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Under Pressure : Microcirculatory Dynamics and Capillary Refill Assessment in Provocation and Hemodynamic Stress
No full textBackground: All patients seeking emergency care or admitted to hospital need to be assessed and often monitored over a period. Vital functions are assessed at the bedside with technical equipment and clinical judgement. A commonly performed test, the capillary refill test (CRtest), is supposed to assess circulatory function. The test is performed by pressing the examiners’ index finger onto the patient skin, often for 5 seconds, then rapidly remove the finger and watch the skin regain its original colour as it was before the blanching pressure was applied. The time it takes is called the capillary refill time (CRtime) and less than 2-3 seconds have been recommended as normal, and times longer than that as a sign of circulatory compromise. The CRtest, despite widely used, has been questioned due to its subjectivity, and uncertainty of the test’s external validity. Objectives: The purpose of the study in Paper I was to investigate the repeatability of the CRtest, In Paper II, inter- and intra-observer reliability of the test was investigated, In Paper III, the outcome of the test in a blood loss shock model was investigated. The relationship between the changes in microcirculation to the CRtime in a blood loss shock model was investigated in Paper IV. Methods: In Paper I, CRtests were performed on study subjects on the sternum, the forehead and the finger, in series of 2 and 5 minutes apart. Objectively quantified CRtime, (qCRtime), was obtained through polarized reflectance imaging and a software program. In Paper II, CRtests were performed on pediatric patients in an emergency department and video filmed, and qRCtimes were obtained. The video films were shown to health care staff in a pediatric clinic, and the staff was asked to assess CRtime with naked eye. In Paper III, healthy volunteers were subjected to lower body negative pressure, (LBNP), in a blood loss shock model and CRtests performed and qCRtimes obtained. In Paper IV, the qCRtimes from the healthy study subjects in the LBNP model were compared with simultaneous changes in perfusion, measured as speed resolved perfusion reflecting flow in different vessels, and tissue oxygenation was also measured. Results: In Paper I, there were no statistical differences in qCRtime in a series of CRtests, regardless of when in the series the test was performed. In Paper II, naked eye assessment of CRtimes in children showed poor reproducibility in pediatric nurses and pediatricians, as well as in comparison to qCRtimes. In Paper III, in a blood loss shock model, qCRtimes shortened statistically significantly. In Paper IV, the shortened qCRtimes in Paper III, correlated to a decrease in perfusion and in tissue oxygenation as well as reduced flow in the smallest vessels. Conclusion: The CRtest shows good repeatability, but the test, as it is commonly performed in clinical practice with naked eye assessment, could be questioned for its lack of reproducibility. The CRtest also shows shortening of qCRtime in a blood loss shock model, contradictory to previously believed. The shortening of qCRtime is associated with changes in perfusion. Objective methods for quantification of CRtime with biooptical imaging techniques, as in these studies with polarized reflectance imaging, is valuable in the study of the CRtest and changes in perfusion in provocations and hemodynamic stress
Propagation of Opinions on Signed Graphs : Stability and Collective Wisdom
No full textThis thesis investigates how collective opinions evolve in social networks, focusing on two crucial, real-world factors: individual stubbornness and antagonistic inter-actions. Classical models of opinion dynamics typically assume a cooperative environment, where all individuals collaborate to reach an agreement, causing opinions to naturally draw closer to each other. However, many real-world scenarios—from political debates to online discussions—are defined by stubbornness, where individuals resist changing their stance, and by rivalry or distrust, which can actively push opinions apart. We address these phenomena through the framework of signed networks, which explicitly encodes antagonistic relationships. Unlike models that rely on structural balance—a clean division into two opposing camps—we adopt a repelling interaction mechanism, treating negative ties as additive repulsive forces. This approach offers a more flexible and realistic representation of complex, unbalanced social structures. The first contribution is a thorough analysis of the signed Friedkin–Johnsen (SFJ) model, which combines stubborn attachment to initial opinions with antagonistic interactions. This combination fundamentally changes system behavior: while the classical FJ model is always stable, the SFJ model can diverge. Therefore, we establish sufficient stability conditions and show that even when the model is stable, antagonism allows opinions to escape the the convex hull of the initial opinions, meaning that agents can adopt positions more extreme than anyone held at the start. The thesis then examines repeated discussions through a concatenated SFJ model, reflecting scenarios such as a series of negotiations. Here, stability in an individual discussion does not imply stability for the repeated process. Two distinct behaviors emerge when the individual discussion rounds are stable: opinions may temporarily move apart before reconverging to consensus inside the convex hull, or they may drift farther apart with each round, leading to divergence. The first case corresponds to a transient amplification, which is a known consequence of non-normal matrices and is often referred to as reactivity. Given these possibilities, we provide sufficient stability conditions for the concatenated SFJ model. This analysis is extended to explore the dynamics in more complex scenarios, including time-varying interaction structures and bipartite (two-camp) networks. Next, we address multidimensional opinion dynamics models, where agents debate several interdependent topics (for example, climate policy is inherently linked to economic policy). We show that a set of topics that would be stable if discussed independently can become unstable and diverge when discussed together. The analysis of repeated (concatenated) multidimensional interactions reveal diverse outcomes, from full or partial or bipartite consensus to divergence. Finally, we shift the focus from opinion convergence to the quality of resulting collective judgement and study the wisdom of crowds problem, i.e., analyze the conditions under which a group’s aggregated opinion becomes more accurate due to collective interactions. The improvement of wisdom depends entirely on the allocation of the social power vector—the centrality measure that each individual has in the group. In classical cooperative systems, the social power vector is positive, which confines the concentration region (the set of allocations that improve wisdom) to a simplex. In contrast, signed networks allow for negative social powers, which expands the concentration region beyond the simplex, to a hyperplane. The analysis on signed networks also leads to a critical insight: agreement does not imply accuracy. The group can become confidently wrong—converging with high certainty to a false truth. We also analyze the case where the agents’ initial opinions are correlated, and characterize the new concentration regions and their properties under these conditions
From analysis to findings: How do process mining analysts discover results?
No full textProcess mining involves analyzing event data from business process executions to uncover valuable insights. Although obtaining meaningful results is crucial for any process mining initiative, there is still little understanding of how process analysts derive these insights. In this paper, we fill this gap by characterizing findings of process mining analysis, the processes that lead to these findings, and the role of process mining expertise in guiding these processes. To this end, we leverage empirical data from a study with process mining analysts, including user interactions from process mining tools and inference steps from think-aloud protocols. Our empirical insights provide a comprehensive understanding of how analysts interact with process mining tools, highlighting approaches that lead to valuable findings. The results of our analysis lay the groundwork for the design of tools and visualizations that can support process analysts in their analysis and reasoning processes.Funding Agencies|Swiss National Science Foundation, Switzerland [2000 21_197032]</p
Results from a Swedish model-based analysis of the cost-effectiveness of AI-assisted digital mammography
No full textObjectiveTo evaluate the cost-effectiveness of AI-assisted digital mammography (AI-DM) compared to conventional biennial breast cancer digital mammography screening (cDM) with double reading of screening mammograms, and to investigate the change in cost-effectiveness based on four different sub-strategies of AI-DM.Materials and methodsA decision-analytic state-transition Markov model was used to analyse the decision of whether to use cDM or AI-DM in breast cancer screening. In this Markov model, one-year cycles were used, and the analysis was performed from a healthcare perspective with a lifetime horizon. In the model, we analysed 1000 hypothetical individuals attending mammography screenings assessed with AI-DM compared with 1000 hypothetical individuals assessed with cDM.ResultsThe total costs, including both screening-related costs and breast cancer-related costs, were &lt;euro&gt;3,468,967 and &lt;euro&gt;3,528,288 for AI-DM and cDM, respectively. AI-DM resulted in a cost saving of &lt;euro&gt;59,320 compared to cDM. Per 1000 individuals, AI-DM gained 10.8 quality-adjusted life years (QALYs) compared to cDM. Gained QALYs at a lower cost means that the AI-DM screening strategy was dominant compared to cDM. Break-even occurred at the second screening at age 42 years.ConclusionThis analysis showed that AI-assisted mammography for biennial breast cancer screening in a Swedish population of women aged 40-74 years is a cost-saving strategy compared to a conventional strategy using double human screen reading. Further clinical studies are needed, as scenario analyses showed that other strategies, more dependent on AI, are also cost-saving.Key PointsQuestionTo evaluate the cost-effectiveness of AI-DM in comparison to conventional biennial breast cDM screening.FindingsAI-DM is cost-effective, and the break-even point occurred at the second screening at age 42 years.Clinical relevanceThe implementation of AI is clearly cost-effective as it reduces the total cost for the healthcare system and simultaneously results in a gain in QALYs.Key PointsQuestionTo evaluate the cost-effectiveness of AI-DM in comparison to conventional biennial breast cDM screening.FindingsAI-DM is cost-effective, and the break-even point occurred at the second screening at age 42 years.Clinical relevanceThe implementation of AI is clearly cost-effective as it reduces the total cost for the healthcare system and simultaneously results in a gain in QALYs.Key PointsQuestionTo evaluate the cost-effectiveness of AI-DM in comparison to conventional biennial breast cDM screening.FindingsAI-DM is cost-effective, and the break-even point occurred at the second screening at age 42 years.Clinical relevanceThe implementation of AI is clearly cost-effective as it reduces the total cost for the healthcare system and simultaneously results in a gain in QALYs.Funding Agencies|Region Ostergotland and Linkoping University; Linkoping University</p
Mass Casualty Response in a Low-Resource Context : Challenges and Opportunities in Rwanda’s Mass Casualty Incident Response
No full textBackground In a mass casualty incident (MCI), sudden patient surges can overburden the health system and cause material and human resource limitations, as well as challenges in adapting systems and structures to the changed needs. This leads to an increased risk of avoidable patient morbidity and mortality. Low-resource countries bear the brunt of the global trauma and disaster burden, and, although not formally assessed, are more likely to be more frequently exposed to MCIs. The ability to adequately manage a sudden patient influx is called “surge capacity”, and can be measured using the 4S-Framework, which assesses the dimensions staff, stuff, systems, and space. However, current MCI research primarily originates from high-resource settings, with uncertain generalizability to low-resource settings. Objectives This thesis aimed to increase the understanding of MCI epidemiology in Rwanda, including at the incident level (event type, location, and timing) and at the patient level (injury patterns, patient outcomes, treatment provided) (studies I and IV). Secondly, this thesis aimed to assess the surge capacity to manage mass casualty incidents in Rwanda (studies II, III, and IV), and to develop a knowledge base for future surge capacity strengthening efforts. Materials and Methods This thesis employed multiple study designs and analysis methods. Study I was a pilot study for a new data collection method (the media review), based on a scoping review methodology using a database of news items. Study II was a qualitative study with semi-structured interviews with trauma care responders, which were analyzed using qualitative content analysis. Study III was a cross-sectional survey study of surge capacity perceptions with clinical department leaders at Rwanda’s leading trauma hospitals. Study IV was a retrospective study of routine prehospital data from emergency medical services (EMS). Studies I, III, and IV utilized descriptive statistics and parametric and non-parametric hypothesis tests for group comparisons. Study III additionally utilized analysis of one-way variance to assess intra-class correlation between respondents from the same hospital, and study IV utilized mixed-model analysis based on logistic and linear regression to evaluate the role of confounders in EMS MCI dispatch. Main results Studying MCIs and surge capacity in Rwanda is challenged by the lack of appropriate registers, the sudden onset of events, and resource limitations. In Rwanda, the media review demonstrated extensive reporting on the number of injured victims, on-site deaths, and the geographic location of the MCI, indicating that this method can be used as a complementary method to assess epidemiological patterns in MCIs in the absence of trauma registers. Rwanda has a high MCI exposure, with road-traffic accidents being the most frequent, but natural hazards appear to be on the rise. The majority of mass casualty incidents are small to moderately sized. MCIs are managed at all levels of the health system. Perceived surge capacity to manage low- to moderately sized mass casualty incidents is high in Rwanda. Trauma care responders attribute this to the wealth of real-life experience in MCI management and having a supportive team. The successful resolution of dilemmas during MCIs can lead to positive effects such as self-confidence, teambuilding, and personal or professional growth. Surge capacity is higher in tertiary “level 1” hospitals, located in urban areas. There are specific challenges in the Rwandan context, primarily resource and staff shortages, as well as limited EMS coverage in rural areas, that limit the generalizability of surge capacity paradigms from high-income countries. In formal assessment, surge capacity is limited in all 4S-domains metrics, including low levels of disaster plan uptake and limited awareness of existing plans. Formal surge capacity routines are also limited in the pre-hospital setting. Yet, Rwandan trauma care workers and emergency medical services utilize surge capacity strategies, including patient distribution to multiple facilities, on-site patient EMS treatment to reduce hospital referrals, and patient co-transportation. However, MCIs in rural areas are less likely to be managed by formal EMS. Viewed in the light of limited in-hospital surge capacity in rural areas, rural patients are likely at higher risk of poor outcomes in mass casualty incidents in Rwanda. Conclusions Despite limited formal disaster planning and routines, Rwanda appears to have developed a strong surge capacity to manage small- to moderately sized mass casualty incidents organically. However, there are limitations to surge capacity and areas for improvement in all 4S-domains, including staff, stuff, systems, and space, especially in rural areas. Trauma systems and emergency medical services need further development to ensure adequate surge capacity
Nocturnal gastro-oesophageal reflux and pulmonary abnormalities on chest CT in a general population: the Swedish CArdioPulmonary BioImage Study
No full textBackground Nocturnal gastro-oesophageal reflux (nGER) is common in people with respiratory diseases, but its association with pulmonary abnormalities is not known.Aim Investigate the association between nGER and pulmonary abnormalities on chest CT in an adult general population.Methods In total, 28 846 individuals from the general population aged 50-64 years completed questionnaires and underwent chest CT, in the Swedish CArdioPulmonary BioImage Study (www.scapis.org). Participants with nGER symptoms on &gt;= 1 night per week were defined as having nGER. Chest CT was evaluated for bronchial wall thickening, bronchiectasis, reticular abnormalities, honeycombing, cysts and ground glass opacities. Ever-smoking, current asthma, inflammatory bowel disease and autoimmune disease were defined as risk factors for pulmonary abnormalities. Analyses were adjusted for sex, age, body mass index, education level and study centre.Results The prevalence of nGER was 9.4%. Among participants with risk factors for pulmonary abnormalities (n=4004), having nGER was positively associated with bronchial wall thickening (adjusted OR (aOR) (95% CI): 1.25 (1.07 to 1.48)) and reticular abnormalities (aOR (95% CI): 1.51 (1.04 to 2.17)), but negatively associated with cysts (aOR (95% CI): 0.68 (0.48 to 0.97)). Among participants without risk factors for CT abnormalities (n=2555), nGER did not relate with pulmonary abnormalities.Conclusions In a middle-aged general population, nGER was not associated with pulmonary abnormalities on chest CT. However, in the presence of other risk factors for pulmonary abnormalities, nGER was associated with bronchial wall thickening and reticular abnormalities. Persons with nGER and risk factors for pulmonary abnormalities should, therefore, be evaluated for respiratory disease and treated appropriately.Funding Agencies|Swedish Heart and Lung Foundation [20210558, 20230610]; Knut and Alice Wallenberg Foundation; Swedish Research Council, VINNOVA (Sweden's Innovation Agency); University of Gothenburg; Sahlgrenska University Hospital, Lund University; Skane University Hospital, Linkoeping University; University Hospital, Karolinska Institutet; Karolinska University Hospital; Uppsala University and University Hospital; Umea University and University Hospital</p
Self-care: a well-known but yet elusive concept. A discussion of theories, concepts, interventions, and measurement
No full textGood self-care can improve survival, decrease health care costs, and improve quality of life of persons with cardiovascular illness. Health care professionals from different disciplines have a role in self-care support. Many definitions, theories, and measurement instruments exist addressing self-care and this plethora might be confusing to clinicians and researchers. In this discussion article, we will guide the reader to find the right terminology and discuss theoretical foundations and instruments available to frame patient care and research addressing the self-care of persons with cardiovascular illness
Student then, now and forward : Assessment narratives and student performativity in development and grade dialogues
No full textBetygs- och utvecklingssamtal är återkommande inslag i skolgången och är centrala för såväl skolans styrning som elevers syn på sig själva och sin förmåga. I avhandlingen studeras betygs- och utvecklingssamtal med elever som får betyg i årskurs 4–6. Syftet är att bidra med kunskap om det elever, lärare och vårdnadshavare gör genom samtalen och belysa betydelser detta kan ha för elever och skolan. Fokus är att förstå hur betygs- och utvecklingssamtal formar elever i ett skolsystem präglat av performativ styrning. Frågeställningarna rör hur berättelser formas och används, hur elever positioneras, hur nationell bedömningspolicy och lokala villkor kommer till uttryck samt hur föreställningar om elever konstrueras och förhandlas i relation till skolans bredare uppdrag. Avhandlingen utgår från en interaktionsorienterad narrativ ansats med perspektiv på positionering, policygörande och performativitet. Empirin består av ljudinspelningar från betygs- och utvecklingssamtal från fem skolor och analyseras genom en positioneringsanalys. I avhandlingen ingår tre artiklar som visar hur deltagarna (I) formar narrativ om elevers framtidsutsikter, (II) förhandlar förväntningar om elevers muntliga aktivitet och (III) gör betyg till en emotionell angelägenhet. Resultaten diskuteras genom begreppen individualisering och temporalitet som synliggör hur elevers förmåga, ansvar och utveckling förstås, förhandlas och värderas över tid. För att fördjupa diskussionen introduceras begreppen elevperformativitet och bedömningsberättelser. Elevperformativitet synliggör hur elever förväntas framställa sig själva som ansvarstagande och strategiska i linje med skolans mål och ideal. Bedömningsberättelser synliggör hur samtalets deltagare i samspel med bedömningspolicy formar berättelser om elever och deras prestationer. Avhandlingen visar hur betygs- och utvecklingssamtal fungerar som styrningsmekanismer som kan stabilisera, utmana eller omförhandla bedömningsberättelser om elever, som därigenom kan forma hur elever ser på sin förmåga och sig själva i skolan.Development and grade dialogues are recurring meetings, central for both educational governing and students’ perceptions of themselves and their abilities. This thesis examines development and grade dialogues with students who receive grades in Years 4–6. The aim is to contribute to knowledge about the actions of students, teachers and parents in these meetings and their implications for students and school. The focus is on how these dialogues shape students within a performativity-driven school system. The research questions address how narratives are formed, how students are positioned, how national assessment policies and local conditions interact, and how notions of students are constructed in relation to broader educational goals. The thesis uses an interaction-oriented narrative approach combined with perspectives on positioning, policy enactment and performativity. The data consists of audio recordings of development and grade dialogues in five schools, analysed through positioning analysis. The included articles show how participants (I) construct narratives about students’ paths, (II) negotiate expectations about students’ verbal participation and (III) construct grades as an emotional concern. The findings are discussed using the concepts of individualisation and temporality, illustrating how the students’ responsibility and progress are negotiated, understood and valued over time. The thesis also introduces the concepts of student performativity and assessment narratives. Student performativity refers to expectations for students to present themselves as responsible and strategic in line with school objectives. Assessment narratives demonstrate how participants, in interaction with assessment policies, form stories about students and their performance. The thesis demonstrates that development and grade dialogues function as mechanisms that can stabilise, challenge or negotiate assessment narratives, shaping how students understand themselves and their abilities in school.
Strain engineering of ScN thin films and its effect on optical, electrical, and thermoelectric properties
No full textScandium nitride (ScN) is a cubic NaCl-structured, degenerate, narrow-bandgap, n-type semiconductor that exhibits remarkable semiconducting, thermoelectric and plasmonic properties. However, its properties are sensitive to several types of defects, such as crystal defects, morphology, intentional or unintentional doping. For the purpose of reducing the deposition temperature of ScN, a series of films were deposited in the temperature range of 250–850 °C using a high-power impulse magnetron sputtering technique. While the stoichiometry and crystal structure remained unaffected in the sample series, the optical and electrical properties were affected when the temperature was decreased. Using in-depth XRD, optical and electrical characterizations, the effect of strain and dislocations on the semiconductor properties of ScN was evaluated. A reduction in the deposition temperature from 850 °C to 450 °C yielded a slow change in the electrical and optical properties, while a drastic change occurred for the films deposited below 450 °C. The main cause of the deterioration of the electrical transport properties (σ/10 000; n/100, and µ/100) was attributed to a high dislocation density (1011 cm−2) along with a rhombohedral distortion of the ScN cell (α: 90° → 88.6°), which was the main cause of the variation in the electrical transport. The presence of dislocations/crystal defects in the film generated defect states near the edges of the valence and conduction bands, softening the edges and impacting the electron density and mobility. The best thermoelectric properties of ScN were obtained when it was grown at 850 °C and were further modified and altered by strain engineering.Funding Agencies|Funding Agencies|Fundao para a Cincia e a Tecnologia [LA/P/0037/2020 (10.54499/LA/P/0037/2020), UID/50025/2025 (10.54499/UID/50025/2025)]; Vetenskapsrdet [2019-00191, 2021-03826]; Carl Tryggers Stiftelse fr Vetenskaplig Forskning [CTS14:310, CTS16:303, CTS20:272, CTS23:2746, CTS25:3972]; Agence Nationale de la Recherche [ANR-11-LABEX-0017-01, ANR-18-EURE-0010, ANR-21-EXES-0013]; Stiftelsen fr Strategisk Forskning [RIF14-0053]; Energimyndigheten [436061]; Knut och Alice Wallenbergs Stiftelse [KAW-2020.0196]</p
Olfaction and Memory Related Brain Connectivity : In Health and Parkinson’s Disease
No full textParkinson's Disease (PD) is among the most prevalent neurodegenerative diseases, primarily recognized for its motor symptoms. However, PD also encompasses debilitating non-motor symptoms (NMS), such as olfactory dysfunction and memory decline, both strongly associated with cognitive deficit. As the disease progresses, combined with long-term oral levodopa therapy, patients experience frequent and unpredictable motor fluctuations, marking the so called "complication phase". At this phase, device-aided Parkinson therapy (DAPT), which provides continuous dopaminergic stimulation, can effectively restore motor control. Despite its efficacy, some patients exhibit increased apathy and cognitive decline following DAPT, highlighting the need for new markers of cognitive decline in PD before DAPT selection. The objectives of this thesis are: (1) to explore dynamic functional connectivity (dFC) underlying olfaction and memory processes, with a particular emphasis on episodic odor memory, and (2) to map hippocampal dFC patterns during task-based and resting-state conditions and assess their implications for olfactory function and declarative memory in individuals with PD, awaiting evaluation for DAPT. By using independent component analysis and k-means clustering as main methodological approaches in this thesis, data analysis relied minimally on theoretical assumptions and was predominantly explorative and data-driven. Study I identified an overlapping neural network encompassing regions of the olfactory cortex engaged during passive smelling, odor encoding and odor recognition memory (ORM). A distinct ORM-related network involving the hippocampus exhibited delayed reactivity. Moreover, successful recognition of previously encoded odors was associated with neuronal suppression. Study II revealed that four hippocampal networks were sequentially activated during ORM. One network, incorporating regions of the dorsal attention network, showed shorter and less frequent activations, along with reduced asymmetric hippocampal activity (AHA), a pattern linked to impaired successful ORM in PD. Study III uncovered two resting-state hippocampal networks that distinguish individuals with PD from healthy controls. The first network, involving occipitoparietal regions and the cerebellum, exhibited shorter activations, whereas the second network, including regions of the central executive network, showed less frequent activations in PD. Individuals with PD who demonstrated reduced AHA within these networks, exhibited a general trend toward deficit in semantic odor memory and auditory-verbal memory. Taken together, ORM not only engages primary olfactory regions but also recruits higher-order cognitive areas such as the hippocampus. Individuals with PD exhibit shorter and less frequent activations of specific hippocampal networks, along with reduced AHA, both during episodic olfactory memory task and at rest. These hippocampal dFC patterns are associated with deficits in declarative odor memory and auditory-verbal memory, suggesting their potential as markers of cognitive decline in PD, particularly prior to the selection of DAPT. Nevertheless, longitudinal studies with larger, more diverse, and well-characterized cohorts are essential before these markers can be translated into clinical practice.Parkinsons sjukdom är en av de vanligaste neurodegenerativa sjukdomarna och är främst känd för sina motoriska symptom. Sjukdomen innefattar dock även inskränkande icke-motoriska symptom, som nedsatt luktsinne och minnesfunktion. Båda är nära relaterade till kognitiv svikt. I takt med sjukdomens progression och vid långtidsbehandling med oral levodopa, upplever patienter frekventa och oförutsägbara motoriska fluktuationer, vilket kännetecknar den så kallade "komplikationsfasen". Vid denna fas kan apparatassisterad behandling vid Parkinsons sjukdom, som ger kontinuerlig dopaminerg stimulering, effektivt återställa motorisk kontroll. Trots behandlingens effektivitet, uppvisar vissa patienter ökad apati och kognitiv försämring efter apparatassisterad behandling. Detta understryker behovet av nya markörer för kognitiv svikt vid Parkinsons sjukdom före valet av apparatassisterad behandling. Avhandlingens syften är: (1) att undersöka dynamisk funktionell konnektivitet (dFC) som ligger till grund för lukt- och minnesprocesser, med särskilt fokus på episodiskt luktminne och (2) att kartlägga hippocampala dFC-mönster under uppgiftsbaserade betingelser och vilotillstånd samt bedöma deras betydelse för luktfunktion och deklarativt minne hos individer med Parkinsons sjukdom inför utredning och val av apparatassisterad behandling. Användningen av oberoende komponentanalys och k-means klustring som centrala metodologiska angreppssätt innebar att dataanalysen i denna avhandling i begränsad grad baserades på teoretiska antaganden och i stället präglades av ett explorativt samt datadrivet förhållningssätt. Studie I identifierade ett överlappande neuralt nätverk som inkluderade områden i luktbarken vid passivt luktande, luktinlärning och luktigenkänning (ORM). Ett distinkt ORM-relaterat nätverk som inkluderade hippocampus uppvisade fördröjd reaktivitet. Utöver detta, framgångsrik luktigenkänning av tidigare inlärda dofter associerades med dämpad neuronal aktivitet. Studie II visade att fyra hippocampala nätverk aktiverades sekventiellt under ORM. Ett nätverk som inkluderade områden i det dorsala uppmärksamhetsnätverket uppvisade kortare och mindre frekventa aktiveringar samt reducerad asymmetrisk hippocampal aktivering (AHA), ett mönster kopplat till nedsatt ORM hos individer med Parkinsons sjukdom. Studie III identifierade två hippocampala vilonätverk som skilde individer med Parkinsons sjukdom från friska kontroller. Det första nätverket, omfattande områden i nackloben, hjässloben och lillhjärnan, uppvisade kortare aktiveringar, medan det andra nätverket, som inkluderade områden i det centrala exekutiva nätverket, uppvisade lägre aktiveringsfrekvens vid Parkinsons sjukdom. Individer med Parkinsons sjukdom som hade reducerad AHA inom dessa nätverk hade en generell tendens till nedsatt semantiskt luktminne och audioverbalt minne. Sammanfattningsvis engagerar ORM inte bara primära luktrelaterade områden utan även högre kognitiva områden som hippocampus. Individer med Parkinsons sjukdom uppvisar kortare och mindre frekventa aktiveringar i specifika hippocampala nätverk samt reducerad AHA, både under episodiska luktminnesuppgifter och i vila. De här hippocampala dFC-mönstren är associerade med nedsättningar i deklarativt luktminne och audioverbalt minne. Detta tyder på deras potential att fungera som markörer för kognitiv svikt vid Parkinsons sjukdom, särskilt före valet av apparatassisterad behandling. Longitudinella studier med större, mer heterogen och välkarakteriserade kohorter är dock nödvändiga innan dessa markörer är tillräckligt valida och reliabla för att implementeras kliniskt.Funding agencies: County Council of Östergötland, Lions Research Foundation against Endemic Diseases, Medical Research Council of Southeast Sweden (FORSS), The Swedish Parkinson Foundation, The Swedish Research Council</p