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| 2. |
- Dahlin, Erika, 1981-
(author)
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Train your brain : updating, transfer, and neural changes
- 2009
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Doctoral thesis (other academic/artistic)abstract
- An initial aim of this thesis was to determine whether training of a specific executive function (updating) produces improvements in performance on trained and transfer tasks, and whether the effects are maintained over time. Neural systems underlying training and transfer effects were also investigated and one question considered is whether transfer depends on general or specific neural overlap between training and transfer tasks. An additional aim was to identify how individual differences in executive functioning are mapped to functional brain changes. In Study I, significant training-related changes in performance on the letter memory criterion task were found in both young and older adults after 5 weeks of updating training. Transfer to a 3-back test of updating was also demonstrated in the young adults. Functional Magnetic Resonance Imaging (fMRI) revealed overlapping activity in letter memory and 3-back tasks in fronto-parietal areas and striatum pre-training, and a joint training-related activity increase for the tasks in a striatal region. No transfer was observed to a task (Stroop) that engaged fronto-parietal areas, but not the striatal region and updating per se. Moreover, age-related striatal changes imposed constraints on transfer. In Study II, additional transfer tasks and a test of long-term maintenance were included. Results revealed that training-related gains in performance were maintained 18 months post-training in both young and older adults, whereas transfer effects were limited to tasks requiring updating and restricted to young participants. In Study III, analyses of brain activity and performance during n-back (1/2/3-back) were executed. This task enables manipulation of executive demand, which permits examination of how individual differences in executive functioning can be mapped to functional brain changes. Relative to a young high- performing group, capacity constraints in executive functioning were apparent between 1–2-back for the elderly participants and between 2–3-back for a young low-performing group. Capacity constraints in neural activity followed this pattern by showing a monotonically increasing response in the parietal cortex and the thalamus for young high performers, whereas activity levelled off at 1-back for elderly performers and at 2-back for young low performers. The response in the dorsal frontal cortex followed a similar pattern. Together, these findings indicate that fronto-parietal as well as sub-cortical areas are important for individual differences in executive functioning, training of updating and transfer effects.
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| 3. |
- Darki, Fahimeh, et al.
(author)
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DCDC2 polymorphism is associated with left temporoparietal gray and white matter structures during development.
- 2014
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In: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 34:43, s. 14455-62
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Journal article (peer-reviewed)abstract
- Three genes, DYX1C1, DCDC2, and KIAA0319, have been previously associated with dyslexia, neuronal migration, and ciliary function. Three polymorphisms within these genes, rs3743204 (DYX1C1), rs793842 (DCDC2), and rs6935076 (KIAA0319) have also been linked to normal variability of left temporoparietal white matter volume connecting the middle temporal cortex to the angular and supramarginal gyri. Here, we assessed whether these polymorphisms are also related to the cortical thickness of the associated regions during childhood development using a longitudinal dataset of 76 randomly selected children and young adults who were scanned up to three times each, 2 years apart. rs793842 in DCDC2 was significantly associated with the thickness of left angular and supramarginal gyri as well as the left lateral occipital cortex. The cortex was significantly thicker for T-allele carriers, who also had lower white matter volume and lower reading comprehension scores. There was a negative correlation between white matter volume and cortical thickness, but only white matter volume predicted reading comprehension 2 years after scanning. These results show how normal variability in reading comprehension is related to gene, white matter volume, and cortical thickness in the inferior parietal lobe. Possibly, the variability of gray and white matter structures could both be related to the role of DCDC2 in ciliary function, which affects both neuronal migration and axonal outgrowth.
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| 4. |
- Darki, Fahimeh, et al.
(author)
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Human ROBO1 regulates white matter structure in corpus callosum.
- 2017
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In: Brain Structure and Function. - : Springer Science and Business Media LLC. - 1863-2653 .- 1863-2661. ; 222:2, s. 707-716
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Journal article (peer-reviewed)abstract
- The axon guidance receptor, Robo1, controls the pathfinding of callosal axons in mice. To determine whether the orthologous ROBO1 gene is involved in callosal development also in humans, we studied polymorphisms in the ROBO1 gene and variation in the white matter structure in the corpus callosum using both structural magnetic resonance imaging and diffusion tensor magnetic resonance imaging. We found that five polymorphisms in the regulatory region of ROBO1 were associated with white matter density in the posterior part of the corpus callosum pathways. One of the polymorphisms, rs7631357, was also significantly associated with the probability of connections to the parietal cortical regions. Our results demonstrate that human ROBO1 may be involved in the regulation of the structure and connectivity of posterior part of corpus callosum.
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| 5. |
- Darki, Fahimeh, et al.
(author)
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Three dyslexia susceptibility genes, DYX1C1, DCDC2, and KIAA0319, affect temporo-parietal white matter structure.
- 2012
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In: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 72:8, s. 671-6
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Journal article (peer-reviewed)abstract
- BACKGROUND: Volume and integrity of white matter correlate with reading ability, but the underlying factors contributing to this variability are unknown.METHODS: We investigated single nucleotide polymorphisms in three genes previously associated with dyslexia and implicated in neuronal migration (DYX1C1, DCDC2, KIAA0319) and white matter volume in a cohort of 76 children and young adults from the general population.RESULTS: We found that all three genes contained polymorphisms that were significantly associated with white matter volume in the left temporo-parietal region and that white matter volume influenced reading ability.CONCLUSIONS: The identified region contained white matter pathways connecting the middle temporal gyrus with the inferior parietal lobe. The finding links previous neuroimaging and genetic results and proposes a mechanism underlying variability in reading ability in both normal and impaired readers.
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| 6. |
- Dumontheil, Iroise, et al.
(author)
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Influence of the COMT genotype on working memory and brain activity changes during development.
- 2011
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In: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 70:3, s. 222-9
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Journal article (peer-reviewed)abstract
- BACKGROUND: The Valine158Methionine (Val158Met) polymorphism of the COMT gene leads to lower enzymatic activity and higher dopamine availability in Met carriers. The Met allele is associated with better performance and reduced prefrontal cortex activation during working memory (WM) tasks in adults. Dopaminergic system changes during adolescence may lead to a reduction of basal dopamine levels, potentially affecting Met allele benefits during development.METHODS: We investigated the association of COMT genotype with behavioral (n = 322) and magnetic resonance imaging data (n = 81-84) collected during performance of a visuospatial WM task and potential changes in these effects during development (reflected in age × genotype interactions). Data were collected from a cross-sectional and longitudinal typically developing sample of 6- to 20-year-olds.RESULTS: Visuospatial WM capacity exhibited an age × genotype interaction, with a benefit of the Met allele emerging after 10 years of age. There was a parallel age × genotype interaction on WM-related activation in the right inferior frontal gyrus and intraparietal sulcus (IPS), with increases in activation with age in the Val/Val group only. Main effects of COMT genotype were also observed in the IPS, with greater gray matter volumes bilaterally and greater right IPS activation in the Val/Val group compared with the Met carriers.CONCLUSIONS: These results suggest that COMT genotype effects on WM brain activity and behavior are not static during development. The full developmental picture should be considered when trying to understand the impact of genetic polymorphisms on the mature cognition of healthy adult or psychiatric populations.
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| 7. |
- Edin, Fredrik, et al.
(author)
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Mechanism for top-down control of working memory capacity
- 2009
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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. ; 106:16, s. 6802-6807
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Journal article (peer-reviewed)abstract
- Working memory capacity, the maximum number of items that we can transiently store in working memory, is a good predictor of our general cognitive abilities. Neural activity in both dorsolateral prefrontal cortex and posterior parietal cortex has been associated with memory retention during visuospatial working memory tasks. The parietal cortex is thought to store the memories. However, the role of the dorsolateral prefrontal cortex, a top-down control area, during pure information retention is debated, and the mechanisms regulating capacity are unknown. Here, we propose that a major role of the dorsolateral prefrontal cortex in working memory is to boost parietal memory capacity. Furthermore, we formulate the boosting mechanism computationally in a biophysical cortical microcircuit model and derive a simple, explicit mathematical formula relating memory capacity to prefrontal and parietal model parameters. For physiologically realistic parameter values, lateral inhibition in the parietal cortex limits mnemonic capacity to a maximum of 2-7 items. However, at high loads inhibition can be counteracted by excitatory prefrontal input, thus boosting parietal capacity. Predictions from the model were confirmed in an fMRI study. Our results show that although memories are stored in the parietal cortex, interindividual differences in memory capacity are partly determined by the strength of prefrontal top-down control. The model provides a mechanistic framework for understanding top-down control of working memory and specifies two different contributions of prefrontal and parietal cortex to working memory capacity.
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| 8. |
- Edin, Fredrik, et al.
(author)
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Stronger fronto-parietal connectivity accounts for development of working memory-related brain activity
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Other publication (other academic/artistic)abstract
- Cognitive functions, including working memory capacity, improve during childhood and early adulthood. Several maturational processes take place during that time, most importantly the myelination of axons, pruning of synapses and strengthening of the remaining synapses. However, it has not yet been shown how to directly relate these cellular changes to working memory development and associated changes in brain activity. Here, we bridge this gap by integrating biophysically-based computational modelling and functional MRI of the visuospatial working memory. Cellular mechanisms corresponding to different maturational processes were implemented in in silico 'child' networks, and the predicted difference in activity between 'child' and a reference 'adult' network was then compared to measured brain activity in children and adults. Network models with stronger connectivity between brain areas, but not networks with faster conduction or increased neuronal specificity, were supported by measured developmental increases in brain activity and correlations between frontal and parietal areas. The 'adult' networks with stronger fronto-parietal connections also exhibited greater stability during distraction, which was consistent with the developmental improvement in working memory performance.
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| 9. |
- Edin, Fredrik, et al.
(author)
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Stronger synaptic connectivity as a mechanism behind development of working memory-related brain activity during childhood
- 2007
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In: Journal of cognitive neuroscience. - : MIT Press - Journals. - 0898-929X .- 1530-8898. ; 19:5, s. 750-760
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Journal article (peer-reviewed)abstract
- The cellular maturational processes behind cognitive development during childhood, including the development of working memory capacity, are still unknown. By using the most standard computational model of visuospatial working memory, we investigated the consequences of cellular maturational processes, including myelination, synaptic strengthening, and synaptic pruning, on working memory-related brain activity and performance. We implemented five structural developmental changes occurring as a result of the cellular maturational processes in the biophysically based computational network model. The developmental changes in memory activity predicted from the simulations of the model were then compared to brain activity measured with functional magnetic resonance imaging in children and adults. We found that networks with stronger fronto-parietal synaptic connectivity between cells coding for similar stimuli, but not those with faster conduction, stronger connectivity within a region, or increased coding specificity, predict measured developmental increases in both working memory-related brain activity and in correlations of activity between regions. Stronger fronto-parietal synaptic connectivity between cells coding for similar stimuli was thus the only developmental process that accounted for the observed changes in brain activity associated with development of working memory during childhood.
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| 10. |
- Einarsdottir, Elisabet, et al.
(author)
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Identification of NCAN as a candidate gene for developmental dyslexia.
- 2017
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Journal article (peer-reviewed)abstract
- A whole-genome linkage analysis in a Finnish pedigree of eight cases with developmental dyslexia (DD) revealed several regions shared by the affected individuals. Analysis of coding variants from two affected individuals identified rs146011974G > A (Ala1039Thr), a rare variant within the NCAN gene co-segregating with DD in the pedigree. This variant prompted us to consider this gene as a putative candidate for DD. The RNA expression pattern of the NCAN gene in human tissues was highly correlated (R > 0.8) with that of the previously suggested DD susceptibility genes KIAA0319, CTNND2, CNTNAP2 and GRIN2B. We investigated the association of common variation in NCAN to brain structures in two data sets: young adults (Brainchild study, Sweden) and infants (FinnBrain study, Finland). In young adults, we found associations between a common genetic variant in NCAN, rs1064395, and white matter volume in the left and right temporoparietal as well as the left inferior frontal brain regions. In infants, this same variant was found to be associated with cingulate and prefrontal grey matter volumes. Our results suggest NCAN as a new candidate gene for DD and indicate that NCAN variants affect brain structure.
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