| 1. |
- Nyberg, Lars, et al.
(författare)
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Striatal dopamine D2 binding is related to frontal BOLD response during updating of long-term memory representations
- 2009
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Ingår i: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 46:4, s. 1194-1199
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Tidskriftsartikel (refereegranskat)abstract
- Multi-modal brain imaging was used to examine the relation between individual differences in resting-state striatal dopamine D2 binding and the magnitude of prefrontal BOLD activation during updating of long-term memory (LTM) representations. Increased activity in the left prefrontal cortex was observed when LTM updating was required, and there was a positive correlation between striatal D2 activity and the magnitude of left prefrontal activity during updating. These findings support predictions from neurocomputational models of a relation of dopaminergic neurotransmission to transient cognitive operations and related brain activity.
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| 2. |
- Bäckman, Lars, et al.
(författare)
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Dopamine and cognitive aging : a strong relationship
- 2006
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Ingår i: Progress in psychological science around the world. Volume 1 neural, cognitive and developmental issues. - : Psychology Press. - 9780203783122 - 9781841699615 - 9781138883314 ; , s. 455-469
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Konferensbidrag (refereegranskat)
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| 3. |
- Bäckman, Lars, et al.
(författare)
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Dopamine D(1) receptors and age differences in brain activation during working memory
- 2011
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Ingår i: Neurobiology of Aging. - Fayetteville, N.Y : Elsevier. - 0197-4580 .- 1558-1497. ; 32:10, s. 1849-1856
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Tidskriftsartikel (refereegranskat)abstract
- In an fMRI study, 20 younger and 20 healthy older adults were scanned while performing a spatial working-memory task under two levels of load. On a separate occasion, the same subjects underwent PET measurements using the radioligand [(11)C] SCH23390 to determine dopamine D(1) receptor binding potential (BP) in caudate nucleus and dorsolateral prefrontal cortex (DLPFC). The fMRI study revealed a significant load modulation of brain activity (higher load>lower load) in frontal and parietal regions for younger, but not older, adults. The PET measurements showed marked age-related reductions of D(1) BP in caudate and DLPFC. Statistical control of caudate and DLPFC D(1) binding eliminated the age-related reduction in load-dependent BOLD signal in left frontal cortex, and attenuated greatly the reduction in right frontal and left parietal cortex. These findings suggest that age-related alterations in dopaminergic neurotransmission may contribute to underrecruitment of task-relevant brain regions during working-memory performance in old age.
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| 4. |
- 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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| 5. |
- Duarte Fernandes, Carla Patricia, et al.
(författare)
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Lack of association of the rs1344706 ZNF804A variant with cognitive functions and DTI indices of white matter microstructure in two independent healthy populations
- 2014
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0925-4927 .- 1872-7506. ; 222:1-2, s. 60-66
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Tidskriftsartikel (refereegranskat)abstract
- The rs1344706 single nucleotide polymorphism with in intron 2 of the ZNF804A gene is strongly associated with schizophrenia and bipolar disorder. This variant has also been associated in some studies with a range of cognitive and neuro imaging phenotypes, but several studies have reported no effect on the same phenotypes in other samples. Here, we genotyped 670 healthy adult Norwegian subjects and 1753 healthy adult Swedish subjects for rs1344706, and tested for associations with cognitive phenotypes including general intellectual abilities, memory functions and cognitive inhibition. We also tested whether rs1344706 is associated with white matter microstructural properties using diffusion tensor imaging (DTI) data from 250 to 340 of the Norwegian and Swedish subjects, respectively. Whole-brain voxel-wise statistical modeling of the effect of the ZNF804A variant on two DTI indices, fractional anisotropy (FA) and radial diffusivity (RD), was performed using tract-based spatial statistics (TBSS), and commonly reported effect sizes were calculated within several large-scale white matter pathways based on neuroanatomic atlases. No significant associations were found between rs1344706 and the cognitive traits or white matter microstructure. We conclude that the rs1344706 SNP has no significant effect on these phenotypes in our two reasonably powered samples.
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| 6. |
- Karalija, Nina, 1984-, et al.
(författare)
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A common polymorphism in the dopamine transporter gene predicts working memory performance and in vivo dopamine integrity in aging
- 2021
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 245
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine (DA) integrity is suggested as a potential cause of individual differences in working memory (WM) performance among older adults. Still, the principal dopaminergic mechanisms giving rise to WM differences remain unspecified. Here, 61 single-nucleotide polymorphisms, located in or adjacent to various dopamine-related genes, were assessed for their links to WM performance in a sample of 1313 adults aged 61–80 years from the Berlin Aging Study II. Least Absolute Shrinkage and Selection Operator (LASSO) regression was conducted to estimate associations between polymorphisms and WM. Rs40184 in the DA transporter gene, SLC6A3, showed allelic group differences in WM, with T-carriers performing better than C homozygotes (p<0.01). This finding was replicated in an independent sample from the Cognition, Brain, and Aging study (COBRA; baseline: n = 181, ages: 64–68 years; 5-year follow up: n = 129). In COBRA, in vivo DA integrity was measured with 11C-raclopride and positron emission tomography. Notably, WM as well as in vivo DA integrity was higher for rs40184 T-carriers at baseline (p<0.05 for WM and caudate and hippocampal D2-receptor availability) and at the 5-year follow-up (p<0.05 for WM and hippocampal D2 availability). Our findings indicate that individual differences in DA transporter function contribute to differences in WM performance in old age, presumably by regulating DA availability.
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| 7. |
- 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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| 8. |
- Lind, Johanna, et al.
(författare)
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Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers
- 2006
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 129:5, s. 1240-1248
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Tidskriftsartikel (refereegranskat)abstract
- The apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE epsilon4 carriers (age range: 49-74 years; 19 females), of which 10 were homozygous for the epsilon4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE epsilon4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE epsilon4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.
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| 9. |
- Lind, Johanna, et al.
(författare)
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Reduced hippocampal volume in non-demented carriers fo the apolipoprotein E ε4 : Relation to chronological age and recognition memory
- 2006
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 396:1, s. 23-27
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein E ε4 (APOE ε4) is the main known genetic risk factor for Alzheimer's disease (AD). Some previous studies have reported structural brain changes as well as cognitive deficits in non-demented APOE ε4 carriers, but the pattern of results is inconsistent and studies with larger sample sizes have been called for. Here we compared hippocampal volume and recognition–memory performance between AD-symptom-free carriers (N = 30) and non-carriers (N = 30) of the APOE ε4 (age range: 49–79 years). We observed reduced right hippocampal volume in APOE ε4 carriers, and found that the difference was most pronounced before the age of 65. Further, the APOE ε4 carriers made significantly more false alarms in the recognition–memory test, and the number of false alarms correlated significantly with right hippocampus volume. These results indicate that relatively young individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. A question for the future is whether smaller hippocampal volume represents early-onset hippocampal volume reduction or an inherent trait.
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| 10. |
- Maitland, Scott B., et al.
(författare)
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On the structure of personality : Are there separate temperament and character factors?
- 2009
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Ingår i: Personality and Individual Differences. - : Elsevier. - 0191-8869 .- 1873-3549. ; 47:3, s. 180-184
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Tidskriftsartikel (refereegranskat)abstract
- The Temperament and Character Inventory (TCI) is a widely used measure of psychobiological aspects of personality. Theoretically, the TCI is defined as comprising four temperament and three character factors. Most previous examinations of the factor structure have used exploratory factor methods with mixed results. We used confirmatory factor analyses (CFA) to examine the TCI in a sample of 2423 adults aged 35–90 years (1093 women, 1330 men) from the Betula study. Support for the seven TCI factors was mixed. Models including second-order factors provided no evidence that the seven first-order TCI factors reflect higher-order temperament and character constructs. Our findings provide no support that individual differences on the seven first-order TCI factors reflect distinct temperament or character dimensions of personality. Whereas more complex modeling strategies rejected separate character and temperament models, the simultaneous (seven-factor) model, and the use of second-order factors; the harm avoidance, self-directedness, and cooperativeness factors were acceptable examined individually. Results for novelty seeking were marginal and self-transcendence, reward dependence and/or persistence factors were not acceptable.
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