Improving Reading Skills Using a Computerized Phonological Training Program in Early Readers with Reading Difficulties

In the last years, there has been a big effort to identify risk factors for reading difficulties and to develop new methodologies to help struggling readers. It has been shown that early intervention is more successful than late intervention, and that intensive training programs can benefit children with reading difficulties. The aim of our study is to investigate the effectiveness of an intensive computerized phonological training program designed to improve reading performance in a sample of children with reading difficulties at the early stages of their reading learning process. Thirty-two children with reading difficulties were randomly assigned to one of the two intervention groups: RDIR (children with reading difficulties following a computerized intensive remediation strategy) (n = 20) (7.01 +/- 0.69 years), focused on training phonemic awareness, decoding and reading fluency through the computational training; and RDOR (children with reading difficulties following an ordinary remediation strategy) (n = 12) (6.92 +/- 0.82 years), which consisted of a reinforcement of reading with a traditional training approach at school. Normal readers (NR) were assigned to the control group (n = 24) (7.32 +/- 0.66 years). Our results indicate that both the RDIR and RDOR groups showed an increased reading performance after the intervention. However, children in the RDIR group showed a stronger benefit than the children in the RDOR group, whose improvement was weaker. The control group did not show significant changes in reading performance during the same period. In conclusion, results suggest that intensive early intervention based on phonics training is an effective strategy to remediate reading difficulties, and that it can be used at school as the first approach to tackle such difficulties

Alteraciones en la conectividad funcional cerebral asociadas a las dificultades lectoras y numéricas en la infancia

[spa] La investigación que se presenta en esta tesis doctoral está centrada en la identificación de las alteraciones de la conectividad funcional en dos de los trastornos del aprendizaje con mayor prevalencia en nuestra sociedad, como son el trastorno de aprendizaje de la lectura y el trastorno de aprendizaje de las matemáticas, durante la etapa crítica de adquisición de estas habilidades. Estas aptitudes son esenciales para un correcto desarrollo cognitivo y social. La investigación se ha desarrollado en 4 estudios, en los cuales se han reclutado un grupo de niños/as de 6-7 años con dificultades lectoras (RD: n = 30, edad = 7.01 ± 0.69), un grupo de niños/as de 7-8 años con dificultades matemáticas (MD: n = 15, edad = 7.78 ± 0.94), y sus respectivos grupos control (grupo control de niños normolectores (NR): n = 34; edad = 7.32 ± 0.66; grupo control de niños normonuméricos (C): n = 15; edad = 8.21 ± 1.02) . El análisis de los datos fMRI en reposo se han realizado mediante 2 metodologías no apriorísticas. La primera es el Multivariate pattern analysis (MVPA), mediante el cual se han observado áreas que presentan un patrón alterado de conectividad en ambos trastornos. En concreto, el grupo con dificultades lectoras ha mostrado una conectividad funcional incrementada entre la región frontal y la red neural por defecto (DMN), aunque reducida con áreas pertenecientes a la red de saliencia, además de una menor conectividad en la comunicación interna de la DMN. Por su parte, el grupo con dificultades en el aprendizaje de las matemáticas ha mostrado una conectividad funcional aumentada entre las áreas temporales que componen la DMN y la red sensoriomotora, además de entre el precuneus y el sulco intraparietal derecho, aunque disminuida en la conectividad interna de la DMN. La segunda metodología usada es el Independent component analysis (ICA), el cual permite extraer el conjunto de redes neurales como componentes independientes entre sí, y analizar su conectividad funcional interna. La investigación se ha centrado en la búsqueda de alteraciones en la conectividad interna de la DMN. Los resultados en ambos grupos con trastornos de aprendizaje han mostrado resultados muy parecidos. Concretamente, se ha puesto de manifiesto una menor conectividad interna de esta red en ambos grupos con trastornos de aprendizaje con relación al grupo control, observándose esta alteración en las conexiones del precuneus. Los resultados obtenidos en el conjunto de los análisis realizados sugieren que ambos trastornos presentan una comunicación alterada que implica distintas redes neurales, como la DMN, la red de saliencia o la red sensoriomotora. La DMN se considera un núcleo de procesamiento de la información neural y desarrolla un papel importante en la modulación de la atención entre los estímulos internos y externos. La alteración de esta red en ambos trastornos de aprendizaje no había sido descrita previamente de una manera tan robusta y con un patrón tan claro. En conjunto, los resultados encontrados ponen de manifiesto que en ambos trastornos hay una alteración de la red neural intrínseca a los procesos lectores, y al procesamiento numérico y el cálculo respectivamente, además de una alteración global de redes neurales implicadas en otros procesos, como el control atencional y la distribución de recursos cognitivos, entre las que destaca la alteración de la DMN. Estos resultados pueden abrir nuevas vías de conocimiento en la comprensión de estos trastornos del neurodesarrollo, en su detección precoz y en su reeducación.[eng] The research presented in this dissertation consists in the identification of alterations in functional connectivity in two of the learning disorders with greater prevalence in our society, namely reading learning disorder and the disorder of mathematics learning, during the critical stage of acquiring these skills. These abilities are essential for adequate cognitive and social development in children. The research has been carried out in 4 studies, in which a group of children aged 6-7 years old with reading difficulties (n=30), a group of children aged 7-8 years old with mathematical difficulties have been recruited (n=15), and their respective control groups. The analysis of the fMRI data at rest has been carried out using 2 non- aprioristic methodologies. First one is the Multivariate pattern analysis (MVPA), whereby areas that have an altered pattern of connectivity in both disorders have been observed. The results have shown an altered connectivity between several neural networks in both groups of patients. The reading difficulties group has shown anomalous increased connectivity between the frontal areas and the default neural network (DMN), and reduced connectivity with areas pertaining to the salience network, as well as a slight reduced connectivity in the internal communication of the DMN. On the other hand, the group with difficulties in mathematics learning has shown an altered communication between the areas that make up the DMN and the sensorimotor network, precuneus and right intraparietal sulcus. Moreover, it has been showed a decreased DMN internal connectivity. The second methodology used in the research is the Independent component analysis (ICA), which makes it possible to isolate a set of neural networks as independent components from each other and analyze their internal functional connectivity. The set of analyses performed have focused on the identification of alterations in the internal connectivity of the DMN. They have yielded very similar results in both groups. They show a characteristically lower internal connectivity of this network, mainly in the precuneus area, when compared to the control group. The data resulting from the research suggests that both disorders are related to altered communication patterns between different neural networks, especially the DMN and the sensorimotor network. The DMN is a core neural information processing actor and plays a key role in the modulation of attention between internal and external stimuli. The role of this network in both reading and mathematics learning disorders hadn't been previously described in such a robust manner and clear pattern. Together, the results found show that in both disorders there is an alteration of the neural network intrinsic to the reading processes, and to the numerical processing and calculation respectively, in addition to a global alteration of neural networks involved in other cognitive processes, among which highlights the alteration of the DMN. The research opens new paths of knowledge for the understanding of these neurodevelopmental disorders, regarding its early detection and and its reeducation

Quantification of gene expression patterns to reveal the origins of abnormal morphogenesis

The earliest developmental origins of dysmorphologies are poorly understood in many congenital diseases. They often remain elusive because the first signs of genetic misregulation may initiate as subtle changes in gene expression, which are hard to detect and can be obscured later in development by secondary effects. Here, we develop a method to trace back the origins of phenotypic abnormalities by accurately quantifying the 3D spatial distribution of gene expression domains in developing organs. By applying Geometric Morphometrics to 3D gene expression data obtained by Optical Projection Tomography, we determined that our approach is sensitive enough to find regulatory abnormalities that have never been detected previously. We identified subtle but significant differences in the gene expression of a downstream target of a Fgfr2 mutation associated with Apert syndrome, demonstrating that these mouse models can further our understanding of limb defects in the human condition. Our method can be applied to different organ systems and models to investigate the etiology of malformations.The research leading to these results received funding from the following grants: a European Union Seventh Framework Program (FP7/2007-2013) under grant agreement Marie Curie Fellowship FP7-PEOPLE-2012-IIF 327382, National Institutes of Health grants NICHD P01HD078233 and NIDCR R01DE02298, and a Burroughs-Welcome Fund 2013 Collaborative Research Travel Grant

Reconstructions of embryonic limbs and Dusp6 gene expression domains from OPT scans of Apert syndrome mouse models.

This zip folder contains the surface files (.stl) of the limbs and the Dusp6 gene expression domains obtained from OPT scanning mouse embryos of Apert syndrome mouse models at E10.5 and E11.5. Surface files are grouped into forelimbs and hindlimbs of Early, Mid and Late developmental periods as specified in Table 2

Data from: Quantification of gene expression patterns to reveal the origins of abnormal morphogenesis

The earliest developmental origins of dysmorphologies are poorly understood in many congenital diseases. They often remain elusive because the first signs of genetic misregulation may initiate as subtle changes in gene expression, which are hard to detect and can be obscured later in development by secondary effects. Here, we develop a method to trace the origins of phenotypic abnormalities by accurately quantifying the 3D spatial distribution of gene expression domains in developing organs. By applying geometric morphometrics to 3D gene expression data obtained by Optical Projection Tomography, we determined that our approach is sensitive enough to find regulatory abnormalities that have never been detected previously. We identified subtle but significant differences in the gene expression of a downstream target of the Fgfr2 mutation that were associated with Apert syndrome, demonstrating that these mouse models can further our understanding of limb defects in the human condition. Our method can be applied to different organ systems and models to investigate the etiology of malformations