Interaction entre les émotions et les fonctions exécutives (étude comparative en IRMf chez les témoins et les patients anxieux)

Nous avons étudié en IRMf la relation entre le réseau cérébral des émotions et celui des fonctions cognitives les plus complexes. L'objectif était de vérifier l'hypothèse de " filtrage émotionnel " : pour optimiser l'activation des structures cérébrales impliquées dans les fonctions exécutives (cortex préfrontal dorso-latéral), il est nécessaire de filtrer les signaux émotionnels négatifs pouvant interférer avec les performances. Quinze patients anxieux et quinze témoins ont été inclus. Ces sujets ont effectué un paradigme de mémoire de travail (les épreuves du PASAT) durant l'IRMf. Le paradigme a comporté trois conditions: l'une, moins stressante à intervalle fixe entre les stimuli (PASAT fixe), l'autre plus stressante à intervalle variable (PASAT aléatoire), et une tache contrôle. Des marqueurs psychométriques et neurovégétatifs de l'intensité émotionnelle ont été enregistrés pendant la réalisation du paradigme. La condition PASAT aléatoire engendre plus de stress et fait diminuer les performances. L'activation IRMf montre un profil inverse d'activation entre les témoins et les patients. Chez les témoins il existe une activation optimale durant les deux conditions du PASAT du réseau exécutif dorso-latéral. L'activation de ce réseau est sous optimale chez les patients. Durant la condition PASAT aléatoire, les témoins inhibent le réseau émotionnel orbito-frontal latéral. L'hyperactivité de ce réseau, chez les patients, pourrait être impliquée dans le maintien des affects négatifs, créant des interférences au sein du système exécutif. Ces données suggèrent que le filtrage émotionnel est opérant chez les témoins et inopérant chez les patients.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Clinical Phenotypes in Corticobasal Syndrome with or without Amyloidosis Biomarkers

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Imaging Biomarkers of Neurodegeneration in Alzheimer’s Disease: Distinct Contributions of Cortical MRI Atrophy and FDG-PET Hypometabolism

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Extent and neural basis of semantic memory impairment in mild cognitive impairment.

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

Functional connectivity changes differ in early and late-onset alzheimer's disease

International audienceAbstract At a similar stage, patients with early onset Alzheimer's disease (EOAD) have greater neocortical but less medial temporal lobe dysfunction and atrophy than the late‐onset form of the disease (LOAD). Whether the organization of neural networks also differs has never been investigated. This study aims at characterizing basal functional connectivity (FC) patterns of EOAD and LOAD in two groups of 14 patients matched for disease duration and severity, relative to age‐matched controls. All subjects underwent an extensive neuropsychological assessment. Magnetic resonance imaging was used to quantify atrophy and resting‐state FC focusing on : the default mode network (DMN), found impaired in earlier studies on AD, and the anterior temporal network (ATN) and dorso‐lateral prefrontal network (DLPFN), respectively involved in declarative memory and executive functions. Patterns of atrophy and cognitive impairment in EOAD and LOAD were in accordance with previous reports. FC within the DMN was similarly decreased in both EOAD and LOAD relative to controls. However, a double‐dissociated pattern of FC changes in ATN and DLPFN was found. EOAD exhibited decreased FC in the DLPFN and increased FC in the ATN relative to controls, while the reverse pattern was found in LOAD. In addition, ATN and DLPFN connectivity correlated respectively with memory and executive performances, suggesting that increased FC is here likely to reflect compensatory mechanisms. Thus, large‐scale neural network changes in EOAD and LOAD endorse both common features and differences, probably related to a distinct distribution of pathological changes. Hum Brain Mapp 35:2978–2994, 2014. © 2013 Wiley Periodicals, Inc

A Spatial Decision Eye-Tracking Task in Patients with Prodromal and Mild Alzheimer’s Disease

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Prodromal Alzheimer’s Disease Demonstrates Increased Errors at a Simple and Automated Anti-Saccade Task

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Validation of ELISA assays for the calculation of FLC indices for the diagnosis of intrathecal immunoglobulin synthesis

International audienceAbstract Objectives Define the cutoff thresholds of the Kappa (K) and Lambda (L) free light chains (FLC) indices for the detection of intrathecal immunoglobulin synthesis (IIS) using the new K and L FLC ELISA from SEBIA. The reference technique, which is not readily standardized between laboratories, is based on the demonstration of oligoclonal banding (OCB) in cerebrospinal fluid (CSF) which is absent in serum. For the past 6 years, we have also routinely calculated the K FLC index using The Binding Site (TBS) reagents on an Optilite instrument, an approach increasingly used as an alternative and/or a complement to electrophoretic analysis. Methods We analyzed 391 serum/CSF pairs divided into three groups. The first group were cases without OCB and with normal albumin CSF/serum ratio (n=174). The second group were cases with specific OCB (n=73). The last group included patients with increased albumin CSF/sera ratio without OCB (n=142). Results Analysis of the first group determined that the cutoffs for detection of IIS are respectively 2.55 and 1.02 for the K FLC and L FLC indices. Of the 73 cases with IIS, only 2 had a K FLC index below this threshold (sensitivity of 97.26%), while 16 out of 73 cases (78.08%) and 13 out of 72 cases (81.94%) had an IgG and L FLC index below the cutoffs, respectively. Additionally, we illustrate equivalent performances for prediction of the presence of OCB between SEBIA and TBS methods. Conclusions Sebia K FLC and L FLC assays are adequate alternative methods for the diagnosis of IIS

Difference in imaging biomarkers of neurodegeneration between early and late-onset amnestic Alzheimer's disease

International audienceNeuroimaging biomarkers differ between patients with early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Whether these changes reflect cognitive heterogeneity or differences in disease severity is still unknown. This study aimed at investigating changes in neuroimaging biomarkers, according to the age of onset of the disease, in mild amnestic Alzheimer's disease patients with positive amyloid biomarkers in cerebrospinal fluid. Both patient groups were impaired on tasks assessing verbal and visual recognition memory. EOAD patients showed greater executive and linguistic deficits, while LOAD patients showed greater semantic memory impairment. In EOAD and LOAD, hypometabolism involved the bilateral temporoparietal junction and the posterior cingulate cortex. In EOAD, atrophy was widespread, including frontotemporoparietal areas, whereas it was limited to temporal regions in LOAD. Atrophic volumes were greater in EOAD than in LOAD. Hypometabolic volumes were similar in the 2 groups. Greater extent of atrophy in EOAD, despite similar extent of hypometabolism, could reflect different underlying pathophysiological processes, different glucose-based compensatory mechanisms or distinct level of premorbid atrophic lesions