Sans-Sansa B.,FIDMAG Germanes Hospitalaries |
McKenna P.J.,FIDMAG Germanes Hospitalaries |
Canales-Rodriguez E.J.,FIDMAG Germanes Hospitalaries |
Ortiz-Gil J.,FIDMAG Germanes Hospitalaries |
And 6 more authors.
Schizophrenia Research | Year: 2013
Background: Formal thought disorder (FTD) in schizophrenia has been found to be associated with volume reductions in the left superior temporal cortex. However, there have been negative findings and some studies have also found associations in other cortical regions. Method: Fifty-one schizophrenic patients were evaluated for presence of FTD with the Thought, Language and Communication (TLC) scale and underwent whole-brain structural MRI using optimized voxel-based morphometry (VBM). Fifty-nine matched healthy controls were also scanned. Results: Compared to 31 patients without FTD (global TLC rating 0 or 1), 20 patients with FTD (global TLC rating 2-5) showed clusters of volume reduction in the medial frontal and orbitofrontal cortex bilaterally, and in two left-sided areas approximating to Broca's and Wernicke's areas. The pattern of FTD-associated volume reductions was largely different from that found in a comparison between the healthy controls and the patients without FTD. Analysis of correlations within regions-of-interest based on the above clusters indicated that the 'fluent disorganization' component of FTD was correlated with volume reductions in both Broca's and Wernicke's areas, whereas poverty of content of speech was correlated with reductions in the medial frontal/orbitofrontal cortex. Conclusions: The findings point to a relationship between FTD in schizophrenia and structural brain pathology in brain areas involved in language and executive function. © 2013 Elsevier B.V.
Navarra J.,Fundacio Sant Joan de Deu |
Soto-Faraco S.,Catalan Institution for Research and Advanced Studies |
Soto-Faraco S.,University Pompeu Fabra |
Spence C.,University of Oxford
Acta Psychologica | Year: 2014
We investigated the extent to which people can discriminate between languages on the basis of their characteristic temporal, rhythmic information, and the extent to which this ability generalizes across sensory modalities. We used rhythmical patterns derived from the alternation of vowels and consonants in English and Japanese, presented in audition, vision, both audition and vision at the same time, or touch. Experiment 1 confirmed that discrimination is possible on the basis of auditory rhythmic patterns, and extended it to the case of vision, using 'aperture-close' mouth movements of a schematic face. In Experiment 2, language discrimination was demonstrated using visual and auditory materials that did not resemble spoken articulation. In a combined analysis including data from Experiments 1 and 2, a beneficial effect was also found when the auditory rhythmic information was available to participants. Despite the fact that discrimination could be achieved using vision alone, auditory performance was nevertheless better. In a final experiment, we demonstrate that the rhythm of speech can also be discriminated successfully by means of vibrotactile patterns delivered to the fingertip. The results of the present study therefore demonstrate that discrimination between language's syllabic rhythmic patterns is possible on the basis of visual and tactile displays. © 2014 Elsevier B.V.
Salvador R.,Benito Menni C.A.S.M. CIBERSAM |
Sarro S.,Benito Menni C.A.S.M. CIBERSAM |
Gomar J.J.,Benito Menni C.A.S.M. CIBERSAM |
Ortiz-Gil J.,Benito Menni C.A.S.M. CIBERSAM |
And 6 more authors.
Human Brain Mapping | Year: 2010
Abnormal interactions between areas of the brain have been pointed as possible causes for schizophrenia. However, the nature of these disturbances and the anatomical location of the regions involved are still unclear. Here, we describe a method to estimate maps of net levels of connectivity in the resting brain, and we apply it to look for differential patterns of connectivity in schizophrenia. This method uses partial coherences as a basic measure of covariability, and it minimises the effect of major physiological noise. When overall (net) connectivity maps of a sample of 40 patients with schizophrenia were compared with the maps from a matched sample of 40 controls, a single area of abnormality was found. It is an area of patient hyper-connectivity and is located frontally, in medial and orbital structures, clearly overlapping the anterior node of the default mode network (DMN). When this area is used as a region of interest in a second-level analysis, it shows functional hyper-connections with several cortical and subcortical structures. Interestingly, the most significant abnormality is found with the caudate, which has a bilateral pattern of abnormality, pointing to a possible DMN-striatum deviant relation in schizophrenia. However, hyper-connectivity observed with other regions (right hippocampus and amygdala, and other cortical structures) suggests a more pervasive alteration of brain connectivity in this disease. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc.
Pomarol-Clotet E.,Germanes Hospitalaries Del Sagrat Cor Of Jesu S |
Canales-Rodriguez E.J.,Germanes Hospitalaries Del Sagrat Cor Of Jesu S |
Salvador R.,Germanes Hospitalaries Del Sagrat Cor Of Jesu S |
Sarro S.,Germanes Hospitalaries Del Sagrat Cor Of Jesu S |
And 8 more authors.
Molecular Psychiatry | Year: 2010
Neuroimaging studies have found evidence of altered brain structure and function in schizophrenia, but have had complex findings regarding the localization of abnormality. We applied multimodal imaging (voxel-based morphometry (VBM), functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) combined with tractography) to 32 chronic schizophrenic patients and matched healthy controls. At a conservative threshold of P0.01 corrected, structural and functional imaging revealed overlapping regions of abnormality in the medial frontal cortex. DTI found that white matter abnormality predominated in the anterior corpus callosum, and analysis of the anatomical connectivity of representative seed regions again implicated fibres projecting to the medial frontal cortex. There was also evidence of convergent abnormality in the dorsolateral prefrontal cortex, although here the laterality was less consistent across techniques. The medial frontal region identified by these three imaging techniques corresponds to the anterior midline node of the default mode network, a brain system which is believed to support internally directed thought, a state of watchfulness, and/or the maintenance of one's sense of self, and which is of considerable current interest in neuropsychiatric disorders. © 2010 Macmillan Publishers Limited All rights reserved.
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.66M | Year: 2016
The calcium sensing receptor (CaSR) is a class C Gprotein-coupled receptor that plays a pivotal role in systemic calcium metabolism by regulating parathyroid hormone secretion and urinary Ca excretion. Abnormal CaSR function is implicated in calciotropic disorders, and in non-calciotropic disorders such as Alzheimers disease (AD), cardiovascular disease (CVD), diabetes (DM), sarcopenia and cancer, which account for >25% of the global disease burden. The CaSR is a unique GPCR whose principal physiological ligand is the Ca2\ ion; it is expressed almost ubiquitously; interacts with multiple G subtypes regulating highly divergent downstream signalling pathways, depending on the cellular context. The CaSR Biomedicine is a fully translational project that utilises the concept of a single molecule, the CaSR, influencing a range of physiological and disease processes, to develop a unique, strong multidisciplinary and intersectoral scientific training programme preparing 14 young scientists to become specialists in GPCR biology and signalling. The objectives of CaSR Biomedicine are: 1. Educate and train Early Stage Researchers to become highly innovative scientists to enhance their career perspective. 2. Elucidate ligand- and tissue-dependent differences in CaSR physiology by examining its functions at cellular level and thus to contribute to the understanding of GPCR signalling in general. 3. Assess how CaSR function is altered in AD, CVD, DM, sarcopenia, and cancer, and to find innovative CaSR-based therapeutic approaches for these major, age-related disorders. 4. Establish long-lasting interdisciplinary and intersectoral cooperation among researchers and between researchers and industry, to strengthen the European Research Area. Therefore the CaSR Biomedicine will investigate the complexity of CaSR signalling and function to identify CaSR-based therapeutic approaches to diseases linked to changes in CaSR expression or function (AD, CVD, DM, sarcopenia, and cancer).
Agency: European Commission | Branch: FP7 | Program: MC-IRG | Phase: PEOPLE-2007-4-3.IRG | Award Amount: 110.42K | Year: 2007
Neuropsychiatric disorders affect 25% of the population sometime during their life. Aberrant dendritic arbors appear in mental disorders. Although the psychopathological mechanisms are not completely understood, it has been suggested that changes in gene expression contribute to the development and therapy. Several evidences, including the applicant own studies, suggest that misregulation of Sp4 transcription factor could be involved in the pathogenesis and therapy of affective disorders by controlling dendritic patterning. The applicant will explore the possibility that Sp4 and other transcriptional regulators might be altered in postmortem human brains of patients with mental disorders. This research pretends also to investigate the capability to regulate dendritic development by altered novel factors and psychotropic treatment. This project we will test the hypothesis that mood stabilizer and antipsychotic drug leads to a physiological dendritic patterning, in part, through the stabilization/activation of Sp4 transcription factor which leads to changes in expression of genes important for the pathogenesis and therapy of neuropsichiatric disorders. To address that hypothesis (a) we will study whether the levels of Sp4 transcription factor protein or other factors are altered in postmortem brain tissue from patients with schizophrenia or affective disorders. (b) We will perform a novel quantitative proteomic approach (SILAC) and gene expression arrays in postmortem brain of neuropsychiatric patients and whether the new hits module dendritic patterning. (c) And also, we will study the effect of mood stabilizers and antipsychotics on dendritic morphology by Sp4-dependent mechanism. These studies will give a new insight in the transcriptional programs controlled by lithium which may regulate dendritic morphology and, will provide the regulation of Sp4 u others factors as a possible mechanism involved in the pathogenesis and therapy of neuropsychiatric disorders.
Agency: European Commission | Branch: FP7 | Program: MC-IRG | Phase: FP7-PEOPLE-2009-RG | Award Amount: 100.00K | Year: 2011
Recently, some of the neuronal correlates of high level cognitive functions, such as decision making, working memory, visual perception and attention, have been uncovered. Neurophysiologists, powered with new recording techniques, are obtaining crucial information about the neuronal mechanisms that underlay the perception of the objects, confidence in our decisions or our perception of time. With these neuronal recording techniques, we are for the first time in a position to unravel some of the complex mechanisms that underlay basic psychological phenomena. However, the interpretation of the data is often difficult due to their richness and complexity, and a theoretical framework that would allow interpreting these neuronal data coherently is still lacking. To describe and understand the complex, high dimensional neuronal data arising from state of the art recording techniques and being able to link them to behavior, we will develop a new mathematical framework that is algorithmically efficient and at the same time incorporates our knowledge about neuronal electrophysiology. In this multidisciplinary project we will combine computational neuroscience with the analysis of neuronal data to (a) understand how neuronal networks can generate non-trivial behaviours, (b) predict neuronal connectivity from the observed activity patterns, and (c) correlate activity patterns to psychological phenomena. We will analyze and model data from multielectrode recordings in monkey primary visual cortex using state of the art and our own developments of analytical, computational and simulation techniques in order to address the fundamental question of how neurons interact to lead to complex activity patterns. This project will lead to a novel technique for drawing neuronal circuits without seeing them, and migth have important consequences for understanding mental disorders originated in defects of neuronal circuits.
Agency: European Commission | Branch: FP7 | Program: MC-IRG | Phase: FP7-PEOPLE-2009-RG | Award Amount: 100.00K | Year: 2011
Background/Main objective: Neuroblastoma, a solid tumor of the childhood, is the cause of 15% of deaths by cancer in children under the age of 15. Survival of advanced stage neuroblastoma patients remains poor (around 30%), because these tumors rapidly develop resistance to conventional treatments. The poor penetration of chemotherapy agents to the target tumor cells is considered one of the main mechanisms of drug resistance in solid malignancies. Therefore, the main objective of this project is to design pharmacological treatments that circumvent some of the resistance mechanisms and penetrate more efficiently to the neuroblastoma tumor cells. Methodology: We hypothesize that the penetration and activity of the genotoxic drug SN-38 in neuroblastoma tumor xenografts will be improved by its formulation as micelles and by the administration of concomitant nutlin and vandetanib (two new drugs with remarkable anti-neuroblastoma effect). To address this hypothesis, we will prepare SN-38 micelles by the self-assembly of amphiphilic polymers in water. To evaluate the penetration of SN-38 micelles to neuroblastoma xenografts, we will apply a microdialysis technique to sample the extracellular fluid of the tumors and we will analyze drug concentrations in the dialyzates. We will evaluate the effect of nutlin and vandetanib on the tumor penetration and activity of SN-38. Finally, we will test the efficacy of our treatments in a neuroblastoma tumor model and will correlate drug concentrations in plasma and tumor with the observed antineoplastic activity. Expected results: We will identify more effective therapies than the currently available for the treatment of neuroblastoma. We expect that our research will be able to rapidly be translated to the clinic and help rationally design clinical trials for the multidrug resistant neuroblastoma.
Agency: European Commission | Branch: FP7 | Program: MC-CIG | Phase: FP7-PEOPLE-2011-CIG | Award Amount: 100.00K | Year: 2011
Type 2 diabetes (T2D) is a growing global epidemic and new prevention and therapeutic strategies are urgently needed. Insulin resistance is present in high-risk individuals years before the onset of T2D, making the characterization of the complex pathophysiology of insulin resistance a key element of future prevention efforts. The overall goal of our project is to identify and characterize novel molecular mechanisms underlying the development of insulin resistance to find specific targets for prevention and therapeutic strategies. Our analysis of the plasma metabolome of humans at risk for T2D suggests that reductions in betaine levels can contribute to insulin resistance. Consistent with this hypothesis, preliminary studies show that betaine supplementation improves insulin sensitivity and whole-body energy expenditure in a mouse model of diet-induced obesity. First, we propose to determine the mechanisms mediating the beneficial effects of betaine on insulin sensitivity in a diet-induced obese mouse model. For this purpose, C57BL/6 mice will be fed either chow or high-fat diet with or without betaine supplementation. Whole-body and tissue-specific betaine effects will be analyzed to characterize the mechanisms of betaine action. Second, we will apply next generation sequencing of mRNA to analyze the muscle transcriptome associated with high fat feeding and betaine supplementation. As metabolic and molecular changes induced by betaine will be intimately linked to insulin sensitivity, this technique will identify novel genes, alternative splicing isoforms and pathways potentially involved in the development of muscle insulin resistance. This project will constitute a critical first step for future studies aimed at determining whether betaine supplementation is effective in preventing insulin resistance and progression to T2D in humans. Furthermore, it will identify novel targets for designing prevention and therapeutic strategies for the development of T2D.
Agency: European Commission | Branch: H2020 | Program: CSA | Phase: INFRADEV-03-2016-2017 | Award Amount: 3.30M | Year: 2017
Childrens health is a major societal challenge for Europe and the world, requiring development of paediatric medicines and treatments strategies based on evidence derived from clinical trials demonstrating efficacy and safety in infants and children, rather than on uncritical extrapolation from adult data (over 50 % of the medicines used for children had not been tested in this specific age group). Conducting clinical trials in children requires specific competences and infrastructure. ECRIN-ERIC (www.ecrin.org) is a generic infrastructure for multinational trial management, in any disease area. However it does not specifically address the paediatric needs in terms of trial management capacity. In its 2016 Roadmap, ESFRI suggested an upgrade of ECRIN to develop a common infrastructure for paediatric trial management through cooperation with the European Paediatric Clinical Trial Research Infrastructure (EPCTRI). The resulting PedCRIN project is also a unique opportunity to improve ECRIN business model and financial sustainability, attracting more industry-sponsored trials and more Member and Observer countries. PedCRIN builds on five work packages : project coordination (WP1); establishment of a strategy and upgrade of the governance and business plan, through a Sustainability Board jointly involving the scientific partners and the government representatives (WP2); development of tools specific for paediatric and neonatal trials (WP3) (methodology, outcome measures, adverse event reporting, bio-sample management, ethical and regulatory database, monitoring, quality and certification); operational support provided as transnational access to a few pilot trials to test the updated organisation and tools (WP4); communication targeting users communities (including industry), policymakers, patient and parents empowerment (WP5). Two other ESFRI-landmarks, BBMRI-ERIC and EATRIS ERIC, will contribute to PedCRIN.