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  • Authors: Moriceau, Aurélie;

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  • Authors: Droulers, Olivier; Roullet, Bernard;

    Les progrès accomplis récemment par les neurosciences ont permis une révision complète de la compréhension du fonctionnement cérébral. Une révolution est en marche, bouleversant les paradigmes établis en sciences humaines. Le marketing, après avoir assimilé successivement les concepts de psychologie générale puis de psychologie cognitive, doit aujourd'hui s'approprier les notions et concepts des neurosciences pour garder sa place au sein des sciences sociales et humaines.

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  • Authors: Roullet, Bernard; Droulers, Olivier;

    The evolution of marketing concepts under the influence of the psychologicalthought is a constant in the discipline history. The development of cognitive science, andmore specifically of the neurosciences, allow us today to advocate a consumer neuroscience.The author presents here the expected developments of the discipline and its contiguousethical reflections. l'évolution des concepts marketing sous l'influence de la pensée psychologique estune constante dans l'histoire de la discipline. Le développement des sciences cognitives etplus spécifiquement des neurosciences permet aujourd'hui de proposer une neuroscience duconsommateur. L'auteur expose ici les développements attendus et les réflexions éthiquesattenantes. International audience

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    Authors: Tounekti, Slimane;

    L’IRM de diffusion (IRMd) est l’unique technique non invasive qui permet l’exploration de la microstructure cérébrale. En plus d’une large utilisation pour les applications médicales, l’IRMd est aussi utilisée en neuroscience pour comprendre l’organisation et le fonctionnement du cerveau. Toutefois, sa faible résolution spatiale et sa sensibilité aux artéfacts limitent son utilisation chez le primate non humain.L’objectif de cette étude est de développer une nouvelle approche qui permette d’acquérir des données d’IRMd à très haute résolution spatiale sur des cerveaux de macaques anesthésiés. Cette méthode est basée sur un balayage 3D de l’espace de Fourier avec un module de lecture d’Echo Planar-segmenté.Cette méthode a été tout d’abord implémentée sur une machine IRM 3 Tesla (Prisma, Siemens), puis validée et optimisée in-vitro et in-vivo. Par rapport à la méthode d’acquisition classique, un gain de sensibilité de l’ordre de 3 pour la substance grise cérébrale et de 4.7 pour la substance blanche cérébrale a été obtenu grâce à la méthode développée.Cette méthode a permis de réaliser l’IRMd du cerveau de Macaque avec une résolution spatiale isotrope de 0.5 mm jamais atteinte auparavant. L’intérêt de réaliser des données d’IRMd à une telle résolution pour visualiser et analyser in-vivo des structures fines non détectables avec la méthode d’acquisition classique comme les sous-champs de l’hippocampe ou encore la substance blanche superficielle, a été démontré dans cette étude. Des résultats préliminaires très encourageants ont également été obtenus chez l’homme Diffusion MRI (dMRI) is the unique non-invasive technique that allows exploring the cerebral microstructure. Besides a wide use for medical applications, dMRI is also employed in neuroscience to understand the brain organization and connectivity. However, the low spatial resolution and the sensitivity to artefacts limit its application to non-human primates.This work aims to develop a new approach that allows to acquire dMRI at very high spatial resolution on anesthetized macaque brains. This method is based on a 3D sampling of Fourier space with a segmented Echo Planar imaging readout module. This method has been firstly implemented on a 3 Tesla MR scanner (Prisma, Siemens), validated and optimized in-vitro and in-vivo. Compared to the conventional acquisition method, a gain of sensitivity of 3 for the cerebral grey matter and of 4.7 for the white matter was obtained with the proposed approach.This method allowed us to acquire dMRI data on the macaque brain with a spatial isotropic resolution of 0.5 mm ever reached before. The interest to acquire dMRI data with such a spatial resolution to visualize and analyze in-vivo fine structures not detectable with the classical acquisition method, like the sub-fields of hippocampus and the superficial white matter, has also illustrated in this study. Finally, very encouraging preliminary results were also obtained in humans

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    Other literature type . 2019
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      Other literature type . 2019
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    Authors: Ojaroudi, Mohammad; Bila, Stéphane; Salimitorkamani, M.;

    International audience; In this paper, brain hemorrhage stroke detection approach using microwave-imaging system with a novel machine-learning based post-processing method is presented. In order to create a circular array based microwave imaging system sixteen elements of the modified bowtie antennas are simulated in CST medium around the full head phantom. In order to radiate in desired band from 0.5-5 GHz an appropriate matching medium is designed. In addition, a hierarchical preprocessing method is employed to calibrate the reflected signals. In the processing section, a confocal imagereconstructing algorithm based is used. Finally, a new machine learning technique including discrete wavelet transform (DWT) and principle component analysis (PCA) for feature extraction and reduction, respectively. In addition, support vector machine (SVM) is used for segmentation and clustering of hemorrhage stroke detection from reconstructed image is employed. Simulated results are presented to validate the effectiveness of the proposed method for precisely localizing and classifying bleeding targets.

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    Other literature type . 2020
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    Authors: Brodin, Camille;

    Les défauts de translation des études précliniques vers les essais cliniques dans le domaine des AVC ischémiques et l'échec des développements thérapeutiques pourraient être expliqués par trois aspects : (1) le manque de compréhension des mécanismes des deux formes de rtPA, le traitement pharmacologique de l'AVC; (2) le manque d'outils adaptés d'imagerie de perfusion chez le petit animal et (3) l'influence de l'anesthésie sur l’effet des traitements testés dans les modèles animaux.Le tPA utilisé en clinique (Actilyse®) est un mélange de deux formes de tPA: une forme chaîne simple (sc-rtPA) et une double chaîne (tc-rtPA). Malgré des activités fibrinolytiques similaires, ces deux formes de tPA exercent des fonctions cérébrales distinctes influençant différemment la récupération des patients. Ainsi, nous avons décidé d'étudier en détail dans un modèle murin d'AVC thromboembolique les mécanismes pouvant expliquer ces effets divergents. Nous avons confirmé ces observations à savoir que sc-rtPA est bénéfique lorsqu'il est perfusé tôt après le début de l'AVC, alors que le tc-rtPA est délétère en raison d'une altération de la barrière hémato-encéphalique.L'imagerie en temps réel de la perfusion de l'ensemble du cerveau est un atout pour les études cliniques et précliniques. L'émergence des ultrasons ultra-rapides a conduit au développement du Doppler ultra-rapide et de la Microscopie de Localisation à Ultrasons (ULM), deux méthodes avec différents profils de résolutions spatio-temporelles et une excellente sensibilité aux petits flux sanguins. Nous avons combiné ces deux méthodes pour fournir un suivi longitudinal en 3D de la perfusion cérébrale dans un modèle murin d’AVC thromboembolique avec fibrinolyse par rtPA. Nos données montrent que le FUS et l’ULM présentent un intérêt majeur pour le pronostic précoce de l'AVC ischémique et de la réponse au traitement, avec une corrélation étroite entre la reperfusion précoce à 2h et la récupération tissulaire à 24h.Enfin, l’anesthésie utilisée en laboratoire interfère sur la lésion ischémique et les effets des molécules thérapeutiques testées. Nous nous sommes affranchis de ces effets en développant un nouveau modèle d’AVC ischémique chez des souris totalement éveillées. Le débit sanguin cérébral régional a été suivi par laser Doppler avant, pendant et 45min après le début de l’AVC. Le traitement par rtPA (à 20 min) est bénéfique dans les modèles d’AVC vigile et anesthésié, mais l'anesthésie est associée à un manque de corrélation entre la recanalisation et les volumes de lésion post-ischémie. Nous testons actuellement une molécule neuroprotectrice, qui était prometteuse avant d’échouer lors des essais cliniques (NXY-059), afin d’évaluer la pertinence de ce modèle novateur d’AVC pour les futures études pharmacologiques. Dans l’ensemble, ce travail fournit un panel de données précliniques innovantes pour améliorer nos chances de translation en clinique, incluant un modèle pertinent d'AVC thromboembolique chez des animaux vigiles et une méthode d'imagerie du pronostic précoce de réponse aux traitements vasculaires. The lack of translation between preclinical studies and clinical trials in the field of ischemic stroke and the failure of therapeutic developments could be explained by three aspects: (1) the lack of understanding the mechanism of the two forms of tPA, the pharmacological treatment in stroke; (2) the lack of optimized perfusion imaging tools for small animal and (3) the influence of anesthesia on treatment tested in animal models.tPA used in the clinical setting (Actilyse®) is a mix of two forms of tPA: single chain form (sc-rtPA) and two chains form (tc-rtPA). Despite similar fibrinolytic activities, these two forms exert distinct brain functions therefore influencing differentially the outcome patients. We then decided to further investigate in a relevant model of thromboembolic stroke in rodents, the mechanisms that can explain these differential effects. Here, we have confirmed differential outcomes of the two forms: whereas sc-rtPA is clearly beneficial when infused shortly after stroke onset, tc-rtPA is deleterious due to an increased alteration of the blood brain barrier integrity.Live imaging of cerebral perfusion of the whole brain is an asset for both clinical and preclinical studies. The emergence of ultrafast ultrasound led to the development of ultrafast Doppler (fUS) and Ultrasound Localization Microscopy (ULM), two methods with different sets of spatio-temporal resolutions and excellent sensitivity to small blood flows. We combined these two methods to provide a longitudinal monitoring of whole brain perfusion using the thromboembolic stroke model in mice with rtPA-induced reperfusion. Our data show that fUS and ULM are of major interest for early prognosis of ischemic stroke and response to treatment, with a tight correlation between early reperfusion at 2h and tissue recovery at 24h. Finally, we develop a relevant awake ischemic stroke model to test new therapies, avoiding interferences due to anesthesia commonly used during in vivo studies mice. The patern of the MCA was followed using Laser Doppler monitoring before, during and 45 min after the stroke onset. Although rtPA treatment is beneficial in both awake and anesthetized stroke models, anesthesia is associated with a lack of correlation between recanalization and stroke outcome. We are now testing a neuroprotective molecule, which was promising before failing in clinical trials (NXY-059), to assess the relevance of this innovative stroke model for future pharmacological studies. Altogether, we provide here a set of innovative pre-clinical data to improve our chance of translation to clinic, including a relevant model of thromboembolic stroke in awake animals and an early prognosis imaging method of response to vascular treatments.

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    Authors: You, Wonsang; Stadler, Jörg;

    Fractals are self-similar and scale-invariant patterns found ubiquitously in nature. A lot of evidences implying fractal properties such as 1/f power spectrums have been also observed in resting state fMRI time series. To explain the fractal behavior in rs-fMRI, we have proposed the fractal-based model of resting state hemodynamic response function (rs-HRF) whose properties can be summarized by a fractal exponent. Here we show, through a simulation studies, that the fractal behavior of cerebral hemodynamics may cause significant distortion of network properties between neuronal activities and BOLD signals. We simulated neuronal population activities based on the stochastic neural field model from the Macaque brain network, and then obtained their corresponding BOLD signals by convolving them with the rs-HRF filter. The precision of centrality estimated in each node was deteriorated overall in three networks based on transfer entropy, mutual information, and Pearson correlation; particularly the distortion of transfer entropy was more sensitive to the standard deviation of fractal exponents. A node with high centrality was resilient to desynchronized fractal dynamics over all frequencies while a node with small centrality exhibited huge distortion of both wavelet correlation and centrality over low frequencies. This theoretical expectation indicates that the difference of fractal exponents between brain regions leads to discrepancy of statistical network properties, especially at nodes with small centrality, between neuronal activities and BOLD signals, and that the traditional definitions of resting state functional connectivity may not effectively reflect the dynamics of spontaneous neuronal activities. Comment: The 3rd Biennial Conference on Resting State Brain Connectivity

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    arXiv.org e-Print Archive
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    Authors: Gervain, Judit;

    Near-infrared spectroscopy (NIRS) is a relatively new and increasingly widespread brain imaging technique, particularly suitable for use with young infants. The technique employs near-infrared light to assess the concentration changes of oxygenated and deoxygenated hemoglobin, accompanying local brain activity. The basic physical, physiological, and neural principles underlying the use of NIRS and some of the existing developmental studies are reviewed. Issues concerning technological improvements, parameter optimization, possible experimental designs, and data analysis techniques are also discussed and illustrated.

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    https://doi.org/10.1016/b978-0...
    Part of book or chapter of book . 2015 . Peer-reviewed
    License: Elsevier TDM
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    Authors: Cosandier-Rimélé, Delphine; Merlet, Isabelle; Badier, Jean-Michel; Chauvel, Patrick; +1 Authors

    In epileptic patients candidate to surgery, the interpretation of electrophysiological signals recorded non-invasively (scalp EEG) and invasively (depth EEG) is a difficult but central question. Indeed, the localization of the epileptogenic zone, the determination of its organisation and the definition of subsequent therapeutic strategy is still largely based on the analysis of electrophysiological data. This issue is addressed in the present work through a realistic modeling of both scalp and depth EEG signals. The model is based on an anatomically and physiologically relevant description of the neuronal sources of brain electrical activity that combines a distributed dipole source model and a model of coupled neuronal populations. EEG signals are then simulated by solving the forward problem in the head volume conductor, simultaneously on scalp and depth electrodes. The model was used to study the influence, on simulated EEG signals, of source-related parameters (spatial extent, position, synchronization) leading to the generation of transient epileptic activity (interictal spikes). More generally, this modeling approach helps in the understanding of the relationship between the properties of signals collected by electrodes (scalp and depth) and the underlying spatio-temporal organization of the neuronal sources. ISBN : 978-2-9532965-0-1

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      Other literature type . 2008
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    Authors: Leroy, Arnaud;

    Les êtres humains doivent être capables d’intégrer de nombreux stimuli perceptifs mais également de filtrer en priorité les seules informations dignes d’intérêt. Ces stimuli sont priorisés en fonction de leur saillance. Le réseau cérébral de la saillance est composé de l’insula antérieure, du cortex cingulaire antérieur dorsal, de l’amygdale, du striatum ventral, et de la substance noire/aire tegmentale ventrale. Ce réseau focalise l’attention et facilite l’accès à la mémoire de travail une fois qu’un évènement saillant est détecté. Le réseau de saillance joue ainsi un rôle crucial dans la balance cognitive entre stimuli externes et processus mentaux internes. De nombreuses études ont démontré l’existence de liens entre ce réseau et le stress. De même, le réseau de saillance a été impliqué dans de nombreuses pathologies psychiatriques ou neurologiques, dont la démence fronto-temporale, les troubles de l’humeur et anxieux, la schizophrénie, les addictions ou encore la douleur. Plus spécifiquement, une implication du réseau de saillance dans les expériences intrusives a été suggérée, notamment au cours des hallucinations dans la schizophrénie, et potentiellement lors des reviviscences post-traumatiques dans le trouble de stress post-traumatique. L’objectif de ce travail de thèse était d’étudier plus précisément le rôle du réseau de saillance dans les phénomènes intrusifs dans ces deux pathologies. Une première partie est consacrée à l’étude des hallucinations dans la schizophrénie, et une seconde porte sur l’étude des reviviscences post-traumatiques dans le trouble de stress post-traumatique. Nous avons tout d’abord étudié les bases neurales de la saillance dans la schizophrénie, en réalisant une méta-analyse basée sur les coordonnées fonctionnelles (en imagerie par résonance magnétique) d’études se focalisant sur les processus de récompense. Nous avons ainsi montré que l’hypoactivation du striatum ventral retrouvée chez les patients souffrant de schizophrénie lors de ces tâches était corrélée aux symptômes positifs du trouble. Plusieurs études ‘trait’ et ‘état’ ont proposé que le réseau de saillance puisse jouer un rôle modulateur dans les expériences hallucinatoires. Dans une deuxième étude, nous avons donc validé une méthode de capture hallucinatoire à même de comparer le décours temporel des aires hyperactivées dans ces expériences, avec celui des différents réseaux fonctionnels de repos, étape indispensable pour la mesure dynamique du réseau de saillance dans ces phénomènes. Enfin, dans une troisième étude, nous avons étudié le rôle joué par le réseau de saillance, et en particulier de l’insula antérieure, dans la réponse au traitement dans le trouble de stress post-traumatique. En effet, les bases neurales de la réponse au traitement sont encore peu connues, notamment via des mesures de connectivité effective. Nous avons ainsi pu montrer l’importance du rôle modulateur de l’insula antérieure dans la diminution des reviviscences post-traumatiques. Ces résultats laissent entrevoir plusieurs applications concrètes en psychiatrie. En particulier, l’amélioration des connaissances physiopathologiques des phénomènes intrusifs, à la fois dans la schizophrénie et le trouble de stress post-traumatique, avec la perspective de développer des méthodes de capture des reviviscences post-traumatiques sur le modèle de la capture hallucinatoire, ouvre des possibilités d’avancées dans le champ de la médecine personnalisée dans ces deux pathologies. In a sensorially complex world, human beings need to efficiently and effectively filter and respond to relevant stimuli. Stimuli are prioritized according to their saliency. Especially, the salience network is readily identified as an intrinsically connected large-scale network including prominent nodes as the anterior insula, the dorsal anterior cingulate cortex, the amygdala, the ventral striatum, and the substantia nigra/ventral tegmental area. The salience network not only plays an important role in saliency detection and reactivity but also facilitates access to attention and working memory resources once a salient event has been detected. Stress reactions have been previously linked to activation of the salience network. Moreover, network models are now being widely used to characterize deficits in a wide range of psychiatric and neurological disorders. These studies have provided evidence for prominent salience network dysfunctions in frontotemporal dementia, mood and anxiety disorders, schizophrenia, drug addiction, or pain. Especially, the role of the salience network in intrusive experiences has been suggested, during hallucinations in patients with schizophrenia, and more recently, during re-experiencing in patients suffering from post-traumatic stress disorders. The goal of the present thesis is to improve knowledge about the role of the salience network in intrusive thoughts in these two disorders. In a first part, we studied the role of the salience network in hallucinations in patients with schizophrenia. In a second part, we studied its role in re-experiencing in post-traumatic stress disorder. In a coordinate-based meta-analysis, we explored the neural bases of salience in schizophrenia, focusing on reward processing. We showed that the hypoactivation of the ventral striatum found in patients with schizophrenia during such tasks was correlated with positive symptoms of schizophrenia. Furthermore, several ‘trait’ and ‘state’ studies found that the salience network has a modulatory function in the occurrence of hallucinatory experiences. In a second study, we thus validated a method for hallucinations’ capture, making possible the comparison between the time-course of brains areas overactivated during these experiences and conventional resting-state networks, which is a mandatory step for the study of the dynamic role of the salience network during hallucinations. Finally, in a third study, we explored the role of insular cortex in re-experiencing symptoms in post-traumatic stress disorders, and especially its role in response to pre-reactivation propranolol therapy. The neural bases of treatment-response are indeed still poorly understood, notably via effective connectivity analysis. We showed that the anterior insula exerted causal influences over the brain which correlate with reexperiencing in post-traumatic stress disorder. These studies pave the way for future developments. Especially, improvement in the knowledge about the physiopathology of intrusive experiences, both in schizophrenia and post-traumatic stress disorder, are important to develop re-experiencing capture methods, and for the development of personalized medicine in these two disorders.

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  • Authors: Moriceau, Aurélie;

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  • Authors: Droulers, Olivier; Roullet, Bernard;

    Les progrès accomplis récemment par les neurosciences ont permis une révision complète de la compréhension du fonctionnement cérébral. Une révolution est en marche, bouleversant les paradigmes établis en sciences humaines. Le marketing, après avoir assimilé successivement les concepts de psychologie générale puis de psychologie cognitive, doit aujourd'hui s'approprier les notions et concepts des neurosciences pour garder sa place au sein des sciences sociales et humaines.

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  • Authors: Roullet, Bernard; Droulers, Olivier;

    The evolution of marketing concepts under the influence of the psychologicalthought is a constant in the discipline history. The development of cognitive science, andmore specifically of the neurosciences, allow us today to advocate a consumer neuroscience.The author presents here the expected developments of the discipline and its contiguousethical reflections. l'évolution des concepts marketing sous l'influence de la pensée psychologique estune constante dans l'histoire de la discipline. Le développement des sciences cognitives etplus spécifiquement des neurosciences permet aujourd'hui de proposer une neuroscience duconsommateur. L'auteur expose ici les développements attendus et les réflexions éthiquesattenantes. International audience

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    Authors: Tounekti, Slimane;

    L’IRM de diffusion (IRMd) est l’unique technique non invasive qui permet l’exploration de la microstructure cérébrale. En plus d’une large utilisation pour les applications médicales, l’IRMd est aussi utilisée en neuroscience pour comprendre l’organisation et le fonctionnement du cerveau. Toutefois, sa faible résolution spatiale et sa sensibilité aux artéfacts limitent son utilisation chez le primate non humain.L’objectif de cette étude est de développer une nouvelle approche qui permette d’acquérir des données d’IRMd à très haute résolution spatiale sur des cerveaux de macaques anesthésiés. Cette méthode est basée sur un balayage 3D de l’espace de Fourier avec un module de lecture d’Echo Planar-segmenté.Cette méthode a été tout d’abord implémentée sur une machine IRM 3 Tesla (Prisma, Siemens), puis validée et optimisée in-vitro et in-vivo. Par rapport à la méthode d’acquisition classique, un gain de sensibilité de l’ordre de 3 pour la substance grise cérébrale et de 4.7 pour la substance blanche cérébrale a été obtenu grâce à la méthode développée.Cette méthode a permis de réaliser l’IRMd du cerveau de Macaque avec une résolution spatiale isotrope de 0.5 mm jamais atteinte auparavant. L’intérêt de réaliser des données d’IRMd à une telle résolution pour visualiser et analyser in-vivo des structures fines non détectables avec la méthode d’acquisition classique comme les sous-champs de l’hippocampe ou encore la substance blanche superficielle, a été démontré dans cette étude. Des résultats préliminaires très encourageants ont également été obtenus chez l’homme Diffusion MRI (dMRI) is the unique non-invasive technique that allows exploring the cerebral microstructure. Besides a wide use for medical applications, dMRI is also employed in neuroscience to understand the brain organization and connectivity. However, the low spatial resolution and the sensitivity to artefacts limit its application to non-human primates.This work aims to develop a new approach that allows to acquire dMRI at very high spatial resolution on anesthetized macaque brains. This method is based on a 3D sampling of Fourier space with a segmented Echo Planar imaging readout module. This method has been firstly implemented on a 3 Tesla MR scanner (Prisma, Siemens), validated and optimized in-vitro and in-vivo. Compared to the conventional acquisition method, a gain of sensitivity of 3 for the cerebral grey matter and of 4.7 for the white matter was obtained with the proposed approach.This method allowed us to acquire dMRI data on the macaque brain with a spatial isotropic resolution of 0.5 mm ever reached before. The interest to acquire dMRI data with such a spatial resolution to visualize and analyze in-vivo fine structures not detectable with the classical acquisition method, like the sub-fields of hippocampus and the superficial white matter, has also illustrated in this study. Finally, very encouraging preliminary results were also obtained in humans

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    Authors: Ojaroudi, Mohammad; Bila, Stéphane; Salimitorkamani, M.;

    International audience; In this paper, brain hemorrhage stroke detection approach using microwave-imaging system with a novel machine-learning based post-processing method is presented. In order to create a circular array based microwave imaging system sixteen elements of the modified bowtie antennas are simulated in CST medium around the full head phantom. In order to radiate in desired band from 0.5-5 GHz an appropriate matching medium is designed. In addition, a hierarchical preprocessing method is employed to calibrate the reflected signals. In the processing section, a confocal imagereconstructing algorithm based is used. Finally, a new machine learning technique including discrete wavelet transform (DWT) and principle component analysis (PCA) for feature extraction and reduction, respectively. In addition, support vector machine (SVM) is used for segmentation and clustering of hemorrhage stroke detection from reconstructed image is employed. Simulated results are presented to validate the effectiveness of the proposed method for precisely localizing and classifying bleeding targets.

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    Authors: Brodin, Camille;

    Les défauts de translation des études précliniques vers les essais cliniques dans le domaine des AVC ischémiques et l'échec des développements thérapeutiques pourraient être expliqués par trois aspects : (1) le manque de compréhension des mécanismes des deux formes de rtPA, le traitement pharmacologique de l'AVC; (2) le manque d'outils adaptés d'imagerie de perfusion chez le petit animal et (3) l'influence de l'anesthésie sur l’effet des traitements testés dans les modèles animaux.Le tPA utilisé en clinique (Actilyse®) est un mélange de deux formes de tPA: une forme chaîne simple (sc-rtPA) et une double chaîne (tc-rtPA). Malgré des activités fibrinolytiques similaires, ces deux formes de tPA exercent des fonctions cérébrales distinctes influençant différemment la récupération des patients. Ainsi, nous avons décidé d'étudier en détail dans un modèle murin d'AVC thromboembolique les mécanismes pouvant expliquer ces effets divergents. Nous avons confirmé ces observations à savoir que sc-rtPA est bénéfique lorsqu'il est perfusé tôt après le début de l'AVC, alors que le tc-rtPA est délétère en raison d'une altération de la barrière hémato-encéphalique.L'imagerie en temps réel de la perfusion de l'ensemble du cerveau est un atout pour les études cliniques et précliniques. L'émergence des ultrasons ultra-rapides a conduit au développement du Doppler ultra-rapide et de la Microscopie de Localisation à Ultrasons (ULM), deux méthodes avec différents profils de résolutions spatio-temporelles et une excellente sensibilité aux petits flux sanguins. Nous avons combiné ces deux méthodes pour fournir un suivi longitudinal en 3D de la perfusion cérébrale dans un modèle murin d’AVC thromboembolique avec fibrinolyse par rtPA. Nos données montrent que le FUS et l’ULM présentent un intérêt majeur pour le pronostic précoce de l'AVC ischémique et de la réponse au traitement, avec une corrélation étroite entre la reperfusion précoce à 2h et la récupération tissulaire à 24h.Enfin, l’anesthésie utilisée en laboratoire interfère sur la lésion ischémique et les effets des molécules thérapeutiques testées. Nous nous sommes affranchis de ces effets en développant un nouveau modèle d’AVC ischémique chez des souris totalement éveillées. Le débit sanguin cérébral régional a été suivi par laser Doppler avant, pendant et 45min après le début de l’AVC. Le traitement par rtPA (à 20 min) est bénéfique dans les modèles d’AVC vigile et anesthésié, mais l'anesthésie est associée à un manque de corrélation entre la recanalisation et les volumes de lésion post-ischémie. Nous testons actuellement une molécule neuroprotectrice, qui était prometteuse avant d’échouer lors des essais cliniques (NXY-059), afin d’évaluer la pertinence de ce modèle novateur d’AVC pour les futures études pharmacologiques. Dans l’ensemble, ce travail fournit un panel de données précliniques innovantes pour améliorer nos chances de translation en clinique, incluant un modèle pertinent d'AVC thromboembolique chez des animaux vigiles et une méthode d'imagerie du pronostic précoce de réponse aux traitements vasculaires. The lack of translation between preclinical studies and clinical trials in the field of ischemic stroke and the failure of therapeutic developments could be explained by three aspects: (1) the lack of understanding the mechanism of the two forms of tPA, the pharmacological treatment in stroke; (2) the lack of optimized perfusion imaging tools for small animal and (3) the influence of anesthesia on treatment tested in animal models.tPA used in the clinical setting (Actilyse®) is a mix of two forms of tPA: single chain form (sc-rtPA) and two chains form (tc-rtPA). Despite similar fibrinolytic activities, these two forms exert distinct brain functions therefore influencing differentially the outcome patients. We then decided to further investigate in a relevant model of thromboembolic stroke in rodents, the mechanisms that can explain these differential effects. Here, we have confirmed differential outcomes of the two forms: whereas sc-rtPA is clearly beneficial when infused shortly after stroke onset, tc-rtPA is deleterious due to an increased alteration of the blood brain barrier integrity.Live imaging of cerebral perfusion of the whole brain is an asset for both clinical and preclinical studies. The emergence of ultrafast ultrasound led to the development of ultrafast Doppler (fUS) and Ultrasound Localization Microscopy (ULM), two methods with different sets of spatio-temporal resolutions and excellent sensitivity to small blood flows. We combined these two methods to provide a longitudinal monitoring of whole brain perfusion using the thromboembolic stroke model in mice with rtPA-induced reperfusion. Our data show that fUS and ULM are of major interest for early prognosis of ischemic stroke and response to treatment, with a tight correlation between early reperfusion at 2h and tissue recovery at 24h. Finally, we develop a relevant awake ischemic stroke model to test new therapies, avoiding interferences due to anesthesia commonly used during in vivo studies mice. The patern of the MCA was followed using Laser Doppler monitoring before, during and 45 min after the stroke onset. Although rtPA treatment is beneficial in both awake and anesthetized stroke models, anesthesia is associated with a lack of correlation between recanalization and stroke outcome. We are now testing a neuroprotective molecule, which was promising before failing in clinical trials (NXY-059), to assess the relevance of this innovative stroke model for future pharmacological studies. Altogether, we provide here a set of innovative pre-clinical data to improve our chance of translation to clinic, including a relevant model of thromboembolic stroke in awake animals and an early prognosis imaging method of response to vascular treatments.

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    Authors: You, Wonsang; Stadler, Jörg;

    Fractals are self-similar and scale-invariant patterns found ubiquitously in nature. A lot of evidences implying fractal properties such as 1/f power spectrums have been also observed in resting state fMRI time series. To explain the fractal behavior in rs-fMRI, we have proposed the fractal-based model of resting state hemodynamic response function (rs-HRF) whose properties can be summarized by a fractal exponent. Here we show, through a simulation studies, that the fractal behavior of cerebral hemodynamics may cause significant distortion of network properties between neuronal activities and BOLD signals. We simulated neuronal population activities based on the stochastic neural field model from the Macaque brain network, and then obtained their corresponding BOLD signals by convolving them with the rs-HRF filter. The precision of centrality estimated in each node was deteriorated overall in three networks based on transfer entropy, mutual information, and Pearson correlation; particularly the distortion of transfer entropy was more sensitive to the standard deviation of fractal exponents. A node with high centrality was resilient to desynchronized fractal dynamics over all frequencies while a node with small centrality exhibited huge distortion of both wavelet correlation and centrality over low frequencies. This theoretical expectation indicates that the difference of fractal exponents between brain regions leads to discrepancy of statistical network properties, especially at nodes with small centrality, between neuronal activities and BOLD signals, and that the traditional definitions of resting state functional connectivity may not effectively reflect the dynamics of spontaneous neuronal activities. Comment: The 3rd Biennial Conference on Resting State Brain Connectivity

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    Authors: Gervain, Judit;

    Near-infrared spectroscopy (NIRS) is a relatively new and increasingly widespread brain imaging technique, particularly suitable for use with young infants. The technique employs near-infrared light to assess the concentration changes of oxygenated and deoxygenated hemoglobin, accompanying local brain activity. The basic physical, physiological, and neural principles underlying the use of NIRS and some of the existing developmental studies are reviewed. Issues concerning technological improvements, parameter optimization, possible experimental designs, and data analysis techniques are also discussed and illustrated.

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    https://doi.org/10.1016/b978-0...
    Part of book or chapter of book . 2015 . Peer-reviewed
    License: Elsevier TDM
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    Authors: Cosandier-Rimélé, Delphine; Merlet, Isabelle; Badier, Jean-Michel; Chauvel, Patrick; +1 Authors

    In epileptic patients candidate to surgery, the interpretation of electrophysiological signals recorded non-invasively (scalp EEG) and invasively (depth EEG) is a difficult but central question. Indeed, the localization of the epileptogenic zone, the determination of its organisation and the definition of subsequent therapeutic strategy is still largely based on the analysis of electrophysiological data. This issue is addressed in the present work through a realistic modeling of both scalp and depth EEG signals. The model is based on an anatomically and physiologically relevant description of the neuronal sources of brain electrical activity that combines a distributed dipole source model and a model of coupled neuronal populations. EEG signals are then simulated by solving the forward problem in the head volume conductor, simultaneously on scalp and depth electrodes. The model was used to study the influence, on simulated EEG signals, of source-related parameters (spatial extent, position, synchronization) leading to the generation of transient epileptic activity (interictal spikes). More generally, this modeling approach helps in the understanding of the relationship between the properties of signals collected by electrodes (scalp and depth) and the underlying spatio-temporal organization of the neuronal sources. ISBN : 978-2-9532965-0-1

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    Other literature type . 2008
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      Other literature type . 2008
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    Authors: Leroy, Arnaud;

    Les êtres humains doivent être capables d’intégrer de nombreux stimuli perceptifs mais également de filtrer en priorité les seules informations dignes d’intérêt. Ces stimuli sont priorisés en fonction de leur saillance. Le réseau cérébral de la saillance est composé de l’insula antérieure, du cortex cingulaire antérieur dorsal, de l’amygdale, du striatum ventral, et de la substance noire/aire tegmentale ventrale. Ce réseau focalise l’attention et facilite l’accès à la mémoire de travail une fois qu’un évènement saillant est détecté. Le réseau de saillance joue ainsi un rôle crucial dans la balance cognitive entre stimuli externes et processus mentaux internes. De nombreuses études ont démontré l’existence de liens entre ce réseau et le stress. De même, le réseau de saillance a été impliqué dans de nombreuses pathologies psychiatriques ou neurologiques, dont la démence fronto-temporale, les troubles de l’humeur et anxieux, la schizophrénie, les addictions ou encore la douleur. Plus spécifiquement, une implication du réseau de saillance dans les expériences intrusives a été suggérée, notamment au cours des hallucinations dans la schizophrénie, et potentiellement lors des reviviscences post-traumatiques dans le trouble de stress post-traumatique. L’objectif de ce travail de thèse était d’étudier plus précisément le rôle du réseau de saillance dans les phénomènes intrusifs dans ces deux pathologies. Une première partie est consacrée à l’étude des hallucinations dans la schizophrénie, et une seconde porte sur l’étude des reviviscences post-traumatiques dans le trouble de stress post-traumatique. Nous avons tout d’abord étudié les bases neurales de la saillance dans la schizophrénie, en réalisant une méta-analyse basée sur les coordonnées fonctionnelles (en imagerie par résonance magnétique) d’études se focalisant sur les processus de récompense. Nous avons ainsi montré que l’hypoactivation du striatum ventral retrouvée chez les patients souffrant de schizophrénie lors de ces tâches était corrélée aux symptômes positifs du trouble. Plusieurs études ‘trait’ et ‘état’ ont proposé que le réseau de saillance puisse jouer un rôle modulateur dans les expériences hallucinatoires. Dans une deuxième étude, nous avons donc validé une méthode de capture hallucinatoire à même de comparer le décours temporel des aires hyperactivées dans ces expériences, avec celui des différents réseaux fonctionnels de repos, étape indispensable pour la mesure dynamique du réseau de saillance dans ces phénomènes. Enfin, dans une troisième étude, nous avons étudié le rôle joué par le réseau de saillance, et en particulier de l’insula antérieure, dans la réponse au traitement dans le trouble de stress post-traumatique. En effet, les bases neurales de la réponse au traitement sont encore peu connues, notamment via des mesures de connectivité effective. Nous avons ainsi pu montrer l’importance du rôle modulateur de l’insula antérieure dans la diminution des reviviscences post-traumatiques. Ces résultats laissent entrevoir plusieurs applications concrètes en psychiatrie. En particulier, l’amélioration des connaissances physiopathologiques des phénomènes intrusifs, à la fois dans la schizophrénie et le trouble de stress post-traumatique, avec la perspective de développer des méthodes de capture des reviviscences post-traumatiques sur le modèle de la capture hallucinatoire, ouvre des possibilités d’avancées dans le champ de la médecine personnalisée dans ces deux pathologies. In a sensorially complex world, human beings need to efficiently and effectively filter and respond to relevant stimuli. Stimuli are prioritized according to their saliency. Especially, the salience network is readily identified as an intrinsically connected large-scale network including prominent nodes as the anterior insula, the dorsal anterior cingulate cortex, the amygdala, the ventral striatum, and the substantia nigra/ventral tegmental area. The salience network not only plays an important role in saliency detection and reactivity but also facilitates access to attention and working memory resources once a salient event has been detected. Stress reactions have been previously linked to activation of the salience network. Moreover, network models are now being widely used to characterize deficits in a wide range of psychiatric and neurological disorders. These studies have provided evidence for prominent salience network dysfunctions in frontotemporal dementia, mood and anxiety disorders, schizophrenia, drug addiction, or pain. Especially, the role of the salience network in intrusive experiences has been suggested, during hallucinations in patients with schizophrenia, and more recently, during re-experiencing in patients suffering from post-traumatic stress disorders. The goal of the present thesis is to improve knowledge about the role of the salience network in intrusive thoughts in these two disorders. In a first part, we studied the role of the salience network in hallucinations in patients with schizophrenia. In a second part, we studied its role in re-experiencing in post-traumatic stress disorder. In a coordinate-based meta-analysis, we explored the neural bases of salience in schizophrenia, focusing on reward processing. We showed that the hypoactivation of the ventral striatum found in patients with schizophrenia during such tasks was correlated with positive symptoms of schizophrenia. Furthermore, several ‘trait’ and ‘state’ studies found that the salience network has a modulatory function in the occurrence of hallucinatory experiences. In a second study, we thus validated a method for hallucinations’ capture, making possible the comparison between the time-course of brains areas overactivated during these experiences and conventional resting-state networks, which is a mandatory step for the study of the dynamic role of the salience network during hallucinations. Finally, in a third study, we explored the role of insular cortex in re-experiencing symptoms in post-traumatic stress disorders, and especially its role in response to pre-reactivation propranolol therapy. The neural bases of treatment-response are indeed still poorly understood, notably via effective connectivity analysis. We showed that the anterior insula exerted causal influences over the brain which correlate with reexperiencing in post-traumatic stress disorder. These studies pave the way for future developments. Especially, improvement in the knowledge about the physiopathology of intrusive experiences, both in schizophrenia and post-traumatic stress disorder, are important to develop re-experiencing capture methods, and for the development of personalized medicine in these two disorders.

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    Other literature type . 2020
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