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  • 1.
    Andersson, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University Hospital.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Stiernman, Lars J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Rieckmann, Anna
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Center for the Economics of Aging, Max Planck Institute for Social Law and Social Policy, Germany.
    Cognitive decline in Parkinson’s disease: a subgroup of extreme decliners revealed by a data-driven analysis of longitudinal progression2021In: Frontiers in Psychology, E-ISSN 1664-1078, Vol. 12, article id 729755Article in journal (Refereed)
    Abstract [en]

    Cognitive impairment is an important symptom of Parkinson’s disease (PD) and predicting future cognitive decline is crucial for clinical practice. Here, we aim to identify latent sub-groups of longitudinal trajectories of cognitive change in PD patients, and explore predictors of differences in cognitive change. Longitudinal cognitive performance data from 349 newly diagnosed PD patients and 145 healthy controls from the Parkinson Progression Marker Initiative were modeled using a multivariate latent class linear mixed model. Resultant latent classes were compared on a number of baseline demographics, and clinical variables, as well as cerebrospinal fluid (CSF) biomarkers and striatal dopamine transporter (DAT) density markers of neuropathology. Trajectories of cognitive change in PD were best described by two latent classes. A large subgroup (90%), which showed a subtle impairment in cognitive performance compared to controls but remained stable over the course of the study, and a small subgroup (10%) which rapidly declined in all cognitive performance measures. Rapid decliners did not differ significantly from the larger group in terms of disease duration, severity or motor symptoms at baseline. However, rapid decliners had lower CSF amyloidß42 levels, a higher prevalence of sleep disorder and pronounced loss of caudate DAT density at baseline. These data suggest the existence of a distinct minority sub-type of PD in which rapid cognitive change in PD can occur uncoupled from motor symptoms or disease severity, likely reflecting early pathological change that extends from motor areas of the striatum into associative compartments and cortex.

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  • 2.
    Bergman, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Matsson-Frost, Tove
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Jonasson, Lars S.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Chorell, Elin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Sörlin, Ann
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Öhberg, Fredrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Levine, James A
    Mayo Clinic Rochester MN, USA; Fondation IPSEN, Paris, France.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Danish Research Center for Magnetic Resonance (DRCMR), Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark; Institute of Sports Medicine Copenhagen (ISMC), Copenhagen University Hospital, Copenhagen, Denmark.
    Walking Time Is associated With Hippocampal Volume in Overweight and Obese Office Workers2020In: Frontiers in Human Neuroscience, E-ISSN 1662-5161, Vol. 14, article id 307Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate the long-term effects on cognition and brain function after installing treadmill workstations in offices for 13 months.

    Methods: Eighty healthy overweight or obese office workers aged 40–67 years were individually randomized to an intervention group, receiving a treadmill workstation and encouraging emails, or to a control group, continuing to work as usual. Effects on cognitive function, hippocampal volume, prefrontal cortex (PFC) thickness, and circulating brain-derived neurotrophic factor (BDNF) were analyzed. Further, mediation analyses between changes in walking time and light-intensity physical activity (LPA) on changes in BDNF and hippocampal volume between baseline and 13 months, and multivariate analyses of the baseline data with percentage sitting time as the response variable, were performed.

    Results: No group by time interactions were observed for any of the outcomes. In the mediation analyses, positive associations between changes in walking time and LPA on changes in hippocampal volume were observed, although not mediated by changes in BDNF levels. In the multivariate analyses, a negative association between percentage sitting time and hippocampal volume was observed, however only among those older than 51 years of age.

    Conclusion: Although no group by time interactions were observed, our analyses suggest that increased walking and LPA may have positive effects on hippocampal volume and that sedentary behavior is associated with brain structures of importance for memory functions.

    Trial Registration: www.ClinicalTrials.gov as NCT01997970.

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  • 3.
    Bergman, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mattson-Frost, Tove
    Jonasson, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Chorell, Elin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sörlin, Ann
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Öhberg, Fredrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Levine, James
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Installing treadmill workstations in offices does little for cognitive performance and brain structure, despite a baseline association between sitting time and hippocampus volumeManuscript (preprint) (Other academic)
  • 4.
    Flodin, Pär
    et al.
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Jonasson, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). 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 Adults2017In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 9, article id 267Article in journal (Refereed)
    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.

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  • 5.
    Godbersen, Godber M.
    et al.
    Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria.
    Klug, Sebastian
    Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria.
    Wadsak, Wolfgang
    Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria; Center for Biomarker Research in Medicine (CBmed), Graz, Austria.
    Pichler, Verena
    Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria; Department of Pharmaceutical Sciences, Division of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria.
    Raitanen, Julia
    Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute Applied Diagnostics, Vienna, Austria; Department of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.
    Rieckmann, Anna
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Munich Center for the Economics of Aging, Max Planck Institute for Social Law and Social Policy, Munich, Germany.
    Stiernman, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Cocchi, Luca
    Clinical Brain Networks Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, Australia.
    Breakspear, Michael
    School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, Australia; School of Psychological Sciences, College of Engineering, Science and Environment, University of Newcastle, Callaghan, Australia.
    Hacker, Marcus
    Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
    Lanzenberger, Rupert
    Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria.
    Hahn, Andreas
    Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria.
    Task-evoked metabolic demands of the posteromedial default mode network are shaped by dorsal attention and frontoparietal control networks2023In: eLIFE, E-ISSN 2050-084X, Vol. 12, article id e84683Article in journal (Refereed)
    Abstract [en]

    External tasks evoke characteristic fMRI BOLD signal deactivations in the default mode network (DMN). However, for the corresponding metabolic glucose demands both decreases and increases have been reported. To resolve this discrepancy, functional PET/MRI data from 50 healthy subjects performing Tetris were combined with previously published data sets of working memory, visual and motor stimulation. We show that the glucose metabolism of the posteromedial DMN is dependent on the metabolic demands of the correspondingly engaged task-positive networks. Specifically, the dorsal attention and frontoparietal network shape the glucose metabolism of the posteromedial DMN in opposing directions. While tasks that mainly require an external focus of attention lead to a consistent downregulation of both metabolism and the BOLD signal in the posteromedial DMN, cognitive control during working memory requires a metabolically expensive BOLD suppression. This indicates that two types of BOLD deactivations with different oxygen-to-glucose index may occur in this region. We further speculate that consistent downregulation of the two signals is mediated by decreased glutamate signaling, while divergence may be subject to active GABAergic inhibition. The results demonstrate that the DMN relates to cognitive processing in a flexible manner and does not always act as a cohesive task-negative network in isolation.

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  • 6.
    Grill, Filip
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Guitart-Masip, Marc
    Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Center for Psychiatry Research, Region Stockholm, Stockholm, Sweden; Center for Cognitive and Computational Neuropsychiatry (CCNP), Karolinska Institutet, Stockholm, Sweden; Max Planck UCL Centre for Computational Psychiatry and Ageing Research, University College London, London, United Kingdom.
    Johansson, Jarkko
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Stiernman, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Rieckmann, Anna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Institute for Psychology, University of the Bundeswehr Munich, Neubiberg, Germany.
    Dopamine release in human associative striatum during reversal learning2024In: Nature Communications, E-ISSN 2041-1723, Vol. 15, no 1, article id 59Article in journal (Refereed)
    Abstract [en]

    The dopaminergic system is firmly implicated in reversal learning but human measurements of dopamine release as a correlate of reversal learning success are lacking. Dopamine release and hemodynamic brain activity in response to unexpected changes in action-outcome probabilities are here explored using simultaneous dynamic [11C]Raclopride PET-fMRI and computational modelling of behavior. When participants encounter reversed reward probabilities during a card guessing game, dopamine release is observed in associative striatum. Individual differences in absolute reward prediction error and sensitivity to errors are associated with peak dopamine receptor occupancy. The fMRI response to perseverance errors at the onset of a reversal spatially overlap with the site of dopamine release. Trial-by-trial fMRI correlates of absolute prediction errors show a response in striatum and association cortices, closely overlapping with the location of dopamine release, and separable from a valence signal in ventral striatum. The results converge to implicate striatal dopamine release in associative striatum as a central component of reversal learning, possibly signifying the need for increased cognitive control when new stimuli-responses should be learned.

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  • 7.
    Jakobson Mo, Susanna
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    J. Stiernman, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    af Bjerkén, Sara
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Bäckström, David C.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Gabrielsson Kellgren, Therese
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Varrone, Andrea
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet and Stockholm Health Care Services, Stockholm, Sweden.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    VNTR polymorphism in the SLC6A3 gene does not influence dopamine transporter availability measured by [18F]FE-PE2I PET or [123I]FP-Cit SPECT2022In: Nuclear medicine communications, ISSN 0143-3636, E-ISSN 1473-5628, Vol. 43, no 3, p. 247-255Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the potential impact of polymorphism in the 3'-untranslated region (3'UTR) of the SLC6A3 gene (DAT1) on normal variation in dopamine transporter (DAT) imaging with [18F]FE-PE2I PET and [123I]FP-Cit SPECT.

    METHODS: Thirty-six individuals (mean age 70.4±5.4 years) with normal [18F]FE-PE2I PET and [123I]FP-Cit SPECT were genotyped for variable number of tandem repeats (VNTR) in the 3′UTR of the DAT1 gene. The DAT-availability in the caudate and putamen as measured with [18F]FE-PE2I PET and [123I]FP-Cit SPECT, as well as in the substantia nigra with [18F]FE-PE2I PET were compared between the participants carrying one or two 9-repeat alleles (i.e. 9R+10R or 9R+9R; 47%) and the participants without a 9R allele (i.e. 10R+10R or 10R+11R; 53%). Nonparametric tests, linear regression analysis and mixed model analysis were used to assess any statistical difference in measured DAT availability between the two allele groups.

    RESULTS: The measured DAT-availability in PET- and SPECT-imaging tended to be slightly higher in the 9R-group; however, the difference did not reach statistical significance in either the caudate or the putamen or the substantia nigra. Instead, age did have a significant effect on the DAT level (P < 0.05) notwithstanding the genotype.

    CONCLUSION: No significant effect of DAT1-genotype was detectable in imaging with [18F]FE-PE2I PET or [123I]FP-Cit, instead, age accounted for the normal variation in DAT-PET and DAT-SPECT.

  • 8.
    Jakobson Mo, Susanna
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Jonasson, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Ögren, Mattias J.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Ögren, Margareta
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Varrone, Andrea
    Eriksson, Linda
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Bäckström, David
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    af Bjerkén, Sara
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Dopamine transporter imaging with [18F]FE-PE2I PET and [123I]FP-CIT SPECT – a clinical comparison2018In: EJNMMI Research, E-ISSN 2191-219X, Vol. 8, article id 100Article in journal (Refereed)
    Abstract [en]

    Background: Dopamine transporter (DAT) imaging may be of diagnostic value in patients with clinically suspected parkinsonian disease. The purpose of this study was to compare the diagnostic performance of DAT imaging with positron emission computed tomography (PET), using the recently developed, highly DAT-selective radiopharmaceutical [18F]FE-PE2I (FE-PE2I), to the commercially available and frequently used method with [123I]FP-CIT (FP-CIT) single-photon emission computed tomography (SPECT) in early-stage idiopathic parkinsonian syndrome (PS).

    Methods: Twenty-two patients with a clinical de novo diagnosis of PS and 28 healthy controls (HC) participating in an on-going clinical trial of FE-PE2I were analyzed in this study. Within the trial protocol, participants are clinically reassessed 2 years after inclusion. A commercially available software was used for automatic calculation of FP-CIT-specific uptake ratio (SUR). MRI-based volumes of interest combined with threshold PET segmentation were used for FE-PE2I binding potential relative to non-displaceable binding (BPND) quantification and specific uptake value ratios (SUVR).

    Results: PET with FE-PE2I revealed significant differences between patients with a clinical de novo diagnosis of PS and healthy controls in striatal DAT availability (p < 0.001), with excellent accuracy of predicting dopaminergic deficit in early-stage PS. The effect sizes were calculated for FE-PE2I BPND (Glass’s Δ = 2.95), FE-PE2I SUVR (Glass’s Δ = 2.57), and FP-CIT SUR (Glass’s Δ = 2.29). The intraclass correlation (ICC) between FE-PE2I BPND FP-CIT SUR was high in the caudate (ICC = 0.923), putamen (ICC = 0.922), and striatum (ICC = 0.946), p < 0.001. Five of the 22 patients displayed preserved striatal DAT availability in the striatum with both methods. At follow-up, a non-PS clinical diagnosis was confirmed in three of these, while one was clinically diagnosed with corticobasal syndrome. In these patients, FE-PE2I binding was also normal in the substantia nigra (SN), while significantly reduced in the remaining patients. FE-PE2I measurement of the mean DAT availability in the putamen was strongly correlated with BPND in the SN (R = 0.816, p < 0.001). Olfaction and mean putamen DAT availability was correlated using both FE-PE2I BPND and FP-CIT SUR (R ≥ 0.616, p < 0.001).

    Conclusion: DAT imaging with FE-PE2I PET yields excellent basic diagnostic differentiation in early-stage PS, at least as good as FP-CIT SPECT.

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  • 9.
    Jakobson Mo, Susanna
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jonasson, Lars S.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Validation of dynamic [18F]FE-PE2I PET for estimation of relative regional cerebral blood flow: a comparison with [15O]H2O PET2022In: EJNMMI Research, E-ISSN 2191-219X, Vol. 12, no 1, article id 72Article in journal (Refereed)
    Abstract [en]

    Background: Dopamine transporter (DAT) imaging is used in the diagnostic work-up in suspected parkinsonian syndromes and dementia with Lewy bodies but cannot differentiate between these syndromes, and an extra brain imaging examination of the regional cerebral blood flow (rCBF) or glucose metabolism is often needed for differential diagnosis. The requirement of two different imaging examinations is resource-consuming and inconvenient for the patients. Therefore, imaging of both cortical blood flow and DAT imaging with the same radiotracer would be more convenient and cost-effective. The aim of this study was to test whether relative regional cerebral blood flow (rCBFR) can be measured with the DAT-specific positron emission tomography (PET) tracer [18F]FE-PE2I (FE-PE2I), by validation with cerebral perfusion measured with [15O]H2O PET (H2O).

    Methods: The rCBFR was quantified by kinetic modeling for FE-PE2I (R1) and H2O (F). The R1 was calculated using the simplified reference tissue model, and F was calculated with a modified Koopman double-integration method. The linear relationship and intraclass correlation (ICC) between R1 and F were tested in image data derived from 29 patients with recent onset parkinsonism and 30 healthy controls.

    Results: There was a strong linear correlation across all subjects between R1 and F in the frontal, parietal, temporal, cingulate and occipital cortex as well as in the striatum (r ≥ 0.731–0.905, p < 0.001) with a good-to-excellent ICC, ranging from 0.727 to 0.943 (p < 0.001).

    Conclusions: Our results suggest that FE-PE2I may be used as a proxy for cerebral perfusion, thus potentially serving as a radiotracer for assessment of both DAT availability and rCBFR in one single dynamic scan. This could be valuable in the differential diagnosis of parkinsonian syndromes.

    Trial registration: EUDRA-CT 2015-003045-26. Registered 23 October 2015 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-003045-26

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  • 10.
    Jonasson, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Aerobic fitness and healthy brain aging: cognition, brain structure, and dopamine2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Performing aerobic exercise and maintaining high levels of aerobic fitness may have positive effects on both brain structure and function in older adults. Despite decades of research however, there is still a rather poor understanding of the neurocognitive mechanisms explaining the positive effects of aerobic exercise on cognition. Changes in prefrontal gray matter as well as dopaminergic neurotransmission in striatum are both candidate neurocognitive mechanisms. The main aims of this thesis are: 1. To investigate the effects of aerobic exercise and fitness on cognition and magnetic resonance imaging (MRI) derived gray matter volumes using data from a 6 month physical exercise intervention in older adults (Study I). 2. To simulate the effect of atrophy in longitudinal positron emission tomography (PET) which could pose a challenge to interpreting changes in longitudinal PET imaging (Study II). 3. To study the influence of aerobic exercise and fitness on the dopamine D2-receptor (D2R) system in striatum using [11C]raclopride PET as a potential mechanism for improved cognition (Study III).

    Results: In Study I, aerobic exercise was found to improve cognitive performance in a broad, rather than domain-specific sense. Moreover, aerobic fitness was related to prefrontal cortical thickness, and improved aerobic fitness over 6 months was related to increased hippocampal volume. In Study II, we identified areas in the striatum vulnerable to the effect of shrinkage, which should be considered in longitudinal PET imaging. Finally, in Study III, the effect of being aerobically fit, and improving fitness levels was found to impact dopaminergic neurotransmission in the striatum, which in turn mediated fitness-induced improvements in working memory updating performance.

    Conclusion: The findings in this thesis provide novel evidence regarding the neurocognitive mechanisms of aerobic exercise-induced improvements in cognition, and impacts the interpretation of longitudinal PET imaging. Performing aerobic exercise and staying aerobically fit at an older age have positive effects on cognition and brain systems important for memory and cognition. Specifically, fitness-induced changes to the dopaminergic system stands out as one novel neurocognitive mechanism explaining the positive effects of aerobic fitness on working-memory performance in healthy older adults.

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  • 11.
    Jonasson, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.
    Simulating effects of brain atrophy in longitudinal PET imaging with an anthropomorphic brain phantom2017In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 62, no 13, p. 5213-5227Article in journal (Refereed)
    Abstract [en]

    In longitudinal positron emission tomography (PET), the presence of volumetric changes over time can lead to an overestimation or underestimation of the true changes in the quantified PET signal due to the partial volume effect (PVE) introduced by the limited spatial resolution of existing PET cameras and reconstruction algorithms. Here, a 3D-printed anthropomorphic brain phantom with attachable striata in three sizes was designed to enable controlled volumetric changes. Using a method to eliminate the non-radioactive plastic wall, and manipulating BP levels by adding different number of events from list-mode acquisitions, we investigated the artificial volume dependence of BP due to PVE, and potential bias arising from varying BP. Comparing multiple reconstruction algorithms we found that a high-resolution ordered- subsets maximization algorithm with spatially variant point-spread function resolution modeling provided the most accurate data. For striatum, the BP changed by 0.08% for every 1% volume change, but for smaller volumes such as the posterior caudate the artificial change in BP was as high as 0.7% per 1% volume change. A simple gross correction for striatal volume is unsatisfactory, as the amplitude of the PVE on the BP differs depending on where in the striatum the change occurred. Therefore, to correctly interpret age-related longitudinal changes in the BP, we must account for volumetric changes also within a structure, rather than across the whole volume. The present 3D-printing technology, combined with the wall removal method, can be implemented to gain knowledge about the predictable bias introduced by the PVE differences in uptake regions of varying shape.

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  • 12.
    Jonasson, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Kramer, Arthur F
    Departments of Psychology and Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark..
    Aerobic fitness influences working memory updating via the striatal dopaminergic system in older adultsManuscript (preprint) (Other academic)
    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.

  • 13.
    Jonasson, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Kramer, Arthur
    Departments of Psychology and Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA.
    Lundquist, Anders
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). 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) Study2017In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 8, p. 1-15, article id 336Article in journal (Refereed)
    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.

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  • 14.
    Jonasson, Lars S.
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Social Sciences, Centre for Population Studies (CPS).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Braver, Todd S.
    Department of Psychology,Washington University, St Louis, MO 63130, USA.
    Ögren, Mattias
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bäckman, Lars
    Aging Research Center, Karolinska Institute, SE-113 30 Stockholm, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Dopamine release in nucleus accumbens during rewarded task switching measured by [11C]raclopride2014In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 99, p. 357-364Article in journal (Refereed)
    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.

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  • 15.
    Jonasson, Lars S.
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Kramer, Arthur F.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). 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 training2019In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 202, article id 116044Article in journal (Refereed)
    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.

  • 16.
    Jonasson Stiernman, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Grill, Filip
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Hahn, Andreas
    Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
    Rischka, Lucas
    Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
    Lanzenberger, Rupert
    Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
    Panes Lundmark, Vania
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Rieckmann, Anna
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. The Munich Center for the Economics of Aging, Max Planck Institute for Social Law and Social Policy, Munich, Germany.
    Dissociations between glucose metabolism and blood oxygenation in the human default mode network revealed by simultaneous PET-fMRI2021In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 118, no 27, article id e2021913118Article in journal (Refereed)
    Abstract [en]

    The finding of reduced functional MRI (fMRI) activity in the default mode network (DMN) during externally focused cognitive control has been highly influential to our understanding of human brain function. However, these negative fMRI responses, measured as relative decreases in the blood-oxygenation-level-dependent (BOLD) response between rest and task, have also prompted major questions of interpretation. Using hybrid functional positron emission tomography (PET)-MRI, this study shows that task-positive and -negative BOLD responses do not reflect antagonistic patterns of synaptic metabolism. Task-positive BOLD responses in attention and control networks were accompanied by concomitant increases in glucose metabolism during cognitive control, but metabolism in widespread DMN remained high during rest and task despite negative BOLD responses. Dissociations between glucose metabolism and the BOLD response specific to the DMN reveal functional heterogeneity in this network and demonstrate that negative BOLD responses during cognitive control should not be interpreted to reflect relative increases in metabolic activity during rest. Rather, neurovascular coupling underlying BOLD response patterns during rest and task in DMN appears fundamentally different from BOLD responses in other association networks during cognitive control.

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  • 17.
    Karalija, Nina
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Jonasson, Lars S.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Johansson, Jarkko
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Papenberg, Goran
    Salami, Alireza
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Karolinska Institutet; Stockholm University.
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Copenhagen University Hospital, Hvidovre, Denmark.
    High long-term test-retest reliability for extrastriatal 11C-raclopride binding in healthy older adults2020In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 40, no 9, p. 1859-1868Article in journal (Refereed)
    Abstract [en]

    In vivo dopamine D2-receptor availability is frequently assessed with 11C-raclopride and positron emission tomography. Due to low signal-to-noise ratios for 11C-raclopride in areas with low D2 receptor densities, the ligand has been considered unreliable for measurements outside the dopamine-dense striatum. Intriguingly, recent studies show that extrastriatal 11C-raclopride binding potential (BPND) values are (i) reliably higher than in the cerebellum (where D2-receptor levels are negligible), (ii) correlate with behavior in the expected direction, and (iii) showed good test-retest reliability in a sample of younger adults. The present work demonstrates high seven-month test-retest reliability of striatal and extrastriatal 11C-raclopride BPND values in healthy, older adults (n = 27, age: 64-78 years). Mean 11C-raclopride BPND values were stable between test sessions in subcortical nuclei, and in frontal and temporal cortices (p > 0.05). Across all structures analyzed, intraclass correlation coefficients were high (0.85-0.96), absolute variability was low (mean: 4-8%), and coefficients of variance ranged between 9 and 25%. Furthermore, regional 11C-raclopride BPND values correlated with previously determined 18F-fallypride BPND values (rho = 0.97 and 0.92 in correlations with and without striatal values, respectively, p < 0.01) and postmortem determined D2-receptor densities (including striatum: rho = 0.92; p < 0.001; excluding striatum: rho = 0.75; p = 0.067). These observations suggest that extrastriatal 11C-raclopride measurements represent a true D2 signal.

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

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

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

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

  • 20. Pantzar, Alexandra
    et al.
    Jonasson, Lars S.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Ekblom, Orjan
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Danish Research Center for Magnetic Resonance, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.
    Ekblom, Maria M.
    Relationships Between Aerobic Fitness Levels and Cognitive Performance in Swedish Office Workers2018In: Frontiers in Psychology, E-ISSN 1664-1078, Vol. 9, article id 2612Article in journal (Refereed)
    Abstract [en]

    Objectives: Aerobic exercise influence cognition in elderly, children, and neuropsychiatric populations. Less is known about the influence of aerobic exercise in healthy samples (particularly working age), and of different fitness levels on cognition. Two hypotheses were posed: (1) low fitness levels, compared to moderate and high, will be related to poorer cognitive performance, and (2) breakpoints for the beneficial relationship between VO2 and cognition will be observed within the moderate-to-high fitness span.

    Design and Methods: The sample consisted of n=362 office workers. A submaximal cycle ergometer test estimated maximal oxygen consumption (VO2max, mL·kg−1·min−1). Based on estimated VO2max participants were split into tertiles; low (n = 121), moderate (n = 119), and high (n = 122). A cognitive test battery (9 tests), assessed processing speed, working memory, executive functions and episodic memory.

    Results: Both hypotheses were confirmed. Groups of moderate (≈40) and high (≈49) fitness outperformed the group of low (≈31) fitness for inhibition and episodic recognition, whereas no significant differences between moderate and high fitness were observed (ANCOVAs). Breakpoints between benefits fromVO2maxfor inhibition and recognition were estimated to ≈44/43 mL·kg−1·min−1 (multivariate broken line regressions).

    Conclusions: Results suggest that it is conceivable to expect a beneficial relationship between VO2max and some cognitive domains up to a certain fitness level. In a sample of healthy office workers, this level was estimated to 44 mL·kg−1·min−1. This has implications on organizational and societal levels; where incentives to improve fitness levels from low to moderate could yield desirable cognitive and health benefits in adults.

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  • 21. Papenberg, Goran
    et al.
    Jonasson, Lars S.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Karalija, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Johansson, Jarkko
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Koehncke, Ylva
    Salami, Alireza
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Aging Research Center, Karolinska Institutet and Stockholm University, Tomtebodavägen 18A, 171 65 Solna, Sweden.
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Lindenberger, Ulman
    Lovden, Martin
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Backman, Lars
    Mapping the landscape of human dopamine D2/3 receptors with [11C]raclopride2019In: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 224, no 8, p. 2871-2882Article in journal (Refereed)
    Abstract [en]

    The dopamine D2/3 system is fundamental for sensory, motor, emotional, and cognitive aspects of behavior. Small-scale human histopathological and animal studies show high density of D2/3 dopamine receptors (D2/3DR) in striatum, but also demonstrate the existence of such receptors across cortical and limbic regions. Assessment of D2/3DR BPND in the extrastriatal regions with [C-11]raclopride has long been considered unreliable due to the relatively low density of D2/3DR outside the striatum. We describe the distribution and interregional links of D2/3DR availability measured with PET and [C-11]raclopride across the human brain in a large sample (N = 176; age range 64-68 years). Structural equation modeling revealed that D2/3DR availability can be organized according to anatomical (nigrostriatal, mesolimbic, mesocortical) and functional (limbic, associative, sensorimotor) dopamine pathways. D2/3DR availability in corticolimbic functional subdivisions showed differential associations to corresponding striatal subdivisions, extending animal and pharmacological work. Our findings provide evidence on the dimensionality and organization of [C-11]raclopride D2/3DR availability in the living human brain that conforms to known dopaminergic pathways.

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  • 22.
    Salami, Alireza
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Aging Research Center, Karolinska Institutet and Stockholm University, Sweden.
    Garrett, Douglas D.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Rieckmann, Anna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Papenberg, Goran
    Karalija, Nina
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany.
    Jonasson, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Jarkko
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Lövdén, Martin
    Lindenberger, Ulman
    Bäckman, Lars
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Dopamine D2/3 Binding Potential Modulates Neural Signatures of Working Memory in a Load-Dependent Fashion.2019In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 39, no 3, p. 537-547Article in journal (Refereed)
    Abstract [en]

    Dopamine (DA) modulates corticostriatal connections. Studies in which imaging of the DA system is integrated with functional imaging during cognitive performance have yielded mixed findings. Some work has shown a link between striatal DA (measured by PET) and fMRI activations, whereas others have failed to observe such a relationship. One possible reason for these discrepant findings is differences in task demands, such that a more demanding task with greater prefrontal activations may yield a stronger association with DA. Moreover, a potential DA–BOLD association may be modulated by task performance. We studied 155 (104 normal-performing and 51 low-performing) healthy older adults (43% females) who underwent fMRI scanning while performing a working memory (WM) n-back task along with DA D2/3 PET assessment using [11C]raclopride. Using multivariate partial-least-squares analysis, we observed a significant pattern revealing positive associations of striatal as well as extrastriatal DA D2/3 receptors to BOLD response in the thalamo–striatal–cortical circuit, which supports WM functioning. Critically, the DA–BOLD association in normal-performing, but not low-performing, individuals was expressed in a load-dependent fashion, with stronger associations during 3-back than 1-/2-back conditions. Moreover, normal-performing adults expressing upregulated BOLD in response to increasing task demands showed a stronger DA–BOLD association during 3-back, whereas low-performing individuals expressed a stronger association during 2-back conditions. This pattern suggests a nonlinear DA–BOLD performance association, with the strongest link at the maximum capacity level. Together, our results suggest that DA may have a stronger impact on functional brain responses during more demanding cognitive tasks.

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  • 23.
    Simonsson, Emma
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Physiotherapy. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Jonasson Stiernman, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lundquist, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Rosendahl, Erik
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Physiotherapy.
    Hedlund, Mattias
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Physiotherapy.
    Lindelöf, Nina
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Physiotherapy.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark; Department of Neurology, Institute of Sports Medicine Copenhagen (ISMC), Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark; Faculty of Medical and Health Sciences, Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
    Dopamine d2/3-receptor availability and its association with autonomous motivation to exercise in older adults: an exploratory [11c]-raclopride study2022In: Frontiers in Human Neuroscience, E-ISSN 1662-5161, Vol. 16, article id 997131Article in journal (Refereed)
    Abstract [en]

    Background: Autonomous motivation to exercise occurs when the activity is voluntary and with a perceived inherent satisfaction from the activity itself. It has been suggested that autonomous motivation is related to striatal dopamine D2/3-receptor (D2/3R) availability within the brain. In this study, we hypothesized that D2/3R availability in three striatal regions (nucleus accumbens, caudate nucleus, and putamen) would be positively associated with self-reported autonomous motivation to exercise. We also examined this relationship with additional exploratory analyses across a set of a priori extrastriatal regions of interest (ROI).

    Methods: Our sample comprised 49 older adults (28 females) between 64 and 78 years of age. The D2/3R availability was quantified from positron emission tomography using the non-displaceable binding potential of [11C]-raclopride ligand. The exercise-related autonomous motivation was assessed with the Swedish version of the Behavioral Regulations in Exercise Questionnaire-2.

    Results: No significant associations were observed between self-reported autonomous motivation to exercise and D2/3R availability within the striatum (nucleus accumbens, caudate nucleus, and putamen) using semi-partial correlations controlling for ROI volume on D2/3R availability. For exploratory analyses, positive associations were observed for the superior (r = 0.289, p = 0.023) and middle frontal gyrus (r = 0.330, p = 0.011), but not for the inferior frontal gyrus, orbitofrontal cortex, anterior cingulate cortex, or anterior insular cortex.

    Conclusion: This study could not confirm the suggested link between striatal D2/3R availability and subjective autonomous motivation to exercise among older adults. The exploratory findings, however, propose that frontal brain regions may be involved in the intrinsic regulation of exercise-related behaviors, though this has to be confirmed by future studies using a more suitable ligand and objective measures of physical activity levels.

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  • 24.
    Stiernman Jonasson, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Stillman, Chelsea
    Department of Psychology, University of Pittsburgh, Sennott Square, PA, Pittsburgh, United States.
    Erickson, Kirk I.
    Department of Psychology, University of Pittsburgh, Sennott Square, PA, Pittsburgh, United States.
    Impact of aerobic exercise on brain structure in models of aging: Hippocampus and beyond2021In: Factors Affecting Neurological Aging: Genetics, Neurology, Behavior, and Diet / [ed] Colin R. Martin, Victor R. Preedy, Rajkumar Rajendram, Elsevier, 2021, p. 403-413Chapter in book (Refereed)
    Abstract [en]

    Evidence from multiple scientific disciplines indicates that aerobic exercise could be effective in enhancing brain health and function in aging, and reducing the risk for cognitive impairment and dementia. Animal models have provided convincing evidence that exercise increases the expression of growth factors involved in neuroplasticity. By triggering signaling cascades in the brain, these growth factors promote proliferation, neurogenesis, neural differentiation, and cell survival in the hippocampus, and angiogenesis and/or synaptic plasticity and neural growth throughout the brain more generally. These growth factor-induced effects partly explain why exercise improves memory. Furthermore, they engender neuroprotective effects by influencing regeneration, remyelination, cell survival, and waste removal. Whereas human intervention evidence supports hippocampal plasticity, cross-sectional studies highlight effects in the cortex too, indicating that exercise-induced gross morphological changes may be regionally specific. Aerobic exercise is a promising nonpharmacological therapy to maintain brain health, although knowledge about the effects of specific exercise parameters (i.e., intensity) on different populations is still lacking.

  • 25.
    Stiernman, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Grill, Filip
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    McNulty, Charlotte
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Bahrd, Philip
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Panes Lundmark, Vania
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Salami, Alireza
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Aging Research Center, Karolinska Institutet, Stockholm University, Solna, Stockholm, Sweden.
    Rieckmann, Anna
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences. Munich Center for the Economics of Aging, Max Planck Institute for Social Law and Social Policy, Munich, München, Germany.
    Widespread fMRI BOLD signal overactivations during cognitive control in older adults are not matched by corresponding increases in fPET glucose metabolism2023In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 43, no 14, p. 2527-2536Article in journal (Refereed)
    Abstract [en]

    A common observation in fMRI studies using the BOLD signal is that older adults, compared with young adults, show overactivations, particularly during less demanding tasks. The neuronal underpinnings of such overactivations are not known, but a dominant view is that they are compensatory in nature and involve recruitment of additional neural resources. We scanned 23 young (20-37 years) and 34 older (65-86 years) healthy human adults of both sexes with hybrid positron emission tomography/MRI. The radioligand [18F]fluoro-deoxyglucose was used to assess dynamic changes in glucose metabolism as a marker of task-dependent synaptic activity, along with simultaneous fMRI BOLD imaging. Participants performed two verbal working memory (WM) tasks: one involving maintenance (easy) and one requiring manipulation (difficult) of information in WM. Converging activations to the WM tasks versus rest were observed for both imaging modalities and age groups in attentional, control, and sensorimotor networks. Upregulation of activity to WM-demand, comparing the more difficult to the easier task, also converged between both modalities and age groups. For regions in which older adults showed task-dependent BOLD overactivations compared with the young adults, no corresponding increases in glucose metabolism were found. To conclude, findings from the current study show that task-induced changes in the BOLD signal and synaptic activity as measured by glucose metabolism generally converge, but overactivations observed with fMRI in older adults are not coupled with increased synaptic activity, which suggests that these overactivations are not neuronal in origin.

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