| 1. |
- Duarte Fernandes, Carla Patricia, et al.
(author)
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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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In: Psychiatry Research. - : Elsevier BV. - 0925-4927 .- 1872-7506. ; 222:1-2, s. 60-66
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Journal article (peer-reviewed)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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| 2. |
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| 3. |
- Kauppi, Karolina, 1985-, et al.
(author)
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Decreased medial temporal lobe activation in BDNF 66Met allele carriers during memory encoding
- 2013
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In: Neuropsychologia. - : Elsevier. - 0028-3932 .- 1873-3514. ; 51:12, s. 2462-2468
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Journal article (peer-reviewed)abstract
- The Met allele of the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with impaired activity-dependent secretion of BDNF protein and decreased memory performance. Results from imaging studies relating Val66Met to brain activation during memory processing have been inconsistent, with reports of both increased and decreased activation in the Medial Temporal Lobe (MTL) in Met carriers relative to Val homozygotes. Here, we extensively studied BDNF Val66Met in relation to brain activation and white matter integrity as well as memory performance in a large imaging (n=194) and behavioral (n=2229) sample, respectively. Functional magnetic resonance imaging (fMRI) was used to investigate MTL activation in healthy participants in the age of 55–75 years during a face-name episodic encoding and retrieval task. White matter integrity was measured using diffusion tensor imaging.BDNF Met allele carriers had significantly decreased activation in the MTL during encoding processes, but not during retrieval processes. In contrast to previous proposals, the effect was not modulated by age and the polymorphism was not related to white matter integrity. Met carriers had lower memory performance than Val homozygotes, but differences were subtle and not significant. In conclusion, the BDNF Met allele has a negative influence on MTL functioning, preferentially during encoding processes, which might translate into impaired episodic memory function.
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| 4. |
- Kauppi, Karolina, et al.
(author)
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KIBRA polymorphism is related to enhanced memory and elevated hippocampal processing.
- 2011
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In: The Journal of neuroscience : the official journal of the Society for Neuroscience. - : Society for Neuroscience. - 1529-2401 .- 0270-6474. ; 31:40, s. 14218-22
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Journal article (peer-reviewed)abstract
- Several studies have linked the KIBRA rs17070145 T polymorphism to superior episodic memory in healthy humans. One study investigated the effect of KIBRA on brain activation patterns (Papassotiropoulos et al., 2006) and observed increased hippocampal activation in noncarriers of the T allele during retrieval. Noncarriers were interpreted to need more hippocampal activation to reach the same performance level as T carriers. Using large behavioral (N = 2230) and fMRI (N = 83) samples, we replicated the KIBRA effect on episodic memory performance, but found increased hippocampal activation in T carriers during episodic retrieval. There was no evidence of compensatory brain activation in noncarriers within the hippocampal region. In the main fMRI sample, T carriers performed better than noncarriers during scanning but, importantly, the difference in hippocampus activation remained after post hoc matching according to performance, sex, and age (N = 64). These findings link enhanced memory performance in KIBRA T allele carriers to elevated hippocampal functioning, rather than to neural compensation in noncarriers.
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| 5. |
- Nyberg, Lars, et al.
(author)
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Age-related and genetic modulation of frontal cortex efficiency
- 2014
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In: Journal of cognitive neuroscience. - : MIT Press. - 0898-929X .- 1530-8898. ; 26:4, s. 746-754
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Journal article (peer-reviewed)abstract
- The dorsolateral pFC (DLPFC) is a key region for working memory. It has been proposed that the DLPFC is dynamically recruited depending on task demands. By this view, high DLPFC recruitment for low-demanding tasks along with weak DLPFC upregulation at higher task demands reflects low efficiency. Here, the fMRI BOLD signal during working memory maintenance and manipulation was examined in relation to aging and catechol-O-methyltransferase (COMT) Val(158)Met status in a large representative sample (n = 287). The efficiency hypothesis predicts a weaker DLPFC response during manipulation, along with a stronger response during maintenance for older adults and COMT Val carriers compared with younger adults and COMT Met carriers. Consistent with the hypothesis, younger adults and met carriers showed maximal DLPFC BOLD response during manipulation, whereas older adults and val carriers displayed elevated DLPFC responses during the less demanding maintenance condition. The observed inverted relations support a link between dopamine and DLPFC efficiency.
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| 6. |
- Nyberg, Lars, et al.
(author)
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Longitudinal evidence for diminished frontal-cortex function in aging
- 2010
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:52, s. 22682-22686
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Journal article (peer-reviewed)abstract
- Cross-sectional estimates of age-related changes in brain structure and function were compared with 6-y longitudinal estimates. The results indicated increased sensitivity of the longitudinal approach as well as qualitative differences. Critically, the cross-sectional analyses were suggestive of age-related frontal overrecruitment, whereas the longitudinal analyses revealed frontal underrecruitment with advancing age. The cross-sectional observation of overrecruitment reflected a select elderly sample. However, when followed over time, this sample showed reduced frontal recruitment. These findings dispute inferences of true age changes on the basis of age differences, hence challenging some contemporary models of neurocognitive aging, and demonstrate age-related decline in frontal brain volume as well as functional response.
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| 7. |
- Persson, Jonas, et al.
(author)
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Longitudinal structure – function correlates in elderly reveal MTL dysfunction with cognitive decline
- 2012
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In: Cerebral Cortex. - New York, NY : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 22:10, s. 2297-2304
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Journal article (peer-reviewed)abstract
- By integrating behavioral measures and imaging data, previous investigations have explored the relationship between biological markers of aging and cognitive functions. Evidence from functional and structural neuroimaging has revealed that hippocampal volume and activation patterns in the medial temporal lobe (MTL) may predict cognitive performance in old age. Most past demonstrations of age-related differences in brain structure–function were based on cross-sectional comparisons. Here, the relationship between 6-year intraindividual change in functional magnetic resonance imaging (fMRI) signal and change in memory performance over 2 decades was examined. Correlations between intraindividual change in fMRI signal during episodic encoding and change in memory performance measured outside of scanning were used as an estimate for relating brain–behavior changes. The results revealed a positive relationship between activation change in the hippocampus (HC) and change in memory performance, reflecting reduced hippocampal activation in participants with declining performance. Using a similar analytic approach as for the functional data, we found that individuals with declining performance had reduced HC volume compared with individuals with intact performance. These observations provide a strong link between cognitive change in older adults and MTL structure and function and thus provide insights into brain correlates of individual variability in aging trajectories.
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