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1.
  • Papenberg, Goran, et al. (författare)
  • Mapping the landscape of human dopamine D2/3 receptors with [11C]raclopride
  • 2019
  • Ingår i: Brain Structure and Function. - 1863-2653 .- 1863-2661. ; 224:8, s. 2871-2882
  • Tidskriftsartikel (refereegranskat)abstract
    • The dopamine D2/3 system is fundamental for sensory, motor, emotional, and cognitive aspects of behavior. Small-scale human histopathological and animal studies show high density of D2/3 dopamine receptors (D2/3DR) in striatum, but also demonstrate the existence of such receptors across cortical and limbic regions. Assessment of D2/3DR BPND in the extrastriatal regions with [C-11]raclopride has long been considered unreliable due to the relatively low density of D2/3DR outside the striatum. We describe the distribution and interregional links of D2/3DR availability measured with PET and [C-11]raclopride across the human brain in a large sample (N = 176; age range 64-68 years). Structural equation modeling revealed that D2/3DR availability can be organized according to anatomical (nigrostriatal, mesolimbic, mesocortical) and functional (limbic, associative, sensorimotor) dopamine pathways. D2/3DR availability in corticolimbic functional subdivisions showed differential associations to corresponding striatal subdivisions, extending animal and pharmacological work. Our findings provide evidence on the dimensionality and organization of [C-11]raclopride D2/3DR availability in the living human brain that conforms to known dopaminergic pathways.
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2.
  • Salami, Alireza, et al. (författare)
  • Dopamine D2/3 Binding Potential Modulates Neural Signatures of Working Memory in a Load-Dependent Fashion.
  • 2019
  • Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 39:3, s. 537-547
  • Tidskriftsartikel (refereegranskat)abstract
    • Dopamine (DA) modulates corticostriatal connections. Studies in which imaging of the DA system is integrated with functional imaging during cognitive performance have yielded mixed findings. Some work has shown a link between striatal DA (measured by PET) and fMRI activations, whereas others have failed to observe such a relationship. One possible reason for these discrepant findings is differences in task demands, such that a more demanding task with greater prefrontal activations may yield a stronger association with DA. Moreover, a potential DA–BOLD association may be modulated by task performance. We studied 155 (104 normal-performing and 51 low-performing) healthy older adults (43% females) who underwent fMRI scanning while performing a working memory (WM) n-back task along with DA D2/3 PET assessment using [11C]raclopride. Using multivariate partial-least-squares analysis, we observed a significant pattern revealing positive associations of striatal as well as extrastriatal DA D2/3 receptors to BOLD response in the thalamo–striatal–cortical circuit, which supports WM functioning. Critically, the DA–BOLD association in normal-performing, but not low-performing, individuals was expressed in a load-dependent fashion, with stronger associations during 3-back than 1-/2-back conditions. Moreover, normal-performing adults expressing upregulated BOLD in response to increasing task demands showed a stronger DA–BOLD association during 3-back, whereas low-performing individuals expressed a stronger association during 2-back conditions. This pattern suggests a nonlinear DA–BOLD performance association, with the strongest link at the maximum capacity level. Together, our results suggest that DA may have a stronger impact on functional brain responses during more demanding cognitive tasks.
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3.
  • Thompson, Paul M., et al. (författare)
  • The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
  • 2014
  • Ingår i: BRAIN IMAGING BEHAV. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
  • Tidskriftsartikel (refereegranskat)abstract
    • The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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4.
  • de Boer, Lieke, et al. (författare)
  • Corticostriatal White Matter Integrity and Dopamine D1 Receptor Availability Predict Age Differences in Prefrontal Value Signaling during Reward Learning
  • 2020
  • Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 30:10, s. 5270-5280
  • Tidskriftsartikel (refereegranskat)abstract
    • 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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5.
  • Dima, Danai, et al. (författare)
  • Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3–90 years
  • 2021
  • Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193.
  • Tidskriftsartikel (refereegranskat)abstract
    • Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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6.
  • Elvsåshagen, Torbjørn, et al. (författare)
  • The genetic architecture of human brainstem structures and their involvement in common brain disorders
  • 2020
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723 .- 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders. The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.
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7.
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8.
  • Karalija, Nina, 1984-, et al. (författare)
  • Cardiovascular factors are related to dopamine integrity and cognition in aging
  • 2019
  • Ingår i: Annals of Clinical and Translational Neurology. - : Wiley-Blackwell. - 2328-9503. ; 6:11, s. 2291-2303
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aging brain undergoes several changes, including reduced vascular, structural, and dopamine (DA) system integrity. Such brain changes have been associated with age‐related cognitive deficits. However, their relative importance, interrelations, and links to risk factors remain elusive.Methods: The present work used magnetic resonance imaging and positron emission tomography with 11C‐raclopride to jointly examine vascular parameters (white‐matter lesions and perfusion), DA D2‐receptor availability, brain structure, and cognitive performance in healthy older adults (n = 181, age: 64–68 years) from the Cognition, Brain, and Aging (COBRA) study.Results: Covariance was found among several brain indicators, where top predictors of cognitive performance included caudate and hippocampal integrity (D2DR availability and volumes), and cortical blood flow and regional volumes. White‐matter lesion burden was negatively correlated with caudate DA D2‐receptor availability and white‐matter microstructure. Compared to individuals with smaller lesions, individuals with confluent lesions (exceeding 20 mm in diameter) had reductions in cortical and hippocampal perfusion, striatal and hippocampal D2‐receptor availability, white‐matter microstructure, and reduced performance on tests of episodic memory, sequence learning, and processing speed. Higher cardiovascular risk as assessed by treatment for hypertension, systolic blood pressure, overweight, and smoking was associated with lower frontal cortical perfusion, lower putaminal D2DR availability, smaller grey‐matter volumes, a larger number of white‐matter lesions, and lower episodic memory performance.Interpretation: Taken together, these findings suggest that reduced cardiovascular health is associated with poorer status for brain variables that are central to age‐sensitive cognitive functions, with emphasis on DA integrity.
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9.
  • Karalija, Nina, 1984-, et al. (författare)
  • Sex differences in dopamine integrity and brain structure among healthy older adults : Relationships to episodic memory
  • 2021
  • Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 105, s. 272-279
  • Tidskriftsartikel (refereegranskat)abstract
    • Normal brain aging is a multidimensional process that includes deterioration in various brain structures and functions, with large heterogeneity in patterns and rates of decline. Sex differences have been reported for various cognitive and brain parameters, but little is known in relation to neuromodulatory aspects of brain aging. We examined sex differences in dopamine D2-receptor (D2DR) availability in relation to episodic memory, but also, grey-matter volumes, white-matter lesions, and cerebral perfusion in healthy older adults (n = 181, age: 64-68 years) from the Cognition, Brain, and Aging study. Women had higher D2DR availability in midbrain and left caudate and putamen, as well as superior episodic memory performance. Controlling for left caudate D2DR availability attenuated sex differences in memory performance. In men, lower left caudate D2DR levels were associated with lower cortical perfusion and higher burden of white-matter lesions, as well as with episodic memory performance. However, sex was not a significant moderator of the reported links to D2DR levels. Our findings suggest that sex differences in multiple associations among DA receptor availability, vascular factors, and structural connectivity contribute to sex differences in episodic memory. Future longitudinal studies need to corroborate these patterns by lead-lag associations. This manuscript is part of the Special Issue entitled 'Cognitive Neuroscience of Healthy and Pathological Aging' edited by Drs. M. N. Rajah, S. Belleville, and R. Cabeza. 
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10.
  • Kaufmann, Tobias, et al. (författare)
  • Common brain disorders are associated with heritable patterns of apparent aging of the brain
  • 2019
  • Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
  • Tidskriftsartikel (refereegranskat)abstract
    • Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
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