Publications

@article{Nivins2023b,
title = {Effects of prenatal exposure to maternal diabetes mellitus on deep grey matter structures and attention deficit hyperactivity disorder symptoms in children},
author = {Samson Nivins, Torkel Klingberg},
url = {https://onlinelibrary.wiley.com/doi/full/10.1111/apa.16756},
doi = {https://doi.org/10.1111/apa.16756},
year = {2023},
date = {2023-03-23},
journal = {Acta paediatrica},
abstract = {Aim: The neuronal mechanism linking the association between maternal diabetes mellitus (DM) and risk of attention deficit hyperactivity disorder (ADHD) symptoms and working memory deficits in children was investigated.

Methods: A total of 6291 children (52% boys) born beyond 28 weeks of gestation were included and underwent brain magnetic resonance imaging scans at 9–10 years. Subcortical brain volumes were estimated from the T1-weighted images. ADHD symptoms were assessed using factorial analysis of the Child Behaviour Checklist completed by parents/caregivers. Working memory performance was assessed with the NIH Toolbox.

Results: Compared to unexposed children, those exposed to DM (n = 422) had smaller (β = −0.15, p = 0.001) volumes of pooled deep grey matter (GM). Regional analysis revealed smaller volumes of the caudate nucleus, putamen, thalamus and cerebellum but not of hippocampus. They also had altered cortico-striatal white matter projection tracts. DM was not associated with working memory deficits or inattention, but with increased hyperactivity/impulsivity and Sluggish Cognitive Tempo symptoms in boys. This hyperactivity/impulsivity symptom in boys was partially mediated by smaller deep GM volume.

Conclusion: Exposure to DM during pregnancy leads to altered deep GM development during late childhood in their offspring. This contributed to an increased risk of hyperactivity/impulsivity symptoms in boys.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Nivins2022b,
title = {The Long-Term Impact of Digital Media on Brain Development in Children},
author = {Samson Nivins, Bruno Sauce, Magnus Liebherr, Nicholas Judd, Torkel Klingberg},
url = {https://www.medrxiv.org/content/10.1101/2022.07.01.22277142v2},
doi = {https://doi.org/10.1101/2022.07.01.22277142},
year = {2022},
date = {2022-07-05},
journal = {medRxiv},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Nivins2022,
title = {Digital media does not harm (nor benefit) brain development in children},
author = {Samson Nivins, Bruno Sauce, Magnus Liebherr, Nicholas Judd, Torkel Klingberg},
url = {https://www.medrxiv.org/content/10.1101/2022.07.01.22277142v1?%253fcollection=},
doi = {https://doi.org/10.1101/2022.07.01.22277142},
year = {2022},
date = {2022-01-01},
journal = {medRxiv},
abstract = {Importance: Digital media takes an increasingly large part of children’s time, but the effect on brain development is unclear.

Objective: To investigate the effects of digital media (watching television and videos, using social media, or playing video games respectively) on the development of the cortex, striatum, and cerebellum over two years.

Design, setting, and participants: A prospective, multicenter, longitudinal study of children from the Adolescent Brain and Cognitive Development Study, recruited between 2016-2018. Children underwent magnetic resonance imaging scan at two different time points and completed the Youth Screen Time Survey at first timepoint, answering questions about digital media use. The analysis controlled for differences in socioeconomic status (SES) and polygenic scores for educational attainment.

Exposure: Digital media use.

Main outcome measures: The primary outcome measure was the changes in the global cortical surface area.

Results: 6492 children (age in months, mean [SD] = 118.6 [7.2], i.e., 9.9 years were included at the baseline. Of these, 4502 children (age in months = 142.6 [7.6], i.e., 11.9 years were included at the two years follow-up. The average time spent by children on screen time was 2.2h/day for watching television and videos, 0.4h/day for using social media, and 0.9h/day for playing video games. Over the two-year observation period, the average cortical surface area increased by approximately 2%, reflecting normal cortical development. The amount of time spent playing video games was weakly but positively correlated to change in global cortical surface area (standardised beta, β = 0.03; 95% CI [0.001 – 0.06]; P=.06). No global or regional effect on brain development was observed for a time watching television and videos or using social media. However, the regional analysis showed that playing video games was associated with a larger increase in the volume of the cerebellum (β = 0.01 [0.001 – 0.02]; P=.02).

Conclusions and Relevance: This study does not suggest that digital media use in children harms brain development in mid-childhood and within a window of two years, but a longer follow-up is necessary.

Question: Does the use of digital media affect brain development in children aged 9-10 years of age?

Findings: In this two-year longitudinal study of 4502 children, we found no effect of playing video games, watching television, or using social media on the development of cortical surface area. playing video games was associated with a larger increase in the volume of cerebellum.

Meaning: This study does not indicate that the use of digital media harms brain development.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Klingberg2021,
title = {Assessing the impact of environmental factors on the adolescent brain: the importance of regional analyses and genetic controls},
author = {Torkel Klingberg, Nicholas Judd, Bruno Sauce},
year = {2021},
date = {2021-05-10},
journal = {World Psychiatry},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Judd2021,
title = {Working memory capacity, variability, and response to intervention at age 6 and its association to inattention and mathematics age 9},
author = {Nicholas Judd, Torkel Klingberg, Douglas Sjöwall},
url = {https://www.sciencedirect.com/science/article/pii/S0885201421000083},
doi = {https://doi.org/10.1016/j.cogdev.2021.101013},
year = {2021},
date = {2021-04-01},
journal = {Cognitive Development},
volume = {58},
number = {12},
pages = {101013},
abstract = {Classically, neuropsychological evaluation only estimates an individual’s performance at one time point. For example, working memory (WM) capacity is commonly determined in a single test session. However, recent research in WM plasticity and variability has suggested performance over several sessions/days might aid in evaluating children. Here, we explored four temporal properties of WM: WM measured once, as a mean over three days (multiple-session-baseline performance), variability over 8 weeks, and performance improvement over an 8-week WM training program. To examine independence we controlled for a single-session, multiple task WM assessment while predicting inattention and mathematics three years later (n = 178, mean age 80 months at training, 49 % boys). Our results showed improved prediction for mathematics from WM training improvement and variability, yet this was not the case for inattention. While the additional variance added was not substantial, our results indicate clinically relevant information present in these alternative WM measures.},
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pubstate = {published},
tppubtype = {article}
}

@article{Judd2020,
title = {Cognitive and brain development is independently influenced by socioeconomic status and polygenic scores for educational attainment},
author = {Nicholas Judd and Bruno Sauce and John Wiedenhoeft and Jeshua Tromp and Bader Chaarani and Alexander Schliep 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 Andreas Heinz 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},
url = {http://www.pnas.org/lookup/doi/10.1073/pnas.2001228117},
doi = {10.1073/pnas.2001228117},
issn = {0027-8424},
year = {2020},
date = {2020-06-01},
journal = {Proceedings of the National Academy of Sciences},
volume = {117},
number = {22},
pages = {12411--12418},
abstract = {Genetic factors and socioeconomic status (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 associations independently. Here we used a polygenic score for educational attainment (EduYears-PGS), as well as SES, in a longitudinal study of 551 adolescents to tease apart genetic and environmental associations with 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 associations with 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 association with surface area in the right parietal lobe, a region related to nonverbal cognitive functions, including mathematics, spatial cognition, and WM. SES, but not EduYears-PGS, was related to a change in total cortical surface area from age 14 to 19. This study demonstrates a regional association of EduYears-PGS and the independent prediction of SES with cognitive function and brain development. It suggests that the SES inequalities, in particular parental education, are related to global aspects of cortical development, and exert a persistent influence on brain development during adolescence.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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}
}

@article{Olesen2007,
title = {Brain activity related to working memory and distraction in children and adults},
author = {Pernille J Olesen and Julian Macoveanu and Jesper Tegnér and Torkel Klingberg},
doi = {10.1093/cercor/bhl014},
issn = {10473211},
year = {2007},
date = {2007-01-01},
journal = {Cerebral Cortex},
volume = {17},
number = {5},
pages = {1047--1054},
abstract = {In order to retain information in working memory (WM) during a delay, distracting stimuli must be ignored. This important ability improves during childhood, but the neural basis for this development is not known. We measured brain activity with functional magnetic resonance imaging in adults and 13-year-old children. Data were analyzed with an event-related design to isolate activity during cue, delay, distraction, and response selection. Adults were more accurate and less distractible than children. Activity in the middle frontal gyrus and intraparietal cortex was stronger in adults than in children during the delay, when information was maintained in WM. Distraction during the delay evoked activation in parietal and occipital cortices in both adults and children. However, distraction activated frontal cortex only in children. The larger frontal activation in response to distracters presented during the delay may explain why children are more susceptible to interfering stimuli.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Klingberg2006,
title = {Development of a superior frontal–intraparietal network for visuo-spatial working memory},
author = {Torkel Klingberg},
url = {https://linkinghub.elsevier.com/retrieve/pii/S0028393205003830},
doi = {10.1016/j.neuropsychologia.2005.11.019},
issn = {00283932},
year = {2006},
date = {2006-01-01},
journal = {Neuropsychologia},
volume = {44},
number = {11},
pages = {2171--2177},
abstract = {Working memory capacity increases throughout childhood and adolescence, which is important for the development of a wide range of cognitive abilities, including complex reasoning. The spatial-span task, in which subjects retain information about the order and position of a number of objects, is a sensitive task to measure development of spatial working memory. This review considers results from previous neuroimaging studies investigating the neural correlates of this development. Older children and adolescents, with higher capacity, have been found to have higher brain activity in the intraparietal cortex and in the posterior part of the superior frontal sulcus, during the performance of working memory tasks. The structural maturation of white matter has been investigated by diffusion tensor magnetic resonance imaging (DTI). This has revealed several regions in the frontal lobes in which white matter maturation is correlated with the development of working memory. Among these is a superior fronto-parietal white matter region, located close to the grey matter regions that are implicated in the development of working memory. Furthermore, the degree of white matter maturation is positively correlated with the degree of cortical activation in the frontal and parietal regions. This suggests that during childhood and adolescence, there is development of networks related to specific cognitive functions, such as visuo-spatial working memory. These networks not only consist of cortical areas but also the white matter tracts connecting them. For visuo-spatial working memory, this network could consist of the superior frontal and intraparietal cortex. textcopyright 2005 Elsevier Ltd. All rights reserved.},
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pubstate = {published},
tppubtype = {article}
}