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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. | |
Helena Westerberg, Torkel Klingberg Changes in cortical activity after training of working memory - a single-subject analysis Journal Article Physiology and Behavior, 92 (1-2), pp. 186–192, 2007, ISSN: 00319384. @article{Westerberg2007, title = {Changes in cortical activity after training of working memory - a single-subject analysis}, author = {Helena Westerberg and Torkel Klingberg}, doi = {10.1016/j.physbeh.2007.05.041}, issn = {00319384}, year = {2007}, date = {2007-01-01}, journal = {Physiology and Behavior}, volume = {92}, number = {1-2}, pages = {186--192}, abstract = {Working memory (WM) capacity is an important factor for a wide range of cognitive skills. This capacity has generally been assumed to be fixed. However, recent studies have suggested that WM can be improved by intensive, computerized training [Klingberg T, Fernell E, Olesen P, Johnson M, Gustafsson P, Dahlström K, et al. Computerized training of working memory in children with ADHD - a randomized, controlled trial. J Am Acad Child Adolesc Psych 2005;44:177--86]. A recent study by Olesen, Westerberg and Klingberg [Olesen P, Westerberg H, Klingberg T. Increased prefrontal and parietal brain activity after training of working memory. Nat Neurosci 2004;7:75--9] showed that group analysis of brain activity data show increases in prefrontal and parietal cortices after WM training. In the present study we performed single-subject analysis of the changes in brain activity after five weeks of training. Three young, healthy adults participated in the study. On two separate days before practice and during one day after practice, brain activity was measured with functional magnetic resonance imaging (fMRI) during performance of a WM and a baseline task. Practice on the WM tasks gradually improved performance and this effect lasted several months. The effect of practice also generalized to improve performance on a non-trained WM task and a reasoning task. After training, WM-related brain activity was significantly increased in the middle and inferior frontal gyrus. The changes in activity were not due to activations of any additional area that was not activated before training. Instead, the changes could best be described by small increases in the extent of the area of activated cortex. The effect of training of WM is thus in several respects similar to the changes in the functional map observed in primate studies of skill learning, although the physiological effect in WM training is located in the prefrontal association cortex. textcopyright 2007 Elsevier Inc. All rights reserved.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Working memory (WM) capacity is an important factor for a wide range of cognitive skills. This capacity has generally been assumed to be fixed. However, recent studies have suggested that WM can be improved by intensive, computerized training [Klingberg T, Fernell E, Olesen P, Johnson M, Gustafsson P, Dahlström K, et al. Computerized training of working memory in children with ADHD - a randomized, controlled trial. J Am Acad Child Adolesc Psych 2005;44:177--86]. A recent study by Olesen, Westerberg and Klingberg [Olesen P, Westerberg H, Klingberg T. Increased prefrontal and parietal brain activity after training of working memory. Nat Neurosci 2004;7:75--9] showed that group analysis of brain activity data show increases in prefrontal and parietal cortices after WM training. In the present study we performed single-subject analysis of the changes in brain activity after five weeks of training. Three young, healthy adults participated in the study. On two separate days before practice and during one day after practice, brain activity was measured with functional magnetic resonance imaging (fMRI) during performance of a WM and a baseline task. Practice on the WM tasks gradually improved performance and this effect lasted several months. The effect of practice also generalized to improve performance on a non-trained WM task and a reasoning task. After training, WM-related brain activity was significantly increased in the middle and inferior frontal gyrus. The changes in activity were not due to activations of any additional area that was not activated before training. Instead, the changes could best be described by small increases in the extent of the area of activated cortex. The effect of training of WM is thus in several respects similar to the changes in the functional map observed in primate studies of skill learning, although the physiological effect in WM training is located in the prefrontal association cortex. textcopyright 2007 Elsevier Inc. All rights reserved. | |
Pernille J Olesen, Julian Macoveanu, Jesper Tegnér, Torkel Klingberg Brain activity related to working memory and distraction in children and adults Journal Article Cerebral Cortex, 17 (5), pp. 1047–1054, 2007, ISSN: 10473211. @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} } 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. | |
H Westerberg, H Jacobaeus, T Hirvikoski, P Clevberger, M -L Östensson, A Bartfai, T Klingberg Computerized working memory training after stroke–A pilot study Journal Article Brain Injury, 21 (1), pp. 21–29, 2007, ISSN: 0269-9052. @article{Westerberg2007a, title = {Computerized working memory training after stroke–A pilot study}, author = {H Westerberg and H Jacobaeus and T Hirvikoski and P Clevberger and M -L Östensson and A Bartfai and T Klingberg}, url = {http://www.tandfonline.com/doi/full/10.1080/02699050601148726}, doi = {10.1080/02699050601148726}, issn = {0269-9052}, year = {2007}, date = {2007-01-01}, journal = {Brain Injury}, volume = {21}, number = {1}, pages = {21--29}, abstract = {Aim: To examine the effects of working memory (WM) training in adult patients with stroke. Methods: A randomized pilot study with a treatment group and a passive control group; 18 participants (12 males) in a vocational age group (mean age 54 years) were randomized to either the treatment or the control condition. The intervention consisted of computerized training on various WM tasks for five weeks. A neuropsychological test battery and self-rating on cognitive functioning in daily life (the CFQ) were administered both before and after the treatment. Results: Statistically significant training effects were found on the non-trained tests for WM and attention, i.e., tests that measure related cognitive functions but are not identical to tasks in the training programme (Span board p textless 0.05; PASAT p textless 0.001; Ruff 2 & 7 p textless 0.005). There was a significant decrease in symptoms of cognitive problems as measured by the CFQ (p textless 0.005). Conclusion: More than one year after a stroke, systematic WM training can significantly improve WM and attention.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Aim: To examine the effects of working memory (WM) training in adult patients with stroke. Methods: A randomized pilot study with a treatment group and a passive control group; 18 participants (12 males) in a vocational age group (mean age 54 years) were randomized to either the treatment or the control condition. The intervention consisted of computerized training on various WM tasks for five weeks. A neuropsychological test battery and self-rating on cognitive functioning in daily life (the CFQ) were administered both before and after the treatment. Results: Statistically significant training effects were found on the non-trained tests for WM and attention, i.e., tests that measure related cognitive functions but are not identical to tasks in the training programme (Span board p textless 0.05; PASAT p textless 0.001; Ruff 2 & 7 p textless 0.005). There was a significant decrease in symptoms of cognitive problems as measured by the CFQ (p textless 0.005). Conclusion: More than one year after a stroke, systematic WM training can significantly improve WM and attention. | |
2006 |
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J Macoveanu, T Klingberg, J Tegnér A biophysical model of multiple-item working memory: A computational and neuroimaging study Journal Article Neuroscience, 141 (3), pp. 1611–1618, 2006, ISSN: 03064522. @article{Macoveanu2006, title = {A biophysical model of multiple-item working memory: A computational and neuroimaging study}, author = {J Macoveanu and T Klingberg and J Tegnér}, url = {https://linkinghub.elsevier.com/retrieve/pii/S0306452206006567}, doi = {10.1016/j.neuroscience.2006.04.080}, issn = {03064522}, year = {2006}, date = {2006-01-01}, journal = {Neuroscience}, volume = {141}, number = {3}, pages = {1611--1618}, abstract = {Biophysically based computational models have successfully accounted for the persistent neural activity underlying the maintenance of single items of information in working memory. The aim of the present study was to extend previous models in order to retain multiple items, in agreement with the observed human storage capacity. This was done by implementing cellular mechanisms known to occur during the childhood development of working memory, such as an increased synaptic strength and improved contrast and specificity of the neural response. Our computational study shows that these mechanisms are sufficient to create a neural network which can store information about multiple items through sustained neural activity. Furthermore, by using functional magnetic resonance imaging, we found that the information-activity curve predicted by the model corresponds to that in the human posterior parietal cortex during performance of working memory tasks, which is consistent with previous studies of brain activity related to working memory capacity in humans. textcopyright 2006 IBRO.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Biophysically based computational models have successfully accounted for the persistent neural activity underlying the maintenance of single items of information in working memory. The aim of the present study was to extend previous models in order to retain multiple items, in agreement with the observed human storage capacity. This was done by implementing cellular mechanisms known to occur during the childhood development of working memory, such as an increased synaptic strength and improved contrast and specificity of the neural response. Our computational study shows that these mechanisms are sufficient to create a neural network which can store information about multiple items through sustained neural activity. Furthermore, by using functional magnetic resonance imaging, we found that the information-activity curve predicted by the model corresponds to that in the human posterior parietal cortex during performance of working memory tasks, which is consistent with previous studies of brain activity related to working memory capacity in humans. textcopyright 2006 IBRO. | |
Torkel Klingberg Development of a superior frontal–intraparietal network for visuo-spatial working memory Journal Article Neuropsychologia, 44 (11), pp. 2171–2177, 2006, ISSN: 00283932. @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.}, keywords = {}, pubstate = {published}, tppubtype = {article} } 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. | |
2005 |
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Zoltan Nagy, Katarina Lindström, Helena Westerberg, Stefan Skare, Jesper Andersson, Boubou Hallberg, Anders Lilja, Olof Flodmark, Hugo Lagercrantz, Torkel Klingberg, Elisabeth Fernell Diffusion Tensor Imaging on Teenagers, Born at Term With Moderate Hypoxic-ischemic Encephalopathy Journal Article Pediatric Research, 58 (5), pp. 936–940, 2005, ISSN: 0031-3998. @article{Nagy2005, title = {Diffusion Tensor Imaging on Teenagers, Born at Term With Moderate Hypoxic-ischemic Encephalopathy}, author = {Zoltan Nagy and Katarina Lindström and Helena Westerberg and Stefan Skare and Jesper Andersson and Boubou Hallberg and Anders Lilja and Olof Flodmark and Hugo Lagercrantz and Torkel Klingberg and Elisabeth Fernell}, url = {http://www.nature.com/doifinder/10.1203/01.pdr.0000186516.85702.61}, doi = {10.1203/01.pdr.0000186516.85702.61}, issn = {0031-3998}, year = {2005}, date = {2005-11-01}, journal = {Pediatric Research}, volume = {58}, number = {5}, pages = {936--940}, abstract = {Hypoxic-ischemic encephalopathy (HIE) is graded with three levels of severity-mild, moderate and severe. The outcome of individuals with mild and severe grades can be reliably predicted from this scheme. Individuals with moderate degree are divided in outcome between those who suffer major neurologic problems (e.g., cerebral palsy) and those who are assumed to recover from the incident. It is however not clear if the recovery is complete and unquestionable. A group of adolescents who had been born at term, diagnosed with moderate HIE but had not developed cerebral palsy, were investigated with diffusion tensor imaging. Fractional anisotropy maps were used as a basis of comparison to a group of controls of the same age and gender distribution. In several white matter areas fractional anisotrophy was lower in the group of individuals with a history of moderate HIE. These areas include the internal capsules (bilaterally in the posterior limb and on the right in the anterior limb), the posterior and anterior corpus callosum as well as frontal inferior white matter areas. These results indicate that even in the absence of such major neurologic impairments as cerebral palsy, moderate HIE causes long term white matter disturbances which are not repaired by adolescence. Copyright textcopyright 2005 International Pediatric Research Foundation, Inc.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Hypoxic-ischemic encephalopathy (HIE) is graded with three levels of severity-mild, moderate and severe. The outcome of individuals with mild and severe grades can be reliably predicted from this scheme. Individuals with moderate degree are divided in outcome between those who suffer major neurologic problems (e.g., cerebral palsy) and those who are assumed to recover from the incident. It is however not clear if the recovery is complete and unquestionable. A group of adolescents who had been born at term, diagnosed with moderate HIE but had not developed cerebral palsy, were investigated with diffusion tensor imaging. Fractional anisotropy maps were used as a basis of comparison to a group of controls of the same age and gender distribution. In several white matter areas fractional anisotrophy was lower in the group of individuals with a history of moderate HIE. These areas include the internal capsules (bilaterally in the posterior limb and on the right in the anterior limb), the posterior and anterior corpus callosum as well as frontal inferior white matter areas. These results indicate that even in the absence of such major neurologic impairments as cerebral palsy, moderate HIE causes long term white matter disturbances which are not repaired by adolescence. Copyright textcopyright 2005 International Pediatric Research Foundation, Inc. | |
Torkel Klingberg, Elisabeth Fernell, Pernille J Olesen, Mats Johnson, Per Gustafsson, Kerstin Dahlström, Christopher G Gillberg, Hans Forssberg, Helena Westerberg Computerized Training of Working Memory in Children With ADHD-A Randomized, Controlled Trial Journal Article Journal of the American Academy of Child & Adolescent Psychiatry, 44 (2), pp. 177–186, 2005, ISSN: 08908567. @article{Klingberg2005, title = {Computerized Training of Working Memory in Children With ADHD-A Randomized, Controlled Trial}, author = {Torkel Klingberg and Elisabeth Fernell and Pernille J Olesen and Mats Johnson and Per Gustafsson and Kerstin Dahlström and Christopher G Gillberg and Hans Forssberg and Helena Westerberg}, url = {https://linkinghub.elsevier.com/retrieve/pii/S0890856709614271}, doi = {10.1097/00004583-200502000-00010}, issn = {08908567}, year = {2005}, date = {2005-02-01}, journal = {Journal of the American Academy of Child & Adolescent Psychiatry}, volume = {44}, number = {2}, pages = {177--186}, abstract = {OBJECTIVE Deficits in executive functioning, including working memory (WM) deficits, have been suggested to be important in attention-deficit/hyperactivity disorder (ADHD). During 2002 to 2003, the authors conducted a multicenter, randomized, controlled, double-blind trial to investigate the effect of improving WM by computerized, systematic practice of WM tasks. METHOD Included in the trial were 53 children with ADHD (9 girls; 15 of 53 inattentive subtype), aged 7 to 12 years, without stimulant medication. The compliance criterion (textgreater20 days of training) was met by 44 subjects, 42 of whom were also evaluated at follow-up 3 months later. Participants were randomly assigned to use either the treatment computer program for training WM or a comparison program. The main outcome measure was the span-board task, a visuospatial WM task that was not part of the training program. RESULTS For the span-board task, there was a significant treatment effect both post-intervention and at follow-up. In addition, there were significant effects for secondary outcome tasks measuring verbal WM, response inhibition, and complex reasoning. Parent ratings showed significant reduction in symptoms of inattention and hyperactivity/impulsivity, both post-intervention and at follow-up. CONCLUSIONS This study shows that WM can be improved by training in children with ADHD. This training also improved response inhibition and reasoning and resulted in a reduction of the parent-rated inattentive symptoms of ADHD.}, keywords = {}, pubstate = {published}, tppubtype = {article} } OBJECTIVE Deficits in executive functioning, including working memory (WM) deficits, have been suggested to be important in attention-deficit/hyperactivity disorder (ADHD). During 2002 to 2003, the authors conducted a multicenter, randomized, controlled, double-blind trial to investigate the effect of improving WM by computerized, systematic practice of WM tasks. METHOD Included in the trial were 53 children with ADHD (9 girls; 15 of 53 inattentive subtype), aged 7 to 12 years, without stimulant medication. The compliance criterion (textgreater20 days of training) was met by 44 subjects, 42 of whom were also evaluated at follow-up 3 months later. Participants were randomly assigned to use either the treatment computer program for training WM or a comparison program. The main outcome measure was the span-board task, a visuospatial WM task that was not part of the training program. RESULTS For the span-board task, there was a significant treatment effect both post-intervention and at follow-up. In addition, there were significant effects for secondary outcome tasks measuring verbal WM, response inhibition, and complex reasoning. Parent ratings showed significant reduction in symptoms of inattention and hyperactivity/impulsivity, both post-intervention and at follow-up. CONCLUSIONS This study shows that WM can be improved by training in children with ADHD. This training also improved response inhibition and reasoning and resulted in a reduction of the parent-rated inattentive symptoms of ADHD. | |
2004 |
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Helena Westerberg, Tatja Hirvikoski, Hans Forssberg, Torkel Klingberg Visuo-Spatial Working Memory Span: A Sensitive Measure of Cognitive Deficits in Children With ADHD Journal Article Child Neuropsychology (Neuropsychology, Development and Cognition: Section C), 10 (3), pp. 155–161, 2004, ISSN: 0929-7049. @article{Westerberg2004, title = {Visuo-Spatial Working Memory Span: A Sensitive Measure of Cognitive Deficits in Children With ADHD}, author = {Helena Westerberg and Tatja Hirvikoski and Hans Forssberg and Torkel Klingberg}, url = {http://www.informaworld.com/openurl?genre=article&doi=10.1080/09297040490911014&magic=crossref%7C%7CD404A21C5BB053405B1A640AFFD44AE3}, doi = {10.1080/09297040490911014}, issn = {0929-7049}, year = {2004}, date = {2004-09-01}, journal = {Child Neuropsychology (Neuropsychology, Development and Cognition: Section C)}, volume = {10}, number = {3}, pages = {155--161}, abstract = {Working memory (WM) has been hypothesised to be impaired in attention-deficit/hyperactivity disorder (ADHD). However, there are few studies reported on tests measuring visuo-spatial WM (VSWM) in ADHD. Some of these studies used paradigms including episodic memory, others only used low memory loads. In the present study we used a VSWM test that has not been used previously in ADHD research. The sensitivity of the VSWM test and a choice reaction time (CRT) test was evaluated in a pilot study by comparing them to two commonly used tests in ADHD-research; the Continuous Performance Test (CPT) and a Go/no-go test, in children with and without ADHD. The groups differed significantly in performance on the VSWM test (P textless .01) and CRT (P textless .05) but not on the CPT (P textgreater . 1) or on the Go/no-go test (P textgreater .1). The results from the VSWM and CRT tests were replicated in a larger sample of participants (80 boys; 27 boys with ADHD and 53 controls, mean age 11.4 years). The difference between the groups was significant for both the VSWM test (P textless . 01) and the CRT test (P textless .01). The effect size (ES) of the VSWM test was 1.34. There was a significant age-by-group interaction on the VSWM test, with larger group differences for the older children (P textless .01). Our results show that the VSWM test is a sensitive measure of cognitive deficits in ADHD and it supports the hypothesis that deficits in VSWM is a major component of ADHD.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Working memory (WM) has been hypothesised to be impaired in attention-deficit/hyperactivity disorder (ADHD). However, there are few studies reported on tests measuring visuo-spatial WM (VSWM) in ADHD. Some of these studies used paradigms including episodic memory, others only used low memory loads. In the present study we used a VSWM test that has not been used previously in ADHD research. The sensitivity of the VSWM test and a choice reaction time (CRT) test was evaluated in a pilot study by comparing them to two commonly used tests in ADHD-research; the Continuous Performance Test (CPT) and a Go/no-go test, in children with and without ADHD. The groups differed significantly in performance on the VSWM test (P textless .01) and CRT (P textless .05) but not on the CPT (P textgreater . 1) or on the Go/no-go test (P textgreater .1). The results from the VSWM and CRT tests were replicated in a larger sample of participants (80 boys; 27 boys with ADHD and 53 controls, mean age 11.4 years). The difference between the groups was significant for both the VSWM test (P textless . 01) and the CRT test (P textless .01). The effect size (ES) of the VSWM test was 1.34. There was a significant age-by-group interaction on the VSWM test, with larger group differences for the older children (P textless .01). Our results show that the VSWM test is a sensitive measure of cognitive deficits in ADHD and it supports the hypothesis that deficits in VSWM is a major component of ADHD. | |
Pernille J Olesen, Helena Westerberg, Torkel Klingberg Increased prefrontal and parietal activity after training of working memory Journal Article Nature Neuroscience, 7 (1), pp. 75–79, 2004, ISSN: 1097-6256. @article{Olesen2004, title = {Increased prefrontal and parietal activity after training of working memory}, author = {Pernille J Olesen and Helena Westerberg and Torkel Klingberg}, url = {http://www.nature.com/articles/nn1165}, doi = {10.1038/nn1165}, issn = {1097-6256}, year = {2004}, date = {2004-01-01}, journal = {Nature Neuroscience}, volume = {7}, number = {1}, pages = {75--79}, publisher = {Nature Publishing Group}, abstract = {Increased prefrontal and parietal activity after training of working memory}, keywords = {}, pubstate = {published}, tppubtype = {article} } Increased prefrontal and parietal activity after training of working memory | |
2003 |
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Pernille J Olesen, Zoltan Nagy, Helena Westerberg, Torkel Klingberg Combined analysis of DTI and fMRI data reveals a joint maturation of white and grey matter in a fronto-parietal network Journal Article Cognitive Brain Research, 18 (1), pp. 48–57, 2003, ISSN: 09266410. @article{Olesen2003, title = {Combined analysis of DTI and fMRI data reveals a joint maturation of white and grey matter in a fronto-parietal network}, author = {Pernille J Olesen and Zoltan Nagy and Helena Westerberg and Torkel Klingberg}, url = {https://linkinghub.elsevier.com/retrieve/pii/S092664100300212X}, doi = {10.1016/j.cogbrainres.2003.09.003}, issn = {09266410}, year = {2003}, date = {2003-12-01}, journal = {Cognitive Brain Research}, volume = {18}, number = {1}, pages = {48--57}, abstract = {The aim of this study was to explore whether there are networks of regions where maturation of white matter and changes in brain activity show similar developmental trends during childhood. In a previous study, we showed that during childhood, grey matter activity increases in frontal and parietal regions. We hypothesized that this would be mediated by maturation of white matter. Twenty-three healthy children aged 8-18 years were investigated. Brain activity was measured using the blood oxygen level-dependent (BOLD) contrast with functional magnetic resonance imaging (fMRI) during performance of a working memory (WM) task. White matter microstructure was investigated using diffusion tensor imaging (DTI). Based on the DTI data, we calculated fractional anisotropy (FA), an indicator of myelination and axon thickness. Prior to scanning, WM score was evaluated. WM score correlated independently with FA values and BOLD response in several regions. FA values and BOLD response were extracted for each subject from the peak voxels of these regions. The FA values were used as covariates in an additional BOLD analysis to find brain regions where FA values and BOLD response correlated. Conversely, the BOLD response values were used as covariates in an additional FA analysis. In several cortical and sub-cortical regions, there were positive correlations between maturation of white matter and increased brain activity. Specifically, and consistent with our hypothesis, we found that FA values in fronto-parietal white matter correlated with BOLD response in closely located grey matter in the superior frontal sulcus and inferior parietal lobe, areas that could form a functional network underlying working memory function. textcopyright 2003 Elsevier B.V. All rights reserved.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The aim of this study was to explore whether there are networks of regions where maturation of white matter and changes in brain activity show similar developmental trends during childhood. In a previous study, we showed that during childhood, grey matter activity increases in frontal and parietal regions. We hypothesized that this would be mediated by maturation of white matter. Twenty-three healthy children aged 8-18 years were investigated. Brain activity was measured using the blood oxygen level-dependent (BOLD) contrast with functional magnetic resonance imaging (fMRI) during performance of a working memory (WM) task. White matter microstructure was investigated using diffusion tensor imaging (DTI). Based on the DTI data, we calculated fractional anisotropy (FA), an indicator of myelination and axon thickness. Prior to scanning, WM score was evaluated. WM score correlated independently with FA values and BOLD response in several regions. FA values and BOLD response were extracted for each subject from the peak voxels of these regions. The FA values were used as covariates in an additional BOLD analysis to find brain regions where FA values and BOLD response correlated. Conversely, the BOLD response values were used as covariates in an additional FA analysis. In several cortical and sub-cortical regions, there were positive correlations between maturation of white matter and increased brain activity. Specifically, and consistent with our hypothesis, we found that FA values in fronto-parietal white matter correlated with BOLD response in closely located grey matter in the superior frontal sulcus and inferior parietal lobe, areas that could form a functional network underlying working memory function. textcopyright 2003 Elsevier B.V. All rights reserved. | |
Zoltan Nagy, Helena Westerberg, Stefan Skare, Jesper L Andersson, Anders Lilja, Olof Flodmark, Elisabeth Fernell, Kirsten Holmberg, Birgitta Böhm, Hans Forssberg, Hugo Lagercrantz, Torkel Klingberg Preterm Children Have Disturbances of White Matter at 11 Years of Age as Shown by Diffusion Tensor Imaging Journal Article Pediatric Research, 54 (5), pp. 672–679, 2003, ISSN: 0031-3998. @article{Nagy2003, title = {Preterm Children Have Disturbances of White Matter at 11 Years of Age as Shown by Diffusion Tensor Imaging}, author = {Zoltan Nagy and Helena Westerberg and Stefan Skare and Jesper L Andersson and Anders Lilja and Olof Flodmark and Elisabeth Fernell and Kirsten Holmberg and Birgitta Böhm and Hans Forssberg and Hugo Lagercrantz and Torkel Klingberg}, url = {http://www.nature.com/doifinder/10.1203/01.PDR.0000084083.71422.16}, doi = {10.1203/01.PDR.0000084083.71422.16}, issn = {0031-3998}, year = {2003}, date = {2003-11-01}, journal = {Pediatric Research}, volume = {54}, number = {5}, pages = {672--679}, abstract = {Preterm birth frequently involves white matter injury and affects long-term neurologic and cognitive outcomes. Diffusion tensor imaging has been used to show that the white matter microstructure of newborn, preterm children is compromised in a regionally specific manner. However, until now it was not clear whether these lesions would persist and be detectible on long-term follow-up. Hence, we collected diffusion tensor imaging data on a i.5-T scanner, and computed fractional anisotropy and coherence measures to compare the white matter integrity of children born preterm to that of control subjects. The subjects for the preterm group (10.9 ± 0.29 y; n = 9; birth weight ≤ 5 1500 g; mean gestational age, 28.6 ± 1.05 wk) possessed attention deficits, a common problem in preterms. They were compared with age- and sex-matched control children (10.8 ± 0.33 y; n = 10; birth weight ≥ 2500; gestational age, ≥ 37 wk). We found that the preterm group had lower fractional anisotropy values in the posterior corpus callosum and bilaterally in the internal capsules. In the posterior corpus callosum this difference in fractional anisotropy values may partially be related to a difference in white matter volume between the groups. An analysis of the coherence measure failed to indicate a group difference in the axonal organization. These results are in agreement with previous diffusion tensor imaging findings in newborn preterm children, and indicate that ex-preterm children with attention deficits have white matter disturbances that are not compensated for or repaired before 11 y of age.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Preterm birth frequently involves white matter injury and affects long-term neurologic and cognitive outcomes. Diffusion tensor imaging has been used to show that the white matter microstructure of newborn, preterm children is compromised in a regionally specific manner. However, until now it was not clear whether these lesions would persist and be detectible on long-term follow-up. Hence, we collected diffusion tensor imaging data on a i.5-T scanner, and computed fractional anisotropy and coherence measures to compare the white matter integrity of children born preterm to that of control subjects. The subjects for the preterm group (10.9 ± 0.29 y; n = 9; birth weight ≤ 5 1500 g; mean gestational age, 28.6 ± 1.05 wk) possessed attention deficits, a common problem in preterms. They were compared with age- and sex-matched control children (10.8 ± 0.33 y; n = 10; birth weight ≥ 2500; gestational age, ≥ 37 wk). We found that the preterm group had lower fractional anisotropy values in the posterior corpus callosum and bilaterally in the internal capsules. In the posterior corpus callosum this difference in fractional anisotropy values may partially be related to a difference in white matter volume between the groups. An analysis of the coherence measure failed to indicate a group difference in the axonal organization. These results are in agreement with previous diffusion tensor imaging findings in newborn preterm children, and indicate that ex-preterm children with attention deficits have white matter disturbances that are not compensated for or repaired before 11 y of age. | |
2002 |
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Torkel Klingberg, Hans Forssberg, Helena Westerberg Training of Working Memory in Children With ADHD Journal Article Journal of Clinical and Experimental Neuropsychology, 24 (6), pp. 781–791, 2002, ISSN: 1380-3395. @article{Klingberg2002, title = {Training of Working Memory in Children With ADHD}, author = {Torkel Klingberg and Hans Forssberg and Helena Westerberg}, url = {https://www.tandfonline.com/doi/full/10.1076/jcen.24.6.781.8395}, doi = {10.1076/jcen.24.6.781.8395}, issn = {1380-3395}, year = {2002}, date = {2002-09-01}, journal = {Journal of Clinical and Experimental Neuropsychology}, volume = {24}, number = {6}, pages = {781--791}, abstract = {Purpose: Oral mucositis is a common and severe complication of head and neck radiation therapy. Evaluating the progression and severity of radiation-induced oral mucositis is an important aspect of treatment because oral mucositis often debilitates the patient's quality of life and may interrupt or change the cancer treatment. Localized, time-dependent tissue changes that occur during radiation may be conducive to the development of a clinical model of mucosal tissue damage. Materials and Methods: The secretion of biochemical markers, such as human alpha-defensins, was examined in the oral mucosa from patients receiving radiation therapy using the ProteinChip array, surface-enhanced laser desorption/ionization technology (Ciphergen Biosystems Inc, Fremont, CA) combined with time-of-flight mass spectrometry. This method has also proven to be effective and feasible in detecting and measuring changes of alpha-defensins in a small amount of biological fluids. Results: The concentration of the human alpha-defensins measured in the exudates from the surface in the field of developing oral mucositis lesions changed during the development and healing processes. Conclusion: This method may provide the means to assess oral mucositis during development and resolution and to assist in developing an understanding of the pathogenesis of the condition. In addition, this method may provide a means of assessing developing tissue damage and lead to new approaches to prevent and treat oral mucositis in cancer therapy.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Purpose: Oral mucositis is a common and severe complication of head and neck radiation therapy. Evaluating the progression and severity of radiation-induced oral mucositis is an important aspect of treatment because oral mucositis often debilitates the patient's quality of life and may interrupt or change the cancer treatment. Localized, time-dependent tissue changes that occur during radiation may be conducive to the development of a clinical model of mucosal tissue damage. Materials and Methods: The secretion of biochemical markers, such as human alpha-defensins, was examined in the oral mucosa from patients receiving radiation therapy using the ProteinChip array, surface-enhanced laser desorption/ionization technology (Ciphergen Biosystems Inc, Fremont, CA) combined with time-of-flight mass spectrometry. This method has also proven to be effective and feasible in detecting and measuring changes of alpha-defensins in a small amount of biological fluids. Results: The concentration of the human alpha-defensins measured in the exudates from the surface in the field of developing oral mucositis lesions changed during the development and healing processes. Conclusion: This method may provide the means to assess oral mucositis during development and resolution and to assist in developing an understanding of the pathogenesis of the condition. In addition, this method may provide a means of assessing developing tissue damage and lead to new approaches to prevent and treat oral mucositis in cancer therapy. | |
Torkel Klingberg, Hans Forssberg, Helena Westerberg Increased brain activity in frontal and parietal cortex underlies the development of visuospatial working memory capacity during childhood Journal Article Journal of Cognitive Neuroscience, 14 (1), pp. 1–10, 2002, ISSN: 0898929X. @article{Klingberg2002a, title = {Increased brain activity in frontal and parietal cortex underlies the development of visuospatial working memory capacity during childhood}, author = {Torkel Klingberg and Hans Forssberg and Helena Westerberg}, doi = {10.1162/089892902317205276}, issn = {0898929X}, year = {2002}, date = {2002-01-01}, journal = {Journal of Cognitive Neuroscience}, volume = {14}, number = {1}, pages = {1--10}, abstract = {The aim of this study was to identify changes in brain activity associated with the increase in working memory (WM) capacity that occurs during childhood and early adulthood. Functional MRI (fMRI) was used to measure brain activity in subjects between 9 and 18 years of age while they performed a visuospatial WM task and a baseline task. During performance of the WM task, the older children showed higher activation of cortex in the superior frontal and intraparietal cortex than the younger children did. A second analysis found that WM capacity was significantly correlated with brain activity in the same regions. These frontal and parietal areas are known to be involved in the control of attention and spatial WM. The development of the functionality in these areas may play an important role in cognitive development during childhood.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The aim of this study was to identify changes in brain activity associated with the increase in working memory (WM) capacity that occurs during childhood and early adulthood. Functional MRI (fMRI) was used to measure brain activity in subjects between 9 and 18 years of age while they performed a visuospatial WM task and a baseline task. During performance of the WM task, the older children showed higher activation of cortex in the superior frontal and intraparietal cortex than the younger children did. A second analysis found that WM capacity was significantly correlated with brain activity in the same regions. These frontal and parietal areas are known to be involved in the control of attention and spatial WM. The development of the functionality in these areas may play an important role in cognitive development during childhood. | |
2000 |
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Torkel Klingberg Progress in Brain Research, 126 (i), pp. 95–102, 2000, ISSN: 00796123. @incollection{Klingberg2000, title = {Limitations in information processing in the human brain: neuroimaging of dual task performance and working memory tasks}, author = {Torkel Klingberg}, url = {https://linkinghub.elsevier.com/retrieve/pii/S0079612300260093}, doi = {10.1016/S0079-6123(00)26009-3}, issn = {00796123}, year = {2000}, date = {2000-01-01}, booktitle = {Progress in Brain Research}, volume = {126}, number = {i}, pages = {95--102}, abstract = {This chapter discusses neuroimaging results from dual task performance and tasks where working memory (WM) load is parametrically varied, and discusses whether and how these results could possibly contribute to the understanding of human capacity limitations. Dual tasks have also attracted some interest because they are said to be prototypical executive tasks. Executive functions is a concept often used to denote functions of attentional control, such as switching or dividing of attention, inhibition, planning, coordination, and decision making. It is, however, probably more fruitful to consider these diverse functions separately, rather than referring to executive function as a single entity. The results of increasing information processing demands is somewhat similar in both WM tasks and dual tasks, with a quantitative increase in activity in several areas, often most pronounced in the inferior and middle frontal gyms, particularly in the right hemisphere.}, keywords = {}, pubstate = {published}, tppubtype = {incollection} } This chapter discusses neuroimaging results from dual task performance and tasks where working memory (WM) load is parametrically varied, and discusses whether and how these results could possibly contribute to the understanding of human capacity limitations. Dual tasks have also attracted some interest because they are said to be prototypical executive tasks. Executive functions is a concept often used to denote functions of attentional control, such as switching or dividing of attention, inhibition, planning, coordination, and decision making. It is, however, probably more fruitful to consider these diverse functions separately, rather than referring to executive function as a single entity. The results of increasing information processing demands is somewhat similar in both WM tasks and dual tasks, with a quantitative increase in activity in several areas, often most pronounced in the inferior and middle frontal gyms, particularly in the right hemisphere. | |
2007 |
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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. | |
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. | |
Changes in cortical activity after training of working memory - a single-subject analysis Journal Article Physiology and Behavior, 92 (1-2), pp. 186–192, 2007, ISSN: 00319384. | |
Brain activity related to working memory and distraction in children and adults Journal Article Cerebral Cortex, 17 (5), pp. 1047–1054, 2007, ISSN: 10473211. | |
Computerized working memory training after stroke–A pilot study Journal Article Brain Injury, 21 (1), pp. 21–29, 2007, ISSN: 0269-9052. | |
2006 |
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A biophysical model of multiple-item working memory: A computational and neuroimaging study Journal Article Neuroscience, 141 (3), pp. 1611–1618, 2006, ISSN: 03064522. | |
Development of a superior frontal–intraparietal network for visuo-spatial working memory Journal Article Neuropsychologia, 44 (11), pp. 2171–2177, 2006, ISSN: 00283932. | |
2005 |
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Diffusion Tensor Imaging on Teenagers, Born at Term With Moderate Hypoxic-ischemic Encephalopathy Journal Article Pediatric Research, 58 (5), pp. 936–940, 2005, ISSN: 0031-3998. | |
Computerized Training of Working Memory in Children With ADHD-A Randomized, Controlled Trial Journal Article Journal of the American Academy of Child & Adolescent Psychiatry, 44 (2), pp. 177–186, 2005, ISSN: 08908567. | |
2004 |
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Visuo-Spatial Working Memory Span: A Sensitive Measure of Cognitive Deficits in Children With ADHD Journal Article Child Neuropsychology (Neuropsychology, Development and Cognition: Section C), 10 (3), pp. 155–161, 2004, ISSN: 0929-7049. | |
Increased prefrontal and parietal activity after training of working memory Journal Article Nature Neuroscience, 7 (1), pp. 75–79, 2004, ISSN: 1097-6256. | |
2003 |
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Combined analysis of DTI and fMRI data reveals a joint maturation of white and grey matter in a fronto-parietal network Journal Article Cognitive Brain Research, 18 (1), pp. 48–57, 2003, ISSN: 09266410. | |
Preterm Children Have Disturbances of White Matter at 11 Years of Age as Shown by Diffusion Tensor Imaging Journal Article Pediatric Research, 54 (5), pp. 672–679, 2003, ISSN: 0031-3998. | |
2002 |
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Training of Working Memory in Children With ADHD Journal Article Journal of Clinical and Experimental Neuropsychology, 24 (6), pp. 781–791, 2002, ISSN: 1380-3395. | |
Increased brain activity in frontal and parietal cortex underlies the development of visuospatial working memory capacity during childhood Journal Article Journal of Cognitive Neuroscience, 14 (1), pp. 1–10, 2002, ISSN: 0898929X. | |
2000 |
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Progress in Brain Research, 126 (i), pp. 95–102, 2000, ISSN: 00796123. | |