umu.sePublikasjoner
Endre søk
Begrens søket
1234567 51 - 100 of 1301
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 51.
    Aripaka, Karthik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Gudey, Shyam Kumar
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Zang, Guangxiang
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Schmidt, Alexej
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Åhrling, Samaneh Shabani
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Österman, Lennart
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    von Hofsten, Jonas
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Landström, Maréne
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    TRAF6 function as a novel co-regulator of Wnt3a target genes in prostate cancer2019Inngår i: EBioMedicine, E-ISSN 2352-3964, Vol. 45, s. 192-207Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Tumour necrosis factor receptor associated factor 6 (TRAF6) promotes inflammation in response to various cytokines. Aberrant Wnt3a signals promotes cancer progression through accumulation of β-Catenin. Here we investigated a potential role for TRAF6 in Wnt signaling.

    Methods: TRAF6 expression was silenced by siRNA in human prostate cancer (PC3U) and human colorectal SW480 cells and by CRISPR/Cas9 in zebrafish. Several biochemical methods and analyses of mutant phenotype in zebrafish were used to analyse the function of TRAF6 in Wnt signaling.

    Findings: Wnt3a-treatment promoted binding of TRAF6 to the Wnt co-receptors LRP5/LRP6 in PC3U and LNCaP cells in vitro. TRAF6 positively regulated mRNA expression of β-Catenin and subsequent activation of Wnt target genes in PC3U cells. Wnt3a-induced invasion of PC3U and SW480 cells were significantly reduced when TRAF6 was silenced by siRNA. Database analysis revealed a correlation between TRAF6 mRNA and Wnt target genes in patients with prostate cancer, and high expression of LRP5, TRAF6 and c-Myc correlated with poor prognosis. By using CRISPR/Cas9 to silence TRAF6 in zebrafish, we confirm TRAF6 as a key molecule in Wnt3a signaling for expression of Wnt target genes.

    Interpretation: We identify TRAF6 as an important component in Wnt3a signaling to promote activation of Wnt target genes, a finding important for understanding mechanisms driving prostate cancer progression.

  • 52.
    Armstrong, Irene T
    et al.
    Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
    Judson, Melissa
    Department of Psychology, Queen's University, Kingston, ON, Canada.
    Munoz, Douglas P
    Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada, Department of Psychology, Queen's University, Kingston, ON, Canada, Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
    Johansson, Roland S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Flanagan, J Randall
    Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada, Department of Psychology, Queen's University, Kingston, ON, Canada, Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
    Waiting for a hand: saccadic reaction time increases in proportion to hand reaction time when reaching under a visuomotor reversal2013Inngår i: Frontiers in Human Neuroscience, ISSN 1662-5161, E-ISSN 1662-5161, Vol. 7, s. 319-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Although eye movement onset typically precedes hand movement onset when reaching to targets presented in peripheral vision, arm motor commands appear to be issued at around the same time, and possibly in advance, of eye motor commands. A fundamental question, therefore, is whether eye movement initiation is linked or yoked to hand movement. We addressed this issue by having participants reach to targets after adapting to a visuomotor reversal (or 180° rotation) between the position of the unseen hand and the position of a cursor controlled by the hand. We asked whether this reversal, which we expected to increase hand reaction time (HRT), would also increase saccadic reaction time (SRT). As predicted, when moving the cursor to targets under the reversal, HRT increased in all participants. SRT also increased in all but one participant, even though the task for the eyes-shifting gaze to the target-was unaltered by the reversal of hand position feedback. Moreover, the effects of the reversal on SRT and HRT were positively correlated across participants; those who exhibited the greatest increases in HRT also showed the greatest increases in SRT. These results indicate that the mechanisms underlying the initiation of eye and hand movements are linked. In particular, the results suggest that the initiation of an eye movement to a manual target depends, at least in part, on the specification of hand movement.

  • 53. Armstrong, Stephanie J
    et al.
    Wiberg, Mikael
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi. Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, Giorgio
    Kingham, Paul J
    ECM molecules mediate both Schwann cell proliferation and activation to enhance neurite outgrowth.2007Inngår i: Tissue Eng, ISSN 1076-3279, Vol. 13, nr 12, s. 2863-70Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 54. Armstrong, Stephanie J
    et al.
    Wiberg, Mikael
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi. Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, Giorgio
    Kingham, Paul J
    Laminin activates NF-kappaB in Schwann cells to enhance neurite outgrowth.2008Inngår i: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 439, nr 1, s. 42-6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Extracellular matrix (ECM) molecules and Schwann cells (SCs) are important components of peripheral nerve regeneration. In this study, the role of the transcription factor nuclear factor kappa B (NF-kappaB) in SC activation in response to laminin and the subsequent effect on in vitro neurite outgrowth was investigated. Immunocytochemistry and Western blot analysis showed that compared with poly-d-lysine (PDL), laminin enhanced the phosphorylation of IkappaB and p65 NF-kappaB signalling proteins in SCs. Phospho NF-kappaB-p65 was localised to the nucleus indicating activation of NF-kappaB. To assess the functional effect of NF-kappaB activation, SCs plated on PDL or laminin were pre-treated with NF-kappaB inhibitors, 6-amino-4-(4-phenoxyphenylethylamino)quinazoline (QNZ) or Z-leu-leu-leu-CHO (MG-132) before NG108-15 neuronal cells were seeded on the SC monolayer. After 24h co-culture in the absence of inhibitors, SCs seeded on laminin enhanced the mean number and length of neurites extended by NG108-15 cells (1.87+/-0.13 neurites; 238.74+/-8.53microm) compared with those cultured in the presence of SCs and PDL (1.26+/-0.07 neurites; 157.57+/-9.80microm). At 72h, neurite length had further increased to 321.83+/-6.60microm in the presence of SCs and laminin. Inhibition of NF-kappaB completely abolished the effect of laminin on SC evoked neurite outgrowth at 24h and reduced the enhancement of neurite length by over 60% at 72h. SC proliferation was unaffected by NF-kappaB inhibition suggesting that the NF-kappaB signalling pathway plays a discrete role in the activation of SCs and their neurotrophic potential.

  • 55.
    Asplund, Kjell
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Axelsen, Mette
    Berglund, Göran
    Berne, Christian
    Karlström, Brita
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Lindblom, Jonas
    Norlund, Anders
    Rosén, Måns
    Ränzlöv, Ewalotte
    Toft, Eva
    Täljedal, Inge-Bert
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Wolk, Alicja
    Mat vid diabetes. En systematisk litteraturöversikt.2010Rapport (Annet vitenskapelig)
  • 56. Athanasiu, Lavinia
    et al.
    Giddaluru, Sudheer
    Fernandes, Carla
    Christoforou, Andrea
    Reinvang, Ivar
    Lundervold, Astri J.
    Nilsson, Lars-Göran
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Kauppi, Karolina
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Eriksson, Elias
    Sundet, Kjetil
    Djurovic, Srdjan
    Espeseth, Thomas
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Steen, Vidar M.
    Andreassen, Ole A.
    Le Hellard, Stephanie
    A genetic association study of CSMD1 and CSMD2 with cognitive function2017Inngår i: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 61, s. 209-216Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 57.
    Athanassiadis, Tuija
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Fysiologi. Umeå universitet, Medicinsk fakultet, Odontologi.
    Neural circuits engaged in mastication and orofacial nociception2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    A deeper understanding of both movement control and the effects of nociceptor inputs on our motor systems is critical for proper clinical diagnosis of musculo-skeletal dysfunctions and for development of novel rehabilitation schemes. In the jaw system, masticatory movements are produced by a central pattern generator (CPG) located in the brainstem. Considerable efforts have been made in deciphering this neuronal network. The present thesis contributes towards an increasingly detailed understanding of its essential elements, and presents a hypothesis of how deep somatic pain (i.e. muscle pain) may be evoked and interferes with the masticatory CPG circuitry.

    In Paper I, the expression of c-Fos-like protein was used as a molecular marker to visualize brainstem neurons that were active during induced fictive mastication in the anesthetized and paralyzed rabbit. Our findings provide a previously lacking detailed record of the neuronal populations that form the masticatory motor pattern. Certain cells were located in brainstem areas previously suggested to be involved in the masticatory CPG. However, it was a new finding that neurons in the dorsal part of the trigeminal main sensory nucleus (NVsnpr-d) may belong to this circuitry. Paper II focused on the discovered neurons in NVsnpr in an in vitro slice preparation from young rats.  Intracellular recordings allowed us to define two cell types based on their response to depolarizing current. Microstimulation applied to the trigeminal motor nucleus, its reticular border, the parvocellular reticular formation and the nucleus reticularis pontis caudalis, elicited postsynaptic potentials in 81% of the neurons tested. Responses obtained were predominately excitatory and sensitive to gluta-matergic antagonists DNQX or/and APV. Some inhibitory and biphasic responses were also evoked. Bicuculline methiodide or strychnine blocked the IPSPs indicating that they were mediated by GABAA or glycinergic receptors. About one third of the stimulations activated both types of neurons antidromically. Neurons in NVsnpr-d seem to gather all the conditions that can theoretically account for a role in masticatory rhythm generation.

    In Paper III, the masticatory model system was used to investigate the possible role of muscle spindle primary afferents in development of persistent musculoskeletal pain. Following intramuscular acidic (pH 4.0) saline injections of rat masseter muscles, in vitro whole cell recordings were done from jaw closing muscle spindle somata located in the trigeminal mesencephalic nucleus (NVmes). Compared to control neurons, the somata of afferents exposed to acid had more hyperpolarized membrane potentials, more hyperpolarized thresholds for firing, high frequency membrane oscillations and ectopic bursting of action potentials. These changes in membrane properties lasted for up to 35 days. Within the same time frame experi-mental animals showed hypersensitivity to touch on the skin covering the injected muscle. Similar saline injections also resulted in a significant increase of activity dependent c-Fos expression in NVmes neurons compared to controls. Immuno-fluorescence and lectin binding studies indicated that small-caliber muscle afferents containing known nociceptor markers (CGRP, SP, P2X3, TRPV1 and IB4) and expressing glutamate receptors are found close to the annulo-spiral endings of the NVmes afferents. Combined, our new observations support the hypothesis that excessive release of glutamate, within muscle spindles due to ectopically evoked antidromic action potentials, could lead to development of persistent musculoskeletal pain by activation and/ or sensitization of adjacent muscle afferent nociceptors.

  • 58.
    Athanassiadis, Tuija
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Olsson, Kurt A
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Kolta, A
    Westberg, Karl-Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Identification of c-Fos immunoreactive brainstem neurons activated during fictive mastication in the rabbit2005Inngår i: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 165, nr 4, s. 478-489Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In the present study we used the expression of the c-Fos-like protein as a "functional marker" to map populations of brainstem neurons involved in the generation of mastication. Experiments were conducted on urethane-anesthetized and paralyzed rabbits. In five animals (experimental group), rhythmical bouts of fictive masticatory-like motoneuron activity (cumulative duration 60-130 min) were induced by electrical stimulation of the left cortical "masticatory area" and recorded from the right digastric motoneuron pool. A control group of five animals (non-masticatory) were treated in the same way as the experimental animals with regard to surgical procedures, anesthesia, paralysis, and survival time. To detect the c-Fos-like protein, the animals were perfused, and the brainstems were cryosectioned and processed immunocytochemically. In the experimental group, the number of c-Fos-like immunoreactive neurons increased significantly in several brainstem areas. In rostral and lateral areas, increments occurred bilaterally in the borderzones surrounding the trigeminal motor nucleus (Regio h); the rostrodorsomedial half of the trigeminal main sensory nucleus; subnucleus oralis-gamma of the spinal trigeminal tract; nuclei reticularis parvocellularis pars alpha and nucleus reticularis pontis caudalis (RPc) pars alpha. Further caudally-enhanced labeling occurred bilaterally in nucleus reticularis parvocellularis and nucleus reticularis gigantocellularis (Rgc) including its pars-alpha. Our results provide a detailed anatomical record of neuronal populations that are correlated with the generation of the masticatory motor behavior.

  • 59.
    Athanassiadis, Tuija
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Westberg, Karl-Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Olsson, Kurt A
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Kolta, A
    Physiological characterization, localization and synaptic inputs of bursting and nonbursting neurons in the trigeminal principal sensory nucleus of the rat2005Inngår i: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 22, nr 12, s. 3099-3110Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A population of neurons in the trigeminal principal sensory nucleus (NVsnpr) fire rhythmically during fictive mastication induced in the in vivo rabbit. To elucidate whether these neurons form part of the central pattern generator (CPG) for mastication, we performed intracellular recordings in brainstem slices taken from young rats. Two cell types were defined, nonbursting (63%) and bursting (37%). In response to membrane depolarization, bursting cells, which dominated in the dorsal part of the NVsnpr, fired an initial burst followed by single spikes or recurring bursts. Non-bursting neurons, scattered throughout the nucleus, fired single action potentials. Microstimulation applied to the trigeminal motor nucleus (NVmt), the reticular border zone surrounding the NVmt, the parvocellular reticular formation or the nucleus reticularis pontis caudalis (NPontc) elicited a postsynaptic potential in 81% of the neurons tested for synaptic inputs. Responses obtained were predominately excitatory and sensitive to glutamatergic antagonists DNQX and/or APV. Some inhibitory and biphasic responses were also evoked. Bicuculline methiodide or strychnine blocked the IPSPs indicating that they were mediated by GABA(A) or glycinergic receptors. About one-third of the stimulations activated both types of neurons antidromically, mostly from the masseteric motoneuron pool of NVmt and dorsal part of NPontc. In conclusion, our new findings show that some neurons in the dorsal NVsnpr display both firing properties and axonal connections which support the hypothesis that they may participate in masticatory pattern generation. Thus, the present data provide an extended basis for further studies on the organization of the masticatory CPG network.

  • 60.
    Awad, Amar
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Preserved somatosensory conduction to the brain in a patient with a clinically complete cervical spinal cord injury: an fMRI case report2014Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
  • 61.
    Awad, Amar
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Ryggmärgsskador av ”discomplete” -typ och smärta2015Inngår i: BestPractice Nordic, Vol. 6, nr 12, s. 6-9Artikkel i tidsskrift (Annet vitenskapelig)
  • 62.
    Awad, Amar
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Westling, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Functional imaging of Essential Tremor treated with Deep Brain Stimulation In the caudal Zona incerta2017Konferansepaper (Fagfellevurdert)
  • 63.
    Awad, Amar
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Levi, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Lindgren, Lenita
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Hultling, Claes
    Department of Neurobiology, Care Sciences and Society (Neurorehabilitation), Karolinska Institute, Stockholm, Sweden.
    Westling, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Preserved somatosensory conduction in a patient with complete cervical spinal cord injury2015Inngår i: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 47, nr 5, s. 426-431Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Neurophysiological investigation has shown that patients with clinically complete spinal cord injury can have residual motor sparing ("motor discomplete"). In the current study somatosensory conduction was assessed in a patient with clinically complete spinal cord injury and a novel ethodology for assessing such preservation is described, in this case indicating "sensory discomplete" spinal cord injury. Methods: Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) was used to examine the somatosensory system in a healthy subject and in a subject with a clinically complete cervical spinal cord injury, by applying tactile stimulation above and below the level of spinal cord injury, with and without visual feedback. Results: In the participant with spinal cord injury, somatosensory stimulation below the neurological level of the lesion gave rise to BOLD signal changes in the corresponding areas of the somatosensory cortex. Visual feedback of the stimulation strongly modulated the somatosensory BOLD signal, implying that cortico-cortical rather than spino-cortical connections can drive activity in the somatosensory cortex. Critically, BOLD signal change was also evident when the visual feedback of the stimulation was removed, thus demonstrating sensory discomplete spinal cord injury. Conclusion: Given the existence of sensory discomplete spinal cord injury, preserved but hitherto undetected somatosensory conduction might contribute to the unexplained variability related to, for example, the propensity to develop decubitus ulcers and neuropathic pain among patients with clinically complete spinal cord injury.

  • 64. Azim, Eiman
    et al.
    Alstermark, Bror
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Skilled forelimb movements and internal copy motor circuits2015Inngår i: Current Opinion in Neurobiology, ISSN 0959-4388, E-ISSN 1873-6882, Vol. 33, s. 16-24Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mammalian skilled forelimb movements are remarkable in their precision, a feature that emerges from the continuous adjustment of motor output. Here we discuss recent progress in bridging the gap between theory and neural implementation in understanding the basis of forelimb motor refinement. One influential theory is that feedback from internal copy motor pathways enables fast prediction, through a forward model of the limb, an idea supported by behavioral studies that have explored how forelimb movements are corrected online and can adapt to changing conditions. In parallel, neural substrates of forelimb internal copy pathways are coming into clearer focus, in part through the use of genetically tractable animal models to isolate spinal and cerebellar circuits and explore their contributions to movement.

  • 65.
    Azim, Eiman
    et al.
    Howard Hughes Medical Institute, Kavli Institute for Brain Science, Mortimer B. Zuckerman Mind Brain Behavior Institute, Departments of Neuroscience and Biochemistry and Molecular Biophysics, Columbia University, New York, USA.
    Jiang, Juan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Alstermark, Bror
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Jessell, Thomas M
    Howard Hughes Medical Institute, Kavli Institute for Brain Science, Mortimer B. Zuckerman Mind Brain Behavior Institute, Departments of Neuroscience and Biochemistry and Molecular Biophysics, Columbia University, New York, USA.
    Skilled reaching relies on a V2a propriospinal internal copy circuit2014Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 508, nr 7496, s. 357-363Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The precision of skilled forelimb movement has long been presumed to rely on rapid feedback corrections triggered by internally directed copies of outgoing motor commands, but the functional relevance of inferred internal copy circuits has remained unclear. One class of spinal interneurons implicated in the control of mammalian forelimb movement, cervical propriospinal neurons (PNs), has the potential to convey an internal copy of premotor signals through dual innervation of forelimb-innervating motor neurons and precerebellar neurons of the lateral reticular nucleus. Here we examine whether the PN internal copy pathway functions in the control of goal-directed reaching. In mice, PNs include a genetically accessible subpopulation of cervical V2a interneurons, and their targeted ablation perturbs reaching while leaving intact other elements of forelimb movement. Moreover, optogenetic activation of the PN internal copy branch recruits a rapid cerebellar feedback loop that modulates forelimb motor neuron activity and severely disrupts reaching kinematics. Our findings implicate V2a PNs as the focus of an internal copy pathway assigned to the rapid updating of motor output during reaching behaviour.

  • 66.
    Backman, Lars
    et al.
    Aging Research Center, Karolinska Institute and University of Stockholm, Stockholm,.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Dopamine and training-related working-memory improvement2013Inngår i: Neuroscience and Biobehavioral Reviews, ISSN 0149-7634, E-ISSN 1873-7528, Vol. 37, nr 9, s. 2209-2219Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Converging evidence indicates that the neurotransmitter dopamine (DA) is implicated in working-memory (WM) functioning and that WM is trainable. We review recent work suggesting that DA is critically involved in the ability to benefit from WM interventions. Functional MRI studies reveal increased striatal BOLD activity following certain forms of WM interventions, such as updating training. Increased striatal BOLD activity has also been linked to transfer of learning to non-trained WM tasks, suggesting a neural signature of transfer. The striatal BOLD signal is partly determined by DA activity. Consistent with this assertion, PET research demonstrates increased striatal DA release during updating of information in WM after training. Genetic studies indicate larger increases in WM performance post training for those who carry advantageous alleles of DA-relevant genes. These patterns of results corroborate the role of DA in WM improvement. Future research avenues include: (a) neuromodulatory correlates of transfer; (b) the potential of WM training to enhance DA release in older adults; (c) comparisons among different WM processes (i.e., updating, switching, inhibition) regarding regional patterns of training-related DA release; and (d) gene-gene interactions in relation to training-related WM gains.

  • 67.
    Backman, Ludvig
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Neuropeptide and catecholamine effects on tenocytes in tendinosis development: studies on two model systems with focus on proliferation and apoptosis2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: Achilles tendinopathy is a common clinical syndrome of chronic Achilles tendon pain combined with thickening of the tendon and impaired tendon function. Tendinopathy is often, but not always, induced by mechanical overload, and is frequently accompanied by abnormalities at the tissue level, such as hypercellularity and angiogenesis, in which case the condition is called tendinosis. In tendinosis, there are no signs of intratendinous inflammation, but occasionally increased apoptosis is observed. Tendinosis is often hard to treat and its pathogenesis is still not clear. Recently, a new hypothesis has gained support, suggesting a biochemical model based on the presence of a non-neuronal production of classically neuronal signal substances by the primary tendon cells (tenocytes) in tendinosis. The possible functional importance of these signal substances in tendons is unknown and needs to be studied. In particular, the neuropeptide substance P (SP) and catecholamines are of interest in this regard, since these substances have been found to be up-regulated in tendinosis. As both SP and catecholamines are known to exert effects in other tissues resulting in changes similar to those characteristic of tendinosis, it is possible that they have a role in tendinosis development. It is furthermore unknown what elicits the increased intratendinous neuropeptide production in tendinosis, but given that tendon overload is a prominent riskfactor, it is possible that mechanical stimuli are involved.

    The hypothesis of this thesis work was that intratendinous production of SP is up-regulated in response to load of Achilles tendons/tenocytes, and thatstimulation of the preferred SP receptor, the neurokinin-1 receptor (NK-1 R), aswell as stimulation of the catecholamine α2 adrenoreceptors, contribute to the hypercellularity seen in tendinosis, via increased proliferation and/or decreased apoptosis, and that SP stimulates tendon angiogenesis. The purpose of the studies was to test this hypothesis. To achieve this, two model systems were used: One in vivo (rabbit Achilles tendon overload model of tendinosis) and one in vitro (human primary Achilles tendon cell culture model).

    Results: In the rabbit Achilles tendon tissue, SP and NK-1 R expression was extensive in the blood vessel walls, but also to some extent seen in the tenocytes. Quantification of endogenously produced SP in vivo confirmed intratendinous production of the peptide. The production of SP by human tendon cells in vitro was furthermore demonstrated. The catecholamine synthesizing enzyme tyrosine hydroxylase (TH), as well as the α2A adrenoreceptor (α2A AR), were detected in the tenocytes, both in vivo in the rabbit tissue and in vitro in the human tendon cells. As a response to mechanical loading in the in vivo model, the intratendinous levels of SP increased, and this elevation was found to precede distinct tendinosis changes. The in vitro model demonstrated the same response to load, i.e. an increased SP expression, but in this case also a decrease in the NK-1 R expression. In the in vivo model, exogenously administered SP, as well as clonidine (an α2 AR agonist), accelerated tenocyte hypercellularity, an effect that was not seen when administrating a specific α2A AR antagonist. Exogenous administration of SP also resulted in intratendinous angiogenesis and paratendinous inflammation. In the in vitro model, both SP and clonidine had proliferative effects on the human tenocytes, specifically mediated via NK-1R and α2A AR, respectively; both of which in turn involved activation/phosphorylation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2). Exogenously administered SP, in Anti-Fas induced apoptosis of the tenocytes in vitro, confirmed SP to have an anti-apoptotic effect on these cells. This effect was specifically mediated via NK-1 R and the known anti-apoptotic Akt pathway.

    Conclusions: In summary, this thesis concludes that stimulation of NK-1 R and α2A AR on tenocytes, both in vitro and in vivo, mediates significant cell signalling effects leading to processes known to occur in tendinosis, including hypercellularity. The pathological role of the hypercellularity in tendinosis is still unclear, but it is likely to affect collagen metabolism/turnover and arrangement, and thereby indirectly tendon biomechanical function. Additional evidence is here provided showing that SP not only causes tenocyte proliferation, but also contributes to anti-apoptotic events. Furthermore, it was concluded that SP may be involved in the development of tendinosis, since its production is increased in response to load, preceding tendinosis, and since SP accelerates tendinosis changes, through some mechanistic pathways here delineated. These findings suggest that inhibition of SP, and possibly also catecholamines, could be beneficial in the reconstitution/normalization of tendon structure in tendinosis.

  • 68.
    Backman, Ludvig
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Andersson, Gustav
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Wennstig, Gabriel
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Danielson, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Endogenous substance P production in the Achilles tendon increases with loading in an in vivo model of tendinopathy: peptidergic elevation preceding tendinosis-like tissue changes2011Inngår i: Journal of Musculoskeletal and Neuronal Interactions - JMNI, ISSN 1108-7161, Vol. 11, nr 2, s. 133-140Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: To quantify the intratendinous levels of substance P (SP) at different stages of overload in an established modelfor Achilles tendinopathy (rabbit). Also, to study the distribution of the SP-receptor, the NK-1R, and the source of SP, in thetendon. 

    Methods: Animals were subjected to the overuse protocol for 1, 3 or 6 weeks. One additional group served as unexercisedcontrols. Immunoassay (EIA), immunohistochemistry (IHC), and in situ hybridisation (ISH) were performed.

    Results: EIA revealedincreased SP-levels in the Achilles tendon of the exercised limb in all the experimental groups as compared to in thecontrols (statistically significant; p=0.01). A similar trend in the unexercised Achilles tendon was observed but was not statisticallysignificant (p=0.14). IHC and in ISH illustrated reactions of both SP and NK-1R mainly in blood vessel walls, but the receptorwas also found on tenocytes.

    Conclusions: Achilles tendon SP-levels are elevated already after 1 week of loading. This showsthat increased SP-production precedes tendinosis, as tendinosis-like changes occur only after a minimum of 3 weeks of exercise,as shown in a recent study using this model. We propose that central neuronal mechanism may be involved as similar trends wereobserved in the contralateral Achilles tendon.

  • 69.
    Backman, Ludvig
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Fong, Gloria
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Andersson, Gustav
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Scott, Alexander
    Vancouver Coastal Health and Research Institute, University of British Columbia, Vancouver.
    Danielson, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Substance P is a mechanoresponsive, autocrine regulator of human tenocyte proliferation2011Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 11, s. e27209-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    It has been hypothesised that substance P (SP) may be produced by primary fibroblastic tendon cells (tenocytes), and that this production, together with the widespread distribution of the neurokinin-1 receptor (NK-1 R) in tendon tissue, could play an important role in the development of tendinopathy, a condition of chronic tendon pain and thickening. The aim of this study was to examine the possibility of endogenous SP production and the expression of NK-1 R by human tenocytes. Because tendinopathy is related to overload, and because the predominant tissue pathology (tendinosis) underlying early tendinopathy is characterized by tenocyte hypercellularity, the production of SP in response to loading/strain and the effects of exogenously administered SP on tenocyte proliferation were also studied. A cell culture model of primary human tendon cells was used. The vast majority of tendon cells were immunopositive for the tenocyte/fibroblast markers tenomodulin and vimentin, and immunocytochemical counterstaining revealed that positive immunoreactions for SP and NK-1 R were seen in a majority of these cells. Gene expression analyses showed that mechanical loading (strain) of tendon cell cultures using the FlexCell (R) technique significantly increased the mRNA levels of SP, whereas the expression of NK-1 R mRNA decreased in loaded as compared to unloaded tendon cells. Reduced NK-1 R protein was also observed, using Western blot, after exogenously administered SP at a concentration of 10(-7) M. SP exposure furthermore resulted in increased cell metabolism, increased cell viability, and increased cell proliferation, all of which were found to be specifically mediated via the NK-1 R; this in turn involving a common mitogenic cell signalling pathway, namely phosphorylation of ERK1/2. This study indicates that SP, produced by tenocytes in response to mechanical loading, may regulate proliferation through an autocrine loop involving the NK-1 R.

  • 70.
    Backman, Ludvig J
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Andersson, Gustav
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Fong, Gloria
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Department of Physical Therapy, University of British Columbia and Centre for Hip Health and Mobility, Vancouver Coastal Health and Research Institute, Vancouver, British Columbia, Canada.
    Alfredson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Scott, A
    University of British Columbia, Vancouver, Vancouver Coastal Health and Research Institute.
    Danielson, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Alpha-2 adrenergic stimulation triggers Achilles tenocyte hypercellularity: comparison between two model systems2013Inngår i: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 23, nr 6, s. 687-696Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The histopathology of tendons with painful tendinopathy is often tendinosis, a fibrosis-like condition of unclear pathogenesis characterized by tissue changes including hypercellularity. The primary tendon cells (tenocytes) have been shown to express adrenoreceptors (mainly alpha-2A) as well as markers of catecholamine production, particularly in tendinosis. It is known that adrenergic stimulation can induce proliferation in other cells. The present study investigated the effects of an exogenously administered alpha-2 adrenergic agonist in an established in vivo Achilles tendinosis model (rabbit) and also in an in vitro human tendon cell culture model. The catecholamine producing enzyme tyrosine hydroxylase and the alpha-2A-adrenoreceptor (α(2A) AR) were expressed by tenocytes, and alpha-2 adrenergic stimulation had a proliferative effect on these cells, in both models. The proliferation was inhibited by administration of an α(2A) AR antagonist, and the in vitro model further showed that the proliferative alpha-2A effect was mediated via a mitogenic cell signaling pathway involving phosphorylation of extracellular-signal-regulated kinases 1 and 2. The results indicate that catecholamines produced by tenocytes in tendinosis might contribute to the proliferative nature of the pathology through stimulation of the α(2A) AR, pointing to a novel target for future therapies. The study furthermore shows that animal models are not necessarily required for all aspects of this research.

  • 71.
    Backman, Ludvig J
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Danielson, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Akt-mediated anti-apoptotic effects of substance P in Anti-Fas-induced apoptosis of human tenocytes2013Inngår i: Journal of Cellular and Molecular Medicine (Print), ISSN 1582-1838, E-ISSN 1582-4934, Vol. 17, nr 6, s. 723-733Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Substance P (SP) and its receptor, the neurokinin-1 receptor (NK-1 R), are expressed by human tenocytes, and they are both up-regulated incases of tendinosis, a condition associated with excessive apoptosis. It is known that SP can phosphorylate/activate the protein kinase Akt,which has anti-apoptotic effects. This mechanism has not been studied for tenocytes. The aims of this study were to investigate if Anti-Fastreatment is a good apoptosis model for human tenocytes in vitro, if SP protects from Anti-Fas-induced apoptosis, and by which mechanismsSP mediates an anti-apoptotic response. Anti-Fas treatment resulted in a time- and dose-dependent release of lactate dehydrogenase (LDH), i.e.induction of cell death, and SP dose-dependently reduced the Anti-Fas-induced cell death through a NK-1 R specific pathway. The same trendwas seen for the TUNEL assay, i.e. SP reduced Anti-Fas-induced apoptosis via NK-1 R. In addition, it was shown that SP reduces Anti-Fas-induced decrease in cell viability as shown with crystal violet assay. Protein analysis using Western blot confirmed that Anti-Fas inducescleavage/activation of caspase-3 and cleavage of PARP; both of which were inhibited by SP via NK-1 R. Finally, SP treatment resulted in phosphorylation/activation of Akt as shown with Western blot, and it was confirmed that the anti-apoptotic effect of SP was, at least partly, inducedthrough the Akt-dependent pathway. In conclusion, we show that SP reduces Anti-Fas-induced apoptosis in human tenocytes and that this antiapoptoticeffect of SP is mediated through NK-1 R and Akt-specific pathways.

  • 72.
    Backman, Ludvig J
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Danielson, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Low range of ankle dorsiflexion predisposes for patellar tendinopathy in junior elite basketball players: a 1-year prospective study2011Inngår i: American Journal of Sports Medicine, ISSN 0363-5465, E-ISSN 1552-3365, Vol. 39, nr 12, s. 2626-2633Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Patellar tendinopathy (PT) is one of the most common reasons for sport-induced pain of the knee. Low ankle dorsiflexion range might predispose for PT because of load-bearing compensation in the patellar tendon.

    PURPOSE: The purpose of this 1-year prospective study was to analyze if a low ankle dorsiflexion range increases the risk of developing PT for basketball players. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2.

    METHODS: Ninety junior elite basketball players were examined for different characteristics and potential risk factors for PT, including ankle dorsiflexion range in the dominant and nondominant leg. Data were collected over a 1-year period and follow-up, including reexamination, was made at the end of the year.

    RESULTS: Seventy-five players met the inclusion criteria. At the follow-up, 12 players (16.0%) had developed unilateral PT. These players were found to have had a significantly lower mean ankle dorsiflexion range at baseline than the healthy players, with a mean difference of -4.7° (P = .038) for the dominant limb and -5.1° (P = .024) for the nondominant limb. Complementary statistical analysis showed that players with dorsiflexion range less than 36.5° had a risk of 18.5% to 29.4% of developing PT within a year, as compared with 1.8% to 2.1% for players with dorsiflexion range greater than 36.5°. Limbs with a history of 2 or more ankle sprains had a slightly less mean ankle dorsiflexion range compared to those with 0 or 1 sprain (mean difference, -1.5° to -2.5°), although this was only statistically significant for nondominant legs.

    CONCLUSION: This study clearly shows that low ankle dorsiflexion range is a risk factor for developing PT in basketball players. In the studied material, an ankle dorsiflexion range of 36.5° was found to be the most appropriate cutoff point for prognostic screening. This might be useful information in identifying at-risk individuals in basketball teams and enabling preventive actions. A history of ankle sprains might contribute to reduced ankle dorsiflexion range.

  • 73.
    Backman, Ludvig J.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Eriksson, Daniella E.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Danielson, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Substance P reduces TNF-α-induced apoptosis in human tenocytes through NK-1 receptor stimulation2014Inngår i: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 48, nr 19, s. 1414-1420Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: It has been hypothesised that an upregulation of the neuropeptide substance P (SP) and its preferred receptor, the neurokinin-1 receptor (NK-1 R), is a causative factor in inducing tenocyte hypercellularity, a characteristic of tendinosis, through both proliferative and antiapoptotic stimuli. We have demonstrated earlier that SP stimulates proliferation of human tenocytes in culture.

    AIM: The aim of this study was to investigate whether SP can mediate an antiapoptotic effect in tumour necrosis factor-α (TNF-α)-induced apoptosis of human tenocytes in vitro.

    RESULTS: A majority (approximately 75%) of tenocytes in culture were immunopositive for TNF Receptor-1 and TNF Receptor-2. Exposure of the cells to TNF-α significantly decreased cell viability, as shown with crystal violet staining. TNF-α furthermore significantly increased the amount of caspase-10 and caspase-3 mRNA, as well as both BID and cleaved-poly ADP ribosome polymerase (c-PARP) protein. Incubation of SP together with TNF-α resulted in a decreased amount of BID and c-PARP, and in a reduced lactate dehydrogenase release, as compared to incubation with TNF-α alone. The SP effect was blocked with a NK-1 R inhibitor.

    DISCUSSION: This study shows that SP, through stimulation of the NK-1 R, has the ability to reduce TNF-α-induced apoptosis of human tenocytes. Considering that SP has previously been shown to stimulate tenocyte proliferation, the study confirms SP as a potent regulator of cell-turnover in tendon tissue, capable of stimulating hypercellularity through different mechanisms. This gives further support for the theory that the upregulated amount of SP seen in tendinosis could contribute to hypercellularity.

  • 74.
    Bagge, J.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Alfredson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Nerve ingrowth into tendon tissue in Achilles tendinosis: a Case Report2013Inngår i: International journal of experimental pathology (Print), ISSN 0959-9673, E-ISSN 1365-2613, Vol. 94, nr 4, s. A8-A8Artikkel i tidsskrift (Annet vitenskapelig)
  • 75.
    Bagge, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    TNF-α and neurotrophins in Achilles tendinosis2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Tenocytes are the principal cells of the human Achilles tendon. In tendinosis, changes in the metabolism and morphology of these cells occur. Neurotrophins are growth factors essential for the development of the nervous system. Tumour necrosis factor alpha (TNF-α) has been found to kill sarcomas but has destructive effects in several major diseases. The two systems have interaction effects and are associated with apoptosis, proliferation, and pain signalling in various diseases. Whether these systems are present in the Achilles tendon and in Achilles tendinosis is unknown. The hypothesis is that the tenocytes produce substances belonging to these systems. In Studies I–III, we show that the potent effects of these substances are also likely to occur in the Achilles tendon. We found tenocyte immunoreactions for the neurotrophins brain-derived neurotrophic factor (BDNF), the nerve growth factor (NGF), the neurotrophin receptor p75, and for TNF-α and both of its receptors, TNFR1 and TNFR2. This occurred in both subjects with painful mid-portion Achilles tendinosis, and in controls. Furthermore, we found mRNA expression for BDNF and TNF-α in tenocytes, which proves that these cells produce these substances. TNFR1 mRNA was also detected for the tenocytes, and TNFR1 immunoreactions were upregulated in tendinosis tendons. This might explain why tenocytes in tendinosis undergo apoptosis more often than in normal tendons. Total physical activity (TPA) level and blood concentration of both soluble TNFR1 and BDNF were measured in Study IV. The results showed that the blood concentration of both factors were similar in subjects with tendinosis and in controls. Nevertheless, the TPA level was related to the blood concentration of sTNFR1 in tendinosis, but not in controls. This relationship should be studied further. The findings of this doctoral thesis show that neurotrophin and TNF-α systems are expressed in the Achilles tendon. We believe that the functions include tissue remodelling, proliferation and apoptosis.

  • 76.
    Bagge, Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Danielson, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    In situ hybridization studies favouring the occurrence of a local production of BDNF in the human Achilles tendon2012Inngår i: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 27, nr 9, s. 1239-1246Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Brain derived neurotrophic factor (BDNF) is a multipotent neurotrophin known for its growth-influencing and apoptosis-modulating functions, as well as for its function to interact with neurotransmitters/neuromodulators. BDNF is reported to be mainly produced in the brain. BDNF can be absorbed into peripheral tissue from the blood stream. Expression of this neurotrophin at the protein level, as well as of the neurotrophin receptor p75, has been previously shown for the principal cells (tenocytes) of the Achilles tendon. However, there is no proof at the mRNA level that BDNF is produced by the tenocytes. As the Achilles tendon tenocytes show "neuronal-like" characteristics, in the form of expressions favouring synthesis of several neuromodulators/neurotransmitters, and as BDNF especially is produced in neurons, it is of interest to confirm this. In the present study, therefore, in situ hybridization for demonstration of BDNF mRNA was performed on biopsies from Achilles tendons of patients with tendinosis and pain-free non-tendinosis individuals. The results showed that the tenocytes of both groups exhibited BDNF mRNA reactions. These observations indeed favour the idea that BDNF is produced by tenocytes in the human Achilles tendon, why Achilles tendon tissue is a tissue in which BDNF can be locally produced. BDNF can have modulatory functions for the tenocytes, including apoptosis-modifying effects via actions on the p75 receptor and interactive effects with neurotransmitters/neuromodulators produced in these cells. This possibility should be further studied for Achilles tendon tissue.

  • 77.
    Bagge, Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Gaida, JE
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Danielson, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Alfredson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Physical activity level in Achilles tendinosis is associated with blood levels of pain-related factors: a pilot study2011Inngår i: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 21, nr 6, s. E430-E438Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Physical activity affects the pain symptoms for Achilles tendinosis patients. Brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-alpha) and their receptors have been detected in human Achilles tendon. This pilot study aimed to compare serum BDNF and soluble tumor necrosis factor receptor I (sTNFRI) levels in Achilles tendinosis patients and healthy controls and to examine the influence of physical activity, and BMI and gender, on these levels. Physical activity was measured with a validated questionnaire, total physical activity being the parameter analyzed. Physical activity was strongly correlated with BDNF among tendinosis women [Spearman's rho (rho) = 0.90, P < 0.01] but not among control women (rho = -0.08, P = 0.83), or among tendinosis and control men. Physical activity was significantly correlated with sTNFRI in the entire tendinosis group and among tendinosis men (rho = 0.65, P = 0.01), but not in the entire control group or among control men (rho = 0.04, P = 0.91). Thus, the physical activity pattern is related to the TNF and BDNF systems for tendinosis patients but not controls, the relationship being gender dependent. This is new information concerning the relationship between physical activity and Achilles tendinosis, which may be related to pain for the patients. This aspect should be further evaluated using larger patient materials.

  • 78.
    Bagge, Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Lorentzon, Ronny
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Alfredson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Unexpected presence of the neurotrophins NGF and BDNF and the neurotrophin receptor p75 in the tendon cells of the human Achilles tendon2009Inngår i: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 24, nr 7, s. 839-848Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neurotrophins are substances that have been shown to be important in growth and remodelling phases in different types of tissue. There is no information concerning the possible occurrences of neurotrophins and their receptors in tendons. In this study, sections of both chronic painful (tendinosis) and pain-free (non-tendinosis) human Achilles tendons were immunohistochemically stained with antibodies against the neurotrophins NGF and BDNF, and their receptors TrkA, TrkB and p75. There were marked immunoreactions for NGF and BDNF in the tendon cells (tenocytes) of both tendinosis and non-tendinosis specimens. The tenocytes were also reactive for the receptor p75, but not for the receptors TrkA and TrkB. In addition, p75 immunoreactions were seen in nerve fascicles and in the walls of arterioles. This is the first study to identify neurotrophins in the tenocytes of human tendon. It is clear from this study that the local cells of tendons are sources of neurotrophins. The neurotrophins may play an important role in the tendon through their interaction with the receptor p75 in the tenocytes. These interactions may regulate tropic modulatory, and apoptotic effects. In conclusion, the observations show a new concept concerning production and function of neurotrophins, namely in the tenocytes of tendons.

  • 79.
    Bain, G. I.
    et al.
    Australia .
    Polites, N.
    Australia .
    Higgs, B. G.
    Australia .
    Heptinstall, R. J.
    Unaffiliated .
    McGrath, Aleksandra
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    The functional range of motion of the finger joints2015Inngår i: Journal of Hand Surgery, European Volume, ISSN 1753-1934, E-ISSN 2043-6289, Vol. 40, nr 4, s. 406-411Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The purpose of this study was to measure the functional range of motion of the finger joints needed to perform activities of daily living. Using the Sollerman hand grip function test, 20 activities were assessed in ten volunteers. The active and passive range of motion was measured with a computerized electric goniometer. The position of each finger joint was evaluated in the pre-grasp and grasp positions. The functional range of motion was defined as the range required to perform 90% of the activities, utilizing the pre-grasp and grasp measurements. The functional range of motion was 19 degrees-71 degrees, 23 degrees-87 degrees, and 10 degrees-64 degrees at the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints, respectively. This represents 48%, 59%, and 60% of the active motion of these joints, respectively. There was a significant difference in the functional range of motion between the joints of the fingers, with the ulnar digits having greater active and functional range. The functional range of motion is important for directing indications for surgery and rehabilitation, and assessing outcome of treatment.

  • 80. Bain, Gregory I
    et al.
    McGuire, Duncan T
    McGrath, Aleksandra M
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    A Simplified Lateral Hinge Approach to the Proximal Interphalangeal Joint2015Inngår i: Techniques in Hand & Upper Extremity Surgery, ISSN 1089-3393, E-ISSN 1531-6572, Vol. 19, nr 3, s. 129-132Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Proximal interphalangeal joint replacement is an effective treatment for painful arthritis affecting the joint. However, the complication rate is relatively high, with many of these complications related to soft-tissue imbalance or instability. Volar, dorsal, and lateral approaches have all been described with varying results. We describe a new simplified lateral hinge approach that splits the collateral ligament to provide adequate exposure of the joint. Following insertion of the prosthesis the collateral ligament is simply repaired, side-to-side, which stabilizes the joint. As the central slip, opposite collateral ligament, flexor and extensor tendons have not been violated, early active mobilization without splinting is possible, and the risk of instability, swan-neck, and boutonniere deformity are reduced. The indications, contraindications, surgical technique, and rehabilitation protocol are described.

  • 81.
    Baugh, Lee A.
    et al.
    Queen's University Kingston, Ontario.
    Kao, Michelle
    Queen's University Kingston, Ontario.
    Johansson, Roland S.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Flanagan, J. Randall
    Queen's University Kingston, Ontario.
    Material evidence: interaction of well-learned priors and sensorimotor memory when lifting objects2012Inngår i: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 108, nr 5, s. 1262-1269Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Skilled object lifting requires the prediction of object weight. When lifting new objects, such prediction is based on well-learned size-weight and material-density correlations, or priors. However, if the prediction is erroneous, people quickly learn the weight of the particular object and can use this knowledge, referred to as sensorimotor memory, when lifting the object again. In the present study, we explored how sensorimotor memory, gained when lifting a given object, interacts with well-learned material-density priors when predicting the weight of a larger but otherwise similar-looking object. Different groups of participants 1st lifted 1 of 4 small objects 10 times. These included a pair of wood-filled objects and a pair of brass-filled objects where 1 of each pair was covered in a wood veneer and the other was covered in a brass veneer. All groups then lifted a larger, brass-filled object with the same covering as the small object they had lifted. For each lift, we determined the initial peak rate of change of vertical load-force rate and the load-phase duration, which provide estimates of predicted object weight. Analysis of the 10th lift of the small cube revealed no effects of surface material, indicating participants learned the appropriate forces required to lift the small cube regardless of object appearance. However, both surface material and core material of the small cube affected the 1st lift of the large block. We conclude that sensorimotor memory related to object density can contribute to weight prediction when lifting novel objects but also that long-term priors related to material properties can influence the prediction.

  • 82. Baugh, Lee A.
    et al.
    Yak, Amelie
    Johansson, Roland S.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Flanagan, J. Randall
    Representing multiple object weights: competing priors and sensorimotor memories2016Inngår i: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 116, nr 4, s. 1615-1625Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    When lifting an object, individuals scale lifting forces based on long-term priors relating external object properties (such as material and size) to object weight. When experiencing objects that are poorly predicted by priors, people rapidly form and update sensorimotor memories that can be used to predict an object's atypical size-weight relation in support of predictively scaling lift forces. With extensive experience in lifting such objects, long-term priors, assessed with weight judgments, are gradually updated. The aim of the present study was to understand the formation and updating of these memory processes. Participants lifted, over multiple days, a set of black cubes with a normal size-weight mapping and green cubes with an inverse size-weight mapping. Sensorimotor memory was assessed with lifting forces, and priors associated with the black and green cubes were assessed with the size-weight illusion (SWI). Interference was observed in terms of adaptation of the SWI, indicating that priors were not independently adjusted. Half of the participants rapidly learned to scale lift forces appropriately, whereas reduced learning was observed in the others, suggesting that individual differences may be affecting sensorimotor memory abilities. A follow-up experiment showed that lifting forces are not accurately scaled to objects when concurrently performing a visuomotor association task, suggesting that sensorimotor memory formation involves cognitive resources to instantiate the mapping between object identity and weight, potentially explaining the results of experiment 1. These results provide novel insight into the formation and updating of sensorimotor memories and provide support for the independent adjustment of sensorimotor memory and priors.

  • 83. Bengtsson, Fredrik
    et al.
    Brasselet, Romain
    Johansson, Roland S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Arleo, Angelo
    Jörntell, Henrik
    Integration of sensory quanta in cuneate nucleus neurons in vivo2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 2, s. e56630-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Discriminative touch relies on afferent information carried to the central nervous system by action potentials (spikes) in ensembles of primary afferents bundled in peripheral nerves. These sensory quanta are first processed by the cuneate nucleus before the afferent information is transmitted to brain networks serving specific perceptual and sensorimotor functions. Here we report data on the integration of primary afferent synaptic inputs obtained with in vivo whole cell patch clamp recordings from the neurons of this nucleus. We find that the synaptic integration in individual cuneate neurons is dominated by 4-8 primary afferent inputs with large synaptic weights. In a simulation we show that the arrangement with a low number of primary afferent inputs can maximize transfer over the cuneate nucleus of information encoded in the spatiotemporal patterns of spikes generated when a human fingertip contact objects. Hence, the observed distributions of synaptic weights support high fidelity transfer of signals from ensembles of tactile afferents. Various anatomical estimates suggest that a cuneate neuron may receive hundreds of primary afferents rather than 4-8. Therefore, we discuss the possibility that adaptation of synaptic weight distribution, possibly involving silent synapses, may function to maximize information transfer in somatosensory pathways.

  • 84. Bergdahl, Maud
    et al.
    Bergdahl, Jan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nilsson, Lars-Göran
    Psykologiska institutionen, Stockholms universitet.
    Difference in apolipoprotein E type 4 allele (APOE e4) amongdentate and edentulous subjects2008Inngår i: Gerodontology, ISSN 0734-0664, E-ISSN 1741-2358, Vol. 25, nr 3, s. 179-186Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: To evaluate the frequency of apolipoprotein (APOE) alleles and determine whether APOE type 4 allele (e4) was associated with edentulousness even when certain factors were controlled.Background: The APOE are important in lipid homeostasis, and APOE e4 has been found in many diseases and to have a negative impact on longevity. Tooth loss is more common in ill aged subjects with low income and education.Materials and methods: In a population-based study involving 1860 subjects between 35 and 85 years 1321 dentate (mean age = 54; 54% women, 46% men) and 539 edentulous (mean age = 72; 62% women, 38% men) subjects were studied. Logistic regression was performed with dentate/edentulous as dependent variables and years of education, socio-economic status, social network, stress level, handicap from birth, 23 various diseases and APOE e4 as covariates. Thereafter, APOE e4 frequencies were studied in 342 dentateand 336 edentulous subjects 50–85 years of age. The subjects were matched with regard to age, gender, years of education, living condition, stress level, handicap from birth and 23 various diseases.Results: APOE allele frequency in the total group was e2 = 7.8%, e3 = 76.4% and e4 = 15.8%. Age, living condition, years of education and APOE e4 were significant covariates in edentulous subjects (p £ 0.001).APOE e4 in the matched groups revealed significant differences between the dentate group and the edentulous group (v2 = 5.68; p = 0.017). There was no group effect (F(29,648) = 0.849; p < 0.696; Wilks’ lambda = 0.963). In the dentate group, the frequencies of APOE were: e2 = 8.8%, e3 = 77.9% ande4 = 13.3%. Corresponding frequencies of APOE in the edentulous group were: e2 = 6.6%, e3 = 75.4% and e4 = 18.0%.Conclusion: Despite matching both groups with regard to different background factors, the edentulous group had a higher frequency of APOE e4 than the dentate group. Thus, genetic factors might contribute to greater risk in developing complex oral diseases leading to tooth loss or just be an indication that the subjects in our study carrying APOE e4 are more fragile.

  • 85. Bergdahl, Maud
    et al.
    Habib, Reza
    Bergdahl, Jan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Nilsson, Lars-Göran
    Natural teeth and cognitive function in humans2007Inngår i: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 48, nr 6, s. 557-565Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A number of neurobiological, psychological and social factors may account for cognitive impairment. In animal studies a relation between dental status and cognitive performance has been found. It is unclear whether such a relation exists for humans. In a first step we compared the performance of 1,351 participants (53% women, 47% men; age M = 54.0) with natural teeth to 487 edentulous participants (59% women, 41% men; age M = 71.3) on 12 cognitive tests. The natural teeth group had a lower mean age, fewer women, more years of education, higher mini-mental state (MMSE), and performed significantly higher on several cognitive tests. In a subsequent analysis, the cognitive performance of a subset of the participants (50–85 years) was examined. In this analysis, 211 had natural dentition and 188 were edentulous. The groups were matched for gender, age, social variables, diseases, stress and MMSE. The cognitive disadvantage of the edentulous group was still apparent. The results suggest that functional natural teeth relate to relatively preserved cognitive functioning in older age.

  • 86.
    Bergh, Elisabeth
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    General muscle morphology and satellite cells in master elite skiers2012Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
  • 87.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Ekman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Fatigue after traumatic brain injury is linked to altered striato-thalamic-cortical functioning2017Inngår i: Brain Injury: Accepted Abstracts from the International Brain Injury Association’s 12th World Congress on Brain Injury, 2017, Vol. 31, s. 755-755Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Mental fatigue is a common symptom in the chronic phase of traumatic brain injury. Despite its high prevalence, no treatmentis available for this disabling symptom, and the mechanisms underlying fatigue are poorly understood. Some studies have suggested that fatigue in traumatic brain injury and other neurological disorders might reflect dysfunction within striato-thalamic-cortical loops. In the present study, we investigated whether functional magnetic resonance imaging(fMRI) can be used to detect chronic fatigue after traumatic brain injury (TBI), with emphasis on the striato-thalamic cortical-loops. We included patients who had suffered traumatic brain injury (n = 57, age range 20–64 years) and experienced mental fatigue > 1 year post injury (mean = 8.79 years, SD = 7.35), and age- and sex-matched healthycontrols (n = 27, age range 25–65 years). All participants completed self-assessment scales of fatigue and other symptoms, underwent an extensive neuropsychological test battery and performed a fatiguing 27-minute attention task (the modified Symbol Digit Modalities Test) during fMRI. Accuracy did not differ between groups, but reaction times were slower in the traumatic brain injury group (p < 0.001). Patients showed a greater increase in fatigue than controls from before to after task completion (p < 0.001). Patients showed less fMRI blood oxygen level–dependent activity in several a priori hypothesized regions (family-wise error corrected,p < 0.05), including the bilateral caudate, thalamus and anterior insula. Using the left caudate as a region of interest and testing for sensitivity and specificity, we identified 91% of patients and 81% of controls. As expected, controls showed decreased activation over time in regions of interest—the bilateral caudate and anterior thalamus (p < 0.002, uncorrected)—whereas patients showed no corresponding activity decrease. These results suggest that chronic fatigue after TBI is linked to altered striato-thalamic-cortical functioning. The high precision of fMRI for the detection of fatigue is of great clinical interest, given the lack of objective measures for the diagnosis of fatigue.

  • 88.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Ekman, Urban
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Using Functional Magnetic Resonance Imaging to Detect Chronic Fatigue in Patients With Previous Traumatic Brain Injury: changes linked to altered Striato-Thalamic-Cortical Functioning2018Inngår i: The journal of head trauma rehabilitation, ISSN 0885-9701, E-ISSN 1550-509X, Vol. 33, nr 4, s. 266-274Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To investigate whether functional magnetic resonance imaging (fMRI) can be used to detect fatigue after traumatic brain injury (TBI).

    Setting: Neurorehabilitation clinic.

    Participants: Patients with TBI (n = 57) and self-experienced fatigue more than 1 year postinjury, and age- and gender-matched healthy controls (n = 27).

    Main Measures: Self-assessment scales of fatigue, a neuropsychological test battery, and fMRI scanning during performance of a fatiguing 27-minute attention task.

    Results: During testing within the fMRI scanner, patients showed a higher increase in self-reported fatigue than controls from before to after completing the task (P < .001).The patients also showed lower activity in several regions, including bilateral caudate, thalamus, and anterior insula (all P < .05). Furthermore, the patients failed to display decreased activation over time in regions of interest: the bilateral caudate and anterior thalamus (all P < .01). Left caudate activity correctly identified 91% of patients and 81% of controls, resulting in a positive predictive value of 91%.

    Conclusion: The results suggest that chronic fatigue after TBI is associated with altered striato-thalamic-cortical functioning. It would be of interest to study whether fMRI can be used to support the diagnosis of chronic fatigue in future studies.

  • 89.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    White matter hyperintensities increases with traumatic brain injuryseverity: associations to neuropsychological performance and fatigueManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Objective: To examine the prevalence of white matter hyperintensities (WMHs) in patients with traumatic brain injury (TBI) as compared to healthy controls, and to investigate whether there is an association between WMH lesion burden and performance on neuropsychological tests in patients with TBI.

    Methods: A total of 59 patients with TBI and 27 age- and gender- matched healthy controls underwent thorough neuropsychological testing and magnetic resonance imaging. The quantification of WMH lesions was performed using the fully automated Lesion Segmentation Tool.

    Results: WMH lesions were more common in patients with TBI than in healthy controls (p = 0.032), and increased with higher TBI severity (p = 0.025). Linear regressions showed that WMH lesions in patients with TBI were not related to performance on any neuropsychological tests (p > 0.05 for all). However, a negative relationship between number of WMH lesions in patients with TBI and self-assessed fatigue was found (r = –0.33, p = 0.026).

    Conclusion: WMH lesions are more common in patients with TBI than in healthy controls, and WMH lesions burden increases with TBI severity. However, these lesions do not seem to explain the decreased cognitive functioning or the increased fatigue in patients with TBI.

  • 90.
    Berglöf, Elisabet
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Histologi med cellbiologi.
    Dopamine neurons in ventral mesencephalon: interactions with glia and locus coeruleus2008Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Parkinson’s disease is a progressive neurodegenerative disorder, characterized by a depletion of the dopaminergic neurons in the substantia nigra. The cause of the disease is yet unknown but age, oxidative stress, and neuroinflammation are some of the features involved in the degeneration. In addition, substantial cell death of noradrenergic neurons occurs in the locus coeruleus (LC). Noradrenaline has been suggested to protect the dopamine neurons from oxidative stress and neuroinflammation. The main treatment of Parkinson’s disease is Levo-dopa, although severe side effects arise from this therapy. Hence, grafting fetal ventral mesencephalic (VM) tissue into the adult striatum has been evaluated as an alternative treatment for Parkinsons’s disease. However, the survival of the grafted neurons is limited, and the dopamine-denervated striatum does not become fully reinnervated. Therefore, elucidating factors that enhance dopamine nerve fiber formation and/or survival of the grafted neurons is of utmost importance.

    To investigate dopamine nerve fiber formation and the interactions with glial cells, organotypic VM tissue cultures were utilized. Two morphologically different nerve fiber outgrowths from the tissue slice were observed. Nerve fibers were initially formed in the absence of migrating astrocytes, although thin vimentin-positive astrocytic processes were detected within the same area. A second, persistent nerve fiber outgrowth was observed associated with migrating astrocytes. Hence, both of these nerve fiber outgrowths were to some extent dependent on astrocytes, and appeared as a general feature since this phenomenon was demonstrated in β-tubulin, tyrosine hydroxylase (TH), and aldehyde dehydrogenase A1 (ALDH1)-positive nerve fibers. Neither oligodendrocytes (NG2-positive cells), nor microglia (Iba-1-positive cells) exerted any effect on these two neuronal growths. Since astrocytes appeared to influence the nerve fiber formation, the role of proteoglycans, i.e. extracellular matrix molecules produced by astrocytes, was investigated. β-xyloside was added to the cultures to inhibit proteoglycan synthesis. The results revealed a hampered astrocytic migration and proliferation, as well as a reduction of the glia-associated TH-positive nerve fiber outgrowth. Interestingly, the number of cultures displaying the non-glia-mediated TH-positive nerve fibers increased after β-xyloside treatment, although the amount of TH-protein was not altered. Thus, proteoglycans produced by astrocytes appeared to be important in affecting the dopamine nerve fiber formation.

    The noradrenaline neurons in LC have been suggested to protect dopamine neurons from damage. Therefore, the interaction between VM and LC was evaluated. Using the intraocular grafting method, fetal VM and LC were grafted either as single grafts or as VM+LC co-grafts. Additionally, the recipient animals received 2% blueberry-enriched diet. The direct contact of LC promoted graft volume and survival of TH-positive neurons in the VM grafts. The number of dopamine neurons, derived preferably from the A9 (ALDH1/TH-positive) was increased, whereas the dopamine neurons from the A10 (calbindin/TH-positive) were not affected. A dense dopamine-β-hydroxylase (DBH)-positive innervation was correlated to the improved survival. Blueberry-enriched diet enhanced the number of TH-positive neurons in VM, although the graft size was not altered. The combination of blueberries and the presence of LC did not yield additive effects on the survival of VM grafts. The attachment of VM or the addition of blueberries did not affect the survival of TH-positive neurons in LC grafts. The number of Iba-1-positive microglia was decreased in co-grafted VM compared to single VM transplants. The addition of blueberries reduced the number of Iba-1-positive microglia in single VM transplants. Hence, the direct contact of LC or the addition of blueberries enhanced the survival of VM grafts.

    Taken together, these data demonstrate novel findings regarding the importance of astrocytes for the nerve fiber formation of dopamine neurons. Further, both the direct attachment of LC or antioxidant-enriched diet promote the survival of fetal VM grafts, while LC is not affected.

  • 91.
    Berglöf, Elisabet
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi. Histologi med cellbiologi.
    Af Bjerkén, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi. Histologi med cellbiologi.
    Strömberg, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi. Histologi med cellbiologi.
    Glial influence on nerve fiber formation from rat ventral mesencephalic organotypic tissue cultures.2007Inngår i: Journal of Comparative Neurology, ISSN 0021-9967, Vol. 501, nr 3, s. 431-42Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Rat fetal ventral mesencephalic organotypic cultures have demonstrated two morphologically different dopamine nerve fiber growth patterns, in which the initial nerve fibers are formed in the absence of astrocytes and the second wave is guided by astrocytes. In this study, the presence of subpopulations of dopamine neurons, other neuronal populations, and glial cells was determined. We used "roller-drum" organotypic cultures, and the results revealed that beta-tubulin-positive/tyrosine hydroxylase (TH)-negative nerve fibers were present as early as 1 day in vitro (DIV). A similar growth pattern produced by TH-positive neurons was present from 2 DIV. These neurites grew to reach distances over 4 mm and over time appeared to be degenerating. Thin, vimentin-positive processes were found among these nerve fibers. As the first growth was retracted, a second outgrowth was initiated and formed on migrating astrocytes. TH- and aldehyde dehydrogenase-1 (ALDH1)-positive nerve fibers formed both the nonglia-associated and the glia-associated outgrowth. In cultures with membrane inserts, only the glia-associated outgrowth was found. Vimentin-positive cells preceded migration of NG2-positive oligodendrocytes and Iba-1-positive microglia. Oligodendrocytes appeared not to be involved in guiding neuritic growth, but microglia was absent over areas dense with TH-positive neurons. In conclusion, in "roller-drum" cultures, nerve fibers are generally formed in two sequences. The early-formed nerve fibers grow in the presence of thin, vimentin-positive processes. The second nerve fiber outgrowth is formed on astroglia, with no correlation to the presence of oligodendrocytes or microglia. ALDH1-positive nerve fibers, presumably derived from A9 dopamine neurons, participate in formation of both sequences of outgrowth.

  • 92.
    Berglöf, Elisabet
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Bickford, Paula C.
    Strömberg, Ingrid
    Blueberry-enriched diet enhances the survival of fetal ventral mesencephalic intraocular graftsManuskript (Annet vitenskapelig)
  • 93.
    Berglöf, Elisabet
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Plantman, Stefan
    Johansson, Saga
    Strömberg, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Inhibition of proteoglycan synthesis affects neuronal outgrowth and astrocytic migration in organotypic cultures of fetal ventral mesencephalon2008Inngår i: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 86, nr 1, s. 84-92Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Grafting fetal ventral mesencephalon has been utilized to alleviate the symptoms of Parkinson's disease. One obstacle in using this approach is the limited outgrowth from the transplanted dopamine neurons. Thus, it is important to evaluate factors that promote outgrowth from fetal dopamine neurons. Proteoglycans (PGs) are extracellular matrix molecules that modulate neuritic growth. This study was performed to evaluate the role of PGs in dopamine nerve fiber formation in organotypic slice cultures of fetal ventral mesencephalon. Cultures were treated with the PG synthesis inhibitor methyl-umbelliferyl-beta-D-xyloside (beta-xyloside) and analyzed using antibodies against tyrosine hydroxylase (TH) to visualize dopamine neurons, S100beta to visualize astrocytes, and neurocan to detect PGs. Two growth patterns of TH-positive outgrowth were observed: nerve fibers formed in the presence of astrocytes and nerve fibers formed in the absence of astrocytes. Treatment with beta-xyloside significantly reduced the distance of glial-associated TH-positive nerve fiber outgrowth but did not affect the length of the non-glial-associated nerve fibers. The addition of beta-xyloside shifted the nerve fiber growth pattern from being mostly glial-guided to being non-glial-associated, whereas the total amount of TH protein was not affected. Further, astrocytic migration and proliferation were impaired after beta-xyloside treatment, and levels of non-intact PG increased. beta-Xyloside treatment changed the distribution of neurocan in astrocytes, from being localized in vesicles to being diffusely immunoreactive in the processes. To conclude, inhibition of PG synthesis affects glial-associated TH-positive nerve fiber formation in ventral mesencephalic cultures, which might be an indirect effect of impaired astrocytic migration. (c) 2007 Wiley-Liss, Inc.

  • 94.
    Berglöf, Elisabet
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Small, Brent J
    School of Aging Studies, University of South Florida, Tampa, Florida 33620.
    Bickford, Paula C
    Department of Neurosurgery and Department of Molecular Pharmacology and Physiology, University of South Florida and James A. Haley VA Medical Center, Tampa, Florida 33620.
    Strömberg, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Beneficial effects of antioxidant-enriched diet for tyrosine hydroxylase-positive neurons in ventral mesencephalic tissue in oculo grafts2009Inngår i: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 515, nr 1, s. 72-82Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Supplementation of antioxidants to the diet has been proved to be beneficial in aging and after brain injury. Furthermore, it has been postulated that the locus coeruleus promotes survival of dopamine neurons. Thus, this study was performed to elucidate the effects of a blueberry-enriched diet on fetal ventral mesencephalic tissue in the presence or absence of locus coeruleus utilizing the in oculo grafting method. Sprague-Dawley rats were given control diet or diet supplemented with 2% blueberries, and solid tissue pieces of fetal locus coeruleus and ventral mesencephalon were implanted as single and co-grafts. The results revealed that the presence of locus coeruleus tissue or the addition of blueberries enhanced the survival of ventral mesencephalic tyrosine hydroxylase (TH)-positive neurons, whereas no additive effects were observed for the two treatments. The density of TH-positive nerve fibers in ventral mesencephalic tissue was significantly elevated when it was attached to the locus coeruleus or by blueberry treatment, whereas the innervation of dopamine-beta-hydroxylase-positive nerve fibers was not altered. The presence of locus coeruleus tissue or bluberry supplementation reduced the number of Iba-1-positive microglia in the ventral mesencephalic portion of single and co-grafts, respectively, whereas almost no OX6 immunoreactivity was found. Furthermore, neither the attachment of ventral mesencephalic tissue nor the addition of blueberries improved the survival of TH-positive neurons in the locus coerulean grafts. To conclude, locus coeruleus and blueberries are beneficial for the survival of fetal ventral mesencephalic tissue, findings that could be useful when grafting tissue in Parkinson's disease.

  • 95.
    Berglöf, Elisabet
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Strömberg, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Locus coeruleus promotes survival of dopamine neurons in ventral mesencephalon: An in oculo grafting study2009Inngår i: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 216, nr 1, s. 158-165Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Parkinson's disease is a neurodegenerative disorder where dopamine neurons in the substantia nigra of ventral mesencephalon undergo degeneration. In addition to the loss of dopamine neurons, noradrenaline neurons in the locus coeruleus degenerate, actually to a higher extent than the dopamine neurons. The interaction between these two nuclei is yet not fully known, hence this study was undertaken to investigate the role of locus coeruleus during development of dopamine neurons utilizing the intraocular grafting model. Fetal ventral mesencephalon and locus coeruleus were implanted either as single grafts or co-grafts, placed in direct contact or at a distance. The results revealed that the direct attachment of locus coeruleus to ventral mesencephalon enhanced graft volume and number of tyrosine hydroxylase (TH)-positive neurons in ventral mesencephalic grafts. Cell counts of subpopulations of TH-positive neurons also immunoreactive for aldehyde dehydrogenase 1-A1 (ALDH1) or calbindin, revealed improved survival of ALDH1/TH-positive neurons. However, the number of calbindin/TH-positive neurons was not affected. High density of dopamine-beta-hydroxylase (DBH)-positive innervation in the ventral mesencephalon placed adjacent to locus coeruleus was correlated to the improved survival. Ventral mesencephalic tissue, implanted at a distance to locus coeruleus, did not demonstrate improved survival, although DBH-positive nerve fibers were detected. In conclusion, the direct contact of locus coeruleus resulting in dense noradrenergic innervation of ventral mesencephalon is beneficial for the survival of ventral mesencephalic grafts. Thus, when trying to rescue dopamine neurons in Parkinson's disease, improving the noradrenergic input to the substantia nigra might be worth considering.

  • 96. Bergouignan, Loretxu
    et al.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Ehrsson, H. Henrik
    Out-of-body-induced hippocampal amnesia2014Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, nr 12, s. 4421-4426Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Theoretical models have suggested an association between the ongoing experience of the world from the perspective of one's own body and hippocampus-based episodic memory. This link has been supported by clinical reports of long-term episodic memory impairments in psychiatric conditions with dissociative symptoms, in which individuals feel detached from themselves as if having an out-of-body experience. Here, we introduce an experimental approach to examine the necessary role of perceiving the world from the perspective of one's own body for the successful episodic encoding of real-life events. While participants were involved in a social interaction, an out-of-body illusion was elicited, in which the sense of bodily self was displaced from the real body to the other end of the testing room. This condition was compared with a well-matched in-body illusion condition, in which the sense of bodily self was colocalized with the real body. In separate recall sessions, performed similar to 1 wk later, we assessed the participants' episodic memory of these events. The results revealed an episodic recollection deficit for events encoded out-of-body compared with in-body. Functional magnetic resonance imaging indicated that this impairment was specifically associated with activity changes in the posterior hippocampus. Collectively, these findings show that efficient hippocampus-based episodic-memory encoding requires a first-person perspective of the natural spatial relationship between the body and the world. Our observations have important implications for theoretical models of episodic memory, neurocognitive models of self, embodied cognition, and clinical research into memory deficits in psychiatric disorders.

  • 97.
    Bergström, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    The neural substrates of non-conscious working memory2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: Despite our distinct impression to the contrary, we are only conscious of a fraction of all the neural activity underlying our thoughts and behavior. Most neural processes occur non-consciously, and in parallel with our conscious experience. However, it is still unclear what the limits of non-conscious processes are in terms of higher cognitive functions. Many recent studies have shown that increasingly more advanced functions can operate non-consciously, but non-conscious information is still thought to be fleeting and undetectable within 500 milliseconds. Here we used various techniques to render information non-conscious, together with functional magnetic resonance imaging (fMRI), to investigate if non-consciously presented information can be retained for several seconds, what the neural substrates of such retention are, and if it is consistent with working memory maintenance.

    Results: In Study I we used an attentional blink paradigm to render stimuli (single letters) non-conscious, and a variable delay period (5 – 15 s) prior to memory test. It was found that non-conscious memory performance was above chance after all delay durations, and showed no signs of decline over time. Univariate fMRI analysis showed that the durable retention was associated with sustained BOLD signal change in the prefrontal cortex and cerebellum during the delay period. In Study II we used continuous flash suppression (CFS) to render stimuli (faces and tools) non-conscious, and a variable delay period (5 or 15 s) prior to memory test. The durable retention of up to 15 s was replicated, and it was found that stimuli identity and spatial position was retained until prospective use. In Study III we used CFS to render tools non-conscious, and a variable delay period (5 – 15 s) prior to memory test. It was found that memory performance was not better than chance. However, by using multi-voxel pattern analysis it was nonetheless possible to detect the presence vs. absence of non-conscious stimuli in the frontal cortex,and their spatial position (left vs. right) in the occipital cortex during the delay.

    Conclusions: Overall these findings suggest that non-consciously presented information (identity and/or position) can be retained for several seconds,and is associated with BOLD signal in frontal and posterior regions. These findings are consistent with working memory maintenance of non-consciously presented information, and thereby constrain models of working memory and theories of consciousness.

  • 98.
    Bergström, Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Maintenance of non-consciously presented information engages the prefrontal cortex2014Inngår i: Frontiers in Human Neuroscience, ISSN 1662-5161, E-ISSN 1662-5161, Vol. 8, s. 938-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conscious processing is generally seen as required for flexible and willful actions, as well as for tasks that require durable information maintenance. Here we present research that questions the assumption that only consciously perceived information is durable (>500 ms). Using the attentional blink (AB) phenomenon, we rendered otherwise relatively clearly perceived letters non conscious. In a first experiment we systematically manipulated the delay between stimulus presentation and response, for the purpose of estimating the durability of non-conscious perceptual representations. For items reported not seen, we found that behavioral performance was better than chance across intervals up to 15 s. In a second experiment we used fMRI to investigate the neural correlates underlying the maintenance of non conscious perceptual representations. Critically, the relatively long delay period demonstrated in experiment 1 enabled isolation of the signal change specifically related to the maintenance period, separate from stimulus presentation and response. We found sustained BOLD signal change in the right mid-lateral prefrontal cortex, orbitofrontal cortex, and crus II of the cerebellum during maintenance of non consciously perceived information. These findings are consistent with the controversial claim that working-memory mechanisms are involved in the short-term maintenance of non-conscious perceptual representations.

  • 99.
    Bergström, Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Faculty of Psychology and Educational Sciences, University of Coimbra, Portugal.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Neural evidence for non-conscious working memory2018Inngår i: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 28, nr 9, s. 3217-3228Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent studies have found that non-consciously perceived information can be retained for several seconds, a feat that has been attributed to non-conscious working memory processes. However, these studies have mainly relied on subjective measures of visual experience, and the neural processes responsible for non-conscious short-term retention remains unclear. Here we used continuous flash suppression to render stimuli non-conscious in a delayed match-to-sample task together with fMRI to investigate the neural correlates of non-conscious short-term (5-15 s) retention. The participants' behavioral performance was at chance level when they reported no visual experience of the sample stimulus. Critically, multivariate pattern analyses of BOLD signal during the delay phase could classify presence versus absence of sample stimuli based on signal patterns in frontal cortex, and its spatial position based on signal patterns in occipital cortex. In addition, univariate analyses revealed increased BOLD signal change in prefrontal regions during memory recognition. Thus, our findings demonstrate short-term maintenance of information presented non-consciously, defined by chance performance behaviorally. This non-consciously retained information seems to rely on persistent neural activity in frontal and occipital cortex, and may engage further cognitive control processes during memory recognition.

  • 100.
    Bergström, Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    The conjunction of non-consciously perceived object identity and spatial position can be retained during a visual short-term memory task2015Inngår i: Frontiers in Psychology, ISSN 1664-1078, E-ISSN 1664-1078, Vol. 6, artikkel-id 1470Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Although non-consciously perceived information has previously been assumed to be short-lived (<500 ms), recent findings show that non-consciously perceived information can be maintained for at least 15s Such findings can be explained as working memory without a conscious experience of the information to be retained. However, whether or not working memory can operate on non-consciously perceived information remains controversial, and little is known about the nature of such non-conscious visual short-term memory (VSTM). Here we used continuous flash suppression to render stimuli non-conscious, to investigate the properties of non-consciously perceived representations in delayed match-to-sample (DMS) tasks. In Experiment I we used variable delays (5 or 15s) and found that performance was significantly better than chance and was unaffected by delay duration, thereby replicating previous findings. In Experiment II the DMS task required participants to combine information of spatial position and object identity on a trial-by-trial basis to successfully solve the task. We found that the conjunction of spatial position and object identity was retained, thereby verifying that non-conscious, trial-specific information can be maintained for prospective use. We conclude that our results are consistent with a working memory interpretation, but that more research is needed to verify this interpretation.

1234567 51 - 100 of 1301
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf