculum) subregions. While anterior/posterior CA show co-metabolism with different regions of the subcortical limbic networks, the anterior/posterior subiculum are parts of cortical networks supporting object-centered memory and higher cognitive demands, respectively. Both networks show relationships with the spatial patterns of gene expression pertaining to cell energy metabolism and AD's process. Finally, while local metabolism is generally lower in posterior regions, the anterior-posterior imbalance is maximal in late mild cognitive impairment with the anterior subiculum being relatively preserved. DISCUSSION: Future studies should consider bidimensional hippocampal differentiation and in particular the posterior subicular region to better understand pathological aging.

Neuropsychological predictions on involuntary autobiographical memory and déjà vu.

I strongly support Barzykowski and Moulin in their proposal that common retrieval mechanisms can lead to distinct phenomenological memory experiences. I emphasize the importance of one of these mechanisms, namely the attribution system. Neuropsychological studies should help clarifying the role of these retrieval mechanisms, notably in cases of medial temporal-lobe lesions and cases of dementia.

Boosting Familiarity-Based Memory Decisions in Alzheimer's Disease: The Importance of Metacognition.

OBJECTIVE: Recent studies in Alzheimer's disease (AD) have suggested that AD patients are not always able to rely on their feeling of familiarity to improve their memory decisions to the same extent as healthy participants. This underuse of familiarity in AD could result from a learned reinterpretation of fluency as a poor cue for memory that would prevent them to attribute a feeling of fluency to a previous encounter. The primary goal of this study was to determine whether AD patients could relearn the association between processing fluency and past exposure after being repeatedly exposed to situations where using this association improves the accuracy of their memory decisions. METHOD: Thirty-nine patients with probable AD were recruited and asked to complete several recognition tests. During these tests, participants were put either in a condition where the positive contingency between fluent processing and previous encounters with an item was systematically confirmed (intervention condition) or in a condition where there was no correlation between fluency and prior exposure (control condition). The efficacy of the intervention was evaluated at three time points (baseline, posttest, and 3-month follow-up). RESULTS: Our results indicated that all AD patients do not benefit to the same extent from the training. Two variables appeared to influence the likelihood that participants increase and maintain their reliance on the fluency cues after the intervention: the ability to detect the fluency manipulation and the preservation of implicit metacognitive skills. CONCLUSION: These findings indicate the importance of metacognition for inferential attribution processes in memory.

Familiarity in Mild Cognitive Impairment as a Function of Patients' Clinical Outcome 4 Years Later.

OBJECTIVES: The current study addresses the nature of memory difficulties in amnestic mild cognitive impairment (aMCI). Whereas recollection is consistently found to be impaired in aMCI, the results on familiarity are divergent. One potential factor that could explain this divergence in findings relates to the heterogeneity of aMCI patients, so that only those aMCI patients who develop Alzheimer disease (AD) may present with impaired familiarity. The present study aimed at testing this hypothesis. METHODS: A group of 45 aMCI patients and a group of 26 healthy older adults performed a verbal recognition memory test with the Remember/Know paradigm to assess recollection and familiarity processes. All participants were followed for 4 years with clinical and neuropsychological testing. At the end of follow-up, 22 aMCI patients progressed to AD and 23 aMCI patients remained stable. Initial memory performance was compared between the 3 groups. RESULTS: Whereas recollection was severely diminished in all aMCI patients, familiarity accuracy (and consequently global recognition accuracy) was found to be impaired only in aMCI patients who subsequently developed AD. CONCLUSION: These findings suggest that the enrichment of the aMCI population with predementia stage patients may modulate the likelihood to observe familiarity deficits, and impaired global recognition accuracy may accompany incipient AD.

Efficacy of Cognitive Rehabilitation Versus Usual Treatment at Home in Patients With Early Stages of Alzheimer Disease.

INTRODUCTION: Assessing the benefit of cognitive rehabilitation (CR) remains difficult. METHOD: An observational study was conducted in 33 patients with early-stage Alzheimer disease and their caregiver included in a clinical CR program at home, compared to 17 patients who received usual treatment. Evaluation of patient's dependence and objective and subjective caregiver's burden was performed by the caregiver with a research tool focusing on impairment in daily activities related to cognitive deficits. RESULTS: Repeated measures analysis of variance showed a time by group interaction (P < .05), with decreased patient's dependence for adapted activities at 1 year in the CR group. Lawton scale for daily activities showed also a time by group interaction (P < .05), with increased dependence at 1 year in the control group. There was a significant decrease in Mini-Mental State Examination scores in both groups at 1-year follow-up (P < .05). Concerning caregiver's subjective burden, there was a trend for the time by group interaction (P = .07), and post hoc Tukey test showed that subjective burden was decreased in the CR group (P < .05). This was confirmed by nonparametric Mann-Whitney analysis on differences between follow-up and baseline evaluation (P < .05). CONCLUSION: This observational study in a clinical setting is in line with the benefit of CR reported in recent randomized controlled trials. The benefit obtained for adapted daily activities remained after 1 year, even if global cognition declined. Moreover, caregiver's subjective burden related to all relevant daily activities evaluated within the CR program was decreased after 1 year in our clinical setting.

Relationship between brain AD biomarkers and episodic memory performance in healthy aging.

The presence of brain biomarkers can be observed decades before the first clinical symptoms of Alzheimer's disease (AD). We aimed to determine whether associations between biomarkers and episodic memory performance already exist in a healthy late middle-aged population or only in participants over 60 years old. Performance at the Free and Cued Selective Reminding Test [FCSRT], the Logical Memory test and the Mnemonic Similarity Task [MST] was determined in sixty healthy participants (50-70 y.) with a negative status for amyloid-beta (Aß) biomarker. We assessed Aß cortical level and tau/neuroinflammation burden using PET scanner, and hippocampal atrophy with MRI scanner. Generalized linear mixed models showed that MST scores (recognition and pattern separation) were positively associated with hippocampal volume in participants over 60 years. No association between memory performance and Aß and tau/neuroinflammation burden was found in the older or in the younger age group. This suggests that visual recognition memory and discrimination of lures may constitute early cognitive markers of memory decline in an older population.

Aging and binding in short-term memory: processes involved in conjunctive and relational binding.

In visual short-term binding memory tasks, some studies suggested that aging disrupts relational binding more than conjunctive binding, whereas others report equivalent age-related differences in both types of binding. Yet, demands in controlled resources are potentially the greatest for relational short-term binding. In order to test the hypothesis that aging would affect preferentially tasks demanding in controlled processes, we assessed the contribution of controlled and automatic memory processes to relational and conjunctive short-term binding. Groups of young and older adults studied shape-colour (Exp.1 and 3) or object-colour (Exp.2) pairs in a relational condition in which items were linked to colour patches and a conjunctive condition where colour was integrated into the items. Memory for bindings was tested with a reconstruction task (Exp. 1 and 2) or with a recognition memory task (Exp. 3) under inclusion and exclusion instructions (Process Dissociation Procedure). The three experiments showed that the retrieval of both relational and conjunctive bindings relied primarily on controlled memory processes, the use of which was diminished in older participants. This study brings additional evidence that age-related differences in top-down control processes explain at least partly decreased short-term binding capacities.

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.

Impaired explicit self-awareness but preserved behavioral regulation in patients with Alzheimer disease.

OBJECTIVES: Impairments of metacognitive skills represent a critical symptom in Alzheimer Disease (AD) because it frequently results in a lack of self-awareness. However, recent findings suggest that, despite an inability to explicitly estimate their own cognitive functioning, patients might demonstrate some implicit recognition of difficulties. In this study, we tested whether a behavioral dissociation between explicit and implicit measures of metacognition can be found in both healthy older controls (n = 20) and AD patients (n = 20). METHODS: Our two groups of participants (AD vs. Controls) were asked to complete a forced-choice perceptual identification test and to explicitly rate their confidence in each decision (i.e. explicit measure of metacognition). Moreover, they also had the opportunity to ask for a cue to help them decide if their response was correct (i.e. implicit measure of metacognition). RESULTS: Data revealed that all participants asked for a cue more often after an incorrect response than after a correct response in the forced-choice identification test, indicating a good ability to implicitly introspect on the results of their cognitive operations. On the contrary, only healthy participants displayed metacognitive sensitivity when making explicit confidence judgments. CONCLUSION: Our findings suggest that implicit metacognition may be less affected than explicit metacognition in Alzheimer's disease.

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.

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.

A gist orientation before retrieval impacts the objective content but not the subjective experience of episodic memory.

A gist retrieval-orientation decreases one's ability to remember objective details from past experiences. Here, we examined whether a gist retrieval-orientation manipulation can impact both the objective and subjective aspects of remembering. Young participants took part in two cued-recollection tasks in which they studied pictures associated with labels; at retrieval, from the labels, they evaluated the vividness of their memories of the corresponding pictures, and recalled picture details. Before retrieval, participants were submitted either to a gist or a control retrieval-orientation (one per task). Results revealed that the amount of recalled details was lower following the gist condition while vividness ratings did not differ between the two retrieval orientations. Critically, the amount of recalled details predicted the corresponding vividness ratings to a similar extent in the gist and control conditions, thus suggesting that recollected memory traces in the gist condition were still rich enough to be judged as subjectively vivid.

Deciphering the relationship between objective and subjective aspects of recollection in healthy aging.

Although healthy aging has been related to a decline in recollection as indexed by objective measures, the subjective experience of recollection sometimes remains stable. To date, however, these age-related differences have only been examined using aggregated data across trials. In the current study, we investigated the relationship between subjective and objective measures of recollection on a trial-by-trial basis to determine whether the magnitude of this relationship was similar in young and older adults. Young and older participants were presented with pictures that were associated with descriptive labels at encoding. At retrieval, they were cued with the labels and were asked to rate the vividness of their memory for the associated picture and to recall as many details of the picture as possible. On average, older adults assigned higher vividness ratings but recalled fewer episodic details than young adults. Mixed-effects modelling revealed that the relationship between subjective (vividness) and objective (number of recalled details) recollection across trials was stronger in young than in older participants. These findings provide evidence that older adults not only retrieve fewer episodic details but also rely on these details to a lesser extent than young adults for judging the subjective quality of their memories.

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.

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.

Anosognosia and default mode subnetwork dysfunction in Alzheimer's disease.

Research on the neural correlates of anosognosia in Alzheimer's disease varied according to methods and objectives: they compared different measures, used diverse neuroimaging modalities, explored connectivity between brain networks, addressed the role of specific brain regions or tried to give support to theoretical models of unawareness. We used resting-state fMRI connectivity with two different seed regions and two measures of anosognosia in different patient samples to investigate consistent modifications of default mode subnetworks and we aligned the results with the Cognitive Awareness Model. In a first study, patients and their relatives were presented with the Memory Awareness Rating Scale. Anosognosia was measured as a patient-relative discrepancy score and connectivity was investigated with a parahippocampal seed. In a second study, anosognosia was measured in patients with brain amyloid (taken as a disease biomarker) by comparing self-reported rating with memory performance, and connectivity was examined with a hippocampal seed. In both studies, anosognosia was consistently related to disconnection within the medial temporal subsystem of the default mode network, subserving episodic memory processes. Importantly, scores were also related to disconnection between the medial temporal and both the core subsystem (participating to self-reflection) and the dorsomedial subsystem of the default mode network (the middle temporal gyrus that might subserve a personal database in the second study). We suggest that disparity in connectivity within and between subsystems of the default mode network may reflect impaired functioning of pathways in cognitive models of awareness.

Characterization of a temporoparietal junction subtype of Alzheimer's disease.

Alzheimer's disease (AD) subtypes have been described according to genetics, neuropsychology, neuropathology, and neuroimaging. Thirty-one patients with clinically probable AD were selected based on perisylvian metabolic decrease on FDG-PET. They were compared to 25 patients with a typical pattern of decreased posterior metabolism. Tree-based machine learning was used on those 56 images to create a classifier that was subsequently applied to 207 Alzheimer's Disease Neuroimaging Initiative (ADNI) patients with AD. Machine learning was also used to discriminate between the two ADNI groups based on neuropsychological scores. Compared to AD patients with a typical precuneus metabolic decrease, the new subtype showed stronger hypometabolism in the temporoparietal junction. The classifier was able to distinguish the two groups in the ADNI population. Both groups could only be distinguished cognitively by Trail Making Test-A scores. This study further confirms that there is more than a typical metabolic pattern in probable AD with amnestic presentation.