| 1. |
- Gauffin, Helena
(författare)
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Epilepsy in young adulthood : medical, psychosocial and functional aspects
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to describe the medical, cognitive and psychosocial consequences of epilepsy in young adulthood. Four studies were carried out with this patient group. The first two papers were based on a follow-up study regarding young adults with epilepsy that investigated medical and psychosocial aspects and compared the present results with those five years earlier. We then conducted focus group interviews with young adults with epilepsy and subjective cognitive decline to assess the deeper meaning of living with epilepsy accompanied by cognitive difficulties. In the fourth study we studied cognitive dysfunction further, choosing the language function in young adults with epilepsy. We firstly examined whether language impairments were associated to functional brain alterations and secondly related the language performance to demographics, clinical data, Quality of Life (QoL) and self-esteem.The five-year follow up of 97 young adults with uncomplicated epilepsy revealed no improvement regarding seizure frequency or side effects from anti-epileptic drugs (AEDs) over time, even though many new-generation AEDs had been established during this period. During the study period 21% had recovered from epilepsy, Seizure frequency among those who still had epilepsy had not improved, and 42% had experienced seizures during the past year. New-generation anti-epileptic drugs (AEDs) had been introduced to PWE, especially to women. There is still need for new and more effective treatment options for this group in the future. It is essential to find alternative approaches to develop better treatment options for this group in the future. However QoL was normal compared to the general population, indicating that new options regarding treatment can have made an impact. Lower QoL was correlated to high seizure frequency and to cognitive side effects. Self-esteem and Sence of Coherence were impaired compared to the situation at adolescence. Self-esteem was correlated to seizure frequency and to side-effects of antiepileptic drugs. Sence of Coherence was not correlated to epilepsy-related factors in the same way as QoL, but mirrored the phenomenon of epilepsy.The qualitative study showed that the consequences of epilepsy are not only restricted to the consequences of seizures, but also concerns many other aspects of life. The interviews revealed four themes: “affecting the whole person“, “influencing daily life”, ”affecting relations” and ”meeting ignorance in society”. Another important factor was language function; when one loses some language ability, this gives a feeling of losing one’s capability.The fourth study examined language by neuropsychological methods and correlated this function to brain activation measured by fMRI. Language functions measured in verbal fluency and abstract language comprehension were impaired in participants with both generalized epilepsy and epilepsy of focal onset. Age at onset of epilepsy and education are the most important factors correlating to language function. An additional factor that impacts abstract language comprehension is the frequency of convulsive seizures, while use of topiramate /zonisamide affect verbal fluency negatively. QoL was not correlated to language impairments, but for patients with focal onset seizures there was a correlation between self-esteem and abstract language comprehension. The fMRI investigation revealed altered activity during language tasks in participants with epilepsy compared to controls. In epilepsy with focal seizures originating in the left hemisphere, we found increased bilateral activation of supporting areas, in the anterior mid-cingulate cortex and the anterior ventral insulae, indicating a compensational functional reorganization. In generalized epilepsy, the functional language network showed an imbalance, as this group expressed an inadequate suppression of activation in the anterior temporal lobe during semantic processing. Subtle language impairment can, even if it does not occur in everyday dialogue, be of importance and have consequences for the person affected. The negative consequences of language decline must be addressed in people with epilepsy of different etiology. Young adults with epilepsy are still substantially affected by the condition. The consequences are not only restricted to the seizures, but concern many aspects of life and there is a great need for new treatment options for this group in the future.
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| 2. |
- Nordanskog, Pia, 1971-
(författare)
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On electroconvulsive therapy in depression : Clinical, cognitive and neurobiological aspects
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Electroconvulsive therapy (ECT) is used worldwide to treat severe mental disorders. The most common mental disorder, and the third leading cause of disease burden in the world is depression. The clinical efficacy of ECT for severe depression is well-established. However, both the pathophysiology of depression and the mechanism of action of ECT remain elusive.The main aims of this thesis are to address the following issues: 1) the use and practice of ECT in Sweden has not been systematically evaluated since 1975, 2) cognitive side-effects (memory disturbances) are a major concern with ECT and 3) the mechanism of action of ECT remain elusive. The neurobiological aspects of ECT focus on two hypotheses. First, the recent years´ preclinical studies that have provided evidence that ECT induces hippocampal cell proliferation, including neurogenesis. Second, that enhanced functional inhibition of neuronal activity is a key feature.Current use and practice of ECT in Sweden (paper I) is based on data from the national quality register for ECT, the mandatory patient register of the National Board of Health and Welfare and a survey. Treated person rate (TPR) in Sweden 2013 was found to be 41 individuals / 100 000, and thus unchanged since the latest systematic investigation in Sweden 1975. In more than 70% of treatment series the indication was a depressive episode. The selection of patients for ECT and treatment technique in Sweden was similar to that in other western countries, but the consent procedure and the involvement of nurses and nursing assistants in the delivery of ECT differ. Data also shows that there is room for improvement in both the specificity of use and availability of ECT.The second study in this thesis is a longitudinal observational trial where 12 (paper II and III) and 14 (paper IV) patients with depression referred for ECT were investigated. Patients underwent a 3 T MRI structural scanning and DSC-MRI perfusion, a neuropsychological test battery and clinical ratings before ECT, within one to two weeks after ECT and after 6 and 12 months. In line with preclinical findings and the plasticity hypothesis of mechanism of action of ECT, the hippocampal volume increased after ECT in patients with depression. However, this increase was transient and returned to baseline levels within 6 months. No correlation was found between volumetric changes and clinical effect or cognitive outcome. Instead our results suggested an association to the number of treatments, without relation to the side of stimulation. A right-sided decrease in frontal blood flow distinguished remission from non-remission after ECT. There were significant impairments in verbal episodic memory and verbal fluency within one week after ending the ECT course, but these impairments were transient and no persistent cognitive impairments were seen during the follow-up.In summary, this thesis present the first update on the use and practice of ECT in Sweden in the last 40 years as well as a pioneering MRI-study on the hippocampal volume increase in the treatment of depression with ECT. Supportive to earlier findings we also found the cognitive side-effects that are measurable after ECT to be transient. Furthermore, we found that a decreased frontal blood flow is of importance for the anti-depressive response to ECT.
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| 3. |
- Drissi, Natasha Morales, 1980-
(författare)
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Brain Networks and Dynamics in Narcolepsy
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Narcolepsy is a chronic sleep disorder, characterised by excessive daytime sleepiness with frequent uncontrollable sleep attacks. In addition to sleeprelated problems, changes in cognition have also been observed in patients with narcolepsy and has been linked to the loss of Orexin-A in a number of studies. Results from previous functional and structural neuroimaging studies would suggest that the loss of Orexin-A has numerous downstream effects in terms of both resting state glucose metabolism and perfusion and reduction in cortical grey matter.Specifically, studies investigating narcolepsy with positron emission tomography (PET) and single photon emission computed tomography (SPECT) have observed aberrant perfusion and glucose metabolism in the hypothalamus and thalamus, as well as in prefrontal cortex. A very recent PET study in a large cohort of adolescents with type 1 narcolepsy further observed that the hypoand hypermetabolism in many of these cortico-frontal and subcortical brain regions also exhibited significant correlations with performance on a number of neurocognitive tests. These findings parallel those found in structural neuroimaging studies, where a reduction of cortical grey matter in frontotemporal areas has been observed.The Aim of this thesis was to investigate mechanisms and aetiology behind the symptoms in narcolepsy through the application of different neuroimaging techniques. I present in this thesis evidence supporting that the complaints about subjective memory deficits in narcolepsy are related to a misallocation of resources.I further describe how this has its seat in defective default mode network activation, possibly involving alterations to GABA and Glutamate signaling. In addition to this, I present our findings of a structural deviation in an area of the brainstem previously not described in the aetiology of narcolepsy.This finding may have implications for further understanding the aetiology of the disease and the specific neuronal populations involved.In addition to this, I show evidence from adipose tissue measurements in specific compartments, confirming that weight gain in narcolepsy is characterized by centrally located weight gain and may be specifically related to OX changes, but maybe not brown adipose tissue volume.The findings presented in this thesis provides new insights to the pathophysiology of narcolepsy beyond the well-known depletion of OX producing neurons in the hypothalamus.
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| 4. |
- Lindmark, Tomas, 1992-
(författare)
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Residential care homes in the age of marketisation : Care workers’ and first-line managers’ psychosocial work environment and well-being across public, outsourced, and private providers
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim was to investigate care workers’ and first-line managers’ (FLMs) psychosocial work environment and well-being across public, outsourced, and private residential care homes. A mixed-methods approach was used, including a systematic review and qualitative and quantitative data. Data included 11 procurement and tender documents, 19 semi-structured interviews with FLMs, and a survey with 253 care workers from three Swedish municipalities. The results did not indicate clear advantages regarding the psychosocial work environment and well-being for any provider type. Internationally, results favoured nonprofit settings for care workers’ well-being concerning commitment, stress, and turnover intentions. The Swedish context had mixed results. FLMs in outsourced and private settings felt they had more influence and better managerial support than in public settings. Care workers in outsourced settings rated emotional demands and burnout higher, while FLMs faced additional stress and demands due to the outsourcing process. Public care workers reported fewer work–life conflicts than private ones. Most care workers reported good job satisfaction, yet about one in four considered leaving their jobs. Marketisation has brought procurement processes that overlook care worker empowerment, with documents emphasising care users while imposing demands on the workforce. There were municipal variations in the documents, FLMs’ work structure, and care workers’ burnout ratings, challenging equality ambitions. The dissertation highlights persistent issues in the psychosocial work environment with high workloads, recruitment challenges, inadequate organisational support, conflicting care logics and a disconnect between political ambitions and the realities of residential care homes. Political decisions do not come with corresponding resources. To address these issues, care workers and FLMs must be prioritised in decisions and policy documents, which could also improve care quality.
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| 5. |
- Lundengård, Karin, 1985-
(författare)
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Mechanistic modelling - a BOLD response to the fMRI information loss problem
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Functional Magnetic Resonance Imaging (fMRI) is a common technique for imaging brain activity in humans. However, the fMRI signal stems from local changes in oxygen level rather than from neuronal excitation. The change in oxygen level is referred to as the Blood Oxygen Level Dependent (BOLD) response, and is connected to neuronal excitation and the BOLD response are connected by the neurovascular coupling. The neurons affect the oxygen metabolism, blood volume and blood flow, and this in turn controls the shape of the BOLD response. This interplay is complex, and therefore fMRI analysis often relies on models. However, none of the previously existing models are based on the intracellular mechanisms of the neurovascular coupling. Systems biology is a relatively new field where mechanistic models are used to integrate data from many different parts of a system in order to holistically analyze and predict system properties. This thesis presents a new framework for analysis of fMRI data, based on mechanistic modelling of the neurovascular coupling, using systems biology methods. Paper I presents the development of the first intracellular signaling model of the neurovascular coupling. Using models, a feed-forward and a feedback hypothesis are tested against each other. The resulting model can mechanistically explain both the initial dip, the main response and the post-peak undershoot of the BOLD response. It is also fitted to estimation data from the visual cortex and validated against variations in frequency and intensity of the stimulus. In Paper II, I present a framework for separating activity from noise by investigating the influence of the astrocytes on the blood vessels via release of vasoactive sub- stances, using observability analysis. This new method can recognize activity in both measured and simulated data, and separate differences in stimulus strength in simulated data. Paper III investigates the effects of the positive allosteric GABA modulator diazepam on working memory in healthy adults. Both positive and negative BOLD was measured during a working memory task, and activation in the cingulate cortex was negatively correlated to the plasma concentration of diazepam. In this area, the BOLD response had decreased below baseline in test subjects with >0.01 mg/L diazepam in the blood. Paper IV expands the model presented in Paper I with a GABA mechanism so that it can describe neuronal inhibition and the negative BOLD response. Sensitization of the GABA receptors by diazepam was added, which enabled the model to explain how changes to the BOLD response described in Paper III could occur without a change in the balance between the GABA and glutamate concentrations.The framework presented herein may serve as the basis for a new method for identification of both brain activity and useful potential biomarkers for brain diseases and disorders, which will bring us a deeper understanding of the functioning of the human brain.
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| 6. |
- Sten, Sebastian, 1993-
(författare)
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Mathematical modeling of neurovascular coupling
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The brain is critically dependent on the continuous supply of oxygen and glucose, which is carried and delivered by blood. When a brain region is activated, metabolism of these substrates increases rapidly, but is quickly offset by a substantially higher increase in blood flow to that region, resulting in a brief oversupply of these substrates. This phenomenon is referred to as functional hyperemia, and forms the foundation of functional neuroimaging techniques such as functional Magnetic Resonance Imaging (fMRI), which captures a Blood Oxygen Level-Dependent (BOLD) signal. fMRI exploits these BOLD signals to infer brain activity, an approach that has revolutionized the research of brain function over the last 30 years. Due to the indirect nature of this measure, a deeper understanding of the connection between brain activity and hemodynamic changes — a neurovascular coupling (NVC) — is essential in order to fully interpret such functional imaging data. NVC connects the synaptic activity of neurons with local changes in cerebral blood flow, cerebral blood volume, and cerebral metabolism of oxygen, through a complex signaling network, consisting of multiple different brain cells which release a myriad of distinct vasoactive messengers with specific vascular targets. To aid with this complexity, mathematical modeling can provide vital help using methods and tools from the field of Systems Biology. Previous models of the NVC exist, conventionally describing quasi-phenomenological steps translating neuronal activity into hemodynamic changes. However, no mechanistic mathematical model that describe the known intracellular mechanisms or hypotheses underlying the NVC, and which can account for a wide variety of NVC related measurements, currently exists. Therefore, in this thesis, we apply a Systems Biology approach to develop such intracellular mechanisms based models using in vivo experimental data consisting of different NVC related measures in rodents, primates, and humans.Paper I investigates two widely discussed hypotheses describing the NVC: the metabolic feedback hypothesis, and the vasoactive feed-forward hypothesis. We illustrate through multiple model rejections that only a model describing a combination of the two hypotheses can capture the qualitative features of the BOLD signal, as measured in humans. This combined model can describe data used for training, as well as predict independent validation data not previously seen by the model before.Paper II extends this model to describe the negative BOLD response, where the blood oxygenation drops below basal levels, which is commonly observed in clinical and cognitive studies. The model explains the negative BOLD response as the result of neuronal inhibition, describing and adequately predicting experimental data from two different experiments.In Paper III, we develop a first model including the cell-specific contributions of GABAergic interneurons and pyramidal neurons to functional hyperemia, using data of optogenetic and sensory stimuli in rodents for both awake and anesthesia conditions. The model captures the effect of the anesthetic as purely acting on the neuronal level if a Michaelis-Menten expression is included, and it also correctly predicts data from experiments with different pharmacological inhibitors.Finally, in Paper IV, we extend the model in Paper III to describe and predict a majority of the relevant hemodynamic NVC measures using data from rodents, primates, and humans. The model suggests an explanation for observed bi-modal behaviors, and can be used to generate new insights regarding the underpinnings of other complicated observed behaviors. This model constitutes the most complete mechanistic model of the NVC to date.This new model-based understanding opens the door for a more integrative approach to the analysis of neuroimaging data, with potential applications in both basic science and in the clinic.
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| 7. |
- van Ettinger-Veenstra, Helene, 1982-
(författare)
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Mind your Language, All Right? Performance-dependent neural patterns of language
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main aim of this dissertation was to investigate the difference in neural language patternsrelated to language ability in healthy adults. The focus lies on unraveling the contributions of theright‐hemispheric homologues to Broca’s area in the inferior frontal gyrus (IFG) and Wernicke’s areain the posterior temporal and inferior parietal lobes. The functions of these regions are far from fullyunderstood at present. Two study populations consisting of healthy adults and a small group ofpeople with generalized epilepsy were investigated. Individual performance scores in tests oflanguage ability were correlated with brain activation obtained with functional magnetic resonanceimaging during semantic and word fluency tasks. Performance‐dependent differences were expectedin the left‐hemispheric Broca’s and Wernicke’s area and in their right‐hemispheric counterparts.PAPER I revealed a shift in laterality towards right‐hemispheric IFG and posterior temporal lobeactivation, related to high semantic performance. The whole‐brain analysis results of PAPER IIrevealed numerous candidate regions for language ability modulation. PAPER II also confirmed thefinding of PAPER I, by showing several performance‐dependent regions in the right‐hemispheric IFGand the posterior temporal lobe.In PAPER III, a new study population of healthy adults was tested.Again, the right posterior temporal lobe was related to high semantic performance. A decrease in lefthemisphericIFG activation could be linked to high word fluency ability. In addition, task difficultywas modulated. Increased task complexity showed to correlate positively with bilateral IFGactivation.Lastly, PAPER IV investigated anti‐correlated regions. These regions are commonly knownas the default mode network (DMN) and are normally suppressed during cognitive tasks. It wasfound that people with generalized epilepsy had an inadequate suppression of regions in the DMN,and showed poorer performance in a complex language test. The results point to neural adaptabilityin the IFG and temporal lobe. Decreased left‐lateralization of the IFG and increased rightlateralizationof the posterior temporal lobe are proposed as characteristics of individuals with highlanguage ability.
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| 8. |
- Engström, Annika
(författare)
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Lärande samspel för effektivitet : En studie av arbetsgrupper i ett mindre industriföretag
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- En viktig arena för samspel kring känsliga gränssnitt (marknad – konstruktion – produktion) i industrin är olika möten där arbetsgrupper kommer samman kring uppgifter. Syftet med avhandlingen är att bidra med kunskap om samspel som sker inom och mellan arbetsgrupper i deras hantering av uppgifter i mindre industriföretag (SME) och vilken betydelse samspelet har för lärande och effektivitet i verksamheten. Studien har närmare bestämt fokus på följande frågeställningar: 1. Vad karaktäriserar samspelet inom och mellan arbetsgrupper som det kommer till uttryck i olika möten? 2. Vilka faktorer underlättar respektive försvårar samspelet inom och mellan arbetsgrupper? 3. Vilka konsekvenser får olika typer av samspel för lärande och effektivitet i arbetsgrupper och i organisationer? Studien utgår från ett kritiskt realistiskt perspektiv på lärande i organisationer samt tidigare forskning om lärande, kommunikation och effektivitet i grupper och organisationer. Studien genomfördes under perioden 2008-2010 och var upplagd utifrån en kvalitativ och interaktiv forskningsansats. Datainsamlingen baserades på intervjuer, observationer av videofilmade möten samt frågeformulär. Analysen rör sig mellan två nivåer: samspel inom grupper samt mellan grupper på organisationsnivå. Samspelet inom och mellan grupper analyserades utifrån kontextuella faktorer och med fokus på i vad mån olika kommunikationsmönster kunde kopplas till olika typer av lärande och effektivitet i verksamheten. Ett rationalistiskt effektivitetsperspektiv utmanas till förmån för ett humanistiskt perspektiv där lärandet är en viktig aspekt. Tre slutsatser dras: Effektivitet grundar sig i att kommunikationsmönster och ledning anpassas efter det behov uppgiften för stunden kräver - utförande eller utveckling. Återkoppling och personliga länkar mellan grupper behöver översyn och ledningsrutiner för att underlätta samspelet. Diskrepanser (motsättningar, konflikter och störningar) som synliggörs i organisationen leder till utveckling. De som förblir i det dolda stör utförandet.
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| 9. |
- Fahlgren, Maria, 1966-
(författare)
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Designing for the integration of dynamic software environments in the teaching of mathematics
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis concerns the challenge of integrating dynamic software environments into the teaching of mathematics. It investigates particular aspects of the design of tasks which employ this type of computer-based system, with a focus on improvement, both of the tasks themselves and of the design process through which they are developed and refined.The thesis reports two research projects: a small initial one preceding a larger main project. The initial case study, involving two graduate students in mathematics, develops a task design model for geometrical locus problems. The main study constitutes the first iteration of a design-based study, conducted in collaboration with four upper-secondary school teachers and their classes. It seeks to identify task design characteristics that foster students’ mathematical reasoning and proficient use of software tools, and examines teachers’ organisation of ‘follow-up’ lessons.The findings concern three particular aspects: features of tasks and task environment relevant to developing a specific plan of action for a lesson; orchestration of a particular task environment to support the instrumental genesis of specific dynamic software tools; how to follow up students’ work on computer-based tasks in a whole-class discussion.
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| 10. |
- Georgiopoulos, Charalampos, 1984-
(författare)
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Imaging Studies of Olfaction in Health and Parkinsonism
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Olfactory loss is a common non-motor symptom of Parkinson’s disease (PD), often preceding the cardinal motor symptoms of the disease. The aim of this thesis was to: (a) evaluate whether olfactory examination can increase diagnostic accuracy, and (b) study the structural and functional neural basis of olfactory dysfunction in PD with different applications of Magnetic Resonance Imaging (MRI).Paper I was a comparison of the diagnostic accuracy between a simple smell identification test and DaTSCAN Single Photon Emission Computerized Tomography (SPECT), a nuclear medicine tomographic imaging technique that is commonly used in patients with suspected parkinsonism. The results indicate that smell test is inferior to DaTSCAN SPECT, but the combination of these two methods can lead to improved diagnostic accuracy.Paper II showed that diffusion MRI could detect discrete microstructural changes in the white matter of brain areas that participate in higher order olfactory neurotransmission, whereas MRI with Magnetization Transfer contrast could not.Paper III was a methodological study on how two different acquisition parameters can affect the activation pattern of olfactory brain areas, as observed with functional MRI (fMRI). The results indicate that brief olfactory stimulation and fast sampling rate should be preferred on olfactory fMRI studies.Paper IV used olfactory fMRI and resting-state fMRI in order to elucidate potentially altered activation patterns and functional connectivity within olfactory brain areas, between PD patients and healthy controls. Olfactory fMRI showed that olfactory impairment in PD is associated with significantly lower recruitment of the olfactory network. Resting-state fMRI did not detect any significant changes in the functional connectivity within the olfactory network of PD patients.In conclusion, the included studies provide evidence of: (a) disease-related structural and functional changes in olfactory brain areas, and (b) beneficial addition of olfactory tests in the clinical work-up of patients with parkinsonism.
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