Silencing of the Ca2+ Channel ORAI1 Improves the Multi-Systemic Phenotype of Tubular Aggregate Myopathy (TAM) and Stormorken Syndrome (STRMK) in Mice.

Tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK) form a clinical continuum associating progressive muscle weakness with additional multi-systemic anomalies of the bones, skin, spleen, and platelets. TAM/STRMK arises from excessive extracellular Ca2+ entry due to gain-of-function mutations in the Ca2+ sensor STIM1 or the Ca2+ channel ORAI1. Currently, no treatment is available. Here we assessed the therapeutic potential of ORAI1 downregulation to anticipate and reverse disease development in a faithful mouse model carrying the most common TAM/STRMK mutation and recapitulating the main signs of the human disorder. To this aim, we crossed Stim1R304W/+ mice with Orai1+/- mice expressing 50% of ORAI1. Systematic phenotyping of the offspring revealed that the Stim1R304W/+Orai1+/- mice were born with a normalized ratio and showed improved postnatal growth, bone architecture, and partly ameliorated muscle function and structure compared with their Stim1R304W/+ littermates. We also produced AAV particles containing Orai1-specific shRNAs, and intramuscular injections of Stim1R304W/+ mice improved the skeletal muscle contraction and relaxation properties, while muscle histology remained unchanged. Altogether, we provide the proof-of-concept that Orai1 silencing partially prevents the development of the multi-systemic TAM/STRMK phenotype in mice, and we also established an approach to target Orai1 expression in postnatal tissues.

Whole-genome sequencing identifies functional noncoding variation in SEMA3C that cosegregates with dyslexia in a multigenerational family.

Dyslexia is a common heritable developmental disorder involving impaired reading abilities. Its genetic underpinnings are thought to be complex and heterogeneous, involving common and rare genetic variation. Multigenerational families segregating apparent monogenic forms of language-related disorders can provide useful entrypoints into biological pathways. In the present study, we performed a genome-wide linkage scan in a three-generational family in which dyslexia affects 14 of its 30 members and seems to be transmitted with an autosomal dominant pattern of inheritance. We identified a locus on chromosome 7q21.11 which cosegregated with dyslexia status, with the exception of two cases of phenocopy (LOD = 2.83). Whole-genome sequencing of key individuals enabled the assessment of coding and noncoding variation in the family. Two rare single-nucleotide variants (rs144517871 and rs143835534) within the first intron of the SEMA3C gene cosegregated with the 7q21.11 risk haplotype. In silico characterization of these two variants predicted effects on gene regulation, which we functionally validated for rs144517871 in human cell lines using luciferase reporter assays. SEMA3C encodes a secreted protein that acts as a guidance cue in several processes, including cortical neuronal migration and cellular polarization. We hypothesize that these intronic variants could have a cis-regulatory effect on SEMA3C expression, making a contribution to dyslexia susceptibility in this family.

Greater reading gain following intervention is associated with low magnetic resonance spectroscopy derived concentrations in the anterior cingulate cortex in children with dyslexia.

BACKGROUND/OBJECTIVE: The "neural noise" hypothesis suggests that individuals with dyslexia have high glutamate concentrations associated with their reading challenges. Different reading intervention programs have showed low GLX (a combined measure for glutamine and glutamate obtained with in vivo magnetic resonance spectroscopy) in association with reading improvement. Several studies demonstrated improved reading and increased activation in the anterior cingulate cortex following an-executive-function (EF)-based reading intervention. The goals of the current study are two-fold: 1) to determine if the effect of the EF-based reading program extends also to the metabolite concentrations and in particular, on the GLX concentrations in the anterior cingulate cortex; 2) to expand the neural noise hypothesis in dyslexia also to neural networks supporting additional parts of the reading networks, i.e. in specific regions related to executive function skills. METHODS: Children with dyslexia and typical readers were trained on the EF-based reading program. Reading ability was assessed before and after training while spectroscopy data was obtained at the end of the program. The association between change in reading scores following intervention and GLX concentrations was examined. RESULTS: Greater "gains" in word reading were associated with low GLX, Glu, Cr, and NAA concentrations for children with dyslexia compared to typical readers. CONCLUSIONS: These results suggest that the improvement reported following the EF-based reading intervention program also involved a low GLX concentration, as well as additional metabolites previously associated with better reading ability (Glx, Cr, NAA) which may point at the decreased neural noise, especially in the anterior cingulate cortex, as a possible mechanism for the effect of this program.

Functional analyses of STIM1 mutations reveal a common pathomechanism for tubular aggregate myopathy and Stormorken syndrome.

Tubular aggregate myopathy (TAM) is a progressive disorder characterized by muscle weakness, cramps, and myalgia. TAM clinically overlaps with Stormorken syndrome (STRMK), combining TAM with miosis, thrombocytopenia, hyposplenism, ichthyosis, short stature, and dyslexia. TAM and STRMK arise from gain-of-function mutations in STIM1 (stromal interaction molecule 1) or ORAI1, both encoding key regulators of Ca2+ homeostasis, and mutations in either gene result in excessive extracellular Ca2+ entry. The pathomechanistic similarities and differences between TAM and STRMK are only partially understood. Here we provide functional in vitro experiments demonstrating that STIM1 harboring the TAM D84G or the STRMK R304W mutation similarly cluster and exert a dominant effect on the wild-type protein. Both mutants recruit ORAI1 to the clusters, increase cytosolic Ca2+ levels, promote major nuclear import of the Ca2+ -dependent transcription factor NFAT (nuclear factor of activated T cells), and trigger the formation of circular membrane stacks. In conclusion, the analyzed TAM and STRMK mutations have a comparable impact on STIM1 protein function and downstream effects of excessive Ca2+ entry, highlighting that TAM and STRMK involve a common pathomechanism.

Association Between Resting-State Functional Connectivity and Reading in Two Writing Systems in Japanese Children With and Without Developmental Dyslexia.

Introduction: Japanese is unique, as it features two distinct writing systems that share the same sound and meaning: syllabic Hiragana and logographic Kanji scripts. Acquired reading difficulties in Hiragana and Kanji have been examined in older patients with brain lesions. However, the precise mechanisms underlying deficits in developmental dyslexia (DD) remain unclear. Materials and Methods: The neural signatures of Japanese children with DD were examined by using resting-state functional magnetic resonance imaging. We examined 22 dyslexic and 46 typically developing (TD) children, aged 7-14 years. Results: Reading performance in each writing system was correlated with neural connectivity in TD children. In contrast, in children with DD, weak associations between neural connectivity and reading performance were observed. In TD children, Hiragana-reading fluency was positively correlated with the left fusiform gyrus network. No significant correlations between Hiragana fluency and neural connectivity were observed in children with DD. Correspondingly, there were fewer correlations between Kanji accuracy and strength of reading-related connectivity in children with DD, whereas positive correlations with the bilateral fronto-parietal network and negative correlations with the left fusiform network were found in TD children. Discussion: These data suggest that positive and negative coupling with neural connectivity is associated with developing Japanese reading skills. Further, different neural connectivity correlations between Hiragana fluency and Kanji accuracy were detected in TD children but less in children with DD. Conclusion: The two writing systems may exert differential effects and deficits on reading in healthy children and in children with DD, respectively.

Dyslexia Candidate Gene and Ciliary Gene Expression Dynamics During Human Neuronal Differentiation.

Developmental dyslexia (DD) is a neurodevelopmental condition with complex genetic mechanisms. A number of candidate genes have been identified, some of which are linked to neuronal development and migration and to ciliary functions. However, expression and regulation of these genes in human brain development and neuronal differentiation remain uncharted. Here, we used human long-term self-renewing neuroepithelial stem (lt-NES, here termed NES) cells derived from human induced pluripotent stem cells to study neuronal differentiation in vitro. We characterized gene expression changes during differentiation by using RNA sequencing and validated dynamics for selected genes by qRT-PCR. Interestingly, we found that genes related to cilia were significantly enriched among upregulated genes during differentiation, including genes linked to ciliopathies with neurodevelopmental phenotypes. We confirmed the presence of primary cilia throughout neuronal differentiation. Focusing on dyslexia candidate genes, 33 out of 50 DD candidate genes were detected in NES cells by RNA sequencing, and seven candidate genes were upregulated during differentiation to neurons, including DYX1C1 (DNAAF4), a highly replicated DD candidate gene. Our results suggest a role of ciliary genes in differentiating neuronal cells and show that NES cells provide a relevant human neuronal model to study ciliary and DD candidate genes.

Saliva cortisol, melatonin levels and circadian rhythm alterations in Chinese primary school children with dyslexia.

Cortisol is the main end product of hypothalamic-pituitary-adrenal gland (HPA axis), and melatonin (MT) has a regulating effect on HPA axis, and both are closely related to individual behavior and cognitive function. We aimed to evaluate cortisol and MT roles on children dyslexia in this study.A total of 72 dyslexic children and 72 controls were recruited in this study. Saliva samples were collected in the morning, afternoon, and night, respectively. The levels of saliva cortisol and MT were measured by enzyme-linked immunosorbent assay method. Differences of cortisol and MT levels between dyslexic and normal children were compared, and the variation trend was also analyzed by dynamic monitoring in 3 time points.The levels of salivary cortisol and MT in children with dyslexia were all lower than those in normal children whether in the morning (7:30-8:30 AM ), at afternoon (15:30-16:30 PM ) or at night (21:30-22:30 PM ) (all P < .001). Compared with normal children, the circadian rhythm variations of salivary cortisol and MT in dyslexic children disappeared and became disordered. The salivary cortisol and MT levels in children with dyslexia were declined throughout the day; and the circadian rhythm was disordered or disappeared.The results suggest that cortisol and MT levels and their circadian rhythm may affect children dyslexia, but the mechanisms need further exploration.

Dyslexia associated functional variants in Europeans are not associated with dyslexia in Chinese.

Genome-wide association studies (GWAS) of developmental dyslexia (DD) often used European samples and identified only a handful associations with moderate or weak effects. This study aims to identify DD functional variants by integrating the GWAS associations with tissue-specific functional data and test the variants in a Chinese DD study cohort named READ. We colocalized associations from nine DD related GWAS with expression quantitative trait loci (eQTL) derived from brain tissues and identified two eSNPs rs349045 and rs201605. Both eSNPs had supportive evidence of chromatin interactions observed in human hippocampus tissues and their respective target genes ZNF45 and DNAH9 both had lower expression in brain tissues in schizophrenia patients than controls. In contrast, an eSNP rs4234898 previously identified based on eQTL from the lymphoblastic cell lines of dyslexic children had no chromatin interaction with its target gene SLC2A3 in hippocampus tissues and SLC2A3 expressed higher in the schizophrenia patients than controls. We genotyped the three eSNPs in the READ cohort of 372 cases and 354 controls and discovered only weak associations in rs201605 and rs4234898 with three DD symptoms (p < .05). The lack of associations could be due to low power in READ but could also implicate different etiology of DD in Chinese.

Effects of psychosocial stress on the hormonal and affective response in children with dyslexia.

INTRODUCTION: Research on stress and dyslexia has mainly focused on chronic and contextual stress caused by the school environment. Our goal was to test individual differences in the hypothalamic-pituitary-adrenal (HPA) axis reactivity of dyslexic and non-dyslexic children and the related emotional manifestations associated with exposure to a psychosocial stressor. METHODS: Eighty-one children (11-14 years old; 38 dyslexic) were exposed to the Trier Social Stress Test adapted to children or to a control condition. The salivary cortisol response, anxiety, and mood were measured before and after the stress. RESULTS: Dyslexic children did not show the expected cortisol response, as the highest percentage of children who were non-reactive to stress was found in this group. Cortisol reactivity to stress was related to higher levels of anxiety and lower positive affect in the non-dyslexic children. CONCLUSION: These results suggest a pattern of hypo-activation of the HPA axis to psychosocial stress in children with dyslexia.

The dyslexia susceptibility KIAA0319 gene shows a specific expression pattern during zebrafish development supporting a role beyond neuronal migration.

Dyslexia is a common neurodevelopmental disorder caused by a significant genetic component. The KIAA0319 gene is one of the most robust dyslexia susceptibility factors but its function remains poorly understood. Initial RNA-interference studies in rats suggested a role in neuronal migration whereas subsequent work with double knock-out mouse models for both Kiaa0319 and its paralogue Kiaa0319-like reported effects in the auditory system but not in neuronal migration. To further understand the role of KIAA0319 during neurodevelopment, we carried out an expression study of its zebrafish orthologue at different embryonic stages. We used different approaches including RNAscope in situ hybridization combined with light-sheet microscopy. The results show particularly high expression during the first few hours of development. Later, expression becomes localized in well-defined structures. In addition to high expression in the brain, we report for the first time expression in the eyes and the notochord. Surprisingly, kiaa0319-like, which generally shows a similar expression pattern to kiaa0319, was not expressed in the notochord suggesting a distinct role for kiaa0319 in this structure. This observation was supported by the identification of notochord enhancers enriched upstream of the KIAA0319 transcription start site, in both zebrafish and humans. This study supports a developmental role for KIAA0319 in the brain as well as in other developing structures, particularly in the notochord which, is key for establishing body patterning in vertebrates.

CRAC channels and disease - From human CRAC channelopathies and animal models to novel drugs.

Ca2+ release-activated Ca2+ (CRAC) channels are intimately linked with health and disease. The gene encoding the CRAC channel, ORAI1, was discovered in part by genetic analysis of patients with abolished CRAC channel function. And patients with autosomal recessive loss-of-function (LOF) mutations in ORAI1 and its activator stromal interaction molecule 1 (STIM1) that abolish CRAC channel function and store-operated Ca2+ entry (SOCE) define essential functions of CRAC channels in health and disease. Conversely, gain-of-function (GOF) mutations in ORAI1 and STIM1 are associated with tubular aggregate myopathy (TAM) and Stormorken syndrome due to constitutive CRAC channel activation. In addition, genetically engineered animal models of ORAI and STIM function have provided important insights into the physiological and pathophysiological roles of CRAC channels in cell types and organs beyond those affected in human patients. The picture emerging from this body of work shows CRAC channels as important regulators of cell function in many tissues, and as potential drug targets for the treatment of autoimmune and inflammatory disorders.

Dyslexia and age related effects in the neurometabolites concentration in the visual and temporo-parietal cortex.

Several etiological theories, in particular neuronal noise and impaired auditory sampling, predicted neurotransmission deficits in dyslexia. Neurometabolites also affect white matter microstructure, where abnormalities were previously reported in dyslexia. However findings from only few magnetic resonance spectroscopy studies using diverse age groups, different brain regions, data processing and reference scaling are inconsistent. We used MEGA-PRESS single-voxel spectroscopy in two ROIs: left temporo-parietal and occipital cortex in 36 adults and 52 children, where half in each group had dyslexia. Dyslexics, on average, had significantly lower total N-acetylaspartate (tNAA) than controls in the occipital cortex. Adults compared to children were characterized by higher choline and creatine in both areas, higher tNAA in left temporo-parietal and lower glutamate in the visual cortex, reflecting maturational changes in cortical microstructure and metabolism. Although the current findings do not support the proposed etiological theories of dyslexia, they show, for the first time, that tNAA, considered to be a neurochemical correlate of white matter integrity, is deficient in the visual cortex in both children and adults with dyslexia. They also point that several neurotransmitters, including ones previously used as reference, change with age.

Gain-of-function mutations in STIM1 and ORAI1 causing tubular aggregate myopathy and Stormorken syndrome.

Calcium (Ca2+) is a key regulator for a large number of cellular functions in all kinds of cells, and small disturbances of Ca2+ homeostasis can severely compromise normal physiology in various tissues and organs. A major mechanism controlling Ca2+ homeostasis is store-operated Ca2+ entry (SOCE), which relies on the concerted action of the reticular Ca2+ sensor STIM1 and the plasma membrane Ca2+ channel ORAI1. Gain-of-function mutations in the respective genes induce excessive Ca2+ entry, and cause tubular aggregate myopathy (TAM) and Stormorken syndrome. Both disorders are part of a clinical continuum and involve muscle weakness and additional variably pronounced features including miosis, thrombocytopenia, hyposplenism, ichthyosis, dyslexia, and short stature. Mutations in the reticular Ca2+ buffer calsequestrin (CASQ1) have moreover been associated with the mild end of the TAM/Stormorken syndrome spectrum. Here we review the clinical and histological characteristics of both disorders, provide an overview on the genetic causes, and thereby focus on the pathomechanisms leading to muscle dysfunction and the multi-systemic phenotype of tubular aggregate myopathy and Stormorken syndrome.

A dual mechanism promotes switching of the Stormorken STIM1 R304W mutant into the activated state.

STIM1 and Orai1 are key components of the Ca2+-release activated Ca2+ (CRAC) current. Orai1, which represents the subunit forming the CRAC channel complex, is activated by the ER resident Ca2+ sensor STIM1. The genetically inherited Stormorken syndrome disease has been associated with the STIM1 single point R304W mutant. The resulting constitutive activation of Orai1 mainly involves the CRAC-activating domain CAD/SOAR of STIM1, the exposure of which is regulated by the molecular interplay between three cytosolic STIM1 coiled-coil (CC) domains. Here we present a dual mechanism by which STIM1 R304W attains the pathophysiological, constitutive activity eliciting the Stormorken syndrome. The R304W mutation induces a helical elongation within the CC1 domain, which together with an increased CC1 homomerization, destabilize the resting state of STIM1. This culminates, even in the absence of store depletion, in structural extension and CAD/SOAR exposure of STIM1 R304W leading to constitutive CRAC channel activation and Stormorken disease.

Familial history of reading difficulty is associated with diffused bilateral brain activation during reading and greater association with visual attention abilities.

Reading difficulty (RD; or dyslexia) is a heritable condition characterized by slow, inaccurate reading accompanied by executive dysfunction, specifically with respect to visual attention. The current study was designed to examine the effect of familial history of RD on the relationship between reading and visual attention abilities in children with RD using a functional MRI reading task. Seventy-one children with RD participated in the study. Based on parental reports of the existence of RD in one or both of each child's parents, children with RD were divided into two groups: (1) those with a familial history of RD and (2) those without a familial history of RD. Reading and visual attention measures were collected from all participants. Functional MRI data during word reading was acquired in 30 participants of the entire cohort. Children with or without a familial history of RD demonstrated below-average reading and visual attention scores, with greater interaction between these measures in the group with a familial history of RD. Greater bilateral and diffused activation during word reading also were found in this group. We suggest that a familial history of RD is related to greater association between lower reading abilities and visual attention abilities. Parental history of RD therefore may be an important preschool screener (before reading age) to prompt early intervention focused on executive functions and reading-related skills.

ORAI1 Mutations with Distinct Channel Gating Defects in Tubular Aggregate Myopathy.

Calcium (Ca2+ ) is a physiological key factor, and the precise modulation of free cytosolic Ca2+ levels regulates multiple cellular functions. Store-operated Ca2+ entry (SOCE) is a major mechanism controlling Ca2+ homeostasis, and is mediated by the concerted activity of the Ca2+ sensor STIM1 and the Ca2+ channel ORAI1. Dominant gain-of-function mutations in STIM1 or ORAI1 cause tubular aggregate myopathy (TAM) or Stormorken syndrome, whereas recessive loss-of-function mutations are associated with immunodeficiency. Here, we report the identification and functional characterization of novel ORAI1 mutations in TAM patients. We assess basal activity and SOCE of the mutant ORAI1 channels, and we demonstrate that the G98S and V107M mutations generate constitutively permeable ORAI1 channels, whereas T184M alters the channel permeability only in the presence of STIM1. These data indicate a mutation-dependent pathomechanism and a genotype/phenotype correlation, as the ORAI1 mutations associated with the most severe symptoms induce the strongest functional cellular effect. Examination of the non-muscle features of our patients strongly suggests that TAM and Stormorken syndrome are spectra of the same disease. Overall, our results emphasize the importance of SOCE in skeletal muscle physiology, and provide new insights in the pathomechanisms involving aberrant Ca2+ homeostasis and leading to muscle dysfunction.

Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor X (RFX) transcription factors through X-box promoter motifs.

DYX1C1, DCDC2, and KIAA0319 are three of the most replicated dyslexia candidate genes (DCGs). Recently, these DCGs were implicated in functions at the cilium. Here, we investigate the regulation of these DCGs by Regulatory Factor X transcription factors (RFX TFs), a gene family known for transcriptionally regulating ciliary genes. We identify conserved X-box motifs in the promoter regions of DYX1C1, DCDC2, and KIAA0319 and demonstrate their functionality, as well as the ability to recruit RFX TFs using reporter gene and electrophoretic mobility shift assays. Furthermore, we uncover a complex regulation pattern between RFX1, RFX2, and RFX3 and their significant effect on modifying the endogenous expression of DYX1C1 and DCDC2 in a human retinal pigmented epithelial cell line immortalized with hTERT (hTERT-RPE1). In addition, induction of ciliogenesis increases the expression of RFX TFs and DCGs. At the protein level, we show that endogenous DYX1C1 localizes to the base of the cilium, whereas DCDC2 localizes along the entire axoneme of the cilium, thereby validating earlier localization studies using overexpression models. Our results corroborate the emerging role of DCGs in ciliary function and characterize functional noncoding elements, X-box promoter motifs, in DCG promoter regions, which thus can be targeted for mutation screening in dyslexia and ciliopathies associated with these genes.-Tammimies, K., Bieder, A., Lauter, G., Sugiaman-Trapman, D., Torchet, R., Hokkanen, M.-E., Burghoorn, J., Castrén, E., Kere, J., Tapia-Páez, I., Swoboda, P. Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor (RF) X transcription factors through X-box promoter motifs.

Calidad de vida a los 6 meses tras un ictus / Quality of life 6 months after a stroke

Objetivo. Describir la calidad de vida (CV) de los pacientes a los 6 meses de evolución del ictus y su relación con variables sociodemográficas, clínicas y funcionales. Material y métodos. Estudio multicéntrico de cohortes longitudinal (n = 157). Los pacientes incluidos ingresaron en la fase subaguda tras un ictus en 2 Servicios de Rehabilitación. Se recogieron los siguientes datos a los 6 meses postictus: género, edad, riesgo social, comorbilidad, disfagia, afasia, estado cognitivo, depresión y grado de discapacidad evaluado mediante el índice de Barthel modificado. Se evaluó la influencia de estas variables en la CV, para lo que se empleó la escala específica de calidad de vida para el ictus ECVI-38. Resultados. La media de edad fue de 70,93 ± 11,85 años; fue significativamente superior en las mujeres. El paciente tipo presentó una elevada comorbilidad, un bajo riesgo social y dependencia moderada. La puntuación media total de la escala ECVI-38 fue de 35,30 ± 16,17 y los dominios más afectados los referentes a las actividades comunes y básicas de la vida diaria. Las variables que más se relacionan con la CV fueron el género, la afasia, la disfagia, la depresión, el déficit cognitivo y el estado funcional. El dolor de elevada intensidad estuvo presente en un 21% de los pacientes. Conclusión. Son muy diversas las variables que influyen en la CV del paciente con ictus que se deben considerar, para su potencial abordaje, en la planificación de las intervenciones rehabilitadoras (AU)

Objective. To describe quality of life (QoL) in patients at 6 months poststroke and its relationship with sociodemographic, clinical and functional characteristics. Material and method. This multicenter longitudinal cohort study (n = 157) included patients from 2 hospital rehabilitation services who were admitted for stroke in the subacute phase. The following data were gathered at 6 months poststroke: gender, age, social risk, comorbidity, dysphagia, aphasia, cognitive status, depression, and disability measured by the modified Barthel Index. The influence of these variables on QoL was evaluated using the stroke-specific quality of life scale, ECVI-38. Results. The mean age was 70.93 ± 11.85 years and was significantly higher in women. Most of the patients had high comorbidity, low social risk and moderate dependence. The mean total score on the ECVI-38 scale was 35.30 ± 16.17 and the most affected domains were those concerning common and basic activities of daily living. The variables associated with QoL were gender, aphasia, dysphagia, depression, cognitive impairment, and functional status. High-intensity pain was present in 21% of patients. Conclusion. Numerous variables influence QoL in patients with stroke and should be considered in the planning of rehabilitation interventions (AU)

Neurociencia y Educación: ¿podemos ir de la investigación básica a su aplicación? Un posible marco de referencia desde la investigación en dislexia1 / Neurociencia y Educación: ¿podemos ir de la investigación básica a su aplicación? Un posible marco de referencia desde la investigación en dislexia

La neurociencia podría transformar la educación, pues proporciona nuevos métodos para comprender el aprendizaje y el desarrollo cognitivo, sus mecanismos causales y una forma empírica de evaluar la eficacia de diferentes pedagogías. No obstante, éste sería un objetivo a largo plazo. Desde la neurociencia educativa se debería empezar estudiando cómo los sistemas cognitivos se construyen sobre los sensoriales a lo largo del desarrollo. Aquí me centraré en el lenguaje. Pequeñas diferencias individuales iniciales en una función sensorial, por ejemplo la auditiva, podrían ser el origen de notables diferencias individuales en el desarrollo lingüístico. La neurociencia podría proporcionar una comprensión detallada de los mecanismos causales del desarrollo que vinculan la audición, el desarrollo fonológico y el desarrollo de la alfabetización. Este tipo de investigación neurocientífica básica podría orientar al campo de la educación y la pedagogía explorando los efectos que sobre estos mecanismos ejercen diferentes contextos pedagógicos y de aprendizaje

Neuroscience has the potential to transform education because it provides novel methods for understanding human learning and cognitive development. It therefore offers deeper understanding of causal mechanisms in learning and an empirical approach to evaluating the efficacy of different pedagogies. However, this will be a long-term enterprise and there will be few immediate pay-offs. Here I set out one possible framework for linking basic research in neuroscience to pedagogical questions in education. I suggest that the developing field of educational neuroscience must first study how sensory systems build cognitive systems over developmental time. I focus on one cognitive system, language, the efficient functioning of which is critical for reading acquisition. Small initial differences in sensory function, for example auditory function, have the potential to cause large differences in linguistic performance over the learning trajectory. The tools offered by neuroscience can enable better understanding of the causal developmental mechanisms linking audition, phonological development and literacy development, in fine-grained detail. Following this basic research, neuroscience can then inform education and pedagogy by exploring the effects on these neural mechanisms of different learning contexts and pedagogies

Moderna investigación educativa en el síndrome de Down / No disponible

Down Syndrome Education International ha publicado 21 breves artículos que describen los modernos avances realizados en la investigación educativa sobre el síndrome de Down, y las cuestiones que aún están por resolver. Ofrecemos los cinco primeros sobre lenguaje de signos, memoria operativa verbal, aprendizaje de la lectura, lenguaje y habla, y perfil de puntos fuertes y débiles

Down Syndrome Education International has edited short articles which describe modern advances in the field of educational research in Down syndrome, and face to the questions that remain unresolved. We offer the first five articles dealing on sign language, verbal working memory, reading as a tool to improve language, communication and speech, and the profile of strengths and weaknesses