Impairment of social cognition in neurological diseases.

Social cognition is impaired in a large number of neurological afflictions, including neurodegenerative diseases, neuropsychiatric disorders and neurodevelopmental syndromes, and has become a significant element in differential diagnoses. This report describes the different processes involved in social cognition and the way in which they work together to allow adapted behaviors. This is then followed by the numerous clinical symptoms of social behavioral disturbances and social cognition performance in different neurological afflictions such as frontotemporal lobar degeneration, Alzheimer's disease and schizophrenia. In addition, the available tasks allowing social cognition assessment in routine clinical practice are also presented.

Hippocampal modifications in transient global amnesia.

Transient global amnesia (TGA) is an acute and transient syndrome with a remarkably stereotypical set of signs and symptoms. It is characterized by the abrupt onset (no forewarning) of massive episodic memory impairment, both anterograde and retrograde. Ever since it was first described, TGA has fascinated neurologists and other memory experts, and in recent years, there has been a surge of neuroimaging studies seeking to pin down the brain dysfunction responsible for it. Several pathophysiological hypotheses have been put forward, including the short-lived suggestion of an epileptic mechanism. All the available data indicate that the brain modifications are reversible, and that the mechanism behind TGA is of a functional nature. However, while diffusion-weighted imaging studies have clearly identified the hippocampus and, more specifically, the CA1 area, as the locus of brain modifications associated with TGA, researchers have yet to determine whether the origin of the mechanism is vascular or neurochemical. Spectroscopy may provide a means of settling this issue once and for all.

Sense of identity in advanced Alzheimer's dementia: a cognitive dissociation between sameness and selfhood?

We looked at whether sense of identity persists in patients with Alzheimer's disease (AD) and if its profile remains the same between two examinations. A specifically designed protocol was administered to 16 AD patients in the mild to severe stages of dementia and to 16 matched healthy controls, both living in the same institution. We showed that sense of identity was broadly preserved in AD patients. The patterns of their responses were similar to those of controls, and remained consistent over a two-week period. However, some qualitative characteristics of sense of identity in AD patients differed significantly from those of controls, suggesting that AD patients may not be able to update their self-knowledge, probably because of their episodic memory deficit. These results are discussed in the light of both current models of the self and philosophical concepts such as sameness and selfhood.

Using PET with 18F-AV-45 (florbetapir) to quantify brain amyloid load in a clinical environment.

PURPOSE: Positron emission tomography (PET) imaging of brain amyloid load has been suggested as a core biomarker for Alzheimer's disease (AD). The aim of this study was to test the feasibility of using PET imaging with (18)F-AV-45 (florbetapir) in a routine clinical environment to differentiate between patients with mild to moderate AD and mild cognitive impairment (MCI) from normal healthy controls (HC). METHODS: In this study, 46 subjects (20 men and 26 women, mean age of 69.0 ± 7.6 years), including 13 with AD, 12 with MCI and 21 HC subjects, were enrolled from three academic memory clinics. PET images were acquired over a 10-min period 50 min after injection of florbetapir (mean ± SD of radioactivity injected, 259 ± 57 MBq). PET images were assessed visually by two individuals blinded to any clinical information and quantitatively via the standard uptake value ratio (SUVr) in the specific regions of interest, which were defined in relation to the cerebellum as the reference region. RESULTS: The mean values of SUVr were higher in AD patients (median 1.20, Q1-Q3 1.16-1.30) than in HC subjects (median 1.05, Q1-Q3 1.04-1.08; p = 0.0001) in the overall cortex and all cortical regions (precuneus, anterior and posterior cingulate, and frontal median, temporal, parietal and occipital cortex). The MCI subjects also showed a higher uptake of florbetapir in the posterior cingulate cortex (median 1.06, Q1-Q3 0.97-1.28) compared with HC subjects (median 0.95, Q1-Q3 0.82-1.02; p = 0.03). Qualitative visual assessment of the PET scans showed a sensitivity of 84.6% (95% CI 0.55-0.98) and a specificity of 38.1% (95% CI 0.18-0.62) for discriminating AD patients from HC subjects; however, the quantitative assessment of the global cortex SUVr showed a sensitivity of 92.3% and specificity of 90.5% with a cut-off value of 1.122 (area under the curve 0.894). CONCLUSION: These preliminary results suggest that PET with florbetapir is a safe and suitable biomarker for AD that can be used routinely in a clinical environment. However, the low specificity of the visual PET scan assessment could be improved by the use of specific training and automatic or semiautomatic quantification tools.

The neural substrates of musical memory revealed by fMRI and two semantic tasks.

Recognizing a musical excerpt without necessarily retrieving its title typically reflects the existence of a memory system dedicated to the retrieval of musical knowledge. The functional distinction between musical and verbal semantic memory has seldom been investigated. In this fMRI study, we directly compared the musical and verbal memory of 20 nonmusicians, using a congruence task involving automatic semantic retrieval and a familiarity task requiring more thorough semantic retrieval. In the former, participants had to access their semantic store to retrieve musical or verbal representations of melodies or expressions they heard, in order to decide whether these were then given the right ending or not. In the latter, they had to judge the level of familiarity of musical excerpts and expressions. Both tasks revealed activation of the left inferior frontal and posterior middle temporal cortices, suggesting that executive and selection processes are common to both verbal and musical retrievals. Distinct patterns of activation were observed within the left temporal cortex, with musical material mainly activating the superior temporal gyrus and verbal material the middle and inferior gyri. This cortical organization of musical and verbal semantic representations could explain clinical dissociations featuring selective disturbances for musical or verbal material.

Musical and verbal semantic memory: two distinct neural networks?

Semantic memory has been investigated in numerous neuroimaging and clinical studies, most of which have used verbal or visual, but only very seldom, musical material. Clinical studies have suggested that there is a relative neural independence between verbal and musical semantic memory. In the present study, "musical semantic memory" is defined as memory for "well-known" melodies without any knowledge of the spatial or temporal circumstances of learning, while "verbal semantic memory" corresponds to general knowledge about concepts, again without any knowledge of the spatial or temporal circumstances of learning. Our aim was to compare the neural substrates of musical and verbal semantic memory by administering the same type of task in each modality. We used high-resolution PET H(2)O(15) to observe 11 young subjects performing two main tasks: (1) a musical semantic memory task, where the subjects heard the first part of familiar melodies and had to decide whether the second part they heard matched the first, and (2) a verbal semantic memory task with the same design, but where the material consisted of well-known expressions or proverbs. The musical semantic memory condition activated the superior temporal area and inferior and middle frontal areas in the left hemisphere and the inferior frontal area in the right hemisphere. The verbal semantic memory condition activated the middle temporal region in the left hemisphere and the cerebellum in the right hemisphere. We found that the verbal and musical semantic processes activated a common network extending throughout the left temporal neocortex. In addition, there was a material-dependent topographical preference within this network, with predominantly anterior activation during musical tasks and predominantly posterior activation during semantic verbal tasks.

The advantage of errorless learning for the acquisition of new concepts' labels in alcoholics.

BACKGROUND: Previous findings revealed that the acquisition of new semantic concepts' labels was impaired in uncomplicated alcoholic patients. The use of errorless learning may therefore allow them to improve learning performance. However, the flexibility of the new knowledge and the memory processes involved in errorless learning remain unclear. METHOD: New concepts' labels acquisition was examined in 15 alcoholic patients and 15 control participants in an errorless learning condition compared with 19 alcoholic patients and 19 control subjects in a trial-and-error learning condition. The flexibility of the new information was evaluated using different photographs from those used in the learning sessions but representing the same concepts. All of the participants carried out an additional explicit memory task and an implicit memory task was also performed by subjects in the errorless learning condition. RESULTS: The alcoholic group in the errorless condition differed significantly from the alcoholic group in the trial-and-error condition but did not differ from the two control groups. There was no significant difference between results in the learning test and the flexibility task. Finally, in the alcoholic group, the naming score in the learning test was correlated with the explicit memory score but not with the implicit memory score. CONCLUSIONS: Using errorless learning, alcoholics improved their abilities to learn new concepts' labels. Moreover, new knowledge acquired with errorless learning was flexible. The errorless learning advantage may rely on explicit rather than implicit memory processes in these alcohol-dependent patients presenting only mild to moderate deficits of explicit memory capacities.

[Sleep and episodic memory: a review of the literature in young healthy subjects and potential links between sleep changes and memory impairment observed during aging and Alzheimer's disease]. / Étude des liens entre sommeil et mémoire épisodique chez le sujet jeune et âgé, et dans la maladie d'Alzheimer.

INTRODUCTION: A large body of evidence indicates that sleep favors memory consolidation. STATE OF THE ART: This process would occur, mainly during slow-wave sleep, by means of a dialogue between the hippocampus and neocortical areas. Low levels of acetylcholine and cortisol are also needed to favor the transfer of memory traces toward the neocortex, where they will be stored for the long-term. PERSPECTIVES: The aim of this article is, first, to give an overview of studies conducted in young healthy subjects and underpinning the hypothesis that sleep is involved in memory consolidation. Then, we will investigate the potential links between changes in sleep architecture and episodic memory impairment in both aging and Alzheimer's disease. Finally, we will see how these results can affect clinical practice. CONCLUSION: Sleep-dependent memory consolidation is impaired both in aging and Alzheimer's disease. These findings suggest the importance of taking into account sleep when assessing memory function in patients.

[The default mode network: cognitive role and pathological disturbances]. / Le réseau cérébral par défaut : rôle cognitif et perturbations dans la pathologie.

INTRODUCTION: A "resting state" or "default mode network" has been highlighted in functional neuroimaging studies as a set of brain regions showing synchronized activity at rest or in task-independent cognitive state. STATE OF THE ART: A considerable and increasing number of studies have been conducted over the last few years so as to unravel the cognitive function(s) of this brain network. PERSPECTIVES: This review gives an overview of anatomical, physiological and phenomenological data regarding the default mode network. Different hypotheses have been proposed regarding the role of this network. Several studies have highlighted its involvement in autobiographical memory, prospection, self, attention, and theory of mind. The influence of the attention level and consciousness onto resting state brain network activity has also been discussed. Specific changes have been described in normal aging, Alzheimer's disease (AD) and multiple sclerosis (MS). CONCLUSIONS: These studies altogether contribute to a better definition of the default mode network, in terms of implicated brain structures, subtending mechanisms, and potential cognitive roles. For instance, similarities and relationships were found between self-related brain activity and resting-state activity in regions belonging to this network, namely posterior cingulate and prefrontal areas that may reflect introspective activity experienced, more or less consciously, when the brain is not specifically engaged in a cognitive task. As a whole, the default mode network appears as a non human-specific intrinsic functional network, active all over the life from birth until aging where it is progressively modified, and sensitive to different pathologies including AD and MS. On the other hand, many points remain to be clarified concerning this network, such as the exact part of its activity dedicated to self-related cognitive processes (introspection, imaginary mental scenario based on past autobiographical experiences) and that involved in a sentinel-like attentional process designated to react to possible environmental events. Indeed, it seems that this network is functional even in case of low level of consciousness, i.e., during light sleep. Conversely, a loss of self and environment perception as in coma, deep sleep or anesthesia might modulate its connectivity along the anteroposterior axis, i.e., frontal activity disappearance associated with a parietal reinforcement of connectivity. Since studies aiming at highlighting these points are still uncommon to date, exhaustive and objective explorations are needed to better understand all these resting state processes.

Direct voxel-based comparison between grey matter hypometabolism and atrophy in Alzheimer's disease.

Although the patterns of structural and metabolic brain alterations in Alzheimer's disease are being refined and discrepancies between them are being underlined, the exact relationships between atrophy and hypometabolism are still unclear. In this study, we aimed to provide a direct comparison between grey matter atrophy and hypometabolism in a sample of patients with clinically probable Alzheimer's disease, using a voxel-based method specially designed to statistically compare the two imaging modalities. Eighteen patients with probable Alzheimer's disease of mild severity and 15 healthy aged controls underwent both high-resolution T1 MRI and resting-state (18)FDG-PET. The MRI data sets were handled using optimized VBM. The PET data were coregistered to their corresponding MRI, corrected voxel-wise for partial volume averaging and spatially normalized using the same parameters as those of their corresponding MRI volume. A differential smoothing was applied on the MRI and PET data sets to equalize their effective smoothness and resolution. For each patient, Z-score maps of atrophy and hypometabolism were created by comparing to the controls data set, respectively averaged to provide the profile of hypometabolism and atrophy, and entered in a voxel-by-voxel SPM analysis to assess the statistical differences between hypometabolism and atrophy. The observed patterns of hypometabolism and atrophy were consistent with previous studies. However, the direct comparison revealed marked regional variability in the relationship between hypometabolism and atrophy. Thus, the hypometabolism significantly exceeded atrophy in most altered structures, particularly in the posterior cingulate-precuneus, orbitofrontal, inferior temporo-parietal, parahippocampal, angular and fusiform areas. In contrast, a few hypometabolic structures among which the hippocampus exhibited similar degrees of atrophy and hypometabolism, a profile that significantly differed from the posterior cingulate. Excessive hypometabolism relative to atrophy suggests the intervention of additional hypometabolism-inducing factors, such as disconnection and amyloid deposition, resulting in genuine functional perturbation ahead of actual atrophy and perhaps of pathology as well. Conversely, in the hippocampus, where disconnection processes are also likely to occur, relative synaptic compensatory mechanisms may be taking place, maintaining neuronal activity in the face of structural alterations.

Three-dimensional surface mapping of hippocampal atrophy progression from MCI to AD and over normal aging as assessed using voxel-based morphometry.

The hippocampus is the brain structure of highest and earliest structural alteration in Alzheimer's disease (AD). New developments in neuroimaging methods recently made it possible to assess the respective involvement of the different hippocampal subfields by mapping atrophy on a 3D hippocampal surface view. In this longitudinal study on patients with mild cognitive impairment (MCI), we used such an approach to map the profile of hippocampal atrophy and its progression over an 18-month follow-up period in rapid converters to AD and "non-converters" compared to age-matched controls. For the sake of comparison, we also assessed the profile of hippocampal atrophy associated with AD and with increasing age in a healthy control population ranging from young adult to elderly. We found major involvement of the lateral part of the superior hippocampus mainly corresponding to the CA1 subfield in MCI and AD while increasing age was mainly associated with subiculum atrophy in the healthy population. Moreover, the CA1 subfield also showed highest atrophy rates during follow-up, in both rapid converters and "non-converters" although increased effects were observed in the former group. This study emphasizes the differences between normal aging and AD processes leading to hippocampal atrophy, pointing to a specific AD-related CA1 involvement while subiculum atrophy would represent a normal aging process. Our findings also suggest that the degree of hippocampal atrophy, more than its spatial localization, predicts rapid conversion to AD in patients with MCI.

Perceptual priming enhances the creation of new episodic memories.

In recent years, most studies of human memory systems have placed the emphasis on differences rather than on similarities. The present study sought to assess the impact of perceptual priming on the creation of new episodic memories. It was composed of three distinct experimental phases: (1) an initial study phase, during which the number of repetitions of target words was manipulated; (2) a perceptual priming test phase, involving both target and new control words, which constituted the incidental encoding phase of (3) a subsequent Remember/Know/Guess recognition task. Results showed that the greater the perceptual priming at encoding, the more the episodic memory performance was enhanced, whereas no such relation was found for know judgments or feeling of familiarity. Furthermore, the words that were associated with the creation of new episodic memories had been perceptually primed to a greater extent during the incidental encoding phase than the words that were subsequently judged to be known or forgotten. These results suggest that the perceptual contents of episodic memories are constituted by the very perceptual representations that generate priming effects. Potential mechanisms linking perceptual priming to the creation of episodic memories are discussed.

[Cerebral imaging in healthy aging: contrast with Alzheimer disease]. / Imagerie cérébrale du vieillissement normal : contraste avec la maladie d'Alzheimer.

With age, the brain undergoes both structural and functional alterations. Overall, the literature consistently reports global brain atrophy in normal adults, generally more pronounced in frontal areas. As a result of different methodologies and inclusion criteria, other brain areas have been the matter of conflicting findings, notably the hippocampus. Regarding resting-state PET studies, they have consistently highlighted a metabolic deterioration of the frontal and anterior cingulated cortices. By contrast, relatively few investigations have sought to identify those areas that remain intact with aging, or undergo the least deterioration. We report a study designed to establish a comprehensive profile of both structural and functional changes in the aging brain, using up-to-date voxel-based methodology in 45 optimally healthy subjects aged 20-83 years. One of the main findings is that the lesser structural deterioration of the anterior hippocampal region, together with the lesser functional alteration of the posterior cingulate cortex, appear to mark the parting of the ways between normal aging and Alzheimer's disease, which is characterized by early and prominent deterioration of both structures. This paper also deals with studies set out to establish the relationship between changes in episodic memory retrieval in normal aging on the one hand and gray matter volume and 18FDG uptake on the other hand. Frontal areas dysfunction is involved in memory decline in older subjects, at least in some conditions, a finding which clearly contrasts with that found in Alzheimer's disease where the hippocampus plays a key role. Finally, compensatory mechanisms are reviewed through activation studies which often show supplementary activations in old subjects compared to young as well as in Alzheimer's disease patients compared to healthy elderly subjects. Paradoxically, those mechanisms seem to be underpinned, at least partially, by frontal areas in both populations, but researches are needed to better identify which subregions are involved.

[The twenty-first century as a neuropsychology era]. / Le XXI(e) siècle sera neuropsychologique ou ne sera pas !

This article reviews how neuropsychology, in the French-speaking world, has evolved as a discipline focused on research, teaching and clinical work. The article targets the last 30 years as this corresponds to the time at which the Société de Neuropsychologie de Langue Française (French-Speaking Neuropsychological Society) was created. The review addresses how the cognitive neuropsychology approach and the advent of brain imaging have shaped the field of neuropsychology in recent years. It presents the status of the discipline in the main French-speaking countries (where neuropsychology is currently developed) including France, Belgium, Switzerland and Canada. It also analyzes a number of indicators that reflect the vitality of the discipline and its cohesion as a science and as a clinical domain. These indicators include the creation of specialized journals, organization of scientific meetings, accessibility to training programs in neuropsychology, development of discipline-oriented clinical programs, and the increase in scientific productivity. The Quebec academic environment is used as an illustration, whereby structured clinical doctoral training programs that meet national standards in neuropsychology were implemented to train clinical neuropsychologists. Finally, the authors emphasize the major role that the discipline is likely to play at different levels of society in the near future.

Voxel-based mapping of grey matter volume and glucose metabolism profiles in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease of the nervous system involving both upper and lower motor neurons. The patterns of structural and metabolic brain alterations are still unclear. Several studies using anatomical MRI yielded a number of discrepancies in their results, and a few PET studies investigated the effect of ALS on cerebral glucose metabolism. The aim of this study was threefold: to highlight the patterns of grey matter (GM) atrophy, hypometabolism and hypermetabolism in patients with ALS, then to understand the neurobehavioral significance of hypermetabolism and, finally, to investigate the regional differences between the morphologic and functional changes in ALS patients, using a specially designed voxel-based method. Thirty-seven patients with ALS and 37 age- and sex-matched healthy individuals underwent both structural MRI and 18[F]-fluorodeoxyglucose (FDG) PET examinations. PET data were corrected for partial volume effects. Structural and metabolic abnormalities were examined in ALS patients compared with control subjects using two-sample t tests in statistical parametric mapping (SPM). Then, we extracted the metabolic values of clusters presenting hypermetabolism to correlate with selected cognitive scores. Finally, GM atrophy and hypometabolism patterns were directly compared with a one-paired t test in SPM. RESULTS: We found GM atrophy as well as hypometabolism in motor and extra motor regions and hypermetabolism in medial temporal lobe and cerebellum. We observed negative correlations between the metabolism of the right and left parahippocampal gyri and episodic memory and between the metabolism of right temporal pole and cognitive theory of mind. GM atrophy predominated in the temporal pole, left hippocampus and right thalamus, while hypometabolism predominated in a single cluster in the left frontal superior medial cortex. CONCLUSIONS: Our findings provide direct evidence of regional variations in the hierarchy and relationships between GM atrophy and hypometabolism in ALS. Moreover, the 18FDG-PET investigation suggests that cerebral hypermetabolism is deleterious to cognitive function in ALS.

Pathophysiology of the behavioral variant of frontotemporal lobar degeneration: A study combining MRI and FDG-PET.

Gray matter (GM) lobar atrophy and glucose hypometabolism are well-described hallmarks of frontotemporal lobar degeneration (FTLD), but the relationships between them are still poorly understood. In this study, we aimed to show the patterns of GM atrophy and hypometabolism in a sample of 15 patients with the behavioral variant of FTLD (bv-FTD), compared to 15 healthy controls, then to provide a direct comparison between GM atrophy and hypometabolism, using a voxel-based method specially designed to statistically compare the two imaging modalities. The participants underwent structural magnetic resonance imaging and 18F-fluorodeoxyglucose (FDG) positron emission tomography examinations. First, between-group comparisons of GM volume and metabolism were performed. Then, in the patient group, correlations between regional alterations and direct between-modality voxelwise comparison were performed. Finally, we examined individual patterns of brain abnormalities for each imaging modality and each patient. The observed patterns of GM atrophy and hypometabolism were consistent with previous studies. We found significant voxelwise correlations between changes in GM and FDG uptake, mainly in the frontal cortex, corresponding to the typical profile of alterations in bv-FTD. The direct comparison revealed regional variability in the relationship between hypometabolism and atrophy. This analysis revealed greater atrophy than hypometabolism in the right putamen and amygdala, and left insula and superior temporal gyrus, whereas hypometabolism was more severe than GM atrophy in the left caudate nucleus and anterior cingulate cortex. Finally, GM atrophy affected the right amygdala/hippocampus and left insula in 95 % of the patients. These findings provide evidence for regional variations in the hierarchy of hypometabolism and GM atrophy and the relationships between them, and enhance our understanding of the pathophysiology of bv-FTD.

[Brain profile of hypometabolism in early Alzheimer's disease: relationships with cognitive deficits and atrophy]. / Profil d'hypométabolisme au stade précoce de la maladie d'Alzheimer: lien avec les déficits mnésiques et le profil d'atrophie.

While accurate and early prediction of patients that will develop Alzheimer's disease (AD) in the near future is urgently needed, the amnestic Mild Cognitive Impairment (MCI) state is of particular interest since it most conveniently represents the pre-dementia stage of AD. Consistently, the profile of brain functional alteration constantly evidenced in resting-state SPECT and PET studies is similar to that observed in mild AD, mainly involving the posterior cingulate and temporo-parietal regions. While the former is a characteristic feature of MCI, since it is present in each patient at this stage, the latter seems specifically associated with the future conversion to AD. Moreover, right temporo-parietal hypometabolism has been found to be the best predictor of subsequent global cognitive decline, over and above neuropsychological and MRI volumetric measurements. This review also presents a discussion on the relationships between the brain profile of hypometabolism on the one hand, and cognitive impairment as well as cerebral structural alterations on the other. Thus, firstly, while functional impairment in the posterior cingulate region seems to be associated with deficits in retrieval of episodic memories in MCI, the relationship between right temporo-parietal hypometabolism and cognitive impairment is still obscure. However, several arguments point to its relation with visuo-spatial deficits, which are often associated with future conversion to AD. Secondly, the discordance between brain areas of major functional changes, and those of highest structural alterations, leads to some relevant questions about the relations between both pathological manifestations and their underlying mechanisms. More specifically, additional hypometabolism-inducing factors could occur in areas of highest hypometabolism compared to atrophy, i.e. mainly in posterior associative cortical regions, leading to genuine functional perturbation in early AD before the development of real atrophy and perhaps of disease as well. By contrast, the hippocampus is the main site of atrophy while its functional alteration is still debated, suggesting that compensation/protective mechanisms probably specifically occur in this structure to maintain a high level of metabolism relative to its structural alteration.

[Alzheimer's disease and human memory]. / La maladie d'Alzheimer et la mémoire humaine.

Memory disorders observed in Alzheimer's disease gave rise, from the eighties, to a detailed analysis into the framework of cognitive neuropsychology which aimed at describing the deficits of very specific processes. Beyond their clinical interest, these studies contributed to the modelisation of human memory thanks to the characterization of different memory systems and their relationships. The first part of this paper gives an overview of the memory deficits in Alzheimer's disease and insists on particular cognitive phenomena. Hence, several examples are developed in the domains of semantic memory (such as hyperpriming and hypopriming effects) and autobiographical memory. Recent results highlight the existence of severe autobiographical amnesia observed in all neurodegenerative diseases, though with contrasting profiles: Ribot's gradient in Alzheimer's disease (showing that remote memories are better preserved than recent ones), reverse gradient in semantic dementia and no clear gradient in the frontal variant of frontotemporal dementia. The second part of this article presents advances in cognitive neuroscience searching to disclose the cerebral substrates of these cognitive deficits in Alzheimer's disease. The studies using functional imaging techniques are the most informative regarding this problematic. While showing the dysfunctions of an extended network, they emphasize the selectivity of cerebral damages that are at the root of very specific cognitive dysfunctions, coming close in that way to the conceptions of cognitive neuropsychology. These neuroimaging studies unravel the existence of compensatory mechanisms, which until recently were clearly missing in the literature on neurodegenerative diseases. These different researches lead to a wide conception of human memory, not just limited to simple instrumental processes (encoding, storage, retrieval), but necessarily covering models of identity and continuity of the subject, which interact in a dynamic way with eminently changing memory representations.

New questions on the hemispheric encoding/retrieval asymmetry (HERA) model assessed by divided visual-field tachistoscopy in normal subjects.

According to the hemispheric encoding/retrieval asymmetry (HERA) model, based on data obtained through functional neuroimaging, the left and right prefrontal cortices are preferentially, and, respectively, involved in long-term episodic memory encoding and retrieval. In this study, the HERA model was tested from a behavioral perspective using divided visual-field tachistoscopy. A recognition paradigm with both verbal and visuospatial materials was devised to differentiate memory-related effects (encoding vs. retrieval) from effects linked to the materials. The paradigm used lists of 12 and four items to assess long-term episodic memory and short-term memory, respectively. The aim of the latter condition was to test whether the HERA model is applicable in short-term memory. For long-term episodic memory, the data obtained validated the HERA model; the direction of the hemispheric asymmetry was found to depend on the type of materials used, whereas its magnitude was determined by the type of memory process. For verbal short-term memory, the HERA model seems to be confirmed. The pre-existing representations of the material could take into account the similarity of the hemispheric asymmetry pattern between short-term memory and long-term memory. In contrast, for visuospatial short-term memory, Baddeley's working memory model seems to better explain our results insofar as the asymmetries were essentially linked to the material in encoding but not in retrieval. This latter difference between short-term memory and long-term indicates that processes involved in LTM depend on episodic processes per se, hence, lending more support for the HERA model. Accordingly, these two memory systems seem to bring into play two different modes of hemisphere specialization.

Healthy aging, memory subsystems and regional cerebral oxygen consumption.

The present study was designed to search for concomitant age-related changes in memory subsystems, defined according to current structural theories, and resting oxygen consumption in selected brain regions. We have investigated a sample of subjects between 20 and 68 years of age and strictly screened for their good health. We applied in the same subjects a battery of neuropsychological tests selected to investigate several memory subsystems, and high-resolution positron imaging with stereotaxic localization to study a purposely limited number of cerebral structures, selected on a priori hypotheses to match the different memory subsystems. Our results showed significant age-related changes in performance on some tests, consistent with the literature, including an increase in semantic memory and a decrease in both working memory (central executive system) and verbal episodic and explicit memory. There was also an age-related linear decrease in global brain oxygen consumption which regionally reached statistical significance for the neocortical areas and the left thalamus. There was a limited number of significant, age-independent correlations between the raw psychometric test scores and resting regional oxidative metabolism. Consistent with our present understanding of the functional anatomy of memory, the Associate Learning scores (verbal episodic and explicit memory) were positively correlated with left hippocampal and thalamic metabolism. The positive relationships found between right hippocampal metabolism and performance in the Associate Learning and the Brown-Peterson tests were less expected but would be consistent with findings from recent PET activation studies. The results from this investigation are discussed in the light of current knowledge concerning the neuropsychology and the neurobiology of both aging and memory.