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Impaired memory is a hallmark of prodromal Alzheimer's disease (AD). Prior knowledge associated with the memoranda improves memory in healthy individuals, but we ignore whether the same occurs in early AD. We used functional MRI to investigate whether prior knowledge enhances memory encoding in early AD, and whether the nature of this prior knowledge matters. Patients with early AD and Controls underwent a task-based fMRI experiment where they learned face-scene associations. Famous faces carried pre-experimental knowledge (PEK), while unknown faces with which participants were familiarized prior to learning carried experimental knowledge (EK). Surprisingly, PEK strongly enhanced subsequent memory in healthy controls, but importantly not in patients. Partly nonoverlapping brain networks supported PEK vs. EK associative encoding in healthy controls. No such networks were identified in patients. In addition, patients displayed impaired activation in a right sub hippocampal region where activity predicted successful associative memory formation for PEK stimuli. Despite the limited sample sizes of this study, these findings suggest that the role prior knowledge in new learning might have been so far overlooked and underestimated in AD patients. Prior knowledge may drive critical differences in the way healthy elderly and early AD patients learn novel associations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

From the 1930s through the early 1960s, Wilder Penfield12 collected a large number of memories induced by electrical brain stimulation (EBS) during awake craniotomy. As a result, he was a major contributor to several neuroscientific and neuropsychological concepts of long-term memory. His 1963 paper, which recorded all the cases of memories he induced in his operating room, remains a substantial point of reference in neuroscience in 2019, although some of his interpretations are now debatable.  However, it is highly surprising that, since Penfield's12 reports, there has been no other surgical publication on memories induced during awake surgery. In this review, we explore this phenomenon and analyze some of the reasons that might explain it. We hypothesize that the main reasons for lack of subsequent reports are related to changes in operative procedures (ie, use of anesthetics, time constraints, and insufficient debriefings) and changes in EBS parameters, rather than to the sites that are stimulated, the pathology treated, or the tasks used. If reminiscences are still induced, they should be reported in detail to add valuable contributions to the understanding of long-term memory networks, especially memories that are difficult to reproduce in the laboratory, such as autobiographical memories., (Copyright © 2020 by the Congress of Neurological Surgeons.)

One key item of information retrieved when surveying our visual world is whether or not objects are familiar. However, there is no consensus on the respective roles of medial temporal lobe structures, particularly the perirhinal cortex (PRC) and hippocampus. We considered whether the PRC could support a fast recognition memory system independently from the hippocampus. We recorded the intracerebral electroencephalograph activity of epileptic patients while they were performing a fast visual recognition memory task, constraining them to use their quickest strategy. We performed event-related potential (ERP) and classification analyses. The PRC was, by far, the earliest region involved in recognition memory. This activity occurred before the first behavioral responses and was found to be related to reaction times, unlike the hippocampus. Single-trial analyses showed that decoding power was equivalent in the PRC and hippocampus but occurred much earlier in the PRC. A critical finding was that recognition memory-related activity occurred in different frontal and parietal regions, including the supplementary motor area, before the hippocampus. These results, based on ERP analyses, suggest that the human brain is equipped with a fast recognition memory system, which may bypass the hippocampus and in which the PRC plays a critical role., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Despite highlighting the role of the attribution system and proposing a coherent large-scale architecture of declarative memory, the integrative memory model would be more "integrative" if the temporal dynamics of the interactions between its components was clarified. This is necessary to make predictions in patients with brain injury and hypothesize dissociations.

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: In contrast to most memory systems that decline with age, semantic memory tends to remain relatively stable across the life span. However, what exactly is stable remains unclear. Is it the quantity of information available or the organization of semantic memory, i.e., the connections between semantic items? Even less is known about semantic memory for celebrities, a subsystem of semantic memory. In the present study, we studied the organization of person-specific semantic memory and its stability in aging., Methods: We designed a word association task based on a previous study, which consisted in providing the first word that came to the mind of the participants (15 participants for each age group 20-30, 40-50 and 60-70 years old) for 144 celebrities. We developed a new taxonomy of associated responses as the responses associated with celebrities name could in principle be very varied., Results: We found that most responses (>90%) could be grouped into five categories (subjective; superordinate general; superordinate specific; imagery and activities). The elderly group did not differ from the other two groups in term of errors or reaction time suggesting they performed the task well. However, they also provided associations that were less precise and less based on imagery. In contrast, the middle-age group provided the most precise associations., Conclusion: These results support the idea of a durable person-specific semantic memory in aging but show changes in the type of associations that elders provide. Future work should aim at studying patients with early semantic impairment, as they could be different from the healthy elders on such semantic association task.

The function of the human mediodorsal thalamic nucleus (MD) has so far eluded a clear definition in terms of specific cognitive processes and tasks. Although it was at first proposed to play a role in long-term memory, a set of recent studies in animals and humans has revealed a more complex, and broader, role in several cognitive functions. The MD seems to play a multifaceted role in higher cognitive functions together with the prefrontal cortex and other cortical and subcortical brain areas. Specifically, we propose that the MD is involved in the regulation of cortical networks especially when the maintenance and temporal extension of persistent activity patterns in the frontal lobe areas are required., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Epileptic patients sometimes report experiential phenomena related to a previous dream they had during seizures or electrical brain stimulation (EBS). This has been alluded to in the literature as "déjà-rêvé" ("already dreamed"). However, there is no neuroscientific evidence to support its existence and this concept is commonly mixed up with déjà-vu. We hypothesized that déjà-rêvé would be a specific entity, i.e., different from other experiential phenomena reported in epileptic patients, induced by EBS of specific brain areas., Methods: We collected all experiential phenomena related to dreams induced by electrical brain stimulations (EBS) in our epileptic patients (2003-2015) and in a review of the literature. The content of these déjà-rêvé and the location of EBS were analyzed., Results: We collected 7 déjà-rêvé in our database and 35 from the literature, which corresponds to an estimated prevalence of 0.3‰ of all EBS-inducing déjà-rêvé. Déjà-rêvé is a generic term for three distinct entities: it can be the recollection of a specific dream ("episodic-like"), reminiscence of a vague dream ("familiarity-like") or experiences in which the subject feels like they are dreaming (literally "a dreamy state"). EBS-inducing "episodic-like" and "familiarity-like" déjà-rêvé were mostly located in the medial temporal lobes. "Dreamy states" were induced by less specific EBS areas although still related to the temporal lobes., Conclusions: This study demonstrates that déjà-rêvé is a heterogeneous entity that is different from déjà-vu, the historical "dreamy state" definition and other experiential phenomena. This may be relevant for clinical practice as it points to temporal lobe dysfunction and could be valuable for studying the neural substrates of dreams., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Electrical brain stimulations (EBS) sometimes induce reminiscences, but it is largely unknown what type of memories they can trigger. We reviewed 80 years of literature on reminiscences induced by EBS and added our own database. We classified them according to modern conceptions of memory. We observed a surprisingly large variety of reminiscences covering all aspects of declarative memory. However, most were poorly detailed and only a few were episodic. This result does not support theories of a highly stable and detailed memory, as initially postulated, and still widely believed as true by the general public. Moreover, memory networks could only be activated by some of their nodes: 94.1% of EBS were temporal, although the parietal and frontal lobes, also involved in memory networks, were stimulated. The qualitative nature of memories largely depended on the site of stimulation: EBS to rhinal cortex mostly induced personal semantic reminiscences, while only hippocampal EBS induced episodic memories. This result supports the view that EBS can activate memory in predictable ways in humans., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The hippocampus plays a pivotal role both in novelty detection and in long-term memory. The physiological mechanisms underlying these behaviors have yet to be understood in humans. We recorded intracerebral evoked potentials within the hippocampus of epileptic patients (n = 10) during both memory and novelty detection tasks (targets in oddball tasks). We found that memory and detection tasks elicited late local field potentials in the hippocampus during the same period, but of opposite polarity (negative during novelty detection tasks, positive during memory tasks, ∼260-600 ms poststimulus onset, P < 0.05). Critically, these potentials had maximal amplitude on the same contact in the hippocampus for each patient. This pattern did not depend on the task as different types of memory and novelty detection tasks were used. It did not depend on the novelty of the stimulus or the difficulty of the task either. Two different hypotheses are discussed to account for this result: it is either due to the activation of CA1 pyramidal neurons by two different pathways such as the monosynaptic and trisynaptic entorhinal-hippocampus pathways, or to the activation of different neuronal populations, that is, differing either functionally (e.g., novelty/familiarity neurons) or located in different regions of the hippocampus (e.g., CA1/subiculum). In either case, these activities may integrate the activity of two distinct large-scale networks implementing externally or internally oriented, mutually exclusive, brain states. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Recognition memory--affected early in the course of Alzheimer Disease (AD)--is supposed to rely on two processes: recollection (i.e., retrieval of details from the encoding episode) and familiarity (i.e., acontextual sense of prior exposure). Recollection has repeatedly been shown to be impaired in patients with amnestic Mild Cognitive Impairment (aMCI)--known to be at high risk for AD. However, studies that evaluated familiarity in these patients have reported conflicting results. Here, we assessed familiarity in single-domain aMCI patients (n = 19) and healthy matched controls (n = 22). All participants underwent a classic yes/no recognition memory paradigm with confidence judgements, allowing an estimation of familiarity and recollection similar to the approach used in previous studies. In addition, they underwent a novel speeded recognition memory task, the Speed and Accuracy Boosting procedure, based on the idea that familiarity is fast and hence that fast answers rely on familiarity. On the classic yes/no task, aMCI patients were found to have impaired performance, reaction times, recollection and familiarity. However, performance and reaction times of aMCI patients did not differ from that of controls in the speeded task. This is noteworthy since this task was comparatively difficult for control subjects. This dissociation within familiarity suggests that a very basic component of declarative memory, probably at the interface between implicit and explicit memory, may be preserved, or possibly released, in patients with aMCI. It is suggested that early subprocesses (e.g., fluency based familiarity) could be preserved in aMCI patients, while delayed ones (e.g., conceptual fluency, post-retrieval monitoring, confidence assessment, or even access to awareness) may be impaired. These findings may provide support for recent suggestions that familiarity may result from the combination of a set of subprocesses, each with its specific temporal signature., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: In the common form of Alzheimer's disease (AD), neurofibrillary tangles, which are associated with cognitive dysfunction, initially develop in the anterior subhippocampal (perirhinal/entorhinal) cortex before reaching the hippocampus. This area plays a key role in visual recognition memory (VRM). Impaired VRM could therefore be an early marker of AD., Methods: An extensive neuropsychological assessment including VRM tasks was performed in 26 patients with single-domain amnestic mild cognitive impairment at baseline. We evaluated the diagnostic accuracy of neuropsychological tests using ROC curve analyses in a prospective longitudinal study until conversion to probable AD or with a follow-up of at least 6 years., Results: VRM performance predicted conversion to AD with a sensitivity of 80% and a specificity of 90.9%. Combining the assessment of VRM with a verbal memory task increased diagnostic accuracy., Conclusions: Cognitive 'biomarkers' evaluating the function of brain areas that are the target of degenerative change should be considered for the early diagnosis of AD., (Copyright © 2013 S. Karger AG, Basel.)

Semantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to healthy older subjects; (ii) investigate the association between naming and semantic knowledge in aMCI and AD; (iii) examine if the semantic impairment was present in different modalities; and (iv) study the relationship between semantic performance and grey matter volume using voxel-based morphometry. Results indicate that both naming and semantic knowledge of objects and famous people were impaired in aMCI and early AD groups, when compared to healthy age- and education-matched controls. Item-by-item analyses showed that anomia in aMCI and early AD was significantly associated with underlying semantic knowledge of famous people but not with semantic knowledge of objects. Moreover, semantic knowledge of the same concepts was impaired in both the visual and the verbal modalities. Finally, voxel-based morphometry analyses revealed that semantic impairment in aMCI and AD was associated with cortical atrophy in the anterior temporal lobe (ATL) region as well as in the inferior prefrontal cortex (IPC), some of the key regions of the semantic cognition network. These findings suggest that the semantic impairment in aMCI may result from a breakdown of semantic knowledge of famous people and objects, combined with difficulties in the selection, manipulation and retrieval of this knowledge., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Through study of clinical cases with brain lesions as well as neuroimaging studies of cognitive processing of words and pictures, it has been established that material-specific hemispheric specialization exists. It remains however unclear whether such specialization holds true for all processes involved in complex tasks, such as recognition memory. To investigate neural signatures of transition from perception to recognition, according to type of material (words or abstract pictures), high-resolution scalp ERPs were recorded in adult humans engaged either in categorization or in memory recognition tasks within the same experimental setup. Several steps in the process from perception to recognition were identified. Source localization showed that the early stage of perception processing (N170) takes place in the fusiform gyrus and is lateralized according to the nature of stimuli (left side for words and right side for pictures). Late stages of processing (N400/P600) corresponding to recognition are material independent and involve anterior medial-temporal and ventral prefrontal structures bilaterally. A crucial transitional process between perception (N170) and recognition (N400/P600) is reflected by the N270, an often overlooked component, which occurs in anterior rhinal cortices and shows material-specific hemispheric lateralization.

Déjà vu and involuntary autobiographical memories (IAM) can be induced by intracranial electric brain stimulation in epileptic patients, sometimes in the same individual. We suggest that there may be different types of IAM which should be taken into account and provide several ideas to test the hypothesis of a continuity between IAM and déjà vu phenomena. [ABSTRACT FROM AUTHOR]

There is a large body of research on discourse production in Alzheimer's disease (AD). Some studies have focused on pause production, revealing that patients make extensive use of pauses during speech. This has been attributed to lexical retrieval difficulties, but pausing may also reflect other forms of cognitive impairment as it increases with cognitive load. The aim of the present study was to analyze autobiographical discourse impairment in AD from a broad perspective, looking at pausing behavior (frequency, duration, and location). Our first objective was to characterize discourse changes in mild cognitive impairment (MCI) due to AD. Our second objective was to determine the cognitive and neuroanatomical correlates of these changes. Fifteen patients with MCI due to AD and 15 matched cognitively normal controls underwent an ecological episodic memory task, a full neuropsychological assessment, and a 3D T1-weighted MRI scans. Autobiographical discourse collected from the ecological episodic memory task was recorded, transcribed, and analyzed, focusing on pausing. Intergroup comparisons showed that although patients did not produce more pauses than controls overall, they did make more between-utterance pauses. The number of these specific pauses was positively correlated with patients' episodic memory performance. Furthermore, neuroimaging analysis showed that, in the patient group, their use was negatively correlated with frontopolar area (BA 10) grey matter density. This region may therefore play an important role in the planning of autobiographical discourse production. These findings demonstrate that pauses in early AD may reflect a compensatory mechanism for improving mental time travel and memory retrieval. [ABSTRACT FROM AUTHOR]

Diagnosis of Alzheimer's disease (AD) in its earliest stages becomes increasingly important as disease modifying agents are being developed. In this area of research, many clinical and neuroimaging studies focus on markers of hippocampal dysfunction. However, during the 'transentorhinal stage' of AD, neurofibrillary tangles (NFT), related to tau protein pathology, develop in the anterior subhippocampal (perirhinal/entorhinal) cortex before the hippocampus. NFT are tightly correlated with clinical symptoms. Therefore, an accurate understanding of the behavioral correlate of transentorhinal dysfunction could critically contribute to the early diagnosis of the disease. Recent findings from studies in animals and human brain-damaged patients suggest that the anterior subhippocampal region, functionally integrated into an anterior mesiotemporal network, is involved in object based context-free memory. In this article, we evaluate the hypothesis according to which tau deposition in the anterior subhippocampal region during the earliest stages of the most common form of AD, with predominant MTL dysfunction, will lead to dysfunction of neural networks implicated in context-free memory. We challenge the view that impaired episodic memory is the hallmark of early AD. Instead, a model that integrates the localization and temporal sequence of NFT within the mesial temporal lobe (MTL) is proposed. Paralleling the development of NFT in anterior subhippocampal areas, impaired context-free, object-based, memory could be the first detectable sign in AD. In a subsequent, 'hippocampal' stage, context-rich, episodic and spatial memory, becomes altered as well. The question as to the 'episodic' nature of 'episodic memory tasks' is also addressed. [ABSTRACT FROM AUTHOR]

Performance in recognition memory differs among patients with medial temporal lobe epilepsy (MTLE). We aimed to determine if distinct recognition performances (normal vs. impaired) could be related to distinct patterns of brain activation during encoding. Event-related functional magnetic resonance imaging (fMRI) activation profiles were obtained during successful encoding of non-material-specific items, in 14 MTLE patients tested for recognition of stimuli afterward. Findings were compared to those of 25 healthy subjects, and voxel-based correlations were assessed between brain activation and performance. Patients with left and right MTLE showed similar activations and similar performances. As a whole, the group of patients demonstrated altered recognition scores, but three of the seven patients with left MTLE and three of the seven patients with right MTLE exhibited normal performance relative to controls. In comparison to healthy subjects and patients with impaired recognition, patients with normal recognition showed weaker activations in left opercular cortex, but stronger activations in bilateral parahippocampal region/fusiform gyrus (PH/FG). By contrast, patients with impaired performance showed weaker activations in bilateral PH/FG, but stronger activations in a frontal/cingulate and parietal network. Recognition performance was correlated positively to bilateral PH/FG activations, and negatively correlated to bilateral frontal/cingulate activations, in the whole group of patients, as well as in subgroups of patients with either left or right MTLE. These results suggest occurrence of effective functional compensation within bilateral PH/FG in MTLE, allowing patients to maintain recognition capability. In contrast, impairment of this perceptive-memory system may lead to alternative activation of an inefficient nonspecific attentional network in patients with altered performance. [ABSTRACT FROM AUTHOR]

In 2006 Mitchell demonstrated that implicit memory was robust to decay. He showed that the ability to identify fragments of pictures seen 17 years before was significantly higher than for new stimuli. Is this true only for implicit memory? In this study, we tested whether explicit memory was still possible for drawings (n = 144) that had been presented once or three times, two seconds each time on average, approximately 12 years earlier. Surprisingly, our data reveal that our participants were able to recognize pictures above chance level. Preserved memory was mainly observed in the youngest subjects, for stimuli seen three times. Despite the fact that confidence judgments were low, reports suggest that recognition could be based on a strong sense of familiarity. These data extend Mitchell's findings and show that familiarity can also be robust to decay. [ABSTRACT FROM AUTHOR]

Although it is known that medial temporal lobe (MTL) structures support declarative memory, the fact these structures have different architectonics and circuitry suggests they may also play different functional roles. Selective lesions of MTL structures offer an opportunity to understand these roles. We report, in this study, on JMG, a patient who presents highly unusual lesions that completely affected all MTL structures except for the right hippocampus and parts of neighbouring medial parahippocampal cortex. We first demonstrate that JMG shows preserved recall for visual material on 5 experimental tasks. This finding suggests that his right hippocampus is functional, even though it appears largely disconnected from most of its MTL afferents. In contrast, JMG performed very poorly, as compared to control subjects, on 7 tasks of visual recognition memory for single items. Although he sometimes performed above chance, neither familiarity nor recollection appeared fully preserved. These results indicate that extrahippocampal structures, damaged bilaterally in JMG, perform critical operations for item recognition; and that the hippocampus cannot take over that role, including recollection, when these structures are largely damaged. Finally, in a set of 3 recognition memory tasks with scenes as stimuli, JMG performed at the level of control participants and obtained normal indices of familiarity and recollection. Overall, our findings suggest that the right hippocampus and remnants of parahippocampal cortex can support recognition memory for scenes in the absence of preserved item-recognition memory. The patterns of dissociations, which we report in the present study, provide support for a representational account of the functional organization of MTL structures. [ABSTRACT FROM AUTHOR]