Bakgrund: Alkoholbrukssyndrom är ett sjukdomstillstånd med mycket stigma. Hur denna patientgrupp bemöts är av stor vikt för omvårdnadens resultat. Sjuksköterskan ska förhålla sig personcentrerat och se hela individens behov och problemför att kunna ge en god vård. Primärvården är oftast patienternas första kontakt med vården, varför ett professionellt förhållningssätt är viktigt. Syfte: Syftet med litteraturstudien är att belysa patienter med alkoholbrukssyndrom och deras upplevelser av primärvård. Metod: Studien använde sig av artiklar med kvalitativ ansats och söktes med Cinahl och Pubmed. Tio artiklar valdes ut för granskning i egenskap av att kunna besvara studiens syfte. För att granska artiklarna användes SBU:s granskningsmall och termer delades in enlig PEO-modellen. Analysen av artiklarnas innehåll gick ut på att granska resultaten. När artiklar valts ut delades de in i färgkoder för att skilja på positiva och negativa upplevelser. Resultat: Patienternas upplevelser av vården delades in i två huvudteman om positiva och negativa upplevelser av vården. Inom positiva upplevelser fanns delaktighet i vården och vårdpersonalens kunskaper. För delaktighet identifierades fyra subteman. Att bli inkluderad, kunna påverka sin vård individanpassad vård och aktivt lyssnande. Vårdpersonalens kunskaper grundades främst av stöd, trygghet och motivation. Inom de negativa upplevelserna fanns relationen till vårdpersonalen, bemötande och självupplevt stigma. Häri var fördomsfullhet och att sätta etiketter det som utmärkte sig mest. Slutsats: Den grundutbildade sjuksköterskan bör reflektera över sina egna fördomar om alkoholbrukssyndrom för att kunna ge en jämlik vård. Stigmatiserande begrepp är något som bör undvikas för att kunna ge en jämlik vård. Att få en etikett visade sig ha ett samband med hur vårdpersonalen benämnde alkoholbrukssyndromet. Patienters upplevelser av att ha ett alkoholbrukssyndrom är komplext och något som behöver forskas mer kring. / Background: Alcohol use syndrome is a medical condition with a lot of stigma. How this patient group is treated is of great importance for the nursing results. The nurse must have a person-centered attitude and see the entire individual's needs and problems in order to provide good care. Primary care is usually patients' first contact with care, which is why a professional approach is important. Purpose: The purpose of the literature study is to shed light on patients with alcohol use syndrome and their experiences of primary care. Method: The study used articles with a qualitative approach and was searched with Cinahl and PubMed. Ten articles were selected for review as being able to answer the purpose of the study. To review the articles, SBU's review template was used and terms were divided according to the PEO model. The analysis of the content of the articles consisted of reviewing the results and seeing if they could answer the purpose. When articles were selected, they were divided into color codes to distinguish between positive and negative experiences. Results: The patients' experiences of the care were divided into two main themes of positive and negative experiences of the care. Within positive experiences was participation in care and the knowledge of the care staff. Four points were identified for participation: Being included, being able to influence one's care, individualized care and active listening. The care staff's knowledge was mainly based on support, security and motivation. Within the negative experiences was the relationship with the healthcare staff, treatment and self-perceived stigma. Here prejudice and labeling stood out the most. Conclusion:The newly graduated nurse should reflect on their own prejudices about alcohol use syndrome. Stigmatizing terms are something that should be avoided in order to provide equal care. The patients' self-perceived stigma was a theme based on prejudices that exist in society. Receiving a label was found to be associated with how health care professionals named the alcohol use syndrome. Patients' experiences of alcohol use syndrome are complex and something that needs more research.

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Background: When a person has a pattern of psychoactive substance and/or alcohol use that is causing damage to health family members are affected. The quality of life of parents, siblings, children, partners and other relatives may be severely impaired. When young adults transition from child/youth to adult care it involves changes for the patients as well as for relatives. To be able to support relatives, deeper knowledge is needed about the way nurses perceive the situation of relatives. Aim: The aim is to investigate how nurses perceive the situation for relatives when a person is being treated in addiction care, as well as the consequences for relatives when patients are being transferred from children/youth care to adult care.  Method: This is a qualitative study with an inductive approach. Eight semi-structured interviews have been carried out with nurses working within addiction care. The collected data was analysed according to qualitative content analysis. Result: Data analysis resulted in the formulation of two categories, with two sub-categories in each. The first category describes relatives’ situation at transition from child/youth care to adult care with two sub-categories are lack of transparency and changed life situation. The second category describes relatives’ situation with constant worry when having a relative with pattern of psychoactive substance and/or alcohol use. This category formulated with sub-categories psychological burden and social burden. Discussions: The result is discussed in relation to Afaf Ibrahim Meleis’ transition theory and other relevant research. Transition theory provides support for changed life situation of relatives within addiction care, which may be important to know in order to develop nursing care. / Bakgrund: I samband med att en person har ett skadligt bruk av alkohol eller droger påverkas anhöriga. Livskvaliteten kan försämras allvarligt för såväl föräldrar, syskon, barn, partner som andra anhöriga. När unga vuxna byter vårdform och övergår till vuxenlivet sker förändringar för patienten men även deras anhöriga. För att stödja anhöriga till närstående som har ett skadligt bruk av alkohol eller droger behövs fördjupade kunskaper om hur sjuksköterskor uppfattar anhörigas situation. Syfte: Syftet är att undersöka hur sjuksköterskor beskriver anhörigas situation när närstående vårdas i beroendevården samt vad som händer med anhöriga när närstående övergår från barn och ungdomsvård till vuxenvård. Metod: Studien är en kvalitativ studie med induktiv ansats där semistrukturerade intervjuer genomfördes med åtta sjuksköterskor verksamma inom beroendevården. Det insamlade datamaterialet analyserades enligt kvalitativ innehållsanalys. Resultat: Dataanalysen resulterade i två kategorier med två underkategorier vardera. Den första kategorin är den som beskriver anhörigas situation vid övergång från barn och ungdomsvård till vuxenvård med underkategorier: bristande insyn och förändrad livssituation. Den andra kategorin beskriver anhörigas situation med ständig oro när man har en närstående med skadligt bruk av alkohol eller droger. Denna kategori formuleras i två underkategorier vilka var psykisk merbelastning och social merbelastning. Diskussion: Resultatet diskuteras utifrån Afaf Ibrahim Meleis transitionsteori samt annan relevant forskning. Transitionsteorin ger stöd för den förändrade livssituationen för anhöriga inom beroendevården, vilket kan vara viktigt att känna till för att utveckla omvårdnaden.

Submitted by Cristiane Chim (cristiane.chim@ucpel.edu.br) on 2018-08-08T12:13:43Z No. of bitstreams: 1 Louise Halla Reydams.pdf: 1479930 bytes, checksum: dbeb9959b561b6b01f81682d8d0dd3b9 (MD5) / Made available in DSpace on 2018-08-08T12:13:43Z (GMT). No. of bitstreams: 1 Louise Halla Reydams.pdf: 1479930 bytes, checksum: dbeb9959b561b6b01f81682d8d0dd3b9 (MD5) Previous issue date: 2018-04-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES# / #2075167498588264571# / #600 / Substance use disorder is related to numerous mental and physical health problems, associated with several functional impairments that affect several aspects of the life of the individual with the disorder. The objective of this study was to evaluate the relationship between psychoactive substances and biological rhythm in a community sample of young people. It is a cross-sectional population-based study with adults aged 24 to 30 years living in the urban area of the city of Pelotas, RS. The sample selection was performed by multi-stage conglomerates. Socio-demographic data were collected from the sample and substance abuse or dependence was assessed through the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), as well as the biological rhythm was evaluated through the Biological Rhythm Interview of Assessment Neuropsychiatry (BRIAN). A total of 1241 subjects were evaluated. The prevalence of substance use disorders in the sample was as follows: alcohol 14.1% (n=175), tobacco 30.8% (n=382), cannabis 10.5% (n=130), cocaine/crack 8.4% (n=104) and other psychoactive substance use disorder 9.2% (n=114). In the model of linear regression adjustment, alcohol use disorder was able to predict change in sleep/social pattern (p<0.001), activity (p=0.024), eating pattern (p=0.049) and overall rhythm (p<0.001). Other psychoactive substance use disorder was also predictive of changes in the sleep/social pattern (p <0.001), activity (p<0.001), eating pattern (p<0.001) and overall rhythm (p<0.001). Our findings suggest that individuals with alcohol and other psychoactive use disorders presented greater changes in sleep/social patterns, activity and food patterns, as well as greater disruptions in maintaining the overall biological rhythm. / O transtorno por uso de substâncias está relacionado a inúmeros problemas de saúde mental e física, associado a diversos prejuízos funcionais que afetam diversos aspectos da vida do indivíduo portador do transtorno. O objetivo deste estudo foi avaliar a relação entre substâncias psicoativas e ritmo biológico em uma amostra comunitária de jovens. Trata-se de um estudo transversal de base populacional com adultos de 24 a 30 anos de idade residentes da zona urbana da cidade de Pelotas-RS. A seleção amostral foi realizada por conglomerados com múltiplos estágios. Foram coletados dados sócio-demográfico da amostra e o abuso ou dependência de substâncias foi avaliado através do Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), bem como o ritmo biológico foi avaliado através da Biological Rhythm Interview of Assessment Neuropsychiatry (BRIAN). Foram avaliados 1241 sujeitos. As prevalências de transtornos por uso de substâncias na amostra foram as seguintes: álcool 14,1% (n=175), tabaco 30,8% (n=382), cannabis 10,5% (n=130), cocaína/crack 8,4% (n=104) e uso de outra substância psicoativas 9,2% (n=114). No modelo de ajuste por Regressão Linear, transtorno por uso de álcool foi capaz de predizer mudança no padrão de sono/social (p<0,001), atividade (p=0,024), alimentação (p=0,049) e ritmo global (p<0,001). Além disso, o transtorno por uso de outras substâncias psicoativas também foi capaz de predizer mudanças no padrão de sono/social (p<0,001), atividade (p<0,001), alimentação (p<0,001) e ritmo global (p<0,001). Nossos sugerem que os indivíduos com transtorno por uso de álcool e outras substâncias psicoativas apresentaram maiores alterações no padrão de sono/social, na atividade e no padrão alimentar, bem como, apresentaram maiores disrupturas na manutenção do ritmo biológico global.

An estimated 13.9% of Americans currently meet criteria for an alcohol (ethanol; EtOH) use disorder (AUD). While there are 4 medications approved by the Food and Drug Administration (FDA) to treat AUD, these treatments have demonstrated poor clinical efficacy. Our ongoing research program encompasses a multi-tiered screening of a natural product library and validation process to provide novel information about the mechanisms underlying EtOH-induced changes in neurobiology and to identify novel chemical scaffolds to be exploited in the development of pharmacological treatments for AUD in a rodent organotypic hippocampal slice culture model. Initial screens of several natural product compounds identified 3 compounds which attenuate 48 h EtOH-induced cytotoxicity in vitro. As analogs of natural products can be developed to have enhanced therapeutic potential over parental structures, Study 1 sought to extend on prior findings via the screening of several natural product analogs for their ability to attenuate EtOH-induced cytoxicity. Nine natural produce analogs demonstrated potent cytoprotective effects against EtOH-induced toxicity at 48 h. Several reports suggest EtOH-induced neurotoxicity may be secondary to the induction of persistent neuroimmune activation, and isoflavonoids have been shown to have effects on neuroimmune signaling. Thus, Study 2 compared the effects of compound 9b, an isoflavonoid analog identified in Study 1, to daidzein (DZ), a prototypical isoflavonoid, in the same 48 h model, with the addition of a neuroimmune component. Specifically, culture media was collected to assess for the release of the neuroimmune mediators HMGB1, TNF-α, IL-6, and IL-10 via ELISA. Compound 9b and DZ protected against EtOH-induced cytotoxicity at 48 h. EtOH exposure significantly increased secretion of HMGB1 and IL-6 into culture media at 48h. Compound 9b and DZ attenuated these increases at all concentrations tested. These results suggest potential neuroimmune modulating properties of isoflavonoids which may contribute to their neuroprotective effects against EtOH in vitro. These findings highlight the potential applications DZ and the novel isoflavonoid analog 9b for use in the treatment of AUD.

Hintergrund. In klinischen und epidemiologischen Untersuchungen wurden retrospektiv Assoziationen zwischen Angst- und Alkoholstörungen bestätigt. Bei Personen, die von beiden Störungen betroffen waren, fand man restrospektiv meist einen früheren Beginn der Angststörungen im Vergleich zu den Alkoholstörungen, was kausal im Sinne der Selbstmedikationshypothese interpretiert wurde. Diese konnte bisher nicht eindeutig bestätigt werden. Zur Aufklärung notwendige prospektive Untersuchungen, die Angststörungen auf diagnostischer Ebene erfassen, zwischen verschiedenen Angststörungen unterscheiden und sich auf Jugendliche beziehen, fehlen bisher. Fragestellung. Die Bedeutung von Angststörungen für die Entwicklung von erhöhtem Alkoholkonsum und Alkoholstörungen bei Jugendlichen und jungen Erwachsenen. Methodik. Die Analysen basieren auf den Daten der prospektiv-longitudinalen EDSP-Studie (Follow-Up: insg. 4 Jahre) mit einer epidemiologischen, repräsentativen Stichprobe von 3021 Personen im Alter zwischen 14 und 24 Jahre zu T0 aus München und Umland. Zur Erhebung von DSM-IV-Diagnosen wurde das M-CIDI verwendet. Ergebnisse. Primäre Panikstörungen, Panikattacken und Soziale Phobie erwiesen sich prospektiv als spezifische Prädiktoren für Beginn und Aufrechterhaltung von Alkoholproblemen. Umgekehrt waren Alkoholprobleme mit einem erhöhten Risiko für den Beginn von Sozialer Phobie und GAS assoziiert. Bezüglich DSM-IV Diagnosekriterien fanden sich phobische Ängste sowie Episoden intensiver Angst als Risikofaktoren für den Beginn von Alkoholproblemen. Vermeidungsverhalten war mit einem verminderten Risiko für nachfolgende Alkoholprobleme verbunden. Schlussfolgerungen. Maßnahmen zur Prävention von Alkoholproblemen können sich zielgruppenorientiert an Jugendliche mit Sozialer Phobie und Paniksymptomatik richten. Bei Patienten, die sich wegen Alkoholproblemen in Behandlung begeben, ist eine umfassende Diagnostik zur Identifikation zusätzlicher Angststörungen ratsam. / Background. Many clinical and epidemiological studies have documented significant cross-sectional comorbidities between anxiety disorders and alcohol use disorders. Analysis of retrospective age-of-onset reports suggests that the anxiety disorders often start earlier than the alcohol disorders. These data have often been interpreted in terms of a self-medication-model implying a causal mechanism. Overall, in former studies this model couldn't definitely be proofed. Prospective studies that follow a sample of adolescents into adulthood assessing different anxiety disorders on an diagnostic level are needed to confirm these associations. Methods. Baseline and four-year-follow-up data from the EDSP-Study, a prospective community survey of 3021 (2548 at follow-up) adolescents and young adults aged 14 to 24 years at baseline carried out in Munich, were used. DSM-IV anxiety disorders, alcohol use and alcohol use disorders were assessed with the M-CIDI. Results. While in retrospective analyses strong associations between nearly all anxiety disorders and alcohol problems, especially harmful use and dependence, were found, prospective analyses showed that only primary panic disorder, panic attack and social phobia are specific predictors of subsequent onset and persistence of alcohol problems. Contrary, primary alcohol problems were related to subsequent onset of social phobia and GAD. Considering the different DSM-IV-criteria, phobic anxiety as well as episodes of intensive anxiety were found to be risk factors for the following onset of alcohol problems. Avoidance behavior was associated with a lower risk for subsequent alcohol problems. Conclusions. Alcohol prevention programs could be directed to target groups with social phobia and panic. Patients with alcohol problems should carefully be screened for comorbid anxiety disorders. In order to prevent relapses the treating of social phobia and panic should be part of the therapy with comorbid alcohol patients.

Alcohol use disorder (AUD) is a widespread mental disease denoted by chronic alcohol use despite significant negative consequences for a person’s life. It affected more than 14 million persons in Europe alone and accounted for more than 5% of deaths worldwide in 2011-2012. Understanding the psychological and neurobiological mechanisms driving the development and maintenance of pathological alcohol use is key to conceptualizing new programs for prevention and therapy of AUD. There has been a variety of etiological models trying to describe and relate these mechanisms. Lately, the view of AUD as a disorder of learning and decision making has received much support proposing dual systems to be at work in AUD – one system being deliberate, forward-planning, and goal-directed and the other one reflexive, automatic, and habitual. Both systems supposedly work in parallel in a framework of value-based decision making and their balance can be flexibly adjusted in healthy agents, while a progressive imbalance favoring habitual over goal-directed choice strategies is assumed in AUD. This imbalance has been theoretically associated to neural adaptations to chronic alcohol use in corticostriatal pathways involved in reward processing, especially in ventral striatum. However, these theoretical models are grounded strongly on animal research while empirical research in the human domain remains rather sparse and inconclusive. Furthermore, alterations in value-based decision-making processes and their neural implementation might not only result from prolonged alcohol misuse but may also represent premorbid interindividual differences posing a risk factor for the development of AUD. Therefore, I here present three studies investigating the relation of alcohol use with the balance between goal-directed and habitual decision systems and with parameters modulating option valuation processes of these systems, namely delay, risk, and valence of option outcomes. To separate the investigation of these decision processes as predisposing risk for or consequence of alcohol use, two samples were examined: one sample of 201 eighteen-year-old men being neither abstinent from nor dependent on alcohol as well as one sample of 114 AUD patients in detoxification treatment and 98 control participants matched for age, sex, educational background, and smoking status. Both samples had a baseline assessment of several behavioral tasks, questionnaires, and neuropsychological testing and were followed-up over one year to examine drinking trajectories in the sample of young men and relapse in detoxified patients. The behavioral tasks included a sequential choice task using model-free and model-based reinforcement learning as operationalization of habitual and goal-directed decision making, respectively, during functional magnetic resonance imaging and four tasks probing participants’ delay discounting, probability discounting for gains and losses, and loss aversion. Study 1 presents the cross-sectional analysis of the sequential choice task in relation to baseline drinking behavior of the young-adult sample. These analyses did not reveal an association between non-pathological alcohol use and habitual and goal-directed control on neither a behavioral nor neural level except for one exploratory finding of increased BOLD responses to model-free habitual learning signals in participants with earlier onset of drinking. Study 2 examined the same task in AUD patients compared to control participants showing no difference in behavioral control or neural correlates between those groups. However, prospectively relapsing AUD patients showed lower BOLD responses associated to model-based goal-directed control than abstaining patients and control participants. Additionally, the interaction of goal-directed control and positive expectancies of alcohol effects discriminated subsequently relapsing and abstaining patients revealing an increased risk of relapse for those patients who showed higher levels of goal-directed control and low alcohol expectancies or low levels of goal-directedness and high expectancies. Study 3 examined modulating features of goal-directed and habitual option valuation – delay, risk, and valence of options – in association to alcohol use in the young-adult sample and AUD status in the sample of patients and matched control participants on a cross-sectional as well as longitudinal level. This study revealed no relation of delay, risk, and loss aversion with current alcohol use and consumption one year later in the young men. In contrast, AUD patients showed systematically more impulsive choice behavior than control participants in all four tasks: a higher preference for immediate rewards, more risky choices when facing gains and less when facing losses, and lower loss aversion. Furthermore, a general tendency to overestimate the probability of uncertain losses could predict relapse risk over the following year in AUD patients. Taken together, these results do not support the hypothesis that mechanisms of value-based decision making might be predisposing risk factors for alcohol consumption. The findings for patients already suffering from AUD are mixed: while choice biases regarding delays, risks, and valence of option outcomes seem to be altered systematically in AUD, there was no indication of an imbalance of habitual and goal-directed control. These findings challenge the assumption of a generalized outcome-unspecific shift of behavioral control from goal-directed to habitual strategies during the development of AUD and point towards several possible future avenues of research to modify or extend the theoretical model.

Cette thèse aborde les processus nationaux d'Evaluation des Technologies de la Santé (HTA) en Europe, en Australie et au Canada, avec comme point de référence le processus proposé par le National Institute for Health and Care Excellence (NICE) en Angleterre. Une attention particulière est portée sur la façon dont les décisions sont prises dans la gestion des soins de santé, sur quelles considérations ces décisions sont fondées, et sur la valeur des différents éléments d'évidence disponibles pour correctement évaluer les implications d'une mise en oeuvre d'un point de vue pratique. Cette thèse analyse le développement de recommandations dans la gestion des soins de santé afin de permettre l'accès aux traitements les plus efficaces d'un point de vue clinique et économique. Ces recommandations sont réalisées à partir des meilleures évidences disponibles et d'un consensus entre cliniciens, scientifiques, économistes de la santé, gestionnaires des services de soin et patients. La pertinence d'une évaluation en continu des différentes étapes de la gestion d'un problème de santé est également abordée durant cette thèse. L'objectif serait de permettre la production optimale de bénéfices de santé publique en reliant l'évaluation des différents stades d'une maladie. Ainsi, on obtiendrait une appréciation générale qui prendrait en considération que certaines recommandations de soin peuvent appeler à plus de flexibilité ou de contraintes selon les différents stades d'une maladie. Appliquée à la gestion de la dépendance à l'alcool, les abus d'alcool et conséquences attribuables, cette thèse contextualise et analyse le développement optimal d'évidences d'efficacité, d'efficience et d'économie de la santé, le choix de méthodologies appropriées et la manière d'interpréter et d'analyser leurs résultats pour la production optimale de bénéfices de santé publique / The current thesis discusses national processes of Health Technology Assessment (HTA) in Europe, Australia and Canada, with a central reference to the one proposed by the National Institute for Health and Care Excellence (NICE) in England. This is with a focus on the manner decisions about healthcare technologies are taken, based on which considerations and evidence, and with which weight the evidence elements are interlinked with regard to public health implications. The thesis analyses the development of recommendations of care to allow access to the most clinicallyand cost-effective treatments available, based on the best and most up-to-date evidence, and on the consensus from collaboration between clinicians, scientists, health economists, health service managers, as well as patients. Additionally, is discussed the value of covering all components of a disease evolution in assessing in continuum the different steps of disease management. This aims to allow the optimal generation of public health benefits in interlinking appraisals across different stages of disease for a generalist assessment of care, considering that recommendations in some aspects of care can call for more flexibility or constraints in other aspects. With an application to the management of alcohol use disorders, alcohol dependence and attributable harmful consequences, the thesis contextualizes and analyses decisions in the development of health economics and outcomes research evidence, the choice of methodology and directions taken, and their interpretation for optimal generation of public health benefits

El cerebro está constituido por numerosos elementos que se encuentran interconectados de forma masiva y organizados en módulos que forman redes jerárquicas. Ciertas patologías cerebrales, como la enfermedad de Alzheimer y el trastorno por consumo de alcohol, se consideran el resultado de efectos en cascada que alteran la conectividad cerebral. La presente tesis tiene como objetivo principal la aplicación de las técnicas de análisis de la ciencia de redes para el estudio de las redes estructurales y funcionales en el cerebro, tanto en un estado control como en un estado patológico. Así, en el primer estudio de la presente tesis se examina la relación entre la conectividad estructural y funcional en la corteza cerebral de la rata. Se lleva a cabo un análisis comparativo entre las conexiones estructurales en la corteza cerebral de la rata y los valores de correlación calculados sobre las mismas regiones. La información acerca de la conectividad estructural se ha obtenido a partir de estudios previos, mientras que la conectividad funcional se ha calculado a partir de imágenes de resonancia magnética funcional. Determinadas propiedades topológicas, y extraídas de la conectividad estructural, se relacionan con la organización modular de las redes funcionales en estado de reposo. Los resultados obtenidos en este primer estudio demuestran que la conectividad estructural y funcional cortical están altamente relacionadas entre sí. Estudios recientes sugieren que el origen de la enfermedad de Alzheimer reside en un mecanismo en el cual depósitos de ovillos neurofibrilares y placas de beta-amiloide se acumulan en ciertas regiones cerebrales, y tienen la capacidad de diseminarse por el cerebro actuando como priones. En el segundo estudio de la presente tesis se investiga si las redes estructurales que se generan con la técnica de resonancia magnética ponderada en difusión podrían ser de utilidad para el diagnóstico de la pre-demencia causada por la enfermedad de Alzheimer. Mediante el uso de imágenes procedentes de la base de datos ADNI, se aplican técnicas de aprendizaje máquina con el fin de identificar medidas de centralidad que se encuentran alteradas en la demencia. En la segunda parte del estudio, se utilizan imágenes procedentes de la base de datos NKI para construir un modelo matemático que simule el proceso de envejecimiento normal, así como otro modelo que simule el proceso de desarrollo de la enfermedad. Con este modelado matemático, se pretende estimar la etapa más temprana que está asociada con la demencia. Los resultados obtenidos de las simulaciones sugieren que en etapas tempranas de la enfermedad de Alzheimer se producen alteraciones estructurales relacionados con la demencia. La cuantificación de la relación estadística entre las señales BOLD de diferentes regiones puede informar sobre el estado funcional cerebral característico de enfermedades neurológicas y psiquiátricas. En el tercer estudio de la presente tesis se estudian las alteraciones en la conectividad funcional que tienen lugar en ratas dependientes del consumo de alcohol cuando se encuentran en estado de reposo. Para ello, se ha aplicado el método NBS. El análisis de este modelo de rata revela diferencias estadísticamente significativas en una subred de regiones cerebrales que están implicadas en comportamientos adictivos. Por lo tanto, estas estructuras cerebrales podrían ser el foco de posibles dianas terapéuticas. La tesis aporta tres innovadoras contribuciones para entender la conectividad cerebral bajo la perspectiva de la ciencia de redes, tanto en un estado control como en un estado patológico. Los resultados destacan que los modelos basados en las redes cerebrales permiten esclarecer la relación entre la estructura y la función en el cerebro. Y quizás más importante, esta perspectiva de red tiene aplicaciones que se podrían trasladar a la práctica clínica. / The brain is composed of massively connected elements arranged into modules that form hierarchical networks. Experimental evidence reveals a well-defined connectivity design, characterized by the presence of strategically connected core nodes that critically contribute to resilience and maintain stability in interacting brain networks. Certain brain pathologies, such as Alzheimer's disease and alcohol use disorder, are thought to be a consequence of cascading maladaptive processes that alter normal connectivity. These findings have greatly contributed to the development of network neuroscience to understand the macroscopic organization of the brain. This thesis focuses on the application of network science tools to investigate structural and functional brain networks in health and disease. To accomplish this goal, three specific studies are conducted using human and rodent data recorded with MRI and tracing technologies. In the first study, we examine the relationship between structural and functional connectivity in the rat cortical network. Using a detailed cortical structural matrix obtained from published histological tracing data, we first compare structural connections in the rat cortex with their corresponding spontaneous correlations extracted empirically from fMRI data. We then show the results of this comparison by relating structural properties of brain connectivity to the functional modularity of resting-state networks. Specifically, we study link reciprocity in both intra- and inter-modular connections as well as the structural motif frequency spectrum within functionally defined modules. Overall, our results provide further evidence that structural connectivity is coupled to and shapes functional connectivity in cortical networks. The pathophysiological process of Alzheimer's disease is thought to begin years before clinical decline, with evidence suggesting pahtogenic seeding and subsequent prion-like spreading processes of neurofibrillary tangles and amyloid plaques. In the second study of this thesis, we investigate whether structural brain networks as measured with dMRI could serve as a complementary diagnostic tool in prodromal dementia. Using imaging data from the ADNI database, we first aim to implement machine learning techniques to extract centrality features that are altered in Alzheimer's dementia. We then incorporate data from the NKI database and create dynamical models of normal aging and Alzheimer's disease to estimate the earliest detectable stage associated with dementia in the simulated disease progression. Our model results suggest that changes associated with dementia begin to manifest structurally at early stages. Statistical dependence measures computed between BOLD signals can inform about brain functional states in studies of neurological and psychiatric disorders. Furthermore, its non-invasive nature allows comparable measurements between clinical and animal studies, providing excellent translational capabilities. In the last study, we apply the NBS method to investigate alterations in the resting-state functional connectivity of the rat brain in a PD state, an established animal model of clinical relevant features in alcoholism. The analysis reveal statistically significant differences in a connected subnetwork of structures with known relevance for addictive behaviors, hence suggesting potential targets for therapy. This thesis provides three novel contributions to understand the healthy and pathological brain connectivity under the perspective of network science. The results obtained in this thesis underscore that brain network models offer further insights into the structure-function coupling in the brain. More importantly, this network perspective provides potential applications for the diagnosis and treatment of neurological and psychiatric disorders. / El cervell està constituït per nombrosos elements que es troben interconnectats de forma massiva i organitzats en mòduls que formen xarxes jeràrquiques. Certes patologies cerebrals, com la malaltia d'Alzheimer i el trastorn per consum d'alcohol, es consideren el resultat d'efectes en cascada que alteren la connectivitat cerebral. La present tesi té com a objectiu principal l'aplicació de les tècniques d'anàlisi de la ciència de xarxes per a l'estudi de les xarxes estructurals i funcionals en el cervell, tant en un estat control com en un estat patològic. Així, en el primer estudi de la present tesi s'examina la relació entre la connectivitat estructural i funcional en l'escorça cerebral de la rata. Es du a terme una anàlisi comparativa entre les connexions estructurals en l'escorça cerebral de la rata i els valors de correlació calculats sobre les mateixes regions. La informació sobre la connectivitat estructural s'ha obtingut a partir d'estudis previs, mentre que la connectivitat funcional s'ha calculat a partir d'imatges de ressonància magnètica funcional. Determinades propietats topològiques, i extretes de la connectivitat estructural, es relacionen amb l'organització modular de les xarxes funcionals en estat de repòs. Els resultats obtinguts en este primer estudi demostren que la connectivitat estructural i funcional cortical estan altament relacionades entre si. Estudis recents suggereixen que l'origen de la malaltia d'Alzheimer resideix en un mecanisme en el qual depòsits d'ovulets neurofibrilars i plaques de beta- miloide s'acumulen en certes regions cerebrals, i tenen la capacitat de disseminar-se pel cervell actuant com a prions. En el segon estudi de la present tesi s'investiga si les xarxes estructurals que es generen amb la tècnica de la imatge per ressonància magnètica ponderada en difusió podrien ser d'utilitat per al diagnòstic de la predemència causada per la malaltia d'Alzheimer. Per mitjà de l'ús d'imatges procedents de la base de dades ADNI, s'apliquen tècniques d'aprenentatge màquina a fi d'identificar mesures de centralitat que es troben alterades en la demència. En la segona part de l'estudi, s'utilitzen imatges procedents de la base de dades NKI per a construir un model matemàtic que simule el procés d'envelliment normal, així com un altre model que simule el procés de desenrotllament de la malaltia. Amb este modelatge matemàtic, es pretén estimar l'etapa més primerenca que està associada amb la demència. Els resultats obtinguts de les simulacions suggereixen que en etapes primerenques de la malaltia d'Alzheimer es produeixen alteracions estructurals relacionats amb la demència. La quantificació de la relació estadística entre els senyals BOLD de diferents regions pot informar sobre l'estat funcional cerebral característic de malalties neurològiques i psiquiàtriques. A més, a causa de la seua naturalesa no invasiva, és possible comparar els resultats obtinguts entre estudis clínics i estudis amb animals d'experimentació. En el tercer estudi de la present tesi s'estudien les alteracions en la connectivitat funcional que tenen lloc en rates dependents del consum d'alcohol quan es troben en estat de repòs. Per a realitzar-ho, s'ha aplicat el mètode NBS. L'anàlisi d'aquest model de rata revela diferències estadísticament significatives en una subxarxa de regions cerebrals que estan implicades en comportaments addictius. Per tant, estes estructures cerebrals podrien ser el focus de possibles dianes terapèutiques. La tesi aporta tres innovadores contribucions per a entendre la connectivitat cerebral davall la perspectiva de la ciència de xarxes, tant en un estat control com en un estat patològic. Els resultats destaquen que els models basats en les xarxes cerebrals permeten aclarir la relació entre l'estructura i la funció en el cervell. I potser més important, esta perspectiva de xarxa té aplicacions que es podrien traslladar a la pràcti / Díaz Parra, A. (2018). A network science approach of the macroscopic organization of the brain: analysis of structural and functional brain networks in health and disease [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/106966 / TESIS