Acrolein is produced endogenously after traumatic brain injury (TBI) and is considered a primary mechanism for secondary damage occurring after TBI. We are using frontal cortex networks derived from mouse embryos and grown on microelectrode arrays in vitro to monitor the spontaneous activity of networks and the changes that occur after acrolein application. Networks exposed to acrolein exhibit a biphasic response profile. An initial increase in network activity, followed by a decrease to 100% activity loss in applications ≥ 50 µM. In applications below 50 µM, acrolein was not toxic but generated activity instability with coordinated but irregular population busts lasting for up to 6 days. The increase in activity preceding toxicity may be linked to a decrease in free spermine, a free radical scavenger that modulates Na+, K+, Ca+ channels as well as NMDA, Kainate, and AMPA receptors. Action potential wave shape analysis after 20 and 30 µM acrolein application revealed a concentration-dependent 15-33% increase in peak to peak amplitude within minutes after exposure. For the same concentrations of acrolein (50 µM), the time required to reach 100% activity loss (IT100) was longer in serum-free medium than in medium with 5% serum, in which IT100 values were reduced by a factor of 4. The greater toxicity in the presence of serum may be explained by acrolein adducts on serum proteins. These reaction products have been shown by other labs to be toxic in cell culture. This in vitro system could be used to expand biochemical analyses such as acrolein-induced spermine depletion and may provide an effective platform for investigating cell culture correlates of secondary TBI damage.

La lésion cérébrale acquise (LCA) engendre des séquelles dont la chronicité est à l’origine de difficultés dans les activités familiales, sociales et professionnelles. L’interaction des facteurs lésionnels, personnels de la personne cérébrolésée et ceux de son environnement vont contribuer au handicap. Face à la complexité de ce handicap, des programmes d’aide à l’intégration communautaire (IC), comme les UEROS, ont été développés pour favoriser l’insertion familiale, sociale et professionnelle des patients et améliorer leur qualité de vie (QDV). Mieux connaitre les déterminants de l’IC et l’évolution des processus psychologiques au cours de ces programmes semble nécessaire. Le premier objectif de ce travail vise à améliorer l’évaluation de l’IC après LCA en validant en français le Community Integration Questionnaire-Revised (CIQ-R) de Callaway et al. (2016). Les résultats de l’étude transversale menée auprès 191 patients cérébrolésés montrent les qualités psychométriques du CIQ-R. Celui-ci permet d’évaluer quatre dimensions de l’IC ainsi qu’un score global. Le deuxième objectif de ce travail est double : repérer les déterminants du devenir professionnel des patients 36 mois après leur entrée à l’UEROS-Aquitaine et étudier l’évolution des processus psychologiques, de la qualité de vie (QDV) et de l’IC tout au long de leur participation au programme. Dans le cadre d’une étude longitudinale, 49 patients cérébrolésés ont été inclus à leur entrée à l’UEROS-Aquitaine. Des données psychologiques, de QDV et d’IC ont été recueillies à 5 reprises sur 24 mois et le devenir professionnel a été évalué à 36 mois. Trois facteurs, parmi ceux évalués à l’inclusion, discriminent les patients ayant retrouvé une activité professionnelle (AP) de ceux sans AP 36 mois plus tard: un âge jeune, un faible besoin d’aides en vie quotidienne et l’utilisation de la pensée positive pour faire face aux difficultés liées à la LCA. Des modélisations par équations structurales montrent que la symptomatologie dépressive et le coping « Evitement » diminuent jusqu’à 1 an après l’inclusion puis augmentent au cours de la deuxième année. La dimension « Soi » de la QDV et la satisfaction de vie augmentent jusqu’à 1 an puis diminuent ensuite. La QDV « Physique » augmente tout au long des 2 ans. Enfin, les résultats indiquent une absence d’évolution significative des scores d’estime de soi, de sentiment d’auto-efficacité et d’IC sur 2 ans. L’ensemble de nos résultats suggère des implications cliniques tant pour l’évaluation de l’IC que pour l’accompagnement à long terme des personnes cérébrolésées. / Acquired brain injury (ABI) causes disorders with chronicity at the origin of difficulties in daily, social and professional activities. The interaction of brain-injured people’s lesional, personal and environmental factors will contribute to the resulting disability. Given the complexity of this disability, Community Integration (CI) training programs have been developed, such as the UEROS, to promote family, social and professional integration. A better understanding of the determinants of CI and the evolution of psychological processes during these programs seems necessary. The first objective of this work aims to enhance the evaluation of CI after ABI by validating, for the french language, the Community Integration Questionnaire-Revised (CIQ-R) by Callaway et. al (2016). The results of the transversal study carried out with 191 ABI patients show the psychometric qualities of the CIQ-R. This tool allows evaluation of four dimensions of CI as well as an overall CI score. The second objective of this work is twofold: to identify determinants of the professional outcome of patients 36 months after their entry into the UEROS-Aquitaine program and to study evolution of psychological processes, quality of life (QoL) and CI throughout their participation in the program. In the context of longitudinal study, 49 ABI patients were included upon entry to UEROS-Aquitaine program. Psychological, QoL and CI data were collected at 5 moments during 24 months and professional outcome was evaluated at 36 months. Three factors among those evaluated upon inclusion discriminate patients having found a professional activity (PA) from those with no PA 36 months later: young age, a low need for aids in daily living and use of positive thinking to cope with the difficulties associated with the ABI. Structural equation modeling indicates that depressive symptomatology and avoidance coping decrease until 1 year after inclusion and then increase in the second year. The "self" dimension of QOL and life satisfaction increase up to the first year and then decrease during the second year. Physical QoL increases over 2 years. Finally, the results indicate a lack of significant change in self-esteem scores, self-efficacy and CI over 2 years. The results as a whole have clinical implications both for the evaluation of ABI patients' CI and for their long-term support.

A traumatic brain injury (TBI) is what its name suggests: an extremely traumatic event that affects the most supremely powerful but fragile organ that controls all our bodily functions and holds the essence that makes individuals unique. Some patients with a traumatic brain injury will recover without realising what the effect could have been and others will be left with effects that will last throughout their lives. “Many sufferers will remain severely incapacitated and a lamentably large number will become part of the statistics on the mortality after TBI” (Burns, 2008a:76). The impairments that an individual faces after a TBI will be dealt with in an acute rehabilitation setting. Significant emotions are experienced by patients with a traumatic brain injury. The researcher believes that this emotional reaction is also experienced by the family members. The event may be even more devastating to the family members, because of the impaired cognitive functions of the injured person. Ross and Deverell (2004:36) state that when individuals are diagnosed with disabling conditions, they experience strong emotional reactions. “Feelings of grief, anxiety, inadequacy, anger, guilt, vulnerability and confusion are some of the more common emotions that clients and their families experience when they encounter a disability in themselves or a family member” (Ross and Deverell, 2004:41). After a traumatic brain injury the patient is usually admitted to an intensive care unit (ICU). Once medically stable and able to participate in an active rehabilitation programme, provided this is authorised by the patient’s medical aid, the patient is transferred to a rehabilitation unit. While in ICU, the outcome is very uncertain and the the family often receives very limited support. Patients are often in a coma and unable to communicate. In working with TBI patients, the researcher found that family members receive very limited support, education on the condition and feedback on the patient’s medical state from team members, and therefore become very anxious when the patient is eventually transferred to a rehabilitation unit. In this study, the researcher focused on the family’s experience from the time of the patient’s admission into ICU until discharge from rehabilitation. During the rehabilitation process, family members are encouraged to support their family member in the rehabilitation unit. This is often very difficult for them, as it entails being confronted with reality and the often devastating impact of the injury. The focus of this study is on the experiences of family members while the patient with a TBI is in hospital and in the rehabilitation unit and the challenges they face. The researcher strove to understand the experiences of family members of patients with TBI, from ICU through until discharge from acute rehabilitation. The goal was to explore the experiences of adult family members of the traumatic brain-injured person in post-acute rehabilitation. The research question was: What were the experiences of adult family members of the person with a traumatic brain injury (TBI) during post-acute rehabilitation? A qualitative approach was used in this study, with a collective case study research design. The population for this study was all the family members of patients who underwent rehabilitation as a result of traumatic brain injury in the Life Eugene Marais Hospital, Pretoria, Gauteng. In this study purposive sampling was used to choose participants who were family members of TBI patients. The criteria for sampling of family members as participants were as follows. The patient <ul> <li> had suffered a traumatic brain injury;</li> <li> had undergone acute rehabilitation at Life Eugene Marais Hospital for the last four years;</li> <li> had completed rehabilitation, in other words had to be post discharge;</li> <li> lived in the province of Gauteng; and</li> <li> was able to speak and understand English or Afrikaans, irrespective of gender, race, religion, culture or age.</li> </ul> Eight participants who were family members of eight TBI patients were chosen for this study. Semi–structured individual interviews were conducted with participants. Interviews were voice recorded with the permission of the participants and were transcribed by the researcher. The data were analysed by the researcher and the themes and sub-themes generated from the data. The research findings were presented by providing a profile of the research participants and then presenting the themes and sub-themes, including literature control and verbatim quotes from the transcriptions. The themes included the following: Theme One – Understanding of TBI; Theme Two – Period of hospitalisation; Theme Three – Family members’ emotional experience of TBI; Theme Four – Period of rehabilitation; Theme Five – Period post discharge; Theme Six – Support systems; Theme Seven – Effects of TBI and Theme Eight – Future. The conclusions of this study are that traumatic brain injury (TBI) is experienced as severe trauma by family members, who struggle to cope not only initially but especially once the person is discharged and has to be cared for at home. In the long term this experience leads to changes in the family regarding structure, roles, functioning, relationships, communication, finances and social life. Recommendations in this study can be used by the multidisciplinary team to better understand the needs and experiences of the family members of TBI patients and by social workers to improve their intervention and support to these families. / Dissertation (MSW)--University of Pretoria, 2012. / Social Work and Criminology / unrestricted

Seit Veröffentlichung der Studien von G. Van den Berghe et al. im Jahre 2001 galt es die strikte Blutzuckereinstellung in normoglykämische Bereiche bei Schwerverletzten anzustreben. Die intensivierte Insulintherapie wurde daraufhin von verschiedensten Fachgesellschaften in Leitlinien und Therapieregimen integriert, so auch auf der neurochirurgischen ITS der Universitätsklinik Leipzig. Kurze Zeit später erschienen große multizentrische Studien, die den Benefit der intensivierten Insulintherapie in Frage stellten und sogar von einer signifikant höheren Letalität bei strikt normoglykäm eingestellten Patienten berichteten. Daher wird in dieser Studie die zwiespältige aktuelle Datenlage zum Anlass genommen, die Beziehungen zwischen Blutzuckereinstellung und ITS-Regime sowie die Auswirkungen hyperglykämischer Stoffwechselsituationen und mögliche Bedeutung des Blutglukosespiegels respektive der intensivierten Insulintherapie speziell für Patienten mit isoliertem mittelschwerem und schwerem Schädel-Hirn-Trauma zu evaluieren. Mit Hilfe der Integration wird erstmalig ein Verfahren zur Blutglukosedarstellung verwendet, dass durch die Flächenberechnung (Area under the Curve (AUC-BG)) ein Abbild von Höhe und Dauer der Hyperglykämie schafft. Es konnte gezeigt werden, dass die Blutzuckereinstellung mit dem klinischen Verlauf, krankheitsspezifischen Therapiekonzepten, Komplikationen und dem Outcome der Patienten korreliert und positiv Einfluss nimmt. Von besonderem Interesse war die Auswirkung auf den Hirndruck und die Notwendigkeit von Dekompressionskraniektomien, als auch auf Infektionsereignisse, die kontrollierte Beatmung, Ernährungsform und das Outcome. Nach Einführung der intensivierten Insulintherapie wurde ein Vergleich mit konventionell therapierten Patienten herbeigeführt. Es wurden vergleichende Analysen zwischen der retrospektiven (n = 65, konventionelle Insulintherapie, Blutzucker < 10,0 mmol/l [< 180 mg/dl]) und prospektiven Gruppe (n = 65, intensivierte Insulintherapie, Blutzucker 4,4 – 6,1 mmol/l [80 – 110 mg/dl]) bezüglich Blutzuckerfläche, Intensivverlauf und Outcome durchgeführt. Nach 1:1-Matching hinsichtlich Alter und Geschlechterzugehörigkeit waren die beiden Therapiegruppen homogen und es zeigten sich keine Unterschiede bezüglich der Aufnahmecharakteristik. Schädelhirntraumatisierte Patienten profitierten von einer intensivierten Insulintherapie im Vergleich zur Kontrollgruppe, auch wenn es nicht gelang, den Blutzuckerspiegel entsprechend der initiierten Therapierichtlinie signifikant hin zur Normoglykämie zu senken. Die positiven Effekte zeigten sich deutlich in Bezug auf die Infektionsrate und Ernährungsform. Die intensivierte Insulintherapie senkte den Hirndruck und die Rate risikobehafteter Dekompressionskraniektomien mit einem deutlicheren Trend zu besseren Outcomemesswerten. Vor allem Patienten mit einem besseren initialem GCS und Nicht-Diabetiker scheinen von einer guten Blutzuckereinstellung zu profitieren. Hypoglykämien (Blutzucker ≤ 3 mmol/l) traten entgegen der Vermutung dabei nicht gehäuft auf und stellten somit kein Gegenargument einer derartigen Therapie dar. Die Senkung des Blutzuckers in einen moderaten, therapeutischen Bereich sollte das Mindestziel in der Gesamttherapie von Patienten mit einem mittelschweren und schweren Schädel-Hirn-Trauma sein, wobei ein Konsens über den optimal therapeutischen Blutzuckerzielbereich bisher noch nicht gefunden wurde und somit weitere Untersuchungen gerechtfertigt sind.:BIBLIOGRAPHISCHE BESCHREIBUNG ABKÜRZUNGSVERZEICHNIS 1 EINFÜHRUNG 1.1 SCHÄDEL-HIRN-TRAUMA – DEFINITION UND EINTEILUNG 1.2 SCHÄDEL-HIRN-TRAUMA – EPIDEMIOLOGIE 1.3 PATHOPHYSIOLOGISCHER HINTERGRUND DES SCHÄDEL-HIRN-TRAUMAS 1.4 KLINIK, MONITORING UND THERAPIE – EIN ÜBERBLICK 1.5 FRAGESTELLUNG UND ZIEL DER ARBEIT 2 MATERIALIEN UND METHODIK 2.1 STUDIENDESIGN 2.1.1 Ein- und Ausschlusskriterien 2.1.2 Studienende 2.1.3 Erfasste Parameter 2.2 PATIENTENMANAGEMENT 2.3 BLUTZUCKERMANAGEMENT 2.3.1 Insulinschema bei konventioneller Insulintherapie 2.3.2 Insulinschema bei intensivierter Insulintherapie 2.4 DATENERFASSUNG 2.5 METHODENBESCHREIBUNG – AREA UNDER THE CURVE 2.6 STATISTISCHE ANALYSE 3 ERGEBNISSE 3.1 PATIENTENCHARAKTERISTIK/DEMOGRAPHIE 3.1.1 Vor Matching 3.1.2 Nach Matching 3.2 INTENSIVVERLAUF UND OUTCOME 3.2.1 Verlaufsparameter 3.2.2 Outcome-Messwerte 3.3 AUSWIRKUNGEN DER EINGANGSVARIABLEN AUF INTENSIVVERLAUF UND OUTCOME 3.4 EINFLUSS VON HÖHE UND DAUER DER HYPERGLYKÄMIE AUF INTENSIVVERLAUF UND OUTCOME 3.4.1 Einfluss auf die Beatmungsdauer 3.4.2 Einfluss auf den Gesamt-SAPS II 3.4.3 Einfluss auf die Dauer bis zur Oralisierung 3.4.4 Einfluss auf das Auftreten von Infektionen 3.4.5 Einfluss auf den intrakraniellen Druck 3.4.5.1 ICP-Sondenliegedauer in Abhängigkeit von der Blutzuckerfläche 3.4.5.2 Zusammenhang zwischen Hirndruckfläche und Blutzuckerfläche 3.4.5.3 Diabetiker versus Nicht-Diabetiker 3.4.6 Einfluss auf die Notwendigkeit einer Dekompressionskraniektomie 3.4.7 Einfluss auf die Dauer der Intensivbehandlung 3.4.8 Einfluss auf das Outcome 3.4.8.1 Glasgow Outcome Score 3.4.8.2 Modified Rankin Scale 3.5 METHODENVERGLEICH 3.5.1 Güte der Therapie 3.5.2 Kontrollierte Beatmung 3.5.3 Gesamt-SAPS II 3.5.4 Dauer bis zur Oralisierung 3.5.5 Auftreten von Infektionen 3.5.6 Hirndruckmanagement 3.5.6.1 Demographie 3.5.6.2 Vergleich des intrakraniellen Druckes 3.5.7 Notwendigkeit einer Dekompressionskraniektomie 3.5.8 Intensivbetreuung und Krankenhausliegedauer 3.5.9 Outcome 3.5.9.1 Glasgow Outcome Score 3.5.9.2 Modified Rankin Scale 3.6 HYPOGLYKÄMIE 3.7 SCHWERE HYPERGLYKÄMIE 3.8 ABHÄNGIGKEIT DES OUTCOMES 3.8.1 Initial- und Verlaufsparameter 3.8.2 Multiple lineare Regressionsanalyse 3.8.2.1 Einfluss der Initialparameter 3.8.2.2 Interaktion von Glasgow Coma Score und Blutzuckerfläche 3.8.2.3 Einfluss der Verlaufsparameter 3.8.2.4 Zusammenfassung der relevanten Initial- und Verlaufsparameter 3.9 ABHÄNGIGKEIT DES HIRNDRUCKES 3.9.1 Multiple lineare Regressionsanalyse 3.9.1.1 Einfluss der Initialparameter 3.9.1.2 Einfluss der Verlaufsparameter 3.10 ZUSAMMENFASSUNG DER ERGEBNISSE 3.10.1 Patientencharakteristik/Demographie 3.10.2 Intensivverlauf und Outcome 3.10.3 Auswirkungen der Eingangsvariablen auf Intensivverlauf und Outcome 3.10.4 Einfluss von Höhe und Dauer der Hyperglykämie auf Intensivverlauf und Outcome 3.10.5 Methodenvergleich 3.10.6 Abhängigkeit des Outcomes 3.10.7 Abhängigkeit des intrakraniellen Druckes 4 DISKUSSION 4.1 PATIENTENCHARAKTERISTIK/DEMOGRAPHIE 4.2 MATERIAL UND METHODIK 4.3 AUSWIRKUNGEN VON HÖHE UND DAUER DER HYPERGLYKÄMIE AUF INTENSIVVERLAUF UND OUTCOME 4.3.1 Einfluss auf allgemeine intensivmedizinische Parameter 4.3.2 Einfluss auf den intrakraniellen Druck und das Outcome 4.4 VERGLEICH BEIDER THERAPIEGRUPPEN 4.4.1 Methodische Aspekte 4.4.2 Klinische Aspekte 4.5 HYPOGLYKÄMIE 4.6 ABHÄNGIGKEIT DES OUTCOMES 4.7 ABHÄNGIGKEIT DES HIRNDRUCKES 4.8 ZUSAMMENFASSUNG 5 ZUSAMMENFASSUNG LITERATURVERZEICHNIS ABBILDUNGSVERZEICHNIS TABELLENVERZEICHNIS ANLAGEN PATIENTENDATENBLATT TABELLEN SAPS II – SCORE VOTUM DER ETHIKKOMMISSION ERKLÄRUNG ÜBER DIE EIGENSTÄNDIGE ABFASSUNG DER ARBEIT LEBENSLAUF DANKSAGUNG

This thesis is focused on quality of life theme, satisfaction with life topic and social self- efficacy subject, with emphasizing of the acquired brain injury context and specific and unique brain injury consequences. Thesis is based on theoretical fundament of all mentioned concepts, but mainly there are actual quantitative data and results of quality of life, satisfaction with life and social self-efficacy and other-efficacy in the framework of acquired brain injury research sample in Czech Republic. Not only description of quality of different life parts subjective perception, but also search of possible relationships strength between quality of life and social efficacy has been probed. All of these has been used in application of lots of standardized and also new questionnaire and methods. Keywords: acquired brain injury, quality of life, satisfaction with life, social self-efficacy, social other- efficacy

Deficient executive functioning influences significantly the ability to manage every day life requirements. Nowdays different structured programmes for EF rehabilitation are available for aquired brain damage patiens. Their efficiency had been confirmed by meta- analysis, yet cognitive-behavioural rehabilitation programmes in clinical praktice still lack some kind of systematic intervention particularly aimed at EF. The topic of the theoretical part is an introduction of selected theoretical models of EF and a summary of existing knowledge about EF rehabilitation. I have created a rehabilitation programme specificly focused on the ability of planning and organizing acitivities, which are complex abilities closely linked to the primary components of EF. This programme was created to help patiens with aquired brain damage to work on improvment of such abilities, whose disruption makes managing every day life requirements difficult. Along with that we tried to improve the quality of their lifes. This programme is also being introduced wihin the theoretical part of this work. Further the process of research is being analyzed. The rehabilitation programme was used with 9 aquired brain damage patiens and it's efficiency was measured. Reasons why I used small-n design are analyzed in detail as well as the...

Cognitive and psychosocial sequelae following hypoxic brain injury Abstract in English Hypoxic brain injury leads to neuronal necrosis and to other cerebral changes which may affect psychosocial functioning. Although the pathophysiology of cerebral hypoxia is multifactorial, and it is not possible to reliably describe the unified clinical picture of hypoxia patients, the most commonly described psychosocial consequences of cerebral hypoxia are cognitive impairment, increased anxiety and depressive symptoms. The aim of the present study is to characterize cognitive functioning and psychosocial changes of the patients exposing mild intermittent cerebral hypoxia (=chronic form of hypoxia, model of obstructive sleep apnea diagnosed by neurologist) and patients after severe one-time cerebral hypoxia (=acute form of hypoxia, model of cardiac arrest diagnosed by cardiologist). Regardless of the different etiology of particular hypoxia forms described in the theoretical part of the thesis, both forms may lead to neuronal death. In the experimental part we test a hypothesis comparing healthy individuals to patients with acute or chronic form of hypoxia in cognitive performance or anxiety and depressive symptoms. We document a decreased cognitive performance and higher level of state anxiety in a group of patients...

Deficits in working memory (WM) functions represent one of the main causes of limited participation in daily life and impaired recovery after brain injury. Based on promising research in clinically healthy individuals, which suggest that repetitive training may improve WM performance and other related cognitive functions, this thesis aimed at exploring the potential and limits of WM training in clinical populations. Existing research on WM training and relevant neuropsychological outcomes were examined with a special focus on individuals with acquired brain injury by means of a meta-analysis (study I). The findings indicated relevant impact of WM training on both behavioral performance and disease-related symptom reduction. To determine the primary outcome variable for the evaluation studies, the Corsi Block-Tapping Task was reviewed (study II). Due to the lack of an appropriate theory-based intervention tailored for the needs of individuals with low WM capacity, the program 'WOME' was developed (study III). Three randomized, double-blind, placebo-controlled trials were carried out to evaluate the efficacy of the new intervention and to provide valuable recommendations for its application in clinical practice (study IV, V and VI). Significant improvements in the trained tasks, moderate to large transfer effects in overall WM performance, and related benefits in daily life were demonstrated. The effects were short-termed with very limited evidence supporting transfer to other cognitive functions. In accordance with the results of the meta-analysis (study I), the number of sessions was identified as an important modulator of efficacy by comparing different training intensities and training tasks. The specific content, in contrast, seemed to be less relevant. Mediation analyses revealed that inter-individual differences influence the successful application of the intervention, in particular initial WM capacity. Implications for clinical application and WM training research are discussed.:1. Introduction 1.1. Definition of the working memory system 1.2. Functional neuroanatomy of working memory 1.3. Functional relevance of working memory 1.4. Training of working memory functions 1.5. Objectives of the current thesis 2. Experimental work 2.1. Study I: Can impaired working memory functioning be improved by training? A meta-analysis with a special focus on brain injured patients 2.2. Study II: „Was misst eigentlich die Blockspanne?“ — Der Gold-Standard im Fokus. 2.3. Study III: WOME working memory training — A new intervention for individuals with low WM capacity 2.4. Study IV: WOME: Theory-based working memory training — A placebo-controlled, double-blind evaluation in older adults 2.5. Study V: Effects of working memory training in patients with acquired brain injury: a double-blind randomized controlled trial. 2.6. Study VI: The effect of high vs. low intensity neuropsychological treatment on working memory in patients with acquired brain injury. 3. General discussion 3.1. Summary of the empirical findings 3.2. Implications for clinical practice 3.2.1. Benefits and limits of working memory training 3.2.2. The importance of training dose and its practical implementation 3.2.3. The influence of inter-individual differences on training efficacy 3.3. Implications for working memory training research 3.4. Critical comments and directions for future research 3.5. Conclusion 4. References 5. Summary 6. Zusammenfassung Appendices List of abbreviations List of Tables List of Figures Supplemental material Curriculum vitae List of publications Selbstständigkeitserklärung

Introduktion: Traumatisk hjärnskada är en av det ledande orsakerna till mortalitet och morbiditet globalt. Traumatisk hjärnskada graderas som mild, måttlig eller svår skada. Prognosen kan variera beroende på allvarlighetsgraden, långvarig medvetslöshet samt storleken på primär och sekundär skada. De förlorade eller nedsatta funktioner som hjärnskadan medfört kan i olika grad påverka individers livssituation. Syfte: Syftet med denna studie var att beskriva hur individer med en traumatisk hjärnskada upplever sin livssituation tiden efter den akuta fasen av skadan. Metod: En kvalitativ systematisk litteraturstudie med beskrivande design. Studiens resultat baserades på 10 vetenskapliga originalartiklar från databaserna PubMed och CINAHL. Resultat: Fyra huvudkategorier identifierades: komplikationer, ett annat liv, mötet med hälso- och sjukvården samt vardagen med traumatisk hjärnskada. De mest framträdande komplikationerna var fysiska, kognitiva och psykosociala svårigheter. En förändrad självbild och att acceptera skadan gav upphov till känslan av ett annat liv efter skadan. Information, kommunikation och stöd var viktiga delar i mötet med hälso- och sjukvården. Vardagen med traumatisk hjärnskada omfattade närståendes betydelse, arbetsliv och återhämtning vilket var viktiga delar för en fungerande vardag. Slutsats: Individer som drabbats av traumatisk hjärnskada upplever i olika grad att livet förändras efter skadan. Hur komplikationer inverkar på livet, känslan av ett annat liv, mötet med hälso- och sjukvården samt vardagen med traumatisk hjärnskada var dominerande upplevelser som alla påverkade och kunde förändra individens livssituation. Upplevelserna av en förändrad livssituation kan bidra till känslan av att inte fylla sin funktion i livet vilket kan resultera i en minskad känsla av sammanhang. För att tillmötesgå dessa individer och optimera förutsättningarna krävs god information, kommunikation, förståelse och planering från hälso- och sjukvården och samhället.  Nyckelord: traumatisk hjärnskada, vuxna, livsavgörande händelser, känsla av sammanhang, kvalitativ systematisk litteraturstudie / Introduction: Traumatic brain injury is a worldwide leading cause of death and disability. Traumatic brain injuries can be graded as mild, moderate and severe. The prognosis can vary depending on severity, length of unconsciousness and the size of the primary and/or secondary trauma. The reduced or lost functions that the brain injury brings can to various extents influence individuals’ life situation. Purpose: The purpose of this study was to describe how individuals with a traumatic brain injury experience their life situation following the acute phase of the injury.  Method: Qualitative systematic literature study with a descriptive design. The result of the study is based on 10 scientific original articles from the databases PubMed and CINAHL. Results: Four main categories were identified: Complications, Another life, Encounter with healthcare and Daily life with traumatic brain injury. The most prominent complications were physical, cognitive and psychosocial difficulties. A changed self-perception and to accept the injury contributed to the sense of another life after the injury. Information, communication and support were crucial factors in the encounter with healthcare. Daily life with traumatic brain injury included the importance of relatives, working life and recovery which were important factors for a functional daily life. Conclusion: Individuals with traumatic brain injury experience life changes in varying degrees after the injury. Important aspects of the individuals’ life situation included: impact of complications, a feeling of a different life, encounters with healthcare and perceptions of daily life. The experiences of life changes may contribute to a feeling of not being able to fulfill life's duties. That may result in a lower sense of coherence. Adjustment and improvement of the conditions for these individuals require adequate information, communication, understanding and planning from healthcare and society.  Keywords: traumatic brain injury, adults, life change events, sense of coherence, qualitative systematic literature study Introduction: Traumatic brain injury is a worldwide leading cause of death and disability. Traumatic brain injuries can be graded as mild, moderate and severe. The prognosis can vary depending on severity, length of unconsciousness and the size of the primary and/or secondary trauma. The reduced or lost functions that the brain injury brings can to various extents influence individuals’ life situation. Purpose: The purpose of this study was to describe how individuals with a traumatic brain injury experience their life situation following the acute phase of the injury.  Method: Qualitative systematic literature study with a descriptive design. The result of the study is based on 10 scientific original articles from the databases PubMed and CINAHL. Results: Four main categories were identified: Complications, Another life, Encounter with healthcare and Daily life with traumatic brain injury. The most prominent complications were physical, cognitive and psychosocial difficulties. A changed self-perception and to accept the injury contributed to the sense of another life after the injury. Information, communication and support were crucial factors in the encounter with healthcare. Daily life with traumatic brain injury included the importance of relatives, working life and recovery which were important factors for a functional daily life. Conclusion: Individuals with traumatic brain injury experience life changes in varying degrees after the injury. Important aspects of the individuals’ life situation included: impact of complications, a feeling of a different life, encounters with healthcare and perceptions of daily life. The experiences of life changes may contribute to a feeling of not being able to fulfill life's duties. That may result in a lower sense of coherence. Adjustment and improvement of the conditions for these individuals require adequate information, communication, understanding and planning from healthcare and society.  Keywords: traumatic brain injury, adults, life change events, sense of coherence, qualitative systematic literature study

Schädel-Hirn-Traumata sind die häufigste Ursache von Tod und Behinderung bei jungen Erwachsenen und oftmals ein Grund für Erwerbsunfähigkeit. Deshalb sind das Verständnis der zugrundeliegenden Pathomechanismen und die Entwicklung von Rehabilitationsstrategien von höchster Wichtigkeit. Einer der Hauptschädigungsmechanismen sind diffuse axonale Schädigungen. Diese treten insbesondere in frontalen Hirnregionen auf und führen entsprechend zu einer Beeinträchtigung exekutiver Funktionen und Veränderungen im Verhalten noch Jahre nach dem Ereignis. Unsere Studie mit Patienten im chronischen Stadium zielte auf eine genauere Charakterisierung frontaler Funktionen nach Schädel-Hirn-Trauma. In einem ersten behavioralen Experiment setzten wir zwei Paradigmen ein, die einerseits mit dem frontolateralen (Stroop-Interferenz-Aufgabe) und andererseits mit dem frontomedianen Kortex (Aufgabe zur Unterdrückung von Handlungsimitation) assoziiert sind (Schroeter et al., 2007). Die Patienten waren spezifisch in der Aufgabe zur Unterdrückung von Handlungsimitation als Hinweis auf eine Alteration des anterioren frontomedianen Kortex beeinträchtigt. Die Defizite waren hierbei eng mit Veränderungen des Verhaltens und der posttraumatischen Amnesie, die das Outcome nach Schädel-Hirn-Trauma vorhersagt, verbunden. In einem zweiten fMRT-Experiment überprüften wir die Hypothese einer frontomedianen Dysfunktion mittels eines Paradigmas, das spezifisch frontomediane Strukturen beansprucht. Hierbei wurden evaluative Urteile mit semantischen Gedächtnisinhalten kontrastiert („Angela Merkel ist eine gute Bundeskanzlerin“ vs. „Angela Merkel ist Bundeskanzlerin“). Die Ergebnisse bestätigen, dass Patienten nach Schädel-Hirn-Trauma durch persistierende frontomediane Beeinträchtigungen charakterisiert sind. Unsere Ergebnisse stimmen gut mit der Literatur überein, welche Defizite bei der „Theory of Mind“ und sozialen Kognition, die ebenfalls wesentlich mit dem frontomedianen Kortex verbunden sind, berichtet. Die Studie trägt zum Verständnis der Pathomechanismen nach Schädel-Hirn-Trauma bei. Frontomediane Alterationen scheinen wesentlich für die Langzeitfolgen verantwortlich zu sein. Deshalb sollten frontomediane Funktionen in der Diagnostik, insbesondere zur Einschätzung der Prognose, und der Rehabilitation eine stärkere Beachtung finden.