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Béatrice Desgranges

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YNICL Journal 2015 Journal Article

Brain structural, functional, and cognitive correlates of recent versus remote autobiographical memories in amnestic Mild Cognitive Impairment

  • Clémence Tomadesso
  • Audrey Perrotin
  • Justine Mutlu
  • Florence Mézenge
  • Brigitte Landeau
  • Stéphanie Egret
  • Vincent de La Sayette
  • Pierre-Yves Jonin

Deficits in autobiographical memory appear earlier for recent than for remote life periods over the course of Alzheimer's disease (AD). The present study aims to further our understanding of this graded effect by investigating the cognitive and neural substrates of recent versus remote autobiographical memories in patients with amnestic Mild Cognitive Impairment (aMCI) thanks to an autobiographical fluency task. 20 aMCI patients and 25 Healthy elderly Controls (HC) underwent neuropsychological tests assessing remote (20-to-30 years old) and recent (the ten last years) autobiographical memory as well as episodic and semantic memory, executive function and global cognition. All patients also had a structural MRI and an FDG-PET scan. Correlations were assessed between each autobiographical memory score and the other tests as well as grey matter volume and metabolism. Within the aMCI, performances for the remote period correlated with personal semantic memory and episodic memory retrieval whereas performances for the recent period only correlated with episodic memory retrieval. Neuroimaging analyses revealed significant correlations between performances for the remote period and temporal pole and temporo-parietal cortex volumes and anterior cingulate gyrus metabolism, while performances for the recent period correlated with hippocampal volume and posterior cingulate, medial prefrontal and hippocampus metabolism. The brain regions related with the retrieval of events from the recent period showed greater atrophy/hypometabolism in aMCI patients compared to HC than those involved in remote memories. Recall of recent memories essentially relies on episodic memory processes and brain network while remote memories also involve other processes such as semantic memory. This is consistent with the semanticization of memories with time and may explain the better resistance of remote memory in AD.

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YNIMG Journal 2014 Journal Article

Morphological brain plasticity induced by musical expertise is accompanied by modulation of functional connectivity at rest

  • Baptiste Fauvel
  • Mathilde Groussard
  • Gaël Chételat
  • Marine Fouquet
  • Brigitte Landeau
  • Francis Eustache
  • Béatrice Desgranges
  • Hervé Platel

The aim of this study was to explore whether musical practice-related gray matter increases in brain regions are accompanied by modifications in their resting-state functional connectivity. 16 young musically experienced adults and 17 matched nonmusicians underwent an anatomical magnetic resonance imaging (MRI) and a resting-state functional MRI (rsfMRI). A whole-brain two-sample t test run on the T1-weighted structural images revealed four clusters exhibiting significant increases in gray matter (GM) volume in the musician group, located within the right posterior and middle cingulate gyrus, left superior temporal gyrus and right inferior orbitofrontal gyrus. Each cluster was used as a seed region to generate and compare whole-brain resting-state functional connectivity maps. The two clusters within the cingulate gyrus exhibited greater connectivity for musicians with the right prefrontal cortex and left temporal pole, which play a role in autobiographical and semantic memory, respectively. The cluster in the left superior temporal gyrus displayed enhanced connectivity with several language-related areas (e. g. , left premotor cortex, bilateral supramarginal gyri). Finally, the cluster in the right inferior frontal gyrus displayed more synchronous activity at rest with claustrum, areas thought to play a role in binding sensory and motor information. We interpreted these findings as the consequence of repeated collaborative use in general networks supporting some of the memory, perceptual-motor and emotional features of musical practice.

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YNICL Journal 2013 Journal Article

Hippocampal subfield volumetry in mild cognitive impairment, Alzheimer's disease and semantic dementia

  • Renaud La Joie
  • Audrey Perrotin
  • Vincent de La Sayette
  • Stéphanie Egret
  • Loïc Doeuvre
  • Serge Belliard
  • Francis Eustache
  • Béatrice Desgranges

BACKGROUND: Hippocampal atrophy is a well-known feature of Alzheimer's disease (AD), but sensitivity and specificity of hippocampal volumetry are limited. Neuropathological studies have shown that hippocampal subfields are differentially vulnerable to AD; hippocampal subfield volumetry may thus prove to be more accurate than global hippocampal volumetry to detect AD. METHODS: CA1, subiculum and other subfields were manually delineated from 40 healthy controls, 18 AD, 17 amnestic Mild Cognitive Impairment (aMCI), and 8 semantic dementia (SD) patients using a previously developed high resolution MRI procedure. Non-parametric group comparisons and receiver operating characteristic (ROC) analyses were conducted. Complementary analyses were conducted to evaluate differences of hemispheric asymmetry and anterior-predominance between AD and SD patients and to distinguish aMCI patients with or without β-amyloid deposition as assessed by Florbetapir-TEP. RESULTS: Global hippocampi were atrophied in all three patient groups and volume decreases were maximal in the CA1 subfield (22% loss in aMCI, 27% in both AD and SD; all p < 0.001). In aMCI, CA1 volumetry was more accurate than global hippocampal measurement to distinguish patients from controls (areas under the ROC curve = 0.88 and 0.76, respectively; p = 0.05) and preliminary analyses suggest that it was independent from the presence of β-amyloid deposition. In patients with SD, whereas the degree of CA1 and subiculum atrophy was similar to that found in AD patients, hemispheric and anterior-posterior asymmetry were significantly more marked than in AD with greater involvement of the left and anterior hippocampal subfields. CONCLUSIONS: The findings suggest that CA1 measurement is more sensitive than global hippocampal volumetry to detect structural changes at the pre-dementia stage, although the predominance of CA1 atrophy does not appear to be specific to AD pathophysiological processes.

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YNIMG Journal 2013 Journal Article

Relationships between brain metabolism decrease in normal aging and changes in structural and functional connectivity

  • Gaël Chételat
  • Brigitte Landeau
  • Eric Salmon
  • Igor Yakushev
  • Mohamed Ali Bahri
  • Florence Mézenge
  • Audrey Perrotin
  • Christine Bastin

Normal aging is characterized by brain glucose metabolism decline predominantly in the prefrontal cortex. The goal of the present study was to assess whether this change was associated with age-related alteration of white matter (WM) structural integrity and/or functional connectivity. FDG-PET data from 40 young and 57 elderly healthy participants from two research centers (n=49/48 in Center 1/2) were analyzed. WM volume from T1-weighted MRI (Center 1), fractional anisotropy from diffusion-tensor imaging (Center 2), and resting-state fMRI data (Center 1) were also obtained. Group comparisons were performed within each imaging modality. Then, positive correlations were assessed, within the elderly, between metabolism in the most affected region and the other neuroimaging modalities. Metabolism decline in the elderly predominated in the left inferior frontal junction (LIFJ). LIFJ hypometabolism was significantly associated with macrostructural and microstructural WM disturbances in long association fronto-temporo-occipital fibers, while no relationship was found with functional connectivity. The findings offer new perspectives to understand normal aging processes and open avenues for future studies to explore causality between age-related metabolism and connectivity changes.

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YNIMG Journal 2013 Journal Article

Relationships between years of education and gray matter volume, metabolism and functional connectivity in healthy elders

  • Eider M. Arenaza-Urquijo
  • Brigitte Landeau
  • Renaud La Joie
  • Katell Mevel
  • Florence Mézenge
  • Audrey Perrotin
  • Béatrice Desgranges
  • David Bartrés-Faz

More educated elders are less susceptible to age-related or pathological cognitive changes. We aimed at providing a comprehensive contribution to the neural mechanism underlying this effect thanks to a multimodal approach. Thirty-six healthy elders were selected based on neuropsychological assessments and cerebral amyloid imaging, i. e. as presenting normal cognition and a negative florbetapir-PET scan. All subjects underwent structural MRI, FDG-PET and resting-state functional MRI scans. We assessed the relationships between years of education and i) gray matter volume, ii) gray matter metabolism and iii) functional connectivity in the brain areas showing associations with both volume and metabolism. Higher years of education were related to greater volume in the superior temporal gyrus, insula and anterior cingulate cortex and to greater metabolism in the anterior cingulate cortex. The latter thus showed both volume and metabolism increases with education. Seed connectivity analyses based on this region showed that education was positively related to the functional connectivity between the anterior cingulate cortex and the hippocampus as well as the inferior frontal lobe, posterior cingulate cortex and angular gyrus. Increased connectivity was in turn related with improved cognitive performances. Reinforcement of the connectivity of the anterior cingulate cortex with distant cortical areas of the frontal, temporal and parietal lobes appears as one of the mechanisms underlying education-related reserve in healthy elders.

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YNIMG Journal 2012 Journal Article

Role of hippocampal CA1 atrophy in memory encoding deficits in amnestic Mild Cognitive Impairment

  • Marine Fouquet
  • Béatrice Desgranges
  • Renaud La Joie
  • Denis Rivière
  • Jean-François Mangin
  • Brigitte Landeau
  • Florence Mézenge
  • Alice Pélerin

Identifying the specific substrates of memory deficits in early Alzheimer's disease would help to develop clinically-relevant therapies. The present study assesses the relationships between encoding versus retrieval deficits in patients with amnestic Mild Cognitive Impairment (aMCI) and atrophy specifically within the hippocampus and throughout the white matter. Twenty-two aMCI patients underwent T1-weighted MRI scans and neuropsychological testing. Grey matter and white matter segments obtained from the MRI images were each entered in correlation analyses, assessed only in the hippocampus for grey matter segments, with encoding and retrieval memory performances. For the grey matter segments, the resulting spmT correlation maps were then superimposed onto a 3D surface view of the hippocampus to identify the relative involvement of the different subfields, a method already used and validated elsewhere. Memory encoding deficits specifically correlated with CA1 subfield atrophy, while no relationship was found with white matter atrophy. In contrast, retrieval deficits were weakly related to hippocampal atrophy and did not involve a particular subfield, while they strongly correlated with loss of white matter, specifically in medial parietal and frontal areas. In aMCI patients, encoding impairment appears specifically related to atrophy of the CA1 hippocampal subfield, consistent with the predominance of encoding deficits and CA1 atrophy in aMCI. In contrast, episodic retrieval deficits seem to be underlain by more distributed tissue losses, consistent with a disruption of a hippocampo-parieto-frontal network.

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YNIMG Journal 2010 Journal Article

Differential effect of age on hippocampal subfields assessed using a new high-resolution 3T MR sequence

  • Renaud La Joie
  • Marine Fouquet
  • Florence Mézenge
  • Brigitte Landeau
  • Nicolas Villain
  • Katell Mevel
  • Alice Pélerin
  • Francis Eustache

Recent advances in neuroimaging have highlighted the interest to differentiate hippocampal subfields for cognitive neurosciences and more notably in assessing the effects of normal and pathological aging. The main goal of the present study is to investigate the effects of normal aging onto the volume of the different hippocampal subfields. For this purpose, we developed a new magnetic resonance sequence together with reliable tracing guidelines to assess the volume of different subfields of the hippocampus using a 3 Tesla scanner, and estimated the validity of a simpler and less time-consuming method based on the widely-used automatic Voxel-Based Morphometry (VBM) technique. Three hippocampal regions of interest were delineated on the right and left hippocampi of 50 healthy subjects between 18 and 68 years old corresponding to the CA1, subiculum and other (including CA2-3-4 and Dentate Gyrus) subfields. A strong effect of age was found on the volume of the subiculum only, with a decrease paralleling that of the global gray matter volume, while CA1 and other subfields seemed relatively spared. Although less precise than the ROI-tracing technique, the VBM-based method appeared as a reliable alternative especially to distinguish CA1 and subiculum subfields. Our findings of a specific effect of age on the subiculum are consistent with the developmental hypothesis (“last-in first-out” theory). This contrasts with the predominant vulnerability of the CA1 subfield to Alzheimer's disease reported in several previous studies, suggesting that the assessment of hippocampal subfields may improve the discrimination between normal and pathological aging.

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YNIMG Journal 2009 Journal Article

Multidimensional classification of hippocampal shape features discriminates Alzheimer's disease and mild cognitive impairment from normal aging

  • Emilie Gerardin
  • Gaël Chételat
  • Marie Chupin
  • Rémi Cuingnet
  • Béatrice Desgranges
  • Ho-Sung Kim
  • Marc Niethammer
  • Bruno Dubois

We describe a new method to automatically discriminate between patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI) and elderly controls, based on multidimensional classification of hippocampal shape features. This approach uses spherical harmonics (SPHARM) coefficients to model the shape of the hippocampi, which are segmented from magnetic resonance images (MRI) using a fully automatic method that we previously developed. SPHARM coefficients are used as features in a classification procedure based on support vector machines (SVM). The most relevant features for classification are selected using a bagging strategy. We evaluate the accuracy of our method in a group of 23 patients with AD (10 males, 13 females, age±standard-deviation (SD)=73±6 years, mini-mental score (MMS)=24. 4±2. 8), 23 patients with amnestic MCI (10 males, 13 females, age±SD=74±8 years, MMS=27. 3±1. 4) and 25 elderly healthy controls (13 males, 12 females, age±SD=64±8 years), using leave-one-out cross-validation. For AD vs controls, we obtain a correct classification rate of 94%, a sensitivity of 96%, and a specificity of 92%. For MCI vs controls, we obtain a classification rate of 83%, a sensitivity of 83%, and a specificity of 84%. This accuracy is superior to that of hippocampal volumetry and is comparable to recently published SVM-based whole-brain classification methods, which relied on a different strategy. This new method may become a useful tool to assist in the diagnosis of Alzheimer's disease.

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YNIMG Journal 2007 Journal Article

Detecting hippocampal hypometabolism in Mild Cognitive Impairment using automatic voxel-based approaches

  • Katell Mevel
  • Béatrice Desgranges
  • Jean-Claude Baron
  • Brigitte Landeau
  • Vincent de La Sayette
  • Fausto Viader
  • Francis Eustache
  • Gaël Chételat

While the hippocampus is constantly reported as the site of earliest and highest structural alteration in Alzheimer's disease (AD), findings regarding the metabolic status of this region are rather heterogeneous. It has been proposed that only a time-consuming individual region-of-interest (ROI) approach would allow the detection of hypometabolism in this complex and small area. Our main goal with this study is to assess whether more automatic and clinically useful methods would be sensitive enough when considering other methodological confounds. From a single PET data set collected in 28 patients with amnestic Mild Cognitive Impairment (aMCI) and 19 controls, we assessed the effects of partial volume effect (PVE) correction, scaling (using vermis or global means), and analysis method (individual ROI versus more automatic template-based ROI or voxel-based approaches) on hippocampal hypometabolism detection in aMCI. PVE correction and scaling both showed a significant effect on group comparison, while the analysis method (individual versus template-based ROI) surprisingly did not. Hippocampal metabolic decrease was significant in all vermis-scaled conditions, and more so after PVE correction. Our findings highlight the crucial relevance of using reference-region-based (instead of global) scaling, and the higher sensitivity of PVE-corrected PET measures, to detect hippocampal hypometabolism in aMCI. They also show that hippocampal metabolic decline can be detected using template-based ROI as well as voxel-based methods. These findings have clinical relevance since they support the validity of more automatic and time-saving approaches to assess hippocampal metabolism changes in aMCI and early AD.

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YNIMG Journal 2004 Journal Article

Re-experiencing old memories via hippocampus: a PET study of autobiographical memory

  • Pascale Piolino
  • Gaëlle Giffard-Quillon
  • Béatrice Desgranges
  • Gaël Chételat
  • Jean-Claude Baron
  • Francis Eustache

The time-scale of medial temporal lobe (MTL) involvement in storage and retrieval of episodic memory is keenly debated. To test competitive theories of long-term memory consolidation, the present work aimed at characterizing which cerebral regions are involved during retrieval of recent and remote strictly episodic autobiographical memory. Using positron emission tomography (PET), we examined mental retrieval of recent (0–1 year) and remote (5–10 years) autobiographical memories, controlling for the nature of the autobiographical memories (i. e. , specificity, state of consciousness, vividness of mental visual imagery, emotion) retrieved during scanning by behavioral measures assessed at debriefing for each event recalled. Cognitive results showed that specificity and emotion did not change with time interval although both autonoetic consciousness and mental image quality were significantly higher for recent memories, suggesting an underlying shift in the phenomenal experience of remembering with the passage of time. The SPM analysis revealed common activations during the recollection of recent and remote memories that involved a widespread but mainly left-sided cerebral network, consistent with previous studies. Subtraction analysis demonstrated that the retrieval of recent (relative to remote) autobiographical memories principally activated the left dorsolateral prefrontal cortex whereas the retrieval of remote (relative to recent) autobiographical memories activated the inferior parietal cortex bilaterally. ROIs analysis revealed more hippocampal activity for remote memories than for recent ones and a preferentially right-sided involvement of the hippocampal responses whatever the remoteness of autobiographical memories. New insights based on higher hippocampal response to the remoteness of episodic autobiographical memories challenge the standard model and are less discrepant with the multiple trace theory.

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YNIMG Journal 2003 Journal Article

Semantic and episodic memory of music are subserved by distinct neural networks

  • Hervé Platel
  • Jean-Claude Baron
  • Béatrice Desgranges
  • Frédéric Bernard
  • Francis Eustache

Numerous functional imaging studies have shown that retrieval from semantic and episodic memory is subserved by distinct neural networks. However, these results were essentially obtained with verbal and visuospatial material. The aim of this work was to determine the neural substrates underlying the semantic and episodic components of music using familiar and nonfamiliar melodic tunes. To study musical semantic memory, we designed a task in which the instruction was to judge whether or not the musical extract was felt as “familiar. ” To study musical episodic memory, we constructed two delayed recognition tasks, one containing only familiar and the other only nonfamiliar items. For each recognition task, half of the extracts (targets) were presented in the prior semantic task. The episodic and semantic tasks were to be contrasted by a comparison to two perceptive control tasks and to one another. Cerebral blood flow was assessed by means of the oxygen-15-labeled water injection method, using high-resolution PET. Distinct patterns of activations were found. First, regarding the episodic memory condition, bilateral activations of the middle and superior frontal gyri and precuneus (more prominent on the right side) were observed. Second, the semantic memory condition disclosed extensive activations in the medial and orbital frontal cortex bilaterally, the left angular gyrus, and predominantly the left anterior part of the middle temporal gyri. The findings from this study are discussed in light of the available neuropsychological data obtained in brain-damaged subjects and functional neuroimaging studies.

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YNIMG Journal 2002 Journal Article

The Neural Basis of Intrusions in Free Recall and Cued Recall: A PET Study in Alzheimer's Disease

  • Béatrice Desgranges
  • Jean-Claude Baron
  • Bénédicte Giffard
  • Gaël Chételat
  • Catherine Lalevée
  • Fausto Viader
  • Vincent de La Sayette
  • Francis Eustache

This study was designed to map in Alzheimer's disease patients the correlations between resting-state brain glucose utilization measured by PET and the number of intrusions obtained by means of a specially designed episodic memory test separately in free recall and in cued recall. SPM revealed significant negative correlations between the number of intrusions in free recall and the metabolism of the right superior frontal gyrus. For the intrusions in cued recall, the negative correlations concerned the left rhinal cortex. Our findings suggest that intrusions in free recall reflect perturbations in strategic processes and that intrusions in cued recall are triggered by the cue in a relatively automatic manner. Frontal dysfunction would be responsible for the former and rhinal dysfunction for the latter.

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YNIMG Journal 1998 Journal Article

The Functional Neuroanatomy of Episodic Memory: The Role of the Frontal Lobes, the Hippocampal Formation, and Other Areas

  • Béatrice Desgranges
  • Jean-Claude Baron
  • Francis Eustache

Because it allows direct mapping of synaptic activity during behavior in the normal subject, functional neuroimaging with the activation paradigm, especially positron emission tomography, has recently provided insight into our understanding of the functional neuroanatomy of episodic memory over and above established knowledge from lesional neuropsychology. The most striking application relates to the ability to distinguish the structures implicated in the encoding and the retrieval of episodic information, as these processes are extremely difficult to differentiate with behavioral tasks, either in healthy subjects or in brain-damaged patients. Regarding encoding and retrieval, the results from most studies converge on the involvement of the prefrontal cortex in these processes, with a hemispheric encoding/retrieval asymmetry (HERA) such that the left side is preferentially involved in encoding, and the right in retrieval. However, there are still some questions, for instance, about bilateral activation during retrieval and a possible specialization within the prefrontal cortex. More expected from human and monkey lesional data, the hippocampal formation appears to play a role in both the encoding and the retrieval of episodic information, but the exact conditions which determine hippocampal activation and its fine-grained functional neuroanatomy have yet to be fully elucidated. Other structures are activated during episodic memory tasks, with asymmetric activation that fits the HERA model, such as preferentially left-sided activation of the association temporal and posterior cingulate areas in encoding tasks and preferentially right-sided activation of the association parietal cortex, cerebellum, and posterior cingulate in retrieval tasks. However, this hemispheric asymmetry appears to depend to some extent on the material used. These new data enhance our capacity to comprehend episodic memory deficits in neuropsychology, as well as the neural mechanisms underlying the age-related changes in episodic memory performances.

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v2026.09.13