Selective attention to emotional stimuli: What IQ and Openness do, and emotional intelligence does not

We examined how general intelligence, personality, and emotional intelligence-measured as an ability using the MSCEIT-predicted performance on a selective-attention task requiring participants to ignore distracting emotion information. We used a visual prime in which participants saw a pair of faces depicting emotions; their task was to focus on one of the faces (the target) while ignoring the other (the distractor). Next, participants categorized a string of letters (word or nonword), which was either congruent to the target or the distractor. The speed of response to categorizing the string was recorded. Given the emotional nature of the stimuli and the emotional information processing involved in the task, we were surprised to see that none of the MSCEIT branches predicted performance. However, general intelligence and openness to experience reduced response time.

Cognitive issues in fingerprint analysis: Inter- and intra-expert consistency and the effect of a "target" comparison

Deciding whether two fingerprint marks originate from the same source requires examination and comparison of their features. Many cognitive factors play a major role in such information processing. In this paper we examined the consistency (both between- and within-experts) in the analysis of latent marks, and whether the presence of a 'target' comparison print affects this analysis. Our findings showed that the context of a comparison print affected analysis of the latent mark, possibly influencing allocation of attention, visual search, and threshold for determining a 'signal'. We also found that even without the context of the comparison print there was still a lack of consistency in analysing latent marks. Not only was this reflected by inconsistency between different experts, but the same experts at different times were inconsistent with their own analysis. However, the characterization of these inconsistencies depends on the standard and definition of what constitutes inconsistent. Furthermore, these effects were not uniform; the lack of consistency varied across fingerprints and experts. We propose solutions to mediate variability in the analysis of friction ridge skin.

Cognitive Issues in Fingerprint Analysis: Inter- and Intra-Expert Consistency and the Effect of a "Target" Comparison

Deciding whether two fingerprint marks originate from the same source requires examination and comparison of their features. Many cognitive factors play a major role in such information processing. In this paper we examined the consistency (both between- and within-experts) in the analysis of latent marks, and whether the presence of a 'target' comparison print affects this analysis. Our findings showed that the context of a comparison print affected analysis of the latent mark, possibly influencing allocation of attention, visual search, and threshold for determining a 'signal'. We also found that even without the context of the comparison print there was still a lack of consistency in analysing latent marks. Not only was this reflected by inconsistency between different experts, but the same experts at different times were inconsistent with their own analysis. However, the characterization of these inconsistencies depends on the standard and definition of what constitutes inconsistent. Furthermore, these effects were not uniform; the lack of consistency varied across fingerprints and experts. We propose solutions to mediate variability in the analysis of friction ridge skin.

Startegy selection during exploratory behavior: sex differences, uncertainty and risk managment

This study deals with the psychological processes underlying the selection of appropriate strategy during exploratory behavior. A new device was used to assess sexual dimorphisms in spatial abilities that do not depend on spatial rotation, map reading or directional vector extraction capacities. Moreover, it makes it possible to investigate exploratory behavior as a specific response to novelty that trades off risk and reward. Risk management under uncertainty was assessed through both spontaneous searching strategies and signal detection capacities. The results of exploratory behavior, detection capacities, and decision-making strategies seem to indicate that women's exploratory behavior is based on risk-reducing behavior while men behavior does not appear to be influenced by this variable. This difference was interpreted as a difference in information processing modifying beliefs concerning the likelihood of uncertain events, and therefore influencing risk evaluation.

Ventral and dorsal pathways of speech perception: An intracerebral ERP study.

Recent theory of physiology of language suggests a dual stream dorsal/ventral organization of speech perception. Using intra-cerebral Event-related potentials (ERPs) during pre-surgical assessment of twelve drug-resistant epileptic patients, we aimed to single out electrophysiological patterns during both lexical-semantic and phonological monitoring tasks involving ventral and dorsal regions respectively. Phonological information processing predominantly occurred in the left supra-marginal gyrus (dorsal stream) and lexico-semantic information occurred in anterior/middle temporal and fusiform gyri (ventral stream). Similar latencies were identified in response to phonological and lexico-semantic tasks, suggesting parallel processing. Typical ERP components were strongly left lateralized since no evoked responses were recorded in homologous right structures. Finally, ERP patterns suggested the inferior frontal gyrus as the likely final common pathway of both dorsal and ventral streams. These results brought out detailed evidence of the spatial-temporal information processing in the dual pathways involved in speech perception.

Interhemispheric visual integration in humans explored by multimodal brain imaging

Résumé: Les récents progrès techniques de l'imagerie cérébrale non invasives ont permis d'améliorer la compréhension des différents systèmes fonctionnels cérébraux. Les approches multimodales sont devenues indispensables en recherche, afin d'étudier dans sa globalité les différentes caractéristiques de l'activité neuronale qui sont à la base du fonctionnement cérébral. Dans cette étude combinée d'imagerie par résonance magnétique fonctionnelle (IRMf) et d'électroencéphalographie (EEG), nous avons exploité le potentiel de chacune d'elles, soit respectivement la résolution spatiale et temporelle élevée. Les processus cognitifs, de perception et de mouvement nécessitent le recrutement d'ensembles neuronaux. Dans la première partie de cette thèse nous étudions, grâce à la combinaison des techniques IRMf et EEG, la réponse des aires visuelles lors d'une stimulation qui demande le regroupement d'éléments cohérents appartenant aux deux hémi-champs visuels pour en faire une seule image. Nous utilisons une mesure de synchronisation (EEG de cohérence) comme quantification de l'intégration spatiale inter-hémisphérique et la réponse BOLD (Blood Oxygenation Level Dependent) pour évaluer l'activité cérébrale qui en résulte. L'augmentation de la cohérence de l'EEG dans la bande beta-gamma mesurée au niveau des électrodes occipitales et sa corrélation linéaire avec la réponse BOLD dans les aires de VP/V4, reflète et visualise un ensemble neuronal synchronisé qui est vraisemblablement impliqué dans le regroupement spatial visuel. Ces résultats nous ont permis d'étendre la recherche à l'étude de l'impact que le contenu en fréquence des stimuli a sur la synchronisation. Avec la même approche, nous avons donc identifié les réseaux qui montrent une sensibilité différente à l'intégration des caractéristiques globales ou détaillées des images. En particulier, les données montrent que l'implication des réseaux visuels ventral et dorsal est modulée par le contenu en fréquence des stimuli. Dans la deuxième partie nous avons a testé l'hypothèse que l'augmentation de l'activité cérébrale pendant le processus de regroupement inter-hémisphérique dépend de l'activité des axones calleux qui relient les aires visuelles. Comme le Corps Calleux présente une maturation progressive pendant les deux premières décennies, nous avons analysé le développement de la fonction d'intégration spatiale chez des enfants âgés de 7 à 13 ans et le rôle de la myelinisation des fibres calleuses dans la maturation de l'activité visuelle. Nous avons combiné l'IRMf et la technique de MTI (Magnetization Transfer Imaging) afin de suivre les signes de maturation cérébrale respectivement sous l'aspect fonctionnel et morphologique (myelinisation). Chez lés enfants, les activations associées au processus d'intégration entre les hémi-champs visuels sont, comme chez l'adulte, localisées dans le réseau ventral mais se limitent à une zone plus restreinte. La forte corrélation que le signal BOLD montre avec la myelinisation des fibres du splenium est le signe de la dépendance entre la maturation des fonctions visuelles de haut niveau et celle des connections cortico-corticales. Abstract: Recent advances in non-invasive brain imaging allow the visualization of the different aspects of complex brain dynamics. The approaches based on a combination of imaging techniques facilitate the investigation and the link of multiple aspects of information processing. They are getting a leading tool for understanding the neural basis of various brain functions. Perception, motion, and cognition involve the formation of cooperative neuronal assemblies distributed over the cerebral cortex. In this research, we explore the characteristics of interhemispheric assemblies in the visual brain by taking advantage of the complementary characteristics provided by EEG (electroencephalography) and fMRI (Functional Magnetic Resonance Imaging) techniques. These are the high temporal resolution for EEG and high spatial resolution for fMRI. In the first part of this thesis we investigate the response of the visual areas to the interhemispheric perceptual grouping task. We use EEG coherence as a measure of synchronization and BOLD (Blood Oxygenar tion Level Dependent) response as a measure of the related brain activation. The increase of the interhemispheric EEG coherence restricted to the occipital electrodes and to the EEG beta band and its linear relation to the BOLD responses in VP/V4 area points to a trans-hemispheric synchronous neuronal assembly involved in early perceptual grouping. This result encouraged us to explore the formation of synchronous trans-hemispheric networks induced by the stimuli of various spatial frequencies with this multimodal approach. We have found the involvement of ventral and medio-dorsal visual networks modulated by the spatial frequency content of the stimulus. Thus, based on the combination of EEG coherence and fMRI BOLD data, we have identified visual networks with different sensitivity to integrating low vs. high spatial frequencies. In the second part of this work we test the hypothesis that the increase of brain activity during perceptual grouping depends on the activity of callosal axons interconnecting the visual areas that are involved. To this end, in children of 7-13 years, we investigated functional (functional activation with fMRI) and morphological (myelination of the corpus callosum with Magnetization Transfer Imaging (MTI)) aspects of spatial integration. In children, the activation associated with the spatial integration across visual fields was localized in visual ventral stream and limited to a part of the area activated in adults. The strong correlation between individual BOLD responses in .this area and the myelination of the splenial system of fibers points to myelination as a significant factor in the development of the spatial integration ability.

ZHARP: three-dimensional motion tracking from a single image plane.

Three-dimensional imaging and quantification of myocardial function are essential steps in the evaluation of cardiac disease. We propose a tagged magnetic resonance imaging methodology called zHARP that encodes and automatically tracks myocardial displacement in three dimensions. Unlike other motion encoding techniques, zHARP encodes both in-plane and through-plane motion in a single image plane without affecting the acquisition speed. Postprocessing unravels this encoding in order to directly track the 3-D displacement of every point within the image plane throughout an entire image sequence. Experimental results include a phantom validation experiment, which compares zHARP to phase contrast imaging, and an in vivo study of a normal human volunteer. Results demonstrate that the simultaneous extraction of in-plane and through-plane displacements from tagged images is feasible.

Astrocyte Ca²⁺ signalling: an unexpected complexity.

Astrocyte Ca(2+) signalling has been proposed to link neuronal information in different spatial-temporal dimensions to achieve a higher level of brain integration. However, some discrepancies in the results of recent studies challenge this view and highlight key insufficiencies in our current understanding. In parallel, new experimental approaches that enable the study of astrocyte physiology at higher spatial-temporal resolution in intact brain preparations are beginning to reveal an unexpected level of compartmentalization and sophistication in astrocytic Ca(2+) dynamics. This newly revealed complexity needs to be attentively considered in order to understand how astrocytes may contribute to brain information processing.

Review: Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates.

A. Costanza, K. Weber, S. Gandy, C. Bouras, P. R. Hof, P. Giannakopoulos and A. Canuto (2011) Neuropathology and Applied Neurobiology37, 570-584 Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates Professional boxers and other contact sport athletes are exposed to repetitive brain trauma that may affect motor functions, cognitive performance, emotional regulation and social awareness. The term of chronic traumatic encephalopathy (CTE) was recently introduced to regroup a wide spectrum of symptoms such as cerebellar, pyramidal and extrapyramidal syndromes, impairments in orientation, memory, language, attention, information processing and frontal executive functions, as well as personality changes and behavioural and psychiatric symptoms. Magnetic resonance imaging usually reveals hippocampal and vermis atrophy, a cavum septum pellucidum, signs of diffuse axonal injury, pituitary gland atrophy, dilated perivascular spaces and periventricular white matter disease. Given the partial overlapping of the clinical expression, epidemiology and pathogenesis of CTE and Alzheimer's disease (AD), as well as the close association between traumatic brain injuries (TBIs) and neurofibrillary tangle formation, a mixed pathology promoted by pathogenetic cascades resulting in either CTE or AD has been postulated. Molecular studies suggested that TBIs increase the neurotoxicity of the TAR DNA-binding protein 43 (TDP-43) that is a key pathological marker of ubiquitin-positive forms of frontotemporal dementia (FTLD-TDP) associated or not with motor neurone disease/amyotrophic lateral sclerosis (ALS). Similar patterns of immunoreactivity for TDP-43 in CTE, FTLD-TDP and ALS as well as epidemiological correlations support the presence of common pathogenetic mechanisms. The present review provides a critical update of the evolution of the concept of CTE with reference to its neuropathological definition together with an in-depth discussion of the differential diagnosis between this entity, AD and frontotemporal dementia.

Rivastigmine for HIV-associated neurocognitive disorders: A randomized crossover pilot study.

OBJECTIVE: To assess the efficacy and safety of rivastigmine for the treatment of HIV-associated neurocognitive disorders (HAND) in a cohort of long-lasting aviremic HIV+ patients. METHODS: Seventeen aviremic HIV+ patients with HAND were enrolled in a randomized, double-blind, placebo-controlled, crossover study to receive either oral rivastigmine (up to 12 mg/day for 20 weeks) followed by placebo (20 weeks) or placebo followed by rivastigmine. Efficacy endpoints were improvement on rivastigmine in the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and individual neuropsychological scores of information processing speed, attention/working memory, executive functioning, and motor skills. Measures of safety included frequency and nature of adverse events and abnormalities on laboratory tests and on plasma concentrations of antiretroviral drugs. Analyses of variance with repeated measures were computed to look for treatment effects. RESULTS: There was no change on the primary outcome ADAS-Cog on drug. For secondary outcomes, processing speed improved on rivastigmine (Trail Making Test A: F(1,13) = 5.57, p = 0.03). One measure of executive functioning just failed to reach significance (CANTAB Spatial Working Memory [strategy]: F(1,13) = 3.94, p = 0.069). No other change was observed. Adverse events were frequent, but not different from those observed in other populations treated with rivastigmine. No safety issues were recorded. CONCLUSIONS: Rivastigmine in aviremic HIV+ patients with HAND seemed to improve psychomotor speed. A larger trial with the better tolerated transdermal form of rivastigmine is warranted. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that rivastigmine is ineffective for improving ADAS-Cog scores, but is effective in improving some secondary outcome measures in aviremic HIV+ patients with HAND.

The future of leadership

The good news with regard to this (or any) chapter on the future of leadership is that there is one. There was a time when researchers called for a moratorium on new leadership theory and research (e.g., Miner, 1975) citing the uncertain future of the field. Then for a time there was a popular academic perspective that leadership did not really matter when it came to shaping organizational outcomes (Meindl & Ehrlich, 1987; Meindl, Ehrlich, & Dukerich, 1985; Pfeffer, 1977). That perspective was laid to rest by "realists" in the field (Day & Antonakis, 2012a) by means of empirical re-interpretation of the results used to support the position that leadership does not matter (Lieberson & O'Connor, 1972; Salancik & Pfeffer, 1977). Specifically, Day and Lord (1988) showed that when proper methodological concerns were addressed (e.g., controlling for industry and company size effects; incorporating appropriate time lags) that the impact of top-level leadership was considerable - explaining as much as 45% of the variance in measures of organizational performance. Despite some recent pessimistic sentiments about the "curiously unformed" state of leadership research and theory (Hackman & Wageman, 2007), others have argued that the field has continued to evolve and is potentially on the threshold of some significant breakthroughs (Day & Antonakis, 2012a). Leadership scholars have been re-energized by new directions in the field and research efforts have revitalized areas previously abandoned for apparent lack of consistency in findings (e.g., leadership trait theory). Our accumulated knowledge now allows us to explain the nature of leadership including its biological bases and other antecedents, and consequences with some degree of confidence. There are other comprehensive sources that review the extensive theoretical and empirical foundation of leadership (Bass, 2008; Day & Antonakis, 2012b) so that will not be the focus of the present chapter. Instead, we will take a future-oriented perspective in identifying particular areas within the leadership field that we believe offer promising perspectives on the future of leadership. Nonetheless, it is worthwhile as background to first provide an overview of how we see the leadership field changing over the past decade or so. This short chronicle will set the stage for a keener understanding of where the future contributions are likely to emerge. Overall, across nine major schools of leadership - trait, behavioural, contingency, contextual, relational, sceptics, information processing, New Leadership, biological and evolutionary - researchers have seen a resurgence in interest in one area, a high level of activity in at least four other areas, inactivity in three areas, and one that was modestly active in the previous decade but we think holds strong promise for the future (Gardner, Lowe, Moss, Mahoney, & Cogliser, 2010). We will next provide brief overviews of these nine schools and their respective levels of research activity (see Figure 1).

MR connectomics: a conceptual framework for studying the developing brain.

THE COMBINATION OF ADVANCED NEUROIMAGING TECHNIQUES AND MAJOR DEVELOPMENTS IN COMPLEX NETWORK SCIENCE, HAVE GIVEN BIRTH TO A NEW FRAMEWORK FOR STUDYING THE BRAIN: "connectomics." This framework provides the ability to describe and study the brain as a dynamic network and to explore how the coordination and integration of information processing may occur. In recent years this framework has been used to investigate the developing brain and has shed light on many dynamic changes occurring from infancy through adulthood. The aim of this article is to review this work and to discuss what we have learned from it. We will also use this body of work to highlight key technical aspects that are necessary in general for successful connectome analysis using today's advanced neuroimaging techniques. We look to identify current limitations of such approaches, what can be improved, and how these points generalize to other topics in connectome research.

Auditory spatio-temporal brain dynamics and their consequences for multisensory interactions in humans.

Recent multisensory research has emphasized the occurrence of early, low-level interactions in humans. As such, it is proving increasingly necessary to also consider the kinds of information likely extracted from the unisensory signals that are available at the time and location of these interaction effects. This review addresses current evidence regarding how the spatio-temporal brain dynamics of auditory information processing likely curtails the information content of multisensory interactions observable in humans at a given latency and within a given brain region. First, we consider the time course of signal propagation as a limitation on when auditory information (of any kind) can impact the responsiveness of a given brain region. Next, we overview the dual pathway model for the treatment of auditory spatial and object information ranging from rudimentary to complex environmental stimuli. These dual pathways are considered an intrinsic feature of auditory information processing, which are not only partially distinct in their associated brain networks, but also (and perhaps more importantly) manifest only after several tens of milliseconds of cortical signal processing. This architecture of auditory functioning would thus pose a constraint on when and in which brain regions specific spatial and object information are available for multisensory interactions. We then separately consider evidence regarding mechanisms and dynamics of spatial and object processing with a particular emphasis on when discriminations along either dimension are likely performed by specific brain regions. We conclude by discussing open issues and directions for future research.

Mice with chronic GSH deficit display phenotypical anomalies that resemble key aspects of schizophrenia

ABSTRACTSchizophrenia is a major psychiatric disorder occurring with a prevalence of 1% in the worldwide population. It develops progressively with psychosis onset in late adolescence or earlyadulthood. The disorder can take many different facets and has a highly diffuse anddistributed neuropathology including deficits in major neurotransmitter systems,myelination, stress regulation, and metabolism. The delayed onset and the heterogeneouspathology suggest that schizophrenia is a developmental disease that arises from interplayof genetic and environmental factors during sensitive periods. Redox dysregulation due to animbalance between pro-oxidants and antioxidant defence mechanisms is among the riskfactors for schizophrenia. Glutathione (GSH) is the major cellular redox regulator andantioxidant. Levels of GSH are decreased in cerebrospinal fluid, prefrontal cortex and postmortemstriatum of schizophrenia patients. Moreover, polymorphisms of the key GSHsynthesizingenzyme, glutamate-cysteine ligase, modifier (GCLM) subunit, are associatedwith the disease, suggesting that GSH deficit is of genetic origin. Here we used miceknockout (KO) for the GCLM gene, which display chronic GSH deficit (~70 to 80% decrease)to investigate the direct link between redox dysregulation and schizophrenia. Accordingly,we evaluated whether GCLM KO compared to normal wildtype mice display behavioralchanges that relate to schizophrenia symptoms and whether their brains showmorphological, functional or metabolic alterations that resemble those in patients.Moreover, we exposed pubertal GCLM mice to repeated mild stress and measured theirhormonal and behavioral stress reactivity. Our data show that chronic GSH deficit isassociated with altered emotion- and stress-related behaviors, deficient prepulse inhibition,pronounced amphetamine-induced hyperlocomotion but normal spatial learning andworking memory. These changes represent important schizophrenia endophenotypes.Moreover, this particular pattern of change indicates impairment of the ventralhippocampus (VH) and related circuitry as opposed to the dorsal hippocampus (DH), which isimplicated in spatial information processing. This is consistent with a selective deficit ofparvalbumin positive interneurons and gamma oscillation in the VH but not DH. Increasedlevels of circulating stress hormones in KO mice following pubertal stress corroborate VHdysfunction as it is involved in negative feedback control of the stress response. VHstructural and functional deficits are frequently found in the schizophrenic brain. Metabolicevaluation of the developing GCLM KO anterior cortex using in vivo magnetic resonancespectroscopy revealed elevated glutamine (Gln), glutamate (Glu), Gln/Glu and N-acetylaspartate(NAA) during the pre-pubertal period. Similar changes are reported in earlyschizophrenia. Overall, we observe phenotypic anomalies in GSH deficient GCLM KO micethat correspond to major schizophrenia endophenotypes. This supports an important rolefor redox dysregulation in schizophrenia and validates the GCLM KO mouse as model for thedisease. Moreover, our results indicate that puberty may be a sensitive period for redoxsensitivechanges highliting the importance of early intervention. Gln, Gln/Glu, Glu and NAAmay qualify as early metabolic biomarkers to identify young at-risk individuals. Since chronictreatment with NAC normalized most metabolic changes in GCLM KO mice, NAC may be oneadjunct treatment of choice for early intervention in patients.RESUMELa schizophrénie est une maladie psychiatrique majeure avec une prévalence de 1% dans lapopulation. Son développement est progressif, les premières psychoses apparaissant àl'adolescence ou au début de l'âge adulte. La maladie a plusieurs présentations et uneneuropathologie étendue, qui inclut des déficits neurochimiques, métaboliques, de lamyélination et de la régulation du stress. L'émergence tardive et l'hétérogénéité de lapathologie suggèrent que la schizophrénie est une maladie développementale, favorisée pardes facteurs génétiques et environnementaux durant des périodes sensibles. La dérégulationrédox, due à un déséquilibre entre facteurs pro-oxidantes et défenses anti-oxidantes,constitue un facteur de risque. Le glutathion (GSH) est le principal régulateur rédox et antioxidantdes cellules, ses taux sont diminués dans le liquide céphalorachidien, le cortexpréfrontal et le striatum de patients. De plus, des variations du gène codant la sous-unitémodulatrice (GCLM) de la glutamate-cystéine ligase, enzyme de synthèse du GSH, sontassociés la maladie, suggérant que le déficit observé chez les patients est d'originegénétique. Nous avons donc utilisé des souris ayant une délétion du gène GCLM (KO), quiont un déficit chronique en GSH (70-80%), afin d'étudier le lien entre une dérégulation rédoxet la schizophrénie. Nous avons évalué si ces souris présentent des altérationscomportementales analogues aux symptômes de la maladie, et des modificationsstructurelles, fonctionnelles et métaboliques au niveau du cerveau, ressemblant à celles despatients. De plus, nous avons soumis les souris à des stresses modérés durant la puberté,puis mesuré les réponses hormonales et comportementales. Les animaux présentent undéficit pré-attentionnel du traitement des informations moto-sensorielles, un déficit pourcertains apprentissages, une réponse accrue à l'amphétamine, mais leurs mémoires spatialeet de travail sont préservées. Ces atteintes comportementales sont analogues à certainsendophénotypes de la schizophrénie. De plus, ces changements comportementaux sontlargement expliqués par une perturbation morphologique et fonctionnelle de l'hippocampeventral (HV). Ainsi, nous avons observé un déficit sélectif des interneurones immunoréactifsà la parvalbumine et une désynchronisation neuronale dans l'HV. L'hippocampe dorsal,impliqué dans l'orientation spatiale, demeure en revanche intact. L'augmentationd'hormones de stress dans le sang des souris KO suite à un stress prépubertal soutien aussil'hypothèse d'une dysfonction de l'HV, connu pour moduler ce type de réponse. Des déficitsstructurels et fonctionnels dans l'hippocampe antérieur (ventral) ont d'ailleurs été rapportéschez des patients schizophrènes. Par de résonance magnétique, nous avons également suivile profil métabolique du le cortex antérieur au cours du développement postnatal des sourisKO. Ces mesures ont révélé des taux élevés de glutamine (Gln), glutamate (Glu), du ratioGln/Glu, et de N-acétyl-aspartate (NAA) durant la période prépubertale. Des altérationssimilaires sont décrites chez les patients durant la phase précoce. Nous avons donc révélédes anomalies phénotypiques chez les souris GCLM KO qui reflètent certainsendophénotypes de la schizophrénie. Nos résultats appuient donc le rôle d'une dérégulationrédox dans l'émergence de la maladie et le potentiel des souris KO comme modèle. De plus,cette étude met en évidence la puberté comme période particulièrement sensible à unedérégulation rédox, renforçant l'importance d'une intervention thérapeutique précoce. Dansce cadre, Gln, Gln/Glu, Glu and NAA seraient des biomarqueurs clés pour identifier de jeunesindividus à risque. De part son efficacité dans notre modèle, NAC pourrait être unesubstance de choix dans le traitement précoce des patients.

Cellular mechanisms underlying the regulation of dendritic development by hepatocyte growth factor.

Acquisition of a mature dendritic morphology is critical for neural information processing. In particular, hepatocyte growth factor (HGF) controls dendritic arborization during brain development. However, the cellular mechanisms underlying the effects of HGF on dendritic growth remain elusive. Here, we show that HGF increases dendritic length and branching of rat cortical neurons through activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Activation of MAPK by HGF leads to the rapid and transient phosphorylation of cAMP response element-binding protein (CREB), a key step necessary for the control of dendritic development by HGF. In addition to CREB phosphorylation, regulation of dendritic growth by HGF requires the interaction between CREB and CREB-regulated transcription coactivator 1 (CRTC1), as expression of a mutated form of CREB unable to bind CRTC1 completely abolished the effects of HGF on dendritic morphology. Treatment of cortical neurons with HGF in combination with brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family that regulates dendritic development via similar mechanisms, showed additive effects on MAPK activation, CREB phosphorylation and dendritic growth. Collectively, these results support the conclusion that regulation of cortical dendritic morphology by HGF is mediated by activation of the MAPK pathway, phosphorylation of CREB and interaction of CREB with CRTC1.