Umeå University's logo

umu.sePublications
Change search
Link to record
Permanent link

Direct link
Alternative names
Publications (10 of 27) Show all publications
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
Show others...
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
Hou, M., Herold, F., Zhang, Z., Ando, S., Cheval, B., Ludyga, S., . . . Zou, L. (2024). Human dopaminergic system in the exercise-cognition link. Trends in Molecular Medicine, Article ID S1471-4914(24)00099-6.
Open this publication in new window or tab >>Human dopaminergic system in the exercise-cognition link
Show others...
2024 (English)In: Trends in Molecular Medicine, ISSN 1471-4914, E-ISSN 1471-499X, article id S1471-4914(24)00099-6Article in journal (Refereed) In press
Abstract [en]

While the dopaminergic system is important for cognitive processes, it is also sensitive to the influence of physical activity (PA). We summarize current evidence on whether PA-related changes in the human dopaminergic system are associated with alterations in cognitive performance, discuss recent advances, and highlight challenges and opportunities for future research.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
brain health, catecholamines, cognition, exercise, fitness, neurotransmitter
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-224337 (URN)10.1016/j.molmed.2024.04.011 (DOI)38719712 (PubMedID)2-s2.0-85192307901 (Scopus ID)
Available from: 2024-05-14 Created: 2024-05-14 Last updated: 2024-05-15
Godbersen, G. M., Klug, S., Wadsak, W., Pichler, V., Raitanen, J., Rieckmann, A., . . . Hahn, A. (2023). Task-evoked metabolic demands of the posteromedial default mode network are shaped by dorsal attention and frontoparietal control networks. eLIFE, 12, Article ID e84683.
Open this publication in new window or tab >>Task-evoked metabolic demands of the posteromedial default mode network are shaped by dorsal attention and frontoparietal control networks
Show others...
2023 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 12, article id e84683Article in journal (Refereed) Published
Abstract [en]

External tasks evoke characteristic fMRI BOLD signal deactivations in the default mode network (DMN). However, for the corresponding metabolic glucose demands both decreases and increases have been reported. To resolve this discrepancy, functional PET/MRI data from 50 healthy subjects performing Tetris were combined with previously published data sets of working memory, visual and motor stimulation. We show that the glucose metabolism of the posteromedial DMN is dependent on the metabolic demands of the correspondingly engaged task-positive networks. Specifically, the dorsal attention and frontoparietal network shape the glucose metabolism of the posteromedial DMN in opposing directions. While tasks that mainly require an external focus of attention lead to a consistent downregulation of both metabolism and the BOLD signal in the posteromedial DMN, cognitive control during working memory requires a metabolically expensive BOLD suppression. This indicates that two types of BOLD deactivations with different oxygen-to-glucose index may occur in this region. We further speculate that consistent downregulation of the two signals is mediated by decreased glutamate signaling, while divergence may be subject to active GABAergic inhibition. The results demonstrate that the DMN relates to cognitive processing in a flexible manner and does not always act as a cohesive task-negative network in isolation.

Place, publisher, year, edition, pages
eLife Sciences Publications Ltd, 2023
Keywords
BOLD signal, deactivation, default mode network, functional PET, glucose metabolism, human, neuroscience
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-209558 (URN)10.7554/eLife.84683 (DOI)37226880 (PubMedID)2-s2.0-85160875279 (Scopus ID)
Available from: 2023-06-12 Created: 2023-06-12 Last updated: 2023-06-12Bibliographically approved
Stiernman, L., Grill, F., McNulty, C., Bahrd, P., Panes Lundmark, V., Axelsson, J., . . . Rieckmann, A. (2023). Widespread fMRI BOLD signal overactivations during cognitive control in older adults are not matched by corresponding increases in fPET glucose metabolism. Journal of Neuroscience, 43(14), 2527-2536
Open this publication in new window or tab >>Widespread fMRI BOLD signal overactivations during cognitive control in older adults are not matched by corresponding increases in fPET glucose metabolism
Show others...
2023 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 43, no 14, p. 2527-2536Article in journal (Refereed) Published
Abstract [en]

A common observation in fMRI studies using the BOLD signal is that older adults, compared with young adults, show overactivations, particularly during less demanding tasks. The neuronal underpinnings of such overactivations are not known, but a dominant view is that they are compensatory in nature and involve recruitment of additional neural resources. We scanned 23 young (20-37 years) and 34 older (65-86 years) healthy human adults of both sexes with hybrid positron emission tomography/MRI. The radioligand [18F]fluoro-deoxyglucose was used to assess dynamic changes in glucose metabolism as a marker of task-dependent synaptic activity, along with simultaneous fMRI BOLD imaging. Participants performed two verbal working memory (WM) tasks: one involving maintenance (easy) and one requiring manipulation (difficult) of information in WM. Converging activations to the WM tasks versus rest were observed for both imaging modalities and age groups in attentional, control, and sensorimotor networks. Upregulation of activity to WM-demand, comparing the more difficult to the easier task, also converged between both modalities and age groups. For regions in which older adults showed task-dependent BOLD overactivations compared with the young adults, no corresponding increases in glucose metabolism were found. To conclude, findings from the current study show that task-induced changes in the BOLD signal and synaptic activity as measured by glucose metabolism generally converge, but overactivations observed with fMRI in older adults are not coupled with increased synaptic activity, which suggests that these overactivations are not neuronal in origin.

Place, publisher, year, edition, pages
Society for Neuroscience, 2023
Keywords
aging, fMRI, glucose metabolism, overactivation, PET, working memory
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-206761 (URN)10.1523/JNEUROSCI.1331-22.2023 (DOI)000976532300008 ()36868855 (PubMedID)2-s2.0-85152165890 (Scopus ID)
Funder
EU, European Research Council, ERC-STG-716065EU, Horizon 2020Swedish Research Council, 2016-01936Knut and Alice Wallenberg FoundationRiksbankens Jubileumsfond, P20-0515
Available from: 2023-05-02 Created: 2023-05-02 Last updated: 2023-09-05Bibliographically approved
Simonsson, E., Jonasson Stiernman, L., Lundquist, A., Rosendahl, E., Hedlund, M., Lindelöf, N. & Boraxbekk, C.-J. (2022). Dopamine d2/3-receptor availability and its association with autonomous motivation to exercise in older adults: an exploratory [11c]-raclopride study. Frontiers in Human Neuroscience, 16, Article ID 997131.
Open this publication in new window or tab >>Dopamine d2/3-receptor availability and its association with autonomous motivation to exercise in older adults: an exploratory [11c]-raclopride study
Show others...
2022 (English)In: Frontiers in Human Neuroscience, E-ISSN 1662-5161, Vol. 16, article id 997131Article in journal (Refereed) Published
Abstract [en]

Background: Autonomous motivation to exercise occurs when the activity is voluntary and with a perceived inherent satisfaction from the activity itself. It has been suggested that autonomous motivation is related to striatal dopamine D2/3-receptor (D2/3R) availability within the brain. In this study, we hypothesized that D2/3R availability in three striatal regions (nucleus accumbens, caudate nucleus, and putamen) would be positively associated with self-reported autonomous motivation to exercise. We also examined this relationship with additional exploratory analyses across a set of a priori extrastriatal regions of interest (ROI).

Methods: Our sample comprised 49 older adults (28 females) between 64 and 78 years of age. The D2/3R availability was quantified from positron emission tomography using the non-displaceable binding potential of [11C]-raclopride ligand. The exercise-related autonomous motivation was assessed with the Swedish version of the Behavioral Regulations in Exercise Questionnaire-2.

Results: No significant associations were observed between self-reported autonomous motivation to exercise and D2/3R availability within the striatum (nucleus accumbens, caudate nucleus, and putamen) using semi-partial correlations controlling for ROI volume on D2/3R availability. For exploratory analyses, positive associations were observed for the superior (r = 0.289, p = 0.023) and middle frontal gyrus (r = 0.330, p = 0.011), but not for the inferior frontal gyrus, orbitofrontal cortex, anterior cingulate cortex, or anterior insular cortex.

Conclusion: This study could not confirm the suggested link between striatal D2/3R availability and subjective autonomous motivation to exercise among older adults. The exploratory findings, however, propose that frontal brain regions may be involved in the intrinsic regulation of exercise-related behaviors, though this has to be confirmed by future studies using a more suitable ligand and objective measures of physical activity levels.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2022
Keywords
aging, autonomous motivation, dopamine, exercise motivation, PET, self-determination theory (SDT)
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-201462 (URN)10.3389/fnhum.2022.997131 (DOI)000889590000001 ()2-s2.0-85142664855 (Scopus ID)
Funder
Swedish Research Council, 2012-00530Region VästerbottenSwedish National Centre for Research in SportsThe Kamprad Family Foundation
Available from: 2022-12-06 Created: 2022-12-06 Last updated: 2024-07-02Bibliographically approved
Jakobson Mo, S., Axelsson, J., Jonasson, L. S. & Riklund, K. (2022). Validation of dynamic [18F]FE-PE2I PET for estimation of relative regional cerebral blood flow: a comparison with [15O]H2O PET. EJNMMI Research, 12(1), Article ID 72.
Open this publication in new window or tab >>Validation of dynamic [18F]FE-PE2I PET for estimation of relative regional cerebral blood flow: a comparison with [15O]H2O PET
2022 (English)In: EJNMMI Research, E-ISSN 2191-219X, Vol. 12, no 1, article id 72Article in journal (Refereed) Published
Abstract [en]

Background: Dopamine transporter (DAT) imaging is used in the diagnostic work-up in suspected parkinsonian syndromes and dementia with Lewy bodies but cannot differentiate between these syndromes, and an extra brain imaging examination of the regional cerebral blood flow (rCBF) or glucose metabolism is often needed for differential diagnosis. The requirement of two different imaging examinations is resource-consuming and inconvenient for the patients. Therefore, imaging of both cortical blood flow and DAT imaging with the same radiotracer would be more convenient and cost-effective. The aim of this study was to test whether relative regional cerebral blood flow (rCBFR) can be measured with the DAT-specific positron emission tomography (PET) tracer [18F]FE-PE2I (FE-PE2I), by validation with cerebral perfusion measured with [15O]H2O PET (H2O).

Methods: The rCBFR was quantified by kinetic modeling for FE-PE2I (R1) and H2O (F). The R1 was calculated using the simplified reference tissue model, and F was calculated with a modified Koopman double-integration method. The linear relationship and intraclass correlation (ICC) between R1 and F were tested in image data derived from 29 patients with recent onset parkinsonism and 30 healthy controls.

Results: There was a strong linear correlation across all subjects between R1 and F in the frontal, parietal, temporal, cingulate and occipital cortex as well as in the striatum (r ≥ 0.731–0.905, p < 0.001) with a good-to-excellent ICC, ranging from 0.727 to 0.943 (p < 0.001).

Conclusions: Our results suggest that FE-PE2I may be used as a proxy for cerebral perfusion, thus potentially serving as a radiotracer for assessment of both DAT availability and rCBFR in one single dynamic scan. This could be valuable in the differential diagnosis of parkinsonian syndromes.

Trial registration: EUDRA-CT 2015-003045-26. Registered 23 October 2015 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-003045-26

Place, publisher, year, edition, pages
Springer Science+Business Media B.V., 2022
Keywords
15O H2O, 18F FE-PE2, Cerebral blood flow, Cerebral perfusion, Parkinsonian syndromes, Parkinsonism, Positron emission tomography
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-201365 (URN)10.1186/s13550-022-00941-8 (DOI)000886120800001 ()2-s2.0-85142139428 (Scopus ID)
Funder
Region VästerbottenParkinsonfonden
Available from: 2022-12-01 Created: 2022-12-01 Last updated: 2023-09-05Bibliographically approved
Jakobson Mo, S., Axelsson, J., J. Stiernman, L., Larsson, A., af Bjerkén, S., Bäckström, D. C., . . . Riklund, K. (2022). VNTR polymorphism in the SLC6A3 gene does not influence dopamine transporter availability measured by [18F]FE-PE2I PET or [123I]FP-Cit SPECT. Nuclear medicine communications, 43(3), 247-255
Open this publication in new window or tab >>VNTR polymorphism in the SLC6A3 gene does not influence dopamine transporter availability measured by [18F]FE-PE2I PET or [123I]FP-Cit SPECT
Show others...
2022 (English)In: Nuclear medicine communications, ISSN 0143-3636, E-ISSN 1473-5628, Vol. 43, no 3, p. 247-255Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To investigate the potential impact of polymorphism in the 3'-untranslated region (3'UTR) of the SLC6A3 gene (DAT1) on normal variation in dopamine transporter (DAT) imaging with [18F]FE-PE2I PET and [123I]FP-Cit SPECT.

METHODS: Thirty-six individuals (mean age 70.4±5.4 years) with normal [18F]FE-PE2I PET and [123I]FP-Cit SPECT were genotyped for variable number of tandem repeats (VNTR) in the 3′UTR of the DAT1 gene. The DAT-availability in the caudate and putamen as measured with [18F]FE-PE2I PET and [123I]FP-Cit SPECT, as well as in the substantia nigra with [18F]FE-PE2I PET were compared between the participants carrying one or two 9-repeat alleles (i.e. 9R+10R or 9R+9R; 47%) and the participants without a 9R allele (i.e. 10R+10R or 10R+11R; 53%). Nonparametric tests, linear regression analysis and mixed model analysis were used to assess any statistical difference in measured DAT availability between the two allele groups.

RESULTS: The measured DAT-availability in PET- and SPECT-imaging tended to be slightly higher in the 9R-group; however, the difference did not reach statistical significance in either the caudate or the putamen or the substantia nigra. Instead, age did have a significant effect on the DAT level (P < 0.05) notwithstanding the genotype.

CONCLUSION: No significant effect of DAT1-genotype was detectable in imaging with [18F]FE-PE2I PET or [123I]FP-Cit, instead, age accounted for the normal variation in DAT-PET and DAT-SPECT.

Place, publisher, year, edition, pages
Wolters Kluwer, 2022
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-192638 (URN)10.1097/MNM.0000000000001514 (DOI)000753310600001 ()34908018 (PubMedID)2-s2.0-85124443503 (Scopus ID)
Funder
Region VästerbottenParkinsonfonden
Available from: 2022-02-22 Created: 2022-02-22 Last updated: 2023-05-24Bibliographically approved
Andersson, S., Josefsson, M., Stiernman, L. J. & Rieckmann, A. (2021). Cognitive decline in Parkinson’s disease: a subgroup of extreme decliners revealed by a data-driven analysis of longitudinal progression. Frontiers in Psychology, 12, Article ID 729755.
Open this publication in new window or tab >>Cognitive decline in Parkinson’s disease: a subgroup of extreme decliners revealed by a data-driven analysis of longitudinal progression
2021 (English)In: Frontiers in Psychology, E-ISSN 1664-1078, Vol. 12, article id 729755Article in journal (Refereed) Published
Abstract [en]

Cognitive impairment is an important symptom of Parkinson’s disease (PD) and predicting future cognitive decline is crucial for clinical practice. Here, we aim to identify latent sub-groups of longitudinal trajectories of cognitive change in PD patients, and explore predictors of differences in cognitive change. Longitudinal cognitive performance data from 349 newly diagnosed PD patients and 145 healthy controls from the Parkinson Progression Marker Initiative were modeled using a multivariate latent class linear mixed model. Resultant latent classes were compared on a number of baseline demographics, and clinical variables, as well as cerebrospinal fluid (CSF) biomarkers and striatal dopamine transporter (DAT) density markers of neuropathology. Trajectories of cognitive change in PD were best described by two latent classes. A large subgroup (90%), which showed a subtle impairment in cognitive performance compared to controls but remained stable over the course of the study, and a small subgroup (10%) which rapidly declined in all cognitive performance measures. Rapid decliners did not differ significantly from the larger group in terms of disease duration, severity or motor symptoms at baseline. However, rapid decliners had lower CSF amyloidß42 levels, a higher prevalence of sleep disorder and pronounced loss of caudate DAT density at baseline. These data suggest the existence of a distinct minority sub-type of PD in which rapid cognitive change in PD can occur uncoupled from motor symptoms or disease severity, likely reflecting early pathological change that extends from motor areas of the striatum into associative compartments and cortex.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2021
Keywords
cognitive decline, Cluster analysis, Longitudinal, Parkinson's disease, subtypes
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-186768 (URN)10.3389/fpsyg.2021.729755 (DOI)000698637400001 ()34566817 (PubMedID)2-s2.0-85115623705 (Scopus ID)
Funder
EU, Horizon 2020, 716065
Available from: 2021-08-20 Created: 2021-08-20 Last updated: 2023-03-24Bibliographically approved
Jonasson Stiernman, L., Grill, F., Hahn, A., Rischka, L., Lanzenberger, R., Panes Lundmark, V., . . . Rieckmann, A. (2021). Dissociations between glucose metabolism and blood oxygenation in the human default mode network revealed by simultaneous PET-fMRI. Proceedings of the National Academy of Sciences of the United States of America, 118(27), Article ID e2021913118.
Open this publication in new window or tab >>Dissociations between glucose metabolism and blood oxygenation in the human default mode network revealed by simultaneous PET-fMRI
Show others...
2021 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 118, no 27, article id e2021913118Article in journal (Refereed) Published
Abstract [en]

The finding of reduced functional MRI (fMRI) activity in the default mode network (DMN) during externally focused cognitive control has been highly influential to our understanding of human brain function. However, these negative fMRI responses, measured as relative decreases in the blood-oxygenation-level-dependent (BOLD) response between rest and task, have also prompted major questions of interpretation. Using hybrid functional positron emission tomography (PET)-MRI, this study shows that task-positive and -negative BOLD responses do not reflect antagonistic patterns of synaptic metabolism. Task-positive BOLD responses in attention and control networks were accompanied by concomitant increases in glucose metabolism during cognitive control, but metabolism in widespread DMN remained high during rest and task despite negative BOLD responses. Dissociations between glucose metabolism and the BOLD response specific to the DMN reveal functional heterogeneity in this network and demonstrate that negative BOLD responses during cognitive control should not be interpreted to reflect relative increases in metabolic activity during rest. Rather, neurovascular coupling underlying BOLD response patterns during rest and task in DMN appears fundamentally different from BOLD responses in other association networks during cognitive control.

Keywords
Default mode network, FDG, Neurovascular coupling, PET-fMRI, Working memory
National Category
Neurosciences Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-186356 (URN)10.1073/pnas.2021913118 (DOI)000685026600001 ()2-s2.0-85109180063 (Scopus ID)
Funder
EU, Horizon 2020, ERC-STG-716065
Available from: 2021-07-23 Created: 2021-07-23 Last updated: 2023-09-05Bibliographically approved
Stiernman Jonasson, L., Stillman, C. & Erickson, K. I. (2021). Impact of aerobic exercise on brain structure in models of aging: Hippocampus and beyond. In: Colin R. Martin, Victor R. Preedy, Rajkumar Rajendram (Ed.), Factors Affecting Neurological Aging: Genetics, Neurology, Behavior, and Diet (pp. 403-413). Elsevier
Open this publication in new window or tab >>Impact of aerobic exercise on brain structure in models of aging: Hippocampus and beyond
2021 (English)In: Factors Affecting Neurological Aging: Genetics, Neurology, Behavior, and Diet / [ed] Colin R. Martin, Victor R. Preedy, Rajkumar Rajendram, Elsevier, 2021, p. 403-413Chapter in book (Refereed)
Abstract [en]

Evidence from multiple scientific disciplines indicates that aerobic exercise could be effective in enhancing brain health and function in aging, and reducing the risk for cognitive impairment and dementia. Animal models have provided convincing evidence that exercise increases the expression of growth factors involved in neuroplasticity. By triggering signaling cascades in the brain, these growth factors promote proliferation, neurogenesis, neural differentiation, and cell survival in the hippocampus, and angiogenesis and/or synaptic plasticity and neural growth throughout the brain more generally. These growth factor-induced effects partly explain why exercise improves memory. Furthermore, they engender neuroprotective effects by influencing regeneration, remyelination, cell survival, and waste removal. Whereas human intervention evidence supports hippocampal plasticity, cross-sectional studies highlight effects in the cortex too, indicating that exercise-induced gross morphological changes may be regionally specific. Aerobic exercise is a promising nonpharmacological therapy to maintain brain health, although knowledge about the effects of specific exercise parameters (i.e., intensity) on different populations is still lacking.

Place, publisher, year, edition, pages
Elsevier, 2021
Keywords
Aerobic exercise, Aging, Angiogenesis, BDNF, Cognition, Fitness, Growth factor, Memory, Neurogenesis, Neuroplasticity
National Category
Neurosciences Neurology
Identifiers
urn:nbn:se:umu:diva-192242 (URN)10.1016/B978-0-12-817990-1.00035-4 (DOI)2-s2.0-85123655263 (Scopus ID)978-0-12-817990-1 (ISBN)
Available from: 2022-06-03 Created: 2022-06-03 Last updated: 2022-06-03Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-6169-5836

Search in DiVA

Show all publications