Helena Westerberg

Computerized Training of Working Memory in Children With ADHD-A Randomized, Controlled Trial

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 (>20 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.

Increased prefrontal and parietal activity after training of working memory

Working memory capacity has traditionally been thought to be constant. Recent studies, however, suggest that working memory can be improved by training. In this study, we have investigated the changes in brain activity that are induced by working memory training. Two experiments were carried out in which healthy, adult human subjects practiced working memory tasks for 5 weeks. Brain activity was measured with functional magnetic resonance imaging (fMRI) before, during and after training. After training, brain activity that was related to working memory increased in the middle frontal gyrus and superior and inferior parietal cortices. The changes in cortical activity could be evidence of training-induced plasticity in the neural systems that underlie working memory.

Training of Working Memory in Children With ADHD

Working memory (WM) capacity is the ability to retain and manipulate information during a short period of time. This ability underlies complex reasoning and has generally been regarded as a fixed trait of the individual. Children with attention deficit hyperactivity disorder (ADHD) represent one group of subjects with a WM deficit, attributed to an impairment of the frontal lobe. In the present study, we used a new training paradigm with intensive and adaptive training of WM tasks and evaluated the effect of training with a double blind, placebo controlled design. Training significantly enhanced performance on the trained WM tasks. More importantly, the training significantly improved performance on a non-trained visuo-spatial WM task and on Ravens Progressive Matrices, which is a nonverbal complex reasoning task. In addition, motor activity - as measured by the number of head movements during a computerized test - was significantly reduced in the treatment group. A second experiment showed that similar training-induced improvements on cognitive tasks are also possible in young adults without ADHD. These results demonstrate that performance on WM tasks can be significantly improved by training, and that the training effect also generalizes to non-trained tasks requiring WM. Training improved performance on tasks related to prefrontal functioning and had also a significant effect on motor activity in children with ADHD. The results thus suggest that WM training potentially could be of clinical use for ameliorating the symptoms in ADHD.

Increased Brain Activity in Frontal and Parietal Cortex Underlies the Development of Visuospatial Working Memory Capacity during Childhood

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.

Maturation of White Matter is Associated with the Development of Cognitive Functions during Childhood

In the human brain, myelination of axons continues until early adulthood and is thought to be important for the development of cognitive functions during childhood. We used diffusion tensor MR imaging and calculated fractional anisotropy, an indicator of myelination and axonal thickness, in children aged between 8 and 18 years. Development of working memory capacity was positively correlated with fractional anisotropy in two regions in the left frontal lobe, including a region between the superior frontal and parietal cortices. Reading ability, on the other hand, was only correlated with fractional anisotropy in the left temporal lobe, in the same white matter region where adults with reading disability are known to have lower fractional anisotropy. Both the temporal and the frontal regions were also correlated with age. These results show that maturation of white matter is an important part of brain maturation during childhood, and that maturation of relatively restricted regions of white matter is correlated with development of specific cognitive functions.

Computerized working memory training after stroke–A pilot study

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-trainedtests 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 < 0.05; PASAT p < 0.001; Ruff 2&7 p < 0.005). There was a significant decrease in symptoms of cognitive problems as measured by the CFQ (p < 0.005). Conclusion: More than one year after a stroke, systematic WM training can significantly improve WM and attention.

Working-memory training in younger and older adults: training gains, transfer, and maintenance

Working memory (WM), a key determinant of many higher-order cognitive functions, declines in old age. Current research attempts to develop process-specific WM training procedures, which may lead to general cognitive improvement. Adaptivity of the training as well as the comparison of training gains to performance changes of an active control group are key factors in evaluating the effectiveness of a specific training program. In the present study, 55 younger adults (20–30 years of age) and 45 older adults (60–70 years of age) received 5 weeks of computerized training on various spatial and verbal WM tasks. Half of the sample received adaptive training (i.e., individually adjusted task difficulty), whereas the other half-worked on the same task material but on a low task difficulty level (active controls). Performance was assessed using criterion, near-transfer, and far-transfer tasks before training, after 5 weeks of intervention, as well as after a 3-month follow-up interval. Results indicate that (a) adaptive training generally led to larger training gains than low-level practice, (b) training and transfer gains were somewhat greater for younger than for older adults in some tasks, but comparable across age groups in other tasks, (c) far-transfer was observed to a test on sustained attention and for a self-rating scale on cognitive functioning in daily life for both young and old, and (d) training gains and transfer effects were maintained across the 3-month follow-up interval across age.

Changes in cortical activity after training of working memory — a single-subject analysis

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.

Preterm Children Have Disturbances of White Matter at 11 Years of Age as Shown by Diffusion Tensor Imaging

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 1.5-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 ≤ 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.

Visuo-Spatial Working Memory Span: A Sensitive Measure of Cognitive Deficits in Children With ADHD

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<.01) and CRT (P<.05) but not on the CPT (P>.1) or on the Go/no-go test (P>.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<.01) and the CRT test (P<.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<.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.