Dynamics of the recruitment of lateral amygdala neurons following successive fear learning to different conditional stimuli

In fear conditioning, an animal learns to associate an unconditioned stimulus (US), such as a shock, and a conditioned stimulus (CS), such as a tone, so that the presentation of the CS alone can trigger conditioned responses. Recent research on the lateral amygdala has shown that following cued fear conditioning, only a subset of higher-excitable neurons are recruited in the memory trace. Their selective deletion after fear conditioning results in a selective erasure of the fearful memory. I hypothesize that the recruitment of highly excitable neurons depends on responsiveness to stimuli, intrinsic excitability and local connectivity. In addition, I hypothesize that neurons recruited for an initial memory also participate in subsequent memories, and that changes in neuronal excitability affect secondary fear learning. To address these hypotheses, I will show that A) a rat can learn to associate two successive short-term fearful memories; B) neuronal populations in the LA are competitively recruited in the memory traces depending on individual neuronal advantages, as well as advantages granted by the local network. By performing two successive cued fear conditioning experiments, I found that rats were able to learn and extinguish the two successive short-term memories, when tested 1 hour after learning for each memory. These rats were equipped with a system of stable extracellular recordings that I developed, which allowed to monitor neuronal activity during fear learning. 233 individual putative pyramidal neurons could modulate their firing rate in response to the conditioned tone (conditioned neurons) and/or non- conditioned tones (generalizing neurons). Out of these recorded putative pyramidal neurons 86 (37%) neurons were conditioned to one or both tones. More precisely, one population of neurons encoded for a shared memory while another group of neurons likely encoded the memories' new features. Notably, in spite of a successful behavioral extinction, the firing rate of those conditioned neurons in response to the conditioned tone remained unchanged throughout memory testing. Furthermore, by analyzing the pre-conditioning characteristics of the conditioned neurons, I determined that it was possible to predict neuronal recruitment based on three factors: 1) initial sensitivity to auditory inputs, with tone-sensitive neurons being more easily recruited than tone- insensitive neurons; 2) baseline excitability levels, with more highly excitable neurons being more likely to become conditioned; and 3) the number of afferent connections received from local neurons, with neurons destined to become conditioned receiving more connections than non-conditioned neurons. - En conditionnement de la peur, un animal apprend à associer un stimulus inconditionnel (SI), tel un choc électrique, et un stimulus conditionné (SC), comme un son, de sorte que la présentation du SC seul suffit pour déclencher des réflexes conditionnés. Des recherches récentes sur l'amygdale latérale (AL) ont montré que, suite au conditionnement à la peur, seul un sous-ensemble de neurones plus excitables sont recrutés pour constituer la trace mnésique. Pour apprendre à associer deux sons au même SI, je fais l'hypothèse que les neurones entrent en compétition afin d'être sélectionnés lors du recrutement pour coder la trace mnésique. Ce recrutement dépendrait d'un part à une activation facilité des neurones ainsi qu'une activation facilité de réseaux de neurones locaux. En outre, je fais l'hypothèse que l'activation de ces réseaux de l'AL, en soi, est suffisante pour induire une mémoire effrayante. Pour répondre à ces hypothèses, je vais montrer que A) selon un processus de mémoire à court terme, un rat peut apprendre à associer deux mémoires effrayantes apprises successivement; B) des populations neuronales dans l'AL sont compétitivement recrutées dans les traces mnésiques en fonction des avantages neuronaux individuels, ainsi que les avantages consentis par le réseau local. En effectuant deux expériences successives de conditionnement à la peur, des rats étaient capables d'apprendre, ainsi que de subir un processus d'extinction, pour les deux souvenirs effrayants. La mesure de l'efficacité du conditionnement à la peur a été effectuée 1 heure après l'apprentissage pour chaque souvenir. Ces rats ont été équipés d'un système d'enregistrements extracellulaires stables que j'ai développé, ce qui a permis de suivre l'activité neuronale pendant l'apprentissage de la peur. 233 neurones pyramidaux individuels pouvaient moduler leur taux d'activité en réponse au son conditionné (neurones conditionnés) et/ou au son non conditionné (neurones généralisant). Sur les 233 neurones pyramidaux putatifs enregistrés 86 (37%) d'entre eux ont été conditionnés à un ou deux tons. Plus précisément, une population de neurones code conjointement pour un souvenir partagé, alors qu'un groupe de neurones différent code pour de nouvelles caractéristiques de nouveaux souvenirs. En particulier, en dépit d'une extinction du comportement réussie, le taux de décharge de ces neurones conditionné en réponse à la tonalité conditionnée est resté inchangée tout au long de la mesure d'apprentissage. En outre, en analysant les caractéristiques de pré-conditionnement des neurones conditionnés, j'ai déterminé qu'il était possible de prévoir le recrutement neuronal basé sur trois facteurs : 1) la sensibilité initiale aux entrées auditives, avec les neurones sensibles aux sons étant plus facilement recrutés que les neurones ne répondant pas aux stimuli auditifs; 2) les niveaux d'excitabilité des neurones, avec les neurones plus facilement excitables étant plus susceptibles d'être conditionnés au son ; et 3) le nombre de connexions reçues, puisque les neurones conditionné reçoivent plus de connexions que les neurones non-conditionnés. Enfin, nous avons constaté qu'il était possible de remplacer de façon satisfaisante le SI lors d'un conditionnement à la peur par des injections bilatérales de bicuculline, un antagoniste des récepteurs de l'acide y-Aminobutirique.

When solving 22-7 is much more difficult than 99-12.

We describe the case of a 69-year-old professor of mathematics (GV) who was examined 2 years after left-hemispheric capsular-thalamic haemorrhage. GV showed disproportionate impairment in subtractions requiring borrowing (22 - 7). For large subtraction problems without borrowing (99 - 12) performance was almost flawless. Subtractions with borrowing mostly relied on inadequate attempts to invert subtractions into the corresponding additions (22 - 7 = x as 7 + x = 22). The hypothesis is advanced that difficulty in the inhibitory components of attention tasks (Stroop test, go-no-go task) might be the responsible factor of his calculation impairment. A deficit in subtractions with borrowing might be related to left-hemispheric damage involving thalamo-cortical connections.

On spectral properties of the modified convolution operator

Vegeu el resum a l'inici del document del fitxer adjunt.

Diffusion spectrum imaging shows the structural basis of functional cerebellar circuits in the human cerebellum in vivo.

BACKGROUND: The cerebellum is a complex structure that can be affected by several congenital and acquired diseases leading to alteration of its function and neuronal circuits. Identifying the structural bases of cerebellar neuronal networks in humans in vivo may provide biomarkers for diagnosis and management of cerebellar diseases. OBJECTIVES: To define the anatomy of intrinsic and extrinsic cerebellar circuits using high-angular resolution diffusion spectrum imaging (DSI). METHODS: We acquired high-resolution structural MRI and DSI of the cerebellum in four healthy female subjects at 3T. DSI tractography based on a streamline algorithm was performed to identify the circuits connecting the cerebellar cortex with the deep cerebellar nuclei, selected brainstem nuclei, and the thalamus. RESULTS: Using in-vivo DSI in humans we were able to demonstrate the structure of the following cerebellar neuronal circuits: (1) connections of the inferior olivary nucleus with the cerebellar cortex, and with the deep cerebellar nuclei (2) connections between the cerebellar cortex and the deep cerebellar nuclei, (3) connections of the deep cerebellar nuclei conveyed in the superior (SCP), middle (MCP) and inferior (ICP) cerebellar peduncles, (4) complex intersections of fibers in the SCP, MCP and ICP, and (5) connections between the deep cerebellar nuclei and the red nucleus and the thalamus. CONCLUSION: For the first time, we show that DSI tractography in humans in vivo is capable of revealing the structural bases of complex cerebellar networks. DSI thus appears to be a promising imaging method for characterizing anatomical disruptions that occur in cerebellar diseases, and for monitoring response to therapeutic interventions.

Roles of mGluR5 in synaptic function and plasticity of the mouse thalamocortical pathway.

The group I metabotropic glutamate receptor 5 (mGluR5) has been implicated in the development of cortical sensory maps. However, its precise roles in the synaptic function and plasticity of thalamocortical (TC) connections remain unknown. Here we first show that in mGluR5 knockout (KO) mice bred onto a C57BL6 background cytoarchitectonic differentiation into barrels is missing, but the representations for large whiskers are identifiable as clusters of TC afferents. The altered dendritic morphology of cortical layer IV spiny stellate neurons in mGluR5 KO mice implicates a role for mGluR5 in the dendritic morphogenesis of excitatory neurons. Next, in vivo single-unit recordings of whisker-evoked activity in mGluR5 KO adults demonstrated a preserved topographical organization of the whisker representation, but a significantly diminished temporal discrimination of center to surround whiskers in the responses of individual neurons. To evaluate synaptic function at TC synapses in mGluR5 KO mice, whole-cell voltage-clamp recording was conducted in acute TC brain slices prepared from postnatal day 4-11 mice. At mGluR5 KO TC synapses, N-methyl-D-aspartate (NMDA) currents decayed faster and synaptic strength was more easily reduced, but more difficult to strengthen by Hebbian-type pairing protocols, despite a normal developmental increase in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated currents and presynaptic function. We have therefore demonstrated that mGluR5 is required for synaptic function/plasticity at TC synapses as barrels are forming, and we propose that these functional alterations at the TC synapse are the basis of the abnormal anatomical and functional development of the somatosensory cortex in the mGluR5 KO mouse.

Performance of an ICU ventilator and two turbin-based ventilators dedicated to non invasive ventilation (NIV) in simulated high inspiratory effort and rate: a NIV-bench-study.

INTRODUCTION. The role of turbine-based NIV ventilators (TBV) versus ICU ventilators with NIV mode activated (ICUV) to deliver NIV in case of severe respiratory failure remains debated. OBJECTIVES. To compare the response time and pressurization capacity of TBV and ICUV during simulated NIV with normal and increased respiratory demand, in condition of normal and obstructive respiratory mechanics. METHODS. In a two-chamber lung model, a ventilator simulated normal (P0.1 = 2 mbar, respiratory rate RR = 15/min) or increased (P0.1 = 6 mbar, RR = 25/min) respiratory demand. NIV was simulated by connecting the lung model (compliance 100 ml/mbar; resistance 5 or 20 l/mbar) to a dummy head equipped with a naso-buccal mask. Connections allowed intentional leaks (29 ± 5 % of insufflated volume). Ventilators to test: Servo-i (Maquet), V60 and Vision (Philips Respironics) were connected via a standard circuit to the mask. Applied pressure support levels (PSL) were 7 mbar for normal and 14 mbar for increased demand. Airway pressure and flow were measured in the ventilator circuit and in the simulated airway. Ventilator performance was assessed by determining trigger delay (Td, ms), pressure time product at 300 ms (PTP300, mbar s) and inspiratory tidal volume (VT, ml) and compared by three-way ANOVA for the effect of inspiratory effort, resistance and the ventilator. Differences between ventilators for each condition were tested by oneway ANOVA and contrast (JMP 8.0.1, p\0.05). RESULTS. Inspiratory demand and resistance had a significant effect throughout all comparisons. Ventilator data figure in Table 1 (normal demand) and 2 (increased demand): (a) different from Servo-i, (b) different from V60.CONCLUSION. In this NIV bench study, with leaks, trigger delay was shorter for TBV with normal respiratory demand. By contrast, it was shorter for ICUV when respiratory demand was high. ICUV afforded better pressurization (PTP 300) with increased demand and PSL, particularly with increased resistance. TBV provided a higher inspiratory VT (i.e., downstream from the leaks) with normal demand, and a significantly (although minimally) lower VT with increased demand and PSL.

COMMIT: Convex Optimization Modeling for Microstructure Informed Tractography.

Tractography is a class of algorithms aiming at in vivo mapping the major neuronal pathways in the white matter from diffusion magnetic resonance imaging (MRI) data. These techniques offer a powerful tool to noninvasively investigate at the macroscopic scale the architecture of the neuronal connections of the brain. However, unfortunately, the reconstructions recovered with existing tractography algorithms are not really quantitative even though diffusion MRI is a quantitative modality by nature. As a matter of fact, several techniques have been proposed in recent years to estimate, at the voxel level, intrinsic microstructural features of the tissue, such as axonal density and diameter, by using multicompartment models. In this paper, we present a novel framework to reestablish the link between tractography and tissue microstructure. Starting from an input set of candidate fiber-tracts, which are estimated from the data using standard fiber-tracking techniques, we model the diffusion MRI signal in each voxel of the image as a linear combination of the restricted and hindered contributions generated in every location of the brain by these candidate tracts. Then, we seek for the global weight of each of them, i.e., the effective contribution or volume, such that they globally fit the measured signal at best. We demonstrate that these weights can be easily recovered by solving a global convex optimization problem and using efficient algorithms. The effectiveness of our approach has been evaluated both on a realistic phantom with known ground-truth and in vivo brain data. Results clearly demonstrate the benefits of the proposed formulation, opening new perspectives for a more quantitative and biologically plausible assessment of the structural connectivity of the brain.

How local excitation-inhibition ratio impacts the whole brain dynamics.

The spontaneous activity of the brain shows different features at different scales. On one hand, neuroimaging studies show that long-range correlations are highly structured in spatiotemporal patterns, known as resting-state networks, on the other hand, neurophysiological reports show that short-range correlations between neighboring neurons are low, despite a large amount of shared presynaptic inputs. Different dynamical mechanisms of local decorrelation have been proposed, among which is feedback inhibition. Here, we investigated the effect of locally regulating the feedback inhibition on the global dynamics of a large-scale brain model, in which the long-range connections are given by diffusion imaging data of human subjects. We used simulations and analytical methods to show that locally constraining the feedback inhibition to compensate for the excess of long-range excitatory connectivity, to preserve the asynchronous state, crucially changes the characteristics of the emergent resting and evoked activity. First, it significantly improves the model's prediction of the empirical human functional connectivity. Second, relaxing this constraint leads to an unrealistic network evoked activity, with systematic coactivation of cortical areas which are components of the default-mode network, whereas regulation of feedback inhibition prevents this. Finally, information theoretic analysis shows that regulation of the local feedback inhibition increases both the entropy and the Fisher information of the network evoked responses. Hence, it enhances the information capacity and the discrimination accuracy of the global network. In conclusion, the local excitation-inhibition ratio impacts the structure of the spontaneous activity and the information transmission at the large-scale brain level.

Especificacions, Anàlisi i Disseny d'un Programari de Gestió de Magatzems

Aquest treball de fi de carrera vol reflectir les necessitats bàsiques per al disseny d'un programari de gestió de magatzems (PGM a partir d'ara). Un PGM té la particularitat d'haver d'establir connexions entre els fluxos físics del treball propi d'un magatzem i els fluxos de dades propis d'un sistema informàtic. Les prestacions del PGM s'hauran de desenvolupar en part en terminals de radiofreqüència, ja que es considera que el treball en línia és bàsic per a gestionar un magatzem.

Eating disorders, overeating and pathological attatchment to food: Independent or addictive disorders?

The thesis of this book is that there are connections between eating disorders and substance abuse. There are similarities in the craving for food to the cravings for substances of addiction; people with eating disorders experience symptoms similar to those of classic addiction. With the increase in obesity in the West, this book hopes to focus future studies on more effective treatment.This resource was contributed by The National Documentation Centre on Drug Use.

Connectome alterations in schizophrenia

Introduction : DTI has proven to be an exquisite biomarker of tissue microstructure integrity. This technique has been successfully applied to schizophrenia in showing that fractional anisotropy (FA, a marker of white matter integrity) is diminished in several areas of the brain (Kyriakopoulos M et al (2008)). New ways of representing diffusion data emerged recently and achieved to create structural connectivity maps in healthy brains (Hagmann P et al. (2008)). These maps have the capacity to study alterations over the entire brain at the connection and network level. This is of high interest in complex disconnection diseases like schizophrenia. We report on the specific network alterations of schizophrenic patients. Methods : 13 patients with chronic schizophrenia were recruited from in-patient, day treatment, out-patient clinics. Comparison subjects were recruited and group-matched to patients on age, sex, handedness, and parental social economic-status. This study was approved by the local IRB and subjects had to give informed written consent. They were scanned with a 3T clinical MRI scanner. DTI and high-resolution anatomical T1w imaging were performed during the same session. The path from diffusion MRI to a multi-resolution structural connection matrices of the entire brain is a five steps process that was performed in a similar way as described in Hagmann P et al. (2008). (1) DTI and T1w MRI of the brain, (2) segmentation of white and gray matter, (3) white matter tractography, (4) segmentation of the cortex into 242 ROIs of equal surface area covering the entire cortex (Fig 1), (5) the connection network was constructed by measuring for each ROI to ROI connection the related average FA along the corresponding tract. Results : For every connection between 2 ROIs of the network we tested the hypothesis H0: "average FA along fiber pathway is larger or equal in patients than in controls". H0 was rejected for connections where average FA in a connection was significantly lower in patients than in controls. Threshold p-value was 0.01 corrected for multiple comparisons with false discovery rate. We identified consistently that temporal, occipito-temporal, precuneo-temporal as well as frontal inferior and precuneo-cingulate connections were altered (Fig 2: significant connections in yellow). This is in agreement with the known literature, which showed across several studies that FA is diminished in several areas of the brain. More precisely, abnormalities were reported in the prefrontal and temporal white matter and to some extent also in the parietal and occipital regions. The alterations reported in the literature specifically included the corpus callosum, the arcuate fasciculus and the cingulum bundle, which was the case here as well. In addition small world indexes are significantly reduced in patients (p<0.01) (Fig. 3). Conclusions : Using connectome mapping to characterize differences in structural connectivity between healthy and diseased subjects we were able to show widespread connectional alterations in schizophrenia patients and systematic small worldness decrease, which is a marker of network desorganization. More generally, we described a method that has the capacity to sensitively identify structure alterations in complex disconnection syndromes where lesions are widespread throughout the connectional network.

The perception of touch and the ventral somatosensory pathway.

In humans, touching the skin is known to activate, among others, the contralateral primary somatosensory cortex on the postcentral gyrus together with the bilateral parietal operculum (i.e. the anatomical site of the secondary somatosensory cortex). But which brain regions beyond the postcentral gyrus specifically contribute to the perception of touch remains speculative. In this study we collected structural magnetic resonance imaging scans and neurological examination reports of patients with brain injuries or stroke in the left or right hemisphere, but not in the postcentral gyrus as the entry site of cortical somatosensory processing. Using voxel-based lesion-symptom mapping, we compared patients with impaired touch perception (i.e. hypoaesthesia) to patients without such touch impairments. Patients with hypoaesthesia as compared to control patients differed in one single brain cluster comprising the contralateral parietal operculum together with the anterior and posterior insular cortex, the putamen, as well as subcortical white matter connections reaching ventrally towards prefrontal structures. This finding confirms previous speculations on the 'ventral pathway of somatosensory perception' and causally links these brain structures to the perception of touch.

Identité et filiation : enfants enlevés-appropriés, adultes restitués dans le contexte de la dernière dictature militaire en Argentine (1976-1983)

Durant la dernière dictature argentine (1976-1983), !a junte militaire organisa le vol de nourrissons, enfants de leurs ennemis, pour qu'ils puissent être élevés dans des familles proches du pouvoir. L'association « Grands-Mères de la Place de Mai » comptabilisa environ 409 vols. Au moment de l'exploration du terrain de récherche, en 2004, une quarantaine avaient été retrouvés dans des familles qui ne connaissaient pas leurs origines tandis qu'une vingtaine étaient dans des familles liées à la junte ; c'est à cette dernière catégorie que s'intéresse ce travail. Durant leur enfance ou à l'âge adulte, ces enfants apprirent un jour la vérité sur leurs origines biologiques et la justice la leur restitua ; c'est pourquoi ils sont dits « restitués ». Cette contribution vise à interroger l'identité individuelle comme une dynamique intime qui s'articule à la filiation et s'insère dans une collectivité, une société. Trois hypothèses l'ont organisée : une première concerne la connaissance des origines biologiques et ses conséquences psychologiques identitaires, qui passe nécessairement par la justice et la société. Une deuxième hypothèse explore les éventelles conséquences traumatiques de l'enlèvement des personnes restituées et de la restitution. Enfin, la troisième hypothèse interroge le rapport de la construction identitaire à la société, qu'elle se fasse par des investissements politiques et associatifs ou par les médias et l'Histoire. Ces hypothèses nourrissent un questionnement sur les liens entre restitution et travail de symbolisation des origines. Sept entretiens semi structurés avec des personnes restituées ont. été menés puis qualitativement analysés dans une perspective que l'on peut référer, de manière large, à une « anthropologique clinique », au croisement d'une psychologie clinique éclairée par la psychanalyse et de l'anthropologie. Au travers d'une analyse approfondie de leur parcours identitaire des personnes enlevées, adoptées et restituées, ce travail se livre à une recherche empirique sur la construction identitaire. Le concept de transmission se trouve mobilisé, qui concerne l'inscription de l'individu dans la subjectivité d'un couple avec le prénom, dans une lignée ou dans un collectif avec le choix professionnel ou les liens avec l'association « Grands-Mères de la Place Mai ». De plus, la thèse apporte une contribution à la compréhension des enjeux du clivage, des blessures primitive et narcissique, des processus d'affiliation et des secrets de famille et propose également de penser, en prolongement, les enjeux de la « défiliation » et de I'« amalgame ». La question du traumatisme, de sa répétition et de son élaboration, ainsi que celle des facteurs de resilience sont également discutées. Ce travail ouvre sur une réflexion plus large du concept d'identité. - During the last dictatorship in Argentina (1976-1983), the military junta organized the kidnapping of infants - children of its enemies - in order to raise them in families close to the authorities. The association "Mothers of the Plaza de Mayo" estimates that approximately 400 children have been kidnapped in this way. During their childhood, or as adults, they have come to learn the truth about their biological origins, restituted to them by justice: They are therefore known as "restituted" children. At the time of the field research in 2004, around 40 children had been found in families unaware of their origins. About 20 other came from families close to the junta. The present work is particularly interested in the latter category. This contribution investigates the individual identity as an intimate dynamics by examining its articulation with filiation and its insertion within a community, a society. It revolves around three hypotheses: the first concerns the knowledge - necessarily transmitted through justice and society - of biological origins and its psychological consequences on the identity. The second explores the eventually traumatic, consequences of kidnapping and restitution among the restituted persons. Finally, the third hypothesis questions the relation between identity construction and society, whether it is made through political and associative involvements, media or History. These hypotheses lead to the examination of affiliations between restitution and symbolization process of the origins. Seven semi-structured interviews with restituted persons have been conducted and qualitatively analyzed in a perspective that can, in a large sense, be referred to as "clinical anthropology": an approach/intersection between clinical psychology, psychoanalysis and anthropology. Through an in-depth analysis of the identity itinerary of the kidnapped, adopted and restituted persons, this work is conducted as an empirical research on identity construction. For that purpose, it uses the concept of transmission to describe an individual's affiliation with the subjectivity of a couple through the first name, with a lineage or a community through professional choices or through his/her connections with the association "Mothers of the Plaza de Mayo". Further, it makes a meaningful contribution to the understanding and implications of the notions of cleavage, of primal and narcissistic wounds, of processes of affiliation and of family secrets. In addition, it also proposes a reflection on and the implication of the notions of "deviation" and "amalgam". The question of trauma, its repetition and elaboration, and of resilience factors are aiso being discussed. This work concludes with results in a iarger consideration of the concept of identity.

Abnormal EEG Synchronization Correlates with Demyelination in Alzheimer's Disease

Introduction : The pathological processes caused by Alzheimer's disease (AD) supposedly disrupt communication between and within the distributed cortical networks due to the dysfunction/loss of synapses and myelination breakdown. Indeed, recently (Knyazeva et al. 2008), we have revealed the whole-head topography of EEG synchronization specific to AD. Here we analyze whether and how these abnormalities of synchronization are related to the demyelination of cortico-cortical fibers. Methods : Fifteen newly diagnosed AD patients (CDR 0.5-1) and 15 controls matched for age, participated in the study. Their multichannel (128) EEGs were recorded during 3-5 min at rest. They were submitted to the multivariate phase synchronization (MPS) analysis for mapping regional synchronization. To obtain individual whole-head maps, the MPS was computed for each sensor considering its 2nd nearest topographical neighbors. Separate calculations were performed for the delta, theta, alpha-1/−2, and beta-1/−2 EEG bands. The same subjects were scanned on a 3 Tesla Philips scanner. The protocol included a high-resolution T1-weighted sequence and a Magnetization Transfer Imaging (MTI) acquisition. For each subject, we defined a 3mm thick layer of white matter exactly below the cortical gray matter. The magnetization transfer ratio (MTR) - an estimator of myelination - was calculated for this layer in 39 Brodmann-defined ROIs per hemisphere. To assess the between-group differences, we used a permutation version of Hotelling's T2 test or two-sample T-test (Pcorrected <0.05). For correlation analysis, Spearman Rank Correlation was calculated. Results : In AD patients, we have found an abnormal landscape of synchronization characterized by a decrease in MPS over the fronto-temporal region of the left hemisphere and an increase over the temporo-parieto-occipital regions bilaterally. Also, we have shown a widespread decrease in regional MTR in the AD patients for all the areas excluding motor, premotor, and primary sensory ones. Assuming that AD-related changes in synchronization are associated with demyelination, we hypothesized a correlation between the regional MTR values and MPS values in the hypo- and hyper-synchronized clusters. We found that MPS in the left fronto-temporal hypo-synchronized cluster directly correlates with myelination in BA42-46 of the left hemisphere: the lower the myelination in individual patients, the lower the EEG synchronization. By contrast, in the posterior hyper-synchronized cluster, MPS inversely correlated with myelination, i.e., the lower the myelination, the higher the synchronization. This posterior hyper-synchronization, more characteristic for early-onset AD, probably, results from the initial effect of the disease on cortical inhibition, reducing cortical capacity for decoupling irrelevant connections. Remarkably, it showed different topography of correlations in early- vs. late-onset patients. In the early-onset patients, hyper-synchronization was mainly related to demyelination in posterior BAs, the effect being significant in all the EEG frequency bands. In the late-onset patients, widely distributed correlations were significant for the EEG delta band, suggesting an interaction between the cerebral manifestations of AD and the age of its onset, i.e., topographically selective impairment of cortical inhibition in early-onset AD vs. its wide-spread weakening in old age. Conclusions : Overall, our results document that the degradation of white matter is a significant factor of AD pathogenesis leading to functional dysconnection, the latter being reflected in EEG synchronization abnormalities.

A Method and Tool to Support the Analysis and Enhance the Understanding of Peer-to-Peer Learning Experiences

In this paper we look at how a web-based social software can be used to make qualitative data analysis of online peer-to-peer learning experiences. Specifically, we propose to use Cohere, a web-based social sense-making tool, to observe, track, annotate and visualize discussion group activities in online courses. We define a specific methodology for data observation and structuring, and present results of the analysis of peer interactions conducted in discussion forum in a real case study of a P2PU course. Finally we discuss how network visualization and analysis can be used to gather a better understanding of the peer-to-peer learning experience. To do so, we provide preliminary insights on the social, dialogical and conceptual connections that have been generated within one online discussion group.