Organization and plasticity of auditory spatial representations

Spatial hearing refers to a set of abilities enabling us to determine the location of sound sources, redirect our attention toward relevant acoustic events, and recognize separate sound sources in noisy environments. Determining the location of sound sources plays a key role in the way in which humans perceive and interact with their environment. Deficits in sound localization abilities are observed after lesions to the neural tissues supporting these functions and can result in serious handicaps in everyday life. These deficits can, however, be remediated (at least to a certain degree) by the surprising capacity of reorganization that the human brain possesses following damage and/or learning, namely, the brain plasticity. In this thesis, our aim was to investigate the functional organization of auditory spatial functions and the learning-induced plasticity of these functions. Overall, we describe the results of three studies. The first study entitled "The role of the right parietal cortex in sound localization: A chronometric single pulse transcranial magnetic stimulation study" (At et al., 2011), study A, investigated the role of the right parietal cortex in spatial functions and its chronometry (i.e. the critical time window of its contribution to sound localizations). We concentrated on the behavioral changes produced by the temporarily inactivation of the parietal cortex with transcranial magnetic stimulation (TMS). We found that the integrity of the right parietal cortex is crucial for localizing sounds in the space and determined a critical time window of its involvement, suggesting a right parietal dominance for auditory spatial discrimination in both hemispaces. In "Distributed coding of the auditory space in man: evidence from training-induced plasticity" (At et al., 2013a), study B, we investigated the neurophysiological correlates and changes of the different sub-parties of the right auditory hemispace induced by a multi-day auditory spatial training in healthy subjects with electroencephalography (EEG). We report a distributed coding for sound locations over numerous auditory regions, particular auditory areas code specifically for precise parts of the auditory space, and this specificity for a distinct region is enhanced with training. In the third study "Training-induced changes in auditory spatial mismatch negativity" (At et al., 2013b), study C, we investigated the pre-attentive neurophysiological changes induced with a training over 4 days in healthy subjects with a passive mismatch negativity (MMN) paradigm. We showed that training changed the mechanisms for the relative representation of sound positions and not the specific lateralization themselves and that it changed the coding in right parahippocampal regions. - L'audition spatiale désigne notre capacité à localiser des sources sonores dans l'espace, de diriger notre attention vers les événements acoustiques pertinents et de reconnaître des sources sonores appartenant à des objets distincts dans un environnement bruyant. La localisation des sources sonores joue un rôle important dans la façon dont les humains perçoivent et interagissent avec leur environnement. Des déficits dans la localisation de sons sont souvent observés quand les réseaux neuronaux impliqués dans cette fonction sont endommagés. Ces déficits peuvent handicaper sévèrement les patients dans leur vie de tous les jours. Cependant, ces déficits peuvent (au moins à un certain degré) être réhabilités grâce à la plasticité cérébrale, la capacité du cerveau humain à se réorganiser après des lésions ou un apprentissage. L'objectif de cette thèse était d'étudier l'organisation fonctionnelle de l'audition spatiale et la plasticité induite par l'apprentissage de ces fonctions. Dans la première étude intitulé « The role of the right parietal cortex in sound localization : A chronometric single pulse study » (At et al., 2011), étude A, nous avons examiné le rôle du cortex pariétal droit dans l'audition spatiale et sa chronométrie, c'est-à- dire le moment critique de son intervention dans la localisation de sons. Nous nous sommes concentrés sur les changements comportementaux induits par l'inactivation temporaire du cortex pariétal droit par le biais de la Stimulation Transcrânienne Magnétique (TMS). Nous avons démontré que l'intégrité du cortex pariétal droit est cruciale pour localiser des sons dans l'espace. Nous avons aussi défini le moment critique de l'intervention de cette structure. Dans « Distributed coding of the auditory space : evidence from training-induced plasticity » (At et al., 2013a), étude B, nous avons examiné la plasticité cérébrale induite par un entraînement des capacités de discrimination auditive spatiale de plusieurs jours. Nous avons montré que le codage des positions spatiales est distribué dans de nombreuses régions auditives, que des aires auditives spécifiques codent pour des parties données de l'espace et que cette spécificité pour des régions distinctes est augmentée par l'entraînement. Dans « Training-induced changes in auditory spatial mismatch negativity » (At et al., 2013b), étude C, nous avons examiné les changements neurophysiologiques pré- attentionnels induits par un entraînement de quatre jours. Nous avons montré que l'entraînement modifie la représentation des positions spatiales entraînées et non-entrainées, et que le codage de ces positions est modifié dans des régions parahippocampales.

Spatial and temporal regulation of " cdc16p " in the fission yeast " Schizosaccharomyces pombe "

Abstract: The fission yeast Schizosaccharomyces pombe has proven to be an excellent model system for the study of eukaryotic cell cycle control. S. pombe cells are rod-shaped and grow mainly by elongation at their tips. They divide by the means of a centrallyplaced division septum which provides two daughter cells of equal size. S. pombe cytokinesis begins at mitotic entry, when the division site is defined by formation of the contractile acto-myosin ring (CAR). Formation of the division septum is triggered at the end of mitosis by the spindle pole body (SPB) associated septation initiation network (SIN) proteins. SIN signalling requires activation of the GTPase spg1p, whose nucleotide status is regulated by the bipartite GAP byr4pcdc16p. Removal of cdc16p from the SPB during early mitosis is thought to allow priming of the SIN by association of cdc7p with both SPBs. During anaphase cdc7p is retained on the new SPB, which also recruits the kinase sid1 p and cdc14p, while the old SP8 reassembles the byr4-cdc16p GAP and is presumed not to signal; SPB asymmetry persists throughout anaphase. The trigger for inactivation of SIN signalling at the new SPB is unknown. This study has concentrated upon cdc16p. We have undertaken the analysis of the localisation of cdc16p using time-lapse microscopy. We have observed that the localisation of cdc16p is regulated at different transitions. We have shown that cdc16p is removed from the SPB prior to the onset of spindle formation and that it reappears asymmetrically at the beginning of anaphase B. We have also demonstrated that the resetting of the SIN at the new SPB is linked to completion of CAR contraction and septum formation. We propose the existence of a mechanism that monitors cytokinesis and that couples the activity of the SI N with the presence of the CAR. During the biochemical characterization of cdc16p, We have found that it is an unstable protein and that it is subjected to polyubiquitination by the SCF and proteasomal degradation. Together, these observations help to shed new light upon the mechanisms by which cytokinesis is regulated in S. pombe. Résumé: La levure Schizosaccharomyces pombe est un excellent organisme modèle pour l'étude du cycle cellulaire eucaryote. Les cellules S. pombe ont la forme de bâtonnets et croissent par l'allongement de leurs extrémités. Elles se divisent en formant, en leur milieu une paroi cellulaire, appelé septum, permettant ainsi l'obtention de deux cellules filles de même taille. Chez S. pombe, la cytokinèse commence en début de mitose lorsque le site de division est déterminé par la formation d'un anneau d'acto-myosine. Le septum, lui, est formé uniquement en fin de mitose par la contraction de l'anneau d'actomyosine. Cette contraction est sous le contrôle d'un réseau de signalisation cellulaire appelé le «réseau d'initiation de synthèse du septum » ou « septation initiation network » (SIN), qui se situe sur les pôles du fuseau mitotique. L'activation du SIN dépend d'une GTPase appelé spg1p dont le statut nucléotidique dépend des protéines cdclóp et byr4p qui forment un complexe qui favorise l'hydrolyse du GTP en GDP. En début de mitose, cdc16p ne se situe plus sur les poles du fuseau mitotique. La GTPase spg1p se retrouve donc principalement sous sa forme couplée au GTP, ce quí va permettre son interaction avec la kinase cdc7p. Cette protéine ainsi que deux autres kinases sid2p (avec mob1p) et sid1p (avec cdc14p) permettent la transmission du signal d'initiation de la contraction de l'anneau d'acto-myosine en fin d'anaphase. Pendant l'anaphase, cdc7p, sid1 p et cdc14p localisent sur un des deux pôles du fuseau mitotique. Il en est de même pour cdc1p et by14p et le pôle contenant cdc16p et byr4p est toujours différent de celui ou les régulateurs positifs du SIN se situent. En fin de cytokinèse, cdc16 et byr4p se retrouvent à nouveau sur chaque pôle des deux cellules filles. Dans cette étude, nous nous sommes concentrés sur l'analyse de la localisation de cdc16p pendant la mitose en utilisant une technique de microscopie en temps réel. Nous avons été en mesure de déterminer que le départ de cdc16p du pole s'effectue juste avant la formation du fuseau mitotique. Nous avons aussi découvert que la localisation asymétrique des composants du SIN dépend fortement de l'entrée en anaphase B. Finalement, Nous avons montré que distribution asymétrique des composants du SIN sur les pôles du fuseau mitotique dépendait aussi fortement de !a présence de l'anneau d'acto-myosine. Ceci nous permet donc de proposer l'existence d'un mécanisme cellulaire qui permet de s'assurer que la cytokinèse est achevée avant de diminuer la signalisation du SIN. Par ailleurs, des études biochimiques nous ont permis de montrer que cdc16p est dégradé par le proteosome. Ces travaux ont permis la découverte de nouveaux modes de régulation du SIN.

Spatial learning by rats across visually disconnected environments

Two spatial tasks were designed to test specific properties of spatial representation in rats. In the first task, rats were trained to locate an escape hole at a fixed position in a visually homogeneous arena. This arena was connected with a periphery where a full view of the room environment existed. Therefore, rats were dependent on their memory trace of the previous position in the periphery to discriminate a position within the central region. Under these experimental conditions, the test animals showed a significant discrimination of the training position without a specific local view. In the second task, rats were trained in a radial maze consisting of tunnels that were transparent at their distal ends only. Because the central part of the maze was non-transparent, rats had to plan and execute appropriate trajectories without specific visual feedback from the environment. This situation was intended to encourage the reliance on prospective memory of the non-visited arms in selecting the following move. Our results show that acquisition performance was only slightly decreased compared to that shown in a completely transparent maze and considerably higher than in a translucent maze or in darkness. These two series of experiments indicate (1) that rats can learn about the relative position of different places with no common visual panorama, and (2) that they are able to plan and execute a sequence of visits to several places without direct visual feed-back about their relative position.

Working memory in schizophrenia: dynamic visuo-spatial information processing

Working memory, commonly defined as the ability to hold mental representations on line transiently and to manipulate these representations, is known to be a core deficit in schizophrenia. The aim of the present study was to investigate the visuo-spatial component of the working memory in schizophrenia, and more precisely to what extent the dynamic visuo-spatial information processing is impaired in schizophrenia patients. For this purpose we used a computerized paradigm in which 29 patients with schizophrenia (DSMIV, Diagnostic Interview for Genetic Studies) and 29 age and sex matched control subjects (DIGS) had to memorize a plane moving across the computer screen and to identify the observed trajectory among 9 plots proposed together. Each trajectory could be seen max. 3 times if needed. The results showed no difference between schizophrenia patients and controls regarding the number of correct trajectory identified after the first presentation. However, when we determine the mean number of correct trajectories on the basis of 3 trials, we observed that schizophrenia patients are significantly less performant than controls (Mann-Whitney, p _ 0.002). These findings suggest that, although schizophrenia patients are able to memorize some dynamic trajectories as well as controls, they do not profit from the repetition of the trajectory presentation. These findings are congruent with the hypothesis that schizophrenia could induce an unbalance between local and global information processing: the patients may be able to focus on details of the trajectory which could allow them to find the right target (bottom-up processes), but may show difficulty to refer to previous experience in order to filter incoming information (top-down processes) and enhance their visuo-spatial working memory abilities.

L'équité d'accès aux ressources en eau : fin ou moyen d'amélioration de l'efficacité de l'irrigation ? : la gestion des ressources en eau dans l'état du Gujarat (Inde) dans la perpective de la political ecology

La thèse présentée ici est le résultat d'une étroite collaboration avec une ONG indienne, AKRSP(I), intervenant dans le développement de l'irrigation au Gujarat depuis plus de 25 ans. Un SIG prototype a été mis en oeuvre et nous permet de proposer ime analyse spatiale et quantitative de l'action de cette ONG ainsi qu'une réflexion plus générale sur les leviers de mise en valeur et de gestion des ressources en eau à des fins agricoles. On peut souligner trois principaux enseignements: Les perspectives d'application des SIG au sein des ONG sont manifestes. Les exigences des bailleurs de fonds peuvent néanmoins faire obstacle à leur développement car, indi-rectement, ils favorisent la mise en oeuvre de SI voués à la justification plutôt qu'à la planification et au suivi des programmes d'actions. Ce résultat soulève la question de la pertinence de l'encadrement, des critères d'évaluation et de la conditionnalité de l'aide publique au développement. Les ONG ont un fort potentiel pour participer à la mise en valeur des ressources en eau en Inde et aider à relever le défi agro-démographique indien, en particulier dans les zones marginales où les services étatiques sont en retrait. Les stratégies d'action basées principalement sur l'application des instruments économiques et techniques doivent cependant être modifiées. Nous montrons qu'elles favorisent une inégalité d'accès aux ressources qui débouche sur une efficacité limitée des pratiques d'irrigation, sur un plan agro-technique. Ces résultats soulignent la nécessité de poursuivre une réflexion critique des discours et solutions dominants en matière de gestion des ressources en eau. Deux pistes d'amélioration sont avancées: 1. considérer l'équité d'accès comme un moyen d'optimiser la gestion de la ressource (limiter le volume d'eau par agriculteur pour encourager les choix de cultures irriguées peu consommatrices et l'adoption des technologies d'économie d'eau), 2. prêter attention à l'ordre dans lequel les différents instruments de gestion disponibles sont employés afin de les articuler dans un séquençage temporel pertinent. La Political Ecology apparait comme un cadre conceptuel très pertinent pour engager cette réflexion critique. Elle permet d'intégrer différentes échelles d'asymétries de pouvoirs à la compréhension des situations et des blocages observables localement : inégalités de capabilités et forces socio-politiques à l'échelle locale, politiques agro-industrielles (coton) et jeux d'alliances politiques des castes à l'échelle nationale, discours et conflits idéologiques ou orientations stratégiques des bailleurs de fonds à l'échelle internationale... Notre recherche empirique contribue modestement au développement de cette Political Ecology de la mise en valeur et de la gestion des ressources en eau. - The present research is based on a close collaboration with an indian NGO, AKRSP(I), which is active in the development of irrigation facilities in Gujarat for the past 25 years. We built a GIS prototype providing quantitative and spatial datas to analyse the NGO intervention and propose a general reflection about water resources development and management issues. Three main findings may be emphasized : The potential of GIS within the workings of an NGO is obvious, as an information ma-nagement tool as much as for developing analytical capacity. However, financial backers expectations may not favour a relevant development of this technology. Indirectly, they promote Information Systems built to justify rather than to plan or monitor action pro¬grammes. This raises the question of stricter framework, conditionality criters and stan¬dardised assessment indicators surrounding official development assistance. There is strong potential that NGOs can assist with the improvement of water resources in India. They can help in overcoming Indian demographic-related agricultural challenges, especially in marginal rural areas neglected by state services. However, intervention strategies mainly based on technical and economic management tools has to be adapted. We found that they lead to inequitable access and distribution of water resources what induces a low efficiency of irrigation practices from an agro-technical point of view. These results underline the need to go further in criticizing dominant ideas and guidelines regarding water resources management. We suggest two other options : 1. to consider equitable access has a tool to improve the effective use of water for agricul¬tural purposes (limiting the volume of water available per farmer would encourage them to adopt low water consumption crops and water saving technics), 2. to consider more carefully the order of use of the various management tools available and to structure them in a relevant sequence. Here, Political Ecology seems to be a relevant conceptual framework to enter into such a critical reflection, integrating different levels and scales of political asymmetries at the core of environmental issues. Indeed, the understanding of regional water situations and social stumbling blocks needs not only to consider local capabilities and socio-political inequities, but also agro-industrial policy (e.i. cotton) and caste political alliances at a national scale, as well as ideological and narrative struggles or strategical orientations of financial backers at an international level. Our empirical research modestly contributes to the development of such a Political Ecology of water resources development and management.

Classification of very high spatial resolution imagery using mathematical morphology and support vector machines

We investigate the relevance of morphological operators for the classification of land use in urban scenes using submetric panchromatic imagery. A support vector machine is used for the classification. Six types of filters have been employed: opening and closing, opening and closing by reconstruction, and opening and closing top hat. The type and scale of the filters are discussed, and a feature selection algorithm called recursive feature elimination is applied to decrease the dimensionality of the input data. The analysis performed on two QuickBird panchromatic images showed that simple opening and closing operators are the most relevant for classification at such a high spatial resolution. Moreover, mixed sets combining simple and reconstruction filters provided the best performance. Tests performed on both images, having areas characterized by different architectural styles, yielded similar results for both feature selection and classification accuracy, suggesting the generalization of the feature sets highlighted.

Postnatal intracerebroventricular administrations of NGF alter spatial memory in adulthood

The present work assessed the effects of intracerebroventricular injections (2x5 mg/2.5 ml) of recombined human nerve growth factor (rhNGF) at postnatal days 2 and 3 upon the development of spatial learning capacities in rats. The treated rats were trained at the age of 22 days to escape onto an invisible platform at a fixed position in space in a Morris navigation task. For half of the subjects, the training position was also cued, a procedure aimed at facilitating escape and reducing attention to the distant spatial cues. At the age of 2 months all the rats were retrained in the same task. Treatment effects were found in both immature and adult rats. The injection of NGF induced a slight alteration of the immature rats' performance. In contrast, a marked impairment of spatial abilities was shown in the 2-month-old rats. The most consistent effects were a significant increase in the escape latency and a decrease bias towards the training platform area during probe trials. The reduction of spatial memory was particularly marked if the subjects had been trained in a cued condition. Taken together, these experiments reveal that an acute pharmacological treatment that leads to transient modifications during early development might induce a behavioural change long after treatment. Thus, the development and the maintenance of an accurate spatial representation are tightly related to the development of brain structures that could be altered by precocious NGF administrations.

The impact of spatial resolution and respiratory motion on MR imaging of atherosclerotic plaque.

PURPOSE: To examine the impact of spatial resolution and respiratory motion on the ability to accurately measure atherosclerotic plaque burden and to visually identify atherosclerotic plaque composition. MATERIALS AND METHODS: Numerical simulations of the Bloch equations and vessel wall phantom studies were performed for different spatial resolutions by incrementally increasing the field of view. In addition, respiratory motion was simulated based on a measured physiologic breathing pattern. RESULTS: While a spatial resolution of > or = 6 pixels across the wall does not result in significant errors, a resolution of < or = 4 pixels across the wall leads to an overestimation of > 20%. Using a double-inversion T2-weighted turbo spin echo sequence, a resolution of 1 pixel across equally thick tissue layers (fibrous cap, lipid, smooth muscle) and a respiratory motion correction precision (gating window) of three times the thickness of the tissue layer allow for characterization of the different coronary wall components. CONCLUSIONS: We found that measurements in low-resolution black blood images tend to overestimate vessel wall area and underestimate lumen area.

Reduced genetic diversity, increased isolation and multiple introductions of invasive giant hogweed in the western Swiss Alps.

Abstract The giant hogweed (Heracleum mantegazzianum) has successfully invaded 19 European countries as well as parts of North America. It has become a problematic species due to its ability to displace native flora and to cause public health hazards. Applying population genetics to species invasion can help reconstruct invasion history and may promote more efficient management practice. We thus analysed levels of genetic variation and population genetic structure of H. mantegazzianum in an invaded area of the western Swiss Alps as well as in its native range (the Caucasus), using eight nuclear microsatellite loci together with plastid DNA markers and sequences. On both nuclear and plastid genomes, native populations exhibited significantly higher levels of genetic diversity compared to invasive populations, confirming an important founder event during the invasion process. Invasive populations were also significantly more differentiated than native populations. Bayesian clustering analysis identified five clusters in the native range that corresponded to geographically and ecologically separated groups. In the invaded range, 10 clusters occurred. Unlike native populations, invasive clusters were characterized by a mosaic pattern in the landscape, possibly caused by anthropogenic dispersal of the species via roads and direct collection for ornamental purposes. Lastly, our analyses revealed four main divergent groups in the western Swiss Alps, likely as a consequence of multiple independent establishments of H. mantegazzianum.

Spatial visualization of DNA in solution.

An image analysis method is presented which allows for the reconstruction of the three-dimensional path of filamentous objects from two of their projections. Starting with stereo pairs, this method is used to trace the trajectory of DNA molecules embedded in vitreous ice and leads to a faithful representation of their three-dimensional shape in solution. This computer-aided reconstruction is superior to the subjective three-dimensional impression generated by observation of stereo pairs of micrographs because it enables one to look at the reconstructed molecules from any chosen direction and distance and allows quantitative analysis such as determination of distances, curvature, persistence length, and writhe of DNA molecules in solution.

Revisiting spatial distribution and biochemical composition of calcium-containing crystals in human osteoarthritic articular cartilage.

INTRODUCTION: Calcium-containing (CaC) crystals, including basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP), are associated with destructive forms of osteoarthritis (OA). We assessed their distribution and biochemical and morphologic features in human knee OA cartilage. METHODS: We prospectively included 20 patients who underwent total knee replacement (TKR) for primary OA. CaC crystal characterization and identification involved Fourier-transform infra-red spectrometry and scanning electron microscopy of 8 to 10 cartilage zones of each knee, including medial and lateral femoral condyles and tibial plateaux and the intercondyle zone. Differential expression of genes involved in the mineralization process between cartilage with and without calcification was assessed in samples from 8 different patients by RT-PCR. Immunohistochemistry and histology studies were performed in 6 different patients. RESULTS: Mean (SEM) age and body mass index of patients at the time of TKR was 74.6 (1.7) years and 28.1 (1.6) kg/m², respectively. Preoperative X-rays showed joint calcifications (chondrocalcinosis) in 4 cases only. The medial femoro-tibial compartment was the most severely affected in all cases, and mean (SEM) Kellgren-Lawrence score was 3.8 (0.1). All 20 OA cartilages showed CaC crystals. The mineral content represented 7.7% (8.1%) of the cartilage weight. All patients showed BCP crystals, which were associated with CPP crystals for 8 joints. CaC crystals were present in all knee joint compartments and in a mean of 4.6 (1.7) of the 8 studied areas. Crystal content was similar between superficial and deep layers and between medial and femoral compartments. BCP samples showed spherical structures, typical of biological apatite, and CPP samples showed rod-shaped or cubic structures. The expression of several genes involved in mineralization, including human homolog of progressive ankylosis, plasma-cell-membrane glycoprotein 1 and tissue-nonspecific alkaline phosphatase, was upregulated in OA chondrocytes isolated from CaC crystal-containing cartilages. CONCLUSIONS: CaC crystal deposition is a widespread phenomenon in human OA articular cartilage involving the entire knee cartilage including macroscopically normal and less weight-bearing zones. Cartilage calcification is associated with altered expression of genes involved in the mineralisation process.