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  • 151.
    Jonsson, Bert
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Stigsdotter Neely, Anna
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Working memory training in children with special education needs: A pilot study2008Conference paper (Other academic)
  • 152.
    Josefsson, Maria
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    de Luna, Xavier
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Daniels, Michael
    University of Texas at Austin.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Causal inference with longitudinal outcomes and non-ignorable drop-out: Estimating the effect of living alone on cognitive decline2016In: Journal of the Royal Statistic Society, Series C: Applied Statistics, ISSN 0035-9254, E-ISSN 1467-9876, Vol. 65, no 1, p. 131-144Article in journal (Refereed)
    Abstract [en]

    We develop a model to estimate the causal effect of living arrangement (living alone versus living with someone) on cognitive decline based on a 15-year prospective cohort study, where episodic memory function is measured every 5 years. One key feature of the model is the combination of propensity score matching to balance confounding variables between the two living arrangement groups—to reduce bias due to unbalanced covariates at baseline, with a pattern–mixture model for longitudinal data—to deal with non-ignorable dropout. A fully Bayesian approach allows us to convey the uncertainty in the estimation of the propensity score and subsequent matching in the inference of the causal effect of interest. The analysis conducted adds to previous studies in the literature concerning the protective effect of living with someone, by proposing a modelling approach treating living arrangement as an exposure.

  • 153.
    Josefsson, Maria
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    de Luna, Xavier
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Pudas, Sara
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nilsson, Lars-Göran
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Population Studies (CPS). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Genetic and lifestyle predictors of 15-Year longitudinal change in episodic memory2012In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 60, no 12, p. 2308-2312Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To reveal distinct longitudinal trajectories in episodic memory over 15 years and to identify demographic, lifestyle, health-related, and genetic predictors of stability or decline. DESIGN: Prospective cohort study. SETTING: The Betula Project, Umeå, Sweden. PARTICIPANTS: One thousand nine hundred fifty-four healthy participants aged 35 to 85 at baseline. MEASUREMENTS: Memory was assessed according to validated episodic memory tasks in participants from a large population-based sample. Data were analyzed using a random-effects pattern-mixture model that considered the effect of attrition over two to four longitudinal sessions. Logistic regression was used to determine significant predictors of stability or decline relative to average change in episodic memory. RESULTS: Of 1,558 participants with two or more test sessions, 18% were classified as maintainers and 13% as decliners, and 68% showed age-typical average change. More educated and more physically active participants, women, and those living with someone were more likely to be classified as maintainers, as were carriers of the met allele of the catechol-O-methyltransferase gene. Less educated participants, those not active in the labor force, and men were more likely to be classified as decliners, and the apolipoprotein E ɛ4 allele was more frequent in decliners. CONCLUSION: Quantitative, attrition-corrected assessment of longitudinal changes in memory can reveal substantial heterogeneity in aging trajectories, and genetic and lifestyle factors predict such heterogeneity.

  • 154.
    Kalpouzos, Gregoria
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Memory Self-Efficacy Beliefs Modulate Brain Activity when Encoding Real-World Future Intentions2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 9, p. e73850-Article in journal (Refereed)
    Abstract [en]

    Background: While the use of different cognitive strategies when encoding episodic memory information has been extensively investigated, modulation of brain activity by memory self-efficacy beliefs has not been studied yet.

    Methodology/Principal Findings: Sixteen young adults completed the prospective and retrospective metamemory questionnaire, providing individual subjective judgments of everyday memory function. The day after, using functional magnetic resonance imaging, the participants had to memorize real-world intentions (e. g., return a book to the library), which were performed later on in a virtual environment. Participants also performed offline cognitive tasks evaluating executive functions, working memory, and attention. During encoding, activity was found in medial temporal lobe, left prefrontal cortex, medial parietal regions, occipital areas, and regions involved in (pre) motor processes. Based on results from the questionnaire, the group was split into low and high memory self-efficacy believers. Comparison of encoding-related brain activity between the 2 groups revealed that the low memory self-efficacy believers activated more the hippocampus bilaterally, right posterior parahippocampal cortex, precuneus, and left lateral temporal cortex. By contrast, more activity was found in dorsal anterior cingulate gyrus for the high-memory believers. In addition, the low-memory believers performed more poorly at feature binding and (at trend) manipulating visuospatial information in working memory.

    Conclusion/Significance: Overall, these findings indicate that memory self-efficacy beliefs modulate brain activity during intentional encoding. Low memory self-efficacy believers activated more brain areas involved in visuospatial operations such as the hippocampus. Possibly, this increase reflects attempts to compensate for poor performance of certain neurocognitive processes, such as feature binding. By contrast, high-memory believers seemed to rely more on executive-like processes involved in cognitive control.

  • 155.
    Kalpouzos, Grégoria
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Sjölie, Daniel
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    Molin, Jonas
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Neurocognitive systems related to real-world prospective memory2010In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 10, p. e13304-Article in journal (Refereed)
    Abstract [en]

    Taken together, these findings show how brain systems complementary interact during real-world PM, and support a more complete model of PM that can be applied to naturalistic PM tasks and that we named PROspective MEmory DYnamic (PROMEDY) model because of its dynamics on both multi-phase iteration and the interactions of distinct neurocognitive networks.

  • 156.
    Kalpouzos, Grégoria
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Persson, Jonas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Local brain atrophy accounts for functional activity differences in normal aging.2012In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 33, no 3, p. 623.e1-623.e13Article in journal (Refereed)
    Abstract [en]

    Functional brain imaging studies of normal aging typically show age-related under- and overactivations during episodic memory tasks. Older individuals also undergo nonuniform gray matter volume (GMv) loss. Thus, age differences in functional brain activity could at least in part result from local atrophy. We conducted a series of voxel-based blood oxygen level-dependent (BOLD)-GMv analyses to highlight whether age-related under- and overrecruitment was accounted for by GMv changes. Occipital GMv loss accounted for underrecruitment at encoding. Efficiency reduction of sensory-perceptual mechanisms underpinned by these areas may partly be due to local atrophy. At retrieval, local GMv loss accounted for age-related overactivation of left dorsolateral prefrontal cortex, but not of left dorsomedial prefrontal cortex. Local atrophy also accounted for age-related overactivation in left lateral parietal cortex. Activity in these frontoparietal regions correlated with performance in the older group. Atrophy in the overrecruited regions was modest in comparison with other regions as shown by a between-group voxel-based morphometry comparison. Collectively, these findings link age-related structural differences to age-related functional under- as well as overrecruitment.

  • 157. Kanitz, Gunter
    et al.
    Cipriani, Christian
    Edin, Benoni B.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Classification of Transient Myoelectric Signals for the Control of Multi-Grasp Hand Prostheses2018In: IEEE transactions on neural systems and rehabilitation engineering, ISSN 1534-4320, E-ISSN 1558-0210, Vol. 26, no 9, p. 1756-1764Article in journal (Refereed)
    Abstract [en]

    Understanding the neurophysiological signals underlying voluntary motor control and decoding them for controlling limb prostheses is one of the major challenges in applied neuroscience and rehabilitation engineering. While pattern recognition of continuous myoelectric (EMG) signals is arguably the most investigated approach for hand prosthesis control, its underlying assumption is poorly supported, i.e., that repeated muscular contractions produce consistent patterns of steady-state EMGs. In fact, it still remains to be shown that pattern recognition-based controllers allow natural control over multiple grasps in hand prosthesis outside well-controlled laboratory settings. Here, we propose an approach that relies on decoding the intended grasp from forearm EMG recordings associated with the onset of muscle contraction as opposed to the steady-state signals. Eight unimpaired individuals and two hand amputees performed four grasping movements with a variety of arm postures while EMG recordings subsequently processed to mimic signals picked up by conventional myoelectric sensors were obtained from their forearms and residual limbs, respectively. Off-line data analyses demonstrated the feasibility of the approach also with respect to the limb position effect. The sampling frequency and length of the classified EMG window that off-line resulted in optimal performance were applied to a controller of a research prosthesis worn by one hand amputee and proved functional in real-time when operated under realistic working conditions.

  • 158.
    Karalija, Amar
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Novikova, Liudmila N.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Orädd, Greger
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Novikov, Lev N.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Differentiation of pre- and postganglionic nerve injury using MRI of the spinal cord2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 12, article id e0168807Article in journal (Refereed)
    Abstract [en]

    Brachial plexus injury (BPI) is a devastating type of nerve injury, potentially causing loss of motor and sensory function. Principally, BPI is either categorized as preganglionic or post- ganglionic, with the early establishment of injury level being crucial for choosing the correct treatment strategy. Despite diagnostic advances, the need for a reliable, non-invasive method for establishing the injury level remains. We studied the usefulness of in vivo mag- netic resonance imaging (MRI) of the spinal cord for determination of injury level. The find- ings were related to neuronal and glial changes. Rats underwent unilateral L4 & L5 ventral roots avulsion or sciatic nerve axotomy. The injuries served as models for pre- and postgan- glionic BPI, respectively. MRI of the L4/L5 spinal cord segments 4 weeks after avulsion showed ventral horn (VH) shrinkage on the injured side compared to the uninjured side. Axotomy induced no change in the VH size on MRI. Following avulsion, histological sections of L4/L5 revealed shrinkage in the VH grey matter area occupied by NeuN-positive neurons, loss of microtubular-associated protein-2 positive dendritic branches (MAP2), pan-neurofila- ment positive axons (PanNF), synaptophysin-positive synapses (SYN) and increase in immunoreactivity for the microglial OX42 and astroglial GFAP markers. Axotomy induced no changes in NeuN-reactivity, modest decrease of MAP2 immunoreactivity, no changes in SYN and PanNF labelling, and a modest increase in OX42 and SYN labeling. Histological and radiological findings were congruent when assessing changes after axotomy, while MRI somewhat underestimated the shrinkage. This study indicates a potential diagnostic value of structural spinal cord MRI following BPI. 

  • 159.
    Karlsson, Linnea
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Wiklund-Hornqvist, Carola
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Jonsson, Bert
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Retrieval practice is characterized by reduced fronto-striatal activity2013In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 25, no Suppl., p. S82-S83Article in journal (Other academic)
  • 160.
    Karlsson, Sari
    et al.
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Karlsson, Per
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm, Sweden.
    Fischer, Håkan
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Thilers, Petra
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    MacDonald, Stuart
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Brehmer, Yvonne
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Rieckmann, Anna
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Halldin, Christer
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm, Sweden.
    Farde, Lars
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm, Sweden.
    Bäckman, Lars
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Modulation of striatal dopamine D1 binding by cognitive processing2009In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 48, no 2, p. 398-404Article in journal (Refereed)
    Abstract [en]

    There is strong evidence that dopamine (DA) is implicated in higher-order cognitive functioning, but it remains controversial whether D1 receptor binding can be modified by cognitive activity. We examined striatal D1 binding potential (BP) in 20 younger (22-30 years) and 20 older (65-75 years) persons who underwent two [(11)C] SCH 23390 PET measurements, one while resting and one while performing a cognitive task taxing inhibitory functioning. The younger persons showed significant task-related BP reductions in sensorimotor, limbic, and associative striatum during cognitive activity compared to rest. Older persons showed no reliable BP reductions in any striatal subregion. These findings demonstrate that D1 receptor binding can be modified by cognitive activity in younger persons, but also provide novel evidence for the notion that human aging is associated not only with lower DA receptor density but also with altered modifiability of the DA system.

  • 161.
    Karlsson, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Cl concentration changes and desensitization of GABAA and glycine receptors2011In: The Journal of General Physiology, ISSN 0022-1295, E-ISSN 1540-7748, Vol. 138, no 6, p. 609-626Article in journal (Refereed)
    Abstract [en]

    Desensitization of ligand-gated ion channels plays a critical role for the information transfer between neurons. The current view on γ-aminobutyric acid (GABA)A and glycine receptors includes significant rapid components of desensitization as well as cross-desensitization between the two receptor types. Here, we analyze the mechanism of apparent cross-desensitization between native GABAA and glycine receptors in rat central neurons and quantify to what extent the current decay in the presence of ligand is a result of desensitization versus changes in intracellular Cl concentration ([Cl]i). We show that apparent cross-desensitization of currents evoked by GABA and by glycine is caused by changes in [Cl]i. We also show that changes in [Cl]i are critical for the decay of current in the presence of either GABA or glycine, whereas changes in conductance often play a minor role only. Thus, the currents decayed significantly quicker than the conductances, which decayed with time constants of several seconds and in some cells did not decay below the value at peak current during 20-s agonist application. By taking the cytosolic volume into account and numerically computing the membrane currents and expected changes in [Cl]i, we provide a theoretical framework for the observed effects. Modeling diffusional exchange of Cl between cytosol and patch pipettes, we also show that considerable changes in [Cl]i may be expected and cause rapidly decaying current components in conventional whole cell or outside-out patch recordings. The findings imply that a reevaluation of the desensitization properties of GABAA and glycine receptors is needed.

  • 162.
    Karlsson, Urban
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology.
    Sundgren-Andersson, Anna K
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology. Fysiologi.
    Krupp, Johannes J
    Capsaicin augments synaptic transmission in the rat medial preoptic nucleus.2005In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1043, no 1-2, p. 1-11Article in journal (Refereed)
    Abstract [en]

    medial preoptic nucleus (MPN) is the major nucleus of the preoptic area (POA), a hypothalamic area involved in the regulation of body-temperature. Injection of capsaicin into this area causes hypothermia in vivo. Capsaicin also causes glutamate release from hypothalamic slices. However, no data are available on the effect of capsaicin on synaptic transmission within the MPN. Here, we have studied the effect of exogenously applied capsaicin on spontaneous synaptic activity in hypothalamic slices of the rat. Whole-cell patch-clamp recordings were made from visually identified neurons located in the MPN. In a subset of the studied neurons, capsaicin enhanced the frequency of spontaneous glutamatergic EPSCs. Remarkably, capsaicin also increased the frequency of GABAergic IPSCs, an effect that was sensitive to removal of extracellular calcium, but insensitive to tetrodotoxin. This suggests an action of capsaicin at presynaptic GABAergic terminals. In contrast to capsaicin, the TRPV4 agonist 4alpha-PDD did not affect GABAergic IPSCs. Our results show that capsaicin directly affects synaptic transmission in the MPN, likely through actions at presynaptic terminals as well as on projecting neurons. Our data add to the growing evidence that capsaicin receptors are not only expressed in primary afferent neurons, but also contribute to synaptic processing in some CNS regions.

  • 163.
    Karlsson-Lindahl, Linda
    et al.
    University of Gothenburg.
    Schmidt, Linnea
    University of Gothenburg.
    Haage, David
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Hansson, Caroline
    University of Gothenburg.
    Taube, Magdalena
    University of Gothenburg.
    Egeciouglu, Emil
    University of Gothenburg.
    Tan, Ying-xia
    University of Uppsala.
    Admyre, Therese
    AstraZeneca, R&D Mölndal.
    Jansson, John-Olov
    University of Gothenburg.
    Vlodavsky, Israel
    Cancer and Vascular Biology Research Center, the Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
    Li, Jin-Ping
    University of Uppsala.
    Lindahl, Ulf
    University of Uppsala.
    Dickson, Suzanne L.
    University of Gothenburg.
    Heparanase Affects Food Intake and Regulates Energy Balance in Mice2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 3, p. e34313-Article in journal (Refereed)
    Abstract [en]

    Mutation of the melanocortin-receptor 4 (MC4R) is the most frequent cause of severe obesity in humans. Binding of agouti-related peptide (AgRP) to MC4R involves the co-receptor syndecan-3, a heparan sulfate proteoglycan. The proteoglycan can be structurally modified by the enzyme heparanase. Here we tested the hypothesis that heparanase plays a role in food intake behaviour and energy balance regulation by analysing body weight, body composition and food intake in genetically modified mice that either lack or overexpress heparanase. We also assessed food intake and body weight following acute central intracerebroventricular administration of heparanase; such treatment reduced food intake in wildtype mice, an effect that was abolished in mice lacking MC4R. By contrast, heparanase knockout mice on a high-fat diet showed increased food intake and maturity-onset obesity, with up to a 40% increase in body fat. Mice overexpressing heparanase displayed essentially the opposite phenotypes, with a reduced fat mass. These results implicate heparanase in energy balance control via the central melanocortin system. Our data indicate that heparanase acts as a negative modulator of AgRP signaling at MC4R, through cleavage of heparan sulfate chains presumably linked to syndecan-3.

  • 164.
    Kauppi, Karolina
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nilsson, Lars-Göran
    Stockholm University.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Eriksson, Elias
    Gothenburg University.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    KIBRA polymorphism is related to enhanced memory and elevated hippocampal processing2011In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 31, no 40, p. 14218-14222Article in journal (Refereed)
    Abstract [en]

    Several studies have linked the KIBRA rs17070145 T polymorphism to superior episodic memory in healthy humans. One study investigated the effect of KIBRA on brain activation patterns (Papassotiropoulos et al., 2006) and observed increased hippocampal activation in noncarriers of the T allele during retrieval. Noncarriers were interpreted to need more hippocampal activation to reach the same performance level as T carriers. Using large behavioral (N = 2230) and fMRI (N = 83) samples, we replicated the KIBRA effect on episodic memory performance, but found increased hippocampal activation in T carriers during episodic retrieval. There was no evidence of compensatory brain activation in noncarriers within the hippocampal region. In the main fMRI sample, T carriers performed better than noncarriers during scanning but, importantly, the difference in hippocampus activation remained after post hoc matching according to performance, sex, and age (N = 64). These findings link enhanced memory performance in KIBRA T allele carriers to elevated hippocampal functioning, rather than to neural compensation in noncarriers.

  • 165.
    Kauppi, Karolina
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nilsson, Lars-Göran
    Stockholm University.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Lundquist, Anders
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Eriksson, Elias
    Gothenburg University.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Decreased medial temporal lobe activation in BDNF 66Met allele carriers during memory encoding2013In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 51, no 12, p. 2462-2468Article in journal (Refereed)
    Abstract [en]

    The Met allele of the Brain-derived neurotrophic factor (BDNF) Val(66)Met polymorphism has been associated with impaired activity-dependent secretion of BDNF protein and decreased memory performance. Results from imaging studies relating Val(66)Met to brain activation during memory processing have been inconsistent, with reports of both increased and decreased activation in the Medial Temporal Lobe (MTL) in Met carriers relative to Val homozygotes. Here, we extensively studied BDNF Val(66)Met in relation to brain activation and white matter integrity as well as memory performance in a large imaging (n=194) and behavioral (n=2229) sample, respectively. Functional magnetic resonance imaging (fMRI) was used to investigate MTL activation in healthy participants in the age of 55-75 years during a face-name episodic encoding and retrieval task. White matter integrity was measured using diffusion tensor imaging.

    BDNF Met allele carriers had significantly decreased activation in the MTL during encoding processes, but not during retrieval processes. In contrast to previous proposals, the effect was not modulated by age and the polymorphism was not related to white matter integrity. Met carriers had lower memory performance than Val homozygotes, but differences were subtle and not significant. In conclusion, the BDNF Met allele has a negative influence on MTL functioning, preferentially during encoding processes, which might translate into impaired episodic memory function.

  • 166.
    Kauppi, Karolina
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Nilsson, Lars-Göran
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Combined gene effects on hippocampal mnemonic processing: a large-scale imaging-genetics study of APOE, BDNF, KIBRA, and CLSTN22013In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 25, no Suppl., p. S140-S141Article in journal (Other academic)
  • 167.
    Kauppi, Karolina
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University,106 91 Stockholm, Stockholm Brain Institute, Sweden.
    Persson, Jonas
    Aging Research Center (ARC), Karolinska Institutet, Gävlegatan 16, SE-11330 Stockholm, Stockholm University, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Additive genetic effect of APOE and BDNF on hippocampus activity2014In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 89, no 1, p. 306-313Article in journal (Refereed)
    Abstract [en]

    Human memory is a highly heritable polygenic trait with complex inheritance patterns. To study the genetics of memory and memory-related diseases, hippocampal functioning has served as an intermediate phenotype. The importance of investigating gene-gene effects on complex phenotypes has been emphasized, but most imaging studies still focus on single polymorphisms. APOE ε4 and BDNF Met, two of the most studied gene variants for variability in memory performance and neuropsychiatric disorders, have both separately been related to poorer episodic memory and altered hippocampal functioning. Here, we investigated the combined effect of APOE and BDNF on hippocampal activation (N=151). No non-additive interaction effects were seen. Instead, the results revealed decreased activation in bilateral hippocampus and parahippocampus as a function of the number of APOE ε4 and BDNF Met alleles present (neither, one, or both). The combined effect was stronger than either of the individual effects, and both gene variables explained significant proportions of variance in BOLD signal change. Thus, there was an additive gene-gene effect of APOE and BDNF on medial temporal lobe (MTL) activation, showing that a larger proportion of variance in brain activation attributed to genetics can be explained by considering more than one gene variant. This effect might be relevant for the understanding of normal variability in memory function as well as memory-related disorders associated with APOE and BDNF.

  • 168.
    Kinoshita, Masaharu
    et al.
    National Institute for Physiological Sciences, Myodaiji, Okazaki .
    Matsui, Ryosuke
    Kyoto University.
    Kato, Shigeki
    Fukushima Medical University School of Medicine, Fukushima.
    Hasegawa, Taku
    Kyoto University.
    Kasahara, Hironori
    Kyoto University.
    Isa, Kaoru
    National Institute for Physiological Sciences, Myodaiji, Okazaki .
    Watakabe, Akiya
    National Institute for Basic Biology, Okazaki, he Graduate University for Advanced Studies (Sokendai), Hayama, Kanagawa.
    Yamamori, Tetsuo
    National Institute for Basic Biology, Okazaki, he Graduate University for Advanced Studies (Sokendai), Hayama, Kanagawa.
    Nishimura, Yukio
    National Institute for Physiological Sciences, Myodaiji, Okazaki .
    Alstermark, Bror
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Watanabe, Dai
    Kyoto University.
    Kobayashi, Kazuto
    Fukushima Medical University School of Medicine, Fukushima.
    Isa, Tadashi
    National Institute for Physiological Sciences, Myodaiji, Okazaki , he Graduate University for Advanced Studies (Sokendai), Hayama, Kanagawa.
    Genetic dissection of the circuit for hand dexterity in primates2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 487, no 7406, p. 235-U1510Article in journal (Refereed)
    Abstract [en]

    It is generally accepted that the direct connection from the motor cortex to spinal motor neurons is responsible for dexterous hand movements in primates(1-3). However, the role of the 'phylogenetically older' indirect pathways from the motor cortex to motor neurons, mediated by spinal interneurons, remains elusive. Here we used a novel double-infection technique to interrupt the transmission through the propriospinal neurons (PNs)(4-6), which act as a relay of the indirect pathway in macaque monkeys (Macaca fuscata and Macaca mulatta). The PNs were double infected by injection of a highly efficient retrograde gene-transfer vector into their target area and subsequent injection of adeno-associated viral vector at the location of cell somata. This method enabled reversible expression of green fluorescent protein (GFP)-tagged tetanus neurotoxin, thereby permitting the selective and temporal blockade of the motor cortex-PN-motor neuron pathway. This treatment impaired reach and grasp movements, revealing a critical role for the PN-mediated pathway in the control of hand dexterity. Anti-GFP immunohistochemistry visualized the cell bodies and axonal trajectories of the blocked PNs, which confirmed their anatomical connection to motor neurons. This pathway-selective and reversible technique for blocking neural transmission does not depend on cell-specific promoters or transgenic techniques, and is a new and powerful tool for functional dissection in system-level neuroscience studies.

  • 169.
    Klement, Göran
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Haage, David
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Malinina, Evgenya
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Århem, Peter
    Karolinska Institute.
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Spontaneous ryanodine-receptor-dependent Ca2+-activated K+ currents and hyperpolarizations in rat medial preoptic neurons2010In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 103, no 5, p. 2900-2911Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to clarify the identity of slow spontaneous currents, the underlying mechanism and possible role for impulse generation in neurons of the rat medial preoptic nucleus (MPN). Acutely dissociated neurons were studied with the perforated patch-clamp technique. Spontaneous outward currents, at a frequency of approximately 0.5 Hz and with a decay time constant of approximately 200 ms, were frequently detected in neurons when voltage-clamped between approximately -70 and -30 mV. The dependence on extracellular K(+) concentration was consistent with K(+) as the main charge carrier. We concluded that the main characteristics were similar to those of spontaneous miniature outward currents (SMOCs), previously reported mainly for muscle fibers and peripheral nerve. From the dependence on voltage and from a pharmacological analysis, we concluded that the currents were carried through small-conductance Ca(2+)-activated (SK) channels, of the SK3 subtype. From experiments with ryanodine, xestospongin C, and caffeine, we concluded that the spontaneous currents were triggered by Ca(2+) release from intracellular stores via ryanodine receptor channels. An apparent voltage dependence was explained by masking of the spontaneous currents as a consequence of steady SK-channel activation at membrane potentials > -30 mV. Under current-clamp conditions, corresponding transient hyperpolarizations occasionally exceeded 10 mV in amplitude and reduced the frequency of spontaneous impulses. In conclusion, MPN neurons display spontaneous hyperpolarizations triggered by Ca(2+) release via ryanodine receptors and SK3-channel activation. Thus such events may affect impulse firing of MPN neurons.

  • 170. Kling, A
    et al.
    Dahlqvist, R
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Bäckström, M
    Mjörndal, T
    Neurologic oral manifestations caused by a new formulation of mirtazapine.2005In: Neurology, ISSN 1526-632X, Vol. 65, no 2, p. 333-4Article in journal (Refereed)
  • 171.
    Kokinovic, Bojana
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. epartment of Neuroscience and Brain Technologies (NBT), Italian Institute of Technology (IIT), Genova, Italy.
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Loss of GABAB-mediated interhemispheric synaptic inhibition in stroke periphery2018In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 596, no 10, p. 1949-1964Article in journal (Refereed)
    Abstract [en]

    Recovery after stroke is mediated by plastic changes largely occurring in the lesion periphery. However, little is known about the microcircuit changes underlying recovery, the extent to which perilesional plasticity occurs at synaptic input vs. spike output level, and the connectivity behind such synaptic plasticity. We combined intrinsic imaging with extracellular and intracellular recordings and pharmacological inactivation in a focal stroke in mouse somatosensory cortex (S1). In vivo whole-cell recordings in hindlimb S1 (hS1) showed synaptic responses also to forelimb stimulation in controls, and such responses were abolished by stroke in the neighbouring forelimb area (fS1), suggesting that, under normal conditions, they originate via horizontal connections from the neighbouring fS1. Synaptic and spike responses to forelimb stimulation in hS1 recovered to quasi-normal levels 2weeks after stroke, without changes in intrinsic excitability and hindlimb-evoked spike responses. Recovered synaptic responses had longer latencies, suggesting a long-range origin of the recovery, prompting us to investigate the role of callosal inputs in the recovery process. Contralesional S1 silencing unmasked significantly larger responses to both limbs in controls, a phenomenon that was not observed when GABAB receptors were antagonized in the recorded area. Conversely, such GABAB-mediated interhemispheric inhibition was not detectable after stroke: callosal input silencing failed to change hindlimb responses, whereas it robustly reduced recovered forelimb responses. Thus, recovery of subthreshold responsiveness in the stroke periphery is accompanied by a loss of interhemispheric inhibition and this is a result of pathway-specific facilitatory action on the affected sensory response from the contralateral cortex.

  • 172.
    Kompus, Kristiina
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Default mode network gates the retrieval of task-irrelevant incidental memories2011In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 487, no 3, p. 318-321Article in journal (Refereed)
    Abstract [en]

    Episodic memories can be retrieved by an intentional search for certain information. Alternatively, a past episode may enter our consciousness without any intention to retrieve it, prompted by a stimulus in our surroundings. Incidental retrieval does not occur upon each encounter with a familiar stimulus, suggesting that a gating mechanism exists which regulates incidental retrieval activity. We analyzed data from a functional magnetic resonance imaging study on incidental retrieval in healthy young adults and found that failure to incidentally retrieve was selectively associated with reduced activation of lateral and medial parietal regions as well as ventromedial frontal cortex, areas implicated in default mode network. This is the first demonstration that relative deactivation of the brain regions associated with the default mode gates the consciousness from currently irrelevant memories.

  • 173.
    Kompus, Kristiina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Eichele, Tom
    University of Bergen.
    Hugdahl, Kenneth
    University of Bergen.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Multimodal imaging of incidental retrieval: the low route to memory2011In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 23, no 4, p. 947-960Article in journal (Refereed)
    Abstract [en]

    Memories of past episodes frequently come to mind incidentally, without directed search. It has remained unclear how incidental retrieval processes are initiated in the brain. Here we used fMRI and ERP recordings to find brain activity that specifically correlates with incidental retrieval, as compared to intentional retrieval. Intentional retrieval was associated with increased activation in the dorsolateral prefrontal cortex. By contrast, incidental retrieval was associated with a reduced fMRI signal in posterior brain regions, including extrastriate and parahippocampal cortex, and a modulation of a posterior ERP component 170 ms after the onset of visual retrieval cues. Successful retrieval under both intentional and incidental conditions was associated with increased activation in hippocampus, precuneus and ventrolateral prefrontal cortex, as well as increased amplitude of the P600 ERP component. These results demonstrate how early bottom-up signals from the posterior cortex can lead to reactivation of episodic memories in the absence of strategic retrieval attempts.

  • 174.
    Kompus, Kristiina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Hugdahl, Kenneth
    Öhman, Arne
    Marklund, Petter
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Distinct control networks for cognition and emotion in the prefrontal cortex2009In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 467, no 2, p. 76-80Article in journal (Refereed)
    Abstract [en]

    The activation of dorsolateral prefrontal cortex (dlPFC) has been suggested to reflect the engagement of a control mechanism for top-down biasing of context processing in resource-demanding memory tasks. Here we tested the hypothesis that the dlPFC subserves a similar function also in attention and emotion tasks. 18 healthy young adults were tested in a functional magnetic resonance imaging (fMRI) study where the demands for context processing were manipulated in three different cognitive domains: auditory attention, episodic retrieval, and emotion regulation. We found that the right dlPFC was jointly sensitive to increased cognitive demands in the attention and memory tasks. By contrast, increased demands in the emotion task (reappraisal) were associated with increased activity in ventromedial PFC along with decreased amygdala activity. Our findings of divergent prefrontal control networks for cognitive and emotional control extend previous separations of cognition and emotion in the anterior cingulate cortex.

  • 175.
    Kompus, Kristiina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). University of Bergen.
    Kalpouzos, Gregoria
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Stockholm University.
    Westerhausen, Rene
    University of Bergen.
    The size of the anterior corpus callosum correlates with the strength of hemispheric encoding-retrieval asymmetry in the ventrolateral prefrontal cortex2011In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1419, p. 61-67Article in journal (Refereed)
    Abstract [en]

    Functional lateralization of episodic memory processes in the frontal lobe is an area of intense study in the field of cognitive neuroimaging. Yet, to date there is insufficient knowledge of what role the interhemispheric structural connectivity plays in this lateralized organization. We analyzed functional and structural magnetic resonance imaging data from healthy adult volunteers who performed an associative encoding and retrieval task. We examined the relationship between functional voxel-based relative asymmetry of encoding and retrieval in the frontal lobes and the size of the anterior corpus callosum (antCC; corrected for brain size). The size of the antCC was strongly associated to the relative encoding-retrieval asymmetry in the ventrolateral prefrontal cortex (BA 47). These findings show that the functional asymmetry of episodic memory processes in the frontal lobes is associated with the structural connectivity between the hemispheres. (C) 2011 Elsevier B.V. All rights reserved.

  • 176.
    Kompus, Kristiina
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Olsson, Carl-Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Social Sciences, Department of Psychology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Dynamic switching between semantic and episodic memory systems2009In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 47, no 11, p. 2252-2260Article in journal (Refereed)
    Abstract [en]

    It has been suggested that episodic and semantic long-term memory systems interact during retrieval. Here we examined the flexibility of memory retrieval in an associative task taxing memories of different strength, assumed to differentially engage episodic and semantic memory. Healthy volunteers were pre-trained on a set of 36 face-name pairs over a 6-week period. Another set of 36 items was shown only once during the same time period. About 3 months after the training period all items were presented in a randomly intermixed order in an event-related fMRI study of face-name memory. Once presented items differentially activated anterior cingulate cortex and a right prefrontal region that previously have been associated with episodic retrieval mode. High-familiar items were associated with stronger activation of posterior cortices and a left frontal region. These findings fit a model of memory retrieval by which early processes determine, on a trial-by-trial basis, if the task can be solved by the default semantic system. If not, there is a dynamic shift to cognitive control processes that guide retrieval from episodic memory.

  • 177. Laschi, C
    et al.
    Asuni, G
    Guglielmelli, E
    Teti, G
    Johansson, Roland
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Konosu, H
    Wasik, Z
    Carrozza, MC
    Dario, P
    A bio-inspired predictive sensory-motor coordination scheme for robot reaching and preshaping2008In: Autonomous Robots, ISSN 0929-5593, E-ISSN 1573-7527, Vol. 25, no 1-2, p. 85-101Article in journal (Refereed)
    Abstract [en]

    This paper presents a sensory-motor coordination scheme for a robot hand-arm-head system that provides the robot with the capability to reach an object while pre-shaping the fingers to the required grasp configuration and while predicting the tactile image that will be perceived after grasping. A model for sensory-motor coordination derived from studies in humans inspired the development of this scheme. A peculiar feature of this model is the prediction of the tactile image.The implementation of the proposed scheme is based on a neuro-fuzzy module that, after a learning phase, starting from visual data, calculates the position and orientation of the hand for reaching, selects the best-suited hand configuration, and predicts the tactile feedback. The implementation of the scheme on a humanoid robot allowed experimental validation of its effectiveness in robotics and provided perspectives on applications of sensory predictions in robot motor control.

  • 178. Laschi, Cecilia
    et al.
    Asuni, Gioel
    Teti, Giancarlo
    Carrozza, Maria Chiara
    Dario, Paolo
    Guglielmelli, Eugenio
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    A Bio-inspired Neural Sensory-Motor Coordination Scheme for Robot Reaching and Preshaping2006In: Proceedings of the First IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics : BioRob 2006: understanding how biological systems work, to guide the design of novel, high performance bio-inspired machines and to develop novel devices that can better act on, substitute parts of, and assist human beings, Piscataway, NJ: IEEE , 2006, p. 531-536Conference paper (Other academic)
    Abstract [en]

    We present a sensory-motor coordination scheme for a robot hand-arm-head system that provides the robot with the capability to reach for and to grasp an object, while pre-shaping the fingers to the required grasp configuration. A model for sensory-motor coordination derived from studies in humans inspired the development of the scheme. A special feature of this model is the prediction of the tactile image perceived after grasping. The proposed scheme is based on a neuro-fuzzy modnle that, after a learning phase, starting from visual data, calculates the position and orientation of the hand for grasping, selects the best-suited hand configuration, and predicts the tactile feedback after grasping. The implementation of the scheme on a humanoid robot ailowed experimental validation of its effectiveness in robotics and provided perspectives on applications of sensory predictions in robot motor control.

  • 179. Laschi, Cecilia
    et al.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Bio-inspired sensory-motor coordination2008In: Autonomous Robots, ISSN 0929-5593, E-ISSN 1573-7527, Vol. 25, no 1-2, p. 1-2Article in journal (Refereed)
  • 180. Lebedeva, A
    et al.
    Sundström, Anna
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Social Sciences, Department of Psychology.
    Lindgren, Lenita
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Stomby, A
    Stomby, Andreas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Jönköping County Hospital, Region Jönköping County, Jönköping, Sweden.
    Aarsland, D
    Westman, E
    Winblad, B
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Longitudinal relationships among depressive symptoms, cortisol, and brain atrophy in the neocortex and the hippocampus2018In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 167, no 6, p. 491-502Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Depression is associated with accelerated aging and age-related diseases. However, mechanisms underlying this relationship remain unclear. The aim of this study was to longitudinally assess the link between depressive symptoms, brain atrophy, and cortisol levels.

    METHOD: Participants from the Betula prospective cohort study (mean age = 59 years, SD = 13.4 years) underwent clinical, neuropsychological and brain 3T MRI assessments at baseline and a 4-year follow-up. Cortisol levels were measured at baseline in four saliva samples. Cortical and hippocampal atrophy rates were estimated and compared between participants with and without depressive symptoms (n = 81) and correlated with cortisol levels (n = 49).

    RESULTS: Atrophy in the left superior frontal gyrus and right lingual gyrus developed in parallel with depressive symptoms, and in the left temporal pole, superior temporal cortex, and supramarginal cortex after the onset of depressive symptom. Depression-related atrophy was significantly associated with elevated cortisol levels. Elevated cortisol levels were also associated with widespread prefrontal, parietal, lateral, and medial temporal atrophy.

    CONCLUSION: Depressive symptoms and elevated cortisol levels are associated with atrophy of the prefrontal and limbic areas of the brain.

  • 181. Lemon, Roger
    et al.
    Sasaki, Shigeto
    Naito, Kimisato
    Yoshimura, Kazuya
    Isa, Tadashi
    Seki, Kazuhiko
    Pettersson, Lars-Gunnar
    Alstermark, Bror
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Ohki, Yukari
    Cortico-motoneuronal system and dexterous finger movements (multiple letters)2004Other (Other academic)
  • 182.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hansson, William
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Diffusion tensor imaging and correlations to Parkinson rating scales2013In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 260, no 11, p. 2823-2830Article in journal (Refereed)
    Abstract [en]

    The contribution of various brain areas to the overall progression of Parkinson's disease remains to be determined. In this study, we apply MRI diffusion tensor imaging to investigate how alterations in diffusion relate to phenotype and symptoms measured by clinical rating scales. Sixty-four patients were investigated at baseline and three follow-ups (1, 3 and 5 years). Thirty-six patients remained in the last follow-up. Regions of interests included frontal white matter, basal ganglia, thalamus, and cerebellum. Scoring on the Unified Parkinson's Disease Rating Scale (UPDRS) I, II, III, Hoehn and Yahr (HY) scale and the Schwab and England scale (SE) was determined. Mean, radial, and axial diffusion and fractional anisotropy were modeled with phenotype and clinical scales in a multivariate/univariate analysis correcting for other covariates. Significance was set at 0.05 Bonferroni corrected. All rating scales except UPDRS III significantly correlated to the diffusion measures, as did clinical phenotype. Specifically, putamen, globus pallidus, and thalamus demonstrated higher diffusion with worsening scores. Diffusion in thalamus was higher in the tremor dominant phenotype than in postural imbalance and gait disturbance. Decline in overall functionality (UPDRS II and SE scale), including mental status (UPDRS I) and stage of the disease (HY scale), in Parkinson's disease is related to altered diffusion in the lentiform nucleus and thalamus. Motor function is not mirrored in diffusion changes, possibly due to medication. Tremor dominant PD patients show diffusion alterations in the thalamus, but the significance of this for tremor generation remains to be determined.

  • 183.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Idiopathic normal pressure hydrocephalus: increased supplementary motor activity accounts for improvement after CSF drainage.2008In: Brain, ISSN 1460-2156, Vol. 131, no Pt 11, p. 2904-2912Article in journal (Refereed)
    Abstract [en]

    In patients with idiopathic normal pressure hydrocephalus (INPH), the changes in brain function that take place in conjunction with improved behavioural performance after CSF drainage is still unknown. In this study, we use functional MRI (fMRI) to investigate the changes in cortical activity that accompany improved motor and cognitive performance after long-term external lumbar drainage (ELD) of CSF in patients with INPH. Eighteen INPH patients were initially included together with age- and sex-matched controls. Data from 11 INPH patients were analysed both before and after ELD. The average drain volume for these 11 patients was 400 ml/3 days. Brain activation was investigated by fMRI before and after the procedure on a 1.5T Philips scanner using protocols taxing motor performance (finger tapping and reaction time) and cognitive functioning (memory and attention). Behavioural data were compared using non-parametric tests at a significance level of 0.05, whereas fMRI data were analysed by statistical parametric mapping including conjunction analysis of areas with enhanced activity after drainage in patients and areas activated in controls (P < 0.005, uncorrected). Improved regions were defined as areas in the INPH brain that increased in activity after ELD with the requirement that the same areas were activated in control subjects. Following ELD, right-hand finger tapping improved from 104 +/- 38 to 117 +/- 25 (mean +/- SD) (P = 0.02). Left-hand finger tapping showed a tendency to improve, the number of keystrokes increasing from 91 +/- 40 to 105 +/- 20 (P = 0.12). Right-hand reaction time improved from 1630 +/- 566 ms to 1409 +/- 442 ms, whereas left-hand reaction time improved from 1760 +/- 600 ms to 1467 +/- 420 ms (both P-values = 0.01). Significant improvements in motor performance were accompanied by bilateral increased activation in the supplementary motor area. No improvement was found in cognitive functioning. The results suggest that motor function recovery in INPH patients after CSF removal is related to enhanced activity in medial parts of frontal motor areas considered crucial for motor planning; a finding consistent with INPH being a syndrome related to a reversible suppression of frontal periventricular cortico-basal ganglia-thalamo-cortical pathways.

  • 184.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eklund, Anders
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Diffusion tensor imaging reveals supplementary lesions to frontal white matter in Idiopathic normal pressure hydrocephalus2011In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 68, no 6, p. 1586-1593Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:: Idiopathic normal pressure hydrocephalus (INPH) is associated with white matter lesions, but the extent and severity of the lesions do not cohere with symptoms or improvement after shunting, implying the presence of further, yet undisclosed, injuries to white matter in INPH. OBJECTIVE:: To apply diffusion tensor imaging (DTI) to explore white matter lesions in patients with INPH before and after drainage of cerebrospinal fluid (CSF). METHODS:: Eighteen patients and ten controls were included. DTI was performed in a 1.5T MRI scanner before and after three-day drainage of 400 ml of CSF. Regions of interest included corpus callosum, capsula interna, frontal and lateral periventricular white matter, and centrum semiovale. White matter integrity was quantified by assessing fractional anisotropies (FA) and apparent diffusion coefficients (ADC), comparing them between patients and controls and between patients before and after drainage. The significance level corresponded to 0.05 (Bonferroni corrected). RESULTS:: Decreased FA in patients was found in three regions (p<0.002, p<0.001 and p<0.0001) in anterior frontal white matter, whereas elevated ADC was found in genu corpus callosum (p<0.0001) and areas of centrum semiovale associated to the precentral gyri (p<0.002). Diffusion patterns in these areas did not change after drainage. CONCLUSION:: DTI reveals subtle injuries - interpreted as axonal loss and gliosis - to anterior frontal white matter where high-order motor systems between frontal cortex and basal ganglia travel, further supporting the notion that motor symptoms in INPH are caused by a chronic ischemia to the neuronal systems involved in the planning processes of movements.

  • 185.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Diffusion measures in early stage parkinsonism: controversial findings including hemispheric lateralisation2013In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 19, no 4, p. 469-471Article in journal (Refereed)
  • 186. Li, Shu-Chen
    et al.
    Chicherio, Christian
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    von Oertzen, Timo
    Nagel, Irene E
    Sander, Thomas
    Heekeren, Hauke R
    Lindenberger, Ulman
    Bäckman, Lars
    Ebbinghaus Revisited: Influences of the BDNF Val66Met Polymorphism on Backward Serial Recall Are Modulated by Human Aging.2010In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 22, no 10, p. 2164-2173Article in journal (Refereed)
    Abstract [en]

    Abstract The brain-derived neurotrophic factor (BDNF) plays an important role in activity-dependent synaptic plasticity, which underlies learning and memory. In a sample of 948 younger and older adults, we investigated whether a common Val66Met missense polymorphism (rs6265) in the BDNF gene affects the serial position curve-a fundamental phenomenon of associative memory identified by Hermann Ebbinghaus more than a century ago. We found a BDNF polymorphism effect for backward recall in older adults only, with Met-allele carriers (i.e., individuals with reduced BDNF signaling) recalling fewer items than Val homozygotes. This effect was specific to the primacy and middle portions of the serial position curve, where intralist interference and associative demands are especially high. The poorer performance of older Met-allele carriers reflected transposition errors, whereas no genetic effect was found for omissions. These findings indicate that effects of the BDNF polymorphism on episodic memory are most likely to be observed when the associative and executive demands are high. Furthermore, the findings are in line with the hypothesis that the magnitude of genetic effects on cognition is greater when brain resources are reduced, as is the case in old age.

  • 187. Li, Shu-Chen
    et al.
    Lindenberger, U
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Heekeren, H R
    Bäckman, Lars
    Dopaminergic modulation of cognition in human aging2009In: Imaging the aging brain / [ed] W Jagust & M DEsposito, Oxford: Oxford University Press , 2009, p. 71-92Chapter in book (Refereed)
  • 188.
    Lindgren, Lenita
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Westling, Göran
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lehtipalo, Stefan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Andersson, Micael
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Pleasant human touch is represented in pregenual anterior cingulate cortex2012In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 59, no 4, p. 3427-3432Article in journal (Refereed)
    Abstract [en]

    Touch massage (TM) is a form of pleasant touch stimulation used as treatment in clinical settings and found to improve well-being and decrease anxiety, stress, and pain. Emotional responses reported during and after TM have been studied, but the underlying mechanisms are still largely unexplored. In this study, we used functional magnetic resonance (fMRI) to test the hypothesis that the combination of human touch (i.e. skin-to-skin contact) with movement is eliciting a specific response in brain areas coding for pleasant sensations. The design included four different touch conditions; human touch with or without movement and rubber glove with or without movement. Force (2.5N) and velocity (1.5cm/s) were held constant across conditions. The pleasantness of the four different touch stimulations was rated on a visual analog scale (VAS-scale) and human touch was rated as most pleasant, particularly in combination with movement. The fMRI results revealed that TM stimulation most strongly activated the pregenual anterior cingulate cortex (pgACC). These results are consistent with findings showing pgACC activation during various rewarding pleasant stimulations. This area is also known to be activated by both opioid analgesia and placebo. Together with these prior results, our finding furthers the understanding of the basis for positive TM treatment effects.

  • 189. Luciw, Matthew D.
    et al.
    Jarocka, Ewa
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Department of Kinesiology, Faculty of Physiotherapy, University School of Physical Education, Wroclaw 51-612, Poland.
    Edin, Benoni B.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Multi-channel EEG recordings during 3,936 grasp and lift trials with varying weight and friction2014In: Scientific Data, E-ISSN 2052-4463, Vol. 1, article id 140047Article in journal (Refereed)
    Abstract [en]

    WAY-EEG-GAL is a dataset designed to allow critical tests of techniques to decode sensation, intention, and action from scalp EEG recordings in humans who perform a grasp-and-lift task. Twelve participants performed lifting series in which the object's weight (165, 330, or 660 g), surface friction (sandpaper, suede, or silk surface), or both, were changed unpredictably between trials, thus enforcing changes in fingertip force coordination. In each of a total of 3,936 trials, the participant was cued to reach for the object, grasp it with the thumb and index finger, lift it and hold it for a couple of seconds, put it back on the support surface, release it, and, lastly, to return the hand to a designated rest position. We recorded EEG (32 channels), EMG (five arm and hand muscles), the 3D position of both the hand and object, and force/torque at both contact plates. For each trial we provide 16 event times (e.g., 'object lift-off') and 18 measures that characterize the behaviour (e. g., 'peak grip force').

  • 190.
    Lund, James P
    et al.
    Faculty of Dentistry, McGill University, Montréal, Québec, Canada .
    Sadeghi, Somayeh
    Faculty of Dentistry, McGill University, Montréal, Québec, Canada .
    Athanassiadis, Tuija
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Caram Salas, Nadia
    Faculty of Dentistry, McGill University, Montréal, Québec, Canada .
    Auclair, François
    Groupe de Recherche sur le Système Nerveux Central du FRSQ, Département de Physiologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada .
    Thiverge, Benoît
    Faculté de Médecine Dentaire, Université de Montréal, Montréal, Québec, Canada.
    Arsenault, Isabel
    Groupe de Recherche sur le Système Nerveux Central du FRSQ, Département de Physiologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada.
    Rompré, Pierre
    Faculté de Médecine Dentaire, Université de Montréal, Montréal, Québec, Canada.
    Westberg, Karl-Gunnar
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Kolta, Arlette
    Groupe de Recherche sur le Système Nerveux Central du FRSQ, Département de Physiologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada .
    Evidence that muscle spindle mechanoreceptor afferents play a role in chronic muscle painManuscript (preprint) (Other academic)
  • 191.
    Lund, James P
    et al.
    Université de Montréal.
    Sadeghi, Somayeh
    McGill University, Montréal.
    Athanassiadis, Tuija
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Caram Salas, Nadia
    McGill University, Montréal.
    Auclair, François
    Université de Montréal.
    Thivierge, Benoît
    Université de Montréal.
    Arsenault, Isabel
    Université de Montréal.
    Rompré, Pierre
    Université de Montréal.
    Westberg, Karl-Gunnar
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Kolta, Arlette
    Université de Montréal, McGill University, Montréal.
    Assessment of the potential role of muscle spindle mechanoreceptor afferents in chronic muscle pain in the rat masseter muscle2010In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 6, p. e11131-Article in journal (Refereed)
    Abstract [en]

    Low pH leads to changes in several electrical properties of MSA, including initiation of ectopic action potentials which could propagate centrally but could also invade the peripheral endings causing glutamate release and activation of nearby nociceptors within the spindle capsule. This peripheral drive could contribute both to the transition to, and maintenance of, persistent muscle pain as seen in some "functional" pain syndromes.

  • 192.
    Lundström, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Olofsson, Birgitta
    Umeå University, Faculty of Medicine, Department of Nursing.
    Stenvall, Michael
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Elinge, Eva
    Englund, Undis
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Edlund, Agneta
    Borssén, Bengt
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Gustafson, Yngve
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Vårdprogram för patienter med höftfrakturer: ortoped-geriatriskt preoperativt vårdprogram för alla patienter med höftfraktur och postoperativt vårdprogram för patienter över 80 år med cervikala och basocervikala höftfrakturer som behandlas vid Norrlands universitets sjukhus i Umeå2004Report (Other academic)
  • 193.
    Lundström, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Olofsson, Birgitta
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Stenvall, Michael
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Karlsson, Stig
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Englund, Undis
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Borssén, Bengt
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Gustafson, Yngve
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Postoperative delirium in old patients with femoral neck fracture: a randomized intervention study.2007In: Aging Clinical and Experimental Research, ISSN 1594-0667, E-ISSN 1720-8319, Vol. 19, no 3, p. 178-186Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Delirium is a common postoperative complication in elderly patients which has a serious impact on outcome in terms of morbidity and costs. We examined whether a postoperative multi-factorial intervention program can reduce delirium and improve outcome in patients with femoral neck fractures.

    METHODS: One hundred and ninety-nine patients, aged 70 years and over (mean age+/-SD, 82+/-6, 74% women), were randomly assigned to postoperative care in a specialized geriatric ward or a conventional orthopedic ward. The intervention consisted of staff education focusing on the assessment, prevention and treatment of delirium and associated complications. The staff worked as a team, applying comprehensive geriatric assessment, management and rehabilitation. Patients were assessed using the Mini Mental State Examination and the Organic Brain Syndrome Scale, and delirium was diagnosed according to DSM-IV criteria.

    RESULTS: The number of days of postoperative delirium among intervention patients was fewer (5.0+/-7.1 days vs 10.2+/-13.3 days, p=0.009) compared with controls. A lower proportion of intervention patients were delirious postoperatively than controls (56/102, 54.9% vs 73/97, 75.3%, p=0.003). Eighteen percent in the intervention ward and 52% of controls were delirious after the seventh postoperative day (p<0.001). Intervention patients suffered from fewer complications, such as decubitus ulcers, urinary tract infections, nutritional complications, sleeping problems and falls, than controls. Total postoperative hospitalization was shorter in the intervention ward (28.0+/-17.9 days vs 38.0+/-40.6 days, p=0.028).

    CONCLUSIONS: Patients with postoperative delirium can be successfully treated, resulting in fewer days of delirium, fewer other complications, and shorter length of hospitalization.

  • 194. MacDonald, Stuart W S
    et al.
    Cervenka, Simon
    Farde, Lars
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Bäckman, Lars
    Extrastriatal dopamine D2 receptor binding modulates intraindividual variability in episodic recognition and executive functioning.2009In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 47, no 11, p. 2299-2304Article in journal (Refereed)
    Abstract [en]

    Intraindividual variability (IIV) reflects lawful but transient within-person changes in performance. Increased IIV in cognition shares systematic associations with numerous conditions characterized by alterations in dopamine (DA) neuromodulation (e.g., old age, ADHD, schizophrenia, and Parkinson's disease). In a group of normal middle-aged adults, we examined links between PET-derived measures of D2 receptor binding in striatum, orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and hippocampus (HC) and IIV for tasks assessing recognition memory and executive functioning. An index of IIV, the intraindividual standard deviation (ISD), was computed across successful response latency trials for each cognitive outcome. Lower D2 binding in OC, ACC, and HC, but not striatum, was associated with increasing ISDs for the memory and executive measures. Consistent with neurocomputational models, the present findings suggest a role for extrastriatal DA neurotransmission in modulating variability in cognitive functioning.

  • 195. MacDonald, Stuart W S
    et al.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Bäckman, Lars
    Intra-individual variability in behavior: links to brain structure, neurotransmission and neuronal activity.2006In: Trends in Neurosciences, ISSN 0166-2236, Vol. 29, no 8, p. 474-80Article in journal (Other academic)
    Abstract [en]

    Intra-individual variability reflects a transient, within-person change in behavioral performance. It is a common component of aging-related cognitive decline and the behavioral changes associated with neurodegenerative and other brain-related disorders such as traumatic brain injury and schizophrenia. Behavioral changes within an individual can reflect alterations at a systems or a cellular level in the brain, and monitoring intra-individual variability can therefore provide a warning of underlying pathology. Despite frequent reports of intra-individual variability, there is little synthesis, and no direct examination of the neural underpinnings. Here, we integrate seminal findings from cognitive research across lifespans of individuals, and also neuropsychological and neurobiological findings, to identify key questions and some potential answers, and to set challenges for fostering future research into intra-individual variability.

  • 196.
    MacDonald, Stuart WS
    et al.
    Department of Psychology, University of Victoria, Victoria, British Columbia, Canada V8W 3P5.
    Karlsson, Sari
    Aging Research Center, Karolinska Institute, S-113 30 Stockholm, Sweden.
    Rieckmann, Anna
    Aging Research Center, Karolinska Institute, S-113 30 Stockholm, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Bäckman, Lars
    Aging Research Center, Karolinska Institute, S-113 30 Stockholm, Sweden.
    Aging-related increases in behavioral variability: relations to losses of dopamine D-1 receptors2012In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 32, no 24, p. 8186-8191Article in journal (Refereed)
    Abstract [en]

    Intraindividual variability (IIV) reflects within-person changes in performance, such as trial-by-trial fluctuations on a reaction-time (RT) task. The neural underpinnings of IIV remain largely unknown. The neurotransmitter dopamine (DA) is of particular interest here, as human populations that exhibit DA alterations, such as the elderly, attention deficit hyperactivity disorder children, persons with schizophrenia, and Parkinson patients, also show increased behavioral IIV. We examined links between DA D-1 binding potential (BP) in multiple brain regions and IIV for the control and interference conditions of the Multi-Source Interference Task (MSIT), tapping the cingulo-fronto-parietal attention network. Participants were 18 young and 20 healthy old adults. PET and the radioligand [C-11]SCH23390 were used to determine D-1 BP. The intraindividual standard deviation (ISD) was computed across successful latency trials of the MSIT conditions, independent of mean RT differences due to age, trial, and condition. Increasing ISDs were associated with increasing age and diminished D-1 binding in several brain regions (anterior cingulate gyrus, dorsolateral prefrontal cortex, and parietal cortex) for the interference, but not control, condition. Analyses of partial associations indicate that the association between age and IIV in the interference condition was linked to D-1 receptor losses in task-relevant brain regions. These findings suggest that dysfunctional DA modulation may contribute to increased variability in cognitive performance among older adults.

  • 197.
    Macefield, Vaughan G
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Häger-Ross, Charlotte
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Control of grip force during restraint of an object held between finger and thumb: responses of cutaneous afferents from the digits1996In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 108, no 1, p. 155-171Article in journal (Refereed)
    Abstract [en]

    Unexpected pulling and pushing loads exerted by an object held with a precision grip evoke automatic and graded increases in the grip force (normal to the grip surfaces) that prevent escape of the object; unloading elicits a decrease in grip force. Anesthesia of the digital nerves has shown that these grip reactions depend on sensory signals from the digits. In the present study we assessed the capacity of tactile afferents from the digits to trigger and scale the evoked grip responses. Using tungsten microelectrodes inserted percutaneously into the median nerve of awake human subjects, unitary recordings were made from ten FA I and 13 FA II rapidly adapting afferents, and 12 SA I and 18 SA II slowly adapting afferents. While the subject held a manipulandum between a finger and the thumb, tangential load forces were applied to the receptor-bearing digit (index, middle, or ring finger or thumb) as trapezoidal load-force profiles with a plateau amplitude of 0.5-2.0 N and rates of loading and unloading at 2-8 N/s, or as "step-loads" of 0.5 N delivered at 32 N/s. Such load trials were delivered in both the distal (pulling) and proximal (pushing) direction. FA I afferents responded consistently to the load forces, being recruited during the loading and unloading phases. During the loading ramp the ensemble discharge of the FA I afferents reflected the first time-derivative of the load force (i.e., the load-force rate). These afferents were relatively insensitive to the subject's grip force responses. However, high static finger forces appeared to suppress excitation of these afferents during the unloading phase. The FA II afferents were largely insensitive to the load trials: only with the step-loads did some afferents respond. Both classes of SA afferents were sensitive to load force and grip force, and discharge rates were graded by the rate of loading. The firing of the SA I afferents appeared to be relatively more influenced by the subject's grip-force response than the discharge of the SA II afferents, which were more influenced by the load-force stimulus. The direction in which the tangential load force was applied to the skin influenced the firing of most afferents and in particular the SA II afferents. Individual afferents within each class (except for the FA IIs) responded to the loading ramp before the onset of the subject's grip response and may thus be responsible for initiating the automatic increase in grip force. However, nearly half of the FA I afferents recruited by the load trials responded to the loading phase early enough to trigger the subject's grip-force response, whereas only ca. one-fifth of the SA Is and SA IIs did so. These observations, together with the high density of FA I receptors in the digits, might place the FA I afferents in a unique position to convey the information required to initiate and scale the reactive grip-force responses to the imposed load forces.

  • 198.
    Macefield, Vaughan G
    et al.
    Prince of Wales Medical Research Institute, UNSW, Barker St., Randwick, Sydney.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Loads applied tangential to a fingertip during an object restraint task can trigger short-latency as well as long-latency EMG responses in hand muscles.2003In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 152, no 2, p. 143-149Article in journal (Refereed)
    Abstract [en]

    Electrical stimulation of the digital nerves can cause short- and long-latency increases in electromyographic activity (EMG) of the hand muscles, but mechanical stimulation of primarily tactile afferents in the digits generally evokes only a long-latency increase in EMG. To examine whether such stimuli can elicit short-latency reflex responses, we recorded EMG over the first dorsal interosseous muscle when subjects (n=13) used the tip of the right index finger to restrain a horizontally oriented plate from moving when very brisk tangential forces were applied in the distal direction. The plate was subjected to ramp-and-hold pulling loads at two intensities (a 1-N load applied at 32 N/s or a 2-N load applied at 64 N/s) at times unpredictable to the subjects (mean interval 2 s; trial duration 500 ms). The contact surface of the manipulandum was covered with rayon--a slippery material. For each load, EMG was averaged for 128 consecutive trials with reference to the ramp onset. In all subjects, an automatic increase in grip force was triggered by the loads applied at 32 N/s; the mean onset latency of the EMG response was 59.8 +/- 0.9 (mean +/- SE) ms. In seven subjects (54%) this long-latency response was preceded by a weak short-latency excitation at 34.6 +/- 2.9 ms. With the loads applied at 64 N/s, the long-latency response occurred slightly earlier (58.9 +/- 1.7 ms) and, with one exception, all subjects generated a short-latency EMG response (34.9 +/- 1.3 ms). Despite the higher background grip force that subjects adopted during the stronger loads (4.9 +/- 0.3 N vs 2.5 +/- 0.2 N), the incidence of slips was higher--the manipulandum escaped from the grasp in 37 +/- 5% of trials with the 64 N/s ramps, but in only 18 +/- 4% with the 32-N/s ramps. The deformation of the fingertip caused by the tangential load, rather than incipient or overt slips, triggered the short-latency responses because such responses occurred even when the finger pad was fixed to the manipulandum with double-sided adhesive tape so that no slips occurred.

  • 199. Maitland, Scott B
    et al.
    Herlitz, Agneta
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Bäckman, Lars
    Nilsson, Lars-Göran
    Selective sex differences in declarative memory.2004In: Mem Cognit, ISSN 0090-502X, Vol. 32, no 7, p. 1160-9Article in journal (Refereed)
    Abstract [en]

    Sex invariance of a six-factor, higher order model of declarative memory (two second-order factors: episodic and semantic memory; and four first-order factors: recall, recognition, fluency, and knowledge) was established for 1,796 participants (35-85 years). Metric invariance of first- and second-order factor loadings across sex was demonstrated. At the second-order level, a female advantage was observed for both episodic and semantic memory. At the first-order level, sex differences in episodic memory were apparent for both recall and recognition, whereas the differences in semantic memory were driven by a female superiority in fluency. Additional tests of sex differences in three age groups (35-50, 55-65, and 70-85 years of age) indicated that the female superiority in declarative memory diminished with advancing age. The factor-specific sex differences are discussed in relation to sex differences in hippocampal function.

  • 200.
    Malinina, Evgenya
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Neurotransmission and functional synaptic plasticity in the rat medial preoptic nucleus2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Brain function implies complex information processing in neuronal circuits, critically dependent on the molecular machinery that enables signal transmission across synaptic contacts between neurons. The types of ion channels and receptors in the neuronal membranes vary with neuron types and brain regions and determine whether neuronal responses will be excitatory or inhibitory and often allow for functional synaptic plasticity which is thought to be the basis for much of the adaptability of the nervous system and for our ability to learn and store memories. The present thesis is a study of synaptic transmission in the medial preoptic nucleus (MPN), a regulatory center for several homeostatic functions but with most clearly established roles in reproductive behaviour. The latter behaviour typically shows several distinct phases with dramatically varying neuronal impulse activity and is also subject to experience-dependent modifications. It seems likely that the synapses in the MPN contribute to the behaviour by means of activity-dependent functional plasticity. Synaptic transmission in the MPN, however, has not been extensively studied and is not well understood. The present work was initiated to clarify the synaptic properties in the MPN. The aim was to achieve a better understanding of the functional properties of the MPN, but also to obtain information on the functional roles of ion channel types for neurotransmission and its plastic properties in general. The studies were carried out using a brain slice preparation from rat as well as acutely isolated neurons with adhering nerve terminals. Presynaptic nerve fibres were stimulated electrically or, in a few cases, by raised external K+ concentration, and postsynaptic responses were recorded by tight-seal perforated-patch techniques, often combined with voltage-clamp control of the post-synaptic membrane potential. Glutamate receptors of α-amino-3-hydroxy-5-methyl-4-izoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) types were identified as mediating the main excitatory synaptic signals and γ-aminobutyric acid (GABA)A receptors as mediating the main inhibitory signals. Both types of signals were suppressed by serotonin. The efficacy of AMPA-receptor-mediated transmission displayed several types of short-term plasticity, including paired-pulse potentiation and paired-pulse depression, depending on the stimulus rate and pattern. The observed plasticity was attributed to mainly presynaptic mechanisms. To clarify some of the presynaptic factors controlling synaptic efficacy, the role of presynaptic L-type Ca2+ channels, usually assumed not to directly control transmitter release, was investigated. The analysis showed that (i) L-type channels are present in GABA-containing presynaptic terminals on MPN neurons, (ii) that these channels provide a means for differential control of spontaneous and impulse-evoked GABA release and (iii) that this differential control is prominent during short-term synaptic plasticity. A model where Ca2+ influx through L-type channels may lead to reduced GABA release via effects on Ca2+-activated K+ channels, membrane potential and other Ca2+-channel types explains the observed findings. In addition, massive Ca2+ influx through L-type channels during high-frequency stimulation may contribute to increased GABA release during post-tetanic potentiation. In conclusion, the findings obtained in the present study indicate that complex neurotransmission mechanisms and different forms of synaptic plasticity contribute to the specific functional properties of the MPN.

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