| 1. |
- Jonasson, Lars S., et al.
(författare)
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Dopamine release in nucleus accumbens during rewarded task switching measured by [C-11]raclopride
- 2014
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 99, s. 357-364
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Tidskriftsartikel (refereegranskat)abstract
- Reward and motivation have positive influences on cognitive-control processes in numerous settings. Models of reward implicate corticostriatal loops and the dopamine (DA) system, with special emphasis on D-2 receptors in nucleus accumbens (NAcc). In this study, 11 right-handed males (35-40 years) were scanned with positron emission tomography (PET) in a single [C-11]raclopride dynamic scan during rewarded and non-rewarded task switching. Rewarded task switching (relative to baseline task switching) decreased [11C]raclopride binding in NAcc. Decreasing NAcc [C-11]raclopride binding was strongly associated with task reaction time measures that reflect individual differences in effort and control strategies. Voxelwise analyses additionally revealed reward-related DA release in anterodorsal caudate, a region previously associated with task-switching. These PET findings provide evidence for striatal DA release during motivated cognitive control, and further suggest that NAcc DA release predicts the task reaction time benefits of reward incentives.
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| 2. |
- Köhncke, Ylva, et al.
(författare)
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Self-rated intensity of habitual physical activities is positively associated with dopamine D-2/3 receptor availability and cognition
- 2018
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 181, s. 605-616
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Tidskriftsartikel (refereegranskat)abstract
- Between-person differences in cognitive performance in older age are associated with variations in physical activity. The neurotransmitter dopamine (DA) contributes to cognitive performance, and the DA system deteriorates with advancing age. Animal data and a patient study suggest that physical activity modulates DA receptor availability, but data from healthy humans are lacking. In a cross-sectional study with 178 adults aged 64-68 years, we investigated links among self-reported physical activity, D(2/3)DA receptor (D2/3DR) availability, and cognitive performance. D2/3DR availability was measured with [C-11]raclopride positron emission tomography at rest. We used structural equation modeling to obtain latent factors for processing speed, episodic memory, working memory, physical activity, and D2/3DR availability in caudate, putamen, and hippocampus. Physical activity intensity was positively associated with D2/3DR availability in caudate, but not putamen and hippocampus. Frequency of physical activity was not related to D2/3DR availability. Physical activity intensity was positively related to episodic memory and working memory. D2/3DR availability in caudate and hippocampus was positively related to episodic memory. Taken together, our results suggest that striatal DA availability might be a neurochemical correlate of episodic memory that is also associated with physical activity.
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| 3. |
- Lövdén, Martin, et al.
(författare)
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Latent-Profile Analysis Reveals Behavioral and Brain Correlates of Dopamine-Cognition Associations
- 2018
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 28:11, s. 3894-3907
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Salami, Alireza, et al.
(författare)
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Dopamine D-2/3 Binding Potential Modulates Neural Signatures of Working Memory in a Load-Dependent Fashion
- 2019
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 39:3, s. 537-547
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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 D-2/3 PET assessment using [C-11] raclopride. Using multivariate partial-least-squares analysis, we observed a significant pattern revealing positive associations of striatal as well as extrastriatal DA D-2/3 receptors to BOLD response in the thalamo-striatalcortical 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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| 5. |
- de Boer, Lieke, et al.
(författare)
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Corticostriatal White Matter Integrity and Dopamine D1 Receptor Availability Predict Age Differences in Prefrontal Value Signaling during Reward Learning
- 2020
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 30:10, s. 5270-5280
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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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| 6. |
- Garzón, Benjamín, et al.
(författare)
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Role of dopamine and gray matter density in aging effects and individual differences of functional connectomes
- 2021
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Ingår i: Brain Structure and Function. - : Springer Science and Business Media LLC. - 1863-2653 .- 1863-2661. ; 226, s. 743-758
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Tidskriftsartikel (refereegranskat)abstract
- With increasing age, functional connectomes become dissimilar across normal individuals, reflecting heterogenous aging effects on functional connectivity (FC). We investigated the distribution of these effects across the connectome and their relationship with age-related differences in dopamine (DA) D1 receptor availability and gray matter density (GMD). With this aim, we determined aging effects on mean and interindividual variance of FC using fMRI in 30 younger and 30 older healthy subjects and mapped the contribution of each connection to the patterns of age-related similarity loss. Aging effects on mean FC accounted mainly for the dissimilarity between connectomes of younger and older adults, and were related, across brain regions, to aging effects on DA D1 receptor availability. Aging effects on the variance of FC indicated a global increase in variance with advancing age, explained connectome dissimilarity among older subjects and were related to aging effects on variance of GMD. The relationship between aging and the similarity of connectomes can thus be partly explained by age differences in DA modulation and gray matter structure.
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| 7. |
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| 8. |
- Karalija, Nina, 1984-, et al.
(författare)
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C957T-mediated Variation in Ligand Affinity Affects the Association between C-11-raclopride Binding Potential and Cognition
- 2019
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Ingår i: Journal of cognitive neuroscience. - : MIT Press. - 0898-929X .- 1530-8898. ; 31:2, s. 314-325
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Karalija, Nina, 1984-, et al.
(författare)
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Cardiovascular factors are related to dopamine integrity and cognition in aging
- 2019
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley-Blackwell. - 2328-9503. ; 6:11, s. 2291-2303
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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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| 10. |
- Karalija, Nina, 1984-, et al.
(författare)
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Longitudinal Dopamine D2 Receptor Changes and Cerebrovascular Health in Aging
- 2022
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Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 99
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Cross-sectional studies suggest marked dopamine (DA) decline in aging, but longitudinal evidence is lacking. The aim of this study was to estimate within-person decline rates for DA D2-like receptors (DRD2) in aging and examine factors that may contribute to individual differences in DRD2 decline rates. METHODS: We investigated 5-year within-person changes in DRD2 availability in a sample of older adults. At both occasions, PET with 11C-raclopride and MRI were used to measure DRD2 availability in conjunction with structural and vascular brain integrity. RESULTS: Longitudinal analyses of the sample (baseline: n = 181, ages: 64-68 years, 100 men and 81 women; 5-year follow-up: n = 129, 69 men and 60 women) revealed aging-related striatal and extrastriatal DRD2 decline, along with marked individual differences in rates of change. Notably, the magnitude of striatal DRD2 decline was ∼50% of past cross-sectional estimates, suggesting that the DRD2 decline rate has been overestimated in past cross-sectional studies. Significant DRD2 reductions were also observed in select extrastriatal regions, including hippocampus, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Distinct profiles of correlated DRD2 changes were found across several associative regions (ACC, dorsal striatum, and hippocampus) and in the reward circuit (nucleus accumbens and OFC). DRD2 losses in associative regions were associated with white matter lesion progression, whereas DRD2 losses in limbic regions were related to reduced cortical perfusion. DISCUSSION: These findings provide the first longitudinal evidence for individual and region-specific differences of DRD2 decline in older age and support the hypothesis that cerebrovascular factors are linked to age-related dopaminergic decline.
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