Large-scale network dynamics underlying the first few hundred milliseconds after stimulus presentation: An investigation of visual recognition memory using iEEG.

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.

Intracranial electrical brain stimulation as an approach to studying the (dis)continuum of memory experiential phenomena.

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.

A Meta-Analysis of Semantic Memory in Mild Cognitive Impairment.

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.

A Fast Visual Recognition Memory System in Humans Identified Using Intracerebral ERP.

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.

Déjà vu and prescience in a case of severe episodic amnesia following bilateral hippocampal lesions.

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.

Improving the integrative memory model by integrating the temporal dynamics of memory.

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.

An Analysis of Famous Person Semantic Memory in Aging.

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.

Superior explicit memory despite severe developmental amnesia: In-depth case study and neural correlates.

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.

Hippocampus duality: Memory and novelty detection are subserved by distinct mechanisms.

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.

The neural dynamics of face detection in the wild revealed by MVPA.

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.

Insight on AV-45 binding in white and grey matter from histogram analysis: a study on early Alzheimer's disease patients and healthy subjects.

PURPOSE: AV-45 amyloid biomarker is known to show uptake in white matter in patients with Alzheimer's disease (AD), but also in the healthy population. This binding, thought to be of a non-specific lipophilic nature, has not yet been investigated. The aim of this study was to determine the differential pattern of AV-45 binding in white matter in healthy and pathological populations. METHODS: We recruited 24 patients presenting with AD at an early stage and 17 matched, healthy subjects. We used an optimized positron emission tomography-magnetic resonance imaging (PET-MRI) registration method and an approach based on an intensity histogram using several indices. We compared the results of the intensity histogram analyses with a more canonical approach based on target-to-cerebellum Standard Uptake Value (SUVr) in white and grey matter using MANOVA and discriminant analyses. A cluster analysis on white and grey matter histograms was also performed. RESULTS: White matter histogram analysis revealed significant differences between AD and healthy subjects, which were not revealed by SUVr analysis. However, white matter histograms were not decisive to discriminate groups, and indices based on grey matter only showed better discriminative power than SUVr. The cluster analysis divided our sample into two clusters, showing different uptakes in grey, but also in white matter. CONCLUSION: These results demonstrate that AV-45 binding in white matter conveys subtle information not detectable using the SUVr approach. Although it is not more efficient than standard SUVr in discriminating AD patients from healthy subjects, this information could reveal white matter modifications.

Contextual novelty detection and novelty-related memory enhancement in amnestic mild cognitive impairment.

INTRODUCTION: Though novelty processing plays a critical role in memory function, little is known about how it influences learning in memory-impaired populations, such as amnestic Mild Cognitive Impairment (aMCI). METHODS: 21 aMCI patients and 22 age- and education-matched healthy older participants performed two tasks-(i) an oddball paradigm where fractals that were often repeated (60 % of the stimuli), less frequently repeated (20 %), or novel (presented once each) were shown to assess novelty preference (longer viewing time for novel than familiar stimuli), and (ii) a Von Restorff paradigm assessing novelty-related effects on memory. Participants studied 22 lists of 10 words. Among these lists, 18 contained an isolated word different from the others by its distinctive aspect, here the font size (90-point, 120-point or 150-point against 60-point for non-isolated words). The remaining four were control lists without isolated words. After studying each list, participants freely recalled the maximum words possible. RESULTS: For the oddball task, a group-by-stimulus type ANOVA on median viewing times revealed a significant effect of stimulus type, but not of group. Both groups spent more time on novel stimuli. For the Von Restorff task, both aMCI and healthy controls recalled the isolated words (presented in 120-point or 150-point, but not 90-point) better than others (excluding primacy and recency effects). Novelty-related memory benefit-gain factor-was computed as the difference between the recall scores for isolated and other words. A group-by-font size ANOVA on gain factors revealed no group effect, nor interaction, suggesting that aMCI patients benefited from novelty, alike controls. CONCLUSION: Novelty preference and the boosting effect of isolation-related novelty on subsequent recall seem preserved despite impaired episodic memory in aMCI patients. This is discussed in the light of contemporary divergent theories regarding the relationship between novelty and memory, as either being independent or parts of a continuum.

Exploring the impact of the interthalamic adhesion on human cognition: insights from healthy subjects and thalamic stroke patients.

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.

Robust thalamic nuclei segmentation from T1-weighted MRI using polynomial intensity transformation.

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 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 (3T and 7T). 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.

Robust thalamic nuclei segmentation from T1-weighted MRI using polynomial intensity transformation.

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.

Identification of Early Hippocampal Dynamics during Recognition Memory with Independent Component Analysis.

The hippocampus is generally considered to have relatively late involvement in recognition memory, its main electrophysiological signature being between 400 and 800 ms after stimulus onset. However, most electrophysiological studies have analyzed the hippocampus as a single responsive area, selecting only a single-site signal exhibiting the strongest effect in terms of amplitude. These classical approaches may not capture all the dynamics of this structure, hindering the contribution of other hippocampal sources that are not located in the vicinity of the selected site. We combined intracerebral electroencephalogram recordings from epileptic patients with independent component analysis during a recognition memory task involving the recognition of old and new images. We identified two sources with different responses emerging from the hippocampus: a fast one (maximal amplitude at ∼250 ms) that could not be directly identified from raw recordings and a latter one, peaking at ∼400 ms. The former component presented different amplitudes between old and new items in 6 out of 10 patients. The latter component had different delays for each condition, with a faster activation (∼290 ms after stimulus onset) for recognized items. We hypothesize that both sources represent two steps of hippocampal recognition memory, the faster reflecting the input from other structures and the latter the hippocampal internal processing. Recognized images evoking early activations would facilitate neural computation in the hippocampus, accelerating memory retrieval of complementary information. Overall, our results suggest that the hippocampal activity is composed of several sources with an early activation related to recognition memory.

Impaired visual recognition memory predicts Alzheimer's disease in amnestic mild cognitive impairment.

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.

MR, (18)F-FDG, and (18)F-AV45 PET correlate with AD PSEN1 original phenotype.

We report the case of a 37-year-old man suffering from insidious visual agnosia and spastic paraparesis due to a PSEN1 mutation. His mother was diagnosed with Alzheimer disease after a biopsy. He was assessed by multimodal neuroimaging, including new in vivo positron emission tomography amyloid imaging (F-AV45). His data were compared with those from healthy participants and patients with sporadic predemential Alzheimer disease. He exhibited posterior cortical thickness reduction, posterior hypometabolism, and increased amyloid ligand uptake in the posterior cortex and the striatum. We show that F-AV45 positron emission tomography allows visualization of the unusual pattern of amyloid deposits that co-localize with cortical atrophy in this genetic form of Alzheimer disease.

Why and when do you look away when trying to remember? Gaze aversion as a marker of the attentional switch to the internal world during memory retrieval.

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.

Attentional switch to memory: An early and critical phase of the cognitive cascade allowing autobiographical memory retrieval.

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.