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  • 101. Koehncke, Ylva
    et al.
    Papenberg, Goran
    Jonasson, Lars S.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Karalija, Nina
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Salami, Alireza
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bäckman, Lars
    Lindenberger, Ulman
    Lövdén, Martin
    Self-rated intensity of habitual physical activities is positively associated with dopamine D-2/3 receptor availability and cognition2018In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 181, p. 605-616Article in journal (Refereed)
    Abstract [en]

    Between-person differences in cognitive performance in older age are associated with variations in physical activity. The neurotransmitter dopamine (DA) contributes to cognitive performance, and the DA system deteriorates with advancing age. Animal data and a patient study suggest that physical activity modulates DA receptor availability, but data from healthy humans are lacking. In a cross-sectional study with 178 adults aged 64-68 years, we investigated links among self-reported physical activity, D(2/3)DA receptor (D2/3DR) availability, and cognitive performance. D2/3DR availability was measured with [C-11]raclopride positron emission tomography at rest. We used structural equation modeling to obtain latent factors for processing speed, episodic memory, working memory, physical activity, and D2/3DR availability in caudate, putamen, and hippocampus. Physical activity intensity was positively associated with D2/3DR availability in caudate, but not putamen and hippocampus. Frequency of physical activity was not related to D2/3DR availability. Physical activity intensity was positively related to episodic memory and working memory. D2/3DR availability in caudate and hippocampus was positively related to episodic memory. Taken together, our results suggest that striatal DA availability might be a neurochemical correlate of episodic memory that is also associated with physical activity.

  • 102.
    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.

  • 103.
    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.

  • 104.
    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.

  • 105. 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.

  • 106.
    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.

  • 107.
    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.

  • 108.
    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.

  • 109.
    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)
  • 110.
    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.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Fractional anisotropy in the substantia nigra in Parkinson's disease: a complex picture2015In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 22, no 10, p. 1410-1416Article in journal (Refereed)
    Abstract [en]

    Background and purpose: This study employs magnetic resonance imaging (MRI) diffusion tensor imaging to compare diffusion measures in the brains of patients with Parkinson's disease (PD) with healthy controls using longitudinal data. Methods: One-hundred and twenty-two patients and 34 controls were included at baseline. The MRI investigations were repeated after 1, 3 and 5 years. The diffusion measures were quantified using fractional anisotropy and mean, radial and axial diffusion (FA, MD, RD, AD). Regions of interest included the anterior, middle and posterior substantia nigra (SN), but also other areas. Linear models were used to test for the effect of disease and hemispheric lateralization. The P value was set at 0.05 (Bonferroni corrected). Results: Fractional anisotropy and AD were increased in the three nigral subareas in PD (P < 0.01), but MD and RD were unaltered. The right SN had higher FA than the left in all subareas (P < 0.01). MD and AD were increased in the right anterior part (P < 0.04), whereas MD and RD were decreased in the right middle and posterior parts (P < 0.001). The left middle cerebellar peduncle had increased FA and AD (P < 0.001) and decreased MD and RD (P < 0.01) compared to the right. Diffusion measures did not progress over time and side differences were not related to disease or lateralization of symptoms. Conclusions: Increased FA in the SN in PD indicates gliosis and inflammation in the nuclei, but possibly also intrusion of surrounding fibres into the shrinking structure. The hemispheric side differences of diffusion might reflect natural lateralization of connectivity, but their relation to PD must be studied further.

  • 111. 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.

  • 112. 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)
  • 113.
    Lind, Johanna
    et al.
    Department of Clinical Neuroscience, Karolinska Institute, MR Research Center, Karolinska Hospital.
    Ingvar, Martin
    Department of Clinical Neuroscience, Karolinska Institute, MR Research Center, Karolinska Hospital.
    Persson, Jonas
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Sleegers, Kristel
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium.
    Van Broeckhoven, Christine
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Stockholm.
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Parietal cortex activation predicts memory decline in apolipoprotein E-epsilon 4 carriers2006In: NeuroReport, ISSN 0959-4965, E-ISSN 1473-558X, Vol. 17, no 16, p. 1683-1686Article in journal (Refereed)
    Abstract [en]

    Apolipoprotein E-[varepsilon]4 is the main known genetic risk factor for Alzheimer's disease. Functional abnormalities in the parietal cortex have been reported for Alzheimer's disease patients and also for those at risk. Hence, a critical question is whether measurements of parietal cortex integrity may predict negative outcome among at-risk persons. We studied nondementedapolipoprotein E-[varepsilon]4 carriers and found a significant relationship between parietal blood-oxygen-level-dependent functional magnetic resonance imaging response during a word categorization task and subsequent episodic memory performance. Thus, the results show that parietal cortex alterations predict memory decline in nondemented apolipoprotein E-[varepsilon]4 carriers, and hence likely progression to Alzheimer's disease.

  • 114.
    Lind, Johanna
    et al.
    Department of Clinical Neuroscience, MR Research Center, Karolinska Hospital N-8, S-171 76 Stockholm, Sweden.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Persson, Jonas
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Ingvar, Martin
    Department of Clinical Neuroscience, MR Research Center, Karolinska Hospital N-8, S-171 76 Stockholm, Sweden.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, S-106 91 Stockholm, Sweden.
    Bäckman, Lars
    National Centre of Aging, Box 6401, S-113 82 Stockholm, Sweden.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Cruts, Marc
    Department of Molecular Genetics, Flanders Interuniversity, Institute of Biotechnology, University of Antwerp, B-2610 Antwerpen, Belgium.
    Sleegers, Kristel
    Department of Molecular Genetics VIB8, University of Antwerp, Campus CDE, Universiteitsplein 1, B-2610 Antwerp, Belgium.
    Van Broeckhoven, Christine
    Department of Molecular Genetics, Flanders Interuniversity, Institute of Biotechnology, University of Antwerp, B-2610 Antwerpen, Belgium.
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Reduced hippocampal volume in non-demented carriers fo the apolipoprotein E ε4: Relation to chronological age and recognition memory2006In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 396, no 1, p. 23-27Article in journal (Refereed)
    Abstract [en]

    Apolipoprotein E ε4 (APOE ε4) is the main known genetic risk factor for Alzheimer's disease (AD). Some previous studies have reported structural brain changes as well as cognitive deficits in non-demented APOE ε4 carriers, but the pattern of results is inconsistent and studies with larger sample sizes have been called for. Here we compared hippocampal volume and recognition–memory performance between AD-symptom-free carriers (N = 30) and non-carriers (N = 30) of the APOE ε4 (age range: 49–79 years). We observed reduced right hippocampal volume in APOE ε4 carriers, and found that the difference was most pronounced before the age of 65. Further, the APOE ε4 carriers made significantly more false alarms in the recognition–memory test, and the number of false alarms correlated significantly with right hippocampus volume. These results indicate that relatively young individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. A question for the future is whether smaller hippocampal volume represents early-onset hippocampal volume reduction or an inherent trait.

  • 115.
    Lind, Johanna
    et al.
    Department of Clinical Neuroscience, MR Research Center, Karolinska Hospital, Stockholm.
    Persson, Jonas
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Ingvar, Martin
    Department of Clinical Neuroscience, MR Research Center, Karolinska Hospital, Stockholm.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Cruts, Marc
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium.
    Van Broeckhoven, Christine
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Bäckman, Lars
    Stockholm Aging Research Center.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Stockholm.
    Petersson, Karl Magnus
    Department of Clinical Neuroscience, MR Research Center, Karolinska Hospital.
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers2006In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 129, no 5, p. 1240-1248Article in journal (Refereed)
    Abstract [en]

    The apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE epsilon4 carriers (age range: 49-74 years; 19 females), of which 10 were homozygous for the epsilon4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE epsilon4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE epsilon4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.

  • 116.
    Lindgren, Lenita
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Bergdahl, Jan
    Umeå University, Faculty of Social Sciences, Department of Psychology. Department of Clinical Dentistry, Faculty of Health Sciences, UIT - The Arctic University of Norway, Tromsø, Norway.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Longitudinal Evidence for Smaller Hippocampus Volume as a Vulnerability Factor for Perceived Stress2016In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 26, no 8, p. 3527-3533Article in journal (Refereed)
    Abstract [en]

    Hippocampal volume has been found to be smaller in individuals with stress-related disorders, but it remains unclear whether smaller volume is a consequence of stress or rather a vulnerability factor. Here, we examined this issue by relating stress levels to hippocampal volumes in healthy participants examined every 5 years in a longitudinal population-based study. Based on scores of 25- to 60-year-old participants on the perceived stress questionnaire, we defined moderately to high (n = 35) and low (n = 76) stress groups. The groups were re-examined after 5 years (at the 6th study wave). Historical data on subjective stress were available up to 10 years prior to Wave 5. At the first MRI session, the moderately to high stress group had a significantly smaller hippocampal volume, as measured by FreeSurfer (version 5.3), compared with the low-stress group. At follow-up, group differences in stress levels and hippocampal volume remained unchanged. In retrospective analyses of subjective stress, the observed group difference in stress was found to be stable. The long-term stability of group differences in perceived stress and hippocampal volume suggests that a small hippocampal volume may be a vulnerability factor for stress-related disorders.

  • 117.
    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.

  • 118.
    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)
  • 119.
    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.

  • 120. Lövdén, Martin
    et al.
    Karalija, Nina
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Köhncke, Ylva
    Jonasson, Lars S.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Rieckmann, Anna
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Papenberg, Goran
    Garrett, Douglas D.
    Guitart-Masip, Marc
    Salami, Alireza
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bäckman, Lars
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Lindenberger, Ulman
    Latent-profile analysis reveals behavioral and brain correlates of dopamine-cognition associations2018In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 28, no 11, p. 3894-3907Article in journal (Refereed)
    Abstract [en]

    Evidence suggests that associations between the neurotransmitter dopamine and cognition are nonmonotonic and open to modulation by various other factors. The functional implications of a given level of dopamine may therefore differ from person to person. By applying latent-profile analysis to a large (n = 181) sample of adults aged 64-68 years, we probabilistically identified 3 subgroups that explain the multivariate associations between dopamine D2/3R availability (probed with C-11-raclopride-PET, in cortical, striatal, and hippocampal regions) and cognitive performance (episodic memory, working memory, and perceptual speed). Generally, greater receptor availability was associated with better cognitive performance. However, we discovered a subgroup of individuals for which high availability, particularly in striatum, was associated with poor performance, especially for working memory. Relative to the rest of the sample, this subgroup also had lower education, higher body-mass index, and lower resting-state connectivity between caudate nucleus and dorsolateral prefrontal cortex. We conclude that a smaller subset of individuals induces a multivariate non-linear association between dopamine D2/3R availability and cognitive performance in this group of older adults, and discuss potential reasons for these differences that await further empirical scrutiny.

  • 121.
    Lövdén, Martin
    et al.
    Department of Psychology, Stockholm University, Sweden.
    Rönnlund, Michael
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Wahlin, Åke
    Department of Psychology, Stockholm University, Sweden / Aging Research Center (ARC), Karolinska Institute, Sweden.
    Backman, Lars
    Aging Research Center (ARC), Karolinska Institute, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Sweden.
    The extent of stability and change in episodic and semantic memory in old age: Demographic predictors of level and change2004In: The journals of gerontology. Series B, Psychological sciences and social sciences, ISSN 1079-5014, E-ISSN 1758-5368, Vol. 59, no 3, p. 130-134Article in journal (Refereed)
    Abstract [en]

    Structural stability and change in semantic and episodic memory performance as well as interindividual differences in 5-year changes in these constructs are examined within a sample of older adults (age rangeT1 = 60–80; n = 361). Interindividual differences in change were limited but significant. Stability coefficients were higher for semantic memory (.95) than for episodic memory (.87). Changes in episodic and semantic memory performance were strongly associated (r =.68). Across time, variances and covariances increased, and a tendency toward dedifferentiation in terms of increasing correlations was found. Chronological age was related to both level and change, but gender and education were only related to level of memory performance. Collectively, these results depict relatively high degrees of structural stability and stability of interindividual differences in declarative memory in old age.

     

  • 122.
    Lövheim, Hugo
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Norman, Tove
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Herpes Simplex Virus, APOE ɛ4, and Cognitive Decline in Old Age: Results from the Betula Cohort Study2019In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 67, no 1, p. 211-220Article in journal (Refereed)
    Abstract [en]

    Background: Herpes simplex virus (HSV) has been suggested to play a role in Alzheimer’s disease (AD) development.

    Objective: The aim of the present study was to investigate the early AD-related symptom episodic memory decline in relation to HSV and carriage of allele 4 of the apolipoprotein E gene (APOE ɛ4) in a large population-based cohort with a long follow-up time.

    Methods: The study included 3,413 persons, with longitudinal data available for 1,293 persons with a mean follow-up time of 11.6 years. The associations between HSV carriage, APOE ɛ4 carriage, and episodic memory was investigated at baseline, as well as in longitudinal analyses where individuals with and without HSV antibodies (HSV1/2 non-specific) were matched and episodic memory decline compared.

    Results: Cross-sectional analyses revealed an age-dependent association of HSV carriage with lower episodic memory function, particularly among APOE ɛ4 carriers (p = 0.008). Longitudinal analyses showed an increased risk of episodic memory decline in HSV carriers (≥65 years: p < 0.001, all ages: non-significant), and a significant interaction between HSV and APOE ɛ4 for episodic memory decline (p < 0.001).

    Conclusion: In this large population-based cohort study, both cross-sectional and longitudinal results support an association between HSV carriage and declining episodic memory function, especially among APOE ɛ4 carriers. The results strengthen the hypothesis that HSV is associated with AD development.

  • 123. 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.

  • 124. 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.

  • 125. MacDonald, Stuart W S
    et al.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Sandblom, Johan
    Fischer, Håkan
    Bäckman, Lars
    Increased response-time variability is associated with reduced inferior parietal activation during episodic recognition in aging.2008In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 20, no 5, p. 779-786Article in journal (Refereed)
    Abstract [en]

    Intraindividual variability (IIV) in cognitive performance shares systematic associations with aging-related processes, brain injury, and neurodegenerative pathology. However, little research has examined the neural underpinnings of IIV, with no studies investigating brain correlates of IIV in relation to retrieval success. Using functional magnetic resonance imaging, we examined links between IIV, recognition memory performance, and blood oxygenation level dependent activations. Nineteen older adults (70-79 years) were presented with 80 words at encoding, with brain scans and response latencies obtained during subsequent recognition. An index of IIV, the intraindividual standard deviation (ISD), was computed across successful latency trials. Decreasing ISDs were systematically associated with better recognition, faster latencies, and increased activation in the inferior parietal cortex (BA 40). Demonstrated links between less behavioral variability and parietal activations are consistent with the known importance of the parietal cortex for retrieval success. In support of extant findings and theory from neuroscience, neuropsychology, and cognitive aging, the present results suggest that behavioral IIV represents a proxy for neural integrity.

  • 126.
    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.

  • 127. 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.

  • 128.
    Maitland, Scott B
    et al.
    Family Relations and Applied Nutrition, University of Guelph, ON, Canada .
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Bäckman, Lars
    Aging Research Center, Karolinska Institute, Stockholm, Sweden.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Sweden.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    On the structure of personality: are there separate temperament and character factors?2009In: Personality and Individual Differences, ISSN 0191-8869, E-ISSN 1873-3549, Vol. 47, no 3, p. 180-184Article in journal (Refereed)
    Abstract [en]

    The Temperament and Character Inventory (TCI) is a widely used measure of psychobiological aspects of personality. Theoretically, the TCI is defined as comprising four temperament and three character factors. Most previous examinations of the factor structure have used exploratory factor methods with mixed results. We used confirmatory factor analyses (CFA) to examine the TCI in a sample of 2423 adults aged 35–90 years (1093 women, 1330 men) from the Betula study. Support for the seven TCI factors was mixed. Models including second-order factors provided no evidence that the seven first-order TCI factors reflect higher-order temperament and character constructs. Our findings provide no support that individual differences on the seven first-order TCI factors reflect distinct temperament or character dimensions of personality. Whereas more complex modeling strategies rejected separate character and temperament models, the simultaneous (seven-factor) model, and the use of second-order factors; the harm avoidance, self-directedness, and cooperativeness factors were acceptable examined individually. Results for novelty seeking were marginal and self-transcendence, reward dependence and/or persistence factors were not acceptable.

  • 129. Marklund, P
    et al.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Intersecting the divide between working and episodic memory2007In: The Conitive Neruoscience of Working Memory, Oxford: Oxford University Press , 2007, p. 305-331Chapter in book (Other (popular science, discussion, etc.))
  • 130.
    Marklund, Petter
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Fransson, P.
    Cognitive Neurophysiology Research Group, Department of Clinical Neuroscience, Karolinska Institute, Sweden.
    Cabeza, R.
    Center for Cognitive Neuroscience, Duke University, USA.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ingvar, M.
    Cognitive Neurophysiology Research Group, Department of Clinical Neuroscience, Karolinska Institute, 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.
    Unity and diversity of tonic and phasic executive control in episodic and working memory2007In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 36, no 4, p. 1361-1373Article in journal (Refereed)
    Abstract [en]

    The present study aimed to delineate the extent to which unitary executive functions might be shared across the separate domains of episodic and working memory. A mixed blocked/event-related functional magnetic resonance imaging (fMRI) design was employed to assess sustained (tonic control) and transient (phasic control) brain responses arising from incrementing executive demand (source versus item episodic memory - vis-à-vis - two-back versus one-back working memory) using load-dependent activation overlaps as indices of common components. Although an extensive portion of the regional load effects constituted differential control modulations in both sustained and transient responses, commonalities were also found implicating a subset of executive core mechanisms consistent with unitary or domain general control. 'Unitary' control modulations were temporally dissociated into (1) shared tonic components involving medial and lateral prefrontal cortex, striatum, cerebellum and superior parietal cortex, assumed to govern enhanced top-down context processing, monitoring and sustained attention throughout task periods and (2) stimulus-synchronous phasic components encompassing posterior intraparietal sulcus, hypothesized to support dynamic shifting of the 'focus of attention' among internal representations. Taken together, these results converge with theoretical models advocating both unity and diversity among executive control processes.

  • 131.
    Marklund, Petter
    et al.
    Umeå University, Faculty of Social Sciences, Psychology.
    Fransson, Per
    Umeå University, Faculty of Social Sciences, Psychology.
    Cabeza, Roberto
    Petersson, Karl M
    Ingvar, Martin
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Sustained and transient neural modulations in prefrontal cortex related to declarative long-term memory, working memory, and attention.2007In: Cortex, ISSN 0010-9452, Vol. 43, no 1, p. 22-37Article in journal (Refereed)
    Abstract [en]

    Common activations in prefrontal cortex (PFC) during episodic and semantic long-term memory (LTM) tasks have been hypothesized to reflect functional overlap in terms of working memory (WM) and cognitive control. To evaluate a WM account of LTM-general activations, the present study took into consideration that cognitive task performance depends on the dynamic operation of multiple component processes, some of which are stimulus-synchronous and transient in nature; and some that are engaged throughout a task in a sustained fashion. PFC and WM may be implicated in both of these temporally independent components. To elucidate these possibilities we employed mixed blocked/event-related functional magnetic resonance imaging (fMRI) procedures to assess the extent to which sustained or transient activation patterns overlapped across tasks indexing episodic and semantic LTM, attention (ATT), and WM. Within PFC, ventrolateral and medial areas exhibited sustained activity across all tasks, whereas more anterior regions including right frontopolar cortex were commonly engaged in sustained processing during the three memory tasks. These findings do not support a WM account of sustained frontal responses during LTM tasks, but instead suggest that the pattern that was common to all tasks reflects general attentional set/vigilance, and that the shared WM-LTM pattern mediates control processes related to upholding task set. Transient responses during the three memory tasks were assessed relative to ATT to isolate item-specific mnemonic processes and were found to be largely distinct from sustained effects. Task-specific effects were observed for each memory task. In addition, a common item response for all memory tasks involved left dorsolateral PFC (DLPFC). The latter response might be seen as reflecting WM processes during LTM retrieval. Thus, our findings suggest that a WM account of shared PFC recruitment in LTM tasks holds for common transient item-related responses rather than sustained state-related responses that are better seen as reflecting more general attentional/control processes.

  • 132. Marklund, Petter
    et al.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Elgh, Eva
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Riklund Åhlström, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    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.
    Temporal dynamics of basal ganglia under-recruitment in Parkinson's disease: transient caudate abnormalities during updating of working memory.2009In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 132, no Pt 2, p. 336-346Article in journal (Refereed)
    Abstract [en]

    Using hybrid-blocked/event-related fMRI and the 2-back task we aimed to decompose tonic and phasic temporal dynamics of basal ganglia response abnormalities in working memory associated with early untreated Parkinson's disease. In view of the tonic/phasic dopamine hypothesis, which posits a functional division between phasic D(2)-dependent striatal updating processes and tonic D(1)-dependent prefrontal context-maintenance processes, we predicted that newly diagnosed, drug-naïve Parkinson's disease patients, with selective striatal dopamine deprivation, would demonstrate transient rather than sustained activation changes in the basal ganglia during 2-back performance. Task-related activation patterns within discrete basal ganglia structures were directly compared between patients and healthy elderly controls. The obtained results yielded uniquely transient underactivation foci in caudate nuclei, putamen and globus pallidus in Parkinson's disease patients, which indicates suboptimal phasic implementation of striatal D(2)-dependent gating mechanisms during updating. Sustained underactivation was only seen in the anterior putamen, which may reflect initial signs of tonic control impairment. No significant changes were exhibited in prefrontal cortex. The present findings resonate well with the tonic/phasic dopamine account and suggest that basal ganglia under-recruitment associated with executive dysfunction in early Parkinson's disease might predominantly stem from deficiencies in phasic executive components subserved by striatum.

  • 133. Martensson, Johan
    et al.
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Bodammer, Nils Christian
    Lindgren, Magnus
    Johansson, Mikael
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Lovden, Martin
    Growth of language-related brain areas after foreign language learning2012In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 63, no 1, p. 240-244Article in journal (Refereed)
    Abstract [en]

    The influence of adult foreign-language acquisition on human brain organization is poorly understood. We studied cortical thickness and hippocampal volumes of conscript interpreters before and after three months of intense language studies. Results revealed increases in hippocampus volume and in cortical thickness of the left middle frontal gyrus, inferior frontal gyrus, and superior temporal gyrus for interpreters relative to controls. The right hippocampus and the left superior temporal gyrus were structurally more malleable in interpreters acquiring higher proficiency in the foreign language. Interpreters struggling relatively more to master the language displayed larger gray matter increases in the middle frontal gyrus. These findings confirm structural changes in brain regions known to serve language functions during foreign-language acquisition. (C) 2012 Elsevier Inc. All rights reserved.

  • 134. Mattsson, Patrik
    et al.
    Forsberg, Anton
    Persson, Jonas
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Nilsson, Lars-Göran
    Halldin, Christer
    Farde, Lars
    β-Amyloid binding in elderly subjects with declining or stable episodic memory function measured with PET and [11C]AZD21842015In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 42, no 10, p. 1507-1511Article in journal (Refereed)
    Abstract [en]

    Purpose: Cognitive decline has been suggested as an early marker for later onset of Alzheimer's disease. We therefore explored the relationship between decline in episodic memory and β-amyloid using positron emission tomography (PET) and [11C]AZD2184, a radioligand with potential to detect low levels of amyloid deposits. Methods: Healthy elderly subjects with declining (n = 10) or stable (n = 10) episodic memory over 15 years were recruited from the population-based Betula study and examined with PET. Brain radioactivity was measured after intravenous administration of [11C]AZD2184 The binding potential BP ND was calculated using linear graphical analysis with the cerebellum as reference region. Results: The binding of [11C]AZD2184 in total grey matter was generally low in the declining group, whereas some binding could be observed in the stable group. Mean BP ND was significantly higher in the stable group compared to the declining group (p = 0.019). An observation was that the three subjects with the highest BPND were ApoE ε4 allele carriers. Conclusions: We conclude that cognitive decline in the general population does not seem to stand by itself as an early predictor for amyloid deposits.

  • 135.
    Mousavi, Malahat
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nordin, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Bergdahl, Jan
    Umeå University, Faculty of Social Sciences, Department of Psychology. Institute of Clinical Dentistry, University of Tromsø, Tromsø, Norway.
    Eriksson, Kåre
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Moritz, Thomas
    Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences.
    Nilsson, Lars-Göran
    Umeå Center for Functional Brain Imaging, Umeå; Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå Center for Functional Brain Imaging, Umeå.
    Serum metabolomic biomarkers of dementia2014In: Dementia and geriatric cognitive disorders extra, E-ISSN 1664-5464, Vol. 4, no 2, p. 252-62Article in journal (Refereed)
    Abstract [en]

    Aims: This study compared serum metabolites of demented patients (Alzheimer's disease and vascular dementia) and controls, and explored serum metabolite profiles of nondemented individuals 5 years preceding the diagnosis. Methods: Cognitively healthy participants were followed up for 5-20 years. Cognitive assessment, serum sampling, and diagnosis were completed every 5 years. Multivariate analyses were conducted on the metabolite profiles generated by gas chromatography/time-of-flight mass spectrometry. Results: A significant group separation was found between demented patients and controls, and between incident cases and controls. Metabolites that contributed in both analyses were 3,4-dihydroxybutanoic acid, docosapentaenoic acid, and uric acid. Conclusions: Serum metabolite profiles are altered in demented patients, and detectable up to 5 years preceding the diagnosis. Blood sampling can make an important contribution to the early prediction of conversion to dementia.

  • 136.
    Nagel, Irene E
    et al.
    Max Planck Institute for Human Development, Berlin, Freie Universität Berlin.
    Preuschhof, Claudia
    Max Planck Institute for Human Development, Berlin, Freie Universität Berlin.
    Li, Shu-Chen
    Max Planck Institute for Human Development, Berlin.
    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.
    Bäckman, Lars
    Max Planck Institute for Human Development, Berlin, Karolinska Institute.
    Lindenberger, Ulman
    Max Planck Institute for Human Development, Berlin.
    Heekeren, Hauke R
    x Planck Institute for Human Development, Berlin, Freie Universität Berlin.
    Load Modulation of BOLD Response and Connectivity Predicts Working Memory Performance in Younger and Older Adults.2011In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 23, no 8, p. 2030-2045Article in journal (Refereed)
    Abstract [en]

    Individual differences in working memory (WM) performance have rarely been related to individual differences in the functional responsivity of the WM brain network. By neglecting person-to-person variation, comparisons of network activity between younger and older adults using functional imaging techniques often confound differences in activity with age trends in WM performance. Using functional magnetic resonance imaging, we investigated the relations among WM performance, neural activity in the WM network, and adult age using a parametric letter n-back task in 30 younger adults (21-31 years) and 30 older adults (60-71 years). Individual differences in the WM network's responsivity to increasing task difficulty were related to WM performance, with a more responsive BOLD signal predicting greater WM proficiency. Furthermore, individuals with higher WM performance showed greater change in connectivity between left dorsolateral prefrontal cortex and left premotor cortex across load. We conclude that a more responsive WM network contributes to higher WM performance, regardless of adult age. Our results support the notion that individual differences in WM performance are important to consider when studying the WM network, particularly in age-comparative studies.

  • 137. Nagel, Irene E
    et al.
    Preuschhof, Claudia
    Li, Shu-Chen
    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
    Lindenberger, Ulman
    Heekeren, Hauke R
    Performance level modulates adult age differences in brain activation during spatial working memory.2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 52, p. 22552-22557Article in journal (Refereed)
    Abstract [en]

    Working memory (WM) shows pronounced age-related decline. Functional magnetic resonance imaging (fMRI) studies have revealed age differences in task-related brain activation. Evidence based primarily on episodic memory studies suggests that brain activation patterns can be modulated by task difficulty in both younger and older adults. In most fMRI aging studies on WM, however, performance level has not been considered, so that age differences in activation patterns are confounded with age differences in performance level. Here, we address this issue by comparing younger and older low and high performers in an event-related fMRI study. Thirty younger (20-30 years) and 30 older (60-70 years) healthy adults were tested with a spatial WM task with three load levels. A region-of-interest analysis revealed marked differences in the activation patterns between high and low performers in both age groups. Critically, among the older adults, a more "youth-like" load-dependent modulation of the blood oxygen level-dependent signal was associated with higher levels of spatial WM performance. These findings underscore the need of taking performance level into account when studying changes in functional brain activation patterns from early to late adulthood.

  • 138.
    Naghavi, Hamid Reza
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    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 Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Cortical regions underlying successful encoding of semantically congruent and incongruent associations between common auditory and visual objects.2011In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 505, no 2, p. 191-195Article in journal (Refereed)
    Abstract [en]

    Recent studies implicate regions in the frontal, temporal and occipital cortices of the brain in audio-visual (AV) integration of familiar objects. It remains unclear, however, which brain regions contribute to the creation of object-related AV memories, and whether activation of these regions is affected by crossmodal congruency. Here we used event-related functional MRI in a subsequent memory paradigm to investigate the neural substrates of successful encoding of semantically congruent and incongruent AV memories. Creation of both types of memories activated a region in the left inferior frontal gyrus (IFG). In addition, successful encoding of semantically related and unrelated AV pairs was correlated with increased activity in regions within the right lateral occipital cortex and bilateral lateral temporal cortex, respectively. These results may highlight a common role of IFG in retrieval of semantic information during encoding and suggest that the occipital and temporal cortices differentially process perceptual versus conceptual associations of AV memories.

  • 139.
    Naghavi, Hamid Reza
    et al.
    Tehran University of Medical Sciences, Institute for Cognitive Science Studies, Tehran, Iran.
    Eriksson, Johan
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    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 Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    The claustrum/insula region integrates conceptually related sounds and pictures2007In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 422, no 1, p. 77-80Article in journal (Refereed)
    Abstract [en]

    The brain is able to create coherent percepts from multisensory input. This phenomenon, known as multisensory integration (MSI), is a ubiquitous feature of everyday life and has been found to be essential for a reliable interaction with the environment. Recent functional neuroimaging studies suggest that several different networks are engaged in various forms of MSI depending on the nature of information being integrated. However, little is known about the neural basis of a fundamental form of MSI in natural conditions; integration of common auditory and visual objects which are conceptually related, such as when we look at a cat and hear a meowing sound. Here we used event-related fMRI to compare the brain response to conceptually related and unrelated pairs of audio-visual stimuli denoting common objects. Our protocol was designed to preclude contamination of the results by cognitive processes additional to those needed for MSI. The results indicate that higher-order temporal and occipital areas respond to coincident sounds and pictures regardless of their semantic relationship; whereas, the right claustrum/insula region is differentially activated in association with multisensory integration of conceptually related common objects. This observation has important implications for understanding how multimodal information about common objects is represented in the brain.

  • 140.
    Naghavi, Hamid Reza
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Lind, Johanna
    Department of Psychology, University of Oslo, Oslo, Norway.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Stockholm, Sweden.
    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. Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Personality traits predict response to novel and familiar stimuli in the hippocampal region2009In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 173, no 2, p. 94-99Article in journal (Refereed)
    Abstract [en]

    Current evidence from genetic, neurochemical, and clinical research supports the notion that a combination of high novelty seeking and low harm avoidance traits (NS-ha) is reliably dissociable from the opposite personality profile (i.e., low novelty seeking and high harm avoidance, ns-HA). Little is known, however, about how the differences between these two types of personality are regulated by brain function. Here we used functional magnetic resonance imaging (fMRI) and recruited two groups of individuals, one group with the NS-ha profile and the other group with the ns-HA profile, to examine whether there is a difference between the two groups in their brain response to novel versus familiar word stimuli. Results revealed a differential pattern of response in an area in the hippocampal region, with the NS-ha group showing a greater sensitivity to novel stimuli and the ns-HA group demonstrating a greater response to familiar stimuli. We conclude that the response pattern to novel and familiar stimuli in the hippocampal region has a role in mediating differences between the NS-ha and ns-HA temperamental profiles.

  • 141. Naghavi, Hamid Reza
    et al.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Common fronto-parietal activity in attention, memory, and consciousness: shared demands on integration?2005In: Consciousness and Cognition, ISSN 1053-8100, E-ISSN 1090-2376, Vol. 14, no 2, p. 390-425Article in journal (Other academic)
    Abstract [en]

    Fronto-parietal activity has been frequently observed in fMRI and PET studies of attention, working memory, and episodic memory retrieval. Several recent fMRI studies have also reported fronto-parietal activity during conscious visual perception. A major goal of this review was to assess the degree of anatomical overlap among activation patterns associated with these four functions. A second goal was to shed light on the possible cognitive relationship of processes that relate to common brain activity across functions. For all reviewed functions we observed a consistent and overlapping pattern of brain activity. The overlap was most pronounced for the bilateral parietal cortex (BA 7 and BA 40; close to the intraparietal sulcus), and dorsolateral prefrontal cortex (right BA 9 and left BA 6). The common fronto-parietal activity will be discussed in terms of processes related to integration of distributed representations in the brain.

  • 142. Naghavi, HR
    et al.
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Common fronto-parietal activity in attention, memory, and consciousness: Shared demands on integration?2005In: CONSCIOUSNESS AND COGNITION, ISSN 1053-8100, Vol. 14, no 2, p. 390-425Article, review/survey (Other (popular science, discussion, etc.))
  • 143. Naghavi, HR
    et al.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Integrative action in the front-parietal network: A cure for a scattered mind2007In: Behavioral and Brain Sciences, ISSN 0140-525X, E-ISSN 1469-1825, Vol. 30, no 2, p. 161-162Article in journal (Refereed)
  • 144.
    Nevalainen, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ögren, Mattias
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lövdén, M
    Aging Research Center, Karolinska Institutet & Stockholm University, Stockholm.
    Lindenberger, U
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany.
    Bäckman, L
    Aging Research Center, Karolinska Institutet & Stockholm University, Stockholm.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    COBRA: A prospective multimodal imaging study of dopamine, brain structure and function, and cognition.2015In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1612, p. 83-103Article in journal (Refereed)
    Abstract [en]

    Cognitive decline is a characteristic feature of normal human aging. Previous work has demonstrated marked interindividual variability in onset and rate of decline. Such variability has been linked to factors such as maintenance of functional and structural brain integrity, genetics, and lifestyle. Still, few, if any, studies have combined a longitudinal design with repeated multimodal imaging and a comprehensive assessment of cognition as well as genetic and lifestyle factors. The present paper introduces the Cognition, Brain, and Aging (COBRA) study, in which cognitive performance and brain structure and function are measured in a cohort of 181 older adults aged 64 to 68 years at baseline. Participants will be followed longitudinally over a 10-year period, resulting in a total of three equally spaced measurement occasions. The measurement protocol at each occasion comprises a comprehensive set of behavioral and imaging measures. Cognitive performance is evaluated via computerized testing of working memory, episodic memory, perceptual speed, motor speed, implicit sequence learning, and vocabulary. Brain imaging is performed using positron emission tomography with [(11)C]-raclopride to assess dopamine D2/D3 receptor availability. Structural magnetic resonance imaging (MRI) is used for assessment of white and gray-matter integrity and cerebrovascular perfusion, and functional MRI maps brain activation during rest and active task conditions. Lifestyle descriptives are collected, and blood samples are obtained and stored for future evaluation. Here, we present selected results from the baseline assessment along with a discussion of sample characteristics and methodological considerations that determined the design of the study.

  • 145.
    Nilsson, Lars-Göran
    et al.
    Department of Psychology, Stockholm University, Stockholm, Sweden.
    Adolfsson, Rolf
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Bäckman, Lars
    Aging Research Center, Karolinska Institute, Stockholm, Sweden.
    Cruts, Marc
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium.
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Small, Brent J
    School of Aging Studies, University of South Florida.
    Van Broeckoven, Christine
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium.
    The influence of APOE status on episodic and semantic memory: data from a population-based study2006In: Neuropsychology, ISSN 0894-4105, E-ISSN 1931-1559, Vol. 20, no 6, p. 645-57Article in journal (Refereed)
    Abstract [en]

    In a prospective cohort study, the authors demonstrated a more pronounced epsilon4-related deficit for participants 70 years of age and older in tasks assessing episodic recall. Apolipoprotein E (APOE) and age interacted for episodic memory tasks, whereas the interaction for semantic memory tasks was between APOE and test wave. Heterozygotes of epsilon4 between middle-age and young-old participants performed at a higher level than noncarriers of this allele in recall tasks. A dose effect was found such that carriers of 2 epsilon4 alleles failed more profoundly in acquiring and recollecting episodic information than carriers of 1 epsilon4 allele, who in turn failed more than carriers of non-epsilon4 alleles. The pattern of findings observed for older epsilon4 carriers suggests that these individuals have particular difficulty when the executive task demands are high. Several factors (e.g., smaller hippocampal volumes, less effective neural repair mechanisms) may account for these findings. On the basis of the data obtained, the authors argue that analyses of the effect of specific genes in cognition should be accompanied by assessment of performance at a specific level, with due attention to the individual's age.

  • 146. Nilsson, Lars-Göran
    et al.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Bäckman, Lars
    de Frias, Cindy M
    Molander, Bo
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Betula: a prospective cohort study on memory, health and aging2004In: Aging, Neuropsychology and Cognition, ISSN 1382-5585, E-ISSN 1744-4128, Vol. 11, no 2-3, p. 134-148Article in journal (Refereed)
    Abstract [en]

    This article describes the Betula Study with respect to objectives, design, participants, and assessment instruments for health and cognition. Three waves of data collection have been completed in 5-year intervals since 1988-1990. A fourth wave started in 2003 and will be completed in 2005. An overview of Betula research is presented under the headings of memory and cognition and cognitive neuroscience. Health-related issues and sex differences as well as comparisons between cross-sectional and longitudinal studies are discussed in the first section. The influence of different genes and of some brain abnormalities for memory functioning in adulthood and old age constitute main topics in the second section. New data are presented on the association between blood pressure and dementia. We demonstrated that a demented group of participants had higher levels of systolic blood pressure and pulse pressure than non-dementia controls 10 years before diagnosis. The new fourth wave of data collection will, in addition to enriching the Betula database, permit revisiting and reanalyzing the existing data from new perspectives.

  • 147.
    Nilsson, Lars-Göran
    et al.
    Umeå University, Faculty of Social Sciences, Centre for Population Studies (CPS).
    Sternäng, Ola
    Department of Psychology, Stockholm University, Sweden.
    Rönnlund, Michael
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Social Sciences, Centre for Population Studies (CPS).
    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 Social Sciences, Centre for Population Studies (CPS).
    Challenging the notion of an early-onset of cognitive decline.2009In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 30, no 4, p. 521-524; discussion 530Article in journal (Other academic)
    Abstract [en]

    Salthouse claims that cognitive aging starts around 20 years of age. The basis for this claim is cross-sectional data. He dismisses longitudinal data, which typically show the cognitive decline to start much later, around 60 years of age. He states that longitudinal data cannot be trusted because they are flawed. There is a confounding between the effects of maturation and retest effects. We challenge Salthouse's strong claim on four accounts.

  • 148.
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Any novelty in hippocampal formation and memory?2005In: Current Opinion in Neurology, ISSN 1350-7540, E-ISSN 1473-6551, Vol. 18, no 4, p. 424-428Article in journal (Refereed)
    Abstract [en]

    PURPOSE OF REVIEW: Novel events tend to attract attention and become more effectively encoded in memory than predictable events. The hippocampus and medial-temporal cortical regions, along with regions of the prefrontal cortex, have been associated with enhanced memory for novel events. This review provides an update on recent studies of hippocampal novelty responses in relation to memory.

    RECENT FINDINGS: Several different types of novelty have been studied. Stimulus novelty effects have been observed as reduced neural activity in the medial-temporal and prefrontal regions when the same stimulus is repeatedly presented. Contextual novelty effects, the detection of a stimulus or event in an unexpected context, is impaired in patients with hippocampal damage. Single-trial analyses of brain activity show that the hippocampus rapidly habituates to contextually novel situations. Associative novelty, the detection of new arrangements of familiar stimuli, has also been related to the medial-temporal regions. A division of labour among the medial-temporal regions has been proposed such that associative novelty selectively engages the hippocampus, whereas stimulus novelty is mediated by the perirhinal cortex. However, a simple account of when the hippocampus versus other medial-temporal cortical regions is recruited awaits further studies. Increased dopaminergic and cholinergic neurotransmission may account for enhanced memory encoding of novel events, and relate to structural neuronal changes.

    SUMMARY: Interindividual variability in the responsiveness of the hippocampal-novelty system may be genetically mediated, and personality factors can also play a role. A better understanding of such variability can have implications for interventions aimed at supporting memory and for the treatment of drug abuse.

     

  • 149.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Cognitive control in the prefrontal cortex: a central or distributed executive?2018In: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 59, no 1, p. 62-65Article in journal (Refereed)
    Abstract [en]

    Cognitive control is the foundation for attaining goals by flexible adaptation of action to changing environmental demands. It has been hypothesized to be critically dependent upon the prefrontal cortex (PFC). In this mini-review, evidence for domain-general versus domain-specific cognitive control is examined, with a particular focus on attention and memory. The reviewed studies examined different levels of cognitive control in relation to performance and patterns of brain activity, and a few included direct comparisons of cognitive-control modulations across cognitive domains. Within domains, increased demands on cognitive control consistently translated into increased PFC activity, but limited overlap in recruited PFC regions was observed between domains. It is concluded that the PFC supports multiple cognitive-control systems that collectively may be conceived of as a distributed executive.

  • 150.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Den anpassningsbara hjärnan2004In: Stroke - ett slag mot hjärnan: Forskningens dag 2004, Medicinska fakulteten, Umeå , 2004, p. 37-45Chapter in book (Other academic)
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