| 1. |
- Karlsson, Sari, et al.
(författare)
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Modulation of striatal dopamine D1 binding by cognitive processing
- 2009
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Ingår i: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 48:2, s. 398-404
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Tidskriftsartikel (refereegranskat)abstract
- There is strong evidence that dopamine (DA) is implicated in higher-order cognitive functioning, but it remains controversial whether D1 receptor binding can be modified by cognitive activity. We examined striatal D1 binding potential (BP) in 20 younger (22-30 years) and 20 older (65-75 years) persons who underwent two [(11)C] SCH 23390 PET measurements, one while resting and one while performing a cognitive task taxing inhibitory functioning. The younger persons showed significant task-related BP reductions in sensorimotor, limbic, and associative striatum during cognitive activity compared to rest. Older persons showed no reliable BP reductions in any striatal subregion. These findings demonstrate that D1 receptor binding can be modified by cognitive activity in younger persons, but also provide novel evidence for the notion that human aging is associated not only with lower DA receptor density but also with altered modifiability of the DA system.
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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. |
- 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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| 4. |
- 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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| 5. |
- de Frias, Cindy M., et al.
(författare)
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Influence of COMT Gene Polymorphism on fMRI-assessed Sustained and Transient Activity during a Working Memory Task
- 2010
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Ingår i: Journal of cognitive neuroscience. - Cambridge, Mass. : MIT Press. - 0898-929X .- 1530-8898. ; 22:7, s. 1614-1622
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Tidskriftsartikel (refereegranskat)abstract
- The catechol O-methyltransferase (COMT) gene-encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)-contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic-phasic hypothesis, individuals carrying the low-enzyme- activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic-phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, matched on age, education, and cognitive performance. There were no differences in 2-back performance between genotype groups. Met carriers displayed a greater transient medial temporal lobe response in the updating phase of working memory, whereas val carriers showed a greater sustained PFC activation in the maintenance phase. These results support the tonic-phasic theory of DA function in elucidating the specific phenotypic influence of the COMT val(158)met polymorphism on different components of working memory.
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| 6. |
- Ferreira, Daniel, et al.
(författare)
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The interactive effect of demographic and clinical factors on hippocampal volume : A multicohort study on 1958 cognitively normal individuals
- 2017
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Ingår i: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 27:6, s. 653-667
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.
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| 7. |
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| 8. |
- Karlsson, Sari, et al.
(författare)
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Relationship of dopamine D1 receptor binding in striatal and extrastriatal regions to cognitive functioning in healthy humans
- 2011
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Ingår i: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 57:2, s. 346-351
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine (DA) availability in both striatal and extrastriatal brain regions has been implicated in cognitive performance. Given that different brain regions are neuroanatomically and functionally different, DA receptor binding in different brain regions may be selectively important to specific cognitive functions. Using PET and the radioligand SCH23390, we measured D1 receptor binding potential (BP(ND)) in dorsolateral prefrontal cortex (DLPFC), hippocampus (HC), as well as in sensorimotor (SMST), associative (AST), and limbic (LST) striatum in 20 healthy younger persons. Subjects completed tasks assessing executive functioning, episodic memory, speed, and general knowledge. Unlike previous reports, we found no linear or curvilinear relationships between D1 receptor binding in DLPFC and performance in any cognitive task. However, BP(ND) in HC was positively linked to executive performance as well as to speed and knowledge. With regard to the striatal subregions, D1 BP(ND) in SMST was more strongly related to speed compared to the other striatal subregions, whereas D1 BP(ND) in AST was more strongly linked to general knowledge. These findings provide support for the notion that D1 receptors in separate brain regions are differentially related to performance in tasks tapping various cognitive domains.
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| 9. |
- 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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| 10. |
- Rieckmann, Anna, et al.
(författare)
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Dopamine D1 Receptor Associations within and between Dopaminergic Pathways in Younger and Elderly Adults : Links to Cognitive Performance
- 2011
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Ingår i: Cerebral Cortex. - Oxford : Oxford University Press. - 1047-3211 .- 1460-2199. ; 21:9, s. 2023-2032
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Tidskriftsartikel (refereegranskat)abstract
- Age-related dopamine (DA) losses have been extensively demonstrated for the D2 receptor subtype. Comparatively little is known about adult age changes regarding D1 receptors. In this study, we demonstrate marked age-related D1 receptor losses in striatal, limbic, and cortical areas using positron emission tomography and the radioligand [11C]SCH23390 in humans. Interregional correlations of binding potential (BP) values were high for areas within DA pathways in younger and elderly adults alike. Furthermore, interregional correlations in D1 BP between DA pathways were uniformly high in younger adults, indicating that D1 receptor densities in striatal, limbic, and cortical areas are not regulated independently, despite dopaminergic innervation from different midbrain areas. For elderly adults, between-pathway correlations of D1 receptor densities were preserved only between mesolimbic and mesocortical areas, whereas striatal BPs were weakly related to those in limbic and neocortical regions. Importantly, weak between-pathway correlations in elderly adults were found only for the slower half of the sample when BP was estimated during a cognitive interference task. These results suggest that D1 receptor densities in different pathways are not regulated independently in younger adults, but segregate in older age, and that this segregation of D1 receptor systems may be related to age-related cognitive slowing.
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