2019 |
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Nicholas Judd, Bruno Sauce, John Wiedenhoeft, Jeshua Tromp, Bader Chaarani, Alexander Schliep, Argyris Stringaris, Betteke van Noort, Jani Penttilä, Yvonne Grimmer, Corinna Insensee, Andreas Becker, Tobias Banaschewski, Arun L W Bokde, Erin Burke Quinlan, Sylvane Desrivières, Herta Flor, Antoine Grigis, Penny Gowland, Bernd Ittermann, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Sarah Hohmann, Sabina Millenet, Juliane H Fröhner, Michael N Smolka, Henrik Walter, Robert Whelan, Gunter Schumann, Hugh Garavan, Torkel Klingberg Independent effects of socioeconomic status and genetics on adolescent cognition and brain development Journal Article bioRxiv, 2019. @article{Judd2019, title = {Independent effects of socioeconomic status and genetics on adolescent cognition and brain development}, author = {Nicholas Judd and Bruno Sauce and John Wiedenhoeft and Jeshua Tromp and Bader Chaarani and Alexander Schliep and Argyris Stringaris and Betteke van Noort and Jani Penttilä and Yvonne Grimmer and Corinna Insensee and Andreas Becker and Tobias Banaschewski and Arun L W Bokde and Erin Burke Quinlan and Sylvane Desrivi{è}res and Herta Flor and Antoine Grigis and Penny Gowland and Bernd Ittermann and Jean-Luc Martinot and Marie-Laure Paill{è}re Martinot and Eric Artiges and Frauke Nees and Dimitri Papadopoulos Orfanos and Tomáš Paus and Luise Poustka and Sarah Hohmann and Sabina Millenet and Juliane H Fröhner and Michael N Smolka and Henrik Walter and Robert Whelan and Gunter Schumann and Hugh Garavan and Torkel Klingberg}, doi = {10.1101/866624}, year = {2019}, date = {2019-12-06}, journal = {bioRxiv}, abstract = {Genetic factors and socioeconomic (SES) inequalities play a large role in educational attainment, and both have been associated with variations in brain structure and cognition. However, genetics and SES are correlated, and no prior study has assessed their neural effects independently. Here we used polygenic score for educational attainment (EduYears-PGS) as well as SES, in a longitudinal study of 551 adolescents, to tease apart genetic and environmental effects on brain development and cognition. Subjects received a structural MRI scan at ages 14 and 19. At both time-points, they performed three working memory (WM) tasks. SES and EduYears-PGS were correlated (r = 0.27) and had both common and independent effects on brain structure and cognition. Specifically, lower SES was related to less total cortical surface area and lower WM. EduYears-PGS was also related to total cortical surface area, but in addition had a regional effect on surface area in the right parietal lobe, a region related to nonverbal cognitive functions, including mathematics, problem solving and WM. SES, but not EduYears-PGS, affected the change in total cortical surface area from age 14 to 19. This is the first study demonstrating the regional effects of EduYears-PGS and the independent role of SES on cognitive function and brain development. It suggests that the SES effects are substantial, affect global aspects of cortical development, and exert a persistent influence on brain development during adolescence.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Genetic factors and socioeconomic (SES) inequalities play a large role in educational attainment, and both have been associated with variations in brain structure and cognition. However, genetics and SES are correlated, and no prior study has assessed their neural effects independently. Here we used polygenic score for educational attainment (EduYears-PGS) as well as SES, in a longitudinal study of 551 adolescents, to tease apart genetic and environmental effects on brain development and cognition. Subjects received a structural MRI scan at ages 14 and 19. At both time-points, they performed three working memory (WM) tasks. SES and EduYears-PGS were correlated (r = 0.27) and had both common and independent effects on brain structure and cognition. Specifically, lower SES was related to less total cortical surface area and lower WM. EduYears-PGS was also related to total cortical surface area, but in addition had a regional effect on surface area in the right parietal lobe, a region related to nonverbal cognitive functions, including mathematics, problem solving and WM. SES, but not EduYears-PGS, affected the change in total cortical surface area from age 14 to 19. This is the first study demonstrating the regional effects of EduYears-PGS and the independent role of SES on cognitive function and brain development. It suggests that the SES effects are substantial, affect global aspects of cortical development, and exert a persistent influence on brain development during adolescence. | |
Fahimeh Darki, Bruno Sauce, Torkel Klingberg Inter-Individual Differences in Striatal Connectivity Is Related to Executive Function Through Fronto-Parietal Connectivity Journal Article Cerebral Cortex, pp. 1–10, 2019, ISSN: 1047-3211. @article{Darki2019, title = {Inter-Individual Differences in Striatal Connectivity Is Related to Executive Function Through Fronto-Parietal Connectivity}, author = {Fahimeh Darki and Bruno Sauce and Torkel Klingberg}, url = {https://academic.oup.com/cercor/advance-article/doi/10.1093/cercor/bhz117/5543637}, doi = {10.1093/cercor/bhz117}, issn = {1047-3211}, year = {2019}, date = {2019-08-01}, journal = {Cerebral Cortex}, pages = {1--10}, abstract = {The striatum has long been associated with cognitive functions, but the mechanisms behind this are still unclear. Here we tested a new hypothesis that the striatum contributes to executive function (EF) by strengthening cortico-cortical connections. Striatal connectivity was evaluated by measuring the resting-state functional connectivity between ventral and dorsal striatum in 570 individuals, aged 3–20 years. Using structural equation modeling, we found that inter-individual differences in striatal connectivity had an indirect effect (via fronto-parietal functional connectivity) and a direct effect on a compound EF measure of working memory, inhibition, and set-shifting/flexibility. The effect of fronto-parietal connectivity on cognition did not depend on age: the influence was as strong in older as younger children. In contrast, striatal connectivity was closely related to changes in cognitive ability during childhood development, suggesting a specific role of the striatum in cognitive plasticity. These results support a new principle for striatal functioning, according to which striatum promotes cognitive development by strengthening of cortico-cortical connectivity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The striatum has long been associated with cognitive functions, but the mechanisms behind this are still unclear. Here we tested a new hypothesis that the striatum contributes to executive function (EF) by strengthening cortico-cortical connections. Striatal connectivity was evaluated by measuring the resting-state functional connectivity between ventral and dorsal striatum in 570 individuals, aged 3–20 years. Using structural equation modeling, we found that inter-individual differences in striatal connectivity had an indirect effect (via fronto-parietal functional connectivity) and a direct effect on a compound EF measure of working memory, inhibition, and set-shifting/flexibility. The effect of fronto-parietal connectivity on cognition did not depend on age: the influence was as strong in older as younger children. In contrast, striatal connectivity was closely related to changes in cognitive ability during childhood development, suggesting a specific role of the striatum in cognitive plasticity. These results support a new principle for striatal functioning, according to which striatum promotes cognitive development by strengthening of cortico-cortical connectivity. | |
C Shawn Green, Daphne Bavelier, Arthur F Kramer, Sophia Vinogradov, Ulrich Ansorge, Karlene K Ball, Ulrike Bingel, Jason M Chein, Lorenza S Colzato, Jerri D Edwards, Andrea Facoetti, Adam Gazzaley, Susan E Gathercole, Paolo Ghisletta, Simone Gori, Isabela Granic, Charles H Hillman, Bernhard Hommel, Susanne M Jaeggi, Philipp Kanske, Julia Karbach, Alan Kingstone, Matthias Kliegel, Torkel Klingberg, Simone Kühn, Dennis M Levi, Richard E Mayer, Anne Collins McLaughlin, Danielle S McNamara, Martha Clare Morris, Mor Nahum, Nora S Newcombe, Rogerio Panizzutti, Ruchika Shaurya Prakash, Albert Rizzo, Torsten Schubert, Aaron R Seitz, Sarah J Short, Ilina Singh, James D Slotta, Tilo Strobach, Michael S C Thomas, Elizabeth Tipton, Xin Tong, Haley A Vlach, Julie Loebach Wetherell, Anna Wexler, Claudia M Witt Improving Methodological Standards in Behavioral Interventions for Cognitive Enhancement Journal Article Journal of Cognitive Enhancement, 3 (1), pp. 2–29, 2019, ISSN: 2509-3290. @article{ShawnGreen2019, title = {Improving Methodological Standards in Behavioral Interventions for Cognitive Enhancement}, author = {C {Shawn Green} and Daphne Bavelier and Arthur F Kramer and Sophia Vinogradov and Ulrich Ansorge and Karlene K Ball and Ulrike Bingel and Jason M Chein and Lorenza S Colzato and Jerri D Edwards and Andrea Facoetti and Adam Gazzaley and Susan E Gathercole and Paolo Ghisletta and Simone Gori and Isabela Granic and Charles H Hillman and Bernhard Hommel and Susanne M Jaeggi and Philipp Kanske and Julia Karbach and Alan Kingstone and Matthias Kliegel and Torkel Klingberg and Simone Kühn and Dennis M Levi and Richard E Mayer and Anne Collins McLaughlin and Danielle S McNamara and Martha Clare Morris and Mor Nahum and Nora S Newcombe and Rogerio Panizzutti and Ruchika Shaurya Prakash and Albert Rizzo and Torsten Schubert and Aaron R Seitz and Sarah J Short and Ilina Singh and James D Slotta and Tilo Strobach and Michael S C Thomas and Elizabeth Tipton and Xin Tong and Haley A Vlach and Julie Loebach Wetherell and Anna Wexler and Claudia M Witt}, url = {http://link.springer.com/10.1007/s41465-018-0115-y}, doi = {10.1007/s41465-018-0115-y}, issn = {2509-3290}, year = {2019}, date = {2019-03-01}, journal = {Journal of Cognitive Enhancement}, volume = {3}, number = {1}, pages = {2--29}, publisher = {Springer International Publishing}, abstract = {There is substantial interest in the possibility that cognitive skills can be improved by dedicated behavioral training. Yet despite the large amount of work being conducted in this domain, there is not an explicit and widely agreed upon consensus around the best methodological practices. This document seeks to fill this gap. We start from the perspective that there are many types of studies that are important in this domain—e.g., feasibility, mechanistic, efficacy, and effectiveness. These studies have fundamentally different goals, and, as such, the best-practice methods to meet those goals will also differ. We thus make suggestions in topics ranging from the design and implementation of control groups, to reporting of results, to dissemination and communication, taking the perspective that the best practices are not necessarily uniform across all study types. We also explicitly recognize and discuss the fact that there are methodological issues around which we currently lack the theoretical and/or empirical foundation to determine best practices (e.g., as pertains to assessing participant expectations). For these, we suggest important routes forward, including greater interdisciplinary collaboration with individuals from domains that face related concerns. Our hope is that these recommendations will greatly increase the rate at which science in this domain advances.}, keywords = {}, pubstate = {published}, tppubtype = {article} } There is substantial interest in the possibility that cognitive skills can be improved by dedicated behavioral training. Yet despite the large amount of work being conducted in this domain, there is not an explicit and widely agreed upon consensus around the best methodological practices. This document seeks to fill this gap. We start from the perspective that there are many types of studies that are important in this domain—e.g., feasibility, mechanistic, efficacy, and effectiveness. These studies have fundamentally different goals, and, as such, the best-practice methods to meet those goals will also differ. We thus make suggestions in topics ranging from the design and implementation of control groups, to reporting of results, to dissemination and communication, taking the perspective that the best practices are not necessarily uniform across all study types. We also explicitly recognize and discuss the fact that there are methodological issues around which we currently lack the theoretical and/or empirical foundation to determine best practices (e.g., as pertains to assessing participant expectations). For these, we suggest important routes forward, including greater interdisciplinary collaboration with individuals from domains that face related concerns. Our hope is that these recommendations will greatly increase the rate at which science in this domain advances. | |
Lotfi Khemiri, Christoffer Brynte, Angela Stunkel, Torkel Klingberg, Nitya Jayaram-Lindström Working Memory Training in Alcohol Use Disorder: A Randomized Controlled Trial Journal Article Alcoholism: Clinical and Experimental Research, 43 (1), pp. 135–146, 2019, ISSN: 01456008. @article{Khemiri2019, title = {Working Memory Training in Alcohol Use Disorder: A Randomized Controlled Trial}, author = {Lotfi Khemiri and Christoffer Brynte and Angela Stunkel and Torkel Klingberg and Nitya Jayaram-Lindström}, url = {http://doi.wiley.com/10.1111/acer.13910}, doi = {10.1111/acer.13910}, issn = {01456008}, year = {2019}, date = {2019-01-01}, journal = {Alcoholism: Clinical and Experimental Research}, volume = {43}, number = {1}, pages = {135--146}, abstract = {BACKGROUND: Alcohol use disorder (AUD) is associated with cognitive deficits such as impaired executive functions, which are hypothesized to contribute to the progression of the disease and worsen treatment outcome. Training of working memory (WM) to improve cognitive functions and thereby reduce alcohol use has been proposed as a novel treatment strategy. METHODS: Patients with AUD (n = 50) who were recruited to an outpatient addiction clinic were randomized to receive 5 weeks of active WM training or control training. Participants had weekly follow-up visits, and all cognitive training sessions were done online at home. Primary outcomes were WM function and change in self-reported heavy drinking. Secondary outcomes were craving, other drinking outcomes, and performance on a range of neuropsychological tasks from the Cambridge Neuropsychological Test Automated Battery. RESULTS: The active training group demonstrated a significantly greater improvement in verbal WM compared with the control group. No statistically significant effect of training was found on the primary drinking outcome, but a trend was observed indicating that WM training reduces the number of drinks per drinking occasion. WM training had no statistically significant effect on any of the other neuropsychological tasks. CONCLUSIONS: Cognitive training can improve WM function in individuals with AUD, suggesting that such interventions are feasible to administer in this patient population. The results do not support an effect of WM training on heavy drinking or transfer effects to other cognitive domains. Future studies should evaluate WM training as an adjunct to evidence-based treatments for AUD to assess potential synergistic effects.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Alcohol use disorder (AUD) is associated with cognitive deficits such as impaired executive functions, which are hypothesized to contribute to the progression of the disease and worsen treatment outcome. Training of working memory (WM) to improve cognitive functions and thereby reduce alcohol use has been proposed as a novel treatment strategy. METHODS: Patients with AUD (n = 50) who were recruited to an outpatient addiction clinic were randomized to receive 5 weeks of active WM training or control training. Participants had weekly follow-up visits, and all cognitive training sessions were done online at home. Primary outcomes were WM function and change in self-reported heavy drinking. Secondary outcomes were craving, other drinking outcomes, and performance on a range of neuropsychological tasks from the Cambridge Neuropsychological Test Automated Battery. RESULTS: The active training group demonstrated a significantly greater improvement in verbal WM compared with the control group. No statistically significant effect of training was found on the primary drinking outcome, but a trend was observed indicating that WM training reduces the number of drinks per drinking occasion. WM training had no statistically significant effect on any of the other neuropsychological tasks. CONCLUSIONS: Cognitive training can improve WM function in individuals with AUD, suggesting that such interventions are feasible to administer in this patient population. The results do not support an effect of WM training on heavy drinking or transfer effects to other cognitive domains. Future studies should evaluate WM training as an adjunct to evidence-based treatments for AUD to assess potential synergistic effects. | |
2018 |
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Martin Hassler Hallstedt, Torkel Klingberg, Ata Ghaderi Short and long-term effects of a mathematics tablet intervention for low performing second graders. Journal Article Journal of Educational Psychology, 110 (8), pp. 1127–1148, 2018, ISSN: 1939-2176. @article{Hallstedt2018, title = {Short and long-term effects of a mathematics tablet intervention for low performing second graders.}, author = {Martin {Hassler Hallstedt} and Torkel Klingberg and Ata Ghaderi}, url = {http://doi.apa.org/getdoi.cfm?doi=10.1037/edu0000264}, doi = {10.1037/edu0000264}, issn = {1939-2176}, year = {2018}, date = {2018-11-01}, journal = {Journal of Educational Psychology}, volume = {110}, number = {8}, pages = {1127--1148}, abstract = {Using a randomized placebo controlled design, we examined the direct and follow-up effects (at 6 and 12 months) of a mathematics tablet intervention. Math training focused primarily on basic arithmetic (addition and subtraction facts up to 12), and secondarily on number knowledge and word problems. We investigated the moderating effects of IQ and socioeconomic factors, and additive effects of working memory (WM) training. A representative sample of 283 low performing second-grade students were randomly assigned to control ( n = 52), reading placebo ( n = 78), math intervention (MA; n = 76), or math plus WM training (MA + WM; n = 77). Both math conditions scored significantly higher than control and placebo on the posttest of basic arithmetic, but not on arithmetic transfer and problem solving. WM training did not show additive effects. Given the virtually identical patterns, we collapsed the control and placebo, respectively, MA and MA + WM conditions. The collapsed MA/MA + WM condition demonstrated significant medium-sized effects ( d = 0.53–0.67) on basic arithmetic compared with the collapsed control/placebo condition at posttest. There was a fadeout of effects at 6-month follow-up ( d = 0.18–0.28), that declined further at 12 months ( d = 0.03–0.13). IQ was a significant moderator of direct and long-term effects on addition up to 12 and subtraction up to 18, where students with lower IQ benefitted more than higher IQ students. Socioeconomic factors did not moderate outcome. The intervention effectively improved basic arithmetic among low performing second graders. Although the effects waned at 6-month follow-up, there was some indication that children with lower IQ demonstrated sustained gains. (PsycINFO Database Record (c) 2018 APA, all rights reserved) (Source: journal abstract) Impact statementEducational Impact and Implications Statement: This study shows that adaptive math training on tablet can help low performing 8-year-olds catch up about half a year of schooling in critical math skills. Students with lower IQ benefitted in particular and made long-term gains 12 months after training finished. Additional short-term memory training did not result in further math improvement. Because math is a strong predictor of later school achievement, these findings highlight the potential of well-designed adaptive teaching on tablets to significantly improve students' success at school. Evidence-based programs covering the bulk of elementary math might be widely spread, potentially at a low cost. (PsycINFO Database Record (c) 2018 APA, all rights reserved)}, keywords = {}, pubstate = {published}, tppubtype = {article} } Using a randomized placebo controlled design, we examined the direct and follow-up effects (at 6 and 12 months) of a mathematics tablet intervention. Math training focused primarily on basic arithmetic (addition and subtraction facts up to 12), and secondarily on number knowledge and word problems. We investigated the moderating effects of IQ and socioeconomic factors, and additive effects of working memory (WM) training. A representative sample of 283 low performing second-grade students were randomly assigned to control ( n = 52), reading placebo ( n = 78), math intervention (MA; n = 76), or math plus WM training (MA + WM; n = 77). Both math conditions scored significantly higher than control and placebo on the posttest of basic arithmetic, but not on arithmetic transfer and problem solving. WM training did not show additive effects. Given the virtually identical patterns, we collapsed the control and placebo, respectively, MA and MA + WM conditions. The collapsed MA/MA + WM condition demonstrated significant medium-sized effects ( d = 0.53–0.67) on basic arithmetic compared with the collapsed control/placebo condition at posttest. There was a fadeout of effects at 6-month follow-up ( d = 0.18–0.28), that declined further at 12 months ( d = 0.03–0.13). IQ was a significant moderator of direct and long-term effects on addition up to 12 and subtraction up to 18, where students with lower IQ benefitted more than higher IQ students. Socioeconomic factors did not moderate outcome. The intervention effectively improved basic arithmetic among low performing second graders. Although the effects waned at 6-month follow-up, there was some indication that children with lower IQ demonstrated sustained gains. (PsycINFO Database Record (c) 2018 APA, all rights reserved) (Source: journal abstract) Impact statementEducational Impact and Implications Statement: This study shows that adaptive math training on tablet can help low performing 8-year-olds catch up about half a year of schooling in critical math skills. Students with lower IQ benefitted in particular and made long-term gains 12 months after training finished. Additional short-term memory training did not result in further math improvement. Because math is a strong predictor of later school achievement, these findings highlight the potential of well-designed adaptive teaching on tablets to significantly improve students' success at school. Evidence-based programs covering the bulk of elementary math might be widely spread, potentially at a low cost. (PsycINFO Database Record (c) 2018 APA, all rights reserved) | |
Federico Nemmi, Margot A Schel, Torkel Klingberg Connectivity of the Human Number Form Area Reveals Development of a Cortical Network for Mathematics Journal Article Frontiers in Human Neuroscience, 12 (November), pp. 1–15, 2018, ISSN: 1662-5161. @article{Nemmi2018a, title = {Connectivity of the Human Number Form Area Reveals Development of a Cortical Network for Mathematics}, author = {Federico Nemmi and Margot A Schel and Torkel Klingberg}, url = {https://www.frontiersin.org/article/10.3389/fnhum.2018.00465/full}, doi = {10.3389/fnhum.2018.00465}, issn = {1662-5161}, year = {2018}, date = {2018-11-01}, journal = {Frontiers in Human Neuroscience}, volume = {12}, number = {November}, pages = {1--15}, abstract = {The adult brain contains cortical areas thought to be specialized for the analysis of numbers (the putative number form area, NFA) and letters (the visual word form area, VWFA). Although functional development of the VWFA has been investigated, it is largely unknown when and how the NFA becomes specialized and connected to the rest of the brain. One hypothesis is that NFA and VWFA derive their special functions through differential connectivity, but the development of this differential connectivity has not been shown. Here we mapped the resting state connectivity of NFA and VWFA to the rest of the brain in a large sample (n = 437) of individuals (age 3.2 – 21 years). We show that within NFA-math network and within VWFA-reading network the strength of connectivity increases with age. The right NFA is significantly connected to the right intraparietal cortex already at the earliest age tested (age 3), before formal mathematical education has begun. This connection might support or enable an early understanding of magnitude or numerosity In contrast, the functional connectivity from NFA to the left anterior intraparietal cortex and to the right dorsolateral prefrontal cortex is not different from the functional connectivity of VWFA to these regions until around 12-14 years of age. The increase in connectivity to these regions was associated with a gradual increase in mathematical ability in an independent sample. In contrast, VWFA connects significantly to Broca's region around age 6, and this connectivity is correlated with reading ability. These results show how the differential connectivity of the networks for mathematics and reading slowly emerges through years of training and education.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The adult brain contains cortical areas thought to be specialized for the analysis of numbers (the putative number form area, NFA) and letters (the visual word form area, VWFA). Although functional development of the VWFA has been investigated, it is largely unknown when and how the NFA becomes specialized and connected to the rest of the brain. One hypothesis is that NFA and VWFA derive their special functions through differential connectivity, but the development of this differential connectivity has not been shown. Here we mapped the resting state connectivity of NFA and VWFA to the rest of the brain in a large sample (n = 437) of individuals (age 3.2 – 21 years). We show that within NFA-math network and within VWFA-reading network the strength of connectivity increases with age. The right NFA is significantly connected to the right intraparietal cortex already at the earliest age tested (age 3), before formal mathematical education has begun. This connection might support or enable an early understanding of magnitude or numerosity In contrast, the functional connectivity from NFA to the left anterior intraparietal cortex and to the right dorsolateral prefrontal cortex is not different from the functional connectivity of VWFA to these regions until around 12-14 years of age. The increase in connectivity to these regions was associated with a gradual increase in mathematical ability in an independent sample. In contrast, VWFA connects significantly to Broca's region around age 6, and this connectivity is correlated with reading ability. These results show how the differential connectivity of the networks for mathematics and reading slowly emerges through years of training and education. | |
N Kalnak, S Stamouli, M Peyrard-Janvid, I Rabkina, M Becker, T Klingberg, J Kere, H Forssberg, K Tammimies Enrichment of rare copy number variation in children with developmental language disorder Journal Article Clinical Genetics, 94 (3-4), pp. 313–320, 2018, ISSN: 00099163. @article{Kalnak2018, title = {Enrichment of rare copy number variation in children with developmental language disorder}, author = {N Kalnak and S Stamouli and M Peyrard-Janvid and I Rabkina and M Becker and T Klingberg and J Kere and H Forssberg and K Tammimies}, url = {http://doi.wiley.com/10.1111/cge.13389}, doi = {10.1111/cge.13389}, issn = {00099163}, year = {2018}, date = {2018-10-01}, journal = {Clinical Genetics}, volume = {94}, number = {3-4}, pages = {313--320}, abstract = {Developmental Language Disorder (DLD) is a common neurodevelopmental disorder with largely unknown etiology. Rare copy number variants (CNVs) have been implicated in the genetic architecture of other neurodevelopmental disorders (NDDs) which have led to clinical genetic testing recommendations for these disorders; however, the evidence is still lacking for DLD. We analyzed rare and de novo CNVs in 58 probands with severe DLD, their 159 family members and 76 Swedish typically developing children using high-resolution microarray. DLD probands had larger rare CNVs as measured by total length (p=0.05), and average length (p=0.04). Additionally, the rate of rare CNVs overlapping coding genes was increased (p=0.03 and p=0.01) and in average more genes were affected (p=0.006 and p=0.03) in the probands and their siblings, respectively. De novo CNVs were found in 4.8% DLD probands (2/42) and 2.4% (1/42) siblings. Clinically significant CNVs or chromosomal anomalies were found in 6.9% (4/58) of the probands of which two carried 16p11.2 deletions. We provide further evidence that rare CNVs contribute to the etiology of DLD in loci that overlap with other NDDs. Based on our results and earlier literature, families with DLD should be offered molecular genetic testing as a routine in their clinical follow-up. This article is protected by copyright. All rights reserved.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Developmental Language Disorder (DLD) is a common neurodevelopmental disorder with largely unknown etiology. Rare copy number variants (CNVs) have been implicated in the genetic architecture of other neurodevelopmental disorders (NDDs) which have led to clinical genetic testing recommendations for these disorders; however, the evidence is still lacking for DLD. We analyzed rare and de novo CNVs in 58 probands with severe DLD, their 159 family members and 76 Swedish typically developing children using high-resolution microarray. DLD probands had larger rare CNVs as measured by total length (p=0.05), and average length (p=0.04). Additionally, the rate of rare CNVs overlapping coding genes was increased (p=0.03 and p=0.01) and in average more genes were affected (p=0.006 and p=0.03) in the probands and their siblings, respectively. De novo CNVs were found in 4.8% DLD probands (2/42) and 2.4% (1/42) siblings. Clinically significant CNVs or chromosomal anomalies were found in 6.9% (4/58) of the probands of which two carried 16p11.2 deletions. We provide further evidence that rare CNVs contribute to the etiology of DLD in loci that overlap with other NDDs. Based on our results and earlier literature, families with DLD should be offered molecular genetic testing as a routine in their clinical follow-up. This article is protected by copyright. All rights reserved. | |
Fahimeh Darki, Torkel Klingberg Functional differentiation between convergence and non-convergence zones of the striatum in children Journal Article NeuroImage, 173 (January), pp. 384–393, 2018, ISSN: 10538119. @article{Darki2018, title = {Functional differentiation between convergence and non-convergence zones of the striatum in children}, author = {Fahimeh Darki and Torkel Klingberg}, url = {https://linkinghub.elsevier.com/retrieve/pii/S1053811918301617}, doi = {10.1016/j.neuroimage.2018.02.054}, issn = {10538119}, year = {2018}, date = {2018-06-01}, journal = {NeuroImage}, volume = {173}, number = {January}, pages = {384--393}, abstract = {Most cortical areas send projections to the striatum. In some parts of the striatum, the connections converge from several cortical areas. It is unknown whether the convergence and non-convergence zones of the striatum differ functionally. Here, we used diffusion-weighted magnetic resonance imaging and probabilistic fiber tracking to parcellate the striatum based on its connections to dorsolateral prefrontal, parietal and orbitofrontal cortices in two different datasets (children aged 6–7 years and adults). In both samples, quantitative susceptibility mapping (QSM) values were significantly correlated with working memory (WM) in convergence zones, but not in non-convergence zones. In children, this was also true for mean diffusivity, MD. The association of MD to WM specifically in the convergent zone was replicated in the Pediatric Imaging, Neurocognition, and Genetics (PING) dataset for 135 children aged 6–9 years. QSM data was not available in the PING dataset, and the association to QSM still needs to be replicated. These results suggest that connectivity-based segments of the striatum exhibit functionally different characteristics. The association between convergence zones and WM performance might relate to a role in integrating and coordinating activity in different cortical areas.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Most cortical areas send projections to the striatum. In some parts of the striatum, the connections converge from several cortical areas. It is unknown whether the convergence and non-convergence zones of the striatum differ functionally. Here, we used diffusion-weighted magnetic resonance imaging and probabilistic fiber tracking to parcellate the striatum based on its connections to dorsolateral prefrontal, parietal and orbitofrontal cortices in two different datasets (children aged 6–7 years and adults). In both samples, quantitative susceptibility mapping (QSM) values were significantly correlated with working memory (WM) in convergence zones, but not in non-convergence zones. In children, this was also true for mean diffusivity, MD. The association of MD to WM specifically in the convergent zone was replicated in the Pediatric Imaging, Neurocognition, and Genetics (PING) dataset for 135 children aged 6–9 years. QSM data was not available in the PING dataset, and the association to QSM still needs to be replicated. These results suggest that connectivity-based segments of the striatum exhibit functionally different characteristics. The association between convergence zones and WM performance might relate to a role in integrating and coordinating activity in different cortical areas. | |
F Nemmi, C Nymberg, F Darki, T Banaschewski, A L W Bokde, C Büchel, H Flor, V Frouin, H Garavan, P Gowland, A Heinz, J -L Martinot, F Nees, T Paus, M N Smolka, T W Robbins, G Schumann, Torkel Klingberg Interaction between striatal volume and DAT1 polymorphism predicts working memory development during adolescence Journal Article Developmental Cognitive Neuroscience, 30 (February), pp. 191–199, 2018, ISSN: 18789293. @article{Nemmi2018b, title = {Interaction between striatal volume and DAT1 polymorphism predicts working memory development during adolescence}, author = {F Nemmi and C Nymberg and F Darki and T Banaschewski and A L W Bokde and C Büchel and H Flor and V Frouin and H Garavan and P Gowland and A Heinz and J -L Martinot and F Nees and T Paus and M N Smolka and T W Robbins and G Schumann and Torkel Klingberg}, url = {https://doi.org/10.1016/j.dcn.2018.03.006 https://linkinghub.elsevier.com/retrieve/pii/S1878929317301536}, doi = {10.1016/j.dcn.2018.03.006}, issn = {18789293}, year = {2018}, date = {2018-04-01}, journal = {Developmental Cognitive Neuroscience}, volume = {30}, number = {February}, pages = {191--199}, publisher = {Elsevier}, abstract = {There is considerable inter-individual variability in the rate at which working memory (WM) develops during childhood and adolescence, but the neural and genetic basis for these differences are poorly understood. Dopamine-related genes, striatal activation and morphology have been associated with increased WM capacity after training. Here we tested the hypothesis that these factors would also explain some of the inter-individual differences in the rate of WM development. We measured WM performance in 487 healthy subjects twice: at age 14 and 19. At age 14 subjects underwent a structural MRI scan, and genotyping of five single nucleotide polymorphisms (SNPs) in or close to the dopamine genes DRD2, DAT-1 and COMT, which have previously been associated with gains in WM after WM training. We then analyzed which biological factors predicted the rate of increase in WM between ages 14 and 19. We found a significant interaction between putamen size and DAT1/SLC6A3 rs40184 polymorphism, such that TC heterozygotes with a larger putamen at age 14 showed greater WM improvement at age 19. The effect of the DAT1 polymorphism on WM development was exerted in interaction with striatal morphology. These results suggest that development of WM partially share neuro-physiological mechanism with training-induced plasticity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } There is considerable inter-individual variability in the rate at which working memory (WM) develops during childhood and adolescence, but the neural and genetic basis for these differences are poorly understood. Dopamine-related genes, striatal activation and morphology have been associated with increased WM capacity after training. Here we tested the hypothesis that these factors would also explain some of the inter-individual differences in the rate of WM development. We measured WM performance in 487 healthy subjects twice: at age 14 and 19. At age 14 subjects underwent a structural MRI scan, and genotyping of five single nucleotide polymorphisms (SNPs) in or close to the dopamine genes DRD2, DAT-1 and COMT, which have previously been associated with gains in WM after WM training. We then analyzed which biological factors predicted the rate of increase in WM between ages 14 and 19. We found a significant interaction between putamen size and DAT1/SLC6A3 rs40184 polymorphism, such that TC heterozygotes with a larger putamen at age 14 showed greater WM improvement at age 19. The effect of the DAT1 polymorphism on WM development was exerted in interaction with striatal morphology. These results suggest that development of WM partially share neuro-physiological mechanism with training-induced plasticity. | |
2017 |
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Fahimeh Darki, Satu Massinen, Elina Salmela, Hans Matsson, Myriam Peyrard-Janvid, Torkel Klingberg, Juha Kere Human ROBO1 regulates white matter structure in corpus callosum Journal Article Brain Structure and Function, 222 (2), pp. 707–716, 2017, ISSN: 18632661. @article{Darki2017, title = {Human ROBO1 regulates white matter structure in corpus callosum}, author = {Fahimeh Darki and Satu Massinen and Elina Salmela and Hans Matsson and Myriam Peyrard-Janvid and Torkel Klingberg and Juha Kere}, doi = {10.1007/s00429-016-1240-y}, issn = {18632661}, year = {2017}, date = {2017-01-01}, journal = {Brain Structure and Function}, volume = {222}, number = {2}, pages = {707--716}, publisher = {Springer Berlin Heidelberg}, abstract = {textcopyright 2016, The Author(s). 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.}, keywords = {}, pubstate = {published}, tppubtype = {article} } textcopyright 2016, The Author(s). 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. | |
Elisabet Einarsdottir, Myriam Peyrard-Janvid, Fahimeh Darki, Jetro J Tuulari, Harri Merisaari, Linnea Karlsson, Noora M Scheinin, Jani Saunavaara, Riitta Parkkola, Katri Kantojärvi, Antti Jussi Ämmälä, Nancy Yiu-Lin Yu, Hans Matsson, Jaana Nopola-Hemmi, Hasse Karlsson, Tiina Paunio, Torkel Klingberg, Eira Leinonen, Juha Kere Identification of NCAN as a candidate gene for developmental dyslexia Journal Article Scientific Reports, 7 (1), pp. 1–11, 2017, ISSN: 20452322. @article{Einarsdottir2017, title = {Identification of NCAN as a candidate gene for developmental dyslexia}, author = {Elisabet Einarsdottir and Myriam Peyrard-Janvid and Fahimeh Darki and Jetro J Tuulari and Harri Merisaari and Linnea Karlsson and Noora M Scheinin and Jani Saunavaara and Riitta Parkkola and Katri Kantojärvi and Antti Jussi Ämmälä and Nancy {Yiu-Lin Yu} and Hans Matsson and Jaana Nopola-Hemmi and Hasse Karlsson and Tiina Paunio and Torkel Klingberg and Eira Leinonen and Juha Kere}, doi = {10.1038/s41598-017-10175-7}, issn = {20452322}, year = {2017}, date = {2017-01-01}, journal = {Scientific Reports}, volume = {7}, number = {1}, pages = {1--11}, 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 textgreater 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 textgreater 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.}, keywords = {}, pubstate = {published}, tppubtype = {article} } 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 textgreater 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 textgreater 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. | |
Annie Möller, Federico Nemmi, Kim Karlsson, Torkel Klingberg Transcranial Electric Stimulation Can Impair Gains during Working Memory Training and Affects the Resting State Connectivity Journal Article Frontiers in Human Neuroscience, 11 (July), pp. 1–12, 2017. @article{Moller2017, title = {Transcranial Electric Stimulation Can Impair Gains during Working Memory Training and Affects the Resting State Connectivity}, author = {Annie Möller and Federico Nemmi and Kim Karlsson and Torkel Klingberg}, doi = {10.3389/fnhum.2017.00364}, year = {2017}, date = {2017-01-01}, journal = {Frontiers in Human Neuroscience}, volume = {11}, number = {July}, pages = {1--12}, abstract = {Transcranial electric stimulation (tES) is a promising technique that has been shown to improve working memory (WM) performance and enhance the effect of cognitive training. However, experimental set up and electrode placement are not always determined based on neurofunctional knowledge about WM, leading to inconsistent results. Additional research on the effects of tES grounded on neurofunctional evidence is therefore necessary. 60 young, healthy, volunteers, assigned to 6 different groups, participated in 5 days of stimulation or sham treatment. 25 of these subjects also participated in MRI acquisition. We performed 3 experiments: In the first one we evaluated tES using either direct current stimulation (tDCS) with bilateral stimulation of the frontal or parietal lobe; in the second one we used the same tDCS protocol with a different electrode placement (i.e. supraorbital cathode); in the third one we used alternating currents (tACS) of 35 Hz, applied bilaterally to either the frontal or parietal lobes. The behavioral outcome measure was the WM capacity (i.e. number of remembered spatial position) during the 5 days of training. In a subsample of subjects we evaluated the neural effects of tDCS by measuring resting state connectivity with functional MRI, before and after the 5 days of tDCS and visuo-spatial WM training. We found a significant impairment of WM training-related gains associated with parietal tACS and frontal tDCS. Five days of tDCS stimulation was also associated with significant change in resting state connectivity revealed by multivariate pattern analysis (MVPA). None of the stimulation paradigms resulted in improved WM performance or enhanced WM training gains. These results show that tES can have negative effects on cognitive plasticity and affect resting-state functional connectivity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Transcranial electric stimulation (tES) is a promising technique that has been shown to improve working memory (WM) performance and enhance the effect of cognitive training. However, experimental set up and electrode placement are not always determined based on neurofunctional knowledge about WM, leading to inconsistent results. Additional research on the effects of tES grounded on neurofunctional evidence is therefore necessary. 60 young, healthy, volunteers, assigned to 6 different groups, participated in 5 days of stimulation or sham treatment. 25 of these subjects also participated in MRI acquisition. We performed 3 experiments: In the first one we evaluated tES using either direct current stimulation (tDCS) with bilateral stimulation of the frontal or parietal lobe; in the second one we used the same tDCS protocol with a different electrode placement (i.e. supraorbital cathode); in the third one we used alternating currents (tACS) of 35 Hz, applied bilaterally to either the frontal or parietal lobes. The behavioral outcome measure was the WM capacity (i.e. number of remembered spatial position) during the 5 days of training. In a subsample of subjects we evaluated the neural effects of tDCS by measuring resting state connectivity with functional MRI, before and after the 5 days of tDCS and visuo-spatial WM training. We found a significant impairment of WM training-related gains associated with parietal tACS and frontal tDCS. Five days of tDCS stimulation was also associated with significant change in resting state connectivity revealed by multivariate pattern analysis (MVPA). None of the stimulation paradigms resulted in improved WM performance or enhanced WM training gains. These results show that tES can have negative effects on cognitive plasticity and affect resting-state functional connectivity. | |
Douglas Sjöwall, Mattias Hertz, Torkel Klingberg No long-term effect of physical activity intervention on working memory or arithmetic in preadolescents Journal Article Frontiers in Psychology, 8 (AUG), pp. 1–10, 2017, ISSN: 16641078. @article{Sjowall2017, title = {No long-term effect of physical activity intervention on working memory or arithmetic in preadolescents}, author = {Douglas Sjöwall and Mattias Hertz and Torkel Klingberg}, doi = {10.3389/fpsyg.2017.01342}, issn = {16641078}, year = {2017}, date = {2017-01-01}, journal = {Frontiers in Psychology}, volume = {8}, number = {AUG}, pages = {1--10}, abstract = {We investigate if increased physical activity leads to enhanced working memory capacity and arithmetic performance, in a 2-year school-based intervention in preadolescent children (age 6-13). The active school (n = 228) increased physical activity (aimed at increasing cardiovascular fitness) from 2 to 5 days a week while the control school (n = 242) remained at 2 days. Twice a year, participants performed tests of arithmetic as well as verbal and spatial working memory. They also rated stress with a questionnaire at the start and at the end of the intervention. There was no beneficial development of working memory or arithmetic for the active school as compared to the control school. Furthermore, subgroup analyses revealed no favorable intervention effect for high/low baseline fitness, cognition or grit. Unexpectedly, a significant increase in self-rated stress was detected for the active school and this effect was driven by girls rather than boys and by the younger rather than older children. These results indicate that longtime high intensity physical activity does not lead to a beneficial development of working memory or arithmetic in preadolescent children.}, keywords = {}, pubstate = {published}, tppubtype = {article} } We investigate if increased physical activity leads to enhanced working memory capacity and arithmetic performance, in a 2-year school-based intervention in preadolescent children (age 6-13). The active school (n = 228) increased physical activity (aimed at increasing cardiovascular fitness) from 2 to 5 days a week while the control school (n = 242) remained at 2 days. Twice a year, participants performed tests of arithmetic as well as verbal and spatial working memory. They also rated stress with a questionnaire at the start and at the end of the intervention. There was no beneficial development of working memory or arithmetic for the active school as compared to the control school. Furthermore, subgroup analyses revealed no favorable intervention effect for high/low baseline fitness, cognition or grit. Unexpectedly, a significant increase in self-rated stress was detected for the active school and this effect was driven by girls rather than boys and by the younger rather than older children. These results indicate that longtime high intensity physical activity does not lead to a beneficial development of working memory or arithmetic in preadolescent children. | |
Henrik Ullman, Torkel Klingberg Timing of white matter development determines cognitive abilities at school entry but not in late adolescence Journal Article Cerebral Cortex, 27 (9), pp. 4516–4522, 2017, ISSN: 14602199. @article{Ullman2017, title = {Timing of white matter development determines cognitive abilities at school entry but not in late adolescence}, author = {Henrik Ullman and Torkel Klingberg}, doi = {10.1093/cercor/bhw256}, issn = {14602199}, year = {2017}, date = {2017-01-01}, journal = {Cerebral Cortex}, volume = {27}, number = {9}, pages = {4516--4522}, abstract = {The primary aim of this study was to investigate to what degree the age-related white matter development, here called " brain age " , is associated with working memory (WM) and numeric abilities in 6-year-old children. We measured white matter development using diffusion tensor imaging to calculate fractional anisotropy (FA). A " brain age " model was created using multivariate statistics, which described association between FA and age in a sample of 6-to 20-year-old children. This age model was then applied to predict " brain age " in a second sample of 6-year-old children. The predicted brain age correlated with WM performance and numerical ability (NA) (P textless 0.01, P textless 0.05) in the 6-year-old children. More than 50% of the stable variance in WM performance was explained. We found that in children older than 13 years of age, this association between brain age and WM was no longer significant (P textgreater 0.5). The results bear theoretical implications as they suggest that the variability in individual developmental timing strongly affects WM and NA at school start but badly predicts adolescent cognitive functioning. Furthermore, it bears practical implications as one may differentiate maturation lags from persistent low cognitive abilities in school children, complementing cognitive tests.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The primary aim of this study was to investigate to what degree the age-related white matter development, here called " brain age " , is associated with working memory (WM) and numeric abilities in 6-year-old children. We measured white matter development using diffusion tensor imaging to calculate fractional anisotropy (FA). A " brain age " model was created using multivariate statistics, which described association between FA and age in a sample of 6-to 20-year-old children. This age model was then applied to predict " brain age " in a second sample of 6-year-old children. The predicted brain age correlated with WM performance and numerical ability (NA) (P textless 0.01, P textless 0.05) in the 6-year-old children. More than 50% of the stable variance in WM performance was explained. We found that in children older than 13 years of age, this association between brain age and WM was no longer significant (P textgreater 0.5). The results bear theoretical implications as they suggest that the variability in individual developmental timing strongly affects WM and NA at school start but badly predicts adolescent cognitive functioning. Furthermore, it bears practical implications as one may differentiate maturation lags from persistent low cognitive abilities in school children, complementing cognitive tests. | |
2016 |
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Margot A Schel, Torkel Klingberg Specialization of the Right Intraparietal Sulcus for Processing Mathematics During Development Journal Article Cerebral Cortex, 27 (9), pp. 4436–4446, 2016, ISSN: 1047-3211. @article{Schel2017, title = {Specialization of the Right Intraparietal Sulcus for Processing Mathematics During Development}, author = {Margot A Schel and Torkel Klingberg}, url = {http://cercor.oxfordjournals.org/cgi/doi/10.1093/cercor/bhw246}, doi = {10.1093/cercor/bhw246}, issn = {1047-3211}, year = {2016}, date = {2016-08-01}, journal = {Cerebral Cortex}, volume = {27}, number = {9}, pages = {4436--4446}, abstract = {Mathematical ability, especially perception of numbers and performance of arithmetics, is known to rely on the activation of intraparietal sulcus (IPS). However, reasoning ability and working memory, 2 highly associated abilities also activate partly overlapping regions. Most studies aimed at localizing mathematical function have used group averages, where individual variability is averaged out, thus confounding the anatomical specificity when localizing cognitive functions. Here, we analyze the functional anatomy of the intraparietal cortex by using individual analysis of subregions of IPS based on how they are structurally connected to frontal, parietal, and occipital cortex. Analysis of cortical thickness showed that the right anterior IPS, defined by its connections to the frontal lobe, was associated with both visuospatial working memory, and mathematics in 6-year-old children. This region specialized during development to be specifically related to mathematics, but not visuospatial working memory in adolescents and adults. This could be an example of interactive specialization, where interacting with the environment in combination with interactions between cortical regions leads from a more general role of right anterior IPS in spatial processing, to a specialization of this region for mathematics.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Mathematical ability, especially perception of numbers and performance of arithmetics, is known to rely on the activation of intraparietal sulcus (IPS). However, reasoning ability and working memory, 2 highly associated abilities also activate partly overlapping regions. Most studies aimed at localizing mathematical function have used group averages, where individual variability is averaged out, thus confounding the anatomical specificity when localizing cognitive functions. Here, we analyze the functional anatomy of the intraparietal cortex by using individual analysis of subregions of IPS based on how they are structurally connected to frontal, parietal, and occipital cortex. Analysis of cortical thickness showed that the right anterior IPS, defined by its connections to the frontal lobe, was associated with both visuospatial working memory, and mathematics in 6-year-old children. This region specialized during development to be specifically related to mathematics, but not visuospatial working memory in adolescents and adults. This could be an example of interactive specialization, where interacting with the environment in combination with interactions between cortical regions leads from a more general role of right anterior IPS in spatial processing, to a specialization of this region for mathematics. | |
Federico Nemmi, Elin Helander, Ola Helenius, Rita Almeida, Martin Hassler, Pekka Räsänen, Torkel Klingberg Behavior and neuroimaging at baseline predict individual response to combined mathematical and working memory training in children Journal Article Developmental Cognitive Neuroscience, 20 , pp. 43–51, 2016, ISSN: 18789293. @article{Nemmi2016, title = {Behavior and neuroimaging at baseline predict individual response to combined mathematical and working memory training in children}, author = {Federico Nemmi and Elin Helander and Ola Helenius and Rita Almeida and Martin Hassler and Pekka Räsänen and Torkel Klingberg}, url = {http://dx.doi.org/10.1016/j.dcn.2016.06.004 https://linkinghub.elsevier.com/retrieve/pii/S1878929316300500}, doi = {10.1016/j.dcn.2016.06.004}, issn = {18789293}, year = {2016}, date = {2016-08-01}, journal = {Developmental Cognitive Neuroscience}, volume = {20}, pages = {43--51}, publisher = {Elsevier Ltd}, abstract = {Mathematical performance is highly correlated with several general cognitive abilities, including working memory (WM) capacity. Here we investigated the effect of numerical training using a number-line (NLT), WM training (WMT), or the combination of the two on a composite score of mathematical ability. The aim was to investigate if the combination contributed to the outcome, and determine if baseline performance or neuroimaging predict the magnitude of improvement. We randomly assigned 308, 6-year-old children to WMT, NLT, WMT + NLT or a control intervention. Overall, there was a significant effect of NLT but not WMT. The WMT + NLT was the only group that improved significantly more than the controls, although the interaction NLTxWM was non-significant. Higher WM and maths performance predicted larger benefits for WMT and NLT, respectively. Neuroimaging at baseline also contributed significant information about training gain. Different individuals showed as much as a three-fold difference in their responses to the same intervention. These results show that the impact of an intervention is highly dependent on individual characteristics of the child. If differences in responses could be used to optimize the intervention for each child, future interventions could be substantially more effective.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Mathematical performance is highly correlated with several general cognitive abilities, including working memory (WM) capacity. Here we investigated the effect of numerical training using a number-line (NLT), WM training (WMT), or the combination of the two on a composite score of mathematical ability. The aim was to investigate if the combination contributed to the outcome, and determine if baseline performance or neuroimaging predict the magnitude of improvement. We randomly assigned 308, 6-year-old children to WMT, NLT, WMT + NLT or a control intervention. Overall, there was a significant effect of NLT but not WMT. The WMT + NLT was the only group that improved significantly more than the controls, although the interaction NLTxWM was non-significant. Higher WM and maths performance predicted larger benefits for WMT and NLT, respectively. Neuroimaging at baseline also contributed significant information about training gain. Different individuals showed as much as a three-fold difference in their responses to the same intervention. These results show that the impact of an intervention is highly dependent on individual characteristics of the child. If differences in responses could be used to optimize the intervention for each child, future interventions could be substantially more effective. | |
Christos Constantinidis, Torkel Klingberg The neuroscience of working memory capacity and training Journal Article Nature Reviews Neuroscience, 17 (7), pp. 438–449, 2016, ISSN: 1471-003X. @article{Constantinidis2016, title = {The neuroscience of working memory capacity and training}, author = {Christos Constantinidis and Torkel Klingberg}, url = {http://dx.doi.org/10.1038/nrn.2016.43 http://www.nature.com/articles/nrn.2016.43}, doi = {10.1038/nrn.2016.43}, issn = {1471-003X}, year = {2016}, date = {2016-07-01}, journal = {Nature Reviews Neuroscience}, volume = {17}, number = {7}, pages = {438--449}, publisher = {Nature Publishing Group}, abstract = {Working memory (WM) — the ability to maintain and manipulate information over a period of seconds — is a key cognitive skill. Constantinidis and Klingberg discuss non-human-primate, computational-modelling and human-neuroimaging studies that examine the neural bases of WM and training-induced enhancements of WM capacity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Working memory (WM) — the ability to maintain and manipulate information over a period of seconds — is a key cognitive skill. Constantinidis and Klingberg discuss non-human-primate, computational-modelling and human-neuroimaging studies that examine the neural bases of WM and training-induced enhancements of WM capacity. | |
Fahimeh Darki, Federico Nemmi, Annie Möller, Rouslan Sitnikov, Torkel Klingberg Quantitative susceptibility mapping of striatum in children and adults, and its association with working memory performance Journal Article NeuroImage, 136 , pp. 208–214, 2016, ISSN: 10959572. @article{Darki2016, title = {Quantitative susceptibility mapping of striatum in children and adults, and its association with working memory performance}, author = {Fahimeh Darki and Federico Nemmi and Annie Möller and Rouslan Sitnikov and Torkel Klingberg}, url = {http://dx.doi.org/10.1016/j.neuroimage.2016.04.065}, doi = {10.1016/j.neuroimage.2016.04.065}, issn = {10959572}, year = {2016}, date = {2016-01-01}, journal = {NeuroImage}, volume = {136}, pages = {208--214}, publisher = {Elsevier Inc.}, abstract = {Quantitative susceptibility mapping (QSM) is a magnetic resonance imaging (MRI) technique in which the magnetic susceptibility characteristic of molecular and cellular components, including iron and myelin, is quantified. Rapid iron accumulation in subcortical nuclei and myelination of the white matter tracts are two important developmental processes that contribute to cognitive functions. Both also contribute to the magnetic susceptibility of the brain tissues. Here, we used the QSM as indirect measures of iron in subcortical nuclei and myelin in caudo-frontal white matter pathways. We included two groups of participants; 21 children aged 6-7 years and 25 adults aged 21-40 years. All subjects also performed tests estimating their visuo-spatial working memory capacity.Adults had higher magnetic susceptibility in all subcortical nuclei, compared to children. The magnetic susceptibility of these nuclei highly correlated with their previously reported iron content. Moreover, working memory performance correlated significantly with the magnetic susceptibility in caudate nucleus in both children and adults, while the correlation was not significant for gray matter density. QSM of white matter in the caudo-frontal tract also differed between children and adults, but did not correlate with working memory scores. These results indicate that QSM is a feasible technique to measure developmental aspects of changes in the striatum, possibly related to iron content that is relevant to cognition.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Quantitative susceptibility mapping (QSM) is a magnetic resonance imaging (MRI) technique in which the magnetic susceptibility characteristic of molecular and cellular components, including iron and myelin, is quantified. Rapid iron accumulation in subcortical nuclei and myelination of the white matter tracts are two important developmental processes that contribute to cognitive functions. Both also contribute to the magnetic susceptibility of the brain tissues. Here, we used the QSM as indirect measures of iron in subcortical nuclei and myelin in caudo-frontal white matter pathways. We included two groups of participants; 21 children aged 6-7 years and 25 adults aged 21-40 years. All subjects also performed tests estimating their visuo-spatial working memory capacity.Adults had higher magnetic susceptibility in all subcortical nuclei, compared to children. The magnetic susceptibility of these nuclei highly correlated with their previously reported iron content. Moreover, working memory performance correlated significantly with the magnetic susceptibility in caudate nucleus in both children and adults, while the correlation was not significant for gray matter density. QSM of white matter in the caudo-frontal tract also differed between children and adults, but did not correlate with working memory scores. These results indicate that QSM is a feasible technique to measure developmental aspects of changes in the striatum, possibly related to iron content that is relevant to cognition. | |
Torkel Klingberg Neural basis of cognitive training and development Journal Article Current Opinion in Behavioral Sciences, 10 (i), pp. 97–101, 2016, ISSN: 23521546. @article{Klingberg2016, title = {Neural basis of cognitive training and development}, author = {Torkel Klingberg}, url = {http://dx.doi.org/10.1016/j.cobeha.2016.05.003}, doi = {10.1016/j.cobeha.2016.05.003}, issn = {23521546}, year = {2016}, date = {2016-01-01}, journal = {Current Opinion in Behavioral Sciences}, volume = {10}, number = {i}, pages = {97--101}, publisher = {Elsevier Ltd}, abstract = {This paper gives a brief overview of phases in brain development and discusses the hypothesis that mechanisms of working memory development are partly the same as those of working memory training. Brain development could be related to different, but overlapping phases: (i) structural maturation, with a relatively high reliance of preprogrammed processes; (ii) interactive specialization, which is a reorganization of the functional networks, partly in response to the environmental demands; (iii) training or skill learning, which is a qualitative change, such as strengthened connectivity of existent networks. The mechanisms of this skill learning could be similar to those neural processes observed during controlled studies of working memory training, where strengthened connectivity between frontal and parietal regions is suggested to play a central role. Education and formal schooling could be one important factor driving the training and skill-learning phase of executive functions, including improvement of working memory.}, keywords = {}, pubstate = {published}, tppubtype = {article} } This paper gives a brief overview of phases in brain development and discusses the hypothesis that mechanisms of working memory development are partly the same as those of working memory training. Brain development could be related to different, but overlapping phases: (i) structural maturation, with a relatively high reliance of preprogrammed processes; (ii) interactive specialization, which is a reorganization of the functional networks, partly in response to the environmental demands; (iii) training or skill learning, which is a qualitative change, such as strengthened connectivity of existent networks. The mechanisms of this skill learning could be similar to those neural processes observed during controlled studies of working memory training, where strengthened connectivity between frontal and parietal regions is suggested to play a central role. Education and formal schooling could be one important factor driving the training and skill-learning phase of executive functions, including improvement of working memory. | |
2015 |
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Fahimeh Darki, Torkel Klingberg The role of fronto-parietal and fronto-striatal networks in the development of working memory: A longitudinal study Journal Article Cerebral Cortex, 25 (6), pp. 1587–1595, 2015, ISSN: 14602199. @article{Darki2015, title = {The role of fronto-parietal and fronto-striatal networks in the development of working memory: A longitudinal study}, author = {Fahimeh Darki and Torkel Klingberg}, url = {https://academic.oup.com/cercor/article-lookup/doi/10.1093/cercor/bht352}, doi = {10.1093/cercor/bht352}, issn = {14602199}, year = {2015}, date = {2015-06-01}, journal = {Cerebral Cortex}, volume = {25}, number = {6}, pages = {1587--1595}, abstract = {The increase in working memory (WM) capacity is an important part of cognitive development during childhood and adolescence. Cross-sectional analyses have associated this development with higher activity, thinner cortex, and white matter maturation in fronto-parietal networks. However, there is still a lack of longitudinal data showing the dynamics of this development and the role of subcortical structures. We included 89 individuals, aged 6-25 years, who were scanned 1-3 times at 2-year intervals. Functional magnetic resonance imaging (fMRI) was used to identify activated areas in superior frontal, intraparietal cortices, and caudate nucleus during performance on a visuo-spatial WM task. Probabilistic tractography determined the anatomical pathways between these regions. In the cross-sectional analysis, WM capacity correlated with activity in frontal and parietal regions, cortical thickness in parietal cortex, and white matter structure [both fractional anisotropy (FA) and white matter volume] of fronto-parietal and fronto-striatal tracts. However, in the longitudinal analysis, FA in white matter tracts and activity in caudate predicted future WM capacity. The results show a dynamic of neural networks underlying WM development in which cortical activity and structure relate to current capacity, while white matter tracts and caudate activity predict future WM capacity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The increase in working memory (WM) capacity is an important part of cognitive development during childhood and adolescence. Cross-sectional analyses have associated this development with higher activity, thinner cortex, and white matter maturation in fronto-parietal networks. However, there is still a lack of longitudinal data showing the dynamics of this development and the role of subcortical structures. We included 89 individuals, aged 6-25 years, who were scanned 1-3 times at 2-year intervals. Functional magnetic resonance imaging (fMRI) was used to identify activated areas in superior frontal, intraparietal cortices, and caudate nucleus during performance on a visuo-spatial WM task. Probabilistic tractography determined the anatomical pathways between these regions. In the cross-sectional analysis, WM capacity correlated with activity in frontal and parietal regions, cortical thickness in parietal cortex, and white matter structure [both fractional anisotropy (FA) and white matter volume] of fronto-parietal and fronto-striatal tracts. However, in the longitudinal analysis, FA in white matter tracts and activity in caudate predicted future WM capacity. The results show a dynamic of neural networks underlying WM development in which cortical activity and structure relate to current capacity, while white matter tracts and caudate activity predict future WM capacity. | |
Megan Spencer-Smith, Torkel Klingberg Benefits of a working memory training program for inattention in daily life: A systematic review and meta-analysis Journal Article PLoS ONE, 10 (3), pp. 1–18, 2015, ISSN: 19326203. @article{Spencer-Smith2015, title = {Benefits of a working memory training program for inattention in daily life: A systematic review and meta-analysis}, author = {Megan Spencer-Smith and Torkel Klingberg}, doi = {10.1371/journal.pone.0119522}, issn = {19326203}, year = {2015}, date = {2015-01-01}, journal = {PLoS ONE}, volume = {10}, number = {3}, pages = {1--18}, abstract = {BACKGROUND: Many common disorders across the lifespan feature impaired working memory (WM). Reported benefits of a WM training program include improving inattention in daily life, but this has not been evaluated in a meta-analysis. This study aimed to evaluate whether one WM training method has benefits for inattention in daily life by conducting a systematic review and meta-analysis. METHODS: We searched Medline and PsycINFO, relevant journals and contacted authors for studies with an intervention and control group reporting post-training estimates of inattention in daily life. To reduce the influence of different WM training methods on the findings, the review was restricted to trials evaluating the Cogmed method. A meta-analysis calculated the pooled standardised difference in means (SMD) between intervention and control groups. RESULTS: A total of 622 studies were identified and 12 studies with 13 group comparisons met inclusion criteria. The meta-analysis showed a significant training effect on inattention in daily life}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Many common disorders across the lifespan feature impaired working memory (WM). Reported benefits of a WM training program include improving inattention in daily life, but this has not been evaluated in a meta-analysis. This study aimed to evaluate whether one WM training method has benefits for inattention in daily life by conducting a systematic review and meta-analysis. METHODS: We searched Medline and PsycINFO, relevant journals and contacted authors for studies with an intervention and control group reporting post-training estimates of inattention in daily life. To reduce the influence of different WM training methods on the findings, the review was restricted to trials evaluating the Cogmed method. A meta-analysis calculated the pooled standardised difference in means (SMD) between intervention and control groups. RESULTS: A total of 622 studies were identified and 12 studies with 13 group comparisons met inclusion criteria. The meta-analysis showed a significant training effect on inattention in daily life | |
Henrik Ullman, Megan Spencer-Smith, Deanne K Thompson, Lex W Doyle, Terrie E Inder, Peter J Anderson, Torkel Klingberg Neonatal MRI is associated with future cognition and academic achievement in preterm children Journal Article Brain, 138 (11), pp. 3251–3262, 2015, ISSN: 14602156. @article{Ullman2015, title = {Neonatal MRI is associated with future cognition and academic achievement in preterm children}, author = {Henrik Ullman and Megan Spencer-Smith and Deanne K Thompson and Lex W Doyle and Terrie E Inder and Peter J Anderson and Torkel Klingberg}, doi = {10.1093/brain/awv244}, issn = {14602156}, year = {2015}, date = {2015-01-01}, journal = {Brain}, volume = {138}, number = {11}, pages = {3251--3262}, abstract = {textcopyright 2015 The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com. School-age children born preterm are particularly at risk for low mathematical achievement, associated with reduced working memory and number skills. Early identification of preterm children at risk for future impairments using brain markers might assist in referral for early intervention. This study aimed to examine the use of neonatal magnetic resonance imaging measures derived from automated methods (Jacobian maps from deformation-based morphometry; fractional anisotropy maps from diffusion tensor images) to predict skills important for mathematical achievement (working memory, early mathematical skills) at 5 and 7 years in a cohort of preterm children using both univariable (general linear model) and multivariable models (support vector regression). Participants were preterm children born textless30 weeks' gestational age and healthy control children born ≥37 weeks' gestational age at the Royal Women's Hospital in Melbourne, Australia between July 2001 and December 2003 and recruited into a prospective longitudinal cohort study. At term-equivalent age (±2 weeks) 224 preterm and 46 control infants were recruited for magnetic resonance imaging. Working memory and early mathematics skills were assessed at 5 years (n = 195 preterm; n = 40 controls) and 7 years (n = 197 preterm; n = 43 controls). In the preterm group, results identified localized regions around the insula and putamen in the neonatal Jacobian map that were positively associated with early mathematics at 5 and 7 years (both P textless 0.05), even after covarying for important perinatal clinical factors using general linear model but not support vector regression. The neonatal Jacobian map showed the same trend for association with working memory at 7 years (models ranging from P = 0.07 to P = 0.05). Neonatal fractional anisotropy was positively associated with working memory and early mathematics at 5 years (both P textless 0.001) even after covarying for clinical factors using support vector regression but not general linear model. These significant relationships were not observed in the control group. In summary, we identified, in the preterm brain, regions around the insula and putamen using neonatal deformation-based morphometry, and brain microstructural organization using neonatal diffusion tensor imaging, associated with skills important for childhood mathematical achievement. Results contribute to the growing evidence for the clinical utility of neonatal magnetic resonance imaging for early identification of preterm infants at risk for childhood cognitive and academic impairment.}, keywords = {}, pubstate = {published}, tppubtype = {article} } textcopyright 2015 The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com. School-age children born preterm are particularly at risk for low mathematical achievement, associated with reduced working memory and number skills. Early identification of preterm children at risk for future impairments using brain markers might assist in referral for early intervention. This study aimed to examine the use of neonatal magnetic resonance imaging measures derived from automated methods (Jacobian maps from deformation-based morphometry; fractional anisotropy maps from diffusion tensor images) to predict skills important for mathematical achievement (working memory, early mathematical skills) at 5 and 7 years in a cohort of preterm children using both univariable (general linear model) and multivariable models (support vector regression). Participants were preterm children born textless30 weeks' gestational age and healthy control children born ≥37 weeks' gestational age at the Royal Women's Hospital in Melbourne, Australia between July 2001 and December 2003 and recruited into a prospective longitudinal cohort study. At term-equivalent age (±2 weeks) 224 preterm and 46 control infants were recruited for magnetic resonance imaging. Working memory and early mathematics skills were assessed at 5 years (n = 195 preterm; n = 40 controls) and 7 years (n = 197 preterm; n = 43 controls). In the preterm group, results identified localized regions around the insula and putamen in the neonatal Jacobian map that were positively associated with early mathematics at 5 and 7 years (both P textless 0.05), even after covarying for important perinatal clinical factors using general linear model but not support vector regression. The neonatal Jacobian map showed the same trend for association with working memory at 7 years (models ranging from P = 0.07 to P = 0.05). Neonatal fractional anisotropy was positively associated with working memory and early mathematics at 5 years (both P textless 0.001) even after covarying for clinical factors using support vector regression but not general linear model. These significant relationships were not observed in the control group. In summary, we identified, in the preterm brain, regions around the insula and putamen using neonatal deformation-based morphometry, and brain microstructural organization using neonatal diffusion tensor imaging, associated with skills important for childhood mathematical achievement. Results contribute to the growing evidence for the clinical utility of neonatal magnetic resonance imaging for early identification of preterm infants at risk for childhood cognitive and academic impairment. | |
2014 |
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Sissela Bergman-Nutley, Torkel Klingberg Effect of working memory training on working memory, arithmetic and following instructions Journal Article Psychological Research, 78 (6), pp. 869–877, 2014, ISSN: 0340-0727. @article{Bergman-Nutley2014, title = {Effect of working memory training on working memory, arithmetic and following instructions}, author = {Sissela Bergman-Nutley and Torkel Klingberg}, url = {http://link.springer.com/10.1007/s00426-014-0614-0}, doi = {10.1007/s00426-014-0614-0}, issn = {0340-0727}, year = {2014}, date = {2014-11-01}, journal = {Psychological Research}, volume = {78}, number = {6}, pages = {869--877}, abstract = {Abstract Mathematical ability is dependent on specific mathematical training but also associated with a range of cognitive factors, including working memory (WM) capacity. Previous studies have shown that WM training leads to improvement in non-trained WM tasks, but the results regarding transfer to mathematics are inconclusive. In the present study, 176 children with WM deficits, aged 7–15 years performed 5 weeks ofWMtraining. During the training period, they were assessed five times with a test of complex WM (the Odd One Out), a test of remembering and following instructions and a test of arithmetic. The improvements were compared to the performance of a control group of 304 typically developing children aged 7–15 years who performed the same transfer tasks at the same time intervals, but without training. The training group improved significantly more than the control group on all three transfer tests (all p$backslash$0.0001), after correction for baseline performance, age and sex. The effect size for mathematics was small and the effect sizes for the WM tasks were moderate to large. The transfer increased line- arly with the amount of training time and correlated with the amount of improvement on the trained tasks. These results confirm previous findings of training-induced improvements in non-trained WM tasks including the ability to follow instructions, but extend previous findings by showing improvements also for arithmetic. This is encouraging regarding the potential role of cognitive training for education, but it is desirable to find paradigms that would enhance the effect of the training on mathe- matics. One of the future challenges for studying training effects is combining large sample sizes with high quality and compliance, to detect relevant but smaller effects of cognitive training.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Mathematical ability is dependent on specific mathematical training but also associated with a range of cognitive factors, including working memory (WM) capacity. Previous studies have shown that WM training leads to improvement in non-trained WM tasks, but the results regarding transfer to mathematics are inconclusive. In the present study, 176 children with WM deficits, aged 7–15 years performed 5 weeks ofWMtraining. During the training period, they were assessed five times with a test of complex WM (the Odd One Out), a test of remembering and following instructions and a test of arithmetic. The improvements were compared to the performance of a control group of 304 typically developing children aged 7–15 years who performed the same transfer tasks at the same time intervals, but without training. The training group improved significantly more than the control group on all three transfer tests (all p$backslash$0.0001), after correction for baseline performance, age and sex. The effect size for mathematics was small and the effect sizes for the WM tasks were moderate to large. The transfer increased line- arly with the amount of training time and correlated with the amount of improvement on the trained tasks. These results confirm previous findings of training-induced improvements in non-trained WM tasks including the ability to follow instructions, but extend previous findings by showing improvements also for arithmetic. This is encouraging regarding the potential role of cognitive training for education, but it is desirable to find paradigms that would enhance the effect of the training on mathe- matics. One of the future challenges for studying training effects is combining large sample sizes with high quality and compliance, to detect relevant but smaller effects of cognitive training. | |
Torkel Klingberg Childhood cognitive development as a skill Journal Article Trends in Cognitive Sciences, 18 (11), pp. 573–579, 2014, ISSN: 13646613. @article{Klingberg2014, title = {Childhood cognitive development as a skill}, author = {Torkel Klingberg}, url = {http://dx.doi.org/10.1016/j.tics.2014.06.007 https://www.sciencedirect.com/science/article/pii/S1364661314001533 http://linkinghub.elsevier.com/retrieve/pii/S1364661314001533 https://linkinghub.elsevier.com/retrieve/pii/S1364661314001533}, doi = {10.1016/j.tics.2014.06.007}, issn = {13646613}, year = {2014}, date = {2014-11-01}, journal = {Trends in Cognitive Sciences}, volume = {18}, number = {11}, pages = {573--579}, publisher = {Elsevier Current Trends}, abstract = {Theories view childhood development as being either driven by structural maturation of the brain or being driven by skill-learning. It is hypothesized here that working memory (WM) development during childhood is partly driven by training effects in the environment, and that similar neural mechanisms underlie training-induced plasticity and childhood development. In particular, the functional connectivity of a fronto-parietal network is suggested to be associated with WM capacity. The striatum, dopamine receptor D2 (DRD2) activity, and corticostriatal white-matter tracts, on the other hand, seem to be more important for plasticity and change of WM capacity during both training and development. In this view, the development of WM capacity during childhood partly involves the same mechanisms as skill-learning.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Theories view childhood development as being either driven by structural maturation of the brain or being driven by skill-learning. It is hypothesized here that working memory (WM) development during childhood is partly driven by training effects in the environment, and that similar neural mechanisms underlie training-induced plasticity and childhood development. In particular, the functional connectivity of a fronto-parietal network is suggested to be associated with WM capacity. The striatum, dopamine receptor D2 (DRD2) activity, and corticostriatal white-matter tracts, on the other hand, seem to be more important for plasticity and change of WM capacity during both training and development. In this view, the development of WM capacity during childhood partly involves the same mechanisms as skill-learning. | |
Charlotte Nymberg, Tobias Banaschewski, Arun LW Bokde, Christian Büchel, Patricia Conrod, Herta Flor, Vincent Frouin, Hugh Garavan, P Gowland, Andreas Heinz, Bernd Ittermann, Karl Mann, Jean-Luc Martinot, Frauke Nees, Tomas Paus, Zdenka Pausova, Marcella Rietschel, Trevor W Robbins, Michael N Smolka, Andreas Ströhle, Gunter Schumann, Torkel Klingberg DRD2/ANKK1 Polymorphism Modulates the Effect of Ventral Striatal Activation on Working Memory Performance Journal Article Neuropsychopharmacology, 39 (10), pp. 2357–2365, 2014, ISSN: 0893-133X. @article{Nymberg2014, title = {DRD2/ANKK1 Polymorphism Modulates the Effect of Ventral Striatal Activation on Working Memory Performance}, author = {Charlotte Nymberg and Tobias Banaschewski and Arun LW Bokde and Christian Büchel and Patricia Conrod and Herta Flor and Vincent Frouin and Hugh Garavan and P Gowland and Andreas Heinz and Bernd Ittermann and Karl Mann and Jean-Luc Martinot and Frauke Nees and Tomas Paus and Zdenka Pausova and Marcella Rietschel and Trevor W Robbins and Michael N Smolka and Andreas Ströhle and Gunter Schumann and Torkel Klingberg}, url = {http://www.nature.com/articles/npp201483}, doi = {10.1038/npp.2014.83}, issn = {0893-133X}, year = {2014}, date = {2014-09-01}, journal = {Neuropsychopharmacology}, volume = {39}, number = {10}, pages = {2357--2365}, abstract = {Motivation is important for learning and cognition. Although dopaminergic (D2) transmission in the ventral striatum (VS) is associated with motivation, learning, and cognition are more strongly associated with function of the dorsal striatum, including activation in the caudate nucleus. A recent study found an interaction between intrinsic motivation and the DRD2/ANKK1 polymorphism (rs1800497), suggesting that A-carriers of rs1800497 are significantly more sensitive to motivation in order to improve during working memory (WM) training. Using data from the two large-scale imaging genetic data sets, IMAGEN (n=1080, age 13-15 years) and BrainChild (n∼300, age 6-27), we investigated whether rs1800497 is associated with WM. In the IMAGEN data set, we tested whether VS/caudate activation during reward anticipation was associated with WM performance and whether rs1800497 and VS/caudate activation interact to affect WM performance. We found that rs1800497 was associated with WM performance in IMAGEN and BrainChild. Higher VS and caudate activation during reward processing were significantly associated with higher WM performance (ptextless0.0001). An interaction was found between the DRD2/ANKK1 polymorphism rs1800497 and VS activation during reward anticipation on WM (ptextless0.01), such that carriers of the minor allele (A) showed a significant correlation between VS activation and WM, whereas the GG-homozygotes did not, suggesting that the effect of VS BOLD on WM is modified by inter-individual genetic differences related to D2 dopaminergic transmission. textcopyright 2014 American College of Neuropsychopharmacology.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Motivation is important for learning and cognition. Although dopaminergic (D2) transmission in the ventral striatum (VS) is associated with motivation, learning, and cognition are more strongly associated with function of the dorsal striatum, including activation in the caudate nucleus. A recent study found an interaction between intrinsic motivation and the DRD2/ANKK1 polymorphism (rs1800497), suggesting that A-carriers of rs1800497 are significantly more sensitive to motivation in order to improve during working memory (WM) training. Using data from the two large-scale imaging genetic data sets, IMAGEN (n=1080, age 13-15 years) and BrainChild (n∼300, age 6-27), we investigated whether rs1800497 is associated with WM. In the IMAGEN data set, we tested whether VS/caudate activation during reward anticipation was associated with WM performance and whether rs1800497 and VS/caudate activation interact to affect WM performance. We found that rs1800497 was associated with WM performance in IMAGEN and BrainChild. Higher VS and caudate activation during reward processing were significantly associated with higher WM performance (ptextless0.0001). An interaction was found between the DRD2/ANKK1 polymorphism rs1800497 and VS activation during reward anticipation on WM (ptextless0.01), such that carriers of the minor allele (A) showed a significant correlation between VS activation and WM, whereas the GG-homozygotes did not, suggesting that the effect of VS BOLD on WM is modified by inter-individual genetic differences related to D2 dopaminergic transmission. textcopyright 2014 American College of Neuropsychopharmacology. | |
H Ullman, R Almeida, Torkel Klingberg Structural Maturation and Brain Activity Predict Future Working Memory Capacity during Childhood Development Journal Article Journal of Neuroscience, 34 (5), pp. 1592–1598, 2014, ISSN: 0270-6474. @article{Ullman2014, title = {Structural Maturation and Brain Activity Predict Future Working Memory Capacity during Childhood Development}, author = {H Ullman and R Almeida and Torkel Klingberg}, url = {http://www.jneurosci.org/cgi/doi/10.1523/JNEUROSCI.0842-13.2014}, doi = {10.1523/JNEUROSCI.0842-13.2014}, issn = {0270-6474}, year = {2014}, date = {2014-01-01}, journal = {Journal of Neuroscience}, volume = {34}, number = {5}, pages = {1592--1598}, abstract = {Human working memory capacity develops during childhood and is a strong predictor of future academic performance, in particular, achievements in mathematics and reading. Predicting working memory development is important for the early identification of children at risk for poor cognitive and academic development. Here we show that structural and functional magnetic resonance imaging data explain variance in children's working memory capacity 2 years later, which was unique variance in addition to that predicted using cognitive tests. While current working memory capacity correlated with frontoparietal cortical activity, the future capacity could be inferred from structure and activity in basal ganglia and thalamus. This gives a novel insight into the neural mechanisms of childhood development and supports the idea that neuroimaging can have a unique role in predicting children's cognitive development.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Human working memory capacity develops during childhood and is a strong predictor of future academic performance, in particular, achievements in mathematics and reading. Predicting working memory development is important for the early identification of children at risk for poor cognitive and academic development. Here we show that structural and functional magnetic resonance imaging data explain variance in children's working memory capacity 2 years later, which was unique variance in addition to that predicted using cognitive tests. While current working memory capacity correlated with frontoparietal cortical activity, the future capacity could be inferred from structure and activity in basal ganglia and thalamus. This gives a novel insight into the neural mechanisms of childhood development and supports the idea that neuroimaging can have a unique role in predicting children's cognitive development. | |
F Darki, M Peyrard-Janvid, H Matsson, J Kere, T Klingberg DCDC2 Polymorphism Is Associated with Left Temporoparietal Gray and White Matter Structures during Development Journal Article Journal of Neuroscience, 34 (43), pp. 14455–14462, 2014, ISSN: 0270-6474. @article{Darki2014, title = {DCDC2 Polymorphism Is Associated with Left Temporoparietal Gray and White Matter Structures during Development}, author = {F Darki and M Peyrard-Janvid and H Matsson and J Kere and T Klingberg}, doi = {10.1523/jneurosci.1216-14.2014}, issn = {0270-6474}, year = {2014}, date = {2014-01-01}, journal = {Journal of Neuroscience}, volume = {34}, number = {43}, pages = {14455--14462}, abstract = {textcopyright 2014 the authors. 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.}, keywords = {}, pubstate = {published}, tppubtype = {article} } textcopyright 2014 the authors. 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. | |
Sissela Bergman Nutley, Fahimeh Darki, Torkel Klingberg Music practice is associated with development of working memory during childhood and adolescence Journal Article Frontiers in Human Neuroscience, 7 (January), pp. 1–9, 2014. @article{BergmanNutley2014, title = {Music practice is associated with development of working memory during childhood and adolescence}, author = {Sissela {Bergman Nutley} and Fahimeh Darki and Torkel Klingberg}, doi = {10.3389/fnhum.2013.00926}, year = {2014}, date = {2014-01-01}, journal = {Frontiers in Human Neuroscience}, volume = {7}, number = {January}, pages = {1--9}, abstract = {Practicing a musical instrument is associated with cognitive benefits and structural brain changes in correlational and interventional trials; however, the effect of musical training on cognition during childhood is still unclear. In this longitudinal study of child development we analyzed the association between musical practice and performance on reasoning, processing speed and working memory (WM) during development. Subjects (n = 352) between the ages of 6 and 25 years participated in neuropsychological assessments and neuroimaging investigations (n = 64) on two or three occasions, 2 years apart. Mixed model regression showed that musical practice had an overall positive association with WM capacity (visuo-spatial WM}, keywords = {}, pubstate = {published}, tppubtype = {article} } Practicing a musical instrument is associated with cognitive benefits and structural brain changes in correlational and interventional trials; however, the effect of musical training on cognition during childhood is still unclear. In this longitudinal study of child development we analyzed the association between musical practice and performance on reasoning, processing speed and working memory (WM) during development. Subjects (n = 352) between the ages of 6 and 25 years participated in neuropsychological assessments and neuroimaging investigations (n = 64) on two or three occasions, 2 years apart. Mixed model regression showed that musical practice had an overall positive association with WM capacity (visuo-spatial WM | |
Stina Söderqvist, Hans Matsson, Myriam Peyrard-Janvid, Juha Kere, Torkel Klingberg Polymorphisms in the Dopamine Receptor 2 Gene Region Influence Improvements during Working Memory Training in Children and Adolescents Journal Article Journal of Cognitive Neuroscience, 26 (1), pp. 54–62, 2014, ISSN: 0898-929X. @article{Soderqvist2014, title = {Polymorphisms in the Dopamine Receptor 2 Gene Region Influence Improvements during Working Memory Training in Children and Adolescents}, author = {Stina Söderqvist and Hans Matsson and Myriam Peyrard-Janvid and Juha Kere and Torkel Klingberg}, url = {http://www.mitpressjournals.org/doi/10.1162/jocn_a_00478}, doi = {10.1162/jocn_a_00478}, issn = {0898-929X}, year = {2014}, date = {2014-01-01}, journal = {Journal of Cognitive Neuroscience}, volume = {26}, number = {1}, pages = {54--62}, abstract = {Unexpected changes in the location of a target for an upcoming action require both attentional reorienting and motor planning update. In both macaque and human brain, the medial posterior parietal cortex is involved in both phenomena but its causal role is still unclear. Here we used on-line rTMS over the putative human V6A (pV6A), a reach-related region in the dorsal part of the anterior bank of the parieto-occipital sulcus, during an attention and a reaching task requiring covert shifts of attention and planning of reaching movements toward cued targets in space. We found that rTMS increased RTs to invalidly cued but not to validly cued targets during both the attention and reaching task. Furthermore, we found that rTMS induced a deviation of reaching endpoints toward visual fixation and that this deviation was larger for invalidly cued targets. The results suggest that reorienting signals are used by human pV6A area to rapidly update the current motor plan or the ongoing action when a behaviorally relevant object unexpectedly occurs in an unattended location. The current findings suggest a direct involvement of the action-related dorso-medial visual stream in attentional reorienting and a more specific role of pV6A area in the dynamic, on-line control of reaching actions.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Unexpected changes in the location of a target for an upcoming action require both attentional reorienting and motor planning update. In both macaque and human brain, the medial posterior parietal cortex is involved in both phenomena but its causal role is still unclear. Here we used on-line rTMS over the putative human V6A (pV6A), a reach-related region in the dorsal part of the anterior bank of the parieto-occipital sulcus, during an attention and a reaching task requiring covert shifts of attention and planning of reaching movements toward cued targets in space. We found that rTMS increased RTs to invalidly cued but not to validly cued targets during both the attention and reaching task. Furthermore, we found that rTMS induced a deviation of reaching endpoints toward visual fixation and that this deviation was larger for invalidly cued targets. The results suggest that reorienting signals are used by human pV6A area to rapidly update the current motor plan or the ongoing action when a behaviorally relevant object unexpectedly occurs in an unattended location. The current findings suggest a direct involvement of the action-related dorso-medial visual stream in attentional reorienting and a more specific role of pV6A area in the dynamic, on-line control of reaching actions. | |
2013 |
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Marco Ciavarro, Ettore Ambrosini, Annalisa Tosoni, Giorgia Committeri, Patrizia Fattori, Claudio Galletti Reorganization of Retinotopic Maps After Occipital Lobe Infarction Journal Article Journal of Cognitive Neuroscience, 26 (6), pp. 1–10, 2013, ISSN: 0898-929X. @article{Ciavarro2013, title = {Reorganization of Retinotopic Maps After Occipital Lobe Infarction}, author = {Marco Ciavarro and Ettore Ambrosini and Annalisa Tosoni and Giorgia Committeri and Patrizia Fattori and Claudio Galletti}, url = {http://dx.doi.org/10.1162/jocn_a_00409%5Cnhttp://www.mitpressjournals.org/doi/abs/10.1162/jocn_a_00409}, doi = {10.1162/jocn}, issn = {0898-929X}, year = {2013}, date = {2013-01-01}, journal = {Journal of Cognitive Neuroscience}, volume = {26}, number = {6}, pages = {1--10}, abstract = {Unexpected changes in the location of a target for an upcoming action require both attentional reorienting and motor planning update. In both macaque and human brain, the medial posterior parietal cortex is involved in both phenomena but its causal role is still unclear. Here we used on-line rTMS over the putative human V6A (pV6A), a reach-related region in the dorsal part of the anterior bank of the parieto-occipital sulcus, during an attention and a reaching task requiring covert shifts of attention and planning of reaching movements toward cued targets in space. We found that rTMS increased RTs to invalidly cued but not to validly cued targets during both the attention and reaching task. Furthermore, we found that rTMS induced a deviation of reaching endpoints toward visual fixation and that this deviation was larger for invalidly cued targets. The results suggest that reorienting signals are used by human pV6A area to rapidly update the current motor plan or the ongoing action when a behaviorally relevant object unexpectedly occurs in an unattended location. The current findings suggest a direct involvement of the action-related dorso-medial visual stream in attentional reorienting and a more specific role of pV6A area in the dynamic, on-line control of reaching actions.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Unexpected changes in the location of a target for an upcoming action require both attentional reorienting and motor planning update. In both macaque and human brain, the medial posterior parietal cortex is involved in both phenomena but its causal role is still unclear. Here we used on-line rTMS over the putative human V6A (pV6A), a reach-related region in the dorsal part of the anterior bank of the parieto-occipital sulcus, during an attention and a reaching task requiring covert shifts of attention and planning of reaching movements toward cued targets in space. We found that rTMS increased RTs to invalidly cued but not to validly cued targets during both the attention and reaching task. Furthermore, we found that rTMS induced a deviation of reaching endpoints toward visual fixation and that this deviation was larger for invalidly cued targets. The results suggest that reorienting signals are used by human pV6A area to rapidly update the current motor plan or the ongoing action when a behaviorally relevant object unexpectedly occurs in an unattended location. The current findings suggest a direct involvement of the action-related dorso-medial visual stream in attentional reorienting and a more specific role of pV6A area in the dynamic, on-line control of reaching actions. | |
2012 |
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Fahimeh Darki, Myriam Peyrard-Janvid, Hans Matsson, Juha Kere, Torkel Klingberg Three Dyslexia Susceptibility Genes, DYX1C1, DCDC2, and KIAA0319, Affect Temporo-Parietal White Matter Structure Journal Article Biological Psychiatry, 72 (8), pp. 671–676, 2012, ISSN: 00063223. @article{Darki2012, title = {Three Dyslexia Susceptibility Genes, DYX1C1, DCDC2, and KIAA0319, Affect Temporo-Parietal White Matter Structure}, author = {Fahimeh Darki and Myriam Peyrard-Janvid and Hans Matsson and Juha Kere and Torkel Klingberg}, url = {https://www.sciencedirect.com/science/article/pii/S0006322312004453 http://linkinghub.elsevier.com/retrieve/pii/S0006322312004453 http://dx.doi.org/10.1016/j.biopsych.2012.05.008}, doi = {10.1016/j.biopsych.2012.05.008}, issn = {00063223}, year = {2012}, date = {2012-10-01}, journal = {Biological Psychiatry}, volume = {72}, number = {8}, pages = {671--676}, publisher = {Elsevier}, 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.}, keywords = {}, pubstate = {published}, tppubtype = {article} } 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. | |
Iroise Dumontheil, Torkel Klingberg Brain activity during a visuospatial working memory task predicts arithmetical performance 2 years later Journal Article Cerebral Cortex, 22 (5), pp. 1078–1085, 2012, ISSN: 10473211. @article{Dumontheil2012, title = {Brain activity during a visuospatial working memory task predicts arithmetical performance 2 years later}, author = {Iroise Dumontheil and Torkel Klingberg}, doi = {10.1093/cercor/bhr175}, issn = {10473211}, year = {2012}, date = {2012-01-01}, journal = {Cerebral Cortex}, volume = {22}, number = {5}, pages = {1078--1085}, abstract = {Visuospatial working memory (WM) capacity is highly correlated with mathematical reasoning abilities and can predict future development of arithmetical performance. Activity in the intraparietal sulcus (IPS) during visuospatial WM tasks correlates with interindividual differences in WM capacity. This region has also been implicated in numerical representation, and its structure and activity reflect arithmetical performance impairments (e.g., dyscalculia). We collected behavioral (N = 246) and neuroimaging data (N = 46) in a longitudinal sample to test whether IPS activity during a visuospatial WM task could provide more information than psychological testing alone and predict arithmetical performance 2 years later in healthy participants aged 6-16 years. Nonverbal reasoning and verbal and visuospatial WM measures were found to be independent predictors of arithmetical outcome. In addition, WM activation in the left IPS predicted arithmetical outcome independently of behavioral measures. A logistic model including both behavioral and imaging data showed improved sensitivity by correctly classifying more than twice as many children as poor arithmetical performers after 2 years than a model with behavioral measures only. These results demonstrate that neuroimaging data can provide useful information in addition to behavioral assessments and be used to improve the identification of individuals at risk of future low academic performance.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Visuospatial working memory (WM) capacity is highly correlated with mathematical reasoning abilities and can predict future development of arithmetical performance. Activity in the intraparietal sulcus (IPS) during visuospatial WM tasks correlates with interindividual differences in WM capacity. This region has also been implicated in numerical representation, and its structure and activity reflect arithmetical performance impairments (e.g., dyscalculia). We collected behavioral (N = 246) and neuroimaging data (N = 46) in a longitudinal sample to test whether IPS activity during a visuospatial WM task could provide more information than psychological testing alone and predict arithmetical performance 2 years later in healthy participants aged 6-16 years. Nonverbal reasoning and verbal and visuospatial WM measures were found to be independent predictors of arithmetical outcome. In addition, WM activation in the left IPS predicted arithmetical outcome independently of behavioral measures. A logistic model including both behavioral and imaging data showed improved sensitivity by correctly classifying more than twice as many children as poor arithmetical performers after 2 years than a model with behavioral measures only. These results demonstrate that neuroimaging data can provide useful information in addition to behavioral assessments and be used to improve the identification of individuals at risk of future low academic performance. | |
T Ziermans, I Dumontheil, C Roggeman, M Peyrard-Janvid, H Matsson, J Kere, T Klingberg Working memory brain activity and capacity link MAOA polymorphism to aggressive behavior during development Journal Article Translational Psychiatry, 2 (2), pp. e85–9, 2012, ISSN: 21583188. @article{Ziermans2012, title = {Working memory brain activity and capacity link MAOA polymorphism to aggressive behavior during development}, author = {T Ziermans and I Dumontheil and C Roggeman and M Peyrard-Janvid and H Matsson and J Kere and T Klingberg}, url = {http://dx.doi.org/10.1038/tp.2012.7}, doi = {10.1038/tp.2012.7}, issn = {21583188}, year = {2012}, date = {2012-01-01}, journal = {Translational Psychiatry}, volume = {2}, number = {2}, pages = {e85--9}, publisher = {Nature Publishing Group}, abstract = {A developmental increase in working memory capacity is an important part of cognitive development, and low working memory (WM) capacity is a risk factor for developing psychopathology. Brain activity represents a promising endophenotype for linking genes to behavior and for improving our understanding of the neurobiology of WM development. We investigated gene-brain-behavior relationships by focusing on 18 single-nucleotide polymorphisms (SNPs) located in six dopaminergic candidate genes (COMT, SLC6A3/DAT1, DBH, DRD4, DRD5, MAOA). Visuospatial WM (VSWM) brain activity, measured with functional magnetic resonance imaging, and VSWM capacity were assessed in a longitudinal study of typically developing children and adolescents. Behavioral problems were evaluated using the Child Behavior Checklist (CBCL). One SNP (rs6609257), located ~6.6 kb downstream of the monoamine oxidase A gene (MAOA) on human chromosome X, significantly affected brain activity in a network of frontal, parietal and occipital regions. Increased activity in this network, but not in caudate nucleus or anterior prefrontal regions, was correlated with VSWM capacity, which in turn predicted externalizing (aggressive/oppositional) symptoms, with higher WM capacity associated with fewer externalizing symptoms. There were no direct significant correlations between rs6609257 and behavioral symptoms. These results suggest a mediating role of WM brain activity and capacity in linking the MAOA gene to aggressive behavior during development.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A developmental increase in working memory capacity is an important part of cognitive development, and low working memory (WM) capacity is a risk factor for developing psychopathology. Brain activity represents a promising endophenotype for linking genes to behavior and for improving our understanding of the neurobiology of WM development. We investigated gene-brain-behavior relationships by focusing on 18 single-nucleotide polymorphisms (SNPs) located in six dopaminergic candidate genes (COMT, SLC6A3/DAT1, DBH, DRD4, DRD5, MAOA). Visuospatial WM (VSWM) brain activity, measured with functional magnetic resonance imaging, and VSWM capacity were assessed in a longitudinal study of typically developing children and adolescents. Behavioral problems were evaluated using the Child Behavior Checklist (CBCL). One SNP (rs6609257), located ~6.6 kb downstream of the monoamine oxidase A gene (MAOA) on human chromosome X, significantly affected brain activity in a network of frontal, parietal and occipital regions. Increased activity in this network, but not in caudate nucleus or anterior prefrontal regions, was correlated with VSWM capacity, which in turn predicted externalizing (aggressive/oppositional) symptoms, with higher WM capacity associated with fewer externalizing symptoms. There were no direct significant correlations between rs6609257 and behavioral symptoms. These results suggest a mediating role of WM brain activity and capacity in linking the MAOA gene to aggressive behavior during development. | |
Stina Söderqvist, Sissela Bergman Nutley, Myriam Peyrard-Janvid, Hans Matsson, Keith Humphreys, Juha Kere, Torkel Klingberg Dopamine, working memory, and training induced plasticity: Implications for developmental research Journal Article Developmental Psychology, 48 (3), pp. 836–843, 2012, ISSN: 00121649. @article{Soderqvist2012, title = {Dopamine, working memory, and training induced plasticity: Implications for developmental research}, author = {Stina Söderqvist and Sissela Bergman Nutley and Myriam Peyrard-Janvid and Hans Matsson and Keith Humphreys and Juha Kere and Torkel Klingberg}, doi = {10.1037/a0026179}, issn = {00121649}, year = {2012}, date = {2012-01-01}, journal = {Developmental Psychology}, volume = {48}, number = {3}, pages = {836--843}, abstract = {Cognitive deficits and particularly deficits in working memory (WM) capacity are common features in neuropsychiatric disorders. Understanding the underlying mechanisms through which WM capacity can be improved is therefore of great importance. Several lines of research indicate that dopamine plays an important role not only in WM function but also for improving WM capacity. For example, pharmacological interventions acting on the dopaminergic system, such as methylphenidate, improve WM performance. In addition, behavioral interventions for improving WM performance in the form of intensive computerized training have recently been associated with changes in dopamine receptor density. These two different means of improving WM performance--pharmacological and behavioral--are thus associated with similar biological mechanisms in the brain involving dopaminergic systems. This article reviews some of the evidence for the role of dopamine in WM functioning, in particular concerning the link to WM development and cognitive plasticity. Novel data are presented showing that variation in the dopamine transporter gene (DAT1) influences improvements in WM and fluid intelligence in preschool-age children following cognitive training. Our results emphasize the importance of the role of dopamine in determining cognitive plasticity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cognitive deficits and particularly deficits in working memory (WM) capacity are common features in neuropsychiatric disorders. Understanding the underlying mechanisms through which WM capacity can be improved is therefore of great importance. Several lines of research indicate that dopamine plays an important role not only in WM function but also for improving WM capacity. For example, pharmacological interventions acting on the dopaminergic system, such as methylphenidate, improve WM performance. In addition, behavioral interventions for improving WM performance in the form of intensive computerized training have recently been associated with changes in dopamine receptor density. These two different means of improving WM performance--pharmacological and behavioral--are thus associated with similar biological mechanisms in the brain involving dopaminergic systems. This article reviews some of the evidence for the role of dopamine in WM functioning, in particular concerning the link to WM development and cognitive plasticity. Novel data are presented showing that variation in the dopamine transporter gene (DAT1) influences improvements in WM and fluid intelligence in preschool-age children following cognitive training. Our results emphasize the importance of the role of dopamine in determining cognitive plasticity. | |
Stina Söderqvist, Sissela B Nutley, Jon Ottersen, Katja M Grill, Torkel Klingberg Computerized training of non-verbal reasoning and working memory in children with intellectual disability Journal Article Frontiers in Human Neuroscience, 6 (October), pp. 1–8, 2012. @article{Soderqvist2012a, title = {Computerized training of non-verbal reasoning and working memory in children with intellectual disability}, author = {Stina Söderqvist and Sissela B Nutley and Jon Ottersen and Katja M Grill and Torkel Klingberg}, doi = {10.3389/fnhum.2012.00271}, year = {2012}, date = {2012-01-01}, journal = {Frontiers in Human Neuroscience}, volume = {6}, number = {October}, pages = {1--8}, abstract = {Children with intellectual disabilities show deficits in both reasoning ability and working memory (WM) that impact everyday functioning and academic achievement. In this study we investigated the feasibility of cognitive training for improving WM and non-verbal reasoning (NVR) ability in children with intellectual disability. Participants were randomized to a 5-week adaptive training program (intervention group) or non-adaptive version of the program (active control group). Cognitive assessments were conducted prior to and directly after training and 1 year later to examine effects of the training. Improvements during training varied largely and amount of progress during training predicted transfer to WM and comprehension of instructions, with higher training progress being associated with greater transfer improvements. The strongest predictors for training progress were found to be gender, co-morbidity, and baseline capacity on verbal WM. In particular, females without an additional diagnosis and with higher baseline performance showed greater progress. No significant effects of training were observed at the 1-year follow-up, suggesting that training should be more intense or repeated in order for effects to persist in children with intellectual disabilities. A major finding of this study is that cognitive training is feasible in this clinical sample and can help improve their cognitive performance. However, a minimum cognitive capacity or training ability seems necessary for the training to be beneficial, with some individuals showing little improvement in performance. Future studies of cognitive training should take into consideration how inter-individual differences in training progress influence transfer effects and further investigate how baseline capacities predict training outcome.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Children with intellectual disabilities show deficits in both reasoning ability and working memory (WM) that impact everyday functioning and academic achievement. In this study we investigated the feasibility of cognitive training for improving WM and non-verbal reasoning (NVR) ability in children with intellectual disability. Participants were randomized to a 5-week adaptive training program (intervention group) or non-adaptive version of the program (active control group). Cognitive assessments were conducted prior to and directly after training and 1 year later to examine effects of the training. Improvements during training varied largely and amount of progress during training predicted transfer to WM and comprehension of instructions, with higher training progress being associated with greater transfer improvements. The strongest predictors for training progress were found to be gender, co-morbidity, and baseline capacity on verbal WM. In particular, females without an additional diagnosis and with higher baseline performance showed greater progress. No significant effects of training were observed at the 1-year follow-up, suggesting that training should be more intense or repeated in order for effects to persist in children with intellectual disabilities. A major finding of this study is that cognitive training is feasible in this clinical sample and can help improve their cognitive performance. However, a minimum cognitive capacity or training ability seems necessary for the training to be beneficial, with some individuals showing little improvement in performance. Future studies of cognitive training should take into consideration how inter-individual differences in training progress influence transfer effects and further investigate how baseline capacities predict training outcome. | |
S A Bunge, T Klingberg, R B Jacobsen, J D E Gabrieli A resource model of the neural basis of executive working memory Journal Article Proceedings of the National Academy of Sciences, 97 (7), pp. 3573–3578, 2012, ISSN: 0027-8424. @article{Bunge2012, title = {A resource model of the neural basis of executive working memory}, author = {S A Bunge and T Klingberg and R B Jacobsen and J D E Gabrieli}, doi = {10.1073/pnas.97.7.3573}, issn = {0027-8424}, year = {2012}, date = {2012-01-01}, journal = {Proceedings of the National Academy of Sciences}, volume = {97}, number = {7}, pages = {3573--3578}, abstract = {Working memory (WM) refers to the temporary storage and processing of goal-relevant information. WM is thought to include domain-specific short-term memory stores and executive processes, such as coordination, that operate on the contents of WM. To examine the neural substrates of coordination, we acquired functional magnetic resonance imaging data while subjects performed a WM span test designed specifically to measure executive WM. Subjects performed two tasks (sentence reading and short-term memory for five words) either separately or concurrently. Dual-task performance activated frontal-lobe areas to a greater extent than performance of either task in isolation, but no new area was activated beyond those activated by either component task. These findings support a resource theory of WM executive processes in the frontal lobes.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Working memory (WM) refers to the temporary storage and processing of goal-relevant information. WM is thought to include domain-specific short-term memory stores and executive processes, such as coordination, that operate on the contents of WM. To examine the neural substrates of coordination, we acquired functional magnetic resonance imaging data while subjects performed a WM span test designed specifically to measure executive WM. Subjects performed two tasks (sentence reading and short-term memory for five words) either separately or concurrently. Dual-task performance activated frontal-lobe areas to a greater extent than performance of either task in isolation, but no new area was activated beyond those activated by either component task. These findings support a resource theory of WM executive processes in the frontal lobes. | |
2011 |
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Iroise Dumontheil, Chantal Roggeman, Tim Ziermans, Myriam Peyrard-Janvid, Hans Matsson, Juha Kere, Torkel Klingberg Influence of the COMT Genotype on Working Memory and Brain Activity Changes During Development Journal Article Biological Psychiatry, 70 (3), pp. 222–229, 2011, ISSN: 0006-3223. @article{Dumontheil2011, title = {Influence of the COMT Genotype on Working Memory and Brain Activity Changes During Development}, author = {Iroise Dumontheil and Chantal Roggeman and Tim Ziermans and Myriam Peyrard-Janvid and Hans Matsson and Juha Kere and Torkel Klingberg}, url = {https://www.sciencedirect.com/science/article/pii/S0006322311002022?via%3Dihub}, doi = {10.1016/J.BIOPSYCH.2011.02.027}, issn = {0006-3223}, year = {2011}, date = {2011-08-01}, journal = {Biological Psychiatry}, volume = {70}, number = {3}, pages = {222--229}, publisher = {Elsevier}, 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.}, keywords = {}, pubstate = {published}, tppubtype = {article} } 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. | |
Sissela Bergman Nutley, Stina Söderqvist, Sara Bryde, Lisa B Thorell, Keith Humphreys, Torkel Klingberg Gains in fluid intelligence after training non-verbal reasoning in 4-year-old children: a controlled, randomized study Journal Article Developmental Science, 14 (3), pp. 591–601, 2011, ISSN: 1363755X. @article{BergmanNutley2011, title = {Gains in fluid intelligence after training non-verbal reasoning in 4-year-old children: a controlled, randomized study}, author = {Sissela {Bergman Nutley} and Stina Söderqvist and Sara Bryde and Lisa B Thorell and Keith Humphreys and Torkel Klingberg}, url = {http://doi.wiley.com/10.1111/j.1467-7687.2010.01022.x}, doi = {10.1111/j.1467-7687.2010.01022.x}, issn = {1363755X}, year = {2011}, date = {2011-05-01}, journal = {Developmental Science}, volume = {14}, number = {3}, pages = {591--601}, abstract = {Fluid intelligence (Gf) predicts performance on a wide range of cognitive activities, and children with impaired Gf often experience academic difficulties. Previous attempts to improve Gf have been hampered by poor control conditions and single outcome measures. It is thus still an open question whether Gf can be improved by training. This study included 4-year-old children (N = 101) who performed computerized training (15 min/day for 25 days) of either non-verbal reasoning, working memory, a combination of both, or a placebo version of the combined training. Compared to the placebo group, the non-verbal reasoning training group improved significantly on Gf when analysed as a latent variable of several reasoning tasks. Smaller gains on problem solving tests were seen in the combination training group. The group training working memory improved on measures of working memory, but not on problem solving tests. This study shows that it is possible to improve Gf with training, which could have implications for early interventions in children.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Fluid intelligence (Gf) predicts performance on a wide range of cognitive activities, and children with impaired Gf often experience academic difficulties. Previous attempts to improve Gf have been hampered by poor control conditions and single outcome measures. It is thus still an open question whether Gf can be improved by training. This study included 4-year-old children (N = 101) who performed computerized training (15 min/day for 25 days) of either non-verbal reasoning, working memory, a combination of both, or a placebo version of the combined training. Compared to the placebo group, the non-verbal reasoning training group improved significantly on Gf when analysed as a latent variable of several reasoning tasks. Smaller gains on problem solving tests were seen in the combination training group. The group training working memory improved on measures of working memory, but not on problem solving tests. This study shows that it is possible to improve Gf with training, which could have implications for early interventions in children. | |
2010 |
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Stina Söderqvist, Fiona McNab, Myriam Peyrard-Janvid, Hans Matsson, Keith Humphreys, Juha Kere, Torkel Klingberg, Stina Sderqvist, Fiona McNab, Myriam Peyrard-Janvid, Hans Matsson, Keith Humphreys, Juha Kere, Torkel Klingberg The SNAP25 Gene Is Linked to Working Memory Capacity and Maturation of the Posterior Cingulate Cortex During Childhood Journal Article Biological Psychiatry, 68 (12), pp. 1120–1125, 2010, ISSN: 0006-3223. @article{Soderqvist2010, title = {The SNAP25 Gene Is Linked to Working Memory Capacity and Maturation of the Posterior Cingulate Cortex During Childhood}, author = {Stina Söderqvist and Fiona McNab and Myriam Peyrard-Janvid and Hans Matsson and Keith Humphreys and Juha Kere and Torkel Klingberg and Stina Sderqvist and Fiona McNab and Myriam Peyrard-Janvid and Hans Matsson and Keith Humphreys and Juha Kere and Torkel Klingberg}, url = {http://dx.doi.org/10.1016/j.biopsych.2010.07.036 https://www.sciencedirect.com/science/article/pii/S0006322310008851#sec7}, doi = {10.1016/J.BIOPSYCH.2010.07.036}, issn = {0006-3223}, year = {2010}, date = {2010-12-01}, journal = {Biological Psychiatry}, volume = {68}, number = {12}, pages = {1120--1125}, publisher = {Elsevier}, abstract = {BACKGROUND Working memory (WM) is the ability to retain task relevant information. This ability is important for a wide range of cognitive tasks, and WM deficits are a central cognitive impairment in neurodevelopment disorders such as attention-deficit/hyperactivity disorder (ADHD). Although WM capacity is known to be highly heritable, most genes involved remain unidentified. METHODS Single nucleotide polymorphisms in genes previously associated with cognitive functions or ADHD were selected for genotyping. Associations of these with WM tasks were investigated in a community sample of 330 children and young adults. One single nucleotide polymorphisms was also investigated in an independent sample of 88 4-year-old children. Furthermore, association between brain structure and activity, as measured by magnetic resonance imaging techniques, and single nucleotide polymorphisms alleles were estimated in 88 participants. RESULTS Genotype at rs363039, located in the gene coding for synaptosomal-associated protein, 25 kDa (SNAP25) was associated to WM capacity in both samples. Associations in the community sample were also found with measures of other cognitive functions. In addition, this polymorphism affected the gray matter and brain activity in the posterior cingulate cortex, an area included in the so-called default mode network previously correlated to regulation of attention and hypothesized to be implicated in ADHD. CONCLUSIONS A novel gene–brain–behavior network was identified in which a genotype located in SNAP25 affects WM and has age-dependent effects on both brain structure and brain activity. Identifying such networks could be a key to better understanding cognitive development as well as some of its disorders.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND Working memory (WM) is the ability to retain task relevant information. This ability is important for a wide range of cognitive tasks, and WM deficits are a central cognitive impairment in neurodevelopment disorders such as attention-deficit/hyperactivity disorder (ADHD). Although WM capacity is known to be highly heritable, most genes involved remain unidentified. METHODS Single nucleotide polymorphisms in genes previously associated with cognitive functions or ADHD were selected for genotyping. Associations of these with WM tasks were investigated in a community sample of 330 children and young adults. One single nucleotide polymorphisms was also investigated in an independent sample of 88 4-year-old children. Furthermore, association between brain structure and activity, as measured by magnetic resonance imaging techniques, and single nucleotide polymorphisms alleles were estimated in 88 participants. RESULTS Genotype at rs363039, located in the gene coding for synaptosomal-associated protein, 25 kDa (SNAP25) was associated to WM capacity in both samples. Associations in the community sample were also found with measures of other cognitive functions. In addition, this polymorphism affected the gray matter and brain activity in the posterior cingulate cortex, an area included in the so-called default mode network previously correlated to regulation of attention and hypothesized to be implicated in ADHD. CONCLUSIONS A novel gene–brain–behavior network was identified in which a genotype located in SNAP25 affects WM and has age-dependent effects on both brain structure and brain activity. Identifying such networks could be a key to better understanding cognitive development as well as some of its disorders. | |
Torkel Klingberg Training and plasticity of working memory Journal Article Trends in Cognitive Sciences, 14 (7), pp. 317–324, 2010, ISSN: 13646613. @article{Klingberg2010, title = {Training and plasticity of working memory}, author = {Torkel Klingberg}, url = {http://dx.doi.org/10.1016/j.tics.2010.05.002 http://www.ncbi.nlm.nih.gov/pubmed/20630350 https://linkinghub.elsevier.com/retrieve/pii/S1364661310000938}, doi = {10.1016/j.tics.2010.05.002}, issn = {13646613}, year = {2010}, date = {2010-07-01}, journal = {Trends in Cognitive Sciences}, volume = {14}, number = {7}, pages = {317--324}, publisher = {Elsevier Ltd}, abstract = {Working memory (WM) capacity predicts performance in a wide range of cognitive tasks. Although WM capacity has been viewed as a constant trait, recent studies suggest that it can be improved by adaptive and extended training. This training is associated with changes in brain activity in frontal and parietal cortex and basal ganglia, as well as changes in dopamine receptor density. Transfer of the training effects to non-trained WM tasks is consistent with the notion of training-induced plasticity in a common neural network for WM. The observed training effects suggest that WM training could be used as a remediating intervention for individuals for whom low WM capacity is a limiting factor for academic performance or in everyday life.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Working memory (WM) capacity predicts performance in a wide range of cognitive tasks. Although WM capacity has been viewed as a constant trait, recent studies suggest that it can be improved by adaptive and extended training. This training is associated with changes in brain activity in frontal and parietal cortex and basal ganglia, as well as changes in dopamine receptor density. Transfer of the training effects to non-trained WM tasks is consistent with the notion of training-induced plasticity in a common neural network for WM. The observed training effects suggest that WM training could be used as a remediating intervention for individuals for whom low WM capacity is a limiting factor for academic performance or in everyday life. | |
Sissela Bergman Nutley, Stina Söderqvist, Sara Bryde, Keith Humphreys, Torkel Klingberg Measuring Working Memory Capacity With Greater Precision in the Lower Capacity Ranges Journal Article Developmental Neuropsychology, 35 (1), pp. 81–95, 2010, ISSN: 87565641. @article{Nutley2010, title = {Measuring Working Memory Capacity With Greater Precision in the Lower Capacity Ranges}, author = {Sissela Bergman Nutley and Stina Söderqvist and Sara Bryde and Keith Humphreys and Torkel Klingberg}, doi = {10.1080/87565640903325741}, issn = {87565641}, year = {2010}, date = {2010-01-01}, journal = {Developmental Neuropsychology}, volume = {35}, number = {1}, pages = {81--95}, abstract = {Working memory capacity is usually measured as the number of stimuli correctly remembered. However, these measures lack precision when assessing individuals with low capacity. This study aimed to create a more precise measure of visuospatial working memory capacity, using intra-level differences in difficulty between items. In two experiments, children aged 4-6 years (N = 97) were tested on a large number of items. Data showed a large variability of difficulty within each level and the factors contributing to this variability were identified. This variability can be used to provide a precise measure of working memory capacity in the lower ranges.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Working memory capacity is usually measured as the number of stimuli correctly remembered. However, these measures lack precision when assessing individuals with low capacity. This study aimed to create a more precise measure of visuospatial working memory capacity, using intra-level differences in difficulty between items. In two experiments, children aged 4-6 years (N = 97) were tested on a large number of items. Data showed a large variability of difficulty within each level and the factors contributing to this variability were identified. This variability can be used to provide a precise measure of working memory capacity in the lower ranges. | |
2009 |
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F Edin, T Klingberg, P Johansson, F McNab, J Tegner, A Compte Mechanism for top-down control of working memory capacity Journal Article Proceedings of the National Academy of Sciences, 106 (16), pp. 6802–6807, 2009, ISSN: 0027-8424. @article{Edin2009, title = {Mechanism for top-down control of working memory capacity}, author = {F Edin and T Klingberg and P Johansson and F McNab and J Tegner and A Compte}, url = {http://www.pnas.org/cgi/doi/10.1073/pnas.0901894106}, doi = {10.1073/pnas.0901894106}, issn = {0027-8424}, year = {2009}, date = {2009-04-01}, journal = {Proceedings of the National Academy of Sciences}, volume = {106}, number = {16}, pages = {6802--6807}, 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 withmemoryretention during visuospatial workingmemorytasks. 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 mi- crocircuit model and derive a simple, explicit mathematical formula relating memory capacity to prefrontal and parietal model param- eters. For physiologically realistic parameter values, lateral inhibi- tion 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.}, keywords = {}, pubstate = {published}, tppubtype = {article} } 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 withmemoryretention during visuospatial workingmemorytasks. 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 mi- crocircuit model and derive a simple, explicit mathematical formula relating memory capacity to prefrontal and parietal model param- eters. For physiologically realistic parameter values, lateral inhibi- tion 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. | |
Fiona McNab, Andrea Varrone, Lars Farde, Aurelija Jucaite, Paulina Bystritsky, Hans Forssberg, Torkel Klingberg, Fiona McNab, Andrea Varrone, Lars Farde, Aurelija Jucaite, Paulina Bystritsky, Hans Forssberg, Torkel Klingberg Changes in cortical dopamine D1 receptor binding associated with cognitive training Journal Article Science, 323 (5915), pp. 800–802, 2009, ISSN: 00368075. @article{McNab2009, title = {Changes in cortical dopamine D1 receptor binding associated with cognitive training}, author = {Fiona McNab and Andrea Varrone and Lars Farde and Aurelija Jucaite and Paulina Bystritsky and Hans Forssberg and Torkel Klingberg and Fiona McNab and Andrea Varrone and Lars Farde and Aurelija Jucaite and Paulina Bystritsky and Hans Forssberg and Torkel Klingberg}, url = {http://www.sciencemag.org/cgi/doi/10.1126/science.1166102%5Cnpapers3://publication/doi/10.1126/science.1166102 http://www.ncbi.nlm.nih.gov/pubmed/19197069 http://www.sciencemag.org/cgi/doi/10.1126/science.1166102}, doi = {10.1126/science.1166102}, issn = {00368075}, year = {2009}, date = {2009-02-01}, journal = {Science}, volume = {323}, number = {5915}, pages = {800--802}, abstract = {Working memory is a key function for human cognition, dependent on adequate dopamine neurotransmission. Here we show that the training of working memory, which improves working memory capacity, is associated with changes in the density of cortical dopamine D1 receptors. Fourteen hours of training over 5 weeks was associated with changes in both prefrontal and parietal D1 binding potential. This plasticity of the dopamine D1 receptor system demonstrates a reciprocal interplay between mental activity and brain biochemistry in vivo.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Working memory is a key function for human cognition, dependent on adequate dopamine neurotransmission. Here we show that the training of working memory, which improves working memory capacity, is associated with changes in the density of cortical dopamine D1 receptors. Fourteen hours of training over 5 weeks was associated with changes in both prefrontal and parietal D1 binding potential. This plasticity of the dopamine D1 receptor system demonstrates a reciprocal interplay between mental activity and brain biochemistry in vivo. | |
Lisa B Thorell, Sofia Lindqvist, Sissela Bergman Nutley, Gunilla Bohlin, Torkel Klingberg, Sissela Bergman Nutley, Gunilla Bohlin, Torkel Klingberg Training and transfer effects of executive functions in preschool children Journal Article Developmental Science, 12 (1), pp. 106–113, 2009, ISSN: 1363755X. @article{Thorell2009, title = {Training and transfer effects of executive functions in preschool children}, author = {Lisa B Thorell and Sofia Lindqvist and Sissela {Bergman Nutley} and Gunilla Bohlin and Torkel Klingberg and Sissela Bergman Nutley and Gunilla Bohlin and Torkel Klingberg}, url = {http://doi.wiley.com/10.1111/j.1467-7687.2008.00745.x}, doi = {10.1111/j.1467-7687.2008.00745.x}, issn = {1363755X}, year = {2009}, date = {2009-01-01}, journal = {Developmental Science}, volume = {12}, number = {1}, pages = {106--113}, publisher = {Wiley/Blackwell (10.1111)}, abstract = {Executive functions, including working memory and inhibition, are of central importance to much of human behavior. Interventions intended to improve executive functions might therefore serve an important purpose. Previous studies show that working memory can be improved by training, but it is unknown if this also holds for inhibition, and whether it is possible to train executive functions in preschoolers. In the present study, preschool children received computerized training of either visuo-spatial working memory or inhibition for 5 weeks. An active control group played commercially available computer games, and a passive control group took part in only pre- and posttesting. Children trained on working memory improved significantly on trained tasks; they showed training effects on non-trained tests of spatial and verbal working memory, as well as transfer effects to attention. Children trained on inhibition showed a significant improvement over time on two out of three trained task paradigms, but no significant improvements relative to the control groups on tasks measuring working memory or attention. In neither of the two interventions were there effects on non-trained inhibitory tasks. The results suggest that working memory training can have significant effects also among preschool children. The finding that inhibition could not be improved by either one of the two training programs might be due to the particular training program used in the present study or possibly indicate that executive functions differ in how easily they can be improved by training, which in turn might relate to differences in their underlying psychological and neural processes. textcopyright 2008 Blackwell Publishing Ltd.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Executive functions, including working memory and inhibition, are of central importance to much of human behavior. Interventions intended to improve executive functions might therefore serve an important purpose. Previous studies show that working memory can be improved by training, but it is unknown if this also holds for inhibition, and whether it is possible to train executive functions in preschoolers. In the present study, preschool children received computerized training of either visuo-spatial working memory or inhibition for 5 weeks. An active control group played commercially available computer games, and a passive control group took part in only pre- and posttesting. Children trained on working memory improved significantly on trained tasks; they showed training effects on non-trained tests of spatial and verbal working memory, as well as transfer effects to attention. Children trained on inhibition showed a significant improvement over time on two out of three trained task paradigms, but no significant improvements relative to the control groups on tasks measuring working memory or attention. In neither of the two interventions were there effects on non-trained inhibitory tasks. The results suggest that working memory training can have significant effects also among preschool children. The finding that inhibition could not be improved by either one of the two training programs might be due to the particular training program used in the present study or possibly indicate that executive functions differ in how easily they can be improved by training, which in turn might relate to differences in their underlying psychological and neural processes. textcopyright 2008 Blackwell Publishing Ltd. | |
Torkel Klingberg, Fiona Mcnab, Tamminga Working memory remediation and the D1 receptor Journal Article American Journal of Psychiatry, 166 (5), pp. 515–516, 2009, ISSN: 0002953X. @article{Klingberg2009, title = {Working memory remediation and the D1 receptor}, author = {Torkel Klingberg and Fiona Mcnab and Tamminga}, doi = {10.1176/appi.ajp.2009.09030343}, issn = {0002953X}, year = {2009}, date = {2009-01-01}, journal = {American Journal of Psychiatry}, volume = {166}, number = {5}, pages = {515--516}, keywords = {}, pubstate = {published}, tppubtype = {article} } | |
2008 |
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Fiona McNab, Gaëlle Leroux, Fredrik Strand, Lisa Thorell, Sissela Bergman, Torkel Klingberg Common and unique components of inhibition and working memory: An fMRI, within-subjects investigation Journal Article Neuropsychologia, 46 (11), pp. 2668–2682, 2008, ISSN: 00283932. @article{McNab2008a, title = {Common and unique components of inhibition and working memory: An fMRI, within-subjects investigation}, author = {Fiona McNab and Ga{ë}lle Leroux and Fredrik Strand and Lisa Thorell and Sissela Bergman and Torkel Klingberg}, url = {https://linkinghub.elsevier.com/retrieve/pii/S0028393208001693}, doi = {10.1016/j.neuropsychologia.2008.04.023}, issn = {00283932}, year = {2008}, date = {2008-09-01}, journal = {Neuropsychologia}, volume = {46}, number = {11}, pages = {2668--2682}, abstract = {Behavioural findings indicate that the core executive functions of inhibition and working memory are closely linked, and neuroimaging studies indicate overlap between their neural correlates. There has not, however, been a comprehensive study, including several inhibition tasks and several working memory tasks, performed by the same subjects. In the present study, 11 healthy adult subjects completed separate blocks of 3 inhibition tasks (a stop task, a go/no-go task and a flanker task), and 2 working memory tasks (one spatial and one verbal). Activation common to all 5 tasks was identified in the right inferior frontal gyrus, and, at a lower threshold, also the right middle frontal gyrus and right parietal regions (BA 40 and BA 7). Left inferior frontal regions of interest (ROIs) showed a significant conjunction between all tasks except the flanker task. The present study could not pinpoint the specific function of each common region, but the parietal region identified here has previously been consistently related to working memory storage and the right inferior frontal gyrus has been associated with inhibition in both lesion and imaging studies. These results support the notion that inhibitory and working memory tasks involve common neural components, which may provide a neural basis for the interrelationship between the two systems. textcopyright 2008 Elsevier Ltd. All rights reserved.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Behavioural findings indicate that the core executive functions of inhibition and working memory are closely linked, and neuroimaging studies indicate overlap between their neural correlates. There has not, however, been a comprehensive study, including several inhibition tasks and several working memory tasks, performed by the same subjects. In the present study, 11 healthy adult subjects completed separate blocks of 3 inhibition tasks (a stop task, a go/no-go task and a flanker task), and 2 working memory tasks (one spatial and one verbal). Activation common to all 5 tasks was identified in the right inferior frontal gyrus, and, at a lower threshold, also the right middle frontal gyrus and right parietal regions (BA 40 and BA 7). Left inferior frontal regions of interest (ROIs) showed a significant conjunction between all tasks except the flanker task. The present study could not pinpoint the specific function of each common region, but the parietal region identified here has previously been consistently related to working memory storage and the right inferior frontal gyrus has been associated with inhibition in both lesion and imaging studies. These results support the notion that inhibitory and working memory tasks involve common neural components, which may provide a neural basis for the interrelationship between the two systems. textcopyright 2008 Elsevier Ltd. All rights reserved. | |
Fiona McNab, Torkel Klingberg Prefrontal cortex and basal ganglia control access to working memory. Journal Article Nature neuroscience, 11 (1), pp. 103–7, 2008, ISSN: 1097-6256. @article{McNab2008, title = {Prefrontal cortex and basal ganglia control access to working memory.}, author = {Fiona McNab and Torkel Klingberg}, url = {http://www.ncbi.nlm.nih.gov/pubmed/18066057}, doi = {10.1038/nn2024}, issn = {1097-6256}, year = {2008}, date = {2008-01-01}, journal = {Nature neuroscience}, volume = {11}, number = {1}, pages = {103--7}, abstract = {Our capacity to store information in working memory might be determined by the degree to which only relevant information is remembered. The question remains as to how this selection of relevant items to be remembered is accomplished. Here we show that activity in the prefrontal cortex and basal ganglia preceded the filtering of irrelevant information and that activity, particularly in the globus pallidus, predicted the extent to which only relevant information is stored. The preceding frontal and basal ganglia activity were also associated with inter-individual differences in working memory capacity. These findings reveal a mechanism by which frontal and basal ganglia activity exerts attentional control over access to working memory storage in the parietal cortex in humans, and makes an important contribution to inter-individual differences in working memory capacity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Our capacity to store information in working memory might be determined by the degree to which only relevant information is remembered. The question remains as to how this selection of relevant items to be remembered is accomplished. Here we show that activity in the prefrontal cortex and basal ganglia preceded the filtering of irrelevant information and that activity, particularly in the globus pallidus, predicted the extent to which only relevant information is stored. The preceding frontal and basal ganglia activity were also associated with inter-individual differences in working memory capacity. These findings reveal a mechanism by which frontal and basal ganglia activity exerts attentional control over access to working memory storage in the parietal cortex in humans, and makes an important contribution to inter-individual differences in working memory capacity. | |
2007 |
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Edin F, Klingberg T, Stödberg T, Tegnér J Fronto-parietal connection asymmetry regulates working memory distractibility Journal Article Journal of Integrative Neuroscience, 06 (04), pp. 567–596, 2007, ISSN: 0219-6352. @article{F2007, title = {Fronto-parietal connection asymmetry regulates working memory distractibility}, author = {Edin F and Klingberg T and Stödberg T and Tegnér J}, url = {http://www.worldscientific.com/doi/abs/10.1142/S0219635207001702}, doi = {10.1142/S0219635207001702}, issn = {0219-6352}, year = {2007}, date = {2007-12-01}, journal = {Journal of Integrative Neuroscience}, volume = {06}, number = {04}, pages = {567--596}, keywords = {}, pubstate = {published}, tppubtype = {article} } | |
Fredrik Edin, Julian Macoveanu, Pernille Olesen, Jesper Tegnér, Torkel Klingberg Stronger Synaptic Connectivity as a Mechanism behind Development of Working Memory-related Brain Activity during Childhood Journal Article Journal of Cognitive Neuroscience, 19 (5), pp. 750–760, 2007, ISSN: 0898-929X. @article{Fredrik2007, title = {Stronger Synaptic Connectivity as a Mechanism behind Development of Working Memory-related Brain Activity during Childhood}, author = {Fredrik Edin and Julian Macoveanu and Pernille Olesen and Jesper Tegnér and Torkel Klingberg}, url = {http://www.mitpressjournals.org/doi/10.1162/jocn.2007.19.5.750}, doi = {10.1162/jocn.2007.19.5.750}, issn = {0898-929X}, year = {2007}, date = {2007-05-01}, journal = {Journal of Cognitive Neuroscience}, volume = {19}, number = {5}, pages = {750--760}, 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.}, keywords = {}, pubstate = {published}, tppubtype = {article} } 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. | |
Julian Macoveanu, Torkel Klingberg, Jesper Tegnér Neuronal firing rates account for distractor effects on mnemonic accuracy in a visuo-spatial working memory task Journal Article Biological Cybernetics, 96 (4), pp. 407–419, 2007, ISSN: 0340-1200. @article{MacOveanu2007, title = {Neuronal firing rates account for distractor effects on mnemonic accuracy in a visuo-spatial working memory task}, author = {Julian Macoveanu and Torkel Klingberg and Jesper Tegnér}, url = {http://link.springer.com/10.1007/s00422-006-0139-8}, doi = {10.1007/s00422-006-0139-8}, issn = {0340-1200}, year = {2007}, date = {2007-03-01}, journal = {Biological Cybernetics}, volume = {96}, number = {4}, pages = {407--419}, abstract = {Persistent neural activity constitutes one neuronal correlate of working memory, the ability to hold and manipulate information across time, a prerequisite for cognition. Yet, the underlying neuronal mechanisms are still elusive. Here, we design a visuo- spatial delayed-response task to identify the relationship between the cue-distractor spatial distance and mnemonic accuracy. Using a shared experimental and computational test protocol, we probe human subjects in computer experiments, and subsequently we evaluate different neural mechanisms underlying persistent activity using an in silico prefrontal network model. Five modes of action of the network were tested: weak or strong synaptic interactions, wide synaptic arborization, cellular bistability and reduced synaptic NMDA component. The five neural mechanisms and the human behavioral data, all exhibited a significant deterioration of the mnemonic accuracy with decreased spatial distance between the distractor and the cue. A subsequent computational analysis revealed that the firing rate and not the neural mechanism per se, accounted for the positive correlation between mnemonic accuracy and spatial distance. Moreover, the computational modeling predicts an inverse correlation between accuracy and distractibility. In conclusion, any pharmacological modulation, pathological condition or memory training paradigm targeting the underlying neural circuitry and altering the net population firing rate during the delay is predicted to determine the amount of influence of a visual distraction. textcopyright Springer-Verlag 2007.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Persistent neural activity constitutes one neuronal correlate of working memory, the ability to hold and manipulate information across time, a prerequisite for cognition. Yet, the underlying neuronal mechanisms are still elusive. Here, we design a visuo- spatial delayed-response task to identify the relationship between the cue-distractor spatial distance and mnemonic accuracy. Using a shared experimental and computational test protocol, we probe human subjects in computer experiments, and subsequently we evaluate different neural mechanisms underlying persistent activity using an in silico prefrontal network model. Five modes of action of the network were tested: weak or strong synaptic interactions, wide synaptic arborization, cellular bistability and reduced synaptic NMDA component. The five neural mechanisms and the human behavioral data, all exhibited a significant deterioration of the mnemonic accuracy with decreased spatial distance between the distractor and the cue. A subsequent computational analysis revealed that the firing rate and not the neural mechanism per se, accounted for the positive correlation between mnemonic accuracy and spatial distance. Moreover, the computational modeling predicts an inverse correlation between accuracy and distractibility. In conclusion, any pharmacological modulation, pathological condition or memory training paradigm targeting the underlying neural circuitry and altering the net population firing rate during the delay is predicted to determine the amount of influence of a visual distraction. textcopyright Springer-Verlag 2007. | |
