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  • 651.
    Wickström, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Dahle, Charlotte
    Vrethem, Magnus
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Reduced sick leave in multiple sclerosis after one year of natalizumab treatment. A prospective ad hoc analysis of the TYNERGY trial2014In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, no 8, p. 1095-1101Article in journal (Refereed)
    Abstract [en]

    Background: In a retrospective study, we have previously shown that work ability was improved after the initiation of natalizumab treatment in relapsing remitting multiple sclerosis (RRMS). In another prospective trial (TYNERGY) the effect on MS-related fatigue was evaluated after 12 months of treatment with natalizumab. A comprehensive Capacity for Work Questionnaire (CWQ) was used to collect data regarding number of working hours and sickness absence. The predefined intention-to-treat analysis regarding work ability did not, however, show significant results.

    Objectives: The objective of this paper is to assess the amount of sick leave in RRMS before and after one year of natalizumab treatment and correlate it to fatigue and walking ability.

    Methods: This is a post-hoc analysis of the complete data from the CWQ used in the TYNERGY trial. Results: MS patients receiving sickness benefit before start of treatment reduced their sickness benefit by an absolute change of 33% after one year of natalizunnab treatment. Younger age and improvement of walking ability correlated significantly with reduction of sick leave.

    Conclusions: This ad-hoc analysis of prospectively collected data supported our previous retrospective study and thus indicates a positive relationship between natalizumab treatment and improvement in work ability.

  • 652.
    Wikgren, Mikael
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Karlsson, Thomas
    Linköping University, Department of Behavioral Sciences and Learning.
    Lind, Johanna
    University of Oslo, Department of Psychology.
    Nilbrink, Therese
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Sleegers, Kristel
    VIB, Department of Molecular Genetics.
    Van Broeckhoven, Christine
    VIB, Department of Molecular Genetics.
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nilsson, Lars-Göran
    Stockholm University, Department of Psychology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Norrback, Karl-Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Longer leukocyte telomere length is associated with smaller hippocampal volume among non-demented APOE ε3/ε3 subjects2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 4, p. e34292-Article in journal (Refereed)
    Abstract [en]

    Telomere length shortens with cellular division, and leukocyte telomere length is used as a marker for systemic telomere length. The hippocampus hosts adult neurogenesis and is an important structure for episodic memory, and carriers of the apolipoprotein E ε4 allele exhibit higher hippocampal atrophy rates and differing telomere dynamics compared with non-carriers. The authors investigated whether leukocyte telomere length was associated with hippocampal volume in 57 cognitively intact subjects (29 ε3/ε3 carriers; 28 ε4 carriers) aged 49-79 yr. Leukocyte telomere length correlated inversely with left (r(s) = -0.465; p = 0.011), right (r(s) = -0.414; p = 0.025), and total hippocampus volume (r(s) = -0.519; p = 0.004) among APOE ε3/ε3 carriers, but not among ε4 carriers. However, the ε4 carriers fit with the general correlation pattern exhibited by the ε3/ε3 carriers, as ε4 carriers on average had longer telomeres and smaller hippocampi compared with ε3/ε3 carriers. The relationship observed can be interpreted as long telomeres representing a history of relatively low cellular proliferation, reflected in smaller hippocampal volumes. The results support the potential of leukocyte telomere length being used as a biomarker for tapping functional and structural processes of the aging brain.

  • 653.
    Wiklund-Hörnqvist, Carola
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Andersson, Micael
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Jonsson, Bert
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    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.
    Neural activations associated with feedback and retrieval success2017In: npj Science of Learning, E-ISSN 2056-7936, Vol. 2, no 12Article in journal (Refereed)
    Abstract [en]

    There is substantial behavioral evidence for a phenomenon commonly called “the testing effect”, i.e. superior memory performance after repeated testing compared to re-study of to-be-learned materials. However, considerably less is known about the underlying neuro-cognitive processes that are involved in the initial testing phase and thus underlies the actual testing effect. Here, we investigated functional brain activity related to test-enhanced learning with feedback. Subjects learned foreign vocabulary across three consecutive tests with correct-answer feedback. Functional brain-activity responses were analyzed in relation to retrieval and feedback events, respectively. Results revealed up-regulated activity in fronto-striatal regions during the first successful retrieval, followed by a marked reduction in activity as a function of improved learning. Whereas feedback improved behavioral performance across consecutive tests, feedback had a negligable role after the first successful retrieval for functional brain-activity modulations. It is suggested that the beneficial effects of test-enhanced learning is regulated by feedback-induced updating of memory representations, mediated via the striatum, that might underlie the stabilization of memory commonly seen in behavioral studies of the testing effect.

  • 654.
    Wiklund-Hörnqvist, Carola
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Jonsson, Bert
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    An fMRI study of the supportive role of feedback during test-enhanced learning2016In: ICOM-6 Conference Programme: Konferensbidrag. Abstract (Refereegranskat), 2016, 2016, p. 29-29Conference paper (Refereed)
    Abstract [en]

    Considerable research in cognitive psychology has demonstrated that testing improves the performance on later retention tests (i.e., the testing-effect).

    One key factor is the inclusion of feedback which enhances the benefits. Participants (n=21) first studied 60 Swahili-Swedish word-pairs. Subsequently, they underwent fMRI while being tested on each study-item either with or without feedback.

    Contrary to no feedback, several regions were identified as a feedback-network with the strongest contribution from the bilateral MTL regions (anterior hippocampus, amygdala), insula and left IFC. Several of these responses were modulated by type of response (correct/incorrect) and repetition (1,2,3).

    These findings link the effect of feedback on learning to strengthening of semantic representations, providing novel insights about the crucial role of feedback during test-enhanced learning.

  • 655.
    Wilson, Andrew D H
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery. University Department of Surgery, Blond McIndoe Centre, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.
    Hart, Andrew
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery. University Department of Surgery, Blond McIndoe Centre, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Terenghi, Giorgio
    University Department of Surgery, Blond McIndoe Centre, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.
    Primary sensory neuronal rescue with systemic acetyl-L-carnitine following peripheral axotomy. A dose-response analysis2003In: British Journal of Plastic Surgery, ISSN 0007-1226, E-ISSN 1465-3087, Vol. 56, no 8, p. 732-739Article in journal (Refereed)
    Abstract [en]

    The loss of a large proportion of primary sensory neurons after peripheral nerve axotomy is well documented. As a consequence of this loss, the innervation density attained on completion of regeneration will never be normal, regardless of how well the individual surviving neurons regenerate. Acetyl-L-carnitine (ALCAR), an endogenous peptide in man, has been demonstrated to protect sensory neurons, thereby avoiding loss after peripheral nerve injury. In this study we examined the dose-response effect of ALCAR on the primary sensory neurons in the rat dorsal root ganglia (DRG) 2 weeks after sciatic nerve axotomy. Six groups of adult rats (n=5) underwent unilateral sciatic nerve axotomy, without repair, followed by 2 weeks systemic treatment with one of five doses of ALCAR (range 0.5-50 mg/kg/day), or normal saline. L4 and L5 dorsal root ganglia were then harvested bilaterally and sensory neuronal cell counts obtained using the optical disector technique. ALCAR eliminated neuronal loss at higher doses (50 and 10 mg/kg/day), while lower doses did result in loss (12% at 5 mg/kg/day, p<0.05; 19% at 1 mg/kg/day, p<0.001; 23% at 0.5 mg/kg/day, p<0.001) compared to contralateral control ganglia. Treatment with normal saline resulted in a 25% (p<0.001) loss, demonstrating no protective effect in accordance with previous studies.ALCAR preserves the sensory neuronal cell population after axotomy in a dose-responsive manner and as such, has potential for improving the clinical outcome following peripheral nerve trauma when doses in excess of 10 mg/kg/day are employed.

  • 656. Witjas, Tatiana
    et al.
    Carron, Romain
    Krack, Paul
    Eusebio, Alexandre
    Vaugoyeau, Marianne
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Azulay, Jean Philippe
    Régis, Jean
    A prospective single-blind study of Gamma Knife thalamotomy for tremor2015In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 85, no 18, p. 1562-1568Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate the safety and efficacy of unilateral Gamma Knife thalamotomy (GKT) for treatment of severe tremor with a prospective blinded assessment. Methods: Fifty patients (mean age: 74.5 years; 32 men) with severe refractory tremor (36 essential, 14 parkinsonian) were treated with unilateral GKT. Targeting of the ventral intermediate nucleus (Vim) was achieved with Leksell Gamma Knife with a single shot through a 4-mm collimator helmet. The prescription dose was 130 Gy. Neurologic and neuropsychological assessments including a single-blinded video assessment of the tremor severity performed by a movement disorders neurologist from another center were performed before and 12 months after treatment. MRI follow-up occurred at 3, 6, and 12 months. Results: The upper limb tremor score improved by 54.2% on the blinded assessment (p < 0.0001). All tremor components (rest, postural, and intention) were improved. Activities of daily living were improved by 72.2%. Cognitive functions remained unchanged. Following GKT, the median delay of improvement was 5.3 months (range 1-12 months). The only side effect was a transient hemiparesis associated with excessive edema around the thalamotomy in one patient. Conclusion: This blinded prospective assessment demonstrates that unilateral GKT is a safe and efficient procedure for severe medically refractory tremor. Side effects were rare and transient in this study.

  • 657.
    Wixner, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rydh, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Hornsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gastric emptying in hereditary transthyretin amyloidosis: the impact of autonomic neuropathy2012In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 24, no 12, p. 1111-e568Article in journal (Refereed)
    Abstract [en]

    Background: Gastrointestinal (GI) complications are common in hereditary transthyretin amyloidosis and an autonomic dysfunction has been considered to explain these symptoms. The aim of this study was to investigate the impact of autonomic neuropathy on gastric emptying in hereditary transthyretin amyloidosis and to relate these findings to nutritional status, GI symptoms, gender, and age at disease onset.

    Methods: Gastric emptying was evaluated with gastric emptying scintigraphy. Spectral analysis of the heart rate variability and cardiovascular responses after tilt test were used to assess the autonomic function. The nutritional status was evaluated with the modified body mass index (s-albumine x BMI).

    Key Results: Gastric retention was found in about one-third of the patients. A weak correlation was found between the scintigraphic gastric emptying rate and both the sympathetic (rs = -0.397, P < 0.001) and parasympathetic function (rs = -0.282, P = 0.002). The gastric emptying rate was slower in those with lower or both upper and lower GI symptoms compared with those without symptoms (median T50 123 vs 113 min, P = 0.042 and 192 vs 113 min, P = 0.003, respectively). Multiple logistic regression analysis showed that age of onset (OR 0.10, CI 0.020.52) and sympathetic dysfunction (OR 0.23, CI 0.100.51), but not gender (OR 0.76, CI 0.311.84) and parasympathetic dysfunction (OR 1.81, CI 0.724.56), contributed to gastric retention.

    Conclusions and Inferences: Gastric retention is common in hereditary transthyretin amyloidosis early after onset. Autonomic neuropathy only weakly correlates with gastric retention and therefore additional factors must be involved.

  • 658.
    Wu, Junfang
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wuolikainen, Anna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Trupp, Miles
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Marklund, Stefan L.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Andersen, Peter M.
    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.
    Öhman, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    NMR analysis of the CSF and plasma metabolome of rigorously matched amyotrophic lateral sclerosis, Parkinson's disease and control subjects2016In: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 12, no 6, article id 101Article in journal (Refereed)
    Abstract [en]

    Introduction: Amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) are two severe neurodegenerative disorders for which the disease mechanisms are poorly understood and reliable biomarkers are absent.

    Objectives: To identify metabolite biomarkers for ALS and PD, and to gain insights into which metabolic pathways are involved in disease.

    Methods: Nuclear magnetic resonance (NMR) metabolomics was utilized to characterize the metabolite profiles of cerebrospinal fluid (CSF) and plasma from individuals in three age, gender, and sampling-date matched groups, comprising 22 ALS, 22 PD and 28 control subjects.

    Results: Multivariate analysis of NMR data generated robust discriminatory models for separation of ALS from control subjects. ALS patients showed increased concentrations of several metabolites in both CSF and plasma, these are alanine (CSF fold change = 1.22, p = 0.005), creatine (CSF-fc = 1.17, p = 0.001), glucose (CSF-fc = 1.11, p = 0.036), isoleucine (CSF-fc = 1.24, p = 0.002), and valine (CSF-fc = 1.17, p = 0.014). Additional metabolites in CSF (creatinine, dimethylamine and lactic acid) and plasma (acetic acid, glutamic acid, histidine, leucine, pyruvate and tyrosine) were also important for this discrimination. Similarly, panels of CSF-metabolites that discriminate PD from ALS and control subjects were identified.

    Conclusions: The results for the ALS patients suggest an affected creatine/creatinine pathway and an altered branched chain amino acid (BCAA) metabolism, and suggest links to glucose and energy metabolism. Putative metabolic markers specific for ALS (e.g. creatinine and lactic acid) and PD (e.g. 3-hydroxyisovaleric acid and mannose) were identified, while several (e.g. creatine and BCAAs) were shared between ALS and PD, suggesting some overlap in metabolic alterations in these disorders.

  • 659.
    Wuolikainen, Anna
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Acimovic, Jure
    Loevgren-Sandblom, Anita
    Parini, Paolo
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Bjoerkhem, Ingemar
    Cholesterol, Oxysterol, Triglyceride, and Coenzyme Q Homeostasis in ALS. Evidence against the Hypothesis That Elevated 27-Hydroxycholesterol Is a Pathogenic Factor2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 11, p. e113619-Article in journal (Refereed)
    Abstract [en]

    High plasma levels of cholesterol have been suggested to be neuroprotective for the degenerative disease amyotrophic lateral sclerosis (ALS) and to be associated with increased survival time. The gene encoding cholesterol 27-hydroxylase, CYP27A1, was recently identified as a susceptibility gene for sporadic ALS. A product of this enzyme is 27-hydroxycholesterol. We investigated plasma samples from 52 ALS patients and 40 control subjects (spouses) regarding cholesterol homeostasis, lipid profiles, and coenzyme Q. Eleven of the patients carried mutations in C9orf72 and seven in SOD1. Plasma levels of 27-hydroxycholesterol were significantly lower in male patients with ALS than in controls. It was not possible to link the reduced levels to any specific mutation, and there was no significant correlation between 27-hydroxycholesterol and survival. With normalization for diet using the spouses, a correlation was found between survival and total cholesterol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, and coenzyme Q. We conclude that cholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 27-hydroxycholesterol and lipid profiles in plasma are of limited prognostic value in individual ALS patients.

  • 660.
    Wåhlin, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    At the Heart of Cognitive Functioning in Aging2019In: Trends in cognitive sciences, ISSN 1364-6613, E-ISSN 1879-307X, Vol. 23, no 9, p. 717-720Article in journal (Other academic)
    Abstract [en]

    Several neural and non-neural factors contribute to individual differences in cognitive performance. Here we outline a sequence of vascular events where excessive transfer of arterial-pressure pulsatility damages hippocampal capillaries. We argue that the vascular alterations decrease the ability to sustain neural activity and thereby contribute to episodic-memory impairment in aging.

  • 661.
    Xin, D. L.
    et al.
    Department of Surgery, University of Pennsylvania, USA.
    Hadrevi, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Elliott, M. E.
    Department of Neurosurgery, Thomas Jefferson University, USA.
    Amin, M
    Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadephia, USA.
    Harris, M. Y.
    Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, USA.
    Barr-Gillespie, A
    College of Health Professions, Pacific University, USA.
    Barbe, M. F.
    Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, USA.
    Effectiveness of conservative interventions for sickness and pain behaviors induced by a high repetition high force upper extremity task2017In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 18, article id 36Article in journal (Refereed)
    Abstract [en]

    Background: Systemic inflammation is known to induce sickness behaviors, including decreased social interaction and pain. We have reported increased serum inflammatory cytokines in a rat model of repetitive strain injury (rats perform an upper extremity reaching task for prolonged periods). Here, we sought to determine if sickness behaviors are induced in this model and the effectiveness of conservative treatments.

    Methods: Experimental rats underwent initial training to learn a high force reaching task (10 min/day, 5 days/week for 6 weeks), with or without ibuprofen treatment (TRHF vs. TRHF + IBU rats). Subsets of trained animals went on to perform a high repetition high force (HRHF) task for 6 or 12 weeks (2 h/day, 3 days/week) without treatment, or received two secondary interventions: ibuprofen (HRHF + IBU) or a move to a lower demand low repetition low force task (HRHF-to-LRLF), beginning in task week 5. Mixed-effects models with repeated measures assays were used to assay duration of social interaction, aggression, forepaw withdrawal thresholds and reach performance abilities. One-way and two-way ANOVAs were used to assay tissue responses. Corrections for multiple comparisons were made.

    Results: TRHF + IBU rats did not develop behavioral declines or systemic increases in IL-1beta and IL-6, observed in untreated TRHF rats. Untreated HRHF rats showed social interaction declines, difficulties performing the operant task and forepaw mechanical allodynia. Untreated HRHF rats also had increased serum levels of several inflammatory cytokines and chemokines, neuroinflammatory responses (e.g., increased TNFalpha) in the brain, median nerve and spinal cord, and Substance P and neurokinin 1 immunoexpression in the spinal cord. HRHF + IBU and HRHF-to-LRLF rats showed improved social interaction and reduced inflammatory serum, nerve and brain changes. However, neither secondary treatment rescued HRHF-task induced forepaw allodynia, or completely attenuated task performance declines or spinal cord responses.

    Conclusions: These results suggest that inflammatory mechanisms induced by prolonged performance of high physical demand tasks mediate the development of social interaction declines and aggression. However, persistent spinal cord sensitization was associated with persistent behavioral indices of discomfort, despite use of conservative secondary interventions indicating the need for prevention or more effective interventions.

  • 662.
    Yelhekar, Tushar
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Chloride Homeostasis in Central Neurons2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The overall aim of the present thesis is to clarify the control of intracellular chloride homeostasis in central neurons, because of the critical role of chloride ions (Cl) for neuronal function. Normal function of the central nervous system (CNS) depends on a delicate balance between neuronal excitation and inhibition. Inhibition is, in the adult brain, most often mediated by the neurotransmitter γ-aminobutyric acid (GABA). GABA may, however, in some cases cause excitation. GABA acts by activating GABA type A receptors (GABAARs), which are ion channels largely permeable to Cl. The effect of GABAAR-mediated neuronal signaling - inhibitory or excitatory - is therefore mainly determined by the Cl gradient across the membrane. This gradient varies with neuronal activity and may be altered in pathological conditions. Thus, understanding Cl regulation is important to comprehend neuronal function. This thesis is an attempt to clarify several unknown aspects of neuronal Cl regulation. For such clarification, a sufficiently sensitive method for measuring the intracellular Cl concentration, [Cl]i, is necessary. In the first study of this thesis, we examined two electrophysiological methods commonly used to estimate [Cl]i. Both methods, here called the interpolation and the voltage-ramp method, depend on an estimate of the Cl equilibrium potential from the current-voltage relation of GABA- or glycine-evoked Cl currents. Both methods also provide an estimate of the membrane Cl conductance, gCl. With a combination of computational and electrophysiological techniques, we showed that the most common (interpolation) method failed to detect changes in [Cl]i and gCl during prolonged GABA application, whereas the voltage-ramp method accurately detected such changes. Our analysis also provided an explanation as to why the two methods differ. In a second study, we clarified the role of the extracellular matrix (ECM) for the distribution of Cl across the cell membrane of neurons from rat brain. It was recently proposed that immobile charges located within the ECM, rather than as previously thought cation-chloride transporter proteins, determine the low [Cl]i which is critical to GABAAR-mediated inhibition. By using electrophysiological techniques to measure [Cl]i, we showed that digestion of the ECM decreases the expression and function of the neuron-specific K+ Cl cotransporter 2 (KCC2), which normally extrudes Cl- from the neuron, thus causing an increase in resting [Cl]i. As a result of ECM degradation, the action of GABA may be transformed from inhibitory to excitatory. In a third study, we developed a method for quantifying the largely unknown resting Cl (leak) conductance, gCl, and examined the role of gCl for the neuronal Cl homeostasis. In isolated preoptic neurons from rat, resting gCl was about 6 % of total resting conductance, to a major part due to spontaneously open GABAARs and played an important role for recovery after a high Cl load. We also showed that spontaneous, impulse-independent GABA release can significantly enhance recovery when the GABA responses are potentiated by the neurosteroid allopregnanolone. In a final commentary, we formulated the mathematical relation between Cl conductance, KCC2-mediated Cl extrusion capacity and steady-state [Cl]i. In summary, the present thesis (i) clarifies how well common electrophysiological methods describe [Cl]i and gCl, (ii) provides a novel method for quantifying gCl in cell membranes and (iii) clarifies the roles of the ECM, ion channels and ion transporters in the control of [Cl]i homeostasis and GABAAR-mediated signaling in central neurons. 

  • 663.
    Yelhekar, Tushar D.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Karlsson, Urban
    Blomqvist, Erii
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    How to Properly Measure a Current-Voltage Relation? -Interpolation vs. Ramp Methods Applied to Studies of GABA(A) Receptors2016In: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 10, article id 10Article in journal (Refereed)
    Abstract [en]

    The relation between current and voltage, I-V relation, is central to functional analysis of membrane ion channels. A commonly used method, since the introduction of the voltage-clamp technique, to establish the I-V relation depends on the interpolation of current amplitudes recorded at different steady voltages. By a theoretical computational approach as well as by experimental recordings from GABA(A) receptor mediated currents in mammalian central neurons, we here show that this interpolation method may give reversal potentials and conductances that do not reflect the properties of the channels studied under conditions when ion flux may give rise to concentration changes. Therefore, changes in ion concentrations may remain undetected and conclusions on changes in conductance, such as during desensitization, may be mistaken. In contrast, an alternative experimental approach, using rapid voltage ramps, enable I-V relations that much better reflect the properties of the studied ion channels.

  • 664.
    Yelhekar, Tushar
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Kuznetsova, Tatiana
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Malinina, Evgenya
    Ponimaskin, Evgeni
    Dityatev, Alexander
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Extracellular Matrix Regulates Neuronal Chloride Concentration via K+-Cl--cotransporter 2Manuscript (preprint) (Other academic)
  • 665. Yi, W
    et al.
    Haapasalo, H
    Holmlund, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Järvelä, S
    Raheem, O
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Expression of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins in human ependymoma relates to tumor location, WHO grade, and patient age2009In: Clinical Neuropathology, ISSN 0722-5091, Vol. 28, no 1, p. 21-27Article in journal (Refereed)
    Abstract [en]

    Three human leucine-rich repeats and immunoglobulin-like domains (LRIG1-3) genes and proteins have recently been characterized. LRIG1 has been shown to be a suppressor of tumor growth by counteracting the signaling of epidermal growth factor receptor (EGFR) family members, including EGFR (ERBB1). Expression of LRIG proteins seems to be of importance in the pathogenesis of astrocytic tumors. In this study, the expression of LRIG1-3 was evaluated in 51 human ependymomas by immunohistochemistry. LRIG proteins were detected in all ependymomas analyzed, however, with a pronounced heterogeneity in expression and subcellular localization. Higher cytoplasmic immunoreactivity of LRIG1 correlated with older patient age and higher LRIG1 nuclear immunoreactivity with lower WHO Grade. LRIG1 displayed a stronger immunoreactivity in the cytoplasm and nuclei in spinal ependymomas than in the posterior fossa or supratentorial ependymomas, while perinuclear LRIG3 was more highly expressed in supratentorial than in infratentorial ependymomas. The indications that expression and subcellular localization of LRIG proteins could be pathogenetically associated with specific clinicopathological features of ependymoma tumors might be of importance in the carcinogeneses and tumor progression of human ependymomas.

  • 666. Yi, Wei
    et al.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Öhman, Kjell
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Percutaneous biopsy of cavernous sinus tumour via the foramen ovale2009In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 151, no 4, p. 401-407Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Tumours involving the cavernous sinus may be challenging to neurosurgeons and neuro-oncologists to treat. Operation may be hazardous for lesions in this area, radical resection is seldom obtained, and other treatments are often needed. Different types of tumour occur at this location. Radiological examination may not be diagnostic so that a histopathological diagnosis is often needed before treatment can be recommended for the individual patient. If surgical resection is less feasible a biopsy will be necessary. CONCLUSION: We describe a technique for image-guided percutaneous biopsy through the oval foramen ovale and its use in two patients with a cavernous sinus tumour. We also describe and highlight the importance of pre- and intraoperative CT imaging in obtaining a safe and conclusive biopsy.

  • 667. Yuan, Justin P.
    et al.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry. Department of Psychiatry and the Langley Porter Psychiatric Institute Weill Institute for Neurosciences University of California, San Francisco.
    Flynn, Trevor
    Chen, Yiran
    Ho, Tiffany C.
    Connolly, Colm G.
    Dumont Walter, Rebecca A.
    Yang, Tony T.
    Xu, Duan
    Tymofiyeva, Olga
    Test-retest reliability of graph theoretic metrics in adolescent brains2019In: Brain Connectivity, ISSN 2158-0014, E-ISSN 2158-0022, Vol. 9, no 2, p. 144-154Article in journal (Refereed)
    Abstract [en]

    Graph theory analysis of structural brain networks derived from diffusion tensor imaging (DTI) has become a popular analytical method in neuroscience, enabling advanced investigations of neurological and psychiatric disorders. The purpose of this study was to investigate: 1) the effects of edge weighting schemes, and 2) the effects of varying interscan periods on graph metrics' test-retest reliability within the adolescent brain. We compared a binary (B) network definition with three weighting schemes: fractional anisotropy (FA), streamline count (SC), and streamline count with density and length correction (SDL). Two commonly used global and two local graph metrics were examined. The analysis was conducted with two groups of adolescent volunteers who received DTI scans either 12 weeks apart (16.62±1.10yrs) or within the same scanning session (30 minutes apart) (16.65±1.14yrs). The intraclass correlation coefficient (ICC) was used to assess test-retest reliability and the coefficient of variation (CV) was used to assess precision. On average, each edge scheme produced reliable results at both time intervals. Weighted measures outperformed binary measures, with SDL-weights producing the most reliable metrics. All edge schemes except FA displayed high CV values, leaving FA as the only edge scheme that consistently showed high precision while also producing reliable results. Overall findings suggest that FA-weights are more suited for DTI connectome studies in adolescents.

  • 668. Zhao, Charlie W.
    et al.
    Daley, Mark J.
    Pruszynski, J. Andrew
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Dept. of Computer Science, Western University, London, Ontario, Canada; Brain and Mind Institute, Western University, London, Ontario, Canada; Dept. of Physiology and Pharmacology, Western University, London, Ontario, Canada; Dept. of Psychology, Western University, London, Ontario, Canada; Robarts Research Institute, Western University, London, Ontario, Canada.
    Neural network models of the tactile system develop first-order units with spatially complex receptive fields2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 6, article id e0199196Article in journal (Refereed)
    Abstract [en]

    First-order tactile neurons have spatially complex receptive fields. Here we use machine-learning tools to show that such complexity arises for a wide range of training sets and network architectures. Moreover, we demonstrate that this complexity benefits network performance, especially on more difficult tasks and in the presence of noise. Our work suggests that spatially complex receptive fields are normatively good given the biological constraints of the tactile periphery.

  • 669. Zhuravleva, Z.
    et al.
    Titova, N.
    Mukhina, I.
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Preoptic glycine receptors: possible mediators of neuron-glial interaction affecting social behavior in male rats2017In: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 65, p. E298-E299Article in journal (Refereed)
  • 670. Ziaei, Maryam
    et al.
    Salami, Alireza
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Aging Research Center (ARC) at Karolinska Institute and Stockholm University, Stockholm, Sweden.
    Persson, Jonas
    Age-related alterations in functional connectivity patterns during working memory encoding of emotional items2017In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 94, p. 1-12Article in journal (Refereed)
    Abstract [en]

    Previous findings indicate age-related differences in frontal-amygdala connectivity during emotional processing. However, direct evidence for age differences in brain functional activation and connectivity during emotional processing and concomitant behavioral implications is lacking. In the present study, we examined the impact of aging on the neural signature of selective attention to emotional information during working memory (WM) encoding. Participants completed an emotional WM task in which they were asked to attend to emotional targets and ignore irrelevant distractors. Despite an overall reduction in accuracy for older relative to younger adults, no behavioral age effect was observed as a function of emotional valence. The functional connectivity patterns of left ventrolateral prefrontal cortex showed that younger adults recruited one network for encoding of both positive and negative emotional targets and this network contributed to higher memory accuracy in this cohort. Older adults, on the other hand, engaged two distinct networks for encoding of positive and negative targets. The functional connectivity analysis using left amygdala further demonstrated that older adults recruited one single network during encoding of positive as well as negative targets whereas younger adults recruited this network only for encoding of negative items. The engagement of amygdala functional network also contributed to higher memory performance and faster response times in older adults. Our findings provide novel insights into the differential roles of functional brain networks connected to the medial PFC and amygdala during encoding of emotionally-valenced items with advancing age.

  • 671. Zrinzo, Ludvic
    et al.
    Akram, Harith
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, Unit Funct Neurosurg, London WC1N 3BG, England.
    Comment on "Appropriate MRI sequences are required to accurately determine lead location after deep brain stimulation surgery"2014In: Journal of clinical neuroscience, ISSN 0967-5868, E-ISSN 1532-2653, Vol. 21, no 12, p. 2257-2258Article in journal (Refereed)
  • 672.
    Zrinzo, Ludvic
    et al.
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, UK.
    Yoshida, Fumiaki
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, UK.
    Hariz, Marwan I.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Thornton, John
    UCL Institute of Neurology and Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Foltynie, Thomas
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, UK.
    Yousry, Tarek A.
    UCL Institute of Neurology and Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK .
    Limousin, Patricia
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, UK.
    Clinical safety of brain magnetic resonance imaging with implanted deep brain stimulation hardware: large case series and review of the literature2011In: World Neurosurgery, ISSN 1878-8750, Vol. 76, no 1-2, p. 164-172Article in journal (Refereed)
    Abstract [en]

    Background: Over 75,000 patients have undergone deep brain stimulation (DBS) procedures worldwide. Magnetic resonance imaging (MRI) is an important clinical and research tool in analyzing electrode location, documenting postoperative complications, and investigating novel symptoms in DBS patients. Functional MRI may shed light on the mechanism of action of DBS. MRI safety in DBS patients is therefore an important consideration.

    Methods: We report our experience with MRI in patients with implanted DBS hardware and examine the literature for clinical reports on MRI safety with implanted DBS hardware.

    Results: A total of 262 MRI examinations were performed in 223 patients with intracranial DBS hardware, including 45 in patients with an implanted pulse generator. Only 1 temporary adverse event occurred related to patient agitation and movement during immediate postoperative MR imaging. Agitation resolved after a few hours, and an MRI obtained before implanted pulse generator implantation revealed edema around both electrodes. Over 4000 MRI examinations in patients with implanted DBS hardware have been reported in the literature. Only 4 led to adverse events, including 2 hardware failures, 1 temporary and 1 permanent neurological deficit. Adverse neurological events occurred in a unique set of circumstances where appropriate safety protocols were not followed. MRI guidelines provided by DBS hardware manufacturers are inconsistent and vary among devices.

    Conclusions: The importance of MRI in modern medicine places pressure on industry to develop fully MRI-compatible DBS devices. Until then, the literature suggests that, when observing certain precautions, cranial MR images can be obtained with an extremely low risk in patients with implanted DBS hardware.

  • 673. Zuo, Nianming
    et al.
    Salami, Alireza
    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, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Aging Research Center, Karolinska Institute and Stockholm University, Stockholm, Sweden.
    Yang, Yihong
    Yang, Zhengyi
    Sui, Jing
    Jian, Tianzi
    Activation-based association profiles differentiate network roles across cognitive loads2019In: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 40, no 9, p. 2800-2812Article in journal (Refereed)
    Abstract [en]

    Working memory (WM) is a complex and pivotal cognitive system underlying the performance of many cognitive behaviors. Although individual differences in WM performance have previously been linked to the blood oxygenation level-dependent (BOLD) response across several large-scale brain networks, the unique and shared contributions of each large-scale brain network to efficient WM processes across different cognitive loads remain elusive. Using a WM paradigm and functional magnetic resonance imaging (fMRI) from the Human Connectome Project, we proposed a framework to assess the association and shared-association strength between imaging biomarkers and behavioral scales. Association strength is the capability of individual brain regions to modulate WM performance and shared-association strength measures how different regions share the capability of modulating performance. Under higher cognitive load (2-back), the frontoparietal executive control network (FPN), dorsal attention network (DAN), and salience network showed significant positive activation and positive associations, whereas the default mode network (DMN) showed the opposite pattern, namely, significant deactivation and negative associations. Comparing the different cognitive loads, the DMN and FPN showed predominant associations and globally shared-associations. When investigating the differences in association from lower to higher cognitive loads, the DAN demonstrated enhanced association strength and globally shared-associations, which were significantly greater than those of the other networks. This study characterized how brain regions individually and collaboratively support different cognitive loads.

  • 674.
    Ådén, Emma
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Carlsson, Maine
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Poortvliet, Eric
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Edström, Mona
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Håglin, Lena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Dietary intake and olfactory function in patients with newly diagnosed Parkinson's disease: a case-control study.2011In: Nutritional neuroscience, ISSN 1476-8305, Vol. 14, no 1, p. 25-31Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate energy and nutrient intake in newly diagnosed Parkinson's disease (PD) patients and association between olfaction and nutrient density of the diet.

    DESIGN: Baseline data from a prospective cohort study.

    SUBJECTS: Eighty-seven patients and 28 age- and sex-matched controls participated in the study.

    METHODS: Dietary intake was assessed by using 3-day dietary records and 24-hour dietary recalls. The Brief Smell Identification Test (B-SIT) was used to test olfaction.

    RESULTS: Patients, compared with controls, had lower intake of polyunsaturated fatty acids (P = 0.024) and a higher intake of carbohydrates (P = 0.027) in energy percent (E%). Lower intake of protein (E%) (P = 0.045), and a low nutrient density of folate (P = 0.022), magnesium (P = 0.012), and phosphorus (P = 0.029) were associated with lower B-SIT score in both patients and controls. PD patients had a lower B-SIT score than controls (P < 0.001).

    CONCLUSION: The results indicate a higher relative contribution of energy from carbohydrates in PD patients. An association between low protein, folate, magnesium, and phosphorus density of the diet and olfaction was seen in the whole population.

  • 675.
    Ågren-Wilsson, A
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Lekman, A
    Sjöberg, W
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Rosengren, L
    Blennow, K
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    CSF biomarkers in the evaluation of idiopathic normal pressure hydrocephalus2007In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 116, no 5, p. 333-339Article in journal (Refereed)
    Abstract [en]

    BACKGROUND To evaluate cerebrospinal fluid (CSF) markers for neuronal degeneration and demyelination in idiopathic normal pressure hydrocephalus (INPH), subcortical arteriosclerotic encephalopathy (SAE), and neurologically healthy subjects.

    METHODS Lumbar CSF concentrations of sulfatide, neurofilament protein light (NFL), total-tau (T-tau), hyperphosphorylated tau (P-tau), and beta-amyloid(1-42) (Abeta42) were analyzed in 62 INPH patients, 26 SAE patients, and 23 neurologically healthy controls. In INPH patients, samples before and after shunt surgery were analysed.

    RESULTS The CSF concentration of NFL was elevated in INPH and SAE compared with the controls, and levels of T-tau, P-tau, and Abeta42 were lower in INPH compared with SAE and controls. No difference was seen for sulfatide. All markers except Abeta42 were significantly elevated after shunt surgery.

    CONCLUSIONS The most striking finding was the power of the combined pattern of NFL, P-tau, and Abeta42 in distinguishing between the clinical diagnoses of INPH, SAE, and neurologically healthy elderly.

  • 676. Åstrom, Mattias
    et al.
    Samuelsson, Jennifer
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Roothans, Jonas
    Fytagoridis, Anders
    Ryzhkov, Maxim
    Nijlunsing, Rutger
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Prediction of Electrode Contacts for Clinically Effective Deep Brain Stimulation in Essential Tremor2018In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 96, no 5, p. 281-288Article in journal (Refereed)
    Abstract [en]

    Background/Aim: Deep brain stimulation (DBS) is an established neurosurgical treatment that can be used to alleviate symptoms in essential tremor (ET) and other movement disorders. The aim was to develop a method and software tool for the prediction of effective DBS electrode contacts based on probabilistic stimulation maps (PSMs) in patients with ET treated with caudal zona incerta (cZi) DBS. Methods: A total of 33 patients (37 leads) treated with DBS were evaluated with the Essential Tremor Rating Scale (ETRS) 12 months after surgery. In addition, hand tremor and hand function (ETRS items 5/6 and 11-14) were evaluated for every contact during stimulation with best possible outcome without inducing side effects. Prediction of effective DBS electrode contacts was carried out in a retrospective leave-one-out manner based on PSMs, simulated stimulation fields, and a scoring function. Electrode contacts were ranked according to their likelihood of being included in the clinical setting. Ranked electrode contacts were compared to actual clinical settings. Results: Predictions made by the software tool showed that electrode contacts with rank 1 matched the clinically used contacts in 60% of the cases. Contacts with a rank of 1-2 and 1-3 matched the clinical contacts in 83 and 94% of the cases, respectively. Mean improvement of hand tremor and hand function was 79 +/- 21% and 77 +/- 22% for the clinically used and the predicted electrode contacts, respectively. Conclusions: Effective electrode contacts can be predicted based on PSMs in patients treated with cZi DBS for ET. Predictions may in the future be used to reduce the number of clinical assessments that are carried out before a satisfying stimulation setting is defined.

  • 677.
    Åström, Charlotte
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Lindkvist, Markus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Burström, Lage
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Sundelin, Gunnevi
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Karlsson, J Stefan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Changes in EMG activity in the upper trapezius muscle due to local vibration exposure.2009In: Journal of Electromyography & Kinesiology, ISSN 1050-6411, E-ISSN 1873-5711, Vol. 19, no 3, p. 407-415Article in journal (Refereed)
    Abstract [en]

    Exposure to vibration is suggested as a risk factor for developing neck and shoulder disorders in working life. Mechanical vibration applied to a muscle belly or a tendon can elicit a reflex muscle contraction, also called tonic vibration reflex, but the mechanisms behind how vibration could cause musculoskeletal disorders has not yet been described. One suggestion has been that the vibration causes muscular fatigue. This study investigates whether vibration exposure changes the development of muscular fatigue in the trapezius muscle. Thirty-seven volunteers (men and women) performed a sub-maximal isometric shoulder elevation for 3min. This was repeated four times, two times with induced vibration and two times without. Muscle activity was measured before and after each 3-min period to look at changes in the electromyography parameters. The result showed a significantly smaller mean frequency decrease when performing the shoulder elevation with vibration (-2.51Hz) compared to without vibration (-4.04Hz). There was also a slightly higher increase in the root mean square when exposed to vibration (5.7% of maximal voluntary contraction) compared to without (3.8% of maximal voluntary contraction); however, this was not statistically significant. The results of the present study indicate that short-time exposure to vibration has no negative acute effects on the fatiguing of upper trapezius muscle.

  • 678.
    Ögren, Kenneth
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Portrayals of lobotomy in American and Swedish media2013In: Literature, neurology and neuroscience: neurological and psychiatric disorders / [ed] Stanley Finger, François Boller and Anne Stiles, Amsterdam: Elsevier , 2013, p. 201-217Chapter in book (Refereed)
    Abstract [en]

    Psychosurgery has a long history dating back to the 1880s when Gottlieb Burckhardt performed focal cerebral cortical excisions on the brains of six patients diagnosed with schizophrenia. His operations were vividly contested by the medical community of the time. In 1936, when Walter J. Freeman and James W. Watts performed their initial prefrontal lobotomies in the United States, they were met with some professional opposition from superintendents, who would not provide them with patients for the operation. However, Freeman and Watts managed to cope well with the opponents. In newspapers and magazines, the curiosity for lobotomy was obvious. Freeman was instrumental in the way he promoted lobotomy, and he evoked the interest of the press and the journalists for this new surgical treatment on mental illness, something that he regarded as a medico-historical breakthrough. In this chapter, the portrayal of lobotomy in American and Swedish newspapers and magazines is explored and analyzed. How did journalists write about lobotomy for the public in the years spanning 1936 to 1959, a period in which the American and Swedish presses appeared inclined to describe the positive effects of lobotomy, while neglecting the negative and fatal consequences of the operation. There are not only similarities but also interesting differences between the Swedish and the American articles depicting lobotomy. The media can be a powerful factor in the construction of “facts,” which can significantly affect decisions made by people about their health issues. 

  • 679.
    Öhberg, Fredrik
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Grip, Helena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Sterner, Ylva
    Karlsson, J Stefan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Gerdle, Björn
    Chronic whiplash associated disorders and neck movement measurements: an instantaneous helical axis approach.2003In: IEEE transactions on information technology in biomedicine, ISSN 1089-7771, E-ISSN 1558-0032, Vol. 7, no 4, p. 274-282Article in journal (Refereed)
    Abstract [en]

    This paper presents an assessment tool for objective neck movement analysis of subjects suffering from chronic whiplash-associated disorders (WAD). Three-dimensional (3-D) motion data is collected by a commercially available motion analysis system. Head rotation, defined in this paper as the rotation angle around the instantaneous helical axis (IHA), is used for extracting a number of variables (e.g., angular velocity and range, symmetry of motion). Statistically significant differences were found between controls and subjects with chronic WAD in a number of variables.

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