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Simon, Rozalyn
Publications (10 of 19) Show all publications
Jönsson, D., Bergström, A., Forsell, C., Simon, R., Engström, M., Ynnerman, A. & Hotz, I. (2019). A Visual Environment for Hypothesis Formation and Reasoning in Studies with fMRI and Multivariate Clinical Data. In: Eurographics Workshop on Visual Computing for Biology and Medicine: . Paper presented at Eurographics Workshop on Visual Computing for Biology and Medicine.
Open this publication in new window or tab >>A Visual Environment for Hypothesis Formation and Reasoning in Studies with fMRI and Multivariate Clinical Data
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2019 (English)In: Eurographics Workshop on Visual Computing for Biology and Medicine, 2019Conference paper, Published paper (Refereed)
Abstract [en]

We present an interactive visual environment for linked analysis of brain imaging and clinical measurements. The environment is developed in an iterative participatory design process involving neuroscientists investigating the causes of brain-related complex diseases. The hypotheses formation process about correlations between active brain regions and physiological or psychological factors in studies with hundreds of subjects is a central part of the investigation. Observing the reasoning patterns during hypotheses formation, we concluded that while existing tools provide powerful analysis options, they lack effective interactive exploration, thus limiting the scientific scope and preventing extraction of knowledge from available data.Based on these observations, we designed methods that support neuroscientists by integrating their existing statistical analysis of multivariate subject data with interactive visual explorationto enable them to better understand differences between patient groups and the complex bidirectional interplay between clinical measurement and the brain. These exploration concepts enable neuroscientists, for the first time during their investigations, to interactively move between and reason about questions such as ‘which clinical measurements are correlated with a specific brain region?’ or ‘are there differences in brain activity between depressed young and old subjects?’. The environment uses parallel coordinates for effective overview and selection of subject groups, Welch's t-test to filter out brain regions with statistically significant differences, and multiple visualizations of Pearson correlations between brain regions and clinical parameters to facilitate correlation analysis. A qualitative user study was performed with three neuroscientists from different domains. The study shows that the developed environment supports simultaneous analysis of more parameters, provides rapid pathways to insights, and is an effective support tool for hypothesis formation.

National Category
Media and Communication Technology
Identifiers
urn:nbn:se:liu:diva-160856 (URN)10.2312/vcbm.20191232 (DOI)978-3-03868-081-9 (ISBN)
Conference
Eurographics Workshop on Visual Computing for Biology and Medicine
Projects
Seeing Organ Function
Funder
Knut and Alice Wallenberg Foundation, 2013-0076Swedish Research Council, 2015-05462ELLIIT - The Linköping‐Lund Initiative on IT and Mobile CommunicationsSwedish e‐Science Research Center
Available from: 2019-10-10 Created: 2019-10-10 Last updated: 2019-10-29
Simon, R., Engström, M., Icenhour, A., Larsson, M., Ström, M., Tillisch, K., . . . Walter, S. (2019). On Functional Connectivity and Symptom Relief After Gut-directed Hypnotherapy in Irritable Bowel Syndrome: A Preliminary Study [Letter to the editor]. JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY, 25(3), 478-479
Open this publication in new window or tab >>On Functional Connectivity and Symptom Relief After Gut-directed Hypnotherapy in Irritable Bowel Syndrome: A Preliminary Study
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2019 (English)In: JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY, ISSN 2093-0879, Vol. 25, no 3, p. 478-479Article in journal, Letter (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
Seoul, Korea: Korean Society of Neurogastroenterology and Motility, 2019
National Category
Clinical Medicine Basic Medicine
Identifiers
urn:nbn:se:liu:diva-159267 (URN)10.5056/jnm19069 (DOI)000476655500017 ()31327225 (PubMedID)
Note

Funding Agencies|Region Ostergotland; Bengt-Ihre Fond

Available from: 2019-08-07 Created: 2019-08-07 Last updated: 2019-11-15Bibliographically approved
Jönsson, D., Bergström, A., Algström, I., Simon, R., Engström, M., Walter, S. & Hotz, I. (2019). Visual Analysis for Understanding Irritable Bowel Syndrome. In: Paul Rea (Ed.), Biomedical Visualisation: (pp. 111-122). Cham: Springer
Open this publication in new window or tab >>Visual Analysis for Understanding Irritable Bowel Syndrome
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2019 (English)In: Biomedical Visualisation / [ed] Paul Rea, Cham: Springer, 2019, p. 111-122Chapter in book (Refereed)
Abstract [en]

The cause of irritable bowel syndrome (IBS), a chronic disorder characterized by abdominal pain and disturbed bowel habits, is largely unknown. It is believed to be related to physical properties in the gut, central mechanisms in the brain, psychological factors, or a combination of these. To understand the relationships within the gut-brain axis with respect to IBS, large numbers of measurements ranging from stool samples to functional magnetic resonance imaging are collected from patients with IBS and healthy controls. As such, IBS is a typical example in medical research where research turns into a big data analysis challenge. In this chapter we demonstrate the power of interactive visual data analysis and exploration to generate an environment for scientific reasoning and hypothesis formulation for data from multiple sources with different character. Three case studies are presented to show the utility of the presented work.

Place, publisher, year, edition, pages
Cham: Springer, 2019
Series
Advances in Experimental Medicine and Biology ; 1156
Keywords
Explorative data analytics, Visualization in medicine, Irritable bowel syndrome
National Category
Media and Communication Technology
Identifiers
urn:nbn:se:liu:diva-160859 (URN)10.1007/978-3-030-19385-0_8 (DOI)9783030193843 (ISBN)9783030193850 (ISBN)
Funder
Knut and Alice Wallenberg Foundation, 2013-0076Swedish Research Council, 2015-05462ELLIIT - The Linköping‐Lund Initiative on IT and Mobile CommunicationsSwedish e‐Science Research Center
Available from: 2019-10-10 Created: 2019-10-10 Last updated: 2019-10-11Bibliographically approved
Simon, R., Pihlsgård, J., Berglind, U., Söderfeldt, B. & Engström, M. (2017). Mantra meditation suppression of default mode beyond an active task: a pilot study. Journal of Cognitive Enhancement, 1(2), 219-227
Open this publication in new window or tab >>Mantra meditation suppression of default mode beyond an active task: a pilot study
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2017 (English)In: Journal of Cognitive Enhancement, ISSN 2509-3290, Vol. 1, no 2, p. 219-227Article in journal (Refereed) Published
Abstract [en]

Within the field of neuroimaging, the discovery of a constellation of brain regions silently active when we are “resting” has provided a new view into the elusive effects of meditative practice. This network, called the default mode network (DMN), has been shown by functional neuroimaging to be active when an individual is at rest. Meta-analyses of the fMRI neurocorrelates of meditation have shown that across diverse practices, the most common general effect appears to be modulation of regions within the DMN. The specific ...

Place, publisher, year, edition, pages
Springer, 2017
Keywords
Meditation, Mantra, Attention, Default mode network, Anterior cingulate cortex, Posterior cingulate cortex, Precuneus, Functional magnetic resonance imaging (fMRI), Deactivation, Kundalini yoga
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-139581 (URN)10.1007/s41465-017-0028-1 (DOI)
Available from: 2017-08-09 Created: 2017-08-09 Last updated: 2018-01-13Bibliographically approved
Walter, S. A., Forsgren, M., Lundengård, K., Simon, R., Torkildsen Nilsson, M., Söderfeldt, B., . . . Engström, M. (2016). Positive Allosteric Modulator of GABA Lowers BOLD Responses in the Cingulate Cortex. PLoS ONE, 11(3)
Open this publication in new window or tab >>Positive Allosteric Modulator of GABA Lowers BOLD Responses in the Cingulate Cortex
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3Article in journal (Refereed) Published
Abstract [en]

Knowledge about the neural underpinnings of the negative blood oxygen level dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) is still limited. We hypothesized that pharmacological GABAergic modulation attenuates BOLD responses, and that blood concentrations of a positive allosteric modulator of GABA correlate inversely with BOLD responses in the cingulate cortex. We investigated whether or not pure task-related negative BOLD responses were co-localized with pharmacologically modulated BOLD responses. Twenty healthy adults received either 5 mg diazepam or placebo in a double blind, randomized design. During fMRI the subjects performed a working memory task. Results showed that BOLD responses in the cingulate cortex were inversely correlated with diazepam blood concentrations; that is, the higher the blood diazepam concentration, the lower the BOLD response. This inverse correlation was most pronounced in the pregenual anterior cingulate cortex and the anterior mid-cingulate cortex. For subjects with diazepam plasma concentration > 0.1 mg/L we observed negative BOLD responses with respect to fixation baseline. There was minor overlap between cingulate regions with task-related negative BOLD responses and regions where the BOLD responses were inversely correlated with diazepam concentration. We interpret that the inverse correlation between the BOLD response and diazepam was caused by GABA-related neural inhibition. Thus, this study supports the hypothesis that GABA attenuates BOLD responses in fMRI. The minimal overlap between task-related negative BOLD responses and responses attenuated by diazepam suggests that these responses might be caused by different mechanisms.

Place, publisher, year, edition, pages
San Francisco, CA, United States: Public Library of Science, 2016
Keywords
quantitative magnetic resonance imaging; brain tissue modeling; myelin; edema; T-1 relaxation; T-2 relaxation; proton density
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-126192 (URN)10.1371/journal.pone.0148737 (DOI)000371434500011 ()26930498 (PubMedID)
Note

Funding agencies: Linkoping University; County Council of Ostergotland

Available from: 2016-03-18 Created: 2016-03-18 Last updated: 2018-01-10Bibliographically approved
Johansson, L. B. G., Simon, R., Bergström, G., Eriksson, M., Prokop, S., Mandenius, C.-F., . . . Nilsson, P. (2015). An azide functionalized oligothiophene ligand - A versatile tool for multimodal detection of disease associated protein aggregates. Biosensors & bioelectronics, 63, 204-211
Open this publication in new window or tab >>An azide functionalized oligothiophene ligand - A versatile tool for multimodal detection of disease associated protein aggregates
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2015 (English)In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 63, p. 204-211Article in journal (Refereed) Published
Abstract [en]

Ligands for identifying protein aggregates are of great interest as such deposits are the pathological hallmark of a wide range of severe diseases including Alzheimers and Parkinsons disease. Here we report the synthesis of an azide functionalized fluorescent pentameric oligothiophene that can be utilized as a ligand for multimodal detection of disease-associated protein aggregates. The azide functionalization allows for attachment of the ligand to a surface by conventional click chemistry without disturbing selective interaction with protein aggregates and the oligothiophene-aggregate interaction can be detected by fluorescence or surface plasmon resonance. In addition, a methodology where the oligothiophene ligand is employed as a capturing molecule selective for aggregated proteins in combination with an antibody detecting a distinct peptide/protein is also presented. We foresee that this methodology will offer the possibility to create a variety of multiplex sensing systems for sensitive and selective detection of protein aggregates, the pathological hallmarks of several neurodegenerative diseases.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Protein aggregates; Oligothiophene; Fluorescence; Surface plasmon resonance; Click chemistry
National Category
Chemical Sciences Biological Sciences
Identifiers
urn:nbn:se:liu:diva-112169 (URN)10.1016/j.bios.2014.07.042 (DOI)000343337000030 ()25089818 (PubMedID)
Note

Funding Agencies|Swedish Foundation for Strategic Research; Ehrling Persson Foundation; ERC Starting Independent Researcher grant (Project: MUMID)

Available from: 2014-11-18 Created: 2014-11-18 Last updated: 2019-01-22
Simon, R. & Engström, M. (2015). The default mode network as a biomarker for monitoring the therapeutic effects of meditation. Frontiers in Psychology, 6(776)
Open this publication in new window or tab >>The default mode network as a biomarker for monitoring the therapeutic effects of meditation
2015 (English)In: Frontiers in Psychology, ISSN 1664-1078, E-ISSN 1664-1078, Vol. 6, no 776Article in journal (Refereed) Published
Abstract [en]

The default mode network (DMN) is a group of anatomically separate regions in the brain found to have synchronized patterns of activation in functional magnetic resonance imaging (fMRI). Mentation associated with the DMN includes processes such as mind wandering, autobiographical memory, self-reflective thought, envisioning the future, and considering the perspective of others. Abnormalities in the DMN have been linked to symptom severity in a variety of mental disorders indicating that the DMN could be used as a biomarker for diagnosis. These correlations have also led to the use of DMN modulation as a biomarker for assessing pharmacological treatments. Concurrent research investigating the neural correlates of meditation, have associated DMN modulation with practice. Furthermore, meditative practice is increasingly understood to have a beneficial role in the treatment of mental disorders. Therefore we propose the use of DMN measures as a biomarker for monitoring the therapeutic effects of meditation practices in mental disorders. Recent findings support this perspective, and indicate the utility of DMN monitoring in understanding and developing meditative treatments for these debilitating conditions.

Place, publisher, year, edition, pages
Frontiers, 2015
Keywords
meditation; neuroimaging; default mode network; therapy; mindfulness; functional magnetic resonance imaging (fMRI); biomarker; DMN modulation
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-120283 (URN)10.3389/fpsyg.2015.00776 (DOI)000356672000001 ()26106351 (PubMedID)
Available from: 2015-07-24 Created: 2015-07-24 Last updated: 2017-12-04
Simon, R. (2014). Anionic oligothiophenes: Optical tools for multimodal fluorescent assignment of protein aggregates. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Anionic oligothiophenes: Optical tools for multimodal fluorescent assignment of protein aggregates
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Luminescent conjugated oligothiophenes (LCOs) represent a useful and interesting class of materials well known for their abilities as transducers for colorimetric and fluorometric reporting. Specifically, they have the ability to produce a conformation-dependent spectral signature reflective of changes in their local environment.  This physical property makes conjugated polymers an indispensible tool in the toolbox of fluorescent reporters used for distinguishing protein aggregates. Because fluorescence measurements provide a number of parameters for observing changes within a system (e.g., changes in intensity, wavelength, energy transfer, and emission lifetime), the coupling of such measurements with the unique fluorescence reporting capabilities of LCOs has been successful in a number of biological systems. The Nilsson group has demonstrated the use of both polydisperse and monodisperse conjugated polythiophenes for the purpose of amyloid protein aggregate detection both in vitro and ex vivo. My doctoral studies have included synthesis and the photophysical evaluation of pentameric substituted oligothiophenes for utilization as molecular probes for investigating the structure and conformation of amyloid protein aggregates. Through the synthesis of a library of pentameric probes with variations in side-chain substituents, we have studied the effects of pH, solvent, and viscosity on probe behavior and spectral shifts to elucidate the role of chemical structure on probe performance. Through a clearer understanding of the nature of LCOs and their individual chromic responses, we hope to provide researchers and clinicians additional tools for investigating and “bringing to light” the multifaceted nature of amyloids.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2014. p. 41
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1630
National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-111657 (URN)978-91-7519-205-5 (ISBN)
Public defence
2014-11-14, Visionen B-huset, Campus Valla, Linköpings universitet, Linköping, 09:15 (English)
Opponent
Supervisors
Available from: 2014-10-28 Created: 2014-10-28 Last updated: 2014-10-28Bibliographically approved
Magnusson, K., Simon, R., Sjölander, D., Sigurdson, C. J., Hammarström, P. & Nilsson, P. R. (2014). Multimodal fluorescene microscopy of prion strain specific PrP deposits stained by thiophene-bassed amyloid ligands. Prion, 8(4), 319-329
Open this publication in new window or tab >>Multimodal fluorescene microscopy of prion strain specific PrP deposits stained by thiophene-bassed amyloid ligands
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2014 (English)In: Prion, ISSN 1933-6896, E-ISSN 1933-690X, Vol. 8, no 4, p. 319-329Article in journal (Refereed) Published
Abstract [en]

The disease-associated prion protein (PrP) forms aggregates which vary in structural conformation yet share identical primary sequence. These variations in PrP conformation are believed to manifest in prion strains exhibiting distinctly different periods of disease incubation as well as regionally specific aggregate deposition within the brain. The anionic luminescent conjugated polythiophene (LCP), polythiophene acetic acid (PTAA) has previously been used to distinguish PrP deposits associated with distinct mouse adapted strains via distinct fluorescence emission profiles from the dye. Here we employed PTAA and 3 structurally related chemically defined luminescent conjugated oligothiophenes (LCOs) to stain brain tissue sections from mice inoculated with 2 distinct prion strains. Our results showed that in addition to emission spectra, excitation, and fluorescence lifetime imaging microscopy (FLIM) can fruitfully be assessed for optical distinction of PrP deposits associated with distinct prion strains. Our findings support the theory that alterations in LCP/LCO fluorescence are due to distinct conformational restriction of the thiophene backbone upon interaction with PrP aggregates associated with distinct prion strains. We foresee that LCP and LCO staining in combination with multimodal fluorescence microscopy might aid in detecting structural differences among discrete protein aggregates and in linking protein conformational features with disease phenotypes for a variety of neurodegenerative proteinopathies.

Place, publisher, year, edition, pages
Taylor & Francis, 2014
National Category
Chemical Sciences Natural Sciences
Identifiers
urn:nbn:se:liu:diva-106792 (URN)10.4161/pri.29239 (DOI)000348376000006 ()
Available from: 2014-05-23 Created: 2014-05-23 Last updated: 2018-04-25Bibliographically approved
Simon, R., Shirani, H., Åslund, K. O., Bäck, M., Haroutunian, V., Gandy, S. & Nilsson, P. R. (2014). Pentameric Thiophene-Based Ligands that Spectrally Discriminate Amyloid-b and Tau Aggregates Display Distinct Solvatochromism and Viscosity-Induced Spectral Shifts. Chemistry - A European Journal, 20(39), 12537-12543
Open this publication in new window or tab >>Pentameric Thiophene-Based Ligands that Spectrally Discriminate Amyloid-b and Tau Aggregates Display Distinct Solvatochromism and Viscosity-Induced Spectral Shifts
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2014 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 20, no 39, p. 12537-12543Article in journal (Refereed) Published
Abstract [en]

A wide range of neurodegenerative diseases are characterized by the deposition of multiple protein aggregates. Ligands for molecular characterization and discrimination of these pathological hallmarks are thus important for understanding their potential role in pathogenesis as well as for clinical diagnosis of the disease. In this regard, luminescent conjugated oligothiophenes (LCOs) have proven useful for spectral discrimination of amyloid-beta (Aβ) and tau neurofibrillary tangles (NFTs), two of the pathological hallmarks associated with Alzheimer’s disease. Herein, the solvatochromism of a library of anionic pentameric thiophene-based ligands, as well as their ability to spectrally discriminate Aβ and tau aggregates, were investigated. Overall, the results from this study identified distinct solvatochromic and viscosity-dependent behavior of thiophene-based ligands that can be applied as indices to direct the chemical design of improved LCOs for spectral separation of Aβ and tau aggregates in brain tissue sections. The results also suggest that the observed spectral transitions of the ligands are due to their ability to conform by induced fit to specific microenvironments within the binding interface of each particular protein aggregate. We foresee that these findings might aid in the chemical design of thiophene-based ligands that are increasingly selective for distinct disease-associated protein aggregates.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2014
Keywords
fluorescence; imaging agents; luminescent conjugated oligothiophenes; protein aggregates; solvatochromism
National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-111655 (URN)10.1002/chem.201402890 (DOI)000342626200026 ()25111601 (PubMedID)
Available from: 2014-10-28 Created: 2014-10-28 Last updated: 2017-12-05Bibliographically approved
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