umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Andersson, Micael
Alternative names
Publications (10 of 32) Show all publications
Karalija, N., Papenberg, G., Wåhlin, A., Johansson, J., Andersson, M., Axelsson, J., . . . Nyberg, L. (2019). C957T-mediated Variation in Ligand Affinity Affects the Association between C-11-raclopride Binding Potential and Cognition. Journal of cognitive neuroscience, 31(2), 314-325
Open this publication in new window or tab >>C957T-mediated Variation in Ligand Affinity Affects the Association between C-11-raclopride Binding Potential and Cognition
Show others...
2019 (English)In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 31, no 2, p. 314-325Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
MIT Press, 2019
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-155630 (URN)10.1162/jocn_a_01354 (DOI)000454429400011 ()30407135 (PubMedID)
Funder
Swedish Research CouncilKnut and Alice Wallenberg FoundationRagnar Söderbergs stiftelseTorsten Söderbergs stiftelseThe Swedish Brain FoundationVästerbotten County Council
Available from: 2019-01-28 Created: 2019-01-28 Last updated: 2019-01-28Bibliographically approved
Karalija, N., Wåhlin, A., Ek, J., Rieckmann, A., Papenberg, G., Salami, A., . . . Nyberg, L. (2019). Cardiovascular factors are related to dopamine integrity and cognition in aging. Annals of clinical and translational neurology, 6(11), 2291-2303
Open this publication in new window or tab >>Cardiovascular factors are related to dopamine integrity and cognition in aging
Show others...
2019 (English)In: Annals of clinical and translational neurology, E-ISSN 2328-9503, Vol. 6, no 11, p. 2291-2303Article in journal (Refereed) Published
Abstract [en]

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

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

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

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

Place, publisher, year, edition, pages
Wiley-Blackwell, 2019
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-165743 (URN)10.1002/acn3.50927 (DOI)000496520700016 ()31663685 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationTorsten Söderbergs stiftelseRagnar Söderbergs stiftelseThe Swedish Brain FoundationVästerbotten County CouncilMax Planck SocietySwedish Research Council
Available from: 2019-12-10 Created: 2019-12-10 Last updated: 2019-12-10Bibliographically approved
Salami, A., Garrett, D. D., Wåhlin, A., Rieckmann, A., Papenberg, G., Karalija, N., . . . Nyberg, L. (2019). Dopamine D2/3 Binding Potential Modulates Neural Signatures of Working Memory in a Load-Dependent Fashion.. Journal of Neuroscience, 39(3), 537-547
Open this publication in new window or tab >>Dopamine D2/3 Binding Potential Modulates Neural Signatures of Working Memory in a Load-Dependent Fashion.
Show others...
2019 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 39, no 3, p. 537-547Article in journal (Refereed) Published
Abstract [en]

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

Keywords
PET, aging, dopamine, fMRI, working memory
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-155492 (URN)10.1523/JNEUROSCI.1493-18.2018 (DOI)000455849400013 ()30478031 (PubMedID)
Funder
Swedish Research CouncilKnut and Alice Wallenberg FoundationTorsten Söderbergs stiftelseRagnar Söderbergs stiftelseThe Swedish Brain FoundationVästerbotten County Council
Available from: 2019-01-18 Created: 2019-01-18 Last updated: 2019-02-08Bibliographically approved
Nyberg, L., Andersson, M., Lundquist, A., Salami, A. & Wåhlin, A. (2019). Frontal Contribution to Hippocampal Hyperactivity During Memory Encoding in Aging. Frontiers in Molecular Neuroscience, 12, Article ID 229.
Open this publication in new window or tab >>Frontal Contribution to Hippocampal Hyperactivity During Memory Encoding in Aging
Show others...
2019 (English)In: Frontiers in Molecular Neuroscience, ISSN 1662-5099, Vol. 12, article id 229Article in journal (Refereed) Published
Abstract [en]

Hippocampal hypo- as well as hyper-activation have been reported during memory encoding in older individuals. Prefrontal cortex (PFC) provides top-down state signals to the hippocampus that bias its computation during memory encoding and retrieval, and disturbed top-down signals could contribute to hippocampal hyper-activation. Here, we used >500 cross-sectional and longitudinal observations from a face-name encoding-retrieval fMRI task to examine hippocampal hypo-and hyper-activation in aging. Age-related anterior hippocampal hypo-activation was observed during memory encoding. Next, older individuals who longitudinally dropped-out were compared with those who remained in the study. Older dropouts had lower memory performance and higher dementia risk, and hyper-activated right anterior and posterior hippocampus during memory encoding. During encoding, the dropouts also activated right prefrontal regions that instead were active during retrieval in younger and older remainers. Moreover, the dropouts showed altered frontal-hippocampal functional connectivity, notably elevated right PFC to anterior hippocampus (aHC) connectivity during encoding. In the context of a general pattern of age-related anterior hippocampal hypo-activation during encoding, these findings support a top-down contribution to paradoxically high anterior hippocampal activity in older dropouts who were at elevated risk of pathology.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019
Keywords
hippocampus, pattern completion bias, aging, episodic memory, cognitive control
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-164045 (URN)10.3389/fnmol.2019.00229 (DOI)000487635300001 ()
Available from: 2019-10-15 Created: 2019-10-15 Last updated: 2019-10-15Bibliographically approved
Satizabal, C. L., Adams, H. H. H., Hibar, D. P., White, C. C., Knol, M. J., Stein, J. L., . . . Ikram, M. A. (2019). Genetic architecture of subcortical brain structures in 38,851 individuals. Nature Genetics, 51(11), 1624-+
Open this publication in new window or tab >>Genetic architecture of subcortical brain structures in 38,851 individuals
Show others...
2019 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 11, p. 1624-+Article in journal (Refereed) Published
Abstract [en]

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-166483 (URN)10.1038/s41588-019-0511-y (DOI)000494714300011 ()31636452 (PubMedID)
Funder
NIH (National Institute of Health), UL1 TR000153NIH (National Institute of Health), R03 AG054936NIH (National Institute of Health), NIH 1 U24 RR021992NIH (National Institute of Health), NIH 1 U24 RR025736-01NIH (National Institute of Health), C06RR029965NIH (National Institute of Health), K99MH102357NIH (National Institute of Health), 5R01MH094524NIH (National Institute of Health), P20GM103472NIH (National Institute of Health), R01MH117601NIH (National Institute of Health), R01MH111671NIH (National Institute of Health), K99MH116115NIH (National Institute of Health), AG047866NIH (National Institute of Health), R01AG059874NIH (National Institute of Health), AG058854NIH (National Institute of Health), R56 AG058854NIH (National Institute of Health), RF1 AG041915NIH (National Institute of Health), U01 AG024904NIH (National Institute of Health), P01 AG026572NIH (National Institute of Health), P30 AG010133NIH (National Institute of Health), R01 AG019771NIH (National Institute of Health), K01 AG049050NIH (National Institute of Health), R01 AG061788NIH (National Institute of Health), P30 AG10133NIH (National Institute of Health), R01AG033193NIH (National Institute of Health), R01AG050631NIH (National Institute of Health), U01AG046161NIH (National Institute of Health), R01AG053960
Available from: 2020-01-02 Created: 2020-01-02 Last updated: 2020-01-02Bibliographically approved
Papenberg, G., Jonasson, L. S., Karalija, N., Johansson, J., Koehncke, Y., Salami, A., . . . Backman, L. (2019). Mapping the landscape of human dopamine D2/3 receptors with [11C]raclopride. Brain Structure and Function, 224(8), 2871-2882
Open this publication in new window or tab >>Mapping the landscape of human dopamine D2/3 receptors with [11C]raclopride
Show others...
2019 (English)In: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 224, no 8, p. 2871-2882Article in journal (Refereed) Published
Abstract [en]

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

Keywords
[C-11]raclopride, Dopamine D2, 3 receptors, Inter-individual differences, Structural-equation deling, COBRA study
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-165669 (URN)10.1007/s00429-019-01938-1 (DOI)000489147300018 ()31444615 (PubMedID)
Available from: 2019-12-06 Created: 2019-12-06 Last updated: 2019-12-06Bibliographically approved
Papenberg, G., Karalija, N., Salami, A., Andersson, M., Axelsson, J., Riklund, K., . . . Bäckman, L. (2019). The Influence of Hippocampal Dopamine D2 Receptors on Episodic Memory Is Modulated by BDNF and KIBRA Polymorphisms. Journal of cognitive neuroscience, 31(9), 1422-1429
Open this publication in new window or tab >>The Influence of Hippocampal Dopamine D2 Receptors on Episodic Memory Is Modulated by BDNF and KIBRA Polymorphisms
Show others...
2019 (English)In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 31, no 9, p. 1422-1429Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
MIT Press, 2019
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-162391 (URN)10.1162/jocn_a_01429 (DOI)000477974100012 ()31112471 (PubMedID)2-s2.0-85070257740 (Scopus ID)
Available from: 2019-08-20 Created: 2019-08-20 Last updated: 2019-08-20Bibliographically approved
Sjöberg, R. L., Stålnacke, M., Andersson, M. & Eriksson, J. (2019). The supplementary motor area syndrome and cognitive control. Neuropsychologia, 129, 141-145
Open this publication in new window or tab >>The supplementary motor area syndrome and cognitive control
2019 (English)In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 129, p. 141-145Article in journal (Refereed) Published
Abstract [en]

The Supplementary Motor Area (SMA)-syndrome is a transient disturbance of the ability to initiate voluntary motor and speech actions that will often occur immediately after neurosurgical resections in the dorsal superior frontal gyrus but will typically have disappeared after 3 months. The purpose of the present study was to investigate the extent to which this syndrome is associated with alterations in cognitive control. Five patients who were to different extents affected by the SMA-syndrome after surgery for WHO grade II gliomas in the left hemisphere, were tested with the color word interference (Stroop) test; the Bergen dichotic listening test and for letter and category verbal fluency before surgery, 1–2 days after surgery and approximately 3 months after surgery. Results suggest that the motor symptoms known as the SMA syndrome co-occur with pronounced deficits in cognitive control.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Cognitive control, Executive function, SMA-syndrome, Supplementary motor area, Stroop test, Dichotic listening
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-164009 (URN)10.1016/j.neuropsychologia.2019.03.013 (DOI)000493911900014 ()30930302 (PubMedID)
Funder
Västerbotten County Council
Available from: 2019-10-12 Created: 2019-10-12 Last updated: 2019-12-03Bibliographically approved
Lövdén, M., Karalija, N., Andersson, M., Wåhlin, A., Axelsson, J., Köhncke, Y., . . . Lindenberger, U. (2018). Latent-profile analysis reveals behavioral and brain correlates of dopamine-cognition associations. Cerebral Cortex, 28(11), 3894-3907
Open this publication in new window or tab >>Latent-profile analysis reveals behavioral and brain correlates of dopamine-cognition associations
Show others...
2018 (English)In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 28, no 11, p. 3894-3907Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
Oxford University Press, 2018
Keywords
Cognitive Performance, dopamine D-2/3 Receptor Availability, Heterogeneity, Latent Profile Analysis, older Adults, Working Memory
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-153657 (URN)10.1093/cercor/bhx253 (DOI)000449432200011 ()29028935 (PubMedID)
Funder
Swedish Research Council, 446-2013-7189Forte, Swedish Research Council for Health, Working Life and Welfare, 2013-2277Knut and Alice Wallenberg FoundationTorsten Söderbergs stiftelseRagnar Söderbergs stiftelseThe Swedish Brain FoundationVästerbotten County Council
Available from: 2018-11-26 Created: 2018-11-26 Last updated: 2018-11-26Bibliographically approved
Salami, A., Rieckmann, A., Karalija, N., Avelar-Pereira, B., Andersson, M., Wåhlin, A., . . . Nyberg, L. (2018). Neurocognitive Profiles of Older Adults with Working-Memory Dysfunction. Cerebral Cortex, 28(7), 2525-2539
Open this publication in new window or tab >>Neurocognitive Profiles of Older Adults with Working-Memory Dysfunction
Show others...
2018 (English)In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 28, no 7, p. 2525-2539Article in journal (Refereed) Published
Abstract [en]

Individuals differ in how they perceive, remember, and think. There is evidence for the existence of distinct subgroups that differ in cognitive performance within the older population. However, it is less clear how individual differences in cognition in old age are linked to differences in brain-based measures. We used latent-profile analysis on n-back working-memory (WM) performance to identify subgroups in a large sample of older adults (n = 181; age = 64-68 years). Our analysis identified one larger normal subgroup with higher performance (n = 113; 63%), and a second smaller subgroup (n = 55; 31%) with lower performance. The low-performing subgroup showed weaker load-dependent BOLD modulation and lower connectivity within the fronto-parietal network (FPN) as well as between FPN and striatum during n-back, along with lower FPN connectivity at rest. This group also exhibited lower FPN structural integrity, lower frontal dopamine D2 binding potential, inferior performance on offline WM tests, and a trend-level genetic predisposition for lower dopamine-system efficiency. By contrast, this group exhibited relatively intact episodic memory and associated brain measures (i.e., hippocampal volume, structural, and functional connectivity within the default-mode network). Collectively, these data provide converging evidence for the existence of a group of older adults with impaired WM functioning characterized by reduced cortico-striatal coupling and aberrant cortico-cortical integrity within FPN.

Place, publisher, year, edition, pages
Oxford University Press, 2018
Keywords
dopamine, fronto-parietal network, functional connectivity, individual differences, working memory
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-150747 (URN)10.1093/cercor/bhy062 (DOI)000437165800025 ()29901790 (PubMedID)
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-08-16Bibliographically approved
Organisations

Search in DiVA

Show all publications