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AbstractImpairment of motor learning skills in developmental coordination disorder (DCD) has been reported in several studies. Some hypotheses on neural mechanisms of motor learning deficits in DCD have emerged but, to date, brain‐imaging investigations are scarce. The aim of the present study is to assess possible changes in communication between brain areas during practice of a new bimanual coordination task in teenagers with DCD (n = 10) compared to matched controls (n = 10). Accuracy, stability and number of mirror movements were computed as behavioural variables. Neural variables were assessed by electroencephalographic coherence analyses of intra‐hemispheric and inter‐hemispheric fronto‐central electrodes. In both groups, accuracy of the new coordination increased concomitantly with right intra‐hemispheric fronto‐central coherence. Compared to typically developing teenagers, DCD teenagers presented learning difficulties expressed by less stability, no stabilization of the new coordination and a greater number of mirror movements despite practice. These measures correlated with reduced inter‐hemispheric communication, even after practice of the new coordination. For the first time, these findings provide neuro‐imaging evidence of a kind of inter‐hemispheric 'disconnection' related to altered inhibition of mirror movements during motor learning in DCD.

AbstractDevelopmental dyslexia (DD) and developmental coordination disorder (DCD) are distinct diagnostic disorders. However, they also frequently co-occur and may share a common etiology. It was proposed conceptually a neural network framework that explains differences and commonalities between DD and DCD through impairments of distinct or intertwined cortico-subcortical connectivity pathways. The present study addressed this issue by exploring intrinsic cortico-striatal and cortico-cerebellar functional connectivity in a large (n = 136) resting-state fMRI cohort study of 8–12-year-old children with typical development and with DD and/or DCD. We delineated a set of cortico-subcortical functional circuits believed to be associated with the brain's main functions (visual, somatomotor, dorsal attention, ventral attention, limbic, frontoparietal control, and default-mode). Next, we assessed, using general linear and multiple kernel models, whether and which circuits distinguished between the groups. Findings revealed that somatomotor cortico-cerebellar and frontoparietal cortico-striatal circuits are affected in the presence of DCD, including abnormalities in cortico-cerebellar connections targeting motor-related regions and cortico-striatal connections mapping onto posterior parietal cortex. Thus, DCD but not DD may be considered as an impairment of cortico-subcortical functional circuits.

AbstractRhythmic abilities are impaired in developmental coordination disorder (DCD) but learning deficit of procedural skills implying temporal sequence is still unclear. Current contradictory results suggest that procedural learning deficits in DCD highly depend on learning conditions. The present study proposes to test the role of sensory modality of stimulations (visual or auditory) on synchronization, learning, and retention of temporal verbal sequences in children with and without DCD. We postulated a deficit in learning particularly with auditory stimulations, in association with atypical cortical thickness of three regions of interesting: sensorimotor, frontal and parietal regions. Thirty children with and without DCD (a) performed a synchronization task to a regular temporal sequence and (b) practiced and recalled a novel non‐regular temporal sequences with auditory and visual modalities. They also had a magnetic resonance imaging to measure their cortical thickness. Results suggested that children with DCD presented a general deficit in synchronization of a regular temporal verbal sequence irrespective of the sensory modality, but a specific deficit in learning and retention of auditory non‐regular verbal temporal sequence. Stability of audio‐verbal synchronization during practice correlated with cortical thickness of the sensorimotor cortex. For the first time, our results suggest that synchronization deficits in DCD are not limited to manual tasks. This deficit persists despite repeated exposition and practice of an auditory temporal sequence, which suggests a possible alteration in audio‐verbal coupling in DCD. On the contrary, control of temporal parameters with visual stimuli seems to be less affected, which opens perspectives for clinical practice.

11 pages, 6 figures.- PMID: 20832341 [PubMed]PMCID: PMC2946444 [Available on 2011/9/1] ; Tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3) functions downstream of multiple TNF receptors and receptors that induce interferon-alpha (IFN-alpha), IFN-beta, and IFN-lambda production, including Toll-like receptor 3 (TLR3), which is deficient in some patients with herpes simplex virus-1 encephalitis (HSE). Mice lacking TRAF3 die in the neonatal period, preventing direct investigation of the role of TRAF3 in immune responses and host defenses in vivo. Here, we report autosomal dominant, human TRAF3 deficiency in a young adult with a history of HSE in childhood. The TRAF3 mutant allele is loss-of-expression, loss-of-function, dominant-negative and associated with impaired, but not abolished, TRAF3-dependent responses upon stimulation of both TNF receptors and receptors that induce IFN production. TRAF3 deficiency is associated with a clinical phenotype limited to HSE resulting from the impairment of TLR3-dependent induction of IFN. Thus, TLR3-mediated immunity against primary infection by HSV-1 in the central nervous system is critically dependent on TRAF3 ; This study was supported by the AXA Research fund, the Schlumberger Foundation, the BNP-Paribas Foundation, the Groupement d'Intérêt Scientifique Maladies Rares, the Action Concertée Incitative de Microbiologie, the March of Dimes, the Agence Nationale pour la Recherche, the Eppley Foundation, the National Institute of Allergy and Infectious Diseases grant number 1R01AI088364, the Thrasher Research Fund, the Jeffrey Modell Foundation and Talecris Biotherapeutics, the St. Giles Foundation, the Rockefeller University Center for Clinical and Translational Science grant number 5UL1RR024143, and the Rockefeller University. P.R. is supported by a European Union FP6 grant. J.-L.C. was an international scholar of the Howard Hughes Medical Institute until 2008. ; Peer reviewed

Funding: AG and TFMA were supported by the Munich Cluster for Systems Neurology (SyNergy). AG 535 was supported by Fondazione Umberto Veronesi. SP is a Royal Society University Research fellow. BMM, CF, BSP and SEF are supported by the Max Planck Society. AW, BM and HK were funded by the Fraunhofer Society and the Max Planck Society within the 'Pakt für Forschung und Innovation'. HK was also supported by LIFE – Leipzig Research Center for Civilization Diseases funded by means of the European Union; the European Regional Development Fund (ERDF); and the Free State of Saxony within the excellence initiative. FR is supported by Agence Nationale de la Recherche (ANR-06-NEURO-019-01, ANR-17-EURE-542 0017 IEC, ANR-10-IDEX-0001-02 PSL, ANR-11-BSV4-014-01), European Commission (LSHM-CT-2005-018696). TFMA was supported by the BMBF through the DIFUTURE consortium of the Medical Informatics Initiative Germany (grant 01ZZ1804A) and by the European Union's Horizon 2020 Research and Innovation Programme (grant MultipleMS, EU RIA 733161). ; Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40–60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10−6) enrichment of associations at the gene level, for LOC388780 (20p13; uncharacterized gene), and for VEPH1 (3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20–25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (at pT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase; p = 8 × 10−13), bipolar disorder (1.53[1.44; 1.63]; p = 1 × 10−43), schizophrenia (1.36[1.28; 1.45]; p = 4 × 10−22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30]; p = 3 × 10−12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96]; p = 5 × 10−4), educational attainment (0.86[0.82; 0.91]; p = 2 × 10−7), and intelligence (0.72[0.68; 0.76]; p = 9 × 10−29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence. ; Publisher PDF ; Peer reviewed