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Publications (10 of 386) Show all publications
Boen, R., Kaufmann, T., van der Meer, D., Frei, O., Agartz, I., Ames, D., . . . Sønderby, I. E. (2024). Beyond the global brain differences: intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers. Biological Psychiatry, 95(2), 147-160
Open this publication in new window or tab >>Beyond the global brain differences: intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers
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2024 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 95, no 2, p. 147-160Article in journal (Refereed) Published
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.

Keywords
15q11.2 BP1-BP2, 1q21.1 distal, Brain structure, Copy number variants, Intraindividual variability, Magnetic resonance imaging
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-218106 (URN)10.1016/j.biopsych.2023.08.018 (DOI)37661008 (PubMedID)2-s2.0-85178151168 (Scopus ID)
Funder
EU, Horizon 2020NIH (National Institutes of Health)Knut and Alice Wallenberg FoundationThe Research Council of Norway
Available from: 2023-12-15 Created: 2023-12-15 Last updated: 2023-12-15Bibliographically approved
Grill, F., Guitart-Masip, M., Johansson, J., Stiernman, L., Axelsson, J., Nyberg, L. & Rieckmann, A. (2024). Dopamine release in human associative striatum during reversal learning. Nature Communications, 15(1), Article ID 59.
Open this publication in new window or tab >>Dopamine release in human associative striatum during reversal learning
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2024 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 15, no 1, article id 59Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-219310 (URN)10.1038/s41467-023-44358-w (DOI)38167691 (PubMedID)2-s2.0-85181231291 (Scopus ID)
Available from: 2024-01-12 Created: 2024-01-12 Last updated: 2024-01-12Bibliographically approved
Karalija, N., Papenberg, G., Johansson, J., Wåhlin, A., Salami, A., Andersson, M., . . . Nyberg, L. (2024). Longitudinal support for the correlative triad among aging, dopamine D2-like receptor loss, and memory decline. Neurobiology of Aging, 136, 125-132
Open this publication in new window or tab >>Longitudinal support for the correlative triad among aging, dopamine D2-like receptor loss, and memory decline
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2024 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 136, p. 125-132Article in journal (Refereed) Published
Abstract [en]

Dopamine decline is suggested to underlie aging-related cognitive decline, but longitudinal examinations of this link are currently missing. We analyzed 5-year longitudinal data for a sample of healthy, older adults (baseline: n = 181, age: 64–68 years; 5-year follow-up: n = 129) who underwent positron emission tomography with 11C-raclopride to assess dopamine D2-like receptor (DRD2) availability, magnetic resonance imaging to evaluate structural brain measures, and cognitive tests. Health, lifestyle, and genetic data were also collected. A data-driven approach (k-means cluster analysis) identified groups that differed maximally in DRD2 decline rates in age-sensitive brain regions. One group (n = 47) had DRD2 decline exclusively in the caudate and no cognitive decline. A second group (n = 72) had more wide-ranged DRD2 decline in putamen and nucleus accumbens and also in extrastriatal regions. The latter group showed significant 5-year working memory decline that correlated with putamen DRD2 decline, along with higher dementia and cardiovascular risk and a faster biological pace of aging. Taken together, for individuals with more extensive DRD2 decline, dopamine decline is associated with memory decline in aging.

Keywords
11C-raclopride, Aging, Dopamine D2-like receptor, Longitudinal, Magnetic resonance imaging, Positron emission tomography, Working memory
National Category
Geriatrics
Identifiers
urn:nbn:se:umu:diva-221540 (URN)10.1016/j.neurobiolaging.2024.02.001 (DOI)38359585 (PubMedID)2-s2.0-85185304249 (Scopus ID)
Funder
Swedish Research Council, 421-2012-648Swedish Research Council, 2017-02217Swedish Research Council, 2022-01804Umeå UniversityKnut and Alice Wallenberg Foundation, 2015.0277Jonas and Christina af Jochnick FoundationAlzheimerfonden, AF-967710Riksbankens Jubileumsfond, P20-0779Region Västerbotten
Available from: 2024-03-15 Created: 2024-03-15 Last updated: 2024-03-15Bibliographically approved
Han, X., Song, L., Li, Y., Dong, Y., Liu, R., Han, Q., . . . Qiu, C. (2023). Accelerometer-measured sedentary behavior patterns, brain structure, and cognitive function in dementia-free older adults: a population-based study. Journal of Alzheimer's Disease, 96(2), 657-668
Open this publication in new window or tab >>Accelerometer-measured sedentary behavior patterns, brain structure, and cognitive function in dementia-free older adults: a population-based study
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2023 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 96, no 2, p. 657-668Article in journal (Refereed) Published
Abstract [en]

Background: Sedentary behavior is associated with cognitive impairment, but the neuropathological mechanisms underlying their associations are poorly understood.

Objective: To investigate the associations of accelerometer-measured sedentary behavior patterns with brain structure and cognition, and further to explore the potential mechanisms.

Methods: This community-based study included 2,019 older adults (age≥60 years, 59% women) without dementia derived from participants in the baseline examination of MIND-China (2018-2020). We assessed sedentary parameters using an accelerometer and cognitive function using a neuropsychological test battery. Structural brain markers were assessed on the structural brain MRI scans in a subsample (n = 1,009). Data were analyzed using the general linear, isotemporal substitution, and mediation models.

Results: In the total sample (n = 2,019), adjusting for multiple covariates and moderate-to-vigorous-intensity physical activity, longer mean sedentary bout duration was linearly related with lower z-scores of global cognition, verbal fluency, and memory (ptrend < 0.05), whereas greater total sedentary time was linearly associated with lower z-scores of global cognition, verbal fluency, and memory only among individuals with long sedentary time (>10 h/day) (ptrend < 0.05); Breaking up sedentary time with same amount of light-intensity physical activity was significantly associated with higher verbal fluency and memory z-scores (p < 0.05). In the MRI subsample (n = 1,009), separately entering structural brain MRI markers into the mediation models substantially attenuated the associations of mean sedentary bout duration with global cognition, verbal fluency, and memory z-scores.

Conclusion: Prolonged uninterrupted sedentary time is associated with poor global cognition, memory, and verbal fluency among rural older adults, and structural brain markers could partially mediate the association.

Place, publisher, year, edition, pages
IOS Press, 2023
Keywords
Accelerometer, Alzheimer's disease, brain aging, cognition, magnetic resonance imaging, population-based study, sedentary behavior patterns
National Category
Geriatrics Neurology
Identifiers
urn:nbn:se:umu:diva-217213 (URN)10.3233/JAD-230575 (DOI)37840495 (PubMedID)2-s2.0-85176974964 (Scopus ID)
Funder
The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), CH2019-8320Karolinska InstituteSwedish Research Council, 2017-05819Swedish Research Council, 2020-01574
Available from: 2023-11-30 Created: 2023-11-30 Last updated: 2023-11-30Bibliographically approved
Sandberg, P., Boraxbekk, C.-J., Zogaj, I. & Nyberg, L. (2023). Age-independent transfer after successful associative mnemonic training. Journal of Cognitive Enhancement, 7(3-4), 159-172
Open this publication in new window or tab >>Age-independent transfer after successful associative mnemonic training
2023 (English)In: Journal of Cognitive Enhancement, ISSN 2509-3290, Vol. 7, no 3-4, p. 159-172Article in journal (Refereed) Published
Abstract [en]

Generalization of training to support the performance on new tasks—transfer—has been much studied. One hypothesis is that transfer occurs if overlapping neuronal circuits are engaged in both training and transfer tasks. Here, we investigated transfer effects in the domain of episodic memory by following 356 participants between 20 and 83 years who downloaded and used a smart phone application to practice the method of loci (MoL) over 3 months. We measured transfer of MoL training to three associative memory tasks with hypothesized neurocognitive overlap (binding in the hippocampus) with the trained task. Transfer tasks were administered at the beginning of training and when two specific proficiency levels in Loci training were reached. Results showed robust transfer effects across the age span at both levels. These results indicate that app-based strategy training can lead to enhancement of episodic memory beyond the specific training task, which may have clinical implementations.

Place, publisher, year, edition, pages
Springer Nature, 2023
Keywords
Aging, Episodic memory training, Mnemonics, Strategy training, The method of loci, Transfer effects
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-215935 (URN)10.1007/s41465-023-00273-y (DOI)001087509300001 ()2-s2.0-85174607278 (Scopus ID)
Funder
Knut and Alice Wallenberg Foundation, 2015.0277
Available from: 2023-11-02 Created: 2023-11-02 Last updated: 2024-01-11Bibliographically approved
Löding, S., Andersson, U., Kaaks, R., Schulze, M. B., Pala, V., Urbarova, I., . . . Melin, B. S. (2023). Altered plasma metabolite levels can be detected years before a glioma diagnosis. JCI Insight, 8(19), Article ID e171225.
Open this publication in new window or tab >>Altered plasma metabolite levels can be detected years before a glioma diagnosis
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2023 (English)In: JCI Insight, ISSN 2379-3708, Vol. 8, no 19, article id e171225Article in journal (Refereed) Published
Abstract [en]

Genetic and metabolic changes in tissue and blood are reported to occur several years before glioma diagnosis. Since gliomas are currently detected late, a liquid biopsy for early detection could affect the quality of life and prognosis of patients. Here, we present a nested case-control study of 550 prediagnostic glioma cases and 550 healthy controls from the Northern Sweden Health and Disease study (NSHDS) and the European Prospective Investigation into Cancer and Nutrition (EPIC) study. We identified 93 significantly altered metabolites related to glioma development up to 8 years before diagnosis. Out of these metabolites, a panel of 20 selected metabolites showed strong disease correlation and a consistent progression pattern toward diagnosis in both the NSHDS and EPIC cohorts, and they separated future cases from controls independently of biological sex. The blood metabolite panel also successfully separated both lower-grade glioma and glioblastoma cases from controls, up to 8 years before diagnosis in patients within the NSHDS cohort and up to 2 years before diagnosis in EPIC. Pathway enrichment analysis detected metabolites related to the TCA cycle, Warburg effect, gluconeogenesis, and cysteine, pyruvate, and tyrosine metabolism as the most affected.

Place, publisher, year, edition, pages
American Society For Clinical Investigation, 2023
Keywords
Brain cancer, Metabolism, Oncology
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-215372 (URN)10.1172/jci.insight.171225 (DOI)37651185 (PubMedID)2-s2.0-85173580693 (Scopus ID)
Funder
Swedish Research Council, 2017-00650Swedish Research Council, 2019-01566Swedish Cancer Society, CAN2018/390Swedish Cancer Society, 19 0370Cancerforskningsfonden i Norrland, AMP 21-1045Cancerforskningsfonden i Norrland, AMP22-1084Sjöberg Foundation, 2020-01-07-08Public Health Agency of Sweden , 2020-2022World Cancer Research Fund InternationalRegion SkåneRegion Västerbotten
Available from: 2023-10-31 Created: 2023-10-31 Last updated: 2023-10-31Bibliographically approved
Håglin, S., Koch, E., Schäfer Hackenhaar, F., Nyberg, L. & Kauppi, K. (2023). APOE ɛ4, but not polygenic Alzheimer’s disease risk, is related to longitudinal decrease in hippocampal brain activity in non-demented individuals. Scientific Reports, 13(1), Article ID 8433.
Open this publication in new window or tab >>APOE ɛ4, but not polygenic Alzheimer’s disease risk, is related to longitudinal decrease in hippocampal brain activity in non-demented individuals
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2023 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1, article id 8433Article in journal (Refereed) Published
Abstract [en]

The hippocampus is affected early in Alzheimer’s disease (AD) and altered hippocampal functioning influences normal cognitive aging. Here, we used task-based functional MRI to assess if the APOE ɛ4 allele or a polygenic risk score (PRS) for AD was linked to longitudinal changes in memory-related hippocampal activation in normal aging (baseline age 50–95, n = 292; n = 182 at 4 years follow-up, subsequently non-demented for at least 2 years). Mixed-models were used to predict level and change in hippocampal activation by APOE ɛ4 status and PRS based on gene variants previously linked to AD at p ≤ 1, p < 0.05, or p < 5e−8 (excluding APOE). APOE ɛ4 and PRSp<5e−8 significantly predicted AD risk in a larger sample from the same study population (n = 1542), while PRSp≤1 predicted memory decline. APOE ɛ4 was linked to decreased hippocampal activation over time, with the most prominent effect in the posterior hippocampi, while PRS was unrelated to hippocampal activation at all p-thresholds. These results suggests a link for APOE ɛ4, but not for AD genetics in general, on functional changes of the hippocampi in normal aging.

Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Neurosciences Neurology
Identifiers
urn:nbn:se:umu:diva-209143 (URN)10.1038/s41598-023-35316-z (DOI)37225733 (PubMedID)2-s2.0-85160132679 (Scopus ID)
Funder
The Kempe Foundations, SMK-1865Swedish Research Council, 2017-03011Knut and Alice Wallenberg Foundation
Available from: 2023-06-26 Created: 2023-06-26 Last updated: 2023-06-26Bibliographically approved
Johansson, J., Nordin, K., Pedersen, R., Karalija, N., Papenberg, G., Andersson, M., . . . Salami, A. (2023). Biphasic patterns of age-related differences in dopamine D1 receptors across the adult lifespan. Cell Reports, 42(9), Article ID 113107.
Open this publication in new window or tab >>Biphasic patterns of age-related differences in dopamine D1 receptors across the adult lifespan
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2023 (English)In: Cell Reports, E-ISSN 2211-1247, Vol. 42, no 9, article id 113107Article in journal (Refereed) Published
Abstract [en]

Age-related alterations in D1-like dopamine receptor (D1DR) have distinct implications for human cognition and behavior during development and aging, but the timing of these periods remains undefined. Enabled by a large sample of in vivo assessments (n = 180, age 20 to 80 years of age, 50% female), we discover that age-related D1DR differences pivot at approximately 40 years of age in several brain regions. Focusing on the most age-sensitive dopamine-rich region, we observe opposing pre- and post-forties interrelations among caudate D1DR, cortico-striatal functional connectivity, and memory. Finally, particularly caudate D1DR differences in midlife and beyond, but not in early adulthood, associate with manifestation of white matter lesions. The present results support a model by which excessive dopamine modulation in early adulthood and insufficient modulation in aging are deleterious to brain function and cognition, thus challenging a prevailing view of monotonic D1DR function across the adult lifespan.

Keywords
aging, cognition, CP: Neuroscience, dopamine D1, functional connectivity, neuromodulation, protracted development
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-214414 (URN)10.1016/j.celrep.2023.113107 (DOI)2-s2.0-85169884676 (Scopus ID)
Funder
Swedish Research Council, 2016-01936Knut and Alice Wallenberg FoundationRiksbankens Jubileumsfond
Available from: 2023-09-18 Created: 2023-09-18 Last updated: 2024-01-17Bibliographically approved
Elbe, P., Bäcklund, C., Vega-Mendoza, M., Sörman, D., Malmberg Gavelin, H., Nyberg, L. & Ljungberg, J. K. (2023). Computerized cognitive interventions for adults with ADHD: a systematic review and meta-analysis. Neuropsychology, 37(5), 519-530
Open this publication in new window or tab >>Computerized cognitive interventions for adults with ADHD: a systematic review and meta-analysis
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2023 (English)In: Neuropsychology, ISSN 0894-4105, E-ISSN 1931-1559, Vol. 37, no 5, p. 519-530Article, review/survey (Refereed) Published
Abstract [en]

Objective: Treatments for adults with attention-deficit hyperactivity disorder (ADHD) are understudied, compared to children and adolescents with the same condition. In this systematic review and random-effects meta-analysis, we aim to evaluate the outcomes of computerized cognitive training (CCT) interventions in randomized controlled trials (RCTs) including adults with ADHD.

Method: Cognitive outcomes and ADHD symptom severity were analyzed separately. In addition, the Cattell–Horn–Carroll (CHC) theory of cognitive abilities was used to categorize outcome variables into subdomains, which were analyzed separately in a subsequent analysis.

Results: The results revealed a small positive change in overall cognitive functioning, a measure of all cognitive outcomes in each study, for individuals who took part in CCT compared to controls (k = 9, Hedge’s g = 0.235, 95% CI [0.002, 0.467], p = 0.048, τ2 = 0.000, I2 = 0.000). However, neither symptom severity nor specific cognitive outcomes (executive functioning, cognitive speed, or working memory) showed a significant improvement.

Conclusions: We analyzed the risk of bias in the chosen studies and discuss the findings in terms of effect size. It is concluded that CCT has a small positive effect in adults with ADHD. Due to the lack of heterogeneity in intervention designs across the included studies, increased heterogeneity in future studies could help inform clinicians about the aspects of CCT, such as training type and length, that are most beneficial for this group.

Place, publisher, year, edition, pages
American Psychological Association (APA), 2023
Keywords
attention-deficit hyperactivity disorder, computerized cognitive training, meta-analysis, systematic review, executive functions
National Category
Neurosciences Applied Psychology
Identifiers
urn:nbn:se:umu:diva-206344 (URN)10.1037/neu0000890 (DOI)000946153700001 ()36892894 (PubMedID)2-s2.0-85150836585 (Scopus ID)
Funder
Knut and Alice Wallenberg Foundation, KAW 2014.0205Vinnova, 2021-02361
Available from: 2023-04-27 Created: 2023-04-27 Last updated: 2023-08-11Bibliographically approved
Nyberg, L. & Lövdén, M. (2023). Education and neurocognitive aging - is there a relation? (4ed.). In: Robert J. Tierney; Fazal Rizvi; Kadriye Ercikan (Ed.), International encyclopedia of education: fourth edition (pp. 512-519). Oxford: Elsevier
Open this publication in new window or tab >>Education and neurocognitive aging - is there a relation?
2023 (English)In: International encyclopedia of education: fourth edition / [ed] Robert J. Tierney; Fazal Rizvi; Kadriye Ercikan, Oxford: Elsevier, 2023, 4, p. 512-519Chapter in book (Refereed)
Abstract [en]

Aging is associated with declining brain integrity and cognitive functioning, but with marked individual differences regarding onset and rate of decline. Several factors have been suggested to account for this heterogeneity. Here we review evidence for the hypothesis that higher educational attainment relates to better preserved neurocognitive functioning in aging. Collectively, education is shown to be related to an advantage in level but not rate of change. Thus, educational attainment is primarily related to late-life cognitive functioning by playing a role in developmental processes that lead to differences in brain and cognition during early adulthood that persist into older age.

Place, publisher, year, edition, pages
Oxford: Elsevier, 2023 Edition: 4
Keywords
Aging, Brain, Cognition, Education, Reserve
National Category
Neurology Neurosciences Learning
Identifiers
urn:nbn:se:umu:diva-206197 (URN)10.1016/B978-0-12-818630-5.14062-X (DOI)2-s2.0-85150559047 (Scopus ID)9780128186299 (ISBN)
Available from: 2023-04-03 Created: 2023-04-03 Last updated: 2023-04-06Bibliographically approved
Projects
Ansökan från Adam Savine inom programmet Nordic Research Opportunity [2011-02321_VR]; Umeå UniversityCognition, brain, and aging (COBRA): A longitudinal multimodal imaging study [2012-00648_VR]; Umeå UniversityTHE MPRESS STUDY: AN INTERDISCIPLINARY RESEARCH PROGRAM ON MENTAL AND PHYSICAL HEALTH, BRAIN FUNCTIONING, SCHOOL PERFORMANCE, AND PARENTING IN MODERATELY PRETERM BORN CHILDREN AT 10-12 YRS OF AGE [2012-47_Formas]; Umeå UniversityInfrastructure for research on aging and age-related diseases: The Betula database [2014-06381_VR]; Umeå UniversityMethods for non-ignorable missingness in longitudinal brain imaging studies. [P16-0628:1_RJ]; Umeå University
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-3367-1746

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