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  • 51.
    Eriksson, Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Stiernstedt, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Öhlund, Maria
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Changing Zaire to Congo: The fate of no-longer relevant mnemonic information.2014Ingår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 101, s. 1-7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In an ever-changing world there is constant pressure on revising long-term memory, such when people or countries change name. What happens to the old, pre-existing information? One possibility is that old associations gradually are weakened and eventually lost. Alternatively, old and no longer relevant information may still be an integral part of memory traces. To test the hypothesis that old mnemonic information still becomes activated when people correctly retrieve new, currently relevant information, brain activity was measured with fMRI while participants performed a cued-retrieval task. Paired associates (symbol-sound and symbol-face pairs) were first learned during two days. Half of the associations were then updated during the next two days, followed by fMRI scanning on day 5 and also 18months later. As expected, retrieval reactivated sensory cortex related to the most recently learned association (visual cortex for symbol-face pairs, auditory cortex for symbol-sound pairs). Critically, retrieval also reactivated sensory cortex related to the no-longer relevant associate. Eighteen months later, only non-updated symbol-face associations were intact. Intriguingly, a subset of the updated associations was now treated as though the original association had taken over, in that memory performance was significantly worse than chance and that activity in sensory cortex for the original but not the updated associate correlated (negatively) with performance. Moreover, the degree of "residual" reactivation during day 5 inversely predicted memory performance 18months later. Thus, updating of long-term memory involves adding new information to already existing networks, in which old information can stay resilient for a long time.

  • 52.
    Eriksson, Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Vogel, Edward K.
    Lansner, Anders
    Bergström, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Neurocognitive Architecture of Working Memory2015Ingår i: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 88, nr 1, s. 33-46Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    A crucial role for working memory in temporary information processing and guidance of complex behavior has been recognized for many decades. There is emerging consensus that working-memory maintenance results from the interactions among long-term memory representations and basic processes, including attention, that are instantiated as reentrant loops between frontal and posterior cortical areas, as well as sub-cortical structures. The nature of such interactions can account for capacity limitations, lifespan changes, and restricted transfer after working-memory training. Recent data and models indicate that working memory may also be based on synaptic plasticity and that working memory can operate on non-consciously perceived information.

  • 53.
    Fernandes, Carla Patricia Duarte
    et al.
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
    Westlye, Lars Tjelta
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre For Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, Department of Psychology, University of Oslo, Oslo N-0317, Norway.
    Giddaluru, Sudheer
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
    Christoforou, Andrea
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
    Kauppi, Karolina
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University and Stockholm Brain Institute, Uppsala, Sweden.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Lundervold, Astri Johansen
    Department of Biological and Medical Psychology, K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway, Kavli Research Centre for Aging and Dementia, Haraldsplass Deaconess Hospital.
    Reinvang, Ivar
    Department of Psychology, University of Oslo, Oslo N-0317, Norway.
    Steen, Vidar Martin
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
    Le Hellard, Stéphanie
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
    Espeseth, Thomas
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre For Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, Department of Psychology, University of Oslo, Oslo N-0317, Norway.
    Lack of association of the rs1344706 ZNF804A variant with cognitive functions and DTI indices of white matter microstructure in two independent healthy populations2014Ingår i: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 222, nr 1-2, s. 60-66Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The rs1344706 single nucleotide polymorphism within intron 2 of the ZNF804A gene is strongly associated with schizophrenia and bipolar disorder. This variant has also been associated in some studies with a range of cognitive and neuroimaging phenotypes, but several studies have reported no effect on the same phenotypes in other samples. Here, we genotyped 670 healthy adult Norwegian subjects and 1753 healthy adult Swedish subjects for rs1344706, and tested for associations with cognitive phenotypes including general intellectual abilities, memory functions and cognitive inhibition. We also tested whether rs1344706 is associated with white matter microstructural properties using diffusion tensor imaging (DTI) data from 250 to 340 of the Norwegian and Swedish subjects, respectively. Whole-brain voxel-wise statistical modeling of the effect of the ZNF804A variant on two DTI indices, fractional anisotropy (FA) and radial diffusivity (RD), was performed using tract-based spatial statistics (TBSS), and commonly reported effect sizes were calculated within several large-scale white matter pathways based on neuroanatomical atlases. No significant associations were found between rs1344706 and the cognitive traits or white matter microstructure. We conclude that the rs1344706 SNP has no significant effect on these phenotypes in our two reasonably powered samples.

  • 54.
    Figueira, Joao
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nordin Adolfsson, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Öhman, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Serum Metabolite Markers of Dementia Through Quantitative NMR Analysis: The Importance of Threonine-Linked Metabolic Pathways2019Ingår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 69, nr 3, s. 763-774Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is a great need for diagnostic biomarkers of impending dementia. Metabolite markers in blood have been investigated in several studies, but inconclusive findings encourage further investigation, particularly in the pre-diagnostic phase. In the present study, the serum metabolomes of 110 dementia or pre-diagnostic dementia individuals and 201 healthy individuals matched for age, gender, and education were analyzed by nuclear magnetic resonance spectroscopy in combination with multivariate data analysis. 58 metabolites were quantified in each of the 311 samples. Individuals with dementia were discriminated from controls using a panel of seven metabolites, while the pre-diagnostic dementia subjects were distinguished from controls using a separate set of seven metabolites, where threonine was a common significant metabolite in both panels. Metabolite and pathway alterations specific for dementia and pre-diagnostic dementia were identified, in particular a disturbed threonine catabolism at the pre-diagnostic stage that extends to several threonine-linked pathways at the dementia stage.

  • 55.
    Figueira, Joao
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Nordin Adolfsson, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Öhman, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    NMR analysis of the human saliva metabolome distinguishes dementia patients from matched controls2016Ingår i: Molecular Biosystems, ISSN 1742-206X, E-ISSN 1742-2051, Vol. 12, nr 8, s. 2562-2571Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Saliva is a biofluid that is sensitive to metabolic changes and is straightforward to collect in a non-invasive manner, but it is seldom used for metabolite analysis when studying neurodegenerative disorders. We present a procedure for both an untargeted and targeted analysis of the saliva metabolome in which nuclear magnetic resonance (NMR) spectroscopy is used in combination with multivariate data analysis. The applicability of this approach is demonstrated on saliva samples selected from the 25 year prospective Betula study, including samples from dementia subjects with either Alzheimer's disease (AD) or vascular dementia at the time of sampling or who developed it by the next sampling/assessment occasion five years later, and age-, gender-, and education-matched control individuals without dementia. Statistically significant multivariate models were obtained that separated patients with dementia from controls and revealed seven discriminatory metabolites. Dementia patients showed significantly increased concentrations of acetic acid (fold change (fc) = 1.25, p = 2 x 10(-5)), histamine (fc = 1.26, p = 0.019), and propionate (fc = 1.35, p = 0.002), while significantly decreased levels were observed for dimethyl sulfone (fc = 0.81, p = 0.005), glycerol (fc = 0.79, p = 0.04), taurine (fc = 0.70, p = 0.007), and succinate (fc = 0.62, p = 0.008). Histamine, succinate, and taurine are known to be important in AD, and acetic acid and glycerol are involved in related pathways. Dimethyl sulfone and propionate originate from the diet and bacterial flora and might reflect poorer periodontal status in the dementia patients. For these seven metabolites, a weak but statistically significant pre-diagnostic value was observed. Taken together, we present a robust and general NMR analysis approach for studying the saliva metabolome that has potential use for screening and early detection of dementia.

  • 56.
    Fischer, Håkan
    et al.
    Karolinska Institute.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Bäckman, Lars
    Karolinska Institute.
    Age-related differences in brain regions supporting successful encoding of emotional faces.2010Ingår i: Cortex, ISSN 0010-9452, E-ISSN 1973-8102, Vol. 46, nr 4, s. 490-497Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In an event-related functional Magnetic Resonance Imaging (fMRI) study, younger and older adults were presented with negative emotional (i.e., fearful) and neutral face pictures under incidental learning conditions. They were subsequently given a test of face recognition outside the scanner. Both age groups activated amygdala bilaterally as well as the right hippocampus during successful encoding of the fearful faces. Direct age comparisons revealed greater activation in right amygdala and bilateral hippocampus in the young, whereas older adults showed greater activation in the left insular and right prefrontal cortices. None of these brain areas was activated during successful encoding of neutral faces, suggesting specificity of these brain activation patterns. The results indicate an age-related shift in the neural underpinnings of negative emotional face processing from medial-temporal to neocortical regions.

  • 57.
    Fischer, Håkan
    et al.
    Karolinska Institute.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Karlsson, Sari
    Karolinska Institute.
    Karlsson, Per
    Karolinska Hospital.
    Brehmer, Yvonne
    Karolinska Institute.
    Rieckmann, Anna
    Karolinska Institute.
    Macdonald, Stuart WS
    University of Victoria.
    Farde, Lars
    Karolinska Hospital.
    Bäckman, Lars
    Karolinska Institute.
    Simulating neurocognitive aging: effects of a dopaminergic antagonist on brain activity during working memory2010Ingår i: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 67, nr 6, s. 575-580Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Previous correlational studies have indirectly linked dysfunctional dopaminergic neurotransmission to age-related cognitive deficits and associated reductions in task-induced functional brain activity.

    METHODS: We used an experimental-pharmacological functional magnetic resonance imaging (fMRI) approach to more directly examine the role of dopamine in neurocognitive aging. Twenty younger and 20 healthy older adults were included. During fMRI scanning, a spatial working memory (SWM) task was administered under two conditions, varying in cognitive load. Positron emission tomography measurements with the D1 receptor antagonist [(11)C]SCH23390 confirmed that a given experimental dose of unlabeled solution occupied 50% of D1 receptors in younger adults.

    RESULTS: An age-related reduction in SWM performance was observed, and fMRI data revealed that, relative to younger adults under placebo conditions, elderly persons under-recruited load-sensitive fronto-parietal regions during SWM. Critically, in younger adults, the D1 antagonist resulted in a similar reduction in SWM performance and fMRI response.

    CONCLUSIONS: These results suggest that depletion of dopamine, whether ontogenetically or pharmacologically, results in decreased SWM performance as well as reduced load-dependent modulation of the blood oxygen level dependent signal in fronto-parietal regions, possibly by decreasing the signal-to-noise ratio in relevant neural networks.

  • 58. Fischer, Håkan
    et al.
    Sandblom, Johan
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Herlitz, Agneta
    Bäckman, Lars
    Brain activation while forming memories of fearful and neutral faces in women and men.2007Ingår i: Emotion, ISSN 1528-3542, Vol. 7, nr 4, s. 767-773Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Event-related functional MRI (fMRI) was used to assess brain activity during encoding of fearful and neutral faces in 12 women and 12 men. In a subsequent memory analysis, the authors separated successful from unsuccessful encoding of both types of faces, based on whether they were remembered or forgotten in a later recognition memory test. Overall, women and men recruited overlapping neural circuitries. Both sexes activated right-sided medial-temporal regions during successful encoding of fearful faces. Successful encoding of neutral faces was associated with left-sided lateral prefrontal and right-sided superior frontal activation in both sexes. In women, relatively greater encoding related activity for neutral faces was seen in the superior parietal and parahippocampal cortices. By contrast, men activated the left and right superior/middle frontal cortex more than women during successful encoding of the same neutral faces. These findings suggest that women and men use similar neural networks to encode facial information, with only subtle sex differences observed for neutral faces.

  • 59. Fjell, Anders M.
    et al.
    Sørensen, Øystein
    Amlien, Inge K.
    Bartrés-Faz, David
    Bros, Didac Maciá
    Buchmann, Nikolaus
    Demuth, Ilja
    Drevon, Christian A
    Düzel, Sandra
    Ebmeier, Klaus P
    Idland, Ane-Victoria
    Kietzmann, Tim C
    Kievit, Rogier
    Kühn, Simone
    Lindenberger, Ulman
    Mowinckel, Athanasia M
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Price, Darren
    Sexton, Claire E
    Solé-Padullés, Cristina
    Pudas, Sara
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Sederevicius, Donatas
    Suri, Sana
    Wagner, Gerd
    Watne, Leiv Otto
    Westerhausen, René
    Zsoldos, Enikő
    Walhovd, Kristine B
    Self-reported sleep relates to hippocampal atrophy across the adult lifespan: results from the Lifebrain consortium2019Ingår i: Sleep, ISSN 0161-8105, E-ISSN 1550-9109Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Poor sleep is associated with multiple age-related neurodegenerative and neuropsychiatric conditions. The hippocampus plays a special role in sleep and sleep-dependent cognition, and accelerated hippocampal atrophy is typically seen with higher age. Hence, it is critical to establish how the relationship between sleep and hippocampal volume loss unfolds across the adult lifespan.

    Methods: Self-reported sleep measures and MRI-derived hippocampal volumes were obtained from 3105 cognitively normal participants (18-90 years) from major European brain studies in the Lifebrain consortium. Hippocampal volume change was estimated from 5116 MRIs from 1299 participants for whom longitudinal MRIs were available, followed up to 11 years with a mean interval of 3.3 years. Cross-sectional analyses were repeated in a sample of 21390 participants from the UK Biobank.

    Results: No cross-sectional sleep – hippocampal volume relationships were found. However, worse sleep quality, efficiency, problems, and daytime tiredness were related to greater hippocampal volume loss over time, with high scorers showing 0.22% greater annual loss than low scorers. The relationship between sleep and hippocampal atrophy did not vary across age. Simulations showed that the observed longitudinal effects were too small to be detected as age-interactions in the cross-sectional analyses.

    Conclusions: Worse self-reported sleep is associated with higher rates of hippocampal volume decline across the adult lifespan. This suggests that sleep is relevant to understand individual differences in hippocampal atrophy, but limited effect sizes call for cautious interpretation.

  • 60.
    Flodin, Pär
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Jonasson, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.
    Does Aerobic Exercise Influence Intrinsic Brain Activity? An Aerobic Exercise Intervention among Healthy Old Adults2017Ingår i: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 9, artikel-id 267Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64–78 years) were randomized into either an aerobic exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). Additionally, a comprehensive battery of cognitive tasks assessing, e.g., executive function and episodic memory was administered. Both the aerobic and the control group improved in aerobic capacity (VO2-peak) over 6 months, but a significant group by time interaction confirmed that the aerobic group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings. At baseline, VO2-peak was negativly related to BOLD-signal fluctuations (BOLDSTD) in mid temporal areas. Over 6 months, improvements in aerobic capacity were associated with decreased connectivity between left hippocampus and contralateral precentral gyrus, and positively to connectivity between right mid-temporal areas and frontal and parietal regions. Independent component analysis identified a VO2-related increase in coupling between the default mode network and left orbitofrontal cortex, as well as a decreased connectivity between the sensorimotor network and thalamus. Extensive exploratory data analyses of global efficiency, connectome wide multivariate pattern analysis (connectome-MVPA), as well as ASL, did not reveal any relationships between aerobic fitness and intrinsic brain activity. Moreover, fitness-predicted changes in functional connectivity did not relate to changes in cognition, which is likely due to absent cross- sectional or longitudinal relationships between VO2-peak and cognition. We conclude that the aerobic exercise intervention had limited influence on patterns of intrinsic brain activity, although post hoc analyses indicated that individual changes in aerobic capacity preferentially influenced mid-temporal brain areas.

  • 61.
    Fytagoridis, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sjöberg, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Åström, Mattias
    Fredricks, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Effects of deep brain stimulation in the caudal Zona incerta on verbal fluency2013Ingår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 91, nr 1, s. 24-29Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Deep brain stimulation (DBS) of the caudal zona incerta (cZi) is a relatively unexplored and promising treatment in patients with severe essential tremor (ET). Preliminary data further indicate that the ability to produce language may be slightly affected by the treatment.

    Objective: To evaluate the effects on verbal fluency following cZi DBS in patients with ET.

    Method: Seventeen consecutive patients who had undergone DBS of the cZi for ET were tested regarding verbal fluency before surgery, 3 days after surgery and after 1 year. Ten patients were also evaluated by comparing performance on versus off stimulation after 1 year.

    Results: The total verbal fluency score decreased slightly, but significantly, from 22.7 (SD = 10.9) before surgery to 18.1 (SD = 7.5) 3 days after surgery (p = 0.036). After 1 year the score was nonsignificantly decreased to 20.1 (SD = 9.7, p = 0.2678). There was no detectable difference between stimulation on and off after 1 year.

    Conclusion: There was a tendency of an immediate and mostly transient postoperative decline in verbal fluency following cZi DBS for ET. In some of the patients this reduction was, however, more pronounced and also sustained over time.

  • 62. Garrett, Douglas D.
    et al.
    Nagel, Irene E.
    Preuschhof, Claudia
    Burzynska, Agnieszka Z.
    Marchner, Janina
    Wiegert, Steffen
    Jungehuelsing, Gerhard J.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Villringer, Arno
    Li, Shu-Chen
    Heekeren, Hauke R.
    Baeckman, Lars
    Lindenberger, Ulman
    Amphetamine modulates brain signal variability and working memory in younger and older adults2015Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, nr 24, s. 7593-7598Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI-based blood oxygen level-dependent (BOLD) signal variability (SDBOLD) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SDBOLD levels in the presence of AMPH. Drug session order greatly moderated change-change relations between AMPH-driven SDBOLD and reaction time means (RTmean) and SDs (RTSD). Older adults who received AMPH in the first session tended to improve in RTmean and RTSD when SDBOLD was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SDBOLD decreased (for RTmean) or no effect at all (for RTSD). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state-and practice-dependent neurochemical basis of human brain dynamics.

  • 63. Giddaluru, Sudheer
    et al.
    Espeseth, Thomas
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Aging Research Center, Karolinska Institutet and Stockholm University, 11330 Stockholm, Sweden.
    Westlye, Lars T
    Lundquist, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Christoforou, Andrea
    Cichon, Sven
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Steen, Vidar M
    Reinvang, Ivar
    Nilsson, Lars Göran
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). ARC, Karolinska Institutet, Stockholm, Sweden.
    Le Hellard, Stéphanie
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Genetics of structural connectivity and information processing in the brain2016Ingår i: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 221, nr 9, s. 4643-4661Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Understanding the genetic factors underlying brain structural connectivity is a major challenge in imaging genetics. Here, we present results from genome-wide association studies (GWASs) of whole-brain white matter (WM) fractional anisotropy (FA), an index of microstructural coherence measured using diffusion tensor imaging. Data from independent GWASs of 355 Swedish and 250 Norwegian healthy adults were integrated by meta-analysis to enhance power. Complementary GWASs on behavioral data reflecting processing speed, which is related to microstructural properties of WM pathways, were performed and integrated with WM FA results via multimodal analysis to identify shared genetic associations. One locus on chromosome 17 (rs145994492) showed genome-wide significant association with WM FA (meta P value = 1.87 × 10(-08)). Suggestive associations (Meta P value <1 × 10(-06)) were observed for 12 loci, including one containing ZFPM2 (lowest meta P value = 7.44 × 10(-08)). This locus was also implicated in multimodal analysis of WM FA and processing speed (lowest Fisher P value = 8.56 × 10(-07)). ZFPM2 is relevant in specification of corticothalamic neurons during brain development. Analysis of SNPs associated with processing speed revealed association with a locus that included SSPO (lowest meta P value = 4.37 × 10(-08)), which has been linked to commissural axon growth. An intergenic SNP (rs183854424) 14 kb downstream of CSMD1, which is implicated in schizophrenia, showed suggestive evidence of association in the WM FA meta-analysis (meta P value = 1.43 × 10(-07)) and the multimodal analysis (Fisher P value = 1 × 10(-07)). These findings provide novel data on the genetics of WM pathways and processing speed, and highlight a role of ZFPM2 and CSMD1 in information processing in the brain.

  • 64. Glasø de Lange, Ann-Marie
    et al.
    Sjøli Bråthen, Anne Cecilie
    Grydeland, Håkon
    Sexton, Claire
    Johansen-Berg, Heidi
    Andersson, Jesper L. R.
    Rohani, Darius A.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Fjell, Anders M.
    Walhovd, Kristine B.
    White matter integrity as a marker for cognitive plasticity in aging2016Ingår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 47, s. 74-82Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Age-related differences in white matter (WM) integrity are substantial, but it is unknown whether between subject variability in WM integrity influences the capacity for cognitive improvement. We investigated the effects of memory training related to active and passive control conditions in older adults and tested whether WM integrity at baseline was predictive of training benefits. We hypothesized that (1) memory improvement would be restricted to the training group, (2) widespread areas would show greater mean diffusivity (MD) and lower fractional anisotropy in older adults relative to young adults, and (3) within these areas, variability in WM microstructure in the older group would be predictive of training gains. The results showed that only the group receiving training improved their memory. Significant age differences in MD and fractional anisotropy were found in widespread areas. Within these areas, voxelwise analyses showed a negative relationship between MD and memory improvement in 3 clusters, indicating that WM integrity could serve as a marker for the ability to adapt in response to cognitive challenges in aging. 

  • 65.
    Gorbach, Tetiana
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Lundquist, Anders
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    de Luna, Xavier
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden; .
    A Hierarchical Bayesian Mixture Modeling Approach for Analysis of Resting-State Functional Brain Connectivity: An Alternative to ThresholdingManuskript (preprint) (Övrigt vetenskapligt)
  • 66.
    Gorbach, Tetiana
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Lundquist, Anders
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    de Luna, Xavier
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden..
    Bayesian mixture modeling for longitudinal fMRI connectivity studies with dropoutManuskript (preprint) (Övrigt vetenskapligt)
  • 67.
    Gorbach, Tetiana
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Pudas, Sara
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Lundquist, Anders
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    de Luna, Xavier
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Longitudinal association between hippocampus atrophy and episodic-memory decline2017Ingår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 51, s. 167-176Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is marked variability in both onset and rate of episodic-memory decline in aging. Structural magnetic resonance imaging studies have revealed that the extent of age-related brain changes varies markedly across individuals. Past studies of whether regional atrophy accounts for episodic-memory decline in aging have yielded inconclusive findings. Here we related 15-year changes in episodic memory to 4-year changes in cortical and subcortical gray matter volume and in white-matter connectivity and lesions. In addition, changes in word fluency, fluid IQ (Block Design), and processing speed were estimated and related to structural brain changes. Significant negative change over time was observed for all cognitive and brain measures. A robust brain-cognition change-change association was observed for episodic-memory decline and atrophy in the hippocampus. This association was significant for older (65-80 years) but not middle-aged (55-60 years) participants and not sensitive to the assumption of ignorable attrition. Thus, these longitudinal findings highlight medial-temporal lobe system integrity as particularly crucial for maintaining episodic-memory functioning in older age. 

  • 68.
    Guez, Michel
    et al.
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Ortopedi.
    Brännström, Rigmor
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Neurologi.
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskaplig fakultet, Psykologi.
    Toolanen, Göran
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Ortopedi.
    Hildingsson, Christer
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Ortopedi.
    Neuropsychological functioning and MMPI-2 profiles in chronic neck pain: a comparison of whiplash and non-traumatic groups.2005Ingår i: Journal of Clinical and Experimental Neuropsychology, ISSN 1380-3395, E-ISSN 1744-411X, Vol. 27, nr 2, s. 151-163Artikel i tidskrift (Refereegranskat)
  • 69. Habib, Reza
    et al.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Neural Correlates of Availability and Accessibility in Memory2008Ingår i: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 8, nr 7, s. 1720-1726Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Failure to remember can be due to not having information available in memory or to an inability to access information that is available. We used functional magnetic resonance imaging to examine brain responses during encoding and successive cued recall and associative recognition tests of paired associates. Items were classified into 3 categories based on performance on the 2 retrieval tests: 1) successfully remembered (both recalled and recognized), 2) inaccessible (not recalled but later recognized), and 3) forgotten (neither recalled nor recognized). During cued recall, availability in memory was signaled in a network of regions including bilateral medial temporal lobe, left middle temporal cortex, and the parietal cortex. Memory access resulted in heightened activity in these regions as well as in left inferior frontal cortex. Encoding-related activity in hippocampus and inferior temporal cortex predicted subsequent availability and left inferior frontal activity predicted subsequent access. These results suggest that failure to access information that is available in memory may reflect weaker memory representations.

  • 70.
    Habib, Reza
    et al.
    Department of Psychology and School of Medicine, Southern Illinois University Carbondale, Carbondale, Illinois, USA.
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Stockholm, Swede.
    Cognitive and non-cognitive factors contributing to the longitudinal identification of successful older adults in the Betula study2007Ingår i: Aging, Neuropsychology and Cognition, ISSN 1382-5585, E-ISSN 1744-4128, Vol. 14, nr 3, s. 257-273Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Studies of successful aging have typically defined elderly who fall in the upper end of a distribution of test scores as successful. A different definition of successful aging requires that older adults fall at or above the mean level of younger adults and maintain this level over time. Here we examined this definition of successful aging in a sample of 1463 individuals between the ages of 50 of 85. Based on principal coordinate analysis of cognitive and non-cognitive variables, we identified a group of 55 (8.3%) 70-85 years olds that were high functioning. This group of elderly showed elevated performance on a range of cognitive tasks. Non-cognitive factors that characterized this group included education and subjective health. The participants were retested 5 years later and the same type of analysis was repeated. Of the remaining individuals who initially were classified as high functioning, 18 (35%) remained high functioning and thus met the definition for successful aging. Years of education was a significant predictor of who remained successful over time.

  • 71. Hagg, S.
    et al.
    Zhan, Y.
    Karlsson, R.
    Gerritsen, L.
    Ploner, A.
    van der Lee, S. J.
    Broer, L.
    Deelen, J.
    Marioni, R. E.
    Wong, A.
    Lundquist, Anders
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Zhu, G.
    Hansell, N. K.
    Sillanpaa, E.
    Fedko, I. O.
    Amin, N. A.
    Beekman, M.
    de Craen, A. J. M.
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Harris, S. E.
    Kan, K-J
    Martin-Ruiz, C. M.
    Montgomery, G. W.
    Adolfsson, Annelie N.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Reynolds, C. A.
    Samani, N. J.
    Suchiman, H. E. D.
    Viljanen, A.
    von Zglinicki, T.
    Wright, M. J.
    Hottenga, J-J
    Boomsma, D. I.
    Rantanen, T.
    Kaprio, J. A.
    Nyholt, D. R.
    Martin, N. G.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Kuh, D.
    Starr, J. M.
    Deary, I. J.
    Slagboom, P. E.
    van Duijn, C. M.
    Codd, V.
    Pedersen, N. L.
    Short telomere length is associated with impaired cognitive performance in European ancestry cohorts2017Ingår i: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 7, artikel-id e1100Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N = 17 052; mean age = 59.2 +/- 8.8 years) provided results for associations between qPCR-measuredTL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (beta = 0.051 per s. d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P = 0.0002), and MMSE (beta = 0.025; 95% CI: 0.002, 0.047; P = 0.03), and faster STROOP (beta = -0.053; 95% CI: -0.087, -0.018; P = 0.003). Effects for DSST were stronger in APOE epsilon 4 non-carriers (beta = 0.081; 95% CI: 0.045, 0.117; P = 1.0 x 10(-5)), whereas carriers performed better in STROOP (beta = -0.074; 95% CI: -0.140, -0.009; P = 0.03). Causal associations were found for STROOP only (beta = -0.598 per s. d.-increase of TL; 95% CI: -1.125, -0.072; P = 0.026), with a larger effect in epsilon 4-carriers (beta = -0.699; 95% CI: -1.330, -0.069; P = 0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE epsilon 4-carriers might be at differential risk.

  • 72.
    Hansson, Patrik
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Eriksson Sörman, Daniel
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Bergdahl, Jan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Institute of Clinical Dentistry, UIT The Arctic Universityof Norway, Tromsø, Norway.
    Bergdahl, Maud
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nilsson, Lars-Goran
    Dental status is unrelated to risk of dementia: a 20-year prospective study2014Ingår i: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 62, nr 5, s. 979-981Artikel i tidskrift (Refereegranskat)
  • 73.
    Hansson, Patrik
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Sunnegårdh-Grönberg, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Tandhygienistutbildning.
    Bergdahl, Jan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Bergdahl, Maud
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nilsson, Lars-Göran
    Relationship between natural teeth and memory in a healthy elderly population2013Ingår i: European Journal of Oral Sciences, ISSN 0909-8836, E-ISSN 1600-0722, Vol. 121, nr 4, s. 333-340Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The relationship between mastication and cognitive function remains unclear, but both animal and experimental human studies suggest a possible causal relationship. In the present study it was hypothesized that natural teeth are of importance for hippocampus-based cognitive processes, such as episodic long-term memory. A population-based sample of 273 participants (55-80yr of age; 145 women) was investigated in a cross-sectional study. The participants underwent health assessment, completed a battery of cognitive tests, and took part in an extensive clinical oral examination. The number of natural teeth contributed uniquely and significantly to explaining variance (3-4%) in performance on measures of episodic memory and semantic memory over and above individual differences in age, years of education, gender, occupation, living conditions, and medical history. The number of natural teeth did not have an influence on the performance of measures of working memory, visuospatial ability, or processing speed. Within the limitations of the current study, a small, but significant, relationship between episodic memory and number of natural teeth is evident.

  • 74.
    Hedner, Margareta
    et al.
    Stockholm University, Stockholm Brain Institute.
    Nilsson, Lars-Göran
    Stockholm University, Stockholm Brain Institute.
    Olofsson, Jonas K
    Stockholm University, Stockholm Brain Institute.
    Bergman, Olle
    Göteborg University.
    Eriksson, Elias
    Göteborg University.
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Centrum för befolkningsstudier (CBS). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Larsson, Maria
    Stockholm University, Stockholm Brain Institute.
    Age-related olfactory decline is associated with the BDNF Val66met Polymorphism: Evidence from a population-based study2010Ingår i: Frontiers in aging neuroscience, ISSN 1663-4365, Vol. 2, s. 24-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The present study investigates the effect of the brain-derived neurotrophic factor (BDNF) val66met polymorphism on change in olfactory function in a large scale, longitudinal population-based sample (n = 836). The subjects were tested on a 13 item force-choice odor identification test on two test occasions over a 5-year-interval. Sex, education, health-related factors, and semantic ability were controlled for in the statistical analyses. Results showed an interaction effect of age and BDNF val66met on olfactory change, such that the magnitude of olfactory decline in the older age cohort (70-90 years old at baseline) was larger for the val homozygote carriers than for the met carriers. The older met carriers did not display larger age-related decline in olfactory function compared to the younger group. The BDNF val66met polymorphism did not affect the rate of decline in the younger age cohort (45-65 years). The findings are discussed in the light of the proposed roles of BDNF in neural development and maintenance.

  • 75. Hibar, Derrek P.
    et al.
    Adams, Hieab H. H.
    Jahanshad, Neda
    Chauhan, Ganesh
    Stein, Jason L.
    Hofer, Edith
    Renteria, Miguel E.
    Bis, Joshua C.
    Arias-Vasquez, Alejandro
    Ikram, M. Kamran
    Desrivieres, Sylvane
    Vernooij, Meike W.
    Abramovic, Lucija
    Alhusaini, Saud
    Amin, Najaf
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Arfanakis, Konstantinos
    Aribisala, Benjamin S.
    Armstrong, Nicola J.
    Athanasiu, Lavinia
    Axelsson, Tomas
    Beecham, Ashley H.
    Beiser, Alexa
    Bernard, Manon
    Blanton, Susan H.
    Bohlken, Marc M.
    Boks, Marco P.
    Bralten, Janita
    Brickman, Adam M.
    Carmichael, Owen
    Chakravarty, M. Mallar
    Chen, Qiang
    Ching, Christopher R. K.
    Chouraki, Vincent
    Cuellar-Partida, Gabriel
    Crivello, Fabrice
    Den Braber, Anouk
    Doan, Nhat Trung
    Ehrlich, Stefan
    Giddaluru, Sudheer
    Goldman, Aaron L.
    Gottesman, Rebecca F.
    Grimm, Oliver
    Griswold, Michael E.
    Guadalupe, Tulio
    Gutman, Boris A.
    Hass, Johanna
    Haukvik, Unn K.
    Hoehn, David
    Holmes, Avram J.
    Hoogman, Martine
    Janowitz, Deborah
    Jia, Tianye
    Jorgensen, Kjetil N.
    Karbalai, Nazanin
    Kasperaviciute, Dalia
    Kim, Sungeun
    Klein, Marieke
    Kraemer, Bernd
    Lee, Phil H.
    Liewald, David C. M.
    Lopez, Lorna M.
    Luciano, Michelle
    Macare, Christine
    Marquand, Andre F.
    Matarin, Mar
    Mather, Karen A.
    Mattheisen, Manuel
    McKay, David R.
    Milaneschi, Yuri
    Maniega, Susana Munoz
    Nho, Kwangsik
    Nugent, Allison C.
    Nyquist, Paul
    Loohuis, Loes M. Olde
    Oosterlaan, Jaap
    Papmeyer, Martina
    Pirpamer, Lukas
    Puetz, Benno
    Ramasamy, Adaikalavan
    Richards, Jennifer S.
    Risacher, Shannon L.
    Roiz-Santianez, Roberto
    Rommelse, Nanda
    Ropele, Stefan
    Rose, Emma J.
    Royle, Natalie A.
    Rundek, Tatjana
    Saemann, Philipp G.
    Saremi, Arvin
    Satizabal, Claudia L.
    Schmaal, Lianne
    Schork, Andrew J.
    Shen, Li
    Shin, Jean
    Shumskaya, Elena
    Smith, Albert V.
    Sprooten, Emma
    Strike, Lachlan T.
    Teumer, Alexander
    Tordesillas-Gutierrez, Diana
    Toro, Roberto
    Trabzuni, Daniah
    Trompet, Stella
    Vaidya, Dhananjay
    Van der Grond, Jeroen
    Van der Lee, Sven J.
    Van der Meer, Dennis
    Van Donkelaar, Marjolein M. J.
    Van Eijk, Kristel R.
    Van Erp, Theo G. M.
    Van Rooij, Daan
    Walton, Esther
    Westlye, Lars T.
    Whelan, Christopher D.
    Windham, Beverly G.
    Winkler, Anderson M.
    Wittfeld, Katharina
    Woldehawariat, Girma
    Wolf, Christiane
    Wolfers, Thomas
    Yanek, Lisa R.
    Yang, Jingyun
    Zijdenbos, Alex
    Zwiers, Marcel P.
    Agartz, Ingrid
    Almasy, Laura
    Ames, David
    Amouyel, Philippe
    Andreassen, Ole A.
    Arepalli, Sampath
    Assareh, Amelia A.
    Barral, Sandra
    Bastin, Mark E.
    Becker, Diane M.
    Becker, James T.
    Bennett, David A.
    Blangero, John
    van Bokhoven, Hans
    Boomsma, Dorret I.
    Brodaty, Henry
    Brouwer, Rachel M.
    Brunner, Han G.
    Buckner, Randy L.
    Buitelaar, Jan K.
    Bulayeva, Kazima B.
    Cahn, Wiepke
    Calhoun, Vince D.
    Cannon, Dara M.
    Cavalleri, Gianpiero L.
    Cheng, Ching-Yu
    Cichon, Sven
    Cookson, Mark R.
    Corvin, Aiden
    Crespo-Facorro, Benedicto
    Curran, Joanne E.
    Czisch, Michael
    Dale, Anders M.
    Davies, Gareth E.
    De Craen, Anton J. M.
    De Geus, Eco J. C.
    De Jager, Philip L.
    De Zubicaray, Greig I.
    Deary, Ian J.
    Debette, Stephanie
    DeCarli, Charles
    Delanty, Norman
    Depondt, Chantal
    DeStefano, Anita
    Dillman, Allissa
    Djurovic, Srdjan
    Donohoe, Gary
    Drevets, Wayne C.
    Duggirala, Ravi
    Dyer, Thomas D.
    Enzinger, Christian
    Erk, Susanne
    Espeseth, Thomas
    Fedko, Iryna O.
    Fernandez, Guillen
    Ferrucci, Luigi
    Fisher, Simon E.
    Fleischman, Debra A.
    Ford, Ian
    Fornage, Myriam
    Foroud, Tatiana M.
    Fox, Peter T.
    Francks, Clyde
    Fukunaga, Masaki
    Gibbs, J. Raphael
    Glahn, David C.
    Gollub, Randy L.
    Goring, Harald H. H.
    Green, Robert C.
    Gruber, Oliver
    Gudnason, Vilmundur
    Guelfi, Sebastian
    Haberg, Asta K.
    Hansell, Narelle K.
    Hardy, John
    Hartman, Catharina A.
    Hashimoto, Ryota
    Hegenscheid, Katrin
    Heinz, Andreas
    Le Hellard, Stephanie
    Hernandez, Dena G.
    Heslenfeld, Dirk J.
    Ho, Beng-Choon
    Hoekstra, Pieter J.
    Hoffmann, Wolfgang
    Hofman, Albert
    Holsboer, Florian
    Homuth, Georg
    Hosten, Norbert
    Hottenga, Jouke-Jan
    Huentelman, Matthew
    Pol, Hilleke E. Hulshoff
    Ikeda, Masashi
    Jack, Clifford R., Jr.
    Jenkinson, Mark
    Johnson, Robert
    Joensson, Erik G.
    Jukema, J. Wouter
    Kahn, Rene S.
    Kanai, Ryota
    Kloszewska, Iwona
    Knopman, David S.
    Kochunov, Peter
    Kwok, John B.
    Lawrie, Stephen M.
    Lemaitre, Herve
    Liu, Xinmin
    Longo, Dan L.
    Lopez, Oscar L.
    Lovestone, Simon
    Martinez, Oliver
    Martinot, Jean-Luc
    Mattay, Venkata S.
    McDonald, Colm
    McIntosh, Andrew M.
    McMahon, Francis J.
    McMahon, Katie L.
    Mecocci, Patrizia
    Melle, Ingrid
    Meyer-Lindenberg, Andreas
    Mohnke, Sebastian
    Montgomery, Grant W.
    Morris, Derek W.
    Mosley, Thomas H.
    Muhleisen, Thomas W.
    Mueller-Myhsok, Bertram
    Nalls, Michael A.
    Nauck, Matthias
    Nichols, Thomas E.
    Niessen, Wiro J.
    Nothen, Markus M.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Ohi, Kazutaka
    Olvera, Rene L.
    Ophoff, Roel A.
    Pandolfo, Massimo
    Paus, Tomas
    Pausova, Zdenka
    Penninx, Brenda W. J. H.
    Pike, G. Bruce
    Potkin, Steven G.
    Psaty, Bruce M.
    Reppermund, Simone
    Rietschel, Marcella
    Roffman, Joshua L.
    Romanczuk-Seiferth, Nina
    Rotter, Jerome I.
    Ryten, Mina
    Sacco, Ralph L.
    Sachdev, Perminder S.
    Saykin, Andrew J.
    Schmidt, Reinhold
    Schmidt, Helena
    Schofield, Peter R.
    Sigursson, Sigurdur
    Simmons, Andrew
    Singleton, Andrew
    Sisodiya, Sanjay M.
    Smith, Colin
    Smoller, Jordan W.
    Soininen, Hilkka
    Steen, Vidar M.
    Stott, David J.
    Sussmann, Jessika E.
    Thalamuthu, Anbupalam
    Toga, Arthur W.
    Traynor, Bryan J.
    Troncoso, Juan
    Tsolaki, Magda
    Tzourio, Christophe
    Uitterlinden, Andre G.
    Hernandez, Maria C. Valdes
    Van der Brug, Marcel
    van der Lugt, Aad
    van der Wee, Nic J. A.
    Van Haren, Neeltje E. M.
    van't Ent, Dennis
    Van Tol, Marie-Jose
    Vardarajan, Badri N.
    Vellas, Bruno
    Veltman, Dick J.
    Voelzke, Henry
    Walter, Henrik
    Wardlaw, Joanna M.
    Wassink, Thomas H.
    Weale, Michael E.
    Weinberger, Daniel R.
    Weiner, Michael W.
    Wen, Wei
    Westman, Eric
    White, Tonya
    Wong, Tien Y.
    Wright, Clinton B.
    Zielke, Ronald H.
    Zonderman, Alan B.
    Martin, Nicholas G.
    Van Duijn, Cornelia M.
    Wright, Margaret J.
    Longstreth, W. T.
    Schumann, Gunter
    Grabe, Hans J.
    Franke, Barbara
    Launer, Lenore J.
    Medland, Sarah E.
    Seshadri, Sudha
    Thompson, Paul M.
    Ikram, M. Arfan
    Novel genetic loci associated with hippocampal volume2017Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, artikel-id 13624Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

  • 76. Hibar, Derrek P.
    et al.
    Stein, Jason L.
    Renteria, Miguel E.
    Arias-Vasquez, Alejandro
    Desrivieres, Sylvane
    Jahanshad, Neda
    Toro, Roberto
    Wittfeld, Katharina
    Abramovic, Lucija
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Aribisala, Benjamin S.
    Armstrong, Nicola J.
    Bernard, Manon
    Bohlken, Marc M.
    Boks, Marco P.
    Bralten, Janita
    Brown, Andrew A.
    Chakravarty, M. Mallar
    Chen, Qiang
    Ching, Christopher R. K.
    Cuellar-Partida, Gabriel
    den Braber, Anouk
    Giddaluru, Sudheer
    Goldman, Aaron L.
    Grimm, Oliver
    Guadalupe, Tulio
    Hass, Johanna
    Woldehawariat, Girma
    Holmes, Avram J.
    Hoogman, Martine
    Janowitz, Deborah
    Jia, Tianye
    Kim, Sungeun
    Klein, Marieke
    Kraemer, Bernd
    Lee, Phil H.
    Loohuis, Loes M. Olde
    Luciano, Michelle
    Macare, Christine
    Mather, Karen A.
    Mattheisen, Manuel
    Milaneschi, Yuri
    Nho, Kwangsik
    Papmeyer, Martina
    Ramasamy, Adaikalavan
    Risacher, Shannon L.
    Roiz-Santianez, Roberto
    Rose, Emma J.
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Saemann, Philipp G.
    Schmaal, Lianne
    Schork, Andrew J.
    Shin, Jean
    Strike, Lachlan T.
    Teumer, Alexander
    van Donkelaar, Marjolein M. J.
    van Eijk, Kristel R.
    Walters, Raymond K.
    Westlye, Lars T.
    Whelan, Christopher D.
    Winkler, Anderson M.
    Zwiers, Marcel P.
    Alhusaini, Saud
    Athanasiu, Lavinia
    Ehrlich, Stefan
    Hakobjan, Marina M. H.
    Hartberg, Cecilie B.
    Haukvik, Unn K.
    Heister, Angelien J. G. A. M.
    Hoehn, David
    Kasperaviciute, Dalia
    Liewald, David C. M.
    Lopez, Lorna M.
    Makkinje, Remco R. R.
    Matarin, Mar
    Naber, Marlies A. M.
    McKay, D. Reese
    Needham, Margaret
    Nugent, Allison C.
    Puetz, Benno
    Royle, Natalie A.
    Shen, Li
    Sprooten, Emma
    Trabzuni, Daniah
    van der Marel, Saskia S. L.
    van Hulzen, Kimm J. E.
    Walton, Esther
    Wolf, Christiane
    Almasy, Laura
    Ames, David
    Arepalli, Sampath
    Assareh, Amelia A.
    Bastin, Mark E.
    Brodaty, Henry
    Bulayeva, Kazima B.
    Carless, Melanie A.
    Cichon, Sven
    Corvin, Aiden
    Curran, Joanne E.
    Czisch, Michael
    de Zubicaray, Greig I.
    Dillman, Allissa
    Duggirala, Ravi
    Dyer, Thomas D.
    Erk, Susanne
    Fedko, Iryna O.
    Ferrucci, Luigi
    Foroud, Tatiana M.
    Fox, Peter T.
    Fukunaga, Masaki
    Gibbs, J. Raphael
    Goering, Harald H. H.
    Green, Robert C.
    Guelfi, Sebastian
    Hansell, Narelle K.
    Hartman, Catharina A.
    Hegenscheid, Katrin
    Heinz, Andreas
    Hernandez, Dena G.
    Heslenfeld, Dirk J.
    Hoekstra, Pieter J.
    Holsboer, Florian
    Homuth, Georg
    Hottenga, Jouke-Jan
    Ikeda, Masashi
    Jack, Clifford R., Jr.
    Jenkinson, Mark
    Johnson, Robert
    Kanai, Ryota
    Keil, Maria
    Kent, Jack W., Jr.
    Kochunov, Peter
    Kwok, John B.
    Lawrie, Stephen M.
    Liu, Xinmin
    Longo, Dan L.
    McMahon, Katie L.
    Meisenzah, Eva
    Melle, Ingrid
    Mahnke, Sebastian
    Montgomery, Grant W.
    Mostert, Jeanette C.
    Muehleisen, Thomas W.
    Nalls, Michael A.
    Nichols, Thomas E.
    Nilsson, Lars G.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Noethen, Markus M.
    Ohi, Kazutaka
    Olvera, Rene L.
    Perez-Iglesias, Rocio
    Pike, G. Bruce
    Potkin, Steven G.
    Reinvang, Ivar
    Reppermund, Simone
    Rietschel, Marcella
    Romanczuk-Seiferth, Nina
    Rosen, Glenn D.
    Rujescu, Dan
    Schnell, Knut
    Schofield, Peter R.
    Smith, Colin
    Steen, Vidar M.
    Sussmann, Jessika E.
    Thalamuthu, Anbupalam
    Toga, Arthur W.
    Traynor, Bryan J.
    Troncoso, Juan
    Turner, Jessica A.
    Valdes Hernandez, Maria C.
    van't Ent, Dennis
    van der Brug, Marcel
    van der Wee, Nic J. A.
    van Tol, Marie-Jose
    Veltman, Dick J.
    Wassink, Thomas H.
    Westman, Eric
    Zielke, Ronald H.
    Zonderman, Alan B.
    Ashbrook, David G.
    Hager, Reinmar
    Lu, Lu
    McMahon, Francis J.
    Morris, Derek W.
    Williams, Robert W.
    Brunner, Han G.
    Buckner, Randy L.
    Buitelaar, Jan K.
    Cahn, Wiepke
    Calhoun, Vince D.
    Cavalleri, Gianpiero L.
    Crespo-Facorro, Benedicto
    Dale, Anders M.
    Davies, Gareth E.
    Delanty, Norman
    Depondt, Chantal
    Djurovic, Srdjan
    Drevets, Wayne C.
    Espeseth, Thomas
    Gollub, Randy L.
    Ho, Beng-Choon
    Hoffman, Wolfgang
    Hosten, Norbert
    Kahn, Rene S.
    Le Hellard, Stephanie
    Meyer-Lindenberg, Andreas
    Mueller-Myhsok, Bertram
    Nauck, Matthias
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Pandolfo, Massimo
    Penninx, Brenda W. J. H.
    Roffman, Joshua L.
    Sisodiya, Sanjay M.
    Smoller, Jordan W.
    van Bokhoven, Hans
    van Haren, Neeltje E. M.
    Voelzke, Henry
    Walter, Henrik
    Weiner, Michael W.
    Wen, Wei
    White, Tonya
    Agartz, Ingrid
    Andreassen, Ole A.
    Blangero, John
    Boomsma, Dorret I.
    Brouwer, Rachel M.
    Cannon, Dara M.
    Cookson, Mark R.
    de Geus, Eco J. C.
    Deary, Ian J.
    Donohoe, Gary
    Fernandez, Guillen
    Fisher, Simon E.
    Francks, Clyde
    Glahn, David C.
    Grabe, Hans J.
    Gruber, Oliver
    Hardy, John
    Hashimoto, Ryota
    Pol, Hilleke E. Hulshoff
    Joensson, Erik G.
    Kloszewska, Iwona
    Lovestone, Simon
    Mattay, Venkata S.
    Mecocci, Patrizia
    McDonald, Colm
    McIntosh, Andrew M.
    Ophoff, Roel A.
    Paus, Tomas
    Pausova, Zdenka
    Ryten, Mina
    Sachdev, Perminder S.
    Saykin, Andrew J.
    Simmons, Andy
    Singleton, Andrew
    Soininen, Hilkka
    Wardlaw, Joanna M.
    Weale, Michael E.
    Weinberger, Daniel R.
    Adams, Hieab H. H.
    Launer, Lenore J.
    Seiler, Stephan
    Schmidt, Reinhold
    Chauhan, Ganesh
    Satizabal, Claudia L.
    Becker, James T.
    Yanek, Lisa
    van der Lee, Sven J.
    Ebling, Maritza
    Fischl, Bruce
    Longstreth, W. T., Jr.
    Greve, Douglas
    Schmidt, Helena
    Nyquist, Paul
    Vinke, Louis N.
    van Duijn, Cornelia M.
    Xue, Luting
    Mazoyer, Bernard
    Bis, Joshua C.
    Gudnason, Vilmundur
    Seshadri, Sudha
    Ikram, M. Arfan
    Martin, Nicholas G.
    Wright, Margaret J.
    Schumann, Gunter
    Franke, Barbara
    Thompson, Paul M., Jr.
    Medland, Sarah E.
    Common genetic variants influence human subcortical brain structures2015Ingår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 520, nr 7546, s. 224-U216Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume(5) and intracranial volume(6). These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 X 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

  • 77.
    Johansson, Jarkko
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Lundquist, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Longitudinal evidence that reduced hemispheric encoding/retrieval asymmetry predicts episodic-memory impairment in aging2020Ingår i: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 137, artikel-id UNSP 107329Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The HERA (Hemispheric Encoding/Retrieval Asymmetry) model captures hemispheric lateralization of prefrontal cortex (PFC) brain activity during memory encoding and retrieval. Reduced HERA has been observed in cross-sectional aging studies, but there is no longitudinal evidence, to our knowledge, on age-related changes in HERA and whether maintained or reduced HERA relates to well-preserved memory functioning. In the present study we set out to explore HERA in a longitudinal neuroimaging sample from the Betula study [3 Waves over 10 years; Wave-1: n = 363, W2: n = 227, W3: n = 101]. We used fMRI data from a face-name paired-associates task to derive a HERA index. In support of the HERA model, the mean HERA index was positive across the three imaging waves. The longitudinal age-HERA relationship was highly significant (p < 10(-11)), with a HERA decline occurring after age 60. The age-related HERA decline was associated with episodic memory decline (p < 0.05). Taken together, the findings provide large-scale support for the HERA model, and suggest that reduced HERA in the PFC reflects pathological memory aging possibly related to impaired ability to bias mnemonic processing according to the appropriate encoding or retrieval state.

  • 78.
    Johansson, Roland
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Theorin, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Westling, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Ohki, Yukari
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    How a lateralized brain supports symmetrical bimanual tasks2006Ingår i: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 4, nr 6, s. e158-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A large repertoire of natural object manipulation tasks require precisely coupled symmetrical opposing forces by both hands on a single object. We asked how the lateralized brain handles this basic problem of spatial and temporal coordination. We show that the brain consistently appoints one of the hands as prime actor while the other assists, but the choice of acting hand is flexible. When study participants control a cursor by manipulating a tool held freely between the hands, the left hand becomes prime actor if the cursor moves directionally with the left-hand forces, whereas the right hand primarily acts if it moves with the opposing right-hand forces. In neurophysiological (electromyography, transcranial magnetic brain stimulation) and functional magnetic resonance brain imaging experiments we demonstrate that changes in hand assignment parallels a midline shift of lateralized activity in distal hand muscles, corticospinal pathways, and primary sensorimotor and cerebellar cortical areas. We conclude that the two hands can readily exchange roles as dominant actor in bimanual tasks. Spatial relationships between hand forces and goal motions determine hand assignments rather than habitual handedness. Finally, flexible role assignment of the hands is manifest at multiple levels of the motor system, from cortical regions all the way down to particular muscles.

  • 79.
    Jonasson, Lars
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Kramer, Arthur F
    Departments of Psychology and Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark..
    Aerobic fitness influences working memory updating via the striatal dopaminergic system in older adultsManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    There is much evidence that dopamine is vital for cognitive functioning in aging. Here we tested the hypothesis that aerobic exercise and fitness influences dopaminergic neurotransmission in the striatum as measured by positron emission tomography (PET) and the non-displacable binding potential (BPND ) of [11C]raclopride, and in turn performance on offline working-memory updating tasks. In a sample of 58 older sedentary adults undergoing a six-months exercise intervention, aerobic exercise compared to stretching, toning, and resistance training did not have a differential effect on BPND . At baseline, higher aerobic fitness levels (VO2peak ) were associated with higher BPND  in the striatum. Following the intervention, for both forms of training, we found reduced BPND , indicating increased dopamine (DA), in a cluster in the anterior striatum in individuals with larger improvements in VO2peak . This reduction in BPND  mediated a positive indirect effect of VO2peak  on working-memory updating performance. Collectively these findings implicate DA as a neurocognitive mechanism explaining the positive effects of staying physically active at an old age for working memory.

  • 80.
    Jonasson, Lars
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Kramer, Arthur
    Departments of Psychology and Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA.
    Lundquist, Anders
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.
    Aerobic Exercise Intervention, CognitivePerformance, and Brain Structure: results from the Physical Influences on Brain in Aging (PHIBRA) Study2017Ingår i: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 8, s. 1-15, artikel-id 336Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Studies have shown that aerobic exercise has the potential to improve cognition and reduce brain atrophy in older adults. However, the literature is equivocal with regards to the specificity or generality of these effects. To this end, we report results on cognitive function and brain structure from a 6-month training intervention with 60 sedentary adults (64–78 years) randomized to either aerobic training or stretching and toning control training. Cognitive functions were assessed with a neuropsychological test battery in which cognitive constructs were measured using several different tests. Freesurfer was used to estimate cortical thickness in frontal regions and hippocampus volume. Results showed that aerobic exercisers, compared to controls, exhibited a broad, rather than specific, improvement in cognition as indexed by a higher “Cognitive score,” a composite including episodic memory, processing speed, updating, and executive function tasks (p = 0.01). There were no group differences in cortical thickness, but additional analyses revealed that aerobic fitness at baseline was specifically related to larger thickness in dorsolateral prefrontal cortex (dlPFC), and hippocampus volume was positively associated with increased aerobic fitness over time. Moreover, “Cognitive score” was related to dlPFC thickness at baseline, but changes in “Cognitive score” and dlPFC thickness were associated over time in the aerobic group only. However, aerobic fitness did not predict dlPFC change, despite the improvement in “Cognitive score” in aerobic exercisers. Our interpretation of these observations is that potential exercise-induced changes in thickness are slow, and may be undetectable within 6-months, in contrast to change in hippocampus volume which in fact was predicted by the change in aerobic fitness. To conclude, our results add to a growing literature suggesting that aerobic exercise has a broad influence on cognitive functioning, which may aid in explaining why studies focusing on a narrower range of functions have sometimes reported mixed results.

  • 81.
    Jonasson, Lars S.
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Samhällsvetenskapliga fakulteten, Centrum för befolkningsstudier (CBS).
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Braver, Todd S.
    Department of Psychology,Washington University, St Louis, MO 63130, USA.
    Ögren, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Bäckman, Lars
    Aging Research Center, Karolinska Institute, SE-113 30 Stockholm, Sweden.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Dopamine release in nucleus accumbens during rewarded task switching measured by [11C]raclopride2014Ingår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 99, s. 357-364Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Reward and motivation have positive influences on cognitive-control processes in numerous settings. Models of reward implicate corticostriatal loops and the dopamine (DA) system, with special emphasis on D2 receptors in nucleus accumbens (NAcc). In this study, 11 right-handed males (35-40 years) were scanned with positron emission tomography (PET) in a single [(11)C]raclopride dynamic scan during rewarded and non-rewarded task switching. Rewarded task switching (relative to baseline task switching) decreased [(11)C]raclopride binding in NAcc. Decreasing NAcc [(11)C]raclopride binding was strongly associated with task reaction time measures that reflect individual differences in effort and control strategies. Voxelwise analyses additionally revealed reward-related DA release in anterodorsal caudate, a region previously associated with task-switching. These PET findings provide evidence for striatal DA release during motivated cognitive control, and further suggest that NAcc DA release predicts the task reaction time benefits of reward incentives.

  • 82.
    Jonasson, Lars S.
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Kramer, Arthur F.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.
    Higher striatal D2-receptor availability in aerobically fit older adults but non-selective intervention effects after aerobic versus resistance training2019Ingår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 202, artikel-id 116044Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is much evidence that dopamine is vital for cognitive functioning in aging. Here we tested the hypothesis that aerobic exercise and fitness influence dopaminergic neurotransmission in the striatum, and in turn performance on offline working-memory updating tasks. Dopaminergic neurotransmission was measured by positron emission tomography (PET) and the non-displacable binding potential (BPND) of [11C]raclopride, i.e. dopamine (DA) D2-receptor (D2R) availability. Fifty-four sedentary older adults underwent a six-months exercise intervention, performing either aerobic exercise or stretching, toning, and resistance active control training. At baseline, higher aerobic fitness levels (VO2peak) were associated with higher BPND in the striatum, providing evidence of a link between an objective measure of aerobic fitness and D2R in older adults. BPND decreased substantially over the intervention in both groups but the intervention effects were non-selective with respect to exercise group. The decrease was several times larger than any previously estimated annual decline in D2R, potentially due to increased endogenous DA. Working-memory was unrelated to D2R both at baseline and following the intervention. To conclude, we provide partial evidence for a link between physical exercise and DA. Utilizing a PET protocol able to disentangle both D2R and DA levels could shed further light on whether, and how, aerobic exercise impacts the dopaminergic system in older adults.

  • 83. Jones, Sari
    et al.
    Nyberg, Lars
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Fysiologi.
    Sandblom, Johan
    Stigsdotter Neely, Anna
    Ingvar, Martin
    Magnus Petersson, Karl
    Bäckman, Lars
    Cognitive and neural plasticity in aging: general and task-specific limitations.2006Ingår i: Neuroscience Biobehavioral Reviews, ISSN 0149-7634, Vol. 30, nr 6, s. 864-71Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    There is evidence for cognitive as well as neural plasticity across the adult life span, although aging is associated with certain constraints on plasticity. In the current paper, we argue that the age-related reduction in cognitive plasticity may be due to (a) deficits in general processing resources, and (b) failure to engage in task-relevant cognitive operations. Memory-training research suggests that age-related processing deficits (e.g., executive functions, speed) hinder older adults from utilizing mnemonic techniques as efficiently as the young, and that this age difference is reflected by diminished frontal activity during mnemonic use. Additional constraints on memory plasticity in old age are related to difficulties that are specific to the task, such as creating visual images, as well as in binding together the information to be remembered. These deficiencies are paralleled by reduced activity in occipito-parietal and medial-temporal regions, respectively. Future attempts to optimize intervention-related gains in old age should consider targeting both general processing and task-specific origins of age-associated reductions in cognitive plasticity.

  • 84.
    Jonsson, Bert
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Karlsson, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Lithner, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå forskningscentrum för matematikdidaktik (UFM). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för naturvetenskapernas och matematikens didaktik.
    Liljekvist, Yvonne
    Karlstad University.
    Norqvist, Mathias
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för naturvetenskapernas och matematikens didaktik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Mathematical Teaching Method affects Performance and Brain Activity2012Konferensbidrag (Refereegranskat)
  • 85.
    Josefsson, Maria
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    de Luna, Xavier
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Daniels, Michael
    University of Texas at Austin.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Causal inference with longitudinal outcomes and non-ignorable drop-out: Estimating the effect of living alone on cognitive decline2016Ingår i: Journal of the Royal Statistic Society, Series C: Applied Statistics, ISSN 0035-9254, E-ISSN 1467-9876, Vol. 65, nr 1, s. 131-144Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 86.
    Josefsson, Maria
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    de Luna, Xavier
    Umeå universitet, Samhällsvetenskapliga fakulteten, Statistiska institutionen.
    Pudas, Sara
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nilsson, Lars-Göran
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Centrum för befolkningsstudier (CBS). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Genetic and lifestyle predictors of 15-Year longitudinal change in episodic memory2012Ingår i: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 60, nr 12, s. 2308-2312Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 87.
    Josefsson, Maria
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Lundquist, Anders
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Imputation of missing longitudinal fMRI dataManuskript (preprint) (Övrigt vetenskapligt)
  • 88.
    Josefsson, Maria
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Demographic Data Base.
    Sundström, Anna
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Pudas, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nordin Adolfsson, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Memory profiles predict dementia over 23–28 years in normal but not successful aging2019Ingår i: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203XArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Prospective studies suggest that memory deficits are detectable decades before clinical symptoms of dementia emerge. However, individual differences in long-term memory trajectories prior to diagnosis need to be further elucidated. The aim of the current study was to investigate long-term dementia and mortality risk for individuals with different memory trajectory profiles in a well-characterized population-based sample.

    Methods: 1062 adults (aged 45–80 years) who were non-demented at baseline were followed over 23–28 years. Dementia and mortality risk were studied for three previously classified episodic memory trajectory groups: maintained high performance (Maintainers; 26%), average decline (Averages; 64%), and accelerated decline (Decliners; 12%), using multistate modeling to characterize individuals’ transitions from an initial non-demented state, possibly to a state of dementia and/or death.

    Results: The memory groups showed considerable intergroup variability in memory profiles, starting 10–15 years prior to dementia diagnosis, and prior to death. A strong relationship between memory trajectory group and dementia risk was found. Specifically, Decliners had more than a fourfold risk of developing dementia compared to Averages. In contrast, Maintainers had a 2.6 times decreased dementia risk compared to Averages, and in addition showed no detectable memory decline prior to dementia diagnosis. A similar pattern of association was found for the memory groups and mortality risk, although only among non-demented.

    Conclusion: There was a strong relationship between accelerated memory decline and dementia, further supporting the prognostic value of memory decline. The intergroup differences, however, suggest that mechanisms involved in successful memory aging may delay symptom onset.

  • 89.
    Kaboodvand, Neda
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Bäckman, Lars
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    The retrosplenial cortex: a memory gateway between the cortical default mode network and the medial temporal lobe2018Ingår i: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 39, nr 5, s. 2020-2034Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The default mode network (DMN) involves interacting cortical areas, including the posterior cingulate cortex (PCC) and the retrosplenial cortex (RSC), and subcortical areas, including the medial temporal lobe (MTL). The degree of functional connectivity (FC) within the DMN, particularly between MTL and medial-parietal subsystems, relates to episodic memory (EM) processes. However, past resting-state studies investigating the link between posterior DMN-MTL FC and EM performance yielded inconsistent results, possibly reflecting heterogeneity in the degree of connectivity between MTL and specific cortical DMN regions. Animal work suggests that RSC has structural connections to both cortical DMN regions and MTL, and may thus serve as an intermediate layer that facilitates information transfer between cortical and subcortical DMNs. We studied 180 healthy old adults (aged 64-68 years), who underwent comprehensive assessment of EM, along with resting-state fMRI. We found greater FC between MTL and RSC than between MTL and the other cortical DMN regions (e.g., PCC), with the only significant association with EM observed for MTL-RSC FC. Mediational analysis showed that MTL-cortical DMN connectivity increased with RSC as a mediator. Further analysis using a graph-theoretical approach on DMN nodes revealed the highest betweenness centrality for RSC, confirming that a high proportion of short paths among DMN regions pass through RSC. Importantly, the degree of RSC mediation was associated with EM performance, suggesting that individuals with greater mediation have an EM advantage. These findings suggest that RSC forms a critical gateway between MTL and cortical DMN to support EM in older adults.

  • 90.
    Kallin, Kristina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Jensen, Jane
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Sjukgymnastik.
    Olsson, Lillemor Lundin
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Sjukgymnastik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Sjukgymnastik.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Why the elderly fall in residential care facilities, and suggested remedies.2004Ingår i: The Journal of family practice, ISSN 0094-3509, Vol. 53, nr 1, s. 41-52Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To study precipitating factors for falls among older people living in residential care facilities. DESIGN: Prospective cohort study. SETTING: Five residential care facilities. PARTICIPANTS: 140 women and 59 men, mean age +/- SD 82.4 +/- 6.8 (range, 65-97). MEASUREMENTS: After baseline assessments, falls in the population were tracked for 1 year. A physician, a nurse, and a physiotherapist investigated each event, and reached a consensus concerning the most probable precipitating factors for the fall. RESULTS: Previous falls and treatment with antidepressants were found to be the most important predisposing factors for falls. Probable precipitating factors could be determined in 331 (68.7%) of the 482 registered falls. Acute disease or symptoms of disease were judged to be precipitating, alone or in combination in 186 (38.6%) of all falls; delirium was a factor in 48 falls (10.0%), and infection, most often urinary tract infection, was a factor in 38 falls (7.9%). Benzodiazepines or neuroleptics were involved in the majority of the 37 falls (7.7%) precipitated by drugs. External factors, such as material defects and obstacles, precipitated 38 (7.9%) of the falls. Other conditions both related to the individual and the environment, such as misinterpretation (eg, overestimation of capacity or forgetfulness), misuse of a roller walker, or mistakes made by the staff were precipitating factors in 83 (17.2%) of falls. CONCLUSION: Among older people in residential care facilities, acute diseases and side effects of drugs are important precipitating factors for falls. Falls should therefore be regarded as a possible symptom of disease or a drug side effect until proven otherwise. Timely correction of precipitating and predisposing factors will help prevent further falls.

  • 91.
    Kalpouzos, Grégoria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Sjölie, Daniel
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Molin, Jonas
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Neurocognitive systems related to real-world prospective memory2010Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, nr 10, s. e13304-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 92.
    Kalpouzos, Grégoria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Persson, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Local brain atrophy accounts for functional activity differences in normal aging.2012Ingår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 33, nr 3, s. 623.e1-623.e13Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 93.
    Karalija, Nina
    et al.
    Umeå universitet.
    Papenberg, Goran
    Wåhlin, Anders
    Umeå universitet.
    Johansson, Jarkko
    Umeå universitet.
    Andersson, Micael
    Umeå universitet.
    Axelsson, Jan
    Umeå universitet.
    Riklund, Katrine
    Umeå universitet.
    Lövdén, Martin
    Lindenberger, Ulman
    Bäckman, Lars
    Nyberg, Lars
    Umeå universitet.
    C957T-mediated Variation in Ligand Affinity Affects the Association between C-11-raclopride Binding Potential and Cognition2019Ingår i: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 31, nr 2, s. 314-325Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The dopamine (DA) system plays an important role in cognition. Accordingly, normal variation in DA genes has been found to predict individual differences in cognitive performance. However, little is known of the impact of genetic differences on the link between empirical indicators of the DA system and cognition in humans. The present work used PET with C-11-raclopride to assess DA D2-receptor binding potential (BP) and links to episodic memory, working memory, and perceptual speed in 179 healthy adults aged 64-68 years. Previously, the T-allele of a DA D2-receptor single-nucleotide polymorphism, C957T, was associated with increased apparent affinity of C-11-raclopride, giving rise to higher BP values despite similar receptor density values between allelic groups. Consequently, we hypothesized that C-11-raclopride BP measures inflated by affinity rather than D2-receptor density in T-allele carriers would not be predictive of DA integrity and therefore prevent finding an association between C-11-raclopride BP and cognitive performance. In accordance with previous findings, we show that C-11-raclopride BP was increased in T-homozygotes. Importantly, C-11-raclopride BP was only associated with cognitive performance in groups with low or average ligand affinity (C-allele carriers of C957T, n = 124), but not in the high-affinity group (T-homozygotes, n = 55). The strongest C-11-raclopride BP-cognition associations and the highest level of performance were found in C-homozygotes. These findings show that genetic differences modulate the link between BP and cognition and thus have important implications for the interpretation of DA assessments with PET and C-11-raclopride in multiple disciplines ranging from cognitive neuroscience to psychiatry and neurology.

  • 94.
    Karalija, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Ek, Jesper
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Rieckmann, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Papenberg, Goran
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Aging Research Center, Karolinska Institutet & Stockholm University, Tomtebodavägen 18A,S-17165, Stockholm, Sweden.
    Brandmaier, Andreas M.
    Köhncke, Ylva
    Johansson, Jarkko
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Lövdén, Martin
    Lindenberger, Ulman
    Bäckman, Lars
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Cardiovascular factors are related to dopamine integrity and cognition in aging2019Ingår i: Annals of clinical and translational neurology, E-ISSN 2328-9503, Vol. 6, nr 11, s. 2291-2303Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The aging brain undergoes several changes, including reduced vascular, structural, and dopamine (DA) system integrity. Such brain changes have been associated with age‐related cognitive deficits. However, their relative importance, interrelations, and links to risk factors remain elusive.

    Methods: The present work used magnetic resonance imaging and positron emission tomography with 11C‐raclopride to jointly examine vascular parameters (white‐matter lesions and perfusion), DA D2‐receptor availability, brain structure, and cognitive performance in healthy older adults (n = 181, age: 64–68 years) from the Cognition, Brain, and Aging (COBRA) study.

    Results: Covariance was found among several brain indicators, where top predictors of cognitive performance included caudate and hippocampal integrity (D2DR availability and volumes), and cortical blood flow and regional volumes. White‐matter lesion burden was negatively correlated with caudate DA D2‐receptor availability and white‐matter microstructure. Compared to individuals with smaller lesions, individuals with confluent lesions (exceeding 20 mm in diameter) had reductions in cortical and hippocampal perfusion, striatal and hippocampal D2‐receptor availability, white‐matter microstructure, and reduced performance on tests of episodic memory, sequence learning, and processing speed. Higher cardiovascular risk as assessed by treatment for hypertension, systolic blood pressure, overweight, and smoking was associated with lower frontal cortical perfusion, lower putaminal D2DR availability, smaller grey‐matter volumes, a larger number of white‐matter lesions, and lower episodic memory performance.

    Interpretation: Taken together, these findings suggest that reduced cardiovascular health is associated with poorer status for brain variables that are central to age‐sensitive cognitive functions, with emphasis on DA integrity.

  • 95.
    Karlsson, Linnea
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Juslin, Peter
    Olsson, Henrik
    Different neural systems underlie multiple-cue judgment depending on the cue-combination ruleIngår i: Psychological Science, ISSN 0956-7976, E-ISSN 1467-9280Artikel i tidskrift (Refereegranskat)
  • 96.
    Karlsson, Linnea
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Wiklund-Hornqvist, Carola
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Jonsson, Bert
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Retrieval practice is characterized by reduced fronto-striatal activity2013Ingår i: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 25, nr Suppl., s. S82-S83Artikel i tidskrift (Övrigt vetenskapligt)
  • 97.
    Karlsson, Sari
    et al.
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Karlsson, Per
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm, Sweden.
    Fischer, Håkan
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Thilers, Petra
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    MacDonald, Stuart
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Brehmer, Yvonne
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Rieckmann, Anna
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Halldin, Christer
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm, Sweden.
    Farde, Lars
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm, Sweden.
    Bäckman, Lars
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Modulation of striatal dopamine D1 binding by cognitive processing2009Ingår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 48, nr 2, s. 398-404Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 98.
    Karlsson, Sari
    et al.
    Karolinska Institute.
    Rieckmann, Anna
    Karolinska Institute.
    Karlsson, Per
    Karolinska Hospital.
    Farde, Lars
    Karolinska Hospital.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Bäckman, Lars
    Karolinska Institute.
    Relationship of dopamine D1 receptor binding in striatal and extrastriatal regions to cognitive functioning in healthy humans2011Ingår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 57, nr 2, s. 346-351Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dopamine (DA) availability in both striatal and extrastriatal brain regions has been implicated in cognitive performance. Given that different brain regions are neuroanatomically and functionally different, DA receptor binding in different brain regions may be selectively important to specific cognitive functions. Using PET and the radioligand SCH23390, we measured D1 receptor binding potential (BP(ND)) in dorsolateral prefrontal cortex (DLPFC), hippocampus (HC), as well as in sensorimotor (SMST), associative (AST), and limbic (LST) striatum in 20 healthy younger persons. Subjects completed tasks assessing executive functioning, episodic memory, speed, and general knowledge. Unlike previous reports, we found no linear or curvilinear relationships between D1 receptor binding in DLPFC and performance in any cognitive task. However, BP(ND) in HC was positively linked to executive performance as well as to speed and knowledge. With regard to the striatal subregions, D1 BP(ND) in SMST was more strongly related to speed compared to the other striatal subregions, whereas D1 BP(ND) in AST was more strongly linked to general knowledge. These findings provide support for the notion that D1 receptors in separate brain regions are differentially related to performance in tasks tapping various cognitive domains.

  • 99.
    Karlsson Wirebring, Linnea
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Lithner, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för naturvetenskapernas och matematikens didaktik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå forskningscentrum för matematikdidaktik (UFM).
    Jonsson, Bert
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Liljekvist, Yvonne
    Karlstad, Sweden.
    Norqvist, Mathias
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå forskningscentrum för matematikdidaktik (UFM). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Learning mathematics without a suggested solution method: durable effects on performance and brain activity2015Ingår i: Trends in Neuroscience and Education, ISSN 2211-9493, Vol. 4, nr 1-2, s. 6-14Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A dominant mathematics teaching method is to present a solution method and let pupils repeatedly practice it. An alternative method is to let pupils create a solution method themselves. The current study compared these two approaches in terms of lasting effects on performance and brain activity. Seventythree participants practiced mathematics according to one of the two approaches. One week later, participants underwent fMRI while being tested on the practice tasks. Participants who had created the solution method themselves performed better at the test questions. In both conditions, participants engaged a fronto-parietal network more when solving test questions compared to a baseline task. Importantly, participants who had created the solution method themselves showed relatively lower brain activity in angular gyrus, possibly reflecting reduced demands on verbal memory. These results indicate that there might be advantages to creating the solution method oneself, and thus have implications for the design of teaching methods.

  • 100.
    Karlsson Wirebring, Linnea
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Stillesjö, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Juslin, Peter
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    A Similarity-Based Process for Human Judgment in the Parietal Cortex2018Ingår i: Frontiers in Human Neuroscience, ISSN 1662-5161, E-ISSN 1662-5161, Vol. 12, artikel-id 481Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    One important distinction in psychology is between inferences based on associative memory and inferences based on analysis and rules. Much previous empirical work conceive of associative and analytical processes as two exclusive ways of addressing a judgment task, where only one process is selected and engaged at a time, in an either-or fashion. However, related work indicate that the processes are better understood as being in interplay and simultaneously engaged. Based on computational modeling and brain imaging of spontaneously adopted judgment strategies together with analyses of brain activity elicited in tasks where participants were explicitly instructed to perform similarity-based associative judgments or rule-based judgments (n = 74), we identified brain regions related to the two types of processes. We observed considerable overlap in activity patterns. The precuneus was activated for both types of judgments, and its activity predicted how well a similarity-based model fit the judgments. Activity in the superior frontal gyrus predicted the fit of a rule-based judgment model. The results suggest the precuneus as a key node for similarity-based judgments, engaged both when overt responses are guided by similarity-based and rule-based processes. These results are interpreted such that similarity-based processes are engaged in parallel to rule-based-processes, a finding with direct implications for cognitive theories of judgment.

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