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This cover image, by Emmanuel J. Barbeau et al., is based on the Research Article Hippocampus duality: Memory and novelty detection are subserved by distinct mechanisms, DOI: 10.1002/hipo.22699. [ABSTRACT FROM AUTHOR]

ABSTRACT 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. [ABSTRACT FROM AUTHOR]

Remembering and mentally reliving yesterday's lunch is a typical example of episodic autobiographical memory retrieval. In the present review, we reappraised the complex cascade of cognitive processes involved in memory retrieval, by highlighting one particular phase that has received little interest so far: attentional switch to memory (ASM). As attention cannot be simultaneously directed toward external stimuli and internal memories, there has to be an attentional switch from the external to the internal world in order to initiate memory retrieval. We formulated hypotheses and developed hypothetical models of both the cognitive and brain processes that accompany ASM. We suggest that gaze aversion could serve as an objective temporal marker of the point at which people switch their attention to memory, and highlight several fields (neuropsychology, neuroscience, social cognition, comparative psychology) in which ASM markers could be essential. Our review thus provides a new framework for understanding the early stages of autobiographical memory retrieval. [ABSTRACT FROM AUTHOR]

An increasing number of studies indicate that semantic memory is impaired in mild cognitive impairment (MCI). However, the extent and the neural basis of this impairment remain unknown. The aim of the present study was: 1) to evaluate whether all or only a subset of semantic domains are impaired in MCI patients; and 2) to assess the neural substrate of the semantic impairment in MCI patients using voxel-based analysis of MR grey matter density and SPECT perfusion. 29 predominantly amnestic MCI patients and 29 matched control subjects participated in this study. All subjects underwent a full neuropsychological assessment, along with a battery of five tests evaluating different domains of semantic memory. A semantic memory composite Z-score was established on the basis of this battery and was correlated with MRI grey matter density and SPECT perfusion measures. MCI patients were found to have significantly impaired performance across all semantic tasks, in addition to their anterograde memory deficit. Moreover, no temporal gradient was found for famous faces or famous public events and knowledge for the most remote decades was also impaired. Neuroimaging analyses revealed correlations between semantic knowledge and perirhinal/entorhinal areas as well as the anterior hippocampus. Therefore, the deficits in the realm of semantic memory in patients with MCI is more widespread than previously thought and related to dysfunction of brain areas beyond the limbic-diencephalic system involved in episodic memory. The severity of the semantic impairment may indicate a decline of semantic memory that began many years before the patients first consulted. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The phenomenon of ‘déjà vu’ is caused by acute disturbance of mnemonic systems of the medial temporal lobe (MTL). In epileptic patients investigated with intracerebral electrodes, déjà vu can be more readily induced by stimulation of the rhinal cortices (RCs) than the hippocampus (H). Whether déjà vu results from acute dysfunction of the familiarity system alone (sustained by RC) or from more extensive involvement of the MTL region (including H) is debatable. Methods: We analysed the synchronisation of intracerebral electroencephalography (EEG) signals recorded from RC, H and amygdala (A) in epileptic patients in whom déjà vu was induced by electrical stimulation. EEG signal correlations (between signals from RC, A and H) were evaluated using a nonlinear regression. Results: In comparison with RC stimulations that did not lead to déjà vu (DV−), stimulations triggering déjà vu (DV+) were associated with increased broadband EEG correlation (p =0.01). Changes in correlations were significantly different in the theta band for RC–A (p =0.007) and RC–H (p =0.01) and in the beta band for RC–H (p =0.001) interactions. Conclusion: Déjà vu is associated with increased EEG signal correlation between MTL structures. Significance: Results are in favour of a mechanism involving transient co-operation between various MTL structures, not limited to RC alone. [Copyright &y& Elsevier]

There is an ongoing debate regarding the respective role of anterior subhippocampal structures and the hippocampus in recognition memory. Here, we report a double anatomo-functional dissociation observed in two brain-damaged patients, FRG and JMG. They both suffered from complete destruction of left MTL structures. In the right hemisphere however, FRG sustained extensive lesions to the hippocampus sparing anterior subhippocampal structures, while JMG suffered from the reversed pattern of lesion, i.e., extensive damage to anterior subhippocampal structures but preserved hippocampus. FRG was severely amnesic and failed all recall tasks involving visual material, but exhibited normal performance at a large battery of visual recognition memory tasks. JMG was not amnesic and showed the opposite pattern of performance. These results strongly support the view that right anterior subhippocampal structures are a critical relay for visual recognition memory in the human. © 2010 Wiley-Liss, Inc. [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]

Abstract: We encounter many faces each day but relatively few are personally familiar. Once faces are familiar, they evoke semantic and social information known about the person. Neuroimaging studies demonstrate differential brain activity to familiar and non-familiar faces; however, brain responses related to personally familiar faces have been more rarely studied. We examined brain activity with fMRI in adults in response to faces of their mothers and fathers compared to faces of celebrities and strangers. Overall, faces of mothers elicited more activity in core and extended brain regions associated with face processing, compared to fathers, celebrity or stranger faces. Fathers’ faces elicited activity in the caudate, a deep brain structure associated with feelings of love. These new findings of differential brain responses elicited by faces of mothers and fathers are consistent with psychological research on attachment, evident even during adulthood. [ABSTRACT FROM AUTHOR]

Cortical atrophy is correlated with the progression of neuropathological lesions within the medial temporal lobes (MTL) in Alzheimer’s disease (AD). Our aim was to determine which local and remote functional changes result from MTL volume loss at the predementia stage. We studied the relationship between entorhinal and hippocampal MR volumes and whole-brain SPECT perfusion via a voxel-based correlative analysis in 19 patients with amnestic mild cognitive impairment with a memory profile suggestive of early AD. Right MTL volumes were positively correlated with remote posterior perfusion of the posterior cingulate cortex, and negatively correlated with remote anterior perfusion of the right medial and dorsolateral prefrontal cortex. There was no local correlation between volumes and perfusion within the MTL. These findings provide further insight into functional changes that result from MTL volume loss during the predementia stage of AD. The positive correlation between MTL volumes and posterior cingulate perfusion may reflect the deafferentation of a temporocingulate network due to mediotemporal degeneration. The paradoxical negative correlation between MTL volumes and prefrontal perfusion may result from recruitment of an alternative anterior temporofrontal network. It remains to be investigated how the “net sum” of this perfusion modulation affects memory and other cognitive domains through a possible compensatory perspective. [ABSTRACT FROM AUTHOR]

Most of what we know about the human frontal eye field (FEF) is extrapolated from studies in animals. There is ample evidence that this region is crucial for eye movements. However, evidence is accumulating that this region also plays a role in sensory processing and that it belongs to a "fast brain" system. We set out to investigate these issues in humans, using intracerebral recordings in patients with drug-refractory epilepsy. Event-related potential recordings were obtained from 11 epileptic patients from within the FEF region while they passed a series of visual and auditory perceptual tests. No eye movement was required. Ultra-rapid responses were observed, with mean onset latencies at 24 ms after stimulus to auditory stimuli and 45 ms to visual stimuli. Such early responses were compatible with cortical routes as assessed with simultaneous recordings in primary auditory and visual cortices. Components were modulated very early by the sensory characteristics of the stimuli, in the 30-60 ms period for auditory stimuli and in the 45- 60 ms period for visual stimuli. Although the frontal lobes in humans are generally viewed as being involved in high-level cognitive processes, these results indicate that the human FEF is a remarkably quickly activated multimodal region that belongs to a network of low-level neocortical sensory areas. [ABSTRACT FROM AUTHOR]

There is ongoing debate about whether performance on tests of recognition memory can remain preserved after hippocampal damage. In the present study, we report F.R.G., a patient who became severely amnesic following herpes simplex encephalitis. Although F.R.G. failed all tests involving recall and verbal recognition, she obtained normal performance on a wide number of tests evaluating visual recognition memory (14 of 18 different tests). Her performance was independent of various factors, such as test difficulty, duration of exposure to the stimuli, or delay separating encoding and recognition. F.R.G. also achieved normal performance on two tasks requiring that she associate pairs of visual stimuli. In addition, she demonstrated spared feeling of knowing, suggesting that her performance on recognition tests was explicit and likely to rely on familiarity. Brain imaging (MRI) revealed bilateral lesions of the hippocampus and lesions of the left parahippocampal gyrus, while the right parahippocampal gyrus remained relatively spared. The results of this study support the view that recognition memory can be preserved despite severe hippocampal damage and that familiarity is a distinct memory process that can be dissociated from recollection. ©2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

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]

The interthalamic adhesion (IA) is a structure that connects the median borders of both thalami. Its anatomical variants and functions remain poorly studied. The main objective of this study was to explore the role of the IA on cognition. 42 healthy subjects and 40 patients with chronic isolated thalamic strokes underwent a neuroimaging and a neuropsychological assessment. The presence, absence, or lesion of the IA and its anatomical variants were evaluated. 76% of participants had an IA, with a higher prevalence among women (92%) than men (61%). The presence or absence of an IA did not affect the neuropsychological performance of healthy subjects nor did the type of IA variant. Across all the tests and when compared to healthy subjects using a Bayesian rmANOVA, patients exhibiting more cognitive impairments were those without an IA (n = 10, BF10 = 10,648), while those with an IA were more preserved (n = 18, BF10 = 157). More specifically, patients without an IA performed more poorly in verbal memory or the Stroop task versus healthy subjects. This was not explained by age, laterality of the infarct, volume or localization of the lesion. Patients with a lesioned IA (n = 12) presented a similar trend to patients without an IA, which could however be explained by a greater volume of lesions. The IA does not appear to play a major role in cognition in healthy subjects, but could play a compensatory role in patients with thalamic lesions. [ABSTRACT FROM AUTHOR]

Accurate segmentation of thalamic nuclei, crucial for understanding their role in healthy cognition and in pathologies, is challenging to achieve on standard T1-weighted (T1w) magnetic resonance imaging (MRI) due to poor image contrast. White-matter-nulled (WMn) MRI sequences improve intrathalamic contrast but are not part of clinical protocols or extant databases. In this study, we introduce histogram-based polynomial synthesis (HIPS), a fast preprocessing transform step that synthesizes WMn-like image contrast from standard T1w MRI using a polynomial approximation for intensity transformation. HIPS was incorporated into THalamus Optimized Multi-Atlas Segmentation (THOMAS) pipeline, a method developed and optimized for WMn MRI. HIPS-THOMAS was compared to a convolutional neural network (CNN)-based segmentation method and THOMAS modified for the use of T1w images (T1w-THOMAS). The robustness and accuracy of the three methods were tested across different image contrasts (MPRAGE, SPGR, and MP2RAGE), scanner manufacturers (PHILIPS, GE, and Siemens), and field strengths (3 T and 7 T). HIPS-transformed images improved intra-thalamic contrast and thalamic boundaries, and HIPS-THOMAS yielded significantly higher mean Dice coefficients and reduced volume errors compared to both the CNN method and T1w-THOMAS. Finally, all three methods were compared using the frequently travelling human phantom MRI dataset for inter- and intra-scanner variability, with HIPS displaying the least inter-scanner variability and performing comparably with T1w-THOMAS for intra-scanner variability. In conclusion, our findings highlight the efficacy and robustness of HIPS in enhancing thalamic nuclei segmentation from standard T1w MRI. [ABSTRACT FROM AUTHOR]

Recognition memory is the ability to recognize previously encountered objects. Even this relatively simple, yet extremely fast, ability requires the coordinated activity of large‐scale brain networks. However, little is known about the sub‐second dynamics of these networks. The majority of current studies into large‐scale network dynamics is primarily based on imaging techniques suffering from either poor temporal or spatial resolution. We investigated the dynamics of large‐scale functional brain networks underlying recognition memory at the millisecond scale. Specifically, we analyzed dynamic effective connectivity from intracranial electroencephalography while epileptic subjects (n = 18) performed a fast visual recognition memory task. Our data‐driven investigation using Granger causality and the analysis of communities with the Louvain algorithm spotlighted a dynamic interplay of two large‐scale networks associated with successful recognition. The first network involved the right visual ventral stream and bilateral frontal regions. It was characterized by early, predominantly bottom‐up information flow peaking at 115 ms. It was followed by the involvement of another network with predominantly top‐down connectivity peaking at 220 ms, mainly in the left anterior hemisphere. The transition between these two networks was associated with changes in network topology, evolving from a more segregated to a more integrated state. These results highlight that distinct large‐scale brain networks involved in visual recognition memory unfold early and quickly, within the first 300 ms after stimulus onset. Our study extends the current understanding of the rapid network changes during rapid cognitive processes. [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]

Identifying factors whose fluctuations are associated with choice inconsistency is a major issue for rational decision theory. Here, we investigated the neuro-computational mechanisms through which mood fluctuations may bias human choice behavior. Intracerebral EEG data were collected in a large group of subjects (n=30) while they were performing interleaved quiz and choice tasks that were designed to examine how a series of unrelated feedbacks affect decisions between safe and risky options. Neural baseline activity preceding choice onset was confronted first to mood level, estimated by a computational model integrating the feedbacks received in the quiz task, and then to the weighting of option attributes, in a computational model predicting risk attitude in the choice task. Results showed that (1) elevated broadband gamma activity (BGA) in the ventromedial prefrontal cortex (vmPFC) and dorsal anterior insula (daIns) was respectively signaling periods of high and low mood, (2) increased vmPFC and daIns BGA respectively promoted and tempered risk taking by overweighting gain vs. loss prospects. Thus, incidental feedbacks induce brain states that correspond to different moods and bias the evaluation of risky options. More generally, these findings might explain why people experiencing positive (or negative) outcome in some part of their life tend to expect success (or failure) in any other. [ABSTRACT FROM AUTHOR]

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. • We asked if prior knowledge lessens the learning deficit observed in prodromal AD • AD patients did not benefit from pre-experimental knowledge (PEK; famous faces) • Distinct networks subtended associative encoding of (pre-)experimental knowledge • Controls exhibited a memory effect in the perirhinal cortex for PEK associations • By using unfamiliar items to probe memory in AD, a deficit may be underestimated [ABSTRACT FROM AUTHOR]

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 [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]

Several experiments carried out with a subset of patients with temporal lobe epilepsy have demonstrated normal memory performance at standard delays of recall (i.e. minutes to hours) but impaired performance over longer delays (i.e. days or weeks), suggesting altered long-term consolidation mechanisms. These mechanisms were specifically investigated in a group of five adult-onset pharmaco-sensitive patients with temporal lobe epilepsy, exhibiting severe episodic memory complaints despite normal performance at standardized memory assessment. In a first experiment, the magnitude of autobiographical memory loss was evaluated using retrograde personal memory tasks based on verbal and visual cues. In both conditions, results showed an unusual U-shaped pattern of personal memory impairment, encompassing most of the patients’ life, sparing however, periods of the childhood, early adulthood and past several weeks. This profile was suggestive of a long-term consolidation impairment of personal episodes, adequately consolidated over ‘short-term’ delays but gradually forgotten thereafter. Therefore, in a subsequent experiment, patients were submitted to a protocol specifically devised to investigate short and long-term consolidation of contextually-bound experiences (episodic memory) and context-free information (semantic knowledge and single-items). In the short term (1 h), performance at both contextually-free and contextually-bound memory tasks was intact. After a 6-week delay, however, contextually-bound memory performance was impaired while contextually-free memory performance remained preserved. This effect was independent of task difficulty and the modality of retrieval (recall and recognition). Neuroimaging studies revealed the presence of mild metabolic changes within medial temporal lobe structures. Taken together, these results show the existence of different consolidation systems within declarative memory. They suggest that mild medial temporal lobe dysfunction can impede the building and stabilization of episodic memories but leaves long-term semantic and single-items mnemonic traces intact. [ABSTRACT FROM AUTHOR]

Although the semantic memory impairment has been largely documented in Alzheimer's disease, little is known about semantic memory in the preclinical phase of the disease (Mild Cognitive Impairment). The purpose of this study was to document the nature of semantic breakdown using a battery of tests assessing different aspects of conceptual knowledge: knowledge about common objects, famous people and famous public events. Results indicate that all domains of semantic memory were impaired in MCI individuals but knowledge about famous people and famous events was affected to a greater extent than knowledge about objects. This pattern of results suggests that conceptual entities with distinctive and unique properties may be more prone to semantic breakdown in MCI. In summary, results of this study support the view that genuine semantic deficits are present in MCI. It could be useful to investigate the etiological outcome of patients failing or succeeding at such tests. [ABSTRACT FROM AUTHOR]

Several studies pertaining to déjà vu have consistently made a connection with the perirhinal region, a region located below the hippocampus. This idea is strengthened by the fact that déjà vu is an erroneous sense of familiarity and that familiarity appears to largely depend on the perirhinal region in healthy subjects. In this context, the role of the hippocampus is particularly unclear as it is unknown whether or not it plays a role in the genesis of déjà vu. We report on the case of OHVR, an epileptic patient who suffers from severe episodic amnesia related to massive isolated bilateral damage to the hippocampus. In contrast, the perirhinal region is intact structurally and functionally. This patient reports frequent déjà vu but also another experiential phenomenon with a prominent feeling of prescience, which shows some of the characteristics of déjà vécu. She clearly distinguishes both. She also developed a form of synaesthesia by attributing affective valence to numbers. This study shows that déjà vu can occur in cases of amnesia with massively damaged hippocampi and confirms that the perirhinal region is a core region for déjà vu, using a different approach from previous reports. It also provides clues about a potential influence of hippocampal alterations in déjà vécu. [ABSTRACT FROM AUTHOR]

Accumulating evidence over the past decade suggests that semantic deficits represent a consistent feature of Mild Cognitive Impairment (MCI). A meta-analysis was performed to examine if semantic deficits are consistently found in patients with MCI. Studies meeting all inclusion criteria were selected for the current meta-analysis. An effect size and a weight were calculated for each study. A random effect model was performed to assess the overall difference in semantic performances between MCI patients and healthy subjects. 22 studies (476 healthy participants, 476 MCI patients, mean Mini Mental Status Examination of the MCI patients: 27.05 ± 0.58) were included in the meta-analysis. Results indicate that MCI patients systematically performed significantly worse than healthy matched controls in terms of overall semantic performance (mean effect size of 1.02; 95% CI [0.80; 1.24]). Semantic deficits are a key feature of MCI. Semantic tests should be incorporated in routine clinical assessments. [ABSTRACT FROM AUTHOR]

Highlights • Novelty detection is a critical function in memory systems. • We review data on novelty detection and processing in Alzheimer's disease. • Novelty processing is mostly impaired in Alzheimer's disease. • We propose a model of memory impairments in AD including novelty processing. Abstract 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. [ABSTRACT FROM AUTHOR]

Highlights • First recordings of spiking neuronal activity in the tuber and perituberal tissue using new hybrid electrodes equipped with tetrodes. • Gradient of epileptogenicity running from the tuber to perituberal tissue revealed by multi-scale analyses. • Observation of interactions both within and between the tuber and perituber. Abstract Objective The mechanisms underlying epileptogenicity in tuberous sclerosis complex (TSC) are poorly understood. Methods We analysed neuronal spiking activity (84 neurons), fast ripples (FRs), local field potentials and intracranial electroencephalogram during interictal epileptiform discharges (IEDs) in the tuber and perituber of a patient using novel hybrid electrodes equipped with tetrodes. Results IEDs were recorded in the tuber and perituber. FRs were recorded only in the tuber and only with the microelectrodes. A larger proportion of neurons in the tuber (57%) than in the perituber (17%) had firing-rates modulated around IEDs. Conclusions A multi-scale analysis of neuronal activity, FRs and IEDs indicates a gradient of epileptogenicity running from the tuber to the perituber. Significance We demonstrate, for the first time in vivo , a gradient of epileptogenicity from the tuber to the perituber, which paves the way for future models of epilepsy in TSC. Our results also question the extent of the neurosurgical resection, including or not the perituber, that needs to be made in these patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The acquisition of new semantic memories is sometimes preserved in patients with hippocampal amnesia. Robust evidence for this comes from case reports of developmental amnesia suggesting that low‐to‐normal levels of semantic knowledge can be achieved despite compromised episodic learning. However, it is unclear whether this relative preservation of semantic memory results from normal acquisition and retrieval or from residual episodic memory, combined with effortful repetition. Furthermore, lesion studies have mainly focused on the hippocampus itself, and have seldom reported the state of structures in the extended hippocampal system. Preserved components of this system may therefore mediate residual episodic abilities, contributing to the apparent semantic preservation. We report an in‐depth study of Patient KA, a 27‐year‐old man who had severe hypoxia at birth, in which we carefully explored his residual episodic learning abilities. We used novel speeded recognition paradigms to assess whether KA could explicitly acquire and retrieve new context‐free memories. Despite a pattern of very severe amnesia, with a 44‐point discrepancy between his intelligence and memory quotients, KA exhibited normal‐to‐superior levels of knowledge, even under strict time constraints. He also exhibited normal‐to‐superior recognition memory for new material, again under strict time constraints. Multimodal neuroimaging revealed an unusual pattern of selective atrophy within each component of the extended hippocampal system, contrasting with the preservation of anterior subhippocampal cortices. A cortical thickness analysis yielded a pattern of thinner but also thicker regional cortices, pointing toward specific temporal lobe reorganization following early injury. We thus report the first case of superior explicit learning and memory in a severe case of amnesia, raising important questions about how such knowledge can be acquired. [ABSTRACT FROM AUTHOR]

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. Highlights The mediodorsal thalamic nucleus is involved in the cognitive deficits observed in several neurological and psychiatric disorders. The long-standing belief in a role of the mediodorsal thalamic nucleus mainly in long-term memory is now being reconsidered. Recent studies emphasize its function in many cognitive tasks related to the prefrontal cortex. The mediodorsal thalamic nucleus is required for the rapid and accurate performance of cognitive tasks and temporally extends the efficiency of cortical networks involving the prefrontal cortex. We propose that the common ground of multiple lines of evidence from human studies points to a role of the mediodorsal thalamic nucleus in regulating prefrontal activity patterns. These hypotheses can be tested by developing specific neuropsychological tasks, parceling the thalamus with high-resolution MRI, and using intracranial recordings in humans. [ABSTRACT FROM AUTHOR]

It is common to look away while trying to remember specific information, for example during autobiographical memory retrieval, a behavior referred to as gaze aversion. Given the competition between internal and external attention, gaze aversion is assumed to play a role in visual decoupling, i.e., suppressing environmental distractors during internal tasks. This suggests a link between gaze aversion and the attentional switch from the outside world to a temporary internal mental space that takes place during the initial stage of memory retrieval, but this assumption has never been verified so far. We designed a protocol where 33 participants answered 48 autobiographical questions while their eye movements were recorded with an eye-tracker and a camcorder. Results indicated that gaze aversion occurred early (median 1.09 s) and predominantly during the access phase of memory retrieval—i.e., the moment when the attentional switch is assumed to take place. In addition, gaze aversion lasted a relatively long time (on average 6 s), and was notably decoupled from concurrent head movements. These results support a role of gaze aversion in perceptual decoupling. Gaze aversion was also related to higher retrieval effort and was rare during memories which came spontaneously to mind. This suggests that gaze aversion might be required only when cognitive effort is required to switch the attention toward the internal world to help retrieving hard-to-access memories. Compared to eye vergence, another visual decoupling strategy, the association with the attentional switch seemed specific to gaze aversion. Our results provide for the first time several arguments supporting the hypothesis that gaze aversion is related to the attentional switch from the outside world to memory. • Gaze aversion was studied during the attentional switch to an inner mental task. • It occurs early (median 1 s) and more often during the access phase to memory. • It is decoupled from concurrent head movements. • It occurs more often and earlier than changes in eye vergence. • Gaze aversion supports perceptual decoupling during the attentional switch. [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]

Novelty detection is essential to adapt to changes. However, the relationship between novelty detection and visual recognition memory remains unclear. To characterize the temporal dynamics of novelty and its connection to familiarity, we probed early behavioural performance of novelty and familiarity in 31 participants using a speeded go/no-go recognition task with a 600-ms response deadline. Responses to familiarity and novelty produced symmetrical biases and correlated accuracies and biases, but novelty decisions were less accurate and had slower minimal reaction times (410 ms). These processes thus appear to be independent, as suggested by a more efficient system in the case of familiarity, but with common factors bringing overlapping contributions to both processes. This may possibly be explained by the more fluent processing of repeated stimuli, but with familiarity and novelty potentially relying on one decision criterion, as suggested by the correlated and remarkably symmetrical biases. This study supports models that conceptualize novelty and familiarity decisions as two partly overlapping processes. [ABSTRACT FROM PUBLISHER]

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]

Models of recognition memory have postulated that the mammillo-thalamic tract (MTT)/anterior thalamic nucleus (AN) complex would be critical for recollection while the Mediodorsal nucleus (MD) of the thalamus would support familiarity and indirectly also be involved in recollection (Aggleton et al., 2011). 12 patients with left thalamic stroke underwent a neuropsychological assessment, three verbal recognition memory tasks assessing familiarity and recollection each using different procedures and a high-resolution structural MRI. Patients showed poor recollection on all three tasks. In contrast, familiarity was spared in each task. No patient had significant AN lesions. Critically, a subset of 5 patients had lesions of the MD without lesions of the MTT. They also showed impaired recollection but preserved familiarity. Recollection is therefore impaired following MD damage, but familiarity is not. This suggests that models of familiarity, which assign a critical role to the MD, should be reappraised. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Episodic memory impairment is at the core of amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). The origin of memory deficits may result either from an encoding deficit or from an accelerated decline of the memory trace. The present study explores these two hypotheses.Method: We used the delayed-matching-to sample 48 items (DMS-48) memory test in a group of controls, aMCI patients, and AD patients (n= 16 in each group). The DMS-48 offers an incidental learning phase followed by three forced-choice recognition tests at three-minute, one-hour, and one-week delays. Moreover, the forced-choice test distinguishes three kinds of couple items: abstract (meaningless), paired (two similar exemplars), and unique (two different objects) items.Results: As predicted by the accelerated forgetting hypothesis, patients showed a decrease in recognition performance over time. Controls also exhibited a similar decline in performance. As predicted by the encoding deficit hypothesis, abstract items were the most poorly recognized in AD, at both the three-minute and the one-week delays. In AD, recognition of the paired items also dropped after the one-hour delay, followed by unique items after a one-week delay. Patients with aMCI exhibited a performance that was similar to controls, except for abstract items, which dropped at the one-week delay.Conclusions: These results are discussed in light of a third hypothesis, the memory strength hypothesis, in order to better account for the progressive decline in memory performance as a function of the item type in AD. [ABSTRACT FROM PUBLISHER]

Summary Purpose Retrieving a specific name is sometimes difficult and can be even harder when pathology affects the temporal lobes. Word finding difficulties have been well documented in temporal lobe epilepsy (TLE) but analyses have mostly concentrated on the study of accuracy. Our aim here was to go beyond simple accuracy and to provide both a quantitative and a qualitative assessment of naming difficulties and latencies in patients with TLE. Methods Thirty-two patients with temporal lobe epilepsy (16 with epilepsy affecting the cerebral hemisphere dominant for language (D-TLE) and 16 with epilepsy affecting the cerebral hemisphere non-dominant for language (ND-TLE)) and 34 healthy matched control subjects were included in the study. The experiment involved naming 70 photographs of objects and 70 photographs of celebrities as fast as possible. Accuracy and naming reaction times were recorded. Following each trial, a questionnaire was used to determine the specific nature of each subject's difficulty in retrieving the name (e.g., no difficulty, paraphasia, tip of the tongue, feeling of knowing the name, etc). Reaction times were analysed both across subjects and across trials. Key findings D-TLE patients showed consistent and quasi-systematic impairment compared to matched control subjects on both object and famous people naming. This impairment was characterized not only by lower accuracy but also by more qualitative errors and tip of the tongue phenomena. Furthermore, minimum reaction times were slowed down by about 70 ms for objects and 150 ms for famous people naming. In contrast, patients with ND-TLE were less impaired, and their impairment was limited to object naming. Significance These results suggest that patients with TLE, in particular D-TLE, show a general impairment of lexical access. Furthermore, there was evidence of subtle difficulties (increased reaction times) in patients with TLE. [ABSTRACT FROM AUTHOR]

Previous magnetoencephalography/electroencephalography (M/EEG) studies have suggested that face processing is extremely rapid, indeed faster than any other object category. Most studies, however, have been performed using centered, cropped stimuli presented on a blank background resulting in artificially low interstimulus variability. In contrast, the aim of the present study was to assess the underlying temporal dynamics of face detection presented in complex natural scenes. We recorded EEG activity while participants performed a rapid go/no-go categorization task in which they had to detect the presence of a human face. Subjects performed at ceiling (94.8% accuracy), and traditional event-related potential analyses revealed only modest modulations of the two main components classically associated with face processing (P100 and N170). A multivariate pattern analysis conducted across all EEG channels revealed that face category could, however, be readout very early, under 100 ms poststimulus onset. Decoding was linked to reaction time as early as 125 ms. Decoding accuracy did not increase monotonically; we report an increase during an initial 95-140 ms period followed by a plateau ~140-185 ms-perhaps reflecting a transitory stabilization of the face information available-and a strong increase afterward. Further analyses conducted on individual images confirmed these phases, further suggesting that decoding accuracy may be initially driven by low-level stimulus properties. Such latencies appear to be surprisingly short given the complexity of the natural scenes and the large intraclass variability of the face stimuli used, suggesting that the visual system is highly optimized for the processing of natural scenes. [ABSTRACT FROM AUTHOR]

We report the case of a 62-year-old asymptomatic carrier of AβPP gene duplication. He was investigated by MRI and the amyloid ligand 18F-AV45, and compared to Alzheimer's disease patients (n = 11) and healthy controls (n = 11). The neuropsychological examination was normal. Cortical thickness and AV45 retention were comparable to Alzheimer's disease patients. AβPP duplication was diagnosed because cerebral amyloid angiopathy and Alzheimer's disease pathology were found on the neuropathological examination of his youngest brother, who died at 42 from intracerebral hemorrhage. This is the first description of a pre-symptomatic AβPP duplication carrier over 60, despite widespread cerebral amyloid angiopathy, 'Alzheimer's like' atrophy, and amyloid deposition. [ABSTRACT FROM AUTHOR]

An increasing number of studies indicate that semantic memory is impaired in mild cognitive impairment (MCI). However, the extent and the neural basis of this impairment remain unknown. The aim of the present study was: 1) to evaluate whether all or only a subset of semantic domains are impaired in MCI patients; and 2) to assess the neural substrate of the semantic impairment in MCI patients using voxel-based analysis of MR grey matter density and SPECT perfusion. 29 predominantly amnestic MCI patients and 29 matched control subjects participated in this study. All subjects underwent a full neuropsychological assessment, along with a battery of five tests evaluating different domains of semantic memory. A semantic memory composite Z-score was established on the basis of this battery and was correlated with MRI grey matter density and SPECT perfusion measures. MCI patients were found to have significantly impaired performance across all semantic tasks, in addition to their anterograde memory deficit. Moreover, no temporal gradient was found for famous faces or famous public events and knowledge for the most remote decades was also impaired. Neuroimaging analyses revealed correlations between semantic knowledge and perirhinal/entorhinal areas as well as the anterior hippocampus. Therefore, the deficits in the realm of semantic memory in patients with MCI is more widespread than previously thought and related to dysfunction of brain areas beyond the limbic-diencephalic system involved in episodic memory. The severity of the semantic impairment may indicate a decline of semantic memory that began many years before the patients first consulted. [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]

Investigations of the neural correlates of face recognition have typically used old/new paradigms where subjects learn to recognize new faces or identify famous faces. Familiar faces, however, include one's own face, partner's and parents' faces. Using event-related fMRI, we examined the neural correlates of these personally familiar faces. Ten participants were presented with photographs of own, partner, parents, famous and unfamiliar faces and responded to a distinct target. Whole brain, two regions of interest (fusiform gyrus and cingulate gyrus), and multiple linear regression analyses were conducted. Compared with baseline, all familiar faces activated the fusiform gyrus; own faces also activated occipital regions and the precuneus; partner faces activated similar areas, but in addition, the parahippocampal gyrus, middle superior temporal gyri and middle frontal gyrus. Compared with unfamiliar faces, only personally familiar faces activated the cingulate gyrus and the extent of activation varied with face category. Partner faces also activated the insula, amygdala and thalamus. Regions of interest analyses and laterality indices showed anatomical distinctions of processing the personally familiar faces within the fusiform and cingulate gyri. Famous faces were right lateralized whereas personally familiar faces, particularly partner and own faces, elicited bilateral activations. Regression analyses show experiential predictors modulated with neural activity related to own and partner faces. Thus, personally familiar faces activated the core visual areas and extended frontal regions, related to semantic and person knowledge and the extent and areas of activation varied with face type. Hum Brain Mapp, 2009. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

• First in vivo tetrode recordings in humans. • No clinical complications or adverse events. • On average 2.08 ± 2.86 single units per tetrode (sometimes >10). Recordings with tetrodes have proven to be more effective in isolating single neuron spiking activity than with single microwires. However, tetrodes have never been used in humans. We report on the characteristics, safety, compatibility with clinical intracranial recordings in epileptic patients, and performance, of a new type of hybrid electrode equipped with tetrodes. 240 standard clinical macroelectrodes and 102 hybrid electrodes were implanted in 28 patients. Hybrids (diameter 800 μm) are made of 6 or 9 macro-contacts and 2 or 3 tetrodes (diameter 70−80 μm). No clinical complication or adverse event was associated with the hybrids. Impedance and noise of recordings were stable over time. The design enabled multiscale spatial analyses that revealed physiopathological events which were sometimes specific to one tetrode, but could not be recorded on the macro-contacts. After spike sorting, the single-unit yield was similar to other hybrid electrodes and was sometimes as high as >10 neurons per tetrode. This new hybrid electrode has a smaller diameter than other available hybrid electrodes. It provides novel spatial information due to the configuration of the tetrodes. The single-unit yield appears promising. This new hybrid electrode is safe, easy to use, and works satisfactorily for conducting multi-scale seizure and physiological analyses. [ABSTRACT FROM AUTHOR]