Multimodal MRI analysis of structural and functional networks in the human brain : application to two clinical studies : driving abilities under THC intoxication and early white matter changes in FXTAS

Les approches multimodales dans l'imagerie cérébrale non invasive sont de plus en plus considérées comme un outil indispensable pour la compréhension des différents aspects de la structure et de la fonction cérébrale. Grâce aux progrès des techniques d'acquisition des images de Resonance Magnetique et aux nouveaux outils pour le traitement des données, il est désormais possible de mesurer plusieurs paramètres sensibles aux différentes caractéristiques des tissues cérébraux. Ces progrès permettent, par exemple, d'étudier les substrats anatomiques qui sont à la base des processus cognitifs ou de discerner au niveau purement structurel les phénomènes dégénératifs et développementaux. Cette thèse met en évidence l'importance de l'utilisation d'une approche multimodale pour étudier les différents aspects de la dynamique cérébrale grâce à l'application de cette approche à deux études cliniques: l'évaluation structurelle et fonctionnelle des effets aigus du cannabis fumé chez des consommateurs réguliers et occasionnels, et l'évaluation de l'intégrité de la substance grise et blanche chez des jeunes porteurs de la prémutations du gène FMR1 à risque de développer le FXTAS (Fragile-X Tremor Ataxia Syndrome). Nous avons montré que chez les fumeurs occasionnels de cannabis, même à faible concentration du principal composant psychoactif (THC) dans le sang, la performance lors d'une tâche visuo-motrice est fortement diminuée, et qu'il y a des changements dans l'activité des trois réseaux cérébraux impliqués dans les processus cognitifs: le réseau de saillance, le réseau du contrôle exécutif, et le réseau actif par défaut (Default Mode). Les sujets ne sont pas en mesure de saisir les saillances dans l'environnement et de focaliser leur attention sur la tâche. L'augmentation de la réponse hémodynamique dans le cortex cingulaire antérieur suggère une augmentation de l'activité introspective. Une investigation des ef¬fets au niveau cérébral d'une exposition prolongée au cannabis, montre des changements persistants de la substance grise dans les régions associées à la mémoire et au traitement des émotions. Le niveau d'atrophie dans ces structures corrèle avec la consommation de cannabis au cours des trois mois précédant l'étude. Dans la deuxième étude, nous démontrons des altérations structurelles des décennies avant l'apparition du syndrome FXTAS chez des sujets jeunes, asymptomatiques, et porteurs de la prémutation du gène FMR1. Les modifications trouvées peuvent être liées à deux mécanismes différents. Les altérations dans le réseau moteur du cervelet et dans la fimbria de l'hippocampe, suggèrent un effet développemental de la prémutation. Elles incluent aussi une atrophie de la substance grise du lobule VI du cervelet et l'altération des propriétés tissulaires de la substance blanche des projections afférentes correspondantes aux pédoncules cérébelleux moyens. Les lésions diffuses de la substance blanche cérébrale peu¬vent être un marquer précoce du développement de la maladie, car elles sont liées à un phénomène dégénératif qui précède l'apparition des symptômes du FXTAS. - Multimodal brain imaging is becoming a leading tool for understanding different aspects of brain structure and function. Thanks to the advances in Magnetic Resonance imaging (MRI) acquisition schemes and data processing techniques, it is now possible to measure different parameters sensitive to different tissue characteristics. This allows for example to investigate anatomical substrates underlying cognitive processing, or to disentangle, at a pure structural level degeneration and developmental processes. This thesis highlights the importance of using a multimodal approach for investigating different aspects of brain dynamics by applying this approach to two clinical studies: functional and structural assessment of the acute effects of cannabis smoking in regular and occasional users, and grey and white matter assessment in young FMR1 premutation carriers at risk of developing FXTAS. We demonstrate that in occasional smokers cannabis smoking, even at low concentration of the main psychoactive component (THC) in the blood, strongly decrease subjects' performance on a visuo-motor tracking task, and globally alters the activity of the three brain networks involved in cognitive processing: the Salience, the Control Executive, and the Default Mode networks. Subjects are unable to capture saliences in the environment and to orient attention to the task; the increase in Hemodynamic Response in the Anterior Cingulate Cortex suggests an increase in self-oriented mental activity. A further investigation on long term exposure to cannabis, shows a persistent grey matter modification in brain regions associated with memory and affective processing. The degree of atrophy in these structures also correlates with the estimation of drug use in the three months prior the participation to the study. In the second study we demonstrate structural changes in young asymptomatic premutation carriers decades before the onset of FXTAS that might be related to two different mechanisms. Alteration of the cerebellar motor network and of the hippocampal fimbria/ fornix, may reflect a potential neurodevelopmental effect of the premutation. These include grey matter atrophy in lobule VI and modification of white matter tissue property in the corresponding afferent projections through the Middle Cerebellar Peduncles. Diffuse hemispheric white matter lesions that seem to appear closer to the onset of FXTAS and be related to a neurodegenerative phenomenon may mark the imminent onset of FXTAS.

The Possibilities of IP Networks in Strategic Partnership Development

This study focuses on the status of using the Internet in partnership development. The aim is to find out howthe parties in partnership can benefit from the available data networks (the Internet, Intranet and Extranet). The study also explains what the typical practices at the moment are and what features might be exploitable in the future. The research problem is to find out whether there are any possibilities to utilize the web more than is done at the moment. This study is a preliminary study for a more extensive study on the topic 'Information Technology in Business Relationships'.

On the differential evolution algorithm and its appliation to training radial basis function networks

The parameter setting of a differential evolution algorithm must meet several requirements: efficiency, effectiveness, and reliability. Problems vary. The solution of a particular problem can be represented in different ways. An algorithm most efficient in dealing with a particular representation may be less efficient in dealing with other representations. The development of differential evolution-based methods contributes substantially to research on evolutionary computing and global optimization in general. The objective of this study is to investigatethe differential evolution algorithm, the intelligent adjustment of its controlparameters, and its application. In the thesis, the differential evolution algorithm is first examined using different parameter settings and test functions. Fuzzy control is then employed to make control parameters adaptive based on an optimization process and expert knowledge. The developed algorithms are applied to training radial basis function networks for function approximation with possible variables including centers, widths, and weights of basis functions and both having control parameters kept fixed and adjusted by fuzzy controller. After the influence of control variables on the performance of the differential evolution algorithm was explored, an adaptive version of the differential evolution algorithm was developed and the differential evolution-based radial basis function network training approaches were proposed. Experimental results showed that the performance of the differential evolution algorithm is sensitive to parameter setting, and the best setting was found to be problem dependent. The fuzzy adaptive differential evolution algorithm releases the user load of parameter setting and performs better than those using all fixedparameters. Differential evolution-based approaches are effective for training Gaussian radial basis function networks.

Secure many-to-one communications in wireless sensor networks

Wireless Sensor Networks (WSN) are formed by nodes with limited computational and power resources. WSNs are finding an increasing number of applications, both civilian and military, most of which require security for the sensed data being collected by the base station from remote sensor nodes. In addition, when many sensor nodes transmit to the base station, the implosion problem arises. Providing security measures and implosion-resistance in a resource-limited environment is a real challenge. This article reviews the aggregation strategies proposed in the literature to handle the bandwidth and security problems related to many-to-one transmission in WSNs. Recent contributions to secure lossless many-to-one communication developed by the authors in the context of several Spanish-funded projects are surveyed. Ongoing work on the secure lossy many-to-one communication is also sketched.

Integrating defeasible argumentation with fuzzy ART neural networks for pattern classification

Many classification systems rely on clustering techniques in which a collection of training examples is provided as an input, and a number of clusters c1,...cm modelling some concept C results as an output, such that every cluster ci is labelled as positive or negative. Given a new, unlabelled instance enew, the above classification is used to determine to which particular cluster ci this new instance belongs. In such a setting clusters can overlap, and a new unlabelled instance can be assigned to more than one cluster with conflicting labels. In the literature, such a case is usually solved non-deterministically by making a random choice. This paper presents a novel, hybrid approach to solve this situation by combining a neural network for classification along with a defeasible argumentation framework which models preference criteria for performing clustering.

The transcriptional network activated by Cln3 cyclin at the G1-to-S transition of the yeast cell cycle

Background: The G1-to-S transition of the cell cycle in the yeast Saccharomyces cerevisiae involves an extensive transcriptional program driven by transcription factors SBF (Swi4-Swi6) and MBF (Mbp1-Swi6). Activation of these factors ultimately depends on the G1 cyclin Cln3. Results: To determine the transcriptional targets of Cln3 and their dependence on SBF or MBF, we first have used DNA microarrays to interrogate gene expression upon Cln3 overexpression in synchronized cultures of strains lacking components of SBF and/or MBF. Secondly, we have integrated this expression dataset together with other heterogeneous data sources into a single probabilistic model based on Bayesian statistics. Our analysis has produced more than 200 transcription factor-target assignments, validated by ChIP assays and by functional enrichment. Our predictions show higher internal coherence and predictive power than previous classifications. Our results support a model whereby SBF and MBF may be differentially activated by Cln3. Conclusions: Integration of heterogeneous genome-wide datasets is key to building accurate transcriptional networks. By such integration, we provide here a reliable transcriptional network at the G1-to-S transition in the budding yeast cell cycle. Our results suggest that to improve the reliability of predictions we need to feed our models with more informative experimental data.

Modelling bird species richness with neural networks for forest landscape management in NE Spain

Para preservar la biodiversidad de los ecosistemas forestales de la Europa mediterránea en escenarios actuales y futuros de cambio global mediante una gestión forestal sostenible es necesario determinar cómo influye el medio ambiente y las propias características de los bosques sobre la biodiversidad que éstos albergan. Con este propósito, se analizó la influencia de diferentes factores ambientales y de estructura y composición del bosque sobre la riqueza de aves forestales a escala 1 × 1 km en Cataluña (NE de España). Se construyeron modelos univariantes y multivariantes de redes neuronales para respectivamente explorar la respuesta individual a las variables y obtener un modelo parsimonioso (ecológicamente interpretable) y preciso. La superficie de bosque (con una fracción de cabida cubierta superior a 5%), la fracción de cabida cubierta media, la temperatura anual y la precipitación estival medias fueron los mejores predictores de la riqueza de aves forestales. La red neuronal multivariante obtenida tuvo una buena capacidad de generalización salvo en las localidades con una mayor riqueza. Además, los bosques con diferentes grados de apertura del dosel arbóreo, más maduros y más diversos en cuanto a su composición de especies arbóreas se asociaron de forma positiva con una mayor riqueza de aves forestales. Finalmente, se proporcionan directrices de gestión para la planificación forestal que permitan promover la diversidad ornítica en esta región de la Europa mediterránea.

Is blood still thicker than water? A life-course perspective on the transformation of family and friends' roles in personal networks

This thesis addresses the issue of the moving boundaries between family and friends' roles in personal networks, adopting a life-course perspective and using Switzerland as a case study. In a period of major changes in personal life happening in contemporary Western societies, understanding the organization of personal networks intertwined with the unfolding of individual life courses is of prime importance in facing new challenges with regard to social integration. The data stem from a representative national survey carried out in 2011 named Family tiMes, including 803 individuals born either in 1950-1955 or in 1970-1975. An innovative research design was adopted, combing cross-sectional ego-centered network data and retrospective longitudinal life-course data. The results show continuing boundaries between family and friends' roles and that family keeps a prominent role in personal networks despite the notable importance of friendship ties. One relationship stands out above all, that with the partner, followed quite a few steps behind by those with children. Regarding life courses, de-standardization tendencies were found in family formation and also a persistent gendering of occupational trajectories. Two kinds of life trajectories are particularly intertwined with personal networks, co-residence and partnership trajectories, both related to the unfolding of family life. In particular, transition to parenthood functions as a turning point in individuals' lives, deeply transforming their sociability. Finally, a twofold pluralization process was identified, affecting simultaneously the organization of personal networks and the unfolding of individual life courses. This thesis contributes to the literature on the sociology of family and personal life, and to fruitful interlinkage between the network approach and the life-course perspective.

Protective effects of social networks on disability among older adults in Spain

The loss of autonomy at advanced ages is not only associated with ageing, but also with the characteristics of the physical and social environment. Recent investigations have shown that social networks, social engagement and participation act like predictors of disability among the elderly. The aim of this study is to determine whether social networks are related to the development and progression of disability in the early years of old age. The source of data is the first wave of the survey "Processes of Vulnerability among Spanish Elderly", carried out in 2005 to a sample of 1 244 individuals. The population object of study is the cohort aged 70 to 74 years in metropolitan areas (Madrid and Barcelona) and not institutionalized. Disability is measured by the development of basic activities of daily life (ADL), and instrumental activities of daily life (IADL). The structural aspects of the social relationships are measured through the diversity of social networks and participation. We used the social network index (SNI). For each point over the SNI, the risk of developing any type of disability decreased by 49% (HR = 0.51, 95%CI = 0.31-0.82). The SNI was a decisive factor in all forecasting models constructed with some hazard ratios (HR) that ranged from 0.29 (95%CI = 0.14-0.59) in the first model to 0.43 (95%CI 0.20-0.90) in the full model. The results of the present study showed a strong association between an active social life, emotional support provided by friends and confidents and disability. These findings suggest a protective effect of social networks on disability. Also, these results indicate that some family and emotional ties have a significant effect on both the prevalence and the incidence of disability.

Using narratives to study the impact of social networks on the educational paths of immigrant students

This paper presents the qualitative data collection process aimed at the study of the impactsocial relations and networks have on educational paths of immigrant students. In theframework of a R & D longitudinal study funded by the Ministry of Science and Innovation(2012-2014), the research team tracked the path of 87 immigrant students, from whom only 17successfully achieved the transition through the first and second year of Post-16 Education.A vast range of literature notes that relationships are an important part of migration process andsocial integration analysis, as well as school history in terms of success or failure. Through thefieldwork researchers collect the personal networks of all immigrant students from 3 highschools who were at that time attending last course of compulsory school. The network structureinfluences their social capital and therefore determines the resources, goods and types of supportindividuals can access. All these aspects are influential elements in the configuration anddevelopment of academic trajectories of immigrant students.At the end of the second year of Post-16 Education (two years later), the study captures personalnetworks of these students again, analyses and discusses their evolution and influence on theirpaths through qualitative interviews. Such interviews facilitated the discussion of theirrelationships while providing interesting narratives that are presented in the text. In order to do so, the biographical interpretive narrative method of interviewing is implemented.

Using narratives to study the impact of social networks on the educational paths of immigrant students

This paper presents the qualitative data collection process aimed at the study of the impactsocial relations and networks have on educational paths of immigrant students. In theframework of a R & D longitudinal study funded by the Ministry of Science and Innovation(2012-2014), the research team tracked the path of 87 immigrant students, from whom only 17successfully achieved the transition through the first and second year of Post-16 Education.A vast range of literature notes that relationships are an important part of migration process andsocial integration analysis, as well as school history in terms of success or failure. Through thefieldwork researchers collect the personal networks of all immigrant students from 3 highschools who were at that time attending last course of compulsory school. The network structureinfluences their social capital and therefore determines the resources, goods and types of supportindividuals can access. All these aspects are influential elements in the configuration anddevelopment of academic trajectories of immigrant students.At the end of the second year of Post-16 Education (two years later), the study captures personalnetworks of these students again, analyses and discusses their evolution and influence on theirpaths through qualitative interviews. Such interviews facilitated the discussion of theirrelationships while providing interesting narratives that are presented in the text. In order to do so, the biographical interpretive narrative method of interviewing is implemented.

Mobility Management in Packet Switched Mobile Networks

Nykyisin matkaviestinverkot ovat osa jokapäiväistä elämää. Merkittävimpiä eroja kiinteiden ja matkaviestinverkkojen välillä on käyttäjän liikkuvuus, joka voidaan määritellä mahdollisuudeksi soittaa ja vastaanottaa puheluita missä ja milloin tahansa. Työ selittää termin liikkuvuus ja määrittää ongelmat, jotka täytyy ratkaista liikkuvuuden aikaansaamiseksi sekä tavat, joilla nämä ongelmat on ratkaistu matkaviestinverkoissa. Työ luo yleiskatsauksen liikkuvuuden aikaansaamisessa käytettäviin menetelmiin, joita ovat haku, sijainnin päivitys, sijainnin seuranta ja kanavan vaihto. Työ keskittyy liikkuvuuteen kolmannen sukupolven matkaviestinverkkojen paketti-kytkentäisessä osassa, esimerkkinä liikkuvuuden hallinta UMTS:ssa (Universal Mobile Telecommunications System). Erot paketti- ja piirikytkentäisen osan välillä tuodaan esille ja selitetään. Jotta käyttäjät ja heidän päätteensä voisivat liikkua, tiedon täytyy kulkea verkon eri osien välillä. Merkinanto verkkoelementtien välillä ja liikkuvuuden mahdollistavien toimenpiteiden suoritus tehdään yhteyskäytännön avulla. Työ kuvaa yhteyskäytännöt, jotka ovat osallisena liikkuvuuden tarjontaan. Painopiste on GPRS:n liikkuvuuden-hallintayhteyskäytännössä, GMM:ssä. GMM protokollan prototyypin toteutus on esitetty työn käytännön osassa.

Service Management in IP Networks

IP-verkoissa tarjottavat palvelut ovat lisääntyneet, on tullut uusia kanavia, jotka tarjoavat IP-pohjaisia palveluja. Internet-palvelujen tarjonta on tullut mukaan kaapelitelevisio- ja matkapuhelinverkkoihin. Lisääntynyt palvelujen tarjonta ja kysyntä ovat lisänneet palvelujen hallinnan merkitystä. IP-verkoissa on ilmennyt turvallisuuteen, skaalattavuuteen ja palvelun laatuun liittyviä ongelmia. Palvelun laadun tärkeys painottuu reaaliaikaisuutta ja suurta kapasiteettia vaativissa sovelluksissa. Tulevaisuudessa IP-liikenteen on ennustettu kasvavan yli satakertaiseksi nykyisestä tasosta kolmen vuoden kuluessa. Tämän vuoksi on kehitetty uusi verkon ja palvelun hallintamenetelmiä, joista tässä työssä on tutkittu sääntöpohjaista verkon hallintaa.