Impaired Modulation of Corticospinal Excitability in Drug-Free Patients With Major Depressive Disorder: A Theta-Burst Stimulation Study

Impaired neural plasticity may be an important mechanism in the pathophysiology of major depressive disorder (MDD). Coupled with electromyography (EMG), repetitive transcranial magnetic stimulation (rTMS) is a useful tool to evaluate corticospinal excitability and cortical neuroplasticity in living humans. The goal of this study was to compare rTMS-induced cortical plasticity changes in patients with MDD and in healthy volunteers. In this single-blind controlled study, 11 drug-free patients with MDD and 11 matched healthy controls were analyzed. Cortical excitability, measured by the amplitude of motor evoked potentials (MEPs) evoked by single-pulse TMS, was assessed before and repeatedly after (for 30 min) participants received a single session of intermittent theta-burst stimulation (iTBS) and continuous TBS (cTBS). rTMS was applied over the left motor cortex using a neuronavigation system. Intensity was set at 80% of the active motor threshold (AMT). A large interindividual variability was observed after both iTBS and cTBS in the two groups. At the group level, we observed impaired iTBS-induced neuroplasticity in patients with MDD compared to that in controls. No differences were observed between the groups regarding cTBS-induced neuroplasticity. Our results suggest impaired long-term potentiation (LTP)-like mechanisms in MDD.Clinical Trial Registration: www.Clinicaltrials.gov, identifier #NCT02438163

De 20 000 à 18 000 BP en Quercy : apports de la séquence du Cuzoul de Vers à la compréhension de l'évolution des comportements socio-économiques entre Solutréen récent et Badegoulien

Essai de synthèse des travaux menés autour du gisement du Cuzoul de Vers (Lot)

Etude de systèmes d'oxydoréduction susceptibles de contribuer à la consommation de composés thiols au cours du pétrissage des pâtes de farine de blé

Au cours du pétrissage, la consommation des thiols de bas poids moléculaire (BPM) affecte la structure du réseau de gluten, en raison de la participation de ces composés aux réactions d'échanges SH / SS avec les protéines. En panification, récemment, des enzymes fongiques ont été proposées comme alternative plus naturelle à l'emploi des améliorants chimiques (KBrO3, acide ascorbique) pour oxyder ces composés thiols BPM. Dans ce cadre, la sulfhydryle oxydase d'Aspergillus niger a été étudiée et son action a été comparée à celle du KBrO3 et de la glutathion (GSH) déshydrogénase de blé (GSH-DHase). Dans un 1er temps, le protocole de purification de la sax d'A. niger mis au point a permis d'éliminer la catalase, contaminant majeur de l'échantillon. La caractérisation cinétique de la SOX a été menée. Une 2e partie a été consacrée à la mise au point de méthodes de dosage des formes réduite et oxydée (GSSG, CSSC et GSSC) du glutathion et de la cystéine. Ainsi, par CLHP couplée à un détecteur coulométrique ou UV, les GSH, CSH, GSSG, GSSC et CSSC ont pu être séparés et quantifiés. Les 3 disulfures ont été également analysés par gel filtration couplée à une détection UV. Une comparaison de la formation des disulfures par 3 différents systèmes oxydants, SOX, GSH-Dhase et KBrO3, a ensuite été réalisée à partir de mélanges de GSH et CSH. En dernier lieu, des associations enzymatiques en milieux modèles ont été examinées. Le mélange de SOX et de GSH-DHase conduit à une compétition pour la consommation du GSH. Parallèlement, l'association de SOX et de peroxydase de germe de blé (POD) a révélé que la SOX est capable d'activer la POD, en générant l'H2O2. Nous pouvons donc supposer que, dans la pâte, l'ajout de SOX peut influencer les réactions d'oxydoréduction, et par conséquent serait susceptible de modifier les propriétés de la pâte boulangère.During wheat flour dough mixing, low molecular weight (LMW) thiols consumption is known to influence the gluten network structure since these compounds can participate to exchange reactions SH / SS with proteins. In breadmaking, recently, fungal enzymes are proposed as "the natural alternative" to the use of chemical improving agents (KbrO3 ascorbic acid AA) to oxidise LMW thiols. In this respect, sulphydryl oxidase (SOX) from Aspergillus niger was studied and its action was compared to those of KbrO3 and wheat glutathione deshydrogenase (GSH-DHase). Firstly, the developed purification procedure of A. niger SOX allowed to eliminate the catalase, the main contaminating activity present in the enzymatic sample. Kinetic studies have shown that SOX oxidised preferentially glutathione (GSH) and its activity was enhanced by cysteine (CSH). The second part of this work was to develop methods to quantify the oxidised and reduced forms of GSH and CSH. Thus, HPLC equipped with a coulometric or UV detector allowed the separation and simultaneous assay of GSH, CSH, GSSG, GSSC and CSSC. The 3 disulphides were also analysed by gel filtration with an UV detection. The comparison of the disulphide formation by the 3 different oxidising systems from mixtures of GSH and CSH was then investigated. While KbrO3 produces predominantly CSSC, SOX and GSH-DHase generated GSSG and GSSC, respectively. Lastly, enzymatic associations in model systems have been examined. When SOX is in the presence of GSH-DHase, both enzymes competed for the GSH consumption. The association of SOX and wheat germ peroxidase (POD) revealed that SOX was able to activate POD by producing H2O2. Thus, in dough, the use of SOX may influence oxidoreducing systems and consequently modify flour dough properties.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Purification and characterization of recombinant human liver glycolate oxidase

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Non-Cartesian non-Fourier fmri imaging for high-resolution retinotopic mapping at 7 Tesla

International audienceFunctional MRI (fMRI) is an invaluable tool for neuroscience, but it necessitates a trade-off between spatial and temporal resolution to maintain a reasonable temporal signal-to-noise ratio (tSNR). Non-Cartesian acquisition schemes are more efficient sampling strategies as compared to Cartesian ones and were proposed as a way to push the limits of spatiotemporal resolution further. 3D-SPARKLING is a novel non-Cartesian scheme recently evaluated for fMRI applications. However, 3D-SPARKLING is highly sensitive to B0 field imperfections. Such imperfections are detrimental to fMRI applications, especially at ultra-high magnetic fields. In this work, we collect measurements of the static and dynamic B0 field perturbations concurrently with 3D-SPARKLING fMRI data acquisition and retrospectively correct these perturbations during image reconstruction. The advantages of this image reconstruction strategy are assessed on the statistical sensitivity to the BOLD contrast during a retinotopic mapping fMRI experiment. Importantly, a gain of 44% (resp., 159%) additionally activated voxels was quantified when adopting this brain activity-enhanced image reconstruction technique at a type-I statistical control level of 0.001 without multiple comparisons correction (resp., 0.05 with false discovery rate correction). Additionally, significantly improved retinotopic maps were retrieved on the cortical surface

Non-Cartesian non-Fourier fmri imaging for high-resolution retinotopic mapping at 7 Tesla

International audienceFunctional MRI (fMRI) is an invaluable tool for neuroscience, but it necessitates a trade-off between spatial and temporal resolution to maintain a reasonable temporal signal-to-noise ratio (tSNR). Non-Cartesian acquisition schemes are more efficient sampling strategies as compared to Cartesian ones and were proposed as a way to push the limits of spatiotemporal resolution further. 3D-SPARKLING is a novel non-Cartesian scheme recently evaluated for fMRI applications. However, 3D-SPARKLING is highly sensitive to B0 field imperfections. Such imperfections are detrimental to fMRI applications, especially at ultra-high magnetic fields. In this work, we collect measurements of the static and dynamic B0 field perturbations concurrently with 3D-SPARKLING fMRI data acquisition and retrospectively correct these perturbations during image reconstruction. The advantages of this image reconstruction strategy are assessed on the statistical sensitivity to the BOLD contrast during a retinotopic mapping fMRI experiment. Importantly, a gain of 44% (resp., 159%) additionally activated voxels was quantified when adopting this brain activity-enhanced image reconstruction technique at a type-I statistical control level of 0.001 without multiple comparisons correction (resp., 0.05 with false discovery rate correction). Additionally, significantly improved retinotopic maps were retrieved on the cortical surface

Étude pilote des liens entre la presbyacousie et les troubles lexicaux chez les patients atteints de maladie d’Alzheimer ou maladie apparentée

Les troubles neurocognitifs et la presbyacousie constituent deux pathologies très présentes dans la population âgée. Les troubles neurocognitifs sont marqués par la survenue précoce de troubles lexico-sémantiques. Le but de cette étude est de déterminer le lien entre le manque du mot et la presbyacousie chez des patients présentant une maladie d’Alzheimer ou apparentée. Trente-sept sujets présentant un trouble neurocognitif léger à modéré ont répondu au Questionnaire de dépistage des difficultés d’écoute et d’audition, et aux épreuves de dénomination de substantifs et de verbes de la Batterie Informatisée du Manque du Mot (BIMM). Ils ont été répartis en deux groupes : « normo-entendants » et « risque de presbyacousie ». Aucune différence significative pour les scores et les temps en dénomination, les variables psycholinguistiques et les types d’erreurs n’a été observée entre les deux groupes. Aucune corrélation entre le score global obtenu à la BIMM et celui obtenu au questionnaire d’audition n’a été mise en évidence. Ces résultats négatifs peuvent s’expliquer par la présence très précoce de troubles lexico-sémantiques chez les sujets avec une maladie d’Alzheimer ou apparentée

Temporal SNR optimization through RF coil combination in fMRI: The more, the better?

For functional MRI with a multi-channel receiver RF coil, images are often reconstructed channel by channel, resulting into multiple images per time frame. The final image to analyze usually is the result of the covariance Sum-of-Squares (covSoS) combination across these channels. Although this reconstruction is quasi-optimal in SNR, it is not necessarily the case in terms of temporal SNR (tSNR) of the time series, which is yet a more relevant metric for fMRI data quality. In this work, we investigated tSNR optimality through voxel-wise RF coil combination and its effects on BOLD sensitivity. An analytical solution for an optimal RF coil combination is described, which is somewhat tied to the extended Krueger-Glover model involving both thermal and physiological noise covariance matrices. Compared experimentally to covSOS on four volunteers at 7T, the method yielded great improvement of tSNR but, surprisingly, did not result into higher BOLD sensitivity. Solutions to improve the method such as for example the t-score for the mean recently proposed are also explored, but result into similar observations once the statistics are corrected properly. Overall, the work shows that data-driven RF coil combinations based on tSNR considerations alone should be avoided unless additional and unbiased assumptions can be made