Mental number line training in children with developmental dyscalculia.

Developmental dyscalculia (DD) is a specific learning disability that affects the acquisition of mathematical skills in children with normal intelligence and age-appropriate school education (prevalence 3-6%). One essential step in the development of mathematical understanding is the formation and automated access to a spatial representation of numbers. Many children with DD show a deficient development of such a mental number line. The present study aimed to develop a computer-based training program to improve the construction and access to the mental number line. Sixteen children with DD aged 8-10 years and 16 matched control children completed the 5-week computer training. All children played the game 15 min a day for 5 days a week. The efficiency of the training was evaluated by means of neuropsychological tests and functional magnetic resonance imaging (fMRI) during a number line task. In general, children with and without DD showed a benefit from the training indicated by (a) improved spatial representation of numbers and (b) the number of correctly solved arithmetical problems. Regarding group differences in brain activation, children with DD showed less activation in bilateral parietal regions, which reflects neuronal dysfunction in pivotal regions for number processing. Both groups showed reduced recruitment of relevant brain regions for number processing after the training which can be attributed to automatization of cognitive processes necessary for mathematical reasoning. Moreover, results point to a partial remediation of deficient brain activation in dyscalculics after consolidation of acquired and refined number representation. To conclude, the present study represents the first attempt to evaluate a custom-designed training program in a group of dyscalculic children and results indicate that the training leads to an improved spatial representation of the mental number line and a modulation of neural activation, which both facilitate processing of numerical tasks.

Dysfunctional neural network of spatial working memory contributes to developmental dyscalculia.

The underlying neural mechanisms of developmental dyscalculia (DD) are still far from being clearly understood. Even the behavioral processes that generate or influence this heterogeneous disorder are a matter of controversy. To date, the few studies examining functional brain activation in children with DD mainly focus on number and counting related tasks, whereas studies on more general cognitive domains that are involved in arithmetical development, such as working memory are virtually absent. There are several studies showing a close relationship between DD and spatial working memory [Camos, V. (2008). Low working memory capacity impedes both efficiency and learning of number transcoding in children. Journal of Experimental Child Psychology, 99(1), 37-57; McLean, J. F., & Hitch, G. J. (1999). Working memory impairments in children with specific arithmetic learning difficulties. Journal of Experimental Child Psychology, 74(3), 240-260; Rosselli, M., Matute, E., Pinto, N., & Ardila, A. (2006). Memory abilities in children with subtypes of dyscalculia. Developmental Neuropsychology, 30(3), 801-818; Siegel, L. S., & Ryan, E. B. (1989). The development of working memory in normally achieving and subtypes of learning disabled children. Child Development, 60(4), 973-980]. The relationship between these two mechanisms is still matter of debate, but this study follows the assumption that poor spatial working memory capacity may hinder the acquisition of spatial number representations in children with DD [Geary, D. C. (1993). Mathematical disabilities: Cognitive, neuropsychological, and genetic components. Psychological Bulletin, 114(2), 345-362; von Aster, M., & Shalev, R. S. (2007). Number development and developmental dyscalculia. Developmental Medicine and Child Neurology, 49(11), 868-873]. Using functional MRI the current study compares brain activity associated with spatial working memory processes in 8-10-year-old children with DD and normally achieving controls. Both groups showed significant spatial working memory related activity in a network including occipital and parietal regions. Children with DD showed weaker neural activation compared to the control group during a spatial working memory task in the right intraparietal sulcus (IPS), the right insula and the right inferior frontal lobe. Performance tests outside the scanner showed impaired working memory proficiency in children with DD. Bringing behavioral performance and neural activity together we found significant correlations of right IPS activity with performance on the verbal digit span forward and the spatial Corsi Block Tapping test. Our findings demonstrate for the first time an involvement of spatial working memory processes in the neural underpinnings of DD. These poor spatial working memory processes may inhibit the formation of spatial number representations (mental numberline) as well as the storage and retrieval of arithmetical facts.

Novel renal replacement strategies for the elimination of serum free light chains in patients with kappa light chain nephropathy.

Multiple myeloma (MM) is a malignancy with excessive production of monoclonal proteins. At disease presentation 30% of MM patients have significant renal impairment which may progress to renal failure requiring dialysis. Besides chemotherapy extracorporeal elimination procedures such as plasma exchange have been applied as adjuvant strategies to eliminate free light chains from circulating blood, however the efficacy was poor with older techniques. We report about a highly efficient method to eliminate serum free light chain (sFLC) using a newly designed protein leaking membrane in patients suffering from sFLC induced acute renal failure. The protein leaking membrane (HCO 1100) is characterized by increased pore size facilitating elimination of middle molecules such as sFLC kappa (22.5 kD). The HCO 1100 membrane was applied in a hemodialysis and hemodiafiltration mode and compared to standard procedures (high flux hemodialysis, hemodiafiltration and plasma exchange). Hemodiafiltration with the protein leaking membrane HCO 1100 was superior to all other extracorporeal replacement strategies in eliminating sFLC-kappa from circulating blood. A median blood reduction rate of 40.8% (range 13.9%-66.4%) was achieved during hemodiafiltration. The corresponding peak clearance rate was 25 ml/min. Importantly, the poorest elimination rate was achieved by plasma exchange followed by standard high flux hemodialysis. Extracorporeal elimination strategies with the protein leaking membrane HCO 1100 may be a promising adjuvant treatment strategy for patients with sFLC nephropathy requiring dialysis. Hemodiafiltration and to lesser extend also hemodialysis with the HCO 1100 hemofilter are able to eliminate substantial amounts of sFLC kappa in MM patients.

Optimized voxel-based morphometry in children with developmental dyscalculia.

Developmental dyscalculia (DD) is a specific learning disability affecting the normal acquisition of arithmetic skills. Current studies estimate that 3-6% of the school population is affected by DD. Genetic, neurobiological, and epidemiologic evidence indicates that dyscalculia is a brain-based disorder. Imaging studies suggest the involvement of parietal and prefrontal cortices in arithmetic tasks. The aim of the present study was to analyze if children with DD show structural differences in parietal, frontal, and cingulate areas compared to typically achieving children. Magnetic resonance imaging was obtained from 12 children with DD aged 9.3+/-0.2 years and 12 age-matched control children without any learning disabilities on a 1.5 T whole-body scanner. Voxel-based morphometry analysis with an optimization of spatial segmentation and normalization procedures was applied to compare the two groups in order to find differences in cerebral gray and white matter. Compared to controls, children with DD show significantly reduced gray matter volume in the right intraparietal sulcus (IPS), the anterior cingulum, the left inferior frontal gyrus, and the bilateral middle frontal gyri. White matter comparison demonstrates clusters with significantly less volume in the left frontal lobe and in the right parahippocampal gyrus in dyscalculic children. The decreased gray and white matter volumes in the frontoparietal network might be the neurological substrate of impaired arithmetic processing skills. The white matter volume decrease in parahippocampal areas may have influence on fact retrieval and spatial memory processing.