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  • 1.
    Becker, Nina
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Max Planck Institute for Human Development, Germany.
    Kalpouzos, Grégoria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Laukka, Erika J.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Brehmer, Yvonne
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Max Planck Institute for Human Development, Germany.
    Differential Effects of Encoding Instructions on Brain Activity Patterns of Item and Associative Memory2017In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 29, no 3, p. 545-559Article in journal (Refereed)
    Abstract [en]

    Evidence from neuroimaging studies suggests a critical role of hippocampus and inferior frontal gyrus (IFG) in associative relative to item encoding. Here, we investigated similarities and differences in functional brain correlates for associative and item memory as a function of encoding instruction. Participants received either incidental (animacy judgments) or intentional encoding instructions while fMRI was employed during the encoding of associations and items. In a subsequent recognition task, memory performance of participants receiving intentional encoding instructions was higher compared with those receiving incidental encoding instructions. Furthermore, participants remembered more items than associations, regardless of encoding instruction. Greater brain activation in the left anterior hippocampus was observed for intentionally compared with incidentally encoded associations, although activity in this region was not modulated by the type of instruction for encoded items. Furthermore, greater activity in the left anterior hippocampus and left IFG was observed during intentional associative compared with item encoding. The same regions were related to subsequent memory of intentionally encoded associations and were thus task relevant. Similarly, connectivity of the anterior hippocampus to the right superior temporal lobe and IFG was uniquely linked to subsequent memory of intentionally encoded associations. Our study demonstrates the differential involvement of anterior hippocampus in intentional relative to incidental associative encoding. This finding likely reflects that the intent to remember triggers a specific binding process accomplished by this region.

  • 2.
    de Frias, Cindy M.
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Marklund, Petter
    Eriksson, Elias
    Larsson, Anne
    Öman, Lena
    Annerbrink, Kristina
    Bäckman, Lars
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Influence of COMT Gene Polymorphism on fMRI-assessed Sustained and Transient Activity during a Working Memory Task2010In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 22, no 7, p. 1614-1622Article in journal (Refereed)
    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.

  • 3. Karalija, Nina
    et al.
    Papenberg, Goran
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wåhlin, Anders
    Johansson, Jarkko
    Andersson, Micael
    Axelsson, Jan
    Riklund, Katrine
    Lövdén, Martin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lindenberger, Ulman
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Nyberg, Lars
    C957T-mediated Variation in Ligand Affinity Affects the Association between C-11-raclopride Binding Potential and Cognition2019In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 31, no 2, p. 314-325Article in journal (Refereed)
    Abstract [en]

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

  • 4.
    Kühn, Simone
    et al.
    Ghent University, Belgium; University College London, UK.
    Schmiedek, Florian
    Max Planck Institute for Human Development, Berlin, Germany; German Institute for International Educational Research, Frankfurt am Main, Germany.
    Schott, Björn
    Otto-von-Guericke University Magdeburg, Germany; Charité University Medecine, Berlin.
    Ratcliff, Roger
    Ohio State University, Columbus.
    Heinze, Hans-Jochen
    Otto-von-Guericke University Magdeburg, Germany.
    Düzel, Emrah
    University College London, UK; Otto-von-Guericke University Magdeburg, Germany.
    Lindenberger, Ulman
    Max Planck Institute for Human Development, Berlin, Germany.
    Lövden, Martin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Brain areas consistently linked to individual differences in perceptual decision-making in younger as well as older adults before and after training2011In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 23, no 9, p. 2147-2158Article in journal (Refereed)
    Abstract [en]

    Perceptual decision-making performance depends on several cognitive and neural processes. Here, we fit Ratcliff's diffusion model to accuracy data and reaction-time distributions from one numerical and one verbal two-choice perceptual-decision task to deconstruct these performance measures into the rate of evidence accumulation (i.e., drift rate), response criterion setting (i.e., boundary separation), and peripheral aspects of performance (i.e., nondecision time). These theoretical processes are then related to individual differences in brain activation by means of multiple regression. The sample consisted of 24 younger and 15 older adults performing the task in fMRI before and after 100 daily 1-hr behavioral training sessions in a multitude of cognitive tasks. Results showed that individual differences in boundary separation were related to striatal activity, whereas differences in drift rate were related to activity in the inferior parietal lobe. These associations were not significantly modified by adult age or perceptual expertise. We conclude that the striatum is involved in regulating response thresholds, whereas the inferior parietal lobe might represent decision-making evidence related to letters and numbers.

  • 5.
    Lebedev, Alexander V.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Nilsson, Jonna
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lövdén, Martin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Working Memory and Reasoning Benefit from Different Modes of Large-scale Brain Dynamics in Healthy Older Adults2018In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 30, no 7, p. 1033-1046Article in journal (Refereed)
    Abstract [en]

    Researchers have proposed that solving complex reasoning problems, a key indicator of fluid intelligence, involves the same cognitive processes as solving working memory tasks. This proposal is supported by an overlap of the functional brain activations associated with the two types of tasks and by high correlations between interindividual differences in performance. We replicated these findings in 53 older participants but also showed that solving reasoning and working memory problems benefits from different configurations of the functional connectome and that this dissimilarity increases with a higher difficulty load. Specifically, superior performance in a typical working memory paradigm (n-back) was associated with upregulation of modularity (increased between-network segregation), whereas performance in the reasoning task was associated with effective downregulation of modularity. We also showed that working memory training promotes task-invariant increases in modularity. Because superior reasoning performance is associated with downregulation of modular dynamics, training may thus have fostered an inefficient way of solving the reasoning tasks. This could help explain why working memory training does little to promote complex reasoning performance. The study concludes that complex reasoning abilities cannot be reduced to working memory and suggests the need to reconsider the feasibility of using working memory training interventions to attempt to achieve effects that transfer to broader cognition.

  • 6. Li, Shu-Chen
    et al.
    Chicherio, Christian
    Nyberg, Lars
    von Oertzen, Timo
    Nagel, Irene E
    Papenberg, Goran
    Sander, Thomas
    Heekeren, Hauke R
    Lindenberger, Ulman
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Ebbinghaus revisited: influences of the BDNF Val66Met polymorphism on backward serial recall are modulated by human aging2010In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 22, no 10, p. 2164-2173Article in journal (Refereed)
    Abstract [en]

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

  • 7.
    Lundqvist, Mikael
    et al.
    Stockholm University, Faculty of Science, Numerical Analysis and Computer Science (NADA).
    Herman, Pawel
    Stockholm University, Faculty of Science, Numerical Analysis and Computer Science (NADA).
    Lansner, Anders
    Stockholm University, Faculty of Science, Numerical Analysis and Computer Science (NADA).
    Theta and Gamma Power Increases and Alpha/Beta Power Decreases with Memory Load in an Attractor Network Model2010In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 23, no 10, p. 3008-3020Article in journal (Refereed)
    Abstract [en]

    Changes in oscillatory brain activity are strongly correlated with performance in cognitive tasks and modulations in specific frequency bands are associated with working memory tasks. Mesoscale network models allow the study of oscillations as an emergent feature of neuronal activity. Here we extend a previously developed attractor network model, shown to faithfully reproduce single-cell activity during retention and memory recall, with synaptic augmentation. This enables the network to function as a multi-item working memory by cyclic reactivation of up to six items. The reactivation happens at theta frequency, consistently with recent experimental findings, with increasing theta power for each additional item loaded in the network's memory. Furthermore, each memory reactivation is associated with gamma oscillations. Thus, single-cell spike trains as well as gamma oscillations in local groups are nested in the theta cycle. The network also exhibits an idling rhythm in the alpha/beta band associated with a noncoding global attractor. Put together, the resulting effect is increasing theta and gamma power and decreasing alpha/beta power with growing working memory load, rendering the network mechanisms involved a plausible explanation for this often reported behavior.

  • 8. Nagel, Irene E
    et al.
    Preuschhof, Claudia
    Li, Shu-Chen
    Nyberg, Lars
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lindenberger, Ulman
    Heekeren, Hauke R
    Load modulation of BOLD response and connectivity predicts working memory performance in younger and older adults2011In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 23, no 8, p. 2030-2045Article in journal (Refereed)
    Abstract [en]

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

  • 9. Nyberg, Lars
    et al.
    Andersson, Micael
    Kauppi, Karolina
    Lundquist, Anders
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Karolinska Institute, Sweden; Stockholm Brain Institute, Sweden; Umeå center for Functional Brain Imaging, Sweden.
    Pudas, Sara
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm Brain Institute, Sweden; Umeå center for Functional Brain Imaging, Sweden.
    Age-related and Genetic Modulation of Frontal Cortex Efficiency2014In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 26, no 4, p. 746-754Article in journal (Refereed)
    Abstract [en]

    The dorsolateral pFC (DLPFC) is a key region for working memory. It has been proposed that the DLPFC is dynamically recruited depending on task demands. By this view, high DLPFC recruitment for low-demanding tasks along with weak DLPFC upregulation at higher task demands reflects low efficiency. Here, the fMRI BOLD signal during working memory maintenance and manipulation was examined in relation to aging and catechol-O-methyltransferase (COMT) Val(158)Met status in a large representative sample (n = 287). The efficiency hypothesis predicts a weaker DLPFC response during manipulation, along with a stronger response during maintenance for older adults and COMT Val carriers compared with younger adults and COMT Met carriers. Consistent with the hypothesis, younger adults and met carriers showed maximal DLPFC BOLD response during manipulation, whereas older adults and val carriers displayed elevated DLPFC responses during the less demanding maintenance condition. The observed inverted relations support a link between dopamine and DLPFC efficiency.

  • 10.
    Papenberg, Goran
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Nagel, Irene E.
    Nietfeld, Wilfried
    Schröder, Julia
    Bertram, Lars
    Heekeren, Hauke R.
    Lindenberger, Ulman
    Li, Shu-Chen
    Dopaminergic Gene Polymorphisms Affect Long-term Forgetting in Old Age: Further Support for the Magnification Hypothesis2013In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 25, no 4, p. 571-579Article in journal (Refereed)
    Abstract [en]

    Emerging evidence from animal studies suggests that suboptimal dopamine (DA) modulation may be associated with increased forgetting of episodic information. Extending these observations, we investigated the influence of DA-relevant genes on forgetting in samples of younger (n = 433, 20–31 years) and older (n = 690, 59–71 years) adults. The effects of single nucleotide polymorphisms of the DA D2 (DRD2) and D3 (DRD3) receptor genes as well as the DA transporter gene (DAT1; SLC6A3) were examined. Over the course of one week, older adults carrying two or three genotypes associated with higher DA signaling (i.e., higher availability of DA and DA receptors) forgot less pictorial information than older individuals carrying only one or no beneficial genotype. No such genetic effects were found in younger adults. The results are consistent with the view that genetic effects on cognition are magnified in old age. To the best of our knowledge, this is the first report to relate genotypes associated with suboptimal DA modulation to more long-term forgetting in humans. Independent replication studies in other populations are needed to confirm the observed association.

  • 11.
    Papenberg, Goran
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Karalija, Nina
    Salami, Alireza
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Umeå University, Sweden.
    Andersson, Micael
    Axelsson, Jan
    Riklund, Katrine
    Lindenberger, Ulman
    Nyberg, Lars
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    The Influence of Hippocampal Dopamine D2 Receptors on Episodic Memory Is Modulated by BDNF and KIBRA Polymorphisms2019In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 31, no 9, p. 1422-1429Article in journal (Refereed)
    Abstract [en]

    Episodic memory is a polygenic trait influenced by different molecular mechanisms. We used PET and a candidate gene approach to investigate how individual differences at the molecular level translate into between-person differences in episodic memory performance of elderly persons. Specifically, we examined the interactive effects between hippocampal dopamine D2 receptor (D2DR) availability and candidate genes relevant for hippocampus-related memory functioning. We show that the positive effects of high D2DR availability in the hippocampus on episodic memory are confined to carriers of advantageous genotypes of the brain-derived neurotrophic factor (BDNF, rs6265) and the kidney and brain expressed protein (KIBRA, rs17070145) polymorphisms. By contrast, these polymorphisms did not modulate the positive relationship between caudate D2DR availability and episodic memory.

  • 12.
    Papenberg, Göran
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Becker, Nina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Max Planck Institute for Human Development, Germany.
    Ferencz, Beata
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Naveh-Benjamin, Moshe
    Laukka, Erika J.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Brehmer, Yvonne
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Max Planck Institute for Human Development, Germany.
    Dopamine Receptor Genes Modulate Associative Memory in Old Age2017In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 29, no 2, p. 245-253Article in journal (Refereed)
    Abstract [en]

    Previous research shows that associative memory declines more than item memory in aging. Although the underlying mechanisms of this selective impairment remain poorly understood, animal and human data suggest that dopaminergic modulation may be particularly relevant for associative binding. We investigated the influence of dopamine (DA) receptor genes on item and associative memory in a population-based sample of older adults (n = 525, aged 60 years), assessed with a face-scene item associative memory task. The effects of single-nucleotide polymorphisms of DA D1 (DRD1; rs4532), D2 (DRD2/ANKK1/Taq1A; rs1800497), and D3 (DRD3/Ser9Gly; rs6280) receptor genes were examined and combined into a single genetic score. Individuals carrying more beneficial alleles, presumably associated with higher DA receptor efficacy (DRD1 C allele; DRD2 A2 allele; DRD3 T allele), performed better on associative memory than persons with less beneficial genotypes. There were no effects of these genes on item memory or other cognitive measures, such as working memory, executive functioning, fluency, and perceptual speed, indicating a selective association between DA genes and associative memory. By contrast, genetic risk for Alzheimer disease (AD) was associated with worse item and associative memory, indicating adverse effects of APOE epsilon 4 and a genetic risk score for AD (PICALM, BIN1, CLU) on episodic memory in general. Taken together, our results suggest that DA may be particularly important for associative memory, whereas AD-related genetic variations may influence overall episodic memory in older adults without dementia.

  • 13.
    Persson, Jonas
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Larsson, Anne
    Reuter-Lorenz, Patricia A.
    Imaging Fatigue of Interference Control Reveals the Neural Basis of Executive Resource Depletion2013In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 25, no 3, p. 338-351Article in journal (Refereed)
    Abstract [en]

    Executive control coordinates, prioritizes, and selects task-relevant representations under conditions of conflict. Behavioral evidence has documented that executive resources are separable, finite, and can be temporarily depleted; however, the neural basis for such resource limits are largely unknown. Here, we investigate the neural correlates underlying the fatigue or depletion of interference control, an executive process hypothesized to mediate competition among competing memory representations. Using a pre/post continuous acquisition fMRI design, we demonstrate that, compared with a nondepletion control group, the depletion group showed a fatigue-induced performance deficit that was specific to interference control and accompanied by a left-to-right shift in the network of active regions. Specifically, we observed decreased BOLD signal in the left inferior frontal gyrus (IFG), striatum, and the cerebellum, along with a corresponding increase in right hemisphere regions including the IFG, insular, and temporal cortex. Depletion-related changes in activation magnitude correlated with behavioral changes, suggesting that decreased recruitment of task-relevant regions, including left IFG, contributes to impaired interference control. These results provide new evidence about the brain dynamics of "process-specific" fatigue and suggest that depletion may pose a significant limitation on the cognitive and neural resources available for executive control.

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