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  • 1.
    Abdollahi, Nyayesh
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Modifierad constraint-induced movement therapy förbättrar livskvalitet hos unga stroke-patienter2015Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 2.
    Abzhandadze, Tamar
    et al.
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Occupational Therapy and Physiotherapy, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Lundström, Erik
    Department of Neuroscience, Neurology, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden.
    Buvarp, Dongni
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Quinn, Terence J
    Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
    S Sunnerhagen, Katharina
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Neurocare, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Development of a short-form Swedish version of the Montreal Cognitive Assessment (s-MoCA-SWE): Protocol for a cross-sectional study2021In: BMJ Open, E-ISSN 2044-6055, Vol. 11, no 5, article id e049035Article in journal (Refereed)
    Abstract [en]

    Introduction: Short forms of the Montreal Cognitive Assessment (MoCA) have allowed quick cognitive screening. However, none of the available short forms has been created or validated in a Swedish sample of patients with stroke.

    The aim is to develop a short-form Swedish version of the MoCA (s-MoCA-SWE) in a sample of patients with acute and subacute stroke. The specific objectives are: (1) to identify a subgroup of MoCA items that have the potential to form the s-MoCA-SWE; (2) to determine the optimal cut-off value of s-MoCA-SWE for predicting cognitive impairment and (3) and to compare the psychometric properties of s-MoCA-SWE with those of previously developed MoCA short forms.

    Methods and analysis: This is a statistical analysis protocol for a cross-sectional study. The study sample will comprise patients from Väststroke, a local stroke registry from Gothenburg, Sweden and Efficacy oF Fluoxetine - a randomisEd Controlled Trial in Stroke (EFFECTS), a randomised controlled trial in Sweden. The s-MoCA-SWE will be developed by using exploratory factor analysis and the boosted regression tree algorithm. The cut-off value of s-MoCA-SWE for impaired cognition will be determined based on binary logistic regression analysis. The psychometric properties of s-MoCA-SWE will be compared with those of other MoCA short forms by using cross-tabulation and area under the receiving operating characteristic curve analyses.

    Ethics and dissemination: The Väststroke study has received ethical approval from the Regional Ethical Review Board in Gothenburg (346-16) and the Swedish Ethical Review Authority (amendment 2019-04299). The handling of data generated within the framework of quality registers does not require written informed consent from patients. The EFFECTS study has received ethical approval from the Stockholm Ethics Committee (2013/1265-31/2 on 30 September 2013). All participants provided written consent. Results will be published in an international, peer-reviewed journal, presented at conferences and communicated to clinical practitioners in local meetings and seminars.

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  • 3.
    Abzhandadze, Tamar
    et al.
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Occupational Therapy and Physiotherapy, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Lundström, Erik
    Department of Medical Sciences, Neurology, Akademiska Sjukhuset, Uppsala, Sweden.
    Buvarp, Dongni
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Quinn, Terence J.
    Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
    Sunnerhagen, Katharina S.
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Neurocare, Rehabilitation Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Development of a Swedish short version of the montreal cognitive assessment for cognitive screening in patients with stroke2023In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 55, article id jrm4442Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The primary objective was to develop a Swedish short version of the Montreal Cognitive Assessment (s-MoCA-SWE) for use  with patients with stroke. Secondary objectives were to identify an optimal cut-off value for the s-MoCA-SWE to screen for cognitive impairment and to compare its sensitivity with that of previously developed short forms of the Montreal Cognitive Assessment.

    DESIGN: Cross-sectional study.

    SUBJECTS/PATIENTS: Patients admitted to stroke and rehabilitation units in hospitals across Sweden.

    METHODS: Cognition was screened using the Montreal Cognitive Assessment. Working versions of the s-MoCA-SWE were developed using supervised and unsupervised algorithms.

    RESULTS: Data from 3,276 patients were analysed (40% female, mean age 71.5 years, 56% minor stroke at admission). The suggested s-MoCA-SWE comprised delayed recall, visuospatial/executive function, serial 7, fluency, and abstraction. The aggregated scores ranged from 0 to 16. A threshold for impaired cognition ≤ 12 had a sensitivity of 97.41 (95% confidence interval, 96.64-98.03) and positive predictive value of 90.30 (95% confidence interval 89.23-91.27). The s-MoCA-SWE had a higher absolute sensitivity than that of other short forms.

    CONCLUSION: The s-MoCA-SWE (threshold ≤ 12) can detect post-stroke cognitive issues. The high sensitivity makes it a potentially useful "rule-out" tool that may eliminate severe cognitive impairment in people with stoke.

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  • 4.
    Adey, Brett N.
    et al.
    Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom; Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom.
    Cooper-Knock, Johnathan
    Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom.
    Al Khleifat, Ahmad
    Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom.
    Fogh, Isabella
    Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom.
    van Damme, Philip
    Department of Neurosciences, KU Leuven-University of Leuven, Experimental Neurology, Leuven Brain Institute (LBI), Leuven, Belgium; VIB, Center for Brain and Disease Research, Leuven, Belgium; Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
    Corcia, Philippe
    UMR 1253, Université de Tours, Inserm, Tours, France; Centre de référence sur la SLA, CHU de Tours, Tours, France.
    Couratier, Philippe
    Centre de référence sur la SLA, CHRU de Limoges, Limoges, France; UMR 1094, Université de Limoges, Inserm, Limoges, France.
    Hardiman, Orla
    Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
    McLaughlin, Russell
    Complex Trait Genomics Laboratory, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.
    Gotkine, Marc
    Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; Agnes Ginges Center for Human Neurogenetics, Department of Neurology, Hadassah Medical Center, Jerusalem, Israel.
    Drory, Vivian
    Department of Neurology, Tel-Aviv Sourasky Medical Centre, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
    Silani, Vincenzo
    Department of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano, IRCCS, Milan, Italy; Department of Pathophysiology and Transplantation, “Dino Ferrari” Center, Università degli Studi di Milano, Milan, Italy.
    Ticozzi, Nicola
    Department of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano, IRCCS, Milan, Italy; Department of Pathophysiology and Transplantation, “Dino Ferrari” Center, Università degli Studi di Milano, Milan, Italy.
    Veldink, Jan H.
    Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands.
    van den Berg, Leonard H.
    Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands.
    de Carvalho, Mamede
    Instituto de Fisiologia, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
    Pinto, Susana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Instituto de Fisiologia, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
    Mora Pardina, Jesus S.
    ALS Unit, Hospital San Rafael, Madrid, Spain.
    Povedano Panades, Mónica
    Functional Unit of Amyotrophic Lateral Sclerosis (UFELA), Service of Neurology, Bellvitge University Hospital, Barcelona, L’Hospitalet de Llobregat, Spain.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Weber, Markus
    Neuromuscular Diseases Unit/ALS Clinic, St. Gallen, Switzerland.
    Başak, Nazli A.
    Koc University School of Medicine, Translational Medicine Research Center, NDAL, Istanbul, Turkey.
    Shaw, Christopher E.
    Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom.
    Shaw, Pamela J.
    Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom.
    Morrison, Karen E.
    School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, United Kingdom.
    Landers, John E.
    Department of Neurology, University of Massachusetts Medical School, MA, Worcester, United States.
    Glass, Jonathan D.
    Department of Neurology, Emory University School of Medicine, GA, Atlanta, United States.
    Vourc’h, Patrick
    Department of Neurology, University Hospitals Leuven, Leuven, Belgium; Service de Biochimie et Biologie molécularie, CHU de Tours, Tours, France.
    Dobson, Richard J. B.
    Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom; National Institute for Health Research Biomedical Research Centre and Dementia Unit at South London, Maudsley NHS Foundation Trust, King’s College London, London, United Kingdom; Institute of Health Informatics, University College London, London, United Kingdom; NIHR Biomedical Research Centre at University College London Hospitals, NHS Foundation Trust, London, United Kingdom.
    Breen, Gerome
    Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom.
    Al-Chalabi, Ammar
    Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom; King’s College Hospital, London, United Kingdom.
    Jones, Ashley R.
    Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom.
    Iacoangeli, Alfredo
    Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom; National Institute for Health Research Biomedical Research Centre and Dementia Unit at South London, Maudsley NHS Foundation Trust, King’s College London, London, United Kingdom.
    Large-scale analyses of CAV1 and CAV2 suggest their expression is higher in post-mortem ALS brain tissue and affects survival2023In: Frontiers in Cellular Neuroscience, E-ISSN 1662-5102, Vol. 17, article id 1112405Article in journal (Refereed)
    Abstract [en]

    Introduction: Caveolin-1 and Caveolin-2 (CAV1 and CAV2) are proteins associated with intercellular neurotrophic signalling. There is converging evidence that CAV1 and CAV2 (CAV1/2) genes have a role in amyotrophic lateral sclerosis (ALS). Disease-associated variants have been identified within CAV1/2 enhancers, which reduce gene expression and lead to disruption of membrane lipid rafts.

    Methods: Using large ALS whole-genome sequencing and post-mortem RNA sequencing datasets (5,987 and 365 tissue samples, respectively), and iPSC-derived motor neurons from 55 individuals, we investigated the role of CAV1/2 expression and enhancer variants in the ALS phenotype.

    Results: We report a differential expression analysis between ALS cases and controls for CAV1 and CAV2 genes across various post-mortem brain tissues and three independent datasets. CAV1 and CAV2 expression was consistently higher in ALS patients compared to controls, with significant results across the primary motor cortex, lateral motor cortex, and cerebellum. We also identify increased survival among carriers of CAV1/2 enhancer mutations compared to non-carriers within Project MinE and slower progression as measured by the ALSFRS. Carriers showed a median increase in survival of 345 days.

    Discussion: These results add to an increasing body of evidence linking CAV1 and CAV2 genes to ALS. We propose that carriers of CAV1/2 enhancer mutations may be conceptualised as an ALS subtype who present a less severe ALS phenotype with a longer survival duration and slower progression. Upregulation of CAV1/2 genes in ALS cases may indicate a causal pathway or a compensatory mechanism. Given prior research supporting the beneficial role of CAV1/2 expression in ALS patients, we consider a compensatory mechanism to better fit the available evidence, although further investigation into the biological pathways associated with CAV1/2 is needed to support this conclusion.

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  • 5.
    af Bjerkén, Sara
    Umeå University, Faculty of Medicine, Integrative Medical Biology.
    On dopamine neurons: nerve fiber outgrowth and L-DOPA effects2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Parkinson’s disease is a disorder mainly characterized by progressive degeneration of dopamine producing neurons in the substantia nigra of the midbrain. The most commonly used treatment strategy is to pharmacologically restore the lost function by the administration of the dopaminergic precursor L-DOPA. Another treatment strategy is to replace the degenerated neurons with immature fetal ventral mesencephalic tissue, or ultimately stem cell-derived tissue. Grafting trials have, however, revealed poor reinnervation capacity of the grafts, leaving much of the striata dopamine-denervated. An additional drawback is the upcoming of dyskinesia (involuntary movements), a phenomenon also observed during L-DOPA treatment of Parkinson’s disease patients. Attempts to characterize nerve fiber formation from dopamine neurons have demonstrated that the nerve fibers are formed in two morphologically diverse outgrowth patterns, one early outgrowth seen in the absence of astrocytes and one later appearing outgrowth seen in co-existence with astrocytes.

    The overall objective of this thesis has been to study the dopaminergic outgrowth including guidance of nerve fiber formation, and to look into the mechanisms of L-DOPA-induced dyskinesia. The first paper in this thesis characterizes the different outgrowth patterns described above and their relation to different glial cells. The study demonstrated the two different outgrowth patterns to be a general phenomenon, applying not only to dopamine neurons. Attempts of characterization revealed no difference of origin in terms of dopaminergic subpopulations, i.e. A9 or A10, between the outgrowth patterns. Furthermore, the “roller-drum” technique was found optimal for studying the dual outgrowth sequences.

    The second and the third paper also utilized the “roller-drum” technique in order to promote both patterns of neuronal fiber formation. The effects of glial cell line-derived neurotrophic factor (GDNF) on the formation of dopamine nerve fibers, was investigated. Cultures prepared from gdnf knockout mice revealed that dopaminergic neurons survive and form nerve fiber outgrowth in the absence of GDNF. The dopaminergic nerve fibers exhibited an outgrowth pattern consistent with that previous observed in rat. GDNF was found to exert effect on the glial-associated outgrowth whereas the non-glial-associated was not affected. Astrocytic proliferation was inhibited using cytosine β-D-arabinofuranoside, resulting in reduced glial-associated outgrowth. The non-glial-associated dopaminergic outgrowth was on the other hand promoted, and was retained over longer time in culture. Furthermore, the non-glial-associated nerve fibers were found to target the fetal frontal cortex. Different developmental stages were shown to promote and affect the outgrowths differently. Taken together, these data indicate and state the importance of astrocytes and growth factors for neuronal nerve fiber formation and guidance. It also stresses the importance of fetal donor age at the time for transplantation.

    The fourth and fifth studies focus on L-DOPA dynamics and utilize in vivo chronoamperometry. In study four, 6-OHDA dopamine-depleted rats were exposed to chronic L-DOPA treatment and then rated as dyskinetic or non-dyskinetic. The electrochemical recordings demonstrated reduced KCl-evoked release in the intact striatum after chronic L-DOPA treatment. Time for maximal dopamine concentration after L-DOPA administration was found to be shorter in dyskinetic animals than in non-dyskinetic animals. The serotonergic nerve fiber content in the striatum was evaluated and brains from dyskinetic animals were found to exhibit significantly higher nerve fiber density compared to non-dyskinetic animals. Furthermore, the mechanisms behind the conversion of L-DOPA to dopamine in 6-OHDA dopamine-depleted rats were studied. Local administration of L-DOPA in the striatum increased the KCl-evoked dopamine release in the intact striatum. Acute application of L-DOPA resulted sometimes in a rapid conversion to dopamine, probably without vesicle packaging. This type of direct conversion is presumably occurring in non-neuronal tissue. Furthermore, KCl-evoked dopamine releases were present upon local application of L-DOPA in the dopamine-depleted striatum, suggesting that the conversion to dopamine took place elsewhere, than in dopaminergic nerve fibers. In conclusion, these studies state the importance of astrocytes for neuronal nerve fiber formation and elucidate the complexity of L-DOPA conversion in the brain.

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  • 6.
    af Bjerkén, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stenmark Persson, Rasmus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Barkander, Anna
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Karalija, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Pelegrina-Hidalgo, Noelia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Gerhardt, Greg A
    Virel, Ana
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Strömberg, Ingrid
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Noradrenaline is crucial for the substantia nigra dopaminergic cell maintenance2019In: Neurochemistry International, ISSN 0197-0186, E-ISSN 1872-9754, Vol. 131, article id 104551Article in journal (Refereed)
    Abstract [en]

    In Parkinson's disease, degeneration of substantia nigra dopaminergic neurons is accompanied by damage on other neuronal systems. A severe denervation is for example seen in the locus coerulean noradrenergic system. Little is known about the relation between noradrenergic and dopaminergic degeneration, and the effects of noradrenergic denervation on the function of the dopaminergic neurons of substantia nigra are not fully understood. In this study, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) was injected in rats, whereafter behavior, striatal KCl-evoked dopamine and glutamate releases, and immunohistochemistry were monitored at 3 days, 3 months, and 6 months. Quantification of dopamine-beta-hydroxylase-immunoreactive nerve fiber density in the cortex revealed a tendency towards nerve fiber regeneration at 6 months. To sustain a stable noradrenergic denervation throughout the experimental timeline, the animals in the 6-month time point received an additional DSP4 injection (2 months after the first injection). Behavioral examinations utilizing rotarod revealed that DSP4 reduced the time spent on the rotarod at 3 but not at 6 months. KCl-evoked dopamine release was significantly increased at 3 days and 3 months, while the concentrations were normalized at 6 months. DSP4 treatment prolonged both time for onset and reuptake of dopamine release over time. The dopamine degeneration was confirmed by unbiased stereology, demonstrating significant loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra. Furthermore, striatal glutamate release was decreased after DSP4. In regards of neuroinflammation, reactive microglia were found over the substantia nigra after DSP4 treatment. In conclusion, long-term noradrenergic denervation reduces the number of dopaminergic neurons in the substantia nigra and affects the functionality of the nigrostriatal system. Thus, locus coeruleus is important for maintenance of nigral dopaminergic neurons.

  • 7. Agostinelli, Emilio
    et al.
    Gonzalez-Velandia, Kevin Y.
    Hernandez-Clavijo, Andres
    Maurya, Devendra Kumar
    Neurobiology Group, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy.
    Xerxa, Elena
    Lewin, Gary R.
    Dibattista, Michele
    Menini, Anna
    Pifferi, Simone
    A Role for STOML3 in Olfactory Sensory Transduction2021In: eNeuro, E-ISSN 2373-2822, Vol. 8, no 2, article id ENEURO.0565-20.2021Article in journal (Refereed)
    Abstract [en]

    Stomatin-like protein-3 (STOML3) is an integral membrane protein expressed in the cilia of olfactory sensory neurons (OSNs), but its functional role in this cell type has never been addressed. STOML3 is also expressed in dorsal root ganglia neurons, where it has been shown to be required for normal touch sensation. Here, we extended previous results indicating that STOML3 is mainly expressed in the knob and proximal cilia of OSNs. We additionally showed that mice lacking STOML3 have a morphologically normal olfactory epithelium. Because of its presence in the cilia, together with known olfactory transduction components, we hypothesized that STOML3 could be involved in modulating odorant responses in OSNs. To investigate the functional role of STOML3, we performed loose patch recordings from wild-type (WT) and Stoml3 knock-out (KO) OSNs. We found that spontaneous mean firing activity was lower with additional shift in interspike intervals (ISIs) distributions in Stoml3 KOs compared with WT neurons. Moreover, the firing activity in response to stimuli was reduced both in spike number and duration in neurons lacking STOML3 compared with WT neurons. Control experiments suggested that the primary deficit in neurons lacking STOML3 was at the level of transduction and not at the level of action potential generation. We conclude that STOML3 has a physiological role in olfaction, being required for normal sensory encoding by OSNs.

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  • 8. Ahman, Hanna Bozkurt
    et al.
    Giedraitis, Vilmantas
    Cedervall, Ylva
    Lennhed, Bjorn
    Berglund, Lars
    McKee, Kevin
    Kilander, Lena
    Rosendahl, Erik
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Physiotherapy.
    Ingelsson, Martin
    Aberg, Anna Cristina
    Dual-Task Performance and Neurodegeneration: Correlations Between Timed Up-and-Go Dual-Task Test Outcomes and Alzheimer's Disease Cerebrospinal Fluid Biomarkers2019In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 71, p. S75-S83Article in journal (Refereed)
    Abstract [en]

    Background: Tools to identify individuals at preclinical stages of dementia disorders are needed to enable early interventions. Alterations in dual-task performance have been detected early in progressive neurodegenerative disorders. Hence, dual-task testing may have the potential to screen for cognitive impairment caused by neurodegeneration. Exploring correlations between dual-task performance and biomarkers of neurodegeneration is therefore of interest.

    Objective: To investigate correlations between Timed Up-and-Go dual-task (TUGdt) outcomes and Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid-beta 42 (A beta(42)), total tau (t-tau), and phosphorylated tau (p-tau).

    Methods: This cross-sectional cohort study included 90 participants (age range 49-84 years) undergoing memory assessment, who were subsequently diagnosed with AD, other dementia disorders, mild cognitive impairment, or subjective cognitive impairment. TUG combined with "Naming Animals" (TUGdt NA) and "Months Backwards" (TUGdt MB), respectively, were used to assess dual-task performance. The number of correct words and time taken to complete the tests were measured. The CSF biomarkers were analysed by ELISA. Spearman's rank correlation was used for analyses between TUGdt outcomes (TUGdt NA and TUGdt MB), and CSF biomarkers, adjusted for age, gender, and educational level.

    Results: The number of correct words, as well as the number of correct words/10 s during TUGdt NA correlated negatively to CSF t-tau and p-tau. No correlations were found between any time scores and CSF biomarkers.

    Conclusion: The correlations between TUGdt NA and t-tau and p-tau may indicate that neurodegeneration affects dual-task performance. Longitudinal studies are needed to further explore dual-task testing in screening for cognitive impairment due to neurodegeneration.

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  • 9.
    Akimoto, Chizuru
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Birve, Anna
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Backlund, Irene
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Andersson, Jörgen
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Nilsson, Ann-Charloth
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Alstermark, Helena
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    No GGGGCC-hexanucleotide repeat expansion in C9ORF72 in parkinsonism patients in Sweden2013In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, Vol. 14, no 1, p. 26-29Article in journal (Refereed)
    Abstract [en]

    An intronic GGGGCC-hexanucleotide repeat expansion in C9ORF72 was recently identified as a major cause of amyotrophic lateral sclerosis and frontotemporal dementia. Some amyotrophic lateral sclerosis patients have signs of parkinsonism, and many parkinsonism patients develop dementia. In this study we examined if the hexanucleotide repeat expansion was present in parkinsonism patients, to clarify if there could be a relationship between the repeat expansion and disease. We studied the size of the hexanucleotide repeat expansion in a well defined population-based cohort of 135 Parkinson's disease patients and 39 patients with atypical parkinsonism and compared with 645 Swedish control subjects. We found no correlation between Parkinson's disease or atypical parkinsonism and the size of the GGGGCC repeat expansion in C9ORF72. In conclusion, this GGGGCC-repeat expansion in C9ORF72 is not a cause of parkinsonism in the Swedish population.

  • 10. Al Nimer, Faiez
    et al.
    Elliott, Christina
    Bergman, Joakim
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Khademi, Mohsen
    Dring, Ann M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Aeinehband, Shahin
    Bergenheim, Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Christensen, Jeppe Romme
    Sellebjerg, Finn
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Linington, Christopher
    Olsson, Tomas
    Piehl, Fredrik
    Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination2016In: Neurology: Neuroimmunology & Neuroinflammation, E-ISSN 2332-7812, Vol. 3, no 1, article id e191Article in journal (Refereed)
    Abstract [en]

    Objective: We aimed to examine the regulation of lipocalin-2 (LCN2) in multiple sclerosis (MS) and its potential functional relevance with regard to myelination and neurodegeneration. Methods: We determined LCN2 levels in 3 different studies: (1) in CSF and plasma from a case-control study comparing patients with MS (n = 147) with controls (n = 50) and patients with relapsing-remitting MS (n = 75) with patients with progressive MS (n = 72); (2) in CSF and brain tissue microdialysates from a case series of 7 patients with progressive MS; and (3) in CSF at baseline and 60 weeks after natalizumab treatment in a cohort study of 17 patients with progressive MS. Correlation to neurofilament light, a marker of neuroaxonal injury, was tested. The effect of LCN2 on myelination and neurodegeneration was studied in a rat in vitro neuroglial cell coculture model. Results: Intrathecal production of LCN2 was increased predominantly in patients with progressive MS (p < 0.005 vs relapsing-remitting MS) and displayed a positive correlation to neurofilament light (p = 0.005). Levels of LCN2 in brain microdialysates were severalfold higher than in the CSF, suggesting local production in progressive MS. Treatment with natalizumab in progressive MS reduced LCN2 levels an average of 13% (p < 0.0001). LCN2 was found to inhibit remyelination in a dose-dependent manner in vitro. Conclusions: LCN2 production is predominantly increased in progressive MS. Although this moderate increase does not support the use of LCN2 as a biomarker, the correlation to neurofilament light and the inhibitory effect on remyelination suggest that LCN2 might contribute to neurodegeneration through myelination-dependent pathways.

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  • 11. Al Nimer, Faiez
    et al.
    Thelin, Eric
    Nystrom, Harriet
    Dring, Ann M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Piehl, Fredrik
    Nelson, David W.
    Bellander, Bo-Michael
    Comparative Assessment of the Prognostic Value of Biomarkers in Traumatic Brain Injury Reveals an Independent Role for Serum Levels of Neurofilament Light2015In: PLOS ONE, E-ISSN 1932-6203, Vol. 10, no 7, article id e0132177Article in journal (Refereed)
    Abstract [en]

    Traumatic brain injury (TBI) is a common cause of death and disability, worldwide. Early determination of injury severity is essential to improve care. Neurofilament light (NF-L) has been introduced as a marker of neuroaxonal injury in neuroinflammatory/-degenerative diseases. In this study we determined the predictive power of serum (s-) and cerebrospinal fluid (CSF-) NF-L levels towards outcome, and explored their potential correlation to diffuse axonal injury (DAI). A total of 182 patients suffering from TBI admitted to the neurointensive care unit at a level 1 trauma center were included. S-NF-L levels were acquired, together with S100B and neuron-specific enolase (NSE). CSF-NF-L was measured in a subcohort (n = 84) with ventriculostomies. Clinical and neuro-radiological parameters, including computerized tomography (CT) and magnetic resonance imaging, were included in the analyses. Outcome was assessed 6 to 12 months after injury using the Glasgow Outcome Score (1-5). In univariate proportional odds analyses mean s-NF-L, -S100B and -NSE levels presented a pseudo-R-2 Nagelkerke of 0.062, 0.214 and 0.074 in correlation to outcome, respectively. In a multivariate analysis, in addition to a model including core parameters (pseudo-R-2 0.33 towards outcome; Age, Glasgow Coma Scale, pupil response, Stockholm CT score, abbreviated injury severity score, S100B), S-NF-L yielded an extra 0.023 pseudo-R-2 and a significantly better model (p = 0.006) No correlation between DAI or CT assessed-intracranial damage and NF-L was found. Our study thus demonstrates that SNF-L correlates to TBI outcome, even if used in models with S100B, indicating an independent contribution to the prediction, perhaps by reflecting different pathophysiological processes, not possible to monitor using conventional neuroradiology. Although we did not find a predictive value of NF-L for DAI, this cannot be completely excluded. We suggest further

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  • 12.
    Alaerts, Maaike
    et al.
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UA), Belgium.
    Venken, Tine
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UA), Belgium.
    Lenaerts, An-Sofie
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UA), Belgium.
    De Zutter, Sonia
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UA), Belgium.
    Norrback, Karl-Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Del-Favero, Jurgen
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UA), Belgium.
    Lack of association of an insertion/deletion polymorphism in the G protein-coupled receptor 50 with bipolar disorder in a Northern Swedish population2006In: Psychiatric Genetics, ISSN 0955-8829, E-ISSN 1473-5873, Vol. 16, no 6, p. 235-236Article in journal (Refereed)
    Abstract [en]

    GPR50 is a G protein-coupled receptor, located on Xq28 and related to the melatonin receptor family. It is suggested as a functional and positional candidate gene for bipolar disorder (BP). Recently an insertion/deletion polymorphism in GPR50, Delta502-505, was found to be associated with BP in a Scottish association sample (P=0.007). When the analysis was restricted to female subjects, the association increased in significance (P=0.00023). We attempted to replicate this finding in a Northern Swedish association sample, but no significant association was detected (P=0.7, women only: P=0.65).

  • 13.
    Alakpa, Enateri V.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Bahrd, Anton
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Wiklund, Krister
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Andersson, Magnus
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Novikov, Lev N.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Ljungberg, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Kelk, Peyman
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Bioprinted schwann and mesenchymal stem cell co-cultures for enhanced spatial control of neurite outgrowth2023In: Gels, E-ISSN 2310-2861, Vol. 9, no 3, article id 172Article in journal (Refereed)
    Abstract [en]

    Bioprinting nerve conduits supplemented with glial or stem cells is a promising approach to promote axonal regeneration in the injured nervous system. In this study, we examined the effects of different compositions of bioprinted fibrin hydrogels supplemented with Schwann cells and mesenchymal stem cells (MSCs) on cell viability, production of neurotrophic factors, and neurite outgrowth from adult sensory neurons. To reduce cell damage during bioprinting, we analyzed and optimized the shear stress magnitude and exposure time. The results demonstrated that fibrin hydrogel made from 9 mg/mL of fibrinogen and 50IE/mL of thrombin maintained the gel&rsquo;s highest stability and cell viability. Gene transcription levels for neurotrophic factors were significantly higher in cultures containing Schwann cells. However, the amount of the secreted neurotrophic factors was similar in all co-cultures with the different ratios of Schwann cells and MSCs. By testing various co-culture combinations, we found that the number of Schwann cells can feasibly be reduced by half and still stimulate guided neurite outgrowth in a 3D-printed fibrin matrix. This study demonstrates that bioprinting can be used to develop nerve conduits with optimized cell compositions to guide axonal regeneration.

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  • 14. Allocca, Giancarlo
    et al.
    Ma, Sherie
    Martelli, Davide
    Cerri, Matteo
    Del Vecchio, Flavia
    Bastianini, Stefano
    Zoccoli, Giovanna
    Amici, Roberto
    Morairty, Stephen R.
    Aulsebrook, Anne E.
    Blackburn, Shaun
    Lesku, John A.
    Rattenborg, Niels C.
    Vyssotski, Alexei L.
    Wams, Emma
    Porcherer, Kate
    Wulff, Katharina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Centre for Molecular Medicine (WCMM), Umeå University, Sweden.
    Foster, Russell
    Chan, Julia K. M.
    Nicholas, Christian L.
    Freestone, Dean R.
    Johnston, Leigh A.
    Gundlachla, Andrew L.
    Validation of 'Somnivore', a Machine Learning Algorithm for Automated Scoring and Analysis of Polysomnography Data2019In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 13, article id 207Article in journal (Refereed)
    Abstract [en]

    Manual scoring of polysomnography data is labor-intensive and time-consuming, and most existing software does not account for subjective differences and user variability. Therefore, we evaluated a supervised machine learning algorithm, Somnivore (TM), for automated wake-sleep stage classification. We designed an algorithm that extracts features from various input channels, following a brief session of manual scoring, and provides automated wake-sleep stage classification for each recording. For algorithm validation, polysomnography data was obtained from independent laboratories, and include normal, cognitively-impaired, and alcohol-treated human subjects (total n = 52), narcoleptic mice and drug-treated rats (total n = 56), and pigeons (n = 5). Training and testing sets for validation were previously scored manually by 1-2 trained sleep technologists from each laboratory. F-measure was used to assess precision and sensitivity for statistical analysis of classifier output and human scorer agreement. The algorithm gave high concordance with manual visual scoring across all human data (wake 0.91 +/- 0.01; N1 0.57 +/- 0.01; N2 0.81 +/- 0.01; N3 0.86 +/- 0.01; REM 0.87 +/- 0.01), which was comparable to manual inter-scorer agreement on all stages. Similarly, high concordance was observed across all rodent (wake 0.95 +/- 0.01; NREM 0.94 +/- 0.01; REM 0.91 +/- 0.01) and pigeon (wake 0.96 +/- 0.006; NREM 0.97 +/- 0.01; REM 0.86 +/- 0.02) data. Effects of classifier learning from single signal inputs, simple stage reclassification, automated removal of transition epochs, and training set size were also examined. In summary, we have developed a polysomnography analysis program for automated sleep-stage classification of data from diverse species. Somnivore enables flexible, accurate, and high-throughput analysis of experimental and clinical sleep studies.

  • 15. Alping, P.
    et al.
    Islam-Jakobsson, Protik
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Novakova, L.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Björck, A.
    Axelsson, M.
    Malmeström, C.
    Fink, K.
    Frisell, T.
    Lycke, J.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Piehl, F.
    Superior efficacy and tolerability of rituximab as compared to fingolimod for MS patients switching from natalizumab due to positive JC virus serology2015In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, no 11, p. 555-555, article id P1079Article in journal (Other academic)
  • 16. Alping, P.
    et al.
    Svenningsson, A.
    Clinical Science Danderyd´s Hospital, Karolinska Institutet, Stockholm.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Burman, J.
    Dahle, C.
    Fink, K.
    Hillert, J.
    Lycke, J.
    Landtblom, A. -M
    Martin, C.
    Nilsson, P.
    Walentin, F.
    Olsson, T.
    Frisell, T.
    Piehl, F.
    Rituximab in multiple sclerosis: data from the swedish MS registry2016In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, p. 49-49Article in journal (Refereed)
  • 17.
    Alstermark, Bror
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Hultborn, Hans
    University of Copenhagen Department of Neuroscience and Pharmacology Copenhagen N. Denmark.
    Jankowska, E.
    Sahlgrenska Academy, University of Gothenburg Department of Physiology Gothenburg Sweden.
    Pettersson, L-G.
    Sahlgrenska Academy, University of Gothenburg Department of Physiology Gothenburg Sweden.
    Anders Lundberg (1920-2009)2010In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 200, no 3-4, p. 193-195Article in journal (Other (popular science, discussion, etc.))
    Abstract [en]

    Anders Lundberg was one of the founding editorial board members for EBR when it began its life in 1976 under the editorship of John Eccles. He was also one of the most prolific contributors to the journal with a total of 49 papers, including a series of 16 on the topic of "integration in descending motor pathways controlling the forelimb in the cat". He continued as an editor of the journal until volume 16 when he persuaded his younger colleague Hans Hultborn to take his place. Hans is one of the authors of the obituary. –John Rothwell

  • 18.
    Alstermark, Bror
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Isa, Tadashi
    Natl Inst Physiol Sci, Dept Dev Physiol, Okazaki, Aichi 4448585, Japan.
    Circuits for skilled reaching and grasping2012In: Annual Review of Neuroscience, Palo alto: ANNUAL REVIEWS, 2012, p. 559-578Chapter in book (Refereed)
    Abstract [en]

    From an evolutionary perspective, it is clear that basic motor functions such as locomotion and posture are largely controlled by neural circuitries residing in the spinal cord and brain-stem. The control of voluntary movements such as skillful reaching and grasping is generally considered to be governed by neural circuitries in the motor cortex that connect directly to motoneurons via the corticomotoneuronal (CM) pathway. The CM pathway may act together with several brain-stem systems that also act directly with motoneurons. This simple view was challenged by work in the cat, which lacks the direct CM system, showing that the motor commands for reaching and grasping could be mediated via spinal interneurons with input from the motor-cortex and brain-stem systems. It was further demonstrated that the spinal interneurons mediating the descending commands for reaching and grasping constitute separate and distinct populations from those involved in locomotion and posture. The aim of this review is to describe populations of spinal interneurons that are involved in the control of skilled reaching and grasping in the cat, monkey, and human.

  • 19.
    Alstermark, Bror
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Pettersson, Lars-Gunnar
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg Gothenburg, Sweden..
    Endogenous plasticity in neuro-rehabilitation following partial spinal cord lesions2014In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 8, p. 59-Article in journal (Refereed)
    Abstract [en]

    Currently, much interest in neuro-rehabilitation is focused on mechanisms related to axonal outgrowth and formation of new circuits although still little is known about the functionality in motor behavior. This is a highly exciting avenue of research and most important to consider when dealing with large lesions. Here, we address endogenous mechanisms with the potential of modifying the function of already existing spinal circuits via associative plasticity. We forward a hypothesis based on experimental findings suggesting that potentiation of synaptic transmission in un-injured pathways can be monitored and adjusted by a Cerebellar loop involving the Reticulospinal, Rubrospinal and Corticospinal tracts and spinal interneurons with projection to motoneurons. This mechanism could be of relevance when lesions are less extensive and the integrity of the neural circuits remains in part. Endogenous plasticity in the spinal cord could be of clinical importance if stimulated in an adequate manner, e.g., by using optimal training protocols.

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  • 20.
    Alstermark, Bror
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Pettersson, Lars-Gunnar
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg , Gothenburg.
    Skilled reaching and grasping in the rat: lacking effect of corticospinal lesion2014In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 5, article id 103Article in journal (Refereed)
    Abstract [en]

    The corticospinal system is a major motor pathway in the control of skilled voluntary movements such as reaching and grasping. It has developed considerably phylogenetically to reach a peak in humans. Because rodents possess advanced forelimb movements that can be used for reaching and grasping food, it is commonly considered that the corticospinal tract (CST) is of major importance for this control also in rodents. A close homology to primate reaching and grasping has been described but with obvious limitations as to independent digit movements, which are lacking in rodents. Nevertheless, it was believed that there are, as in the primate, direct cortico-motoneuronal connections. Later, it was shown that there are no such connections. The fastest excitatory pathway is disynaptic, mediated via cortico-reticulospinal neurons and in the spinal cord the excitation is mainly polysynaptically mediated via segmental interneurons. Earlier behavioral studies have aimed at investigating the role of the CST by using pyramidotomy in the brainstem. However, in addition to interrupting the CST, a pyramidal transection abolishes the input to reticulospinal neurons. It is therefore not possible to conclude if the deficits after pyramidotomy result from interruption of the CST or the input to reticulospinal neurons or both. We have re-investigated the role of the CST by examining the effect of a CST lesion in the C1-C2 spinal segments on the success rate of reaching and grasping. This lesion spares the cortico-reticulospinal pathway. In contrast to investigations using pyramidal transections, the present study did not demonstrate marked deficits in reaching and grasping. We propose that the difference in results can be explained by the intact cortical input to reticulospinal neurons in our study and thus implicate an important role of this pathway in the control of reaching and grasping in the rat.

  • 21.
    Ambarki, Khalid
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Petr, J.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Wirestam, R.
    Zarrinkoob, Laleh
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Malm, Jan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Partial Volume Correction of Cerebral Perfusion Estimates Obtained by Arterial Spin Labeling2015In: 16th Nordic-Baltic Conference on Biomedical Engineering: 16. NBC & 10. MTD 2014 joint conferences. October 14-16, 2014, Gothenburg, Sweden, 2015, Vol. 48, p. 17-19Conference paper (Refereed)
    Abstract [en]

    Arterial Spin labeling (ASL) is a fully non-invasive MRI method capable to quantify cerebral perfusion. However, gray (GM) and white matter (WM) ASL perfusions are difficult to assess separately due to limited spatial resolution increasing the partial volume effects (PVE). In the present study, ASL PVE correction was implemented based on a regression algorithm in 22 healthy young men. PVE corrected perfusion of GM and WM were compared to previous studies. PVE-corrected GM perfusion was in agreement with literature values. In general, WM perfusion was higher despite the use of PVE correction.

  • 22.
    Ambarki, Khalid
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Zarrinkoob, Laleh
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wirestam, R.
    Petr, J.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Accuracy of Parenchymal Cerebral Blood Flow Measurements Using Pseudocontinuous Arterial Spin-labeling in Healthy Volunteers2015In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 36, no 10, p. 1816-1821Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The arterial spin-labeling method for CBF assessment is widely available, but its accuracy is not fully established. We investigated the accuracy of a whole-brain arterial spin-labeling technique for assessing the mean parenchymal CBF and the effect of aging in healthy volunteers. Phase-contrast MR imaging was used as the reference method. MATERIALS AND METHODS: Ninety-two healthy volunteers were included: 49 young (age range, 20-30 years) and 43 elderly (age range, 65-80 years). Arterial spin-labeling parenchymal CBF values were averaged over the whole brain to quantify the mean pCBF(ASL) value. Total. CBF was assessed with phase-contrast MR imaging as the sum of flows in the internal carotid and vertebral arteries, and subsequent division by brain volume returned the pCBF(PCMRI) value. Accuracy was considered as good as that of the reference method if the systematic difference was less than 5 mL/min/100 g of brain tissue and if the 95% confidence intervals were equal to or better than +/- 10 mL/min/100 g. RESULTS: pCBF(ASL) correlated to pCBF(PCMRI) (r = 0.73; P < .001). Significant differences were observed between the pCBF(ASL) and pCBF(PCMRI) values in the young (P = .001) and the elderly (P < .001) volunteers. The systematic differences (mean 2 standard deviations) were -4 +/- 14 mL/min/100 g in the young subjects and 6 +/- 12 mL/min/100 g in the elderly subjects. Young subjects showed higher values than the elderly subjects for pCBF(PCMRI) (young, 57 +/- 8 mL/min/100 g; elderly, 54 +/- 7 mL/min/100 g; P = .05) and pCBF(ASL) (young, 61 +/- 10 mL/min/100 g; elderly, 48 +/- 10 mL/min/100 g; P < .001). CONCLUSIONS: The limits of agreement were too wide for the arterial spin-labeling method to be considered satisfactorily accurate, whereas the systematic overestimation in the young subjects and underestimation in the elderly subjects were close to acceptable. The age-related decrease in parenchymal CBF was augmented in arterial spin-labeling compared with phase-contrast MR imaging.

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  • 23.
    Amjad, Asma
    et al.
    Neurobiology Group, SISSA, Scuola Internazionale Superiore di Studi Avanzati, Trieste, Italy.
    Hernandez-Clavijo, Andres
    Neurobiology Group, SISSA, Scuola Internazionale Superiore di Studi Avanzati, 34136 Trieste, Italy.
    Pifferi, Simone
    Neurobiology Group, SISSA, Scuola Internazionale Superiore di Studi Avanzati, Trieste, Italy.
    Maurya, Devendra Kumar
    Neurobiology Group, SISSA, Scuola Internazionale Superiore di Studi Avanzati, Trieste, Italy.
    Boccaccio, Anna
    Istituto di Biofisica, National Research Council, Genova, Italy.
    Franzot, Jessica
    Neurobiology Group, SISSA, Scuola Internazionale Superiore di Studi Avanzati, Trieste, Italy.
    Rock, Jason
    Department of Anatomy, University of California, San Francisco, School of Medicine, San Francisco, USA.
    Menini, Anna
    Neurobiology Group, SISSA, Scuola Internazionale Superiore di Studi Avanzati, Trieste, Italy.
    Conditional knockout of TMEM16A/anoctamin1 abolishes the calcium-activated chloride current in mouse vomeronasal sensory neurons2015In: The Journal of General Physiology, ISSN 0022-1295, E-ISSN 1540-7748, Vol. 145, no 4, p. 285-301Article in journal (Refereed)
    Abstract [en]

    Pheromones are substances released from animals that, when detected by the vomeronasal organ of other individuals of the same species, affect their physiology and behavior. Pheromone binding to receptors on microvilli on the dendritic knobs of vomeronasal sensory neurons activates a second messenger cascade to produce an increase in intracellular Ca2+ concentration. Here, we used whole-cell and inside-out patch-clamp analysis to provide a functional characterization of currents activated by Ca2+ in isolated mouse vomeronasal sensory neurons in the absence of intracellular K+. In whole-cell recordings, the average current in 1.5 µM Ca2+ and symmetrical Cl− was −382 pA at −100 mV. Ion substitution experiments and partial blockade by commonly used Cl− channel blockers indicated that Ca2+ activates mainly anionic currents in these neurons. Recordings from inside-out patches from dendritic knobs of mouse vomeronasal sensory neurons confirmed the presence of Ca2+-activated Cl− channels in the knobs and/or microvilli. We compared the electrophysiological properties of the native currents with those mediated by heterologously expressed TMEM16A/anoctamin1 or TMEM16B/anoctamin2 Ca2+-activated Cl− channels, which are coexpressed in microvilli of mouse vomeronasal sensory neurons, and found a closer resemblance to those of TMEM16A. We used the Cre–loxP system to selectively knock out TMEM16A in cells expressing the olfactory marker protein, which is found in mature vomeronasal sensory neurons. Immunohistochemistry confirmed the specific ablation of TMEM16A in vomeronasal neurons. Ca2+-activated currents were abolished in vomeronasal sensory neurons of TMEM16A conditional knockout mice, demonstrating that TMEM16A is an essential component of Ca2+-activated Cl− currents in mouse vomeronasal sensory neurons.

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  • 24.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Amyotrophic lateral sclerosis and CuZn-superoxide dismutase: a clinical, genetic and enzymatic study1997Doctoral thesis, comprehensive summary (Other academic)
  • 25.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Is all ALS genetic?2017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 89, no 3, p. 220-221Article in journal (Other academic)
  • 26.
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Mutation in C9orf72 changes the boundaries of ALS and FTD2012In: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 11, no 3, p. 205-207Article in journal (Refereed)
  • 27.
    Andersen, Peter M.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Abrahams, Sharon
    Borasio, Gian D.
    de Carvalho, Mamede
    Chio, Adriano
    Van Damme, Philip
    Hardiman, Orla
    Kollewe, Katja
    Morrison, Karen E.
    Petri, Susanne
    Pradat, Pierre-Francois
    Silani, Vincenzo
    Tomik, Barbara
    Wasner, Maria
    Weber, Markus
    EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS): revised report of an EFNS task force2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, no 3, p. 360-E24Article in journal (Refereed)
    Abstract [en]

    Background: The evidence base for the diagnosis and management of amyotrophic lateral sclerosis (ALS) is weak. Objectives: To provide evidence-based or expert recommendations for the diagnosis and management of ALS based on a literature search and the consensus of an expert panel. Methods: All available medical reference systems were searched, and original papers, meta-analyses, review papers, book chapters and guidelines recommendations were reviewed. The final literature search was performed in February 2011. Recommendations were reached by consensus. Recommendations: Patients with symptoms suggestive of ALS should be assessed as soon as possible by an experienced neurologist. Early diagnosis should be pursued, and investigations, including neurophysiology, performed with a high priority. The patient should be informed of the diagnosis by a consultant with a good knowledge of the patient and the disease. Following diagnosis, the patient and relatives/carers should receive regular support from a multidisciplinary care team. Medication with riluzole should be initiated as early as possible. Control of symptoms such as sialorrhoea, thick mucus, emotional lability, cramps, spasticity and pain should be attempted. Percutaneous endoscopic gastrostomy feeding improves nutrition and quality of life, and gastrostomy tubes should be placed before respiratory insufficiency develops. Non-invasive positive-pressure ventilation also improves survival and quality of life. Maintaining the patient's ability to communicate is essential. During the entire course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end-of-life care should be discussed early with the patient and carers, respecting the patient's social and cultural background.

  • 28.
    Andersen, Peter M.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Al-Chalabi, Ammar
    Clinical genetics of amyotrophic lateral sclerosis: what do we really know?2011In: Nature Reviews Neurology, ISSN 1759-4758, E-ISSN 1759-4766, Vol. 7, no 11, p. 603-615Article, review/survey (Refereed)
    Abstract [en]

    Hereditary amyotrophic lateral sclerosis (ALS) encompasses a group of genetic disorders characterized by adult-onset loss of the lower and upper motor neuron systems, often with involvement of other parts of the nervous system. Cases of hereditary ALS have been attributed to mutations in 12 different genes, the most common being SOD1, FUS and TARDBP-mutations in the other genes are rare. The identified genes explain 25-35% of cases of familial ALS, but identifying the remaining genes has proved difficult. Only a few genes seem to account for significant numbers of ALS cases, with many others causing a few cases each. Hereditary ALS can be inherited in an autosomal dominant, autosomal recessive or X-linked manner, and families with low disease penetrance are frequently observed. In such families, the genetic predisposition may remain unnoticed, so many patients carry a diagnosis of isolated or sporadic ALS. The only clinical feature that distinguishes recognized hereditary from apparently sporadic ALS is a lower mean age of onset in the former. All the clinical features reported in hereditary cases (including signs of extrapyramidal, cerebellar or cognitive involvement) have also been observed in sporadic cases. Genetic counseling and risk assessment in relatives depend on establishing the specific gene defect and the disease penetrance in the particular family.

  • 29.
    Andersen, Peter M.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hempel, Maja
    Santer, René
    Nordström, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Tsiakas, Konstantinos
    Johannsen, Jessika
    Volk, Alexander E.
    Bierhals, Tatjana
    Zetterström, Per
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Marklund, Stefan L.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Phenotype in an Infant with SOD1 Homozygous Truncating Mutation2019In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 381, no 5, p. 486-488Article in journal (Refereed)
  • 30.
    Andersen, Peter M.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Nilsson, P.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Marklund, Stefan L.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    CuZn-superoxide dismutase, extracellular superoxide dismutase, and glutathione peroxidase in blood from individuals homozygous for ASP90ALA CuZn-superoxide dismutase mutation1998In: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 70, no 2, p. 715-720Article in journal (Refereed)
  • 31.
    Andersen, Peter M.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Nilsson, Peter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Ala-Hurula, Veli
    Keränen, Marja-Leena
    Tarvainen, Ilkka
    Haltia, Tuula
    Nilsson, Lotta
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Binzer, Michael
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Marklund, Stefan L.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Amyotrophic lateral sclerosis associated with homozygosity for an Asp90Ala mutation in CuZn-superoxide dismutase1995In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 10, p. 61-66Article in journal (Refereed)
  • 32.
    Andersson, Axel
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Generating reporter constructs for in vitro studies of the aggregation and prion-like spread of misfolded SOD1 in ALS2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
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  • 33.
    Andersson, Jesper
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Role of pro-inflammatory S100A8 and S100A9 proteins in the neuro-inflammatory amyloid cascade in traumatic brain injury and age-dependent diseases2016Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
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  • 34.
    Andersson, Linus
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology. Department of Occupational and Public Health Sciences, University of Gävle, Box 7629, SE-90712 Umeå, Sweden.
    Sandberg, Petra
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Olofsson, Jonas K.
    Nordin, Steven
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Effects of Task Demands on Olfactory, Auditory, and Visual Event-Related Potentials Suggest Similar Top-Down Modulation Across Senses2018In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 43, no 2, p. 129-134Article in journal (Refereed)
    Abstract [en]

    A widely held view is that top-down modulation of sensory information relies on an amodal control network that acts through the thalamus to regulate incoming signals. Olfaction lacks a direct thalamic projection, which suggests that it may differ from other modalities in this regard. We investigated the late positive complex (LPC) amplitudes of event-related potentials (ERP) from 28 participants, elicited by intensity-matched olfactory, auditory and visual stimuli, during a condition of focused attention, a neutral condition, and a condition in which stimuli were to be actively ignored. Amplitudes were largest during the attend condition, lowest during the ignore condition, with the neutral condition in between. A Bayesian analysis resulted in strong evidence for similar effects of task across sensory modalities. We conclude that olfaction, despite its unique neural projections, does not differ from audition and vision in terms of task-dependent neural modulation of the LPC.

  • 35.
    Andersson, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Grip, Helena
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Lindvall, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Brändström, Helge
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Air transport of patients with intracranial air: computer model of pressure effects2003In: Aviation, Space and Environmental Medicine, ISSN 0095-6562, E-ISSN 1943-4448, Vol. 74, no 2, p. 138-144Article in journal (Refereed)
  • 36.
    Andersson, P.
    et al.
    Center for Life-span Developmental Research (LEADER), School of Behavioral, Social and Legal Sciences, Örebro University, Sweden.
    Samrani, George
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Aging Research Center (ARC), Karolinska Institute and Stockholm University, Sweden.
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Persson, J.
    Center for Life-span Developmental Research (LEADER), School of Behavioral, Social and Legal Sciences, Örebro University, Sweden; Aging Research Center (ARC), Karolinska Institute and Stockholm University, Sweden.
    Hippocampal subfield volumes contribute to working memory interference control in aging: evidence from longitudinal associations over 5 years2023In: Neuroimage: Reports, E-ISSN 2666-9560, Vol. 3, no 4, article id 100189Article in journal (Refereed)
    Abstract [en]

    In memory, familiar but no longer relevant information may disrupt encoding and retrieval of to-be-learned information. While it has been demonstrated that the ability to resolve proactive interference (PI) in working memory (WM) is reduced in aging, the neuroanatomical components of this decline have yet to be determined. Hippocampal (HC) involvement in age-related decline in control of PI is currently not known. In particular, the association between HC subfield volumes and control of PI in WM has not been examined previously. Here we investigate the associations between mean level and 5-year trajectories of gray matter subfield volumes and PI in WM across the adult life span (N = 157). Longitudinal analyses over 5-years across all participants revealed that reduced volume in the subiculum was related to impaired control of PI. Age-stratified analyses showed that this association was most pronounced in older adults. Furthermore, we found that in older adults the effect of age on PI was mediated by GM volume in the HC. The current results show that HC volume is associated with the ability to control PI in WM, and that these associations are modulated by age.

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  • 37.
    Andersson, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University Hospital.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Stiernman, Lars J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Rieckmann, Anna
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Center for the Economics of Aging, Max Planck Institute for Social Law and Social Policy, Germany.
    Cognitive decline in Parkinson’s disease: a subgroup of extreme decliners revealed by a data-driven analysis of longitudinal progression2021In: Frontiers in Psychology, E-ISSN 1664-1078, Vol. 12, article id 729755Article in journal (Refereed)
    Abstract [en]

    Cognitive impairment is an important symptom of Parkinson’s disease (PD) and predicting future cognitive decline is crucial for clinical practice. Here, we aim to identify latent sub-groups of longitudinal trajectories of cognitive change in PD patients, and explore predictors of differences in cognitive change. Longitudinal cognitive performance data from 349 newly diagnosed PD patients and 145 healthy controls from the Parkinson Progression Marker Initiative were modeled using a multivariate latent class linear mixed model. Resultant latent classes were compared on a number of baseline demographics, and clinical variables, as well as cerebrospinal fluid (CSF) biomarkers and striatal dopamine transporter (DAT) density markers of neuropathology. Trajectories of cognitive change in PD were best described by two latent classes. A large subgroup (90%), which showed a subtle impairment in cognitive performance compared to controls but remained stable over the course of the study, and a small subgroup (10%) which rapidly declined in all cognitive performance measures. Rapid decliners did not differ significantly from the larger group in terms of disease duration, severity or motor symptoms at baseline. However, rapid decliners had lower CSF amyloidß42 levels, a higher prevalence of sleep disorder and pronounced loss of caudate DAT density at baseline. These data suggest the existence of a distinct minority sub-type of PD in which rapid cognitive change in PD can occur uncoupled from motor symptoms or disease severity, likely reflecting early pathological change that extends from motor areas of the striatum into associative compartments and cortex.

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  • 38. Andrew, Churchill
    et al.
    Hopkins, Brian
    Rönnqvist, Louise
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Vogt, Stefan
    Vision of the hand and environmental context in human prehension2000In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 134, no 1, p. 81-89Article in journal (Refereed)
    Abstract [en]

    Previous findings on the role of visual contact with the hand in the control of reaching and grasping have been contradictory. Some studies have shown that such contact is largely irrelevant, while more recent ones have emphasised its importance. In contrast, information arising from the surrounding environment has received relatively little attention in the study of prehensile actions. In order to identify the roles of both sources of information, we made kinematic comparisons between three conditions. In the first, reaching was performed in a dimly lit room and compared with a second condition in which reaches in the dark, but with the thumb and first finger illuminated, were made to a luminous object. This contrast allows the effects of environmental context to be identified. A comparison between the second and a third condition, in which both vision of the hand and the environment was removed, but the object was still visually available, enabled the assessment of how and when vision of the hand plays a role. Removing environmental cues had effects both early and late in the reach, while vision of the hand was only crucial in the period after peak deceleration. In addition, removal of both sources of information resulted in larger grip apertures. Differences and similarities between our findings and those of other studies are discussed, as is the ongoing debate about the relative importance of visual feedback of the hand in the control and co-ordination of prehensile actions. We conclude with suggestions for further research based on the set-up used in the present study.

  • 39.
    Annettesdotter, Amanda
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Limited Evidence for Epigenetic Clocks as Brain Aging Biomarkers: Longitudinal Pilot Findings2022Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Chronological age is considered an inadequate estimate of a person’s true biological aging status. Epigenetic clocks based on DNA methylation (DNAm) in blood, on the other hand, are widely used to estimate someone’s biological age, and a higher epigenetic age acceleration (EAA) indicates an older biological age than expected based on the chronological age. Cross- sectional analyses have previously shown associations between EAA and age-sensitive brain characteristics critical to for example cognitive function. The present thesis was a pilot study aiming to test the predictive ability of EAA based on two epigenetic clocks (the Horvath’s clock and the DNAm PhenoAge) on longitudinally measured total gray matter (GM), white matter (WM), and hippocampal (HC) volumes, and white matter hyperintensities (i.e., lesions; WMH), assessed using magnetic resonance imaging (MRI). By implementing linear mixed- effects models on already collected data from N=64 participants (mean age 71.1 years, 43 females) from the Betula study, both a long-term (DNAm measured ~14 years before MRI scanning) and a concurrent (DNAm and MRI measured at the same time) prediction were tested. Initially, the concurrent DNAm PhenoAge could significantly predict a faster decline in GM volume over time, however, this effect was rendered nonsignificant when controlling for high blood pressure. No other model showed any significant EAA effects, which might be due to the small sample size or that the epigenetic clocks are not robust enough. Future research could further investigate these relationships by analyzing bigger samples, targeting the concurrent prediction over the long-term, and including newer epigenetic clocks. 

  • 40.
    Arabuli, Lili
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Department of Natural Sciences, School of Science and Technology, University of Georgia, Tbilisi, Georgia.
    Iashchishyn, Igor
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Romanova, Nina
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Musteikyte, Greta
    Smirnovas, Vytautas
    Chaudhary, Himanshu
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Svedružić, Željko M.
    Morozova-Roche, Ludmilla A.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Co-aggregation of S100A9 with DOPA and cyclen-based compounds manifested in amyloid fibril thickening without altering rates of self-assembly2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 16, article id 8556Article in journal (Refereed)
    Abstract [en]

    The amyloid cascade is central for the neurodegeneration disease pathology, including Alzheimer’s and Parkinson’s, and remains the focus of much current research. S100A9 protein drives the amyloid-neuroinflammatory cascade in these diseases. DOPA and cyclen-based compounds were used as amyloid modifiers and inhibitors previously, and DOPA is also used as a precursor of dopamine in Parkinson’s treatment. Here, by using fluorescence titration experiments we showed that five selected ligands: DOPA-D-H-DOPA, DOPA-H-H-DOPA, DOPA-D-H, DOPA-cyclen, and H-E-cyclen, bind to S100A9 with apparent Kd in the sub-micromolar range. Ligand docking and molecular dynamic simulation showed that all compounds bind to S100A9 in more than one binding site and with different ligand mobility and H-bonds involved in each site, which all together is consistent with the apparent binding determined in fluorescence experiments. By using amyloid kinetic analysis, monitored by thioflavin-T fluorescence, and AFM imaging, we found that S100A9 co-aggregation with these compounds does not hinder amyloid formation but leads to morphological changes in the amyloid fibrils, manifested in fibril thickening. Thicker fibrils were not observed upon fibrillation of S100A9 alone and may influence the amyloid tissue propagation and modulate S100A9 amyloid assembly as part of the amyloid-neuroinflammatory cascade in neurodegenerative diseases.

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  • 41. Armstrong, Stephanie J.
    et al.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Terenghi, Giorgio
    Kingham, Paul J
    ECM molecules mediate both Schwann cell proliferation and activation to enhance neurite outgrowth2007In: Tissue engineering, ISSN 1076-3279, E-ISSN 1557-8690, Vol. 13, no 12, p. 2863-2870Article in journal (Refereed)
    Abstract [en]

    Tissue engineering using a combination of biomaterials and cells represents a new approach to nerve repair. We have investigated the effect that extracellular matrix (ECM) molecules have on Schwann cell (SC) attachment and proliferation on the nerve conduit material poly-3-hydroxybutyrate (PHB), and SC influence on neurite outgrowth in vitro. Initial SC attachment to PHB mats was unaffected by ECM molecules but proliferation increased (laminin > fibronectin > collagen). SCs seeded onto ECM-coated culture inserts suspended above a monolayer of NG108-15 cells determined the effect of released diffusible factors. The effect of direct contact between the two cell types on ECM molecules was also investigated. In both systems SCs enhanced neurite number per cell and percentage of NG108-15 cells sprouting neurites. NG108-15 cells grown in direct contact with SCs had significantly longer neurites than those exposed to diffusible factors when seeded on laminin or fibronectin. Diffusible factors released from SCs cultured on ECM molecules appear to initiate neurite outgrowth, whereas SC-neuron contact promotes neurite elongation. SC proliferation was maximal on poly-D-lysine-coated surfaces, but these cells did not influence neurite outgrowth to the levels of laminin or fibronectin. This suggests that ECM molecules enhance cell number and activate SCs to release neurite promoting factors. Addition of ECM molecules to PHB nerve conduits containing SCs is likely to provide benefits for the treatment of nerve injuries.

  • 42.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Danfors, T
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    PET response and tumor stabilization under erlotinib and bevacizumab treatment of an intracranial lesion non-invasively diagnosed as likely chordoma2011In: Clinical Neuropathology, ISSN 0722-5091, Vol. 30, no 5, p. 242-246Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Chordoma is a rare and a slow-growing tumor originating from the notochord and commonly localized in the skull base. Surgery and occasionally radiotherapy have emerged as the treatments of choice. In the relapsed situations available treatment options are strictly limited; however, recently molecularly targeted agents have been proposed to be of potential beneficial value. THE CASE: A 63-year-old male presenting with seizures and an extradural mass in the left brain hemisphere. An attempt to resect the tumor was followed by severe bradycardia when manipulating with the dura and therefore discontinued. It was considered too hazardous even to take a biopsy specimen. The tumor was considered radiologically and macroscopically as a chordoma. As the tumor progressed after radiotherapy, chemotherapy with erlotinib in combination with cetuximab was initiated. This treatment was interrupted due to progressive disease and toxicity. However, combination treatment with erlotinib and bevacizumab normalized the uptake of [11C]methionine PET signal and resulted in a slight tumor shrinkage on MRI. The patient is still (March 2011) free of symptoms, without cranial nerve deficits or seizures. DISCUSSION: This report shows that erlotinib and bevacizumab in combination may completely quench the transport of the essential amino acid methionine to a treatment refractory intracranial tumor bearing radiological and clinical characteristics of a chordoma. Further studies are necessary to establish this strategy as a treatment option for this indication.

  • 43.
    Asplund, K.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Managing risk factors2011In: Special Issue: Abstracts of the 15th Congress of the EFNS, Budapest, Hungary, 2011, Oxford: Rapid Communications , 2011, Vol. 18, p. 621-621Conference paper (Refereed)
  • 44.
    Asplund, Kjell
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Glader, Eva-Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Norrving, Bo
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Effects of Extending the Time Window of Thrombolysis to 4.5 Hours: Observations in the Swedish Stroke Register (Riks-Stroke)2011In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 42, no 9, p. 2492-2497Article in journal (Refereed)
    Abstract [en]

    Background and Purpose: The European Cooperative Acute Stroke Study (ECASS) III trial and Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register (SITS-ISTR) data were published in 2008. Riks-Stroke, the Swedish Stroke Register, was used to explore how thrombolysis in the 3- to 4.5-hour window has been spread in different hospitals and patient groups and what effects this has had on treatment within 3 hours.

    Methods: All 76 hospitals in Sweden admitting patients with acute stroke participate in Riks-Stroke. During the study period, January 2003 to June 2010, 92 150 18- to 80-year-old patients were hospitalized for acute ischemic stroke.

    Results: After the publication of the ECASS III results in the third quarter of 2008, thrombolysis in the 3- to 4.5-hour window increased from 0.5% before publication to 2.1% in 2010. Thrombolysis in the 3- to 4.5-hour window spread somewhat faster in men than women (P=0.04) but at a similar rate in different age groups. The use of thrombolysis within 3 hours after onset of symptoms increased successively from 0.9% in 2003 to 6.6% in late 2008 and then it stabilized at 6%. The median time from arrival to the hospital to start of treatment remained unchanged at 66 to 69 minutes before and after 2008 (P=0.06).

    Conclusions: Since the end of 2008, there has been a rapid nationwide dissemination of thrombolysis in the 3- to 4.5-hour window, whereas rates in the <3-hour window have leveled off. The extended time window has not affected door-to-needle time.

  • 45.
    Asplund, Kjell
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lundström, Staffan
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    End of life after stroke: a nationwide study of 42,502 deaths occurring within a year after stroke2018In: European Stroke Journal, ISSN 2396-9873, E-ISSN 2396-9881, Vol. 3, no 1, p. 74-81Article in journal (Refereed)
    Abstract [en]

    Introduction: In the scientific literature, there is very limited empirical information on end-of-life issues after stroke in the scientific literature. The present nationwide study describes the circumstances surrounding deaths that occur within a year after a stroke. Patients and methods: Datasets from three nationwide Swedish registers (on stroke, palliative care and cause of death) were linked. Basic information was available for 42,502 unselected cases of death that occurred within a year after a stroke and more detailed information was available for 16,408 deaths. Odds ratios for characteristics of end-of-life care were calculated by logistic regression. Results: In the late phase after stroke (three months to one year), 46% of patients died in a nursing home, whereas 37% of patients died in a hospital after readmission and 10% of patients died at home. Eleven per cent of deaths were reported as being unexpected. A next of kin was present at 49% of deaths. The frequency of unattended deaths (neither next of kin nor staff were present at the time of death) ranged from 5% at home with specialised home care to 25% in hospitals. Discussion: This is, by far, the largest study published on end-of-life issues after stroke. Major differences between countries in healthcare, community services, family structure and culture may limit direct transfer of the present results to other settings. Conclusion: There is considerable discordance between presumed good death' late after stroke (dying at home surrounded by family members) and the actual circumstances at the end of life.

  • 46.
    Asplund, Kjell
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Norrving, B.
    Department of Neurology, Skane University Hospital, Lund.
    Glader, Eva-Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Eriksson, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Implementation in routine clinical practice of thrombolysis in extended time window 3-4.5 h: A nationwide swedish study2011In: Special Issue: Abstracts of the 15th Congress of the EFNS, Budapest, Hungary, 2011, Oxford: Rapid Communications , 2011, Vol. 18, p. 52-52Conference paper (Refereed)
  • 47.
    Asplund, Kjell
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sukhova, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Diagnostic procedures, treatments, and outcomes in stroke patients admitted to different types of hospitals2015In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 46, no 3, p. 806-812Article in journal (Refereed)
    Abstract [en]

    Background and Purpose: In many countries, including Sweden, initiatives have been taken to reduce between-hospital differences in the quality of stroke services. We have explored to what extent hospital type (university, specialized nonuniversity, or community hospital) influences hospital performance. Methods: Riksstroke collects clinical data during hospital stay (national coverage 94%). Follow-up data at 3 months were collected using administrative registers and a questionnaire completed by surviving patients (response rate 88%). Structural data were collected from a questionnaire completed by hospital staff (response rate 100%). Multivariate analyses with adjustment for clustering were used to test differences between types of hospitals. Results: The proportion of patients admitted directly to a stroke unit was highest in community hospitals and lowest in university hospitals. Magnetic resonance, carotid imaging, and thrombectomy were more frequently performed in university hospitals, and the door-to-needle time for thrombolysis was shorter. Secondary prevention with antihypertensive drugs was used less often, and outpatient follow-up was less frequent in university hospitals. Fewer patients in community hospitals were dissatisfied with their rehabilitation. After adjusting for possible confounders, poor outcome (dead or activities of daily living dependency 3 months after stroke) was not significantly different between the 3 types of hospital. Conclusions: In a setting with national stroke guidelines, stroke units in all hospitals, and measurement of hospital performance and benchmarking, outcome (after case-mix adjustment) is similar in university, specialized nonuniversity, and community hospitals. There seems to be fewer barriers to organizing well-functioning stroke services in community hospitals compared with university hospitals.

  • 48.
    Atanasov, Atanas
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Wester, Joel
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Superseding the mystical: finding cognition in psilocybin trips2021Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Over the past decade, there has been a renewed scientific interest in psychedelic science. This renewed interest is primarily driven by potential applications in psychiatry, specifically for the mental health challenges of depression. The Mystical Experience Questionnaire (MEQ30) is widely used to predict assess patient experience and predict possible correlations between psychedelic experience and therapeutic outcome. However, MEQ30 does not describe the subjective aspect of the experience. The research question asked in this paper was: Can a cognitive vocabulary approach be used to interpret descriptions of subjective psilocybin-induced experiences in non-therapeutic settings? Publically available reports of psilocybin-induced experiences that are available on the Internet were collected and analyzed using inductive thematic analysis. Cognitive labels were given to the identified themes post priori, and this indicates that a cognitive vocabulary approach is able to capture the subjective aspect of the psilocybin-induced experience. We conclude that it is unnecessary to resort to mystical terminology as found in the MEQ30 to understand and explain the subjective aspect of the psilocybin-induced experience.

  • 49. Athanasiu, Lavinia
    et al.
    Giddaluru, Sudheer
    Fernandes, Carla
    Christoforou, Andrea
    Reinvang, Ivar
    Lundervold, Astri J.
    Nilsson, Lars-Göran
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Kauppi, Karolina
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Eriksson, Elias
    Sundet, Kjetil
    Djurovic, Srdjan
    Espeseth, Thomas
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Steen, Vidar M.
    Andreassen, Ole A.
    Le Hellard, Stephanie
    A genetic association study of CSMD1 and CSMD2 with cognitive function2017In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 61, p. 209-216Article in journal (Refereed)
    Abstract [en]

    The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for association with cognitive functions in the NCNG sample (Norwegian Cognitive NeuroGenetics; n = 670). Replication testing of SNPs with p-value < 0.001 (7 in CSMD1 and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized Psychosis; n =1025) and the BETULA sample (Betula Longitudinal Study on aging, memory and dementia; n = 1742). Finally, we conducted a meta-analysis of these SNPs using all three samples. The previously identified schizophrenia marker in CSMD1 (SNP rs10503253) was also included. The strongest association was observed between the CSMDI SNP rs2740931 and performance in immediate episodic memory (p-value = 5 Chi 10(-6), minor allele A, MAF 0.48-0.49, negative direction of effect). This association reached the study-wide significance level (p <= 1.2 Chi 10(-5)). SNP rs10503253 was not significantly associated with cognitive functions in our samples. In conclusion, we studied n = 3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. Additional studies of larger samples with cognitive phenotypes will be needed to further clarify the role of CSMD1 in cognitive phenotypes in health and disease.

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  • 50. Auer-Grumbach, Michaela
    et al.
    Bennett, D. L. H.
    Andersen, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Harms, M. B.
    Reilly, M. M.
    Weishaupt, J.
    Strom, T. M.
    Walther, T.
    Scherer, S. S.
    Zuchner, S.
    Martini, R.
    Senderek, J.
    Rare coding variants in the mme gene, encoding the metalloprotease neprilysin, are linked to late-onset axonal neuropathies2016In: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 21, no 3, p. 235-235Article in journal (Other academic)
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