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  • 1. Adams, Hieab H. H.
    et al.
    Hibar, Derrek P.
    Chouraki, Vincent
    Stein, Jason L.
    Nyquist, Paul A.
    Renteria, Miguel E.
    Trompet, Stella
    Arias-Vasquez, Alejandro
    Seshadri, Sudha
    Desrivieres, Sylvane
    Beecham, Ashley H.
    Jahanshad, Neda
    Wittfeld, Katharine
    Van der Lee, Sven J.
    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
    Beiser, Alexa
    Bernard, Manon
    Bis, Joshua C.
    Blanken, Laura M. E.
    Blanton, Susan H.
    Bohlken, Marc M.
    Boks, Marco P.
    Bralten, Janita
    Brickman, Adam M.
    Carmichael, Owen
    Chakravarty, M. Mallar
    Chauhan, Ganesh
    Chen, Qiang
    Ching, Christopher R. K.
    Cuellar-Partida, Gabriel
    Den Braber, Anouk
    Doan, Nhat Trung
    Ehrlich, Stefan
    Filippi, Irina
    Ge, Tian
    Giddaluru, Sudheer
    Goldman, Aaron L.
    Gottesman, Rebecca F.
    Greven, Corina U.
    Grimm, Oliver
    Griswold, Michael E.
    Guadalupe, Tulio
    Hass, Johanna
    Haukvik, Unn K.
    Hilal, Saima
    Hofer, Edith
    Hoehn, David
    Holmes, Avram J.
    Hoogman, Martine
    Janowitz, Deborah
    Jia, Tianye
    Kasperaviciute, Dalia
    Kim, Sungeun
    Klein, Marieke
    Kraemer, Bernd
    Lee, Phil H.
    Liao, Jiemin
    Liewald, David C. M.
    Lopez, Lorna M.
    Luciano, Michelle
    Macare, Christine
    Marquand, Andre
    Matarin, Mar
    Mather, Karen A.
    Mattheisen, Manuel
    Mazoyer, Bernard
    Mckay, David R.
    McWhirter, Rebekah
    Milaneschi, Yuri
    Mirza-Schreiber, Nazanin
    Muetzel, Ryan L.
    Maniega, Susana Munoz
    Nho, Kwangsik
    Nugent, Allison C.
    Loohuis, Loes M. Olde
    Oosterlaan, Jaap
    Papmeyer, Martina
    Pappa, Irene
    Pirpamer, Lukas
    Pudas, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Puetz, Benno
    Rajan, Kumar B.
    Ramasamy, Adaikalavan
    Richards, Jennifer S.
    Risacher, Shannon L.
    Roiz-Santianez, Roberto
    Rommelse, Nanda
    Rose, Emma J.
    Royle, Natalie A.
    Rundek, Tatjana
    Saemann, Philipp G.
    Satizabal, Claudia L.
    Schmaal, Lianne
    Schork, Andrew J.
    Shen, Li
    Shin, Jean
    Shumskaya, Elena
    Smith, Albert V.
    Sprooten, Emma
    Strike, Lachlan T.
    Teumer, Alexander
    Thomson, Russell
    Tordesillas-Gutierrez, Diana
    Toro, Roberto
    Trabzuni, Daniah
    Vaidya, Dhananjay
    Van der Grond, Jeroen
    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.
    Woldehawariat, Girma
    Wolf, Christiane
    Wolfers, Thomas
    Xu, Bing
    Yanek, Lisa R.
    Yang, Jingyun
    Zijdenbos, Alex
    Zwiers, Marcel P.
    Agartz, Ingrid
    Aggarwal, Neelum T.
    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.
    Chen, Christopher
    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 Geus, Eco J. C.
    De Jager, Philip L.
    de Zubicaray, Greig I.
    Delanty, Norman
    Depondt, Chantal
    DeStefano, Anita L.
    Dillman, Allissa
    Djurovic, Srdjan
    Donohoe, Gary
    Drevets, Wayne C.
    Duggirala, Ravi
    Dyer, Thomas D.
    Erk, Susanne
    Espeseth, Thomas
    Evans, Denis A.
    Fedko, Iryna
    Fernandez, Guillen
    Ferrucci, Luigi
    Fisher, Simon E.
    Fleischman, Debra A.
    Ford, Ian
    Foroud, Tatiana M.
    Fox, Peter T.
    Francks, Clyde
    Fukunaga, Masaki
    Gibbs, J. Raphael
    Glahn, David C.
    Gollub, Randy L.
    Goring, Harald H. H.
    Grabe, Hans J.
    Green, Robert C.
    Gruber, Oliver
    Gudnason, Vilmundur
    Guelfi, Sebastian
    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
    Pol, Hilleke E. Hulshoff
    Ikeda, Masashi
    Ikram, M. Kamran
    Jack, Clifford R., Jr.
    Jenldnson, Mark
    Johnson, Robert
    Jonsson, 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.
    Longstreth, W. T., Jr.
    Lopez, Oscar L.
    Lovestone, Simon
    Martinez, Oliver
    Martinot, Jean-Luc
    Mattay, Venkata S.
    McDonald, Colm
    McIntosh, Andrew M.
    McMahon, Katie L.
    McMahon, Francis J.
    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.
    Noethen, 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
    Schofield, Peter R.
    Sigurdsson, Sigurdur
    Simmons, Andy
    Singleton, Andrew
    Sisodiya, Sanjay M.
    Smith, Colin
    Smoller, Jordan W.
    Soininen, Hindu.
    Srikanth, Velandai
    Steen, Vidar M.
    Stott, David J.
    Sussmann, Jessika E.
    Thalamuthu, Anbupalam
    Tiemeier, Henning
    Toga, Arthur W.
    Traynor, Bryan J.
    Troncoso, Juan
    Turner, Jessica A.
    Tzourio, Christophe
    Uitterlinden, Andre G.
    Hernandez, Maria C. Valdes
    Van der Brug, Marcel
    Van der Lugt, Aad
    Van der Wee, Nic J. A.
    Van Duijn, Cornelia M.
    Van Haren, Neeltje E. M.
    Van't Ent, Dennis
    Van Tol, Marie Jose
    Vardarajan, Badri N.
    Veltman, Dick J.
    Vernooij, Meike W.
    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, H. Ronald
    Zonderman, Alan B.
    Deary, Ian J.
    DeCarli, Charles
    Schmidt, Helena
    Martin, Nicholas G.
    De Craen, Anton J. M.
    Wright, Margaret J.
    Launer, Lenore J.
    Schumann, Gunter
    Fornage, Myriam
    Franke, Barbara
    Debette, Stephanie
    Medland, Sarah E.
    Ikram, M. Arfan
    Thompson, Paul M.
    Novel genetic loci underlying human intracranial volume identified through genome-wide association2016Ingår i: Nature Neuroscience, ISSN 1097-6256, E-ISSN 1546-1726, Vol. 19, nr 12, s. 1569-1582Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

  • 2. Alakurtti, Kati
    et al.
    Johansson, Jarkko J.
    Joutsa, Juho
    Laine, Matti
    Backman, Lars
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Rinne, Juha O.
    Long-term test-retest reliability of striatal and extrastriatal dopamine D-2/3 receptor binding: study with [C-11]raclopride and high-resolution PET2015Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 35, nr 7, s. 1199-1205Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We measured the long-term test-retest reliability of [C-11]raclopride binding in striatal subregions, the thalamus and the cortex using the bolus-plus-infusion method and a high-resolution positron emission scanner. Seven healthy male volunteers underwent two positron emission tomography (PET) [C-11]raclopride assessments, with a 5-week retest interval. D-2/3 receptor availability was quantified as binding potential using the simplified reference tissue model. Absolute variability (VAR) and intraclass correlation coefficient (ICC) values indicated very good reproducibility for the striatum and were 4.5%/0.82, 3.9%/0.83, and 3.9%/0.82, for the caudate nucleus, putamen, and ventral striatum, respectively. Thalamic reliability was also very good, with VAR of 3.7% and ICC of 0.92. Test-retest data for cortical areas showed good to moderate reproducibility (6.1% to 13.1%). Our results are in line with previous test-retest studies of [C-11]raclopride binding in the striatum. A novel finding is the relatively low variability of [C-11]raclopride binding, providing suggestive evidence that extrastriatal D-2/3 binding can be studied in vivo with [C-11]raclopride PET to be verified in future studies.

  • 3.
    Andersson, Linus
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Department of Occupational and Public Health Sciences, University of Gävle, Sweden.
    Claeson, Anna-Sara
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nordin, Steven
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Short-term olfactory sensitization involves brain networks relevant for pain, and indicates chemical intolerance2017Ingår i: International journal of hygiene and environmental health (Print), ISSN 1438-4639, E-ISSN 1618-131X, Vol. 220, nr 2, s. 503-509Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Chemical intolerance is a medically unexplained affliction that implies deleterious reactions to non-toxic everyday chemical exposure. Sensitization (i.e. increased reactivity to repeated, invariant stimulation) to odorous stimulation is an important component in theoretical explanations of chemical intolerance, but empirical evidence is scarce. We hypothesized that (1) individuals who sensitize to repeated olfactory stimulation, compared with those who habituate, would express a lower blood oxygenated level dependent (BOLD) response in key inhibitory areas such as the rACC, and higher signal in pain/saliency detection regions, as well as primary and/or secondary olfactory projection areas; and (2) olfactory sensitization, compared with habituation, would be associated with greater self-reported chemical intolerance. More-over, we assessed whether olfactory sensitization was paralleled by comparable trigeminal processing - in terms of perceptual ratings and BOLD responses. We grouped women from a previous functional magnetic imaging study based on intensity ratings of repeated amyl acetate exposure over time. Fourteen women sensitized to the exposure, 15 habituated, and 20 were considered "intermediate" (i.e. neither sensitizers nor habituaters). Olfactory sensitizers, compared with habituaters, displayed a BOLD-pattern in line with the hypothesis, and reported greater problems with odours in everyday life. They also expressed greater reactions to CO2 in terms of both perceived intensity and BOLD signal. The similarities with pain are discussed.

  • 4.
    Andersson, Linus
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Claesson, Anna-Sara
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Stenberg, Berndt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Dermatologi och venereologi.
    Nordin, Steven
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Brain responses to olfactory and trigeminal exposure in idiopathic environmental illness (IEI) attributed to smells: An fMRI study2014Ingår i: Journal of Psychosomatic Research, ISSN 0022-3999, E-ISSN 1879-1360, Vol. 77, nr 5, s. 401-408Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Idiopathic environmental intolerance (IEI) to smells is a prevalent medically unexplained illness. Sufferers attribute severe symptoms to low doses of non-toxic chemicals. Despite the label, IEI is not characterized by acute chemical senses. Theoretical models suggest that sensitized responses in the limbic system of the brain constitute an important mechanism behind the symptoms. The aim was to investigate whether and how brain reactions to low-levels of olfactory and trigeminal stimuli differ in individuals with and without IEI. METHODS: Brain responses to intranasally delivered isoamyl acetate and carbon dioxide were assessed in 25 women with IEI and 26 non-ill controls using functional magnetic resonance imaging. RESULTS: The IEI group had higher blood-oxygenated-level-dependent (BOLD) signal than controls in the thalamus and a number of, mainly, parietal areas, and lower BOLD signal in the superior frontal gyrus. The IEI group did not rate the exposures as more intense than the control group did, and there were no BOLD signal differences between groups in the piriform cortex or olfactory regions of the orbitofrontal cortex. CONCLUSIONS: The IEI reactions were not characterized by hyper-responsiveness in sensory areas. The results can be interpreted as a limbic hyperreactivity and speculatively as an inability to inhibit salient extemal stimuli.

  • 5.
    Andersson, Linus
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Eriksson, Johan
    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). Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Juslin, Peter
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Karlsson Wirebring, Linnea
    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).
    Neurocognitive processes underlying heuristic and normative probability judgments2020Ingår i: Cognition, ISSN 0010-0277, E-ISSN 1873-7838, Vol. 196, s. 1-7, artikel-id 104153Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Judging two events in combination (A&B) as more probable than one of the events (A) is known as a conjunction fallacy. According to dual-process explanations of human judgment and decision making, the fallacy is due to the application of a heuristic, associative cognitive process. Avoiding the fallacy has been suggested to require the recruitment of a separate process that can apply normative rules. We investigated these assumptions using functional magnetic resonance imaging (fMRI) during conjunction tasks. Judgments, whether correct or not, engaged a network of brain regions identical to that engaged during similarity judgments. Avoidance of the conjunction fallacy additionally, and uniquely, involved a fronto-parietal network previously linked to supervisory, analytic control processes. The results lend credibility to the idea that incorrect probability judgments are the result of a representativeness heuristic that requires additional neurocognitive resources to avoid.

  • 6. Athanasiu, Lavinia
    et al.
    Giddaluru, Sudheer
    Fernandes, Carla
    Christoforou, Andrea
    Reinvang, Ivar
    Lundervold, Astri J.
    Nilsson, Lars-Göran
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Kauppi, Karolina
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Eriksson, Elias
    Sundet, Kjetil
    Djurovic, Srdjan
    Espeseth, Thomas
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Steen, Vidar M.
    Andreassen, Ole A.
    Le Hellard, Stephanie
    A genetic association study of CSMD1 and CSMD2 with cognitive function2017Ingår i: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 61, s. 209-216Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for association with cognitive functions in the NCNG sample (Norwegian Cognitive NeuroGenetics; n = 670). Replication testing of SNPs with p-value < 0.001 (7 in CSMD1 and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized Psychosis; n =1025) and the BETULA sample (Betula Longitudinal Study on aging, memory and dementia; n = 1742). Finally, we conducted a meta-analysis of these SNPs using all three samples. The previously identified schizophrenia marker in CSMD1 (SNP rs10503253) was also included. The strongest association was observed between the CSMDI SNP rs2740931 and performance in immediate episodic memory (p-value = 5 Chi 10(-6), minor allele A, MAF 0.48-0.49, negative direction of effect). This association reached the study-wide significance level (p <= 1.2 Chi 10(-5)). SNP rs10503253 was not significantly associated with cognitive functions in our samples. In conclusion, we studied n = 3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. Additional studies of larger samples with cognitive phenotypes will be needed to further clarify the role of CSMD1 in cognitive phenotypes in health and disease.

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  • 7.
    Avelar-Pereira, Barbara
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    Bäckman, Lars
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. 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). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Salami, Alireza
    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). Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    Increased functional homotopy of the prefrontal cortex is associated with corpus callosum degeneration and working memory decline2020Ingår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 96, s. 68-78Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Functional homotopy reflects the link between spontaneous activity in a voxel and its counterpart in the opposite hemisphere. Alterations in homotopic functional connectivity (FC) are seen in normal aging, with highest and lowest homotopy being present in sensory-motor and higher-order regions, respectively. Homotopic FC relates to underlying structural connections, but its neurobiological underpinnings remain unclear. The genu of the corpus callosum joins symmetrical parts of the prefrontal cortex (PFC) and is susceptible to age-related degeneration, suggesting that PFC homotopic connectivity is linked to changes in white-matter integrity. We investigated homotopic connectivity changes and whether these were associated with white-matter integrity in 338 individuals. In addition, we examined whether PFC homotopic FC was related to changes in the genu over 10 years and working memory over 5 years. There were increases and decreases in functional homotopy, with the former being prevalent in subcortical and frontal regions. Increased PFC homotopic FC was partially driven by structural degeneration and negatively associated with working memory, suggesting that it reflects detrimental age-related changes. (C) 2020 The Author(s). Published by Elsevier Inc.

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  • 8.
    Avelar-Pereira, Bárbara
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    Backman, Lars
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    Age-Related Differences in Dynamic Interactions Among Default Mode, Frontoparietal Control, and Dorsal Attention Networks during Resting-State and Interference Resolution2017Ingår i: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 9, artikel-id 152Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Resting-state fMRI (rs-fMRI) can identify large-scale brain networks, including the default mode (DMN), frontoparietal control (FPN) and dorsal attention (DAN) networks. Interactions among these networks are critical for supporting complex cognitive functions, yet the way in which they are modulated across states is not well understood. Moreover, it remains unclear whether these interactions are similarly affected in aging regardless of cognitive state. In this study, we investigated age-related differences in functional interactions among the DMN, FPN and DAN during rest and the Multi-Source Interference task (MSIT). Networks were identified using independent component analysis (ICA), and functional connectivity was measured during rest and task. We found that the FPN was more coupled with the DMN during rest and with the DAN during the MSIT. The degree of FPN-DMN connectivity was lower in older compared to younger adults, whereas no age-related differences were observed in FPN-DAN connectivity in either state. This suggests that dynamic interactions of the FPN are stable across cognitive states. The DMN and DAN were anti correlated and age-sensitive during the MSIT only, indicating variation in a task-dependent manner. Increased levels of anticorrelation from rest to task also predicted successful interference resolution. Additional analyses revealed that the degree of DMN-DAN anticorrelation during the MSIT was associated to resting cerebral blood flow (CBF) within the DMN. This suggests that reduced DMN neural activity during rest underlies an impaired ability to achieve higher levels of anticorrelation during a task. Taken together, our results suggest that only parts of age-related differences in connectivity are uncovered at rest and thus, should be studied in the functional connectome across multiple states for a more comprehensive picture.

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  • 9.
    Awad, Amar
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Grill, Filip
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    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.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Deep brain stimulation does not modulate fMRI resting- state functional connectivity in essential tremorManuskript (preprint) (Övrigt vetenskapligt)
  • 10.
    Awad, Amar
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Levi, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Lindgren, Lenita
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Hultling, Claes
    Department of Neurobiology, Care Sciences and Society (Neurorehabilitation), Karolinska Institute, Stockholm, Sweden.
    Westling, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Preserved somatosensory conduction in a patient with complete cervical spinal cord injury2015Ingår i: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 47, nr 5, s. 426-431Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 11.
    Backeström, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Papadopoulos, Konstantin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Eriksson, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Blennow, Kaj
    Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at University of Gothenburg, Mö lndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mö lndal, Sweden.
    Zetterberg, Henrik
    Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mö lndal, Sweden; Department of Neurodegenerative Disease, Ucl Institute of Neurology, Queen Square, London, United Kingdom; UK Dementia Research Institute at Ucl, London, United Kingdom.
    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.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Acute hyperglycaemia leads to altered frontal lobe brain activity and reduced working memory in type 2 diabetes2021Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 16, nr 3, artikel-id e0247753Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    How acute hyperglycaemia affects memory functions and functional brain responses in individuals with and without type 2 diabetes is unclear. Our aim was to study the association between acute hyperglycaemia and working, semantic, and episodic memory in participants with type 2 diabetes compared to a sex- A nd age-matched control group. We also assessed the effect of hyperglycaemia on working memory-related brain activity. A total of 36 participants with type 2 diabetes and 34 controls (mean age, 66 years) underwent hyperglycaemic clamp or placebo clamp in a blinded and randomised order. Working, episodic, and semantic memory were tested. Overall, the control group had higher working memory (mean z-score 33.15 ± 0.45) than the group with type 2 diabetes (mean z-score 31.8 ± 0.44, p = 0.042) considering both the placebo and hyperglycaemic clamps. Acute hyperglycaemia did not influence episodic, semantic, or working memory performance in either group. Twenty-two of the participants (10 cases, 12 controls, mean age 69 years) were randomly invited to undergo the same clamp procedures to challenge working memory, using 1-, 2-, and 3-back, while monitoring brain activity by blood oxygen level-dependent functional magnetic resonance imaging (fMRI). The participants with type 2 diabetes had reduced working memory during the 1- A nd 2-back tests. fMRI during placebo clamp revealed increased BOLD signal in the left lateral frontal cortex and the anterior cingulate cortex as a function of working memory load in both groups (3>2>1). During hyperglycaemia, controls showed a similar load-dependent fMRI response, whereas the type 2 diabetes group showed decreased BOLD response from 2-to 3-back. These results suggest that impaired glucose metabolism in the brain affects working memory, possibly by reducing activity in important frontal brain areas in persons with type 2 diabetes.

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  • 12.
    Backman, Lars
    et al.
    Aging Research Center, Karolinska Institute and University of Stockholm, Stockholm,.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Dopamine and training-related working-memory improvement2013Ingår i: Neuroscience and Biobehavioral Reviews, ISSN 0149-7634, E-ISSN 1873-7528, Vol. 37, nr 9, s. 2209-2219Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

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

  • 13.
    Bergdahl, Jan
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Nilsson, Lars-Göran
    Riklund Åhlström, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Treatment of chronic stress in employees: subjective, cognitive and neural correlates2005Ingår i: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 46, nr 5, s. 395-402Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study reports the effect of an affect-focused intervention program, the Affect School, on stress, psychological symptoms, cognitive functioning and neural activity. Fifty employees in social service and education, with high levels of chronic stress, were randomly divided into a treatment (N= 27) and control (N= 23) group. Complete sets of data were available in 20 participants in the treatment group and 17 in the control group. The Perceived Stress Questionnaire assessed stress and the Symptom Check List-90 psychological symptoms before and after treatment. Episodic-memory functioning under focused and divided attention conditions was also assessed. Prior and after the Affect School, seven participants in the treatment group were studied with functional magnetic resonance imaging (fMRI) during episodic memory processing. After the Affect School there was a reduction in stress and psychological symptoms for the treatment group but not in the control group. The controls showed a reduction in episodic memory functioning whereas the performance of the treatment group remained intact. The fMRI scanning indicated a qualitative change in the neural network subserving episodic memory. These preliminary results suggest that the Affect School is effective on individuals with high stress.

  • 14. Bergdahl, Maud
    et al.
    Bergdahl, Jan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nilsson, Lars-Göran
    Psykologiska institutionen, Stockholms universitet.
    Difference in apolipoprotein E type 4 allele (APOE e4) amongdentate and edentulous subjects2008Ingår i: Gerodontology, ISSN 0734-0664, E-ISSN 1741-2358, Vol. 25, nr 3, s. 179-186Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 15. Bergdahl, Maud
    et al.
    Habib, Reza
    Bergdahl, Jan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Nilsson, Lars-Göran
    Natural teeth and cognitive function in humans2007Ingår i: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 48, nr 6, s. 557-565Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 16.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Ekman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Fatigue after traumatic brain injury is linked to altered striato-thalamic-cortical functioning2017Ingår i: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 31, nr 6-7, s. 755-755Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 17.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Ekman, Urban
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Using Functional Magnetic Resonance Imaging to Detect Chronic Fatigue in Patients With Previous Traumatic Brain Injury: changes linked to altered Striato-Thalamic-Cortical Functioning2018Ingår i: The journal of head trauma rehabilitation, ISSN 0885-9701, E-ISSN 1550-509X, Vol. 33, nr 4, s. 266-274Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

    Setting: Neurorehabilitation clinic.

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

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

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

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

  • 18.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. School of Sport Sciences, The Arctic University of Norway, Tromsø, Norway Medicine.
    Ekman, Urban
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Eriksson, Johan
    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, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa. School of Sport Sciences, The Arctic University of Norway, Tromsø, Norway.
    Pharmaco-fMRI in Patients With Traumatic Brain Injury: A Randomized Controlled Trial With the Monoaminergic Stabilizer (-)-OSU61622019Ingår i: The journal of head trauma rehabilitation, ISSN 0885-9701, E-ISSN 1550-509X, Vol. 34, nr 3, s. 189-198Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To examine the effects of monoaminergic stabilizer (-)-OSU6162 on brain activity, as measured by blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI), in patients in the chronic phase of traumatic brain injury suffering from fatigue.

    SETTING: Neurorehabilitation clinic.

    PARTICIPANTS: Patients with traumatic brain injury received either placebo (n = 24) or active treatment (n = 28). Healthy controls (n = 27) went through fMRI examination at one point and were used in sensitivity analysis on normalization of BOLD response.

    DESIGN: Randomized, double-blinded, placebo-controlled design.

    MAIN MEASURES: Effects on BOLD signal changes from before to after treatment during performance of a fatiguing attention task.

    RESULTS: The fMRI results revealed treatment effects within the right occipitotemporal cortex and the right orbitofrontal cortex. In these regions, the BOLD response was normalized relative to healthy controls at the postintervention fMRI session. No effects were seen in regions in which we previously observed activity differences between patients and healthy controls while performing this fMRI task, such as the striatum.

    CONCLUSION: (-)-OSU6162 treatment had influences on functional brain activity, although the normalized regional BOLD response was observed in regions that were not a priori hypothesized to be sensitive to this particular treatment, and was not accompanied by any effects on in-scanner test performance or on fatigue.

  • 19.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa. School of Sport Sciences, The Arctic University of Norway, Tromsø, Norway..
    White matter hyperintensities increases with traumatic brain injury severity: associations to neuropsychological performance and fatigue2020Ingår i: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 34, nr 3, s. 415-420Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

    Results: WMH lesions were more common in patients with TBI than in healthy controls (p = .032), and increased with higher TBI severity (p = .025). Linear regressions showed that WMH lesions in patients with TBI were not related to performance on any neuropsychological tests (p > .05 for all). However, a negative relationship between number of WMH lesions in patients with TBI and self-assessed fatigue was found (r = - 0.33, p = .026).

    Conclusion: WMH lesions are more common in patients with TBI than in healthy controls, and WMH lesions burden increases with TBI severity. These lesions could not explain decreased cognitive functioning in patients with TBI but did relate to decreased self-assessment of fatigue after TBI.

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  • 20.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    White matter hyperintensities increases with traumatic brain injuryseverity: associations to neuropsychological performance and fatigueManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

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

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

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

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

  • 21.
    Bergouignan, Loretxu
    et al.
    BCBL, Basque Center on Cognition, Brain and Language, Donostia, Spain.
    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.
    Ehrsson, H. Henrik
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Out-of-body memory encoding causes third-person perspective at recall2022Ingår i: Journal of Cognitive Psychology, ISSN 2044-5911, E-ISSN 2044-592X, Vol. 34, nr 1, s. 160-178Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sigmund Freud famously noted some memories are recalled with a perspective of “an observer from outside the scene”. According to Freud—and most memory researchers today—the third-person perspective occurs due to reconstructive processes at recall. An alternative possibility is that the third-person perspective have been adopted when the actual event is experienced and later recalled in its original form. Here we test this hypothesis using a perceptual out-of-body illusion during the encoding of real events. Participants took part in a social interaction while experiencing an out-of-body illusion where they viewed the event and their own body from a third-person perspective. In recall sessions ∼1 week later, events encoded in the out-of-body compared to the in-body control condition were significantly less recalled from a first-person perspective. An out-of-body experience leads to more third-person perspective during recollection.

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  • 22. Bergouignan, Loretxu
    et al.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Ehrsson, H. Henrik
    Out-of-body-induced hippocampal amnesia2014Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, nr 12, s. 4421-4426Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 23.
    Binnewies, Julia
    et al.
    Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress Program, Amsterdam, Netherlands.
    Nawijn, Laura
    Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress Program, Amsterdam, Netherlands.
    Brandmaier, Andreas M.
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Max Planck, UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany; Department of Psychology, MSB Medical School Berlin, Berlin, Germany.
    Baaré, William F.C.
    Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital – Amager and Hvidovre, Copenhagen, Denmark.
    Bartrés-Faz, David
    Departament de Medicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona and Institut de Neurociències, Universitat de Barcelona, Spain.
    Drevon, Christian A.
    Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo & Vitas Ltd, Oslo Science Park, Oslo, Norway.
    Düzel, Sandra
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Max Planck, UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany.
    Fjell, Anders M.
    Center for Lifespan Changes in Brain and Cognition, University of Oslo, Norway; Department of Radiology and Nuclear Medicine, Oslo University Hospital, Norway.
    Han, Laura K.M.
    Centre for Youth Mental Health, The University of Melbourne, VIC, Parkville, Australia.
    Knights, Ethan
    MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, United Kingdom.
    Lindenberger, Ulman
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Max Planck, UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany.
    Milaneschi, Yuri
    Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress Program, Amsterdam, Netherlands.
    Mowinckel, Athanasia M.
    Center for Lifespan Changes in Brain and Cognition, University of Oslo, Norway.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Plachti, Anna
    Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital – Amager and Hvidovre, Copenhagen, Denmark.
    Madsen, Kathrine Skak
    Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital – Amager and Hvidovre, Copenhagen, Denmark; Radiography, Department of Technology, University College Copenhagen, Copenhagen, Denmark.
    Solé-Padullés, Cristina
    Departament de Medicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona and Institut de Neurociències, Universitat de Barcelona, Spain.
    Suri, Sana
    Wellcome Centre for Integrative Neuroimaging, University of Oxford, United Kingdom; Department of Psychiatry, University of Oxford, United Kingdom.
    Walhovd, Kristine B.
    Center for Lifespan Changes in Brain and Cognition, University of Oslo, Norway; Department of Radiology and Nuclear Medicine, Oslo University Hospital, Norway.
    Zsoldos, Enikő
    Wellcome Centre for Integrative Neuroimaging, University of Oxford, United Kingdom; Department of Psychiatry, University of Oxford, United Kingdom.
    Ebmeier, Klaus P.
    Department of Psychiatry, University of Oxford, United Kingdom.
    Penninx, Brenda W.J.H.
    Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress Program, Amsterdam, Netherlands.
    Associations of depression and regional brain structure across the adult lifespan: Pooled analyses of six population-based and two clinical cohort studies in the European Lifebrain consortium2022Ingår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 36, artikel-id 103180Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Major depressive disorder has been associated with lower prefrontal thickness and hippocampal volume, but it is unknown whether this association also holds for depressive symptoms in the general population. We investigated associations of depressive symptoms and depression status with brain structures across population-based and patient-control cohorts, and explored whether these associations are similar over the lifespan and across sexes.

    Methods: We included 3,447 participants aged 18–89 years from six population-based and two clinical patient-control cohorts of the European Lifebrain consortium. Cross-sectional meta-analyses using individual person data were performed for associations of depressive symptoms and depression status with FreeSurfer-derived thickness of bilateral rostral anterior cingulate cortex (rACC) and medial orbitofrontal cortex (mOFC), and hippocampal and total grey matter volume (GMV), separately for population-based and clinical cohorts.

    Results: Across patient-control cohorts, depressive symptoms and presence of mild-to-severe depression were associated with lower mOFC thickness (rsymptoms = −0.15/ rstatus = −0.22), rACC thickness (rsymptoms = −0.20/ rstatus = −0.25), hippocampal volume (rsymptoms = −0.13/ rstatus = 0.13) and total GMV (rsymptoms = −0.21/ rstatus = −0.25). Effect sizes were slightly larger for presence of moderate-to-severe depression. Associations were similar across age groups and sex. Across population-based cohorts, no associations between depression and brain structures were observed.

    Conclusions: Fitting with previous meta-analyses, depressive symptoms and depression status were associated with lower mOFC, rACC thickness, and hippocampal and total grey matter volume in clinical patient-control cohorts, although effect sizes were small. The absence of consistent associations in population-based cohorts with mostly mild depressive symptoms, suggests that significantly lower thickness and volume of the studied brain structures are only detectable in clinical populations with more severe depressive symptoms.

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  • 24.
    Binnewies, Julia
    et al.
    Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress program, Amsterdam, Netherlands.
    Nawijn, Laura
    Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress program, Amsterdam, Netherlands.
    Brandmaier, Andreas M.
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany; Department of Psychology, MSB Medical School Berlin, Berlin, Germany.
    Baaré, William F.C.
    Danish Research Centre for Magnetic Resonance, centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark.
    Boraxbekk, Carl-Johan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Danish Research Centre for Magnetic Resonance, centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark; Institute for Clinical Medicine, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark; Institute of Sports Medicine Copenhagen (ISMC) and Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
    Demnitz, Naiara
    Danish Research Centre for Magnetic Resonance, centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark.
    Drevon, Christian A.
    Vitas Ltd. Oslo Science Park & Department of Nutrition, IMB, University of Oslo, Norway.
    Fjell, Anders M.
    Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Norway; Computational Radiology and Artificial Intelligence, Department of Radiology and Nuclear Medicine, Oslo University Hospital, Norway.
    Lindenberger, Ulman
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany.
    Madsen, Kathrine Skak
    Danish Research Centre for Magnetic Resonance, centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Topiwala, Anya
    Nuffield Department of Population Health, Big Data Institute, University of Oxford, Oxford, United Kingdom.
    Walhovd, Kristine B.
    Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Norway; Computational Radiology and Artificial Intelligence, Department of Radiology and Nuclear Medicine, Oslo University Hospital, Norway.
    Ebmeier, Klaus P.
    Department of Psychiatry, University of Oxford, United Kingdom.
    Penninx, Brenda W.J.H.
    Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress program, Amsterdam, Netherlands.
    Lifestyle-related risk factors and their cumulative associations with hippocampal and total grey matter volume across the adult lifespan: a pooled analysis in the European Lifebrain consortium2023Ingår i: Brain Research Bulletin, ISSN 0361-9230, E-ISSN 1873-2747, Vol. 200, artikel-id 110692Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Lifestyle-related risk factors, such as obesity, physical inactivity, short sleep, smoking and alcohol use, have been associated with low hippocampal and total grey matter volumes (GMV). However, these risk factors have mostly been assessed as separate factors, leaving it unknown if variance explained by these factors is overlapping or additive. We investigated associations of five lifestyle-related factors separately and cumulatively with hippocampal and total GMV, pooled across eight European cohorts.

    Methods: We included 3838 participants aged 18–90 years from eight cohorts of the European Lifebrain consortium. Using individual person data, we performed cross-sectional meta-analyses on associations of presence of lifestyle-related risk factors separately (overweight/obesity, physical inactivity, short sleep, smoking, high alcohol use) as well as a cumulative unhealthy lifestyle score (counting the number of present lifestyle-related risk factors) with FreeSurfer-derived hippocampal volume and total GMV. Lifestyle-related risk factors were defined according to public health guidelines.

    Results: High alcohol use was associated with lower hippocampal volume (r = −0.10, p = 0.021), and overweight/obesity with lower total GMV (r = −0.09, p = 0.001). Other lifestyle-related risk factors were not significantly associated with hippocampal volume or GMV. The cumulative unhealthy lifestyle score was negatively associated with total GMV (r = −0.08, p = 0.001), but not hippocampal volume (r = −0.01, p = 0.625).

    Conclusions: This large pooled study confirmed the negative association of some lifestyle-related risk factors with hippocampal volume and GMV, although with small effect sizes. Lifestyle factors should not be seen in isolation as there is evidence that having multiple unhealthy lifestyle factors is associated with a linear reduction in overall brain volume.

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  • 25.
    Boen, Rune
    et al.
    Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Kaufmann, Tobias
    Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatry and Psychotherapy, Tübingen Center for Mental Health, University of Tübingen, Germany; German Center for Mental Health (DZPG), partner site Tübingen, Tübingen, Germany.
    van der Meer, Dennis
    Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands.
    Frei, Oleksandr
    Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Centre for Bioinformatics, Department of Informatics, University of Oslo, Oslo, Norway.
    Agartz, Ingrid
    Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Clinical Research, Diakonhjemmet Hospital, Oslo, Norway; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Stockholm, Sweden.
    Ames, David
    University of Melbourne Academic Unit for Psychiatry of Old Age, St George's Hospital, VIC, Kew, Australia; National Ageing Research Institute, VIC, Parkville, Australia.
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Armstrong, Nicola J.
    Department of Mathematics and Statistics, Curtin University, WA, Perth, Australia.
    Artiges, Eric
    Institut National de la Santé et de la Recherche Médicale U1299, École Normale Supérieure Paris-Saclay, Université Paris Saclay, Gif-sur-Yvette, France; Établissement public de santé (EPS) Barthélemy Durand, Etampes, France.
    Atkins, Joshua R.
    School of Biomedical Sciences and Pharmacy, College of Medicine, Health and Wellbeing, University of Newcastle, NSW, Callaghan, Australia; Precision Medicine Research Program, Hunter Medical Research Institute, NSW, Newcastle, Australia; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Bauer, Jochen
    University Clinic for Radiology, University of Münster, Münster, Germany.
    Benedetti, Francesco
    Psychiatry and Clinical Psychobiology Unit, Division of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy; Division of Neuroscience, Psychiatry and Clinical Psychobiology Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.
    Boomsma, Dorret I.
    Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
    Brodaty, Henry
    Centre for Healthy Brain Ageing, School of Clinical Medicine, University of New South Wales, NSW, Sydney, Australia.
    Brosch, Katharina
    Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
    Buckner, Randy L.
    Department of Psychology and Center for Brain Science, Harvard University, MA, Cambridge, United States; Department of Psychiatry, Massachusetts General Hospital, MA, Boston, United States.
    Cairns, Murray J.
    School of Biomedical Sciences and Pharmacy, College of Medicine, Health and Wellbeing, University of Newcastle, NSW, Callaghan, Australia; Precision Medicine Research Program, Hunter Medical Research Institute, NSW, Newcastle, Australia.
    Calhoun, Vince
    Tri-institutional Center for Translational Research in Neuroimaging and Data Science, Georgia State University/Georgia Institute of Technology/Emory University, GA, Atlanta, United States.
    Caspers, Svenja
    Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Institute for Anatomy I, Medical Faculty & University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
    Cichon, Sven
    Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; University Hospital Basel, Institute of Medical Genetics and Pathology, Basel, Switzerland.
    Corvin, Aiden P.
    Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
    Crespo-Facorro, Benedicto
    Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Centro superior de investigaciones científicas (CSIC), Sevilla, Spain; Centro de Investigación Biomédica en Red Salud Mental, Sevilla, Spain; Department of Psychiatry, University of Sevilla, Sevilla, Spain.
    Dannlowski, Udo
    Institute for Translational Psychiatry, University of Münster, Münster, Germany.
    David, Friederike S.
    Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany.
    de Geus, Eco J.C.
    Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
    de Zubicaray, Greig I.
    School of Psychology and Counselling, Queensland University of Technology, QLD, Brisbane, Australia.
    Desrivières, Sylvane
    Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
    Doherty, Joanne L.
    Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom; Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, United Kingdom.
    Donohoe, Gary
    School of Psychology and Center for Neuroimaging, Cognition and Genomics, University of Galway, Galway, Ireland.
    Ehrlich, Stefan
    Translational Developmental Neuroscience Section, Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
    Eising, Else
    Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands.
    Espeseth, Thomas
    Department of Psychology, University of Oslo, Oslo, Norway; Department of Psychology, Oslo New University College, Oslo, Norway.
    Fisher, Simon E.
    Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands.
    Forstner, Andreas J.
    Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany.
    Fortaner-Uyà, Lidia
    Psychiatry and Clinical Psychobiology Unit, Division of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy; Division of Neuroscience, Psychiatry and Clinical Psychobiology Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.
    Frouin, Vincent
    Neurospin, Commissariat a l'Energie Atomique (CEA), Université Paris-Saclay, Gif-sur-Yvette, France.
    Fukunaga, Masaki
    Section of Brain Function Information, National Institute for Physiological Sciences, Okazaki, Japan.
    Ge, Tian
    Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, MA, Boston, United States; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, MA, Boston, United States.
    Glahn, David C.
    Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, MA, Boston, United States; Department of Psychiatry, Harvard Medical School, MA, Boston, United States.
    Goltermann, Janik
    Institute for Translational Psychiatry, University of Münster, Münster, Germany.
    Grabe, Hans J.
    Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
    Green, Melissa J.
    Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, NSW, Sydney, Australia; Neuroscience Research Australia, NSW, Sydney, Australia.
    Groenewold, Nynke A.
    Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
    Grotegerd, Dominik
    Institute for Translational Psychiatry, University of Münster, Münster, Germany.
    Grøntvedt, Gøril Rolfseng
    Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim, Trondheim, Norway.
    Hahn, Tim
    Institute for Translational Psychiatry, University of Münster, Münster, Germany.
    Hashimoto, Ryota
    Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Kodaira, Japan.
    Hehir-Kwa, Jayne Y.
    Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.
    Henskens, Frans A.
    School of Medicine and Public Health, University of Newcastle, NSW, Newcastle, Australia; Priority Research Centre for Health Behaviour, University of Newcastle, NSW, Newcastle, Australia.
    Holmes, Avram J.
    Department of Psychiatry, Rutgers University, NJ, New Brunswick, United States; Brain Health Institute, Rutgers University, NJ, Piscataway, United States.
    Håberg, Asta K.
    Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Radiology and Nuclear Medicine, St. Olav's Hospital, Trondheim, Norway.
    Haavik, Jan
    Department of Biomedicine, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
    Jacquemont, Sebastien
    Sainte Justine Hospital Research Center, QC, Montreal, Canada; Department of Pediatrics, University of Montreal, QC, Montreal, Canada.
    Jansen, Andreas
    Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany; Core-Facility Brainimaging and Department of Psychiatry, Faculty of Medicine, Philipps-University Marburg, Marburg, Germany.
    Jockwitz, Christiane
    Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Institute for Anatomy I, Medical Faculty & University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
    Jönsson, Erik G.
    Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden.
    Kikuchi, Masataka
    Department of Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Science, The University of Tokyo, Chiba, Japan.
    Kircher, Tilo
    Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
    Kumar, Kuldeep
    Sainte Justine Hospital Research Center, QC, Montreal, Canada.
    Le Hellard, Stephanie
    Norwegian Centre for Mental Disorders Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
    Leu, Costin
    Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom; Department of Neurology, McGovern Medical School, UTHealth Houston, TX, Houston, United States.
    Linden, David E.
    Neuroscience and Mental Health Innovation Institute, Cardiff University, Cardiff, United Kingdom; School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands.
    Liu, Jingyu
    Department of Computer Science and Center for Translational Research in Neuroimaging and Data Science, Georgia State University, GA, Atlanta, United States.
    Loughnan, Robert
    Department of Cognitive Science and Population Neuroscience and Genetics Lab, University of California San Diego, CA, La Jolla, United States.
    Mather, Karen A.
    Centre for Healthy Brain Ageing, School of Clinical Medicine, University of New South Wales, NSW, Sydney, Australia.
    McMahon, Katie L.
    School of Clinical Sciences, Queensland University of Technology, QLD, Brisbane, Australia.
    McRae, Allan F.
    Institute for Molecular Bioscience, The University of Queensland, QLD, Brisbane, Australia.
    Medland, Sarah E.
    Psychiatric Genetics, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, QLD, Brisbane, Australia; University of Queensland, QLD, Brisbane, Australia; Queensland University of Technology, QLD, Brisbane, Australia.
    Meinert, Susanne
    Institute for Translational Psychiatry, University of Münster, Münster, Germany; Institute for Translational Neuroscience, University of Münster, Münster, Germany.
    Moreau, Clara A.
    Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, CA, Marina del Rey, United States.
    Morris, Derek W.
    Centre for Neuroimaging, Cognition and Genomics, School of Biological and Chemical Sciences, University of Galway, Galway, Ireland.
    Mowry, Bryan J.
    Queensland Brain Institute and Queensland Centre for Mental Health Research, University of Queensland, QLD, Brisbane, Australia.
    Mühleisen, Thomas W.
    Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Institute for Anatomy I, Medical Faculty & University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland.
    Nenadić, Igor
    Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
    Nöthen, Markus M.
    Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany.
    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).
    Ophoff, Roel A.
    Department of Psychiatry, Erasmus University Medical Center, Rotterdam, Netherlands; Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, University of California Los Angeles, CA, Los Angeles, United States.
    Owen, Michael J.
    Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom; Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom.
    Pantelis, Christos
    Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Carlton South, Victoria, Australia; Western Centre for Health Research and Education, Sunshine Hospital, VIC, St Albans, Australia.
    Paolini, Marco
    Psychiatry and Clinical Psychobiology Unit, Division of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy; Division of Neuroscience, Psychiatry and Clinical Psychobiology Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.
    Paus, Tomas
    Departments of Psychiatry and Neuroscience, Faculty of Medicine and Sainte Justine Hospital Research Center, University of Montreal, QC, Montreal, Canada; Departments of Psychiatry and Psychology, University of Toronto, ON, Toronto, Canada.
    Pausova, Zdenka
    The Hospital for Sick Children, ON, Toronto, Canada; Department of Physiology, University of Toronto, ON, Toronto, Canada.
    Persson, Karin
    Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway; Norwegian National Centre for Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.
    Quidé, Yann
    Neuroscience Research Australia, NSW, Sydney, Australia; School of Psychology, University of New South Wales, NSW, Sydney, Australia.
    Marques, Tiago Reis
    Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
    Sachdev, Perminder S.
    Centre for Healthy Brain Ageing, School of Clinical Medicine, University of New South Wales, NSW, Sydney, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, NSW, Sydney, Australia.
    Sando, Sigrid B.
    Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim, Trondheim, Norway.
    Schall, Ulrich
    Hunter Medical Research Institute, NSW, Newcastle, Australia.
    Scott, Rodney J.
    School of Biomedical Sciences and Pharmacy, College of Medicine, Health and Wellbeing, University of Newcastle, NSW, Callaghan, Australia; Hunter Medical Research Institute, NSW, Newcastle, Australia; Division of Molecular Medicine, New South Wales Health Pathology, NSW, Newcastle, Australia.
    Selbæk, Geir
    Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway; Norwegian National Centre for Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
    Shumskaya, Elena
    Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands.
    Silva, Ana I.
    Neuroscience and Mental Health Innovation Institute, Cardiff University, Cardiff, United Kingdom.
    Sisodiya, Sanjay M.
    Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom; Chalfont Centre for Epilepsy, Chalfont St Peter, United Kingdom.
    Stein, Frederike
    Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
    Stein, Dan J.
    SA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
    Straube, Benjamin
    Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
    Streit, Fabian
    Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
    Strike, Lachlan T.
    Psychiatric Genetics, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, QLD, Brisbane, Australia; School of Psychology and Counselling, Faculty of Health, Queensland University of Technology, Brisbane, Australia.
    Teumer, Alexander
    Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; German Centre for Cardiovascular Research, Greifswald, Germany.
    Teutenberg, Lea
    Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
    Thalamuthu, Anbupalam
    Centre for Healthy Brain Ageing, School of Clinical Medicine, University of New South Wales, NSW, Sydney, Australia.
    Tooney, Paul A.
    School of Biomedical Sciences and Pharmacy, College of Medicine, Health and Wellbeing, University of Newcastle, NSW, Callaghan, Australia; Hunter Medical Research Institute, NSW, Newcastle, Australia.
    Tordesillas-Gutierrez, Diana
    Instituto de Física de Cantabria UC-CSIC, Santander, Spain; Department of Radiology, Marqués de Valdecilla University Hospital, Valdecilla Biomedical Research Institute, Instituto de Investigación Sanitaria Valdecilla, Santander, Spain.
    Trollor, Julian N.
    Department of Developmental Disability Neuropsychiatry and Centre for Healthy Brain Ageing, School of Clinical Medicine, University of New South Wales, NSW, Sydney, Australia.
    van ’t Ent, Dennis
    Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
    van den Bree, Marianne B.M.
    Institute of Psychological Medicine and Clinical Neurosciences and Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom; Institute for Translational Neuroscience, University of Münster, Münster, Germany.
    van Haren, Neeltje E.M.
    Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Centre, Rotterdam, Netherlands; Department of Psychiatry, University Medical Centre Utrecht, Utrecht, Netherlands.
    Vázquez-Bourgon, Javier
    Centro de Investigación Biomédica en Red Salud Mental, Sevilla, Spain; Department of Psychiatry, University Hospital Maqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Santander, Spain; Departamento de Medicina y Psiquiatría, Universidad de Cantabria, Santander, Spain.
    Völzke, Henry
    German Centre for Cardiovascular Research, Greifswald, Germany; Greifswald University Hospital, Greifswald, Germany.
    Wen, Wei
    Centre for Healthy Brain Ageing, School of Clinical Medicine, University of New South Wales, NSW, Sydney, Australia.
    Wittfeld, Katharina
    Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
    Ching, Christopher R.K.
    Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, CA, Marina del Rey, United States.
    Westlye, Lars T.
    Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
    Thompson, Paul M.
    Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, CA, Marina del Rey, United States.
    Bearden, Carrie E.
    Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, University of California Los Angeles, CA, Los Angeles, United States.
    Selmer, Kaja K.
    Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital and the University of Oslo, Oslo, Norway.
    Alnæs, Dag
    Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Kristiania University College, Oslo, Norway.
    Andreassen, Ole A.
    Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
    Sønderby, Ida E.
    Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
    Beyond the global brain differences: intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers2024Ingår i: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 95, nr 2, s. 147-160Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.

    Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference.

    Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.

    Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.

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  • 26.
    Boraxbekk, Carl-Johan
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Lundquist, Anders
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Nordin, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nilsson, Lars-Göran
    Aging Research Center, Karolinska Institutet.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Free Recall Episodic Memory Performance Predicts Dementia 10 Years Prior to Clinical Diagnosis: Findings from the Betula Longitudinal Study2015Ingår i: Dementia and Geriatric Cognitive Disorders Extra, E-ISSN 1664-5464, Vol. 5, nr 2, s. 191-202Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Aims: Early dementia diagnosis is a considerable challenge. The present study examined the predictive value of cognitive performance for a future clinical diagnosis of late-onset Alzheimer's disease or vascular dementia in a random population sample. Methods: Cognitive performance was retrospectively compared between three groups of participants from the Betula longitudinal cohort. Group 1 developed dementia 11-22 years after baseline testing (n = 111) and group 2 after 1-10 years (n = 280); group 3 showed no deterioration towards dementia during the study period (n = 2,855). Multinomial logistic regression analysis was used to investigate the predictive value of tests reflecting episodic memory performance, semantic memory performance, visuospatial ability, and prospective memory performance. Results: Age-and education-corrected performance on two free recall episodic memory tests significantly predicted dementia 10 years prior to clinical diagnosis. Free recall performance also predicted dementia 11-22 years prior to diagnosis when controlling for education, but not when age was added to the model. Conclusion: The present results support the suggestion that two free recall-based tests of episodic memory function may be useful for detecting individuals at risk of developing dementia 10 years prior to clinical diagnosis.

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  • 27.
    Boraxbekk, Carl-Johan
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Aging Research Center (ARC), Karolinska Institute, Stockholm, Sweden.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    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.
    Physical activity over a decade modifies age-related decline in perfusion, gray matter volume, and functional connectivity of the posterior default mode network: a multimodal approach2016Ingår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 131, s. 133-141Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    One step toward healthy brain aging may be to entertain a physically active lifestyle. Studies investigating physical activity effects on brain integrity have, however, mainly been based on single brain markers, and few used a multimodal imaging approach. In the present study, we used cohort data from the Betula study to examine the relationships between scores reflecting current and accumulated physical activity and brain health. More specifically, we first examined if physical activity scores modulated negative effects of age on seven resting state networks previously identified by Salami, Pudas, and Nyberg (2014). The results revealed that one of the most age-sensitive RSN was positively altered by physical activity, namely, the posterior default-mode network involving the posterior cingulate cortex (PCC). Second, within this physical activity-sensitive RSN, we further analyzed the association between physical activity and gray matter (GM) volumes, white matter integrity, and cerebral perfusion using linear regression models. Regions within the identified DMN displayed larger GM volumes and stronger perfusion in relation to both current and 10-years accumulated scores of physical activity. No associations of physical activity and white matter integrity were observed. Collectively, our findings demonstrate strengthened PCC–cortical connectivity within the DMN, larger PCC GM volume, and higher PCC perfusion as a function of physical activity. In turn, these findings may provide insights into the mechanisms of how long-term regular exercise can contribute to healthy brain aging.

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  • 28.
    Boraxbekk, Carl-Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Centrum för befolkningsstudier (CBS).
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Larsson, Christel
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Göteborgs Universitet.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Diet-Induced Weight Loss alters Functional Brain Responses during an Episodic Memory Task2015Ingår i: Obesity Facts, ISSN 1662-4025, E-ISSN 1662-4033, Vol. 8, s. 261-272Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. Methods: 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Results: Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Conclusions: Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity.

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  • 29.
    Burzynska, A Z
    et al.
    Max Planck Institute for Human Development, Berlin.
    Preuschhof, C
    Max Planck Institute for Human Development, Berlin.
    Bäckman, L
    Max Planck Institute for Human Development, Berlin, Karolinska Institute.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Li, S-C
    Max Planck Institute for Human Development, Berlin.
    Lindenberger, U
    Max Planck Institute for Human Development, Berlin, .
    Heekeren, H R
    Max Planck Institute for Human Development, Berlin, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig.
    Age-related differences in white matter microstructure: region-specific patterns of diffusivity.2010Ingår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 49, nr 3, s. 2104-2112Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We collected MRI diffusion tensor imaging data from 80 younger (20-32 years) and 63 older (60-71 years) healthy adults. Tract-based spatial statistics (TBSS) analysis revealed that white matter integrity, as indicated by decreased fractional anisotropy (FA), was disrupted in numerous structures in older compared to younger adults. These regions displayed five distinct region-specific patterns of age-related differences in other diffusivity properties: (1) increases in both radial and mean diffusivity; (2) increases in radial diffusivity; (3) no differences in parameters other than FA; (4) a decrease in axial and an increase in radial diffusivity; and (5) a decrease in axial and mean diffusivity. These patterns suggest different biological underpinnings of age-related decline in FA, such as demyelination, Wallerian degeneration, gliosis, and severe fiber loss, and may represent stages in a cascade of age-related degeneration in white matter microstructure. This first simultaneous description of age-related differences in FA, mean, axial, and radial diffusivity requires histological and functional validation as well as analyses of intermediate age groups and longitudinal samples.

  • 30. Bäckman, L
    et al.
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Linderiberger, U
    Li, SC
    Farde, L
    The correlative triad among aging, dopamine, and cognition: Current status and future prospects2006Ingår i: NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, ISSN 0149-7634, Vol. 30, nr 6, s. 791-807Artikel, forskningsöversikt (Övrig (populärvetenskap, debatt, mm))
  • 31.
    Bäckman, Lars
    et al.
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden.
    Karlsson, Sari
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden.
    Fischer, Håkan
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden.
    Karlsson, Per
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm, Sweden.
    Brehmer, Yvonne
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden.
    Rieckmann, Anna
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden.
    Macdonald, Stuart WS
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden; Department of Psychology, University of Victoria, Canada .
    Farde, Lars
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm, Sweden.
    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).
    Dopamine D(1) receptors and age differences in brain activation during working memory2011Ingår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 32, nr 10, s. 1849-1856Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In an fMRI study, 20 younger and 20 healthy older adults were scanned while performing a spatial working-memory task under two levels of load. On a separate occasion, the same subjects underwent PET measurements using the radioligand [(11)C] SCH23390 to determine dopamine D(1) receptor binding potential (BP) in caudate nucleus and dorsolateral prefrontal cortex (DLPFC). The fMRI study revealed a significant load modulation of brain activity (higher load>lower load) in frontal and parietal regions for younger, but not older, adults. The PET measurements showed marked age-related reductions of D(1) BP in caudate and DLPFC. Statistical control of caudate and DLPFC D(1) binding eliminated the age-related reduction in load-dependent BOLD signal in left frontal cortex, and attenuated greatly the reduction in right frontal and left parietal cortex. These findings suggest that age-related alterations in dopaminergic neurotransmission may contribute to underrecruitment of task-relevant brain regions during working-memory performance in old age.

  • 32. Bäckman, Lars
    et al.
    Lindenberger, Ulman
    Li, Shu-Chen
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Linking cognitive aging to alterations in dopamine neurotransmitter functioning: Recent data and future avenues2010Ingår i: Neuroscience and Biobehavioral Reviews, ISSN 0149-7634, E-ISSN 1873-7528, Vol. 34, nr 5, s. 670-677Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Molecular-imaging studies of dopaminergic neurotransmission measure biomarkers of dopamine (DA), such as the DA transporter and D(1) and D(2) receptor densities in the living brain. These studies indicate that individual differences in DA functions are linked to cognitive performance irrespective of age, and serve as powerful mediators of age-related decline in executive functioning, episodic memory, and perceptual speed. This focused review targets several recent findings pertaining to these relationships. Specifically, we discuss novel evidence concerning (a) the role of DA in within-person cognitive variability; (b) age-related differences in DA release during cognitive processing; (c) DA release following cognitive training in younger and older adults; and (d) the relationship between DA and task-induced functional brain activity. Based on these lines of empirical inquiry, we outline a series of avenues for future research on aging, DA, and cognition.

  • 33.
    Bäckman, Lars
    et al.
    Aging Research Center, Stockholm, Sweden.
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Farde, Lars
    Department of Clinical Neuroscience, Section of Psychiatry, Karolinska Institute, Stockholm, Sweden.
    Dopamine and cognitive aging: a strong relationship2006Ingår i: Progress in psychological science around the world. Volume 1 neural, cognitive and developmental issues: Proceedings of the 28th international congress of psychology / [ed] Qicheng Jing; Mark R. Rosenzweig; Gery d'Ydewalle; Houcan Zhang; Hsuan-Chih Chen; Kan Zhang, Psychology Press, 2006, s. 455-469Konferensbidrag (Refereegranskat)
  • 34. Bäckman, Lars
    et al.
    Nyberg, Lars
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Fysiologi.
    Lindenberger, Ulman
    Li, Shu-Chen
    Farde, Lars
    The correlative triad among aging, dopamine, and cognition: current status and future prospects.2006Ingår i: Neuroscience and Biobehavioral Review, ISSN 0149-7634, Vol. 30, nr 6, s. 791-807Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    The brain neuronal systems defined by the neurotransmitter dopamine (DA) have since long a recognized role in the regulation of motor functions. More recently, converging evidence from patient studies, animal research, pharmacological intervention, and molecular genetics indicates that DA is critically implicated also in higher-order cognitive functioning. Many cognitive functions and multiple markers of striatal and extrastriatal DA systems decline across adulthood and aging. Research examining the correlative triad among adult age, DA, and cognition has found strong support for the view that age-related DA losses are associated with age-related cognitive deficits. Future research strategies for examining the DA-cognitive aging link include assessing (a) the generality/specificity of the effects; (b) the relationship between neuromodulation and functional brain activation; and (c) the release of DA during actual task performance.

  • 35.
    Bäckman, Lars
    et al.
    Aging Research Center, Karolinska Institute, Stockholm, Sweden.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Soveri, Anna
    Department of Psychology and Logopedics, Åbo Akademi University, Turku, Finland.
    Johansson, Jarkko
    Turku PET Center, University of Turku, Turku, Finland.
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Dahlin, Erika
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Neely, Anna S
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Virta, Jere
    Turku PET Center, University of Turku, Turku, Finland.
    Laine, Matti
    Department of Psychology and Logopedics, Åbo Akademi University, Turku, Finland.
    Rinne, Juha O
    Turku PET Center, University of Turku, Turku, Finland.
    Effects of working-memory training on striatal dopamine release2011Ingår i: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 333, nr 6043, s. 718-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Updating of working memory has been associated with striato-frontal brain regions and phasic dopaminergic neurotransmission. We assessed raclopride binding to striatal dopamine (DA) D2 receptors during a letter-updating task and a control condition before and after 5 weeks of updating training. Results showed that updating affected DA activity before training and that training further increased striatal DA release during updating. These findings highlight the pivotal role of transient neural processes associated with D2 receptor activity in working memory.

  • 36. Bäckman, Lars
    et al.
    Waris, Otto
    Johansson, Jarkko
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Rinne, Juha O.
    Alakurtti, Kati
    Soveri, Anna
    Laine, Matti
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Increased dopamine release after working-memory updating training: Neurochemical correlates of transfer2017Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 7, artikel-id 7160Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous work demonstrates that working-memory (WM) updating training results in improved performance on a letter-memory criterion task, transfers to an untrained n-back task, and increases striatal dopamine (DA) activity during the criterion task. Here, we sought to replicate and extend these findings by also examining neurochemical correlates of transfer. Four positron emission tomography (PET) scans using the radioligand raclopride were performed. Two of these assessed DAD2 binding (letter memory; n-back) before 5 weeks of updating training, and the same two scans were performed post training. Key findings were (a) pronounced training-related behavioral gains in the lettermemory criterion task, (b) altered striatal DAD2 binding potential after training during letter-memory performance, suggesting training-induced increases in DA release, and (c) increased striatal DA activity also during the n-back transfer task after the intervention, but no concomitant behavioral transfer. The fact that the training-related DA alterations during the transfer task were not accompanied by behavioral transfer suggests that increased DA release may be a necessary, but not sufficient, condition for behavioral transfer to occur.

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  • 37. Cabeza, Roberto
    et al.
    Albert, Marilyn
    Belleville, Sylvie
    Craik, Fergus I. M.
    Duarte, Audrey
    Grady, Cheryl L.
    Lindenberger, Ulman
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Park, Denise C.
    Reuter-Lorenz, Patricia A.
    Rugg, Michael D.
    Steffener, Jason
    Rajah, M. Natasha
    Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing2018Ingår i: Nature Reviews Neuroscience, ISSN 1471-003X, E-ISSN 1471-0048, Vol. 19, nr 11, s. 701-710Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Cognitive ageing research examines the cognitive abilities that are preserved and/or those that decline with advanced age. There is great individual variability in cognitive ageing trajectories. Some older adults show little decline in cognitive ability compared with young adults and are thus termed ‘optimally ageing’. By contrast, others exhibit substantial cognitive decline and may develop dementia. Human neuroimaging research has led to a number of important advances in our understanding of the neural mechanisms underlying these two outcomes. However, interpreting the age-related changes and differences in brain structure, activation and functional connectivity that this research reveals is an ongoing challenge. Ambiguous terminology is a major source of difficulty in this venture. Three terms in particular — compensation, maintenance and reserve — have been used in a number of different ways, and researchers continue to disagree about the kinds of evidence or patterns of results that are required to interpret findings related to these concepts. As such inconsistencies can impede progress in both theoretical and empirical research, here, we aim to clarify and propose consensual definitions of these terms.

  • 38. Cabeza, Roberto
    et al.
    Albert, Marilyn
    Belleville, Sylvie
    Craik, Fergus I. M.
    Duarte, Audrey
    Grady, Cheryl L.
    Lindenberger, Ulman
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Park, Denise C.
    Reuter-Lorenz, Patricia A.
    Rugg, Michael D.
    Steffener, Jason
    Rajah, M. Natasha
    Reply to 'Mechanisms underlying resilience in ageing'2019Ingår i: Nature Reviews Neuroscience, ISSN 1471-003X, E-ISSN 1471-0048, Vol. 20, nr 4, s. 247-247Artikel i tidskrift (Refereegranskat)
  • 39. Cabeza, Roberto
    et al.
    Daselaar, Sander M
    Dolcos, Florin
    Prince, Steven E
    Budde, Matthew
    Nyberg, Lars
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Fysiologi. Umeå universitet, Samhällsvetenskaplig fakultet, Psykologi.
    Task-independent and task-specific age effects on brain activity during working memory, visual attention and episodic retrieval.2004Ingår i: Cerebral Cortex, ISSN 1047-3211, Vol. 14, nr 4, s. 364-75Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is controversial whether the effects of aging on various cognitive functions have the same common cause or several different causes. To investigate this issue, we scanned younger and older adults with functional magnetic resonance imaging (fMRI) while performing three different tasks: working memory, visual attention and episodic retrieval. There were three main results. First, in all three tasks, older adults showed weaker occipital activity and stronger prefrontal and parietal activity than younger adults. The occipital reduction is consistent with the view that sensory processing decline is a common cause in cognitive aging, and the prefrontal increase may reflect functional compensation. Secondly, older adults showed more bilateral patterns of prefrontal activity than younger adults during working memory and visual attention tasks. These findings are consistent with the Hemispheric Asymmetry Reduction in Older Adults (HAROLD) model. Finally, compared to younger adults, older adults showed weaker hippocampal formation activity in all three tasks but stronger parahippocampal activity in the episodic retrieval task. The former finding suggests that age-related hippocampal deficits may have a global effect in cognition, and the latter is consistent with an age-related increase in familiarity-based recognition. Taken together, the results indicate that both common and specific factors play an important role in cognitive aging.

  • 40. Cabeza, Roberto
    et al.
    Nyberg, LarsUmeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.Park, Denise
    Cognitive neuroscience of aging: linking cognitive and cerebral aging2005Samlingsverk (redaktörskap) (Övrigt vetenskapligt)
    Abstract [en]

    Until recently, the cognitive and neural mechanisms of age-related changes in cognition were usually studied independently of each other.

    On one hand, studies in the domain of cognitive psychology of aging investigated the effects of aging on behavioral measures of cognition and characterized a variety of age-related deficits in memory, attention, and the like. On the other hand, studies in the domain of neuroscience of aging investigated the effects of aging on the anatomy and physiology of the brain and described forms of age-related neural decline, such as cerebral atrophy and synaptic loss. Although it is reasonable to assume that cognitive aging is largely a consequence of cerebral aging, the relationships between these two phenomena are still largely unknown. Fortunately, this void is being rapidly resolved by studies focusing on the relationships between the effects of aging on the cognition and on the brain. This group of studies constitutes the new discipline of cognitive neuroscience of aging (CNA). Although CNA has a long past, only lately has it achieved the critical mass to be considered an autonomous discipline. The main goal of this book is to provide an introduction to this exciting new field.

  • 41. Córdova-Palomera, Aldo
    et al.
    van der Meer, Dennis
    Kaufmann, Tobias
    Bettella, Francesco
    Wang, Yunpeng
    Alnaes, Dag
    Doan, Nhat Trung
    Agartz, Ingrid
    Bertolino, Alessandro
    Buitelaar, Jan K.
    Coynel, David
    Djurovic, Srdjan
    Dørum, Erlend S.
    Espeseth, Thomas
    Fazio, Leonardo
    Franke, Barbara
    Frei, Oleksandr
    Håberg, Asta
    Le Hellard, Stephanie
    Jönsson, Erik G.
    Kolskår, Knut K.
    Lund, Martina J.
    Moberget, Torgeir
    Nordvik, Jan E.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Papassotiropoulos, Andreas
    Pergola, Giulio
    de Quervain, Dominique
    Rampino, Antonio
    Richard, Genevieve
    Rokicki, Jaroslav
    Sanders, Anne-Marthe
    Schwarz, Emanuel
    Smeland, Olav B.
    Steen, Vidar M.
    Starrfelt, Jostein
    Sønderby, Ida E.
    Ulrichsen, Kristine M.
    Andreassen, Ole A.
    Westlye, Lars T.
    Genetic control of variability in subcortical and intracranial volumes2021Ingår i: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 26, nr 8, s. 3876-3883Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sensitivity to external demands is essential for adaptation to dynamic environments, but comes at the cost of increased risk of adverse outcomes when facing poor environmental conditions. Here, we apply a novel methodology to perform genome-wide association analysis of mean and variance in ten key brain features (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, intracranial volume, cortical surface area, and cortical thickness), integrating genetic and neuroanatomical data from a large lifespan sample (n = 25,575 individuals; 8-89 years, mean age 51.9 years). We identify genetic loci associated with phenotypic variability in thalamus volume and cortical thickness. The variance-controlling loci involved genes with a documented role in brain and mental health and were not associated with the mean anatomical volumes. This proof-of-principle of the hypothesis of a genetic regulation of brain volume variability contributes to establishing the genetic basis of phenotypic variance (i.e., heritability), allows identifying different degrees of brain robustness across individuals, and opens new research avenues in the search for mechanisms controlling brain and mental health.

  • 42.
    Dahlin, Erika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Bäckman, Lars
    Aging Research Center, Karolinska institutet,Stockholm.
    Stigsdotter Neely, Anna
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Training of the executive component of working memory: subcortial areas mediate transfer effects2009Ingår i: Restorative Neurology and Neuroscience, ISSN 0922-6028, E-ISSN 1878-3627, Vol. 27, nr 5, s. 405-419Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Several recent studies show that training can improve working memory (WM) performance. In this review, many issues related to WM training, such as neural basis, transfer effects, and age-related changes are addressed.

    Method: We focus on our own studies investigating training on tasks taxing the executive updating function and discuss our findings in relation to results from other studies investigating training of the executive component of WM.

    Results: The review confirms positive behavioral effects of training on working memory. The most common neural pattern following training is fronto-parietal activity decreases. Increases in sub-cortical areas are also frequently reported after training, and we suggest that such increases indicate changes in the underlying skill following training. Transfer effects are in general difficult to demonstrate. Some studies show that older adults increase their performance after WM training. However, transfer effects are small or nonexistent in old age.

    Conclusions: The main finding in this review is that sub-cortical areas seem to have a critical role in mediating transfer effects to untrained tasks after at least some forms of working memory training (such as updating).

  • 43.
    Dahlin, Erika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Bäckman, Lars
    Stigsdotter Neely, Anna
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Plasticity of executive functioning in young and older adults: immediative training gains, transfer, and long-term maintenance2008Ingår i: Psychology and Aging, ISSN 0882-7974, E-ISSN 1939-1498, Vol. 23, nr 4, s. 720-730Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The authors investigated immediate training gains, transfer effects, and 18-month maintenance after 5 weeks of computer-based training in updating of information in working memory in young and older subjects. Trained young and older adults improved significantly more than controls on the criterion task (letter memory), and these gains were maintained 18 months later. Transfer effects were in general limited and restricted to the young participants, who showed transfer to an untrained task that required updating (3-back). The findings demonstrate substantial and durable plasticity of executive functioning across adulthood and old age, although there appear to be age-related constraints in the ability to generalize the acquired updating skill.

  • 44.
    Dahlin, Erika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Stigsdotter-Neely, Anna
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Bäckman, Lars
    Aging Research Center, Karolinska Institute, 11330 Stockholm, Sweden.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Transfer of learning after updating training mediated by the striatum2008Ingår i: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 320, nr 5882, s. 1510-1512Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Process-specific training can improve performance on untrained tasks, but the magnitude of gain is variable and often there is no transfer at all. We demonstrate transfer to a 3-back test of working memory after 5 weeks of training in updating. The transfer effect was based on a joint training-related activity increase for the criterion (letter memory) and transfer tasks in a striatal region that also was recruited pretraining. No transfer was observed to a task that did not engage updating and striatal regions, and age-related striatal changes imposed constraints on transfer. These findings indicate that transfer can occur if the criterion and transfer tasks engage specific overlapping processing components and brain regions.

  • 45. Davies, G.
    et al.
    Armstrong, N.
    Bis, J. C.
    Bressler, J.
    Chouraki, V.
    Giddaluru, S.
    Hofer, E.
    Ibrahim-Verbaas, C. A.
    Kirin, M.
    Lahti, J.
    van der Lee, S. J.
    Le Hellard, S.
    Liu, T.
    Marioni, R. E.
    Oldmeadow, C.
    Postmus, I.
    Smith, A. V.
    Smith, J. A.
    Thalamuthu, A.
    Thomson, R.
    Vitart, V.
    Wang, J.
    Yu, L.
    Zgaga, L.
    Zhao, W.
    Boxall, R.
    Harris, S. E.
    Hill, W. D.
    Liewald, D. C.
    Luciano, M.
    Adams, H.
    Ames, D.
    Amin, N.
    Amouyel, P.
    Assareh, A. A.
    Au, R.
    Becker, J. T.
    Beiser, A.
    Berr, C.
    Bertram, L.
    Boerwinkle, E.
    Buckley, B. M.
    Campbell, H.
    Corley, J.
    De Jager, P. L.
    Dufouil, C.
    Eriksson, J. G.
    Espeseth, T.
    Faul, J. D.
    Ford, I.
    Gottesman, R. F.
    Griswold, M. E.
    Gudnason, V.
    Harris, T. B.
    Heiss, G.
    Hofman, A.
    Holliday, E. G.
    Huffman, J.
    Kardia, S. L. R.
    Kochan, N.
    Knopman, D. S.
    Kwok, J. B.
    Lambert, J-C
    Lee, T.
    Li, G.
    Li, S-C
    Loitfelder, M.
    Lopez, O. L.
    Lundervold, A. J.
    Lundquist, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Mather, K. A.
    Mirza, S. S.
    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).
    Oostra, B. A.
    Palotie, A.
    Papenberg, G.
    Pattie, A.
    Petrovic, K.
    Polasek, O.
    Psaty, B. M.
    Redmond, P.
    Reppermund, S.
    Rotter, J. I.
    Schmidt, H.
    Schuur, M.
    Schofield, P. W.
    Scott, R. J.
    Steen, V. M.
    Stott, D. J.
    Van Swieten, J. C.
    Taylor, K. D.
    Trollor, J.
    Trompet, S.
    Uitterlinden, A. G.
    Weinstein, G.
    Widen, E.
    Windham, B. G.
    Jukema, J. W.
    Wright, A. F.
    Wright, M. J.
    Yang, Q.
    Amieva, H.
    Attia, J. R.
    Bennett, D. A.
    Brodaty, H.
    de Craen, A. J. M.
    Hayward, C.
    Ikram, M. A.
    Lindenberger, U.
    Nilsson, Lars-Göran
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). ARC, Karolinska Institutet, Stockholm.
    Porteous, D. J.
    Raikkonen, K.
    Reinvang, I.
    Rudan, I.
    Sachdev, P. S.
    Schmidt, R.
    Schofield, P. R.
    Srikanth, V.
    Starr, J. M.
    Turner, S. T.
    Weir, D. R.
    Wilson, J. F.
    Van Duijn, C.
    Launer, L.
    Fitzpatrick, A. L.
    Seshadri, S.
    Jr, T. H. Mosley
    Deary, I. J.
    Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)2015Ingår i: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 20, nr 2, s. 183-192Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health-and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N = 53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P = 3.93 x 10(-9), MIR2113; rs17522122, P = 2.55 x 10(-8), AKAP6; rs10119, P = 5.67 x 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P = 1x10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N = 6617) and the Health and Retirement Study (N = 5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e. = 5%) and 28% (s.e. = 7%), respectively. Using polygenic prediction analysis, similar to 1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N = 5487; P = 1.5 x 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

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  • 46. Davies, Gail
    et al.
    Lam, Max
    Harris, Sarah E.
    Trampush, Joey W.
    Luciano, Michelle
    Hill, W. David
    Hagenaars, Saskia P.
    Ritchie, Stuart J.
    Marioni, Riccardo E.
    Fawns-Ritchie, Chloe
    Liewald, David C. M.
    Okely, Judith A.
    Ahola-Olli, Ari V.
    Barnes, Catriona L. K.
    Bertram, Lars
    Bis, Joshua C.
    Burdick, Katherine E.
    Christoforou, Andrea
    DeRosse, Pamela
    Djurovic, Srdjan
    Espeseth, Thomas
    Giakoumaki, Stella
    Giddaluru, Sudheer
    Gustavson, Daniel E.
    Hayward, Caroline
    Hofer, Edith
    Ikram, M. Arfan
    Karlsson, Robert
    Knowles, Emma
    Lahti, Jari
    Leber, Markus
    Li, Shuo
    Mather, Karen A.
    Melle, Ingrid
    Morris, Derek
    Oldmeadow, Christopher
    Palviainen, Teemu
    Payton, Antony
    Pazoki, Raha
    Petrovic, Katja
    Reynolds, Chandra A.
    Sargurupremraj, Muralidharan
    Scholz, Markus
    Smith, Jennifer A.
    Smith, Albert V.
    Terzikhan, Natalie
    Thalamuthu, Anbupalam
    Trompet, Stella
    van der Lee, Sven J.
    Ware, Erin B.
    Windham, B. Gwen
    Wright, Margaret J.
    Yang, Jingyun
    Yu, Jin
    Ames, David
    Amin, Najaf
    Amouyel, Philippe
    Andreassen, Ole A.
    Armstrong, Nicola J.
    Assareh, Amelia A.
    Attia, John R.
    Attix, Deborah
    Avramopoulos, Dimitrios
    Bennett, David A.
    Boehmer, Anne C.
    Boyle, Patricia A.
    Brodaty, Henry
    Campbell, Harry
    Cannon, Tyrone D.
    Cirulli, Elizabeth T.
    Congdon, Eliza
    Conley, Emily Drabant
    Corley, Janie
    Cox, Simon R.
    Dale, Anders M.
    Dehghan, Abbas
    Dick, Danielle
    Dickinson, Dwight
    Eriksson, Johan G.
    Evangelou, Evangelos
    Faul, Jessica D.
    Ford, Ian
    Freimer, Nelson A.
    Gao, He
    Giegling, Ina
    Gillespie, Nathan A.
    Gordon, Scott D.
    Gottesman, Rebecca F.
    Griswold, Michael E.
    Gudnason, Vilmundur
    Harris, Tamara B.
    Hartmann, Annette M.
    Hatzimanolis, Alex
    Heiss, Gerardo
    Holliday, Elizabeth G.
    Joshi, Peter K.
    Kahonen, Mika
    Kardia, Sharon L. R.
    Karlsson, Ida
    Kleineidam, Luca
    Knopman, David S.
    Kochan, Nicole A.
    Konte, Bettina
    Kwok, John B.
    Le Hellard, Stephanie
    Lee, Teresa
    Lehtimaki, Terho
    Li, Shu-Chen
    Liu, Tian
    Koini, Marisa
    London, Edythe
    Longstreth, Will T., Jr.
    Lopez, Oscar L.
    Loukola, Anu
    Luck, Tobias
    Lundervold, Astri J.
    Lundquist, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Lyytikainen, Leo-Pekka
    Martin, Nicholas G.
    Montgomery, Grant W.
    Murray, Alison D.
    Need, Anna C.
    Noordam, Raymond
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Ollier, William
    Papenberg, Goran
    Pattie, Alison
    Polasek, Ozren
    Poldrack, Russell A.
    Psaty, Bruce M.
    Reppermund, Simone
    Riedel-Heller, Steffi G.
    Rose, Richard J.
    Rotter, Jerome I.
    Roussos, Panos
    Rovio, Suvi P.
    Saba, Yasaman
    Sabb, Fred W.
    Sachdev, Perminder S.
    Satizabal, Claudia L.
    Schmid, Matthias
    Scott, Rodney J.
    Scult, Matthew A.
    Simino, Jeannette
    Slagboom, P. Eline
    Smyrnis, Nikolaos
    Soumare, Aicha
    Stefanis, Nikos C.
    Stott, David J.
    Straub, Richard E.
    Sundet, Kjetil
    Taylor, Adele M.
    Taylor, Kent D.
    Tzoulaki, Ioanna
    Tzourio, Christophe
    Uitterlinden, Andre
    Vitart, Veronique
    Voineskos, Aristotle N.
    Kaprio, Jaakko
    Wagner, Michael
    Wagner, Holger
    Weinhold, Leonie
    Wen, K. Hoyan
    Widen, Elisabeth
    Yang, Qiong
    Zhao, Wei
    Adams, Hieab H. H.
    Arking, Dan E.
    Bilder, Robert M.
    Bitsios, Panos
    Boerwinkle, Eric
    Chiba-Falek, Ornit
    Corvin, Aiden
    De Jager, Philip L.
    Debette, Stephanie
    Donohoe, Gary
    Elliott, Paul
    Fitzpatrick, Annette L.
    Gill, Michael
    Glahn, David C.
    Hagg, Sara
    Hansell, Narelle K.
    Hariri, Ahmad R.
    Ikram, M. Kamran
    Jukema, J. Wouter
    Vuoksimaa, Eero
    Keller, Matthew C.
    Kremen, William S.
    Launer, Lenore
    Lindenberger, Ulman
    Palotie, Aarno
    Pedersen, Nancy L.
    Pendleton, Neil
    Porteous, David J.
    Raikkonen, Katri
    Raitakari, Olli T.
    Ramirez, Alfredo
    Reinvang, Ivar
    Rudan, Igor
    Rujescu, Dan
    Schmidt, Reinhold
    Schmidt, Helena
    Schofield, Peter W.
    Schofield, Peter R.
    Starr, John M.
    Steen, Vidar M.
    Trollor, Julian N.
    Turner, Steven T.
    Van Duijn, Cornelia M.
    Villringer, Arno
    Weinberger, Daniel R.
    Weir, David R.
    Wilson, James F.
    Malhotra, Anil
    McIntosh, Andrew M.
    Gale, Catharine R.
    Seshadri, Sudha
    Mosley, Thomas H., Jr.
    Bressler, Jan
    Lencz, Todd
    Deary, Ian J.
    Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function2018Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 9, artikel-id 2098Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 x 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

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  • 47. de Boer, Lieke
    et al.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Chowdhury, Rumana
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Dolan, Raymond J.
    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.
    Backman, Lars
    Guitart-Masip, Marc
    Dorsal striatal dopamine D1 receptor availability predicts an instrumental bias in action learning2019Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 116, nr 1, s. 261-270Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Learning to act to obtain reward and inhibit to avoid punishment is easier compared with learning the opposite contingencies. This coupling of action and valence is often thought of as a Pavlovian bias, although recent research has shown it may also emerge through instrumental mechanisms. We measured this learning bias with a rewarded go/no-go task in 60 adults of different ages. Using computational modeling, we characterized the bias as being instrumental. To assess the role of endogenous dopamine (DA) in the expression of this bias, we quantified DA D1 receptor availability using positron emission tomography (PET) with the radioligand [11C]SCH23390. Using principal-component analysis on the binding potentials in a number of cortical and striatal regions of interest, we demonstrated that cortical, dorsal striatal, and ventral striatal areas provide independent sources of variance in DA D1 receptor availability. Interindividual variation in the dorsal striatal component was related to the strength of the instrumental bias during learning. These data suggest at least three anatomical sources of variance in DA D1 receptor availability separable using PET in humans, and we provide evidence that human dorsal striatal DA D1 receptors are involved in the modulation of instrumental learning biases.

  • 48. de Boer, Lieke
    et al.
    Axelsson, Jan
    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, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    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).
    Dayan, Peter
    Backman, Lars
    Guitart-Masip, Marc
    Attenuation of dopamine-modulated prefrontal value signals underlies probabilistic reward learning deficits in old age2017Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 6, artikel-id e2642Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Probabilistic reward learning is characterised by individual differences that become acute in aging. This may be due to age-related dopamine (DA) decline affecting neural processing in striatum, prefrontal cortex, or both. We examined this by administering a probabilistic reward learning task to younger and older adults, and combining computational modelling of behaviour, fMRI and PET measurements of DA D1 availability. We found that anticipatory value signals in ventromedial prefrontal cortex (vmPFC) were attenuated in older adults. The strength of this signal predicted performance beyond age and was modulated by D1 availability in nucleus accumbens. These results uncover that a value-anticipation mechanism in vmPFC declines in aging, and that this mechanism is associated with DA D1 receptor availability.

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  • 49. de Boer, Lieke
    et al.
    Garzón, Benjamín
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Department of Radiation Sciences, Diagnostic Radiology, University Hospital, Umeå University, Umeå, Sweden.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Department of Radiation Sciences, Diagnostic Radiology, University Hospital, Umeå University, Umeå, Sweden.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Department of Radiation Sciences, Diagnostic Radiology, University Hospital, Umeå University, Umeå, Sweden.
    Bäckman, Lars
    Guitart-Masip, Marc
    Corticostriatal White Matter Integrity and Dopamine D1 Receptor Availability Predict Age Differences in Prefrontal Value Signaling during Reward Learning2020Ingår i: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 30, nr 10, s. 5270-5280Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Probabilistic reward learning reflects the ability to adapt choices based on probabilistic feedback. The dopaminergically innervated corticostriatal circuit in the brain plays an important role in supporting successful probabilistic reward learning. Several components of the corticostriatal circuit deteriorate with age, as it does probabilistic reward learning. We showed previously that D1 receptor availability in NAcc predicts the strength of anticipatory value signaling in vmPFC, a neural correlate of probabilistic learning that is attenuated in older participants and predicts probabilistic reward learning performance. We investigated how white matter integrity in the pathway between nucleus accumbens (NAcc) and ventromedial prefrontal cortex (vmPFC) relates to the strength of anticipatory value signaling in vmPFC in younger and older participants. We found that in a sample of 22 old and 23 young participants, fractional anisotropy in the pathway between NAcc and vmPFC predicted the strength of value signaling in vmPFC independently from D1 receptor availability in NAcc. These findings provide tentative evidence that integrity in the dopaminergic and white matter pathways of corticostriatal circuitry supports the expression of value signaling in vmPFC which supports reward learning, however, the limited sample size calls for independent replication. These and future findings could add to the improved understanding of how corticostriatal integrity contributes to reward learning ability.

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  • 50.
    de Frias, Cindy M
    et al.
    Stockholm University.
    Marklund, Petter
    Stockholm University, Stockholm Brain Institute.
    Eriksson, Elias
    Göteborg University.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Öman, Lena
    Umeå universitet.
    Annerbrink, Kristina
    Göteborg University.
    Bäckman, Lars
    Karolinska Institute.
    Nilsson, Lars-Göran
    Stockholm University.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Influence of COMT gene polymorphism on fMRI-assessed sustained and transient activity during a working memory task.2010Ingår i: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 22, nr 7, s. 1614-1622Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The catechol O-methyltransferase (COMT) gene--encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)--contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic-phasic hypothesis, individuals carrying the low-enzyme-activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic-phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, matched on age, education, and cognitive performance. There were no differences in 2-back performance between genotype groups. Met carriers displayed a greater transient medial temporal lobe response in the updating phase of working memory, whereas val carriers showed a greater sustained PFC activation in the maintenance phase. These results support the tonic-phasic theory of DA function in elucidating the specific phenotypic influence of the COMT val(158)met polymorphism on different components of working memory.

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