Functional rescue in an Angelman syndrome model following treatment with lentivector transduced hematopoietic stem cells.

Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by impaired communication skills, ataxia, motor and balance deficits, intellectual disabilities, and seizures. The genetic cause of AS is the neuronal loss of UBE3A expression in the brain. A novel approach, described here, is a stem cell gene therapy which uses lentivector-transduced hematopoietic stem and progenitor cells to deliver functional UBE3A to affected cells. We have demonstrated both the prevention and reversal of AS phenotypes upon transplantation and engraftment of human CD34+ cells transduced with a Ube3a lentivector in a novel immunodeficient Ube3amat-/pat+ IL2rg-/y mouse model of AS. A significant improvement in motor and cognitive behavioral assays as well as normalized delta power measured by electroencephalogram was observed in neonates and adults transplanted with the gene modified cells. Human hematopoietic profiles observed in the lymphoid organs by detection of human immune cells were normal. Expression of UBE3A was detected in the brains of the adult treatment group following immunohistochemical staining illustrating engraftment of the gene-modified cells expressing UBE3A in the brain. As demonstrated with our data, this stem cell gene therapy approach offers a promising treatment strategy for AS, not requiring a critical treatment window.

Acute motor deficit and subsequent remyelination-associated recovery following internal capsule demyelination in mice.

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by accumulated motor disability. However, whether remyelination promotes motor recovery following demyelinating injury remains unclear. Damage to the internal capsule (IC) is known to result in motor impairment in multiple sclerosis and stroke. Here, we induced focal IC demyelination in mice by lysophosphatidylcholine (LPC) injection, and examined its effect on motor behavior. We also compared the effect of LPC-induced IC damage to that produced by endothelin-1 (ET1), a potent vasoconstrictor used in experimental stroke lesions. We found that LPC or ET1 injections induced asymmetric motor deficit at 7 days post-lesion (dpl), and that both lesion types displayed increased microglia/macrophage density, myelin loss, and axonal dystrophy. The motor deficit and lesion pathology remained in ET1-injected mice at 28 dpl. In contrast, LPC-injected mice regained motor function by 28 dpl, with corresponding reduction in activated microglia/macrophage density, and recovery of myelin staining and axonal integrity in lesions. These results suggest that LPC-induced IC demyelination results in acute motor deficit and subsequent recovery through remyelination, and may be used to complement future drug screens to identify drugs for promoting remyelination.

Pathogenic variants in TNRC6B cause a genetic disorder characterised by developmental delay/intellectual disability and a spectrum of neurobehavioural phenotypes including autism and ADHD.

BACKGROUND: Rare variants in hundreds of genes have been implicated in developmental delay (DD), intellectual disability (ID) and neurobehavioural phenotypes. TNRC6B encodes a protein important for RNA silencing. Heterozygous truncating variants have been reported in three patients from large cohorts with autism, but no full phenotypic characterisation was described. METHODS: Clinical and molecular characterisation was performed on 17 patients with TNRC6B variants. Clinical data were obtained by retrospective chart review, parent interviews, direct patient interaction with providers and formal neuropsychological evaluation. RESULTS: Clinical findings included DD/ID (17/17) (speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17) of subjects), autism or autistic traits (13/17), attention deficit and hyperactivity disorder (ADHD) (11/17), other behavioural problems (7/17) and musculoskeletal findings (12/17). Other congenital malformations or clinical findings were occasionally documented. The majority of patients exhibited some dysmorphic features but no recognisable gestalt was identified. 17 heterozygous TNRC6B variants were identified in 12 male and five female unrelated subjects by exome sequencing (14), a targeted panel (2) and a chromosomal microarray (1). The variants were nonsense (7), frameshift (5), splice site (2), intragenic deletions (2) and missense (1). CONCLUSIONS: Variants in TNRC6B cause a novel genetic disorder characterised by recurrent neurocognitive and behavioural phenotypes featuring DD/ID, autism, ADHD and other behavioural abnormalities. Our data highly suggest that haploinsufficiency is the most likely pathogenic mechanism. TNRC6B should be added to the growing list of genes of the RNA-induced silencing complex associated with ID/DD, autism and ADHD.

Differences in White Matter Microstructure Among Children With Developmental Coordination Disorder.

Importance: Developmental coordination disorder (DCD) is a motor impairment that significantly interferes with activities of daily living. Little is known about the cause of DCD and how it develops, making it difficult to understand why children with DCD struggle in learning motor skills and to determine the best intervention to optimize function. Objective: To characterize white matter differences using diffusion tensor imaging in children with and without DCD. Design, Setting, and Participants: This cross-sectional study collected diffusion tensor imaging data at BC Children's Hospital Research Institute in Vancouver, British Columbia, Canada, from September 2014 to January 2017. Using a sample of convenience, children with DCD and children without DCD aged 8 to 12 years underwent magnetic resonance imaging. Data analysis was conducted from January 2017 to January 2020. Main Outcomes and Measures: The main outcome measures were diffusion parameters, including fractional anisotropy and mean, axial, and radial diffusivity, which are thought to provide an indirect measure of white matter microstructure. Tract-based spatial statistics, a voxelwise statistical analysis of diffusion parameters, were conducted using a 2-group comparison design matrix with age and attention as covariates. Results: Thirty children without DCD (mean [SD] age, 9.9 [1.4] years; 21 [70%] boys) and 31 children with DCD (mean [SD] age, 10.1 [1.2] years; 26 [84%] boys) were included in the study. Compared with children without DCD, children with DCD were characterized by significantly lower fractional anisotropy and axial diffusivity in regions of white matter pathways associated with motor and sensorimotor processing, including the corticospinal tract (fractional anisotropy: mean [SD], 0.54 [0.03] vs 0.51 [0.03]; P < .001; axial diffusivity: mean [SD], 0.13 [0.98] vs 0.12 [0.46]; P = .01), posterior thalamic radiation at the retrolenticular part of the internal capsule (axial diffusivity: mean [SD], 0.14 [0.57] vs 0.14 [0.44]; P = .01), and cerebellar pathways (eg, superior cerebellar peduncle, fractional anisotropy: mean [SD], 0.49 [0.05] vs 0.46 [0.03]; P = .03; axial diffusivity: mean [SD], 0.14 [0.66] vs 0.14 [0.63]; P = .009). There were no significant differences in mean diffusivity and radial diffusivity between children with and without DCD. Conclusions and Relevance: These findings suggest that children with DCD show significant brain differences in motor and sensorimotor white matter pathways compared with children without DCD. The pattern of diffusion parameters in children with DCD suggests that axonal development may be disrupted in this neurodevelopmental disorder.

Using a mouse model to gain insights into developmental coordination disorder.

Motor impairments are a common feature of many neurodevelopmental disorders; in fact, over 50% of children with Attentional Deficit Hyperactivity Disorder or Autism Spectrum Disorder may have a co-occurring diagnosis of developmental coordination disorder (DCD). DCD is a neurodevelopmental disorder of unknown etiology that affects motor coordination and learning, significantly impacting a child's ability to carry out everyday activities. Animal models play an important role in scientific investigation of behaviour and the mechanisms and processes that are involved in control of motor actions. The purpose of this paper is to present an approach in the mouse directed to gain behavioral and genetic insights into DCD that is designed with high face validity, construct validity and predictive validity. Pre-clinical and clinical expertise is used to establish a set of scientific criteria that the model will meet in order to investigate the potential underlying causes of DCD.

Very preterm children at risk for developmental coordination disorder have brain alterations in motor areas.

AIM: Brain alterations in very preterm children at risk for developmental coordination disorder were investigated. METHODS: Infants born very preterm with gestation age <30 weeks or birthweight <1250 g were recruited from Royal Women's Hospital Melbourne from 2001 to 2003. Volumetric imaging was performed at term equivalent age; at seven years, volumetric imaging and diffusion tensor imaging were performed. At seven years, 53 of 162 children without cerebral palsy had scores ≤16th percentile on the Movement Assessment Battery for Children-Second Edition and were considered at risk for developmental coordination disorder. RESULTS: At term equivalent age, smaller brain volumes were found for total brain tissue, cortical grey matter, cerebellum, caudate accumbens, pallidum and thalamus in children at risk for developmental coordination disorder (p < 0.05); similar patterns were present at seven years. There was no evidence for catch-up brain growth in at-risk children. At seven years, at-risk children displayed altered microstructural organisation in many white matter tracts (p < 0.05). CONCLUSION: Infants born very preterm at risk for developmental coordination disorder displayed smaller brain volumes at term equivalent age and seven years, and altered white matter microstructure at seven years, particularly in motor areas. There was no catch-up growth from infancy to seven years.

Astroglial-targeted expression of the fragile X CGG repeat premutation in mice yields RAN translation, motor deficits and possible evidence for cell-to-cell propagation of FXTAS pathology.

The fragile X premutation is a CGG trinucleotide repeat expansion between 55 and 200 repeats in the 5'-untranslated region of the fragile X mental retardation 1 (FMR1) gene. Human carriers of the premutation allele are at risk of developing the late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS). Characteristic neuropathology associated with FXTAS includes intranuclear inclusions in neurons and astroglia. Previous studies recapitulated these histopathological features in neurons in a knock-in mouse model, but without significant astroglial pathology. To determine the role of astroglia in FXTAS, we generated a transgenic mouse line (Gfa2-CGG99-eGFP) that selectively expresses a 99-CGG repeat expansion linked to an enhanced green fluorescent protein (eGFP) reporter in astroglia throughout the brain, including cerebellar Bergmann glia. Behaviorally these mice displayed impaired motor performance on the ladder-rung test, but paradoxically better performance on the rotarod. Immunocytochemical analysis revealed that CGG99-eGFP co-localized with GFAP and S-100ß, but not with NeuN, Iba1, or MBP, indicating that CGG99-eGFP expression is specific to astroglia. Ubiquitin-positive intranuclear inclusions were found in eGFP-expressing glia throughout the brain. In addition, intracytoplasmic ubiquitin-positive inclusions were found outside the nucleus in distal astrocyte processes. Intriguingly, intranuclear inclusions, in the absence of eGFP mRNA and eGFP fluorescence, were present in neurons of the hypothalamus and neocortex. Furthermore, intranuclear inclusions in both neurons and astrocytes displayed immunofluorescent labeling for the polyglycine peptide FMRpolyG, implicating FMRpolyG in the pathology found in Gfa2-CGG99 mice. Considered together, these results show that Gfa2-CGG99 expression in mice is sufficient to induce key features of FXTAS pathology, including formation of intranuclear inclusions, translation of FMRpolyG, and deficits in motor function.

Adaptive behavior impaired in children with low-grade glioma.

BACKGROUND: Adaptive behavior, i.e., the performance on daily activities required for personal and social independence, is essential to estimate in children with low-grade glioma (LGG) since most of them are long-term survivors. Our aim was to investigate adaptive behavior in children with LGG. METHODS: In a cross-sectional study, adaptive behavior was assessed using the paper pencil version of the Parent Form of the Vineland Adaptive Behavior Scales 2nd edition (VABS-II) testing communication, daily living skills, social skills, and motor skills. Scores of children with LGG, younger than 20 years, and diagnosed between 2004 and 2014 were compared with family controls. Correlations between clinical variables and adaptive behavior were explored. RESULTS: Fifty-six children with LGG (median age, 12.1 years; 52% male) and 46 controls (median age, 11.0 years; 43% male) were included in the analyses. Compared with controls, the LGG group was more impaired on total adaptive behavior, communication, and motor skills and in the subdomain gross motor skills (effect sizes d, 0.64-0.86, P < 0.003). Younger age at diagnosis (r = -0.357, P < 0.01) and chemotherapy (r = -0.342, P < 0.05) were associated with poorer motor skills. Residual disease was associated with poorer total adaptive behavior (r = -0.282, P < 0.05). No other significant correlations were found. CONCLUSION: At the group level, adaptive functioning of children with LGG is impaired compared with family controls. Regular structured monitoring of adaptive behavior is recommended to be able to define the needs for tailored rehabilitation in daily life at home as well as at school.

Assessing the potential of the qualitative trajectory calculus to detect gait pathologies: a case study of children with developmental coordination disorder.

The Qualitative Trajectory Calculus (QTC) is a qualitative spatio-temporal calculus for describing interactions between moving point objects. So far, it remained unclear whether QTC is useful for describing subtle differences, such as between the movements of different parts of a human body. We tested the applicability of QTC to detect differences in the gait patterns of children with or without Developmental Coordination Disorder (DCD). We found that using a combination of three markers (i.e. ankle, toe and trochanter), QTC can achieve a high classification accuracy (i.e. 83.3%) of classifying subjects correctly to either the DCD group or the control group.

Developmental coordination disorder: the impact on the family.

PURPOSE: Developmental coordination disorder (DCD) is a neurodevelopmental disorder with an estimated prevalence of 2-6% in school-aged children. Children with DCD score lower in multiple quality of life (QOL) domains. However, the effect of a child's DCD on their parents' and family's QOL has not previously been assessed in a UK population. We aimed to assess parental and family QOL within UK families containing at least one child aged 6-18 years who was diagnosed with DCD. METHODS: A mixed-methods study was designed, using an online questionnaire that incorporated the Family QOL Scale and the 12-Item Short Form Health Survey. RESULTS: The emotional and disability support domains of family QOL were markedly negatively affected by DCD, with lack of support by medical and educational professionals cited as a major source of stress. Parental mental health was also negatively affected. In many cases, the child's DCD impacted on parental work life, family social life and siblings' well-being. CONCLUSIONS: Having a child with DCD has a considerable impact on families. This needs to be recognised by healthcare and other professionals; otherwise, services and support may not be appropriately targeted and the negative sequelae of DCD may ripple beyond the individual with costly social and economic consequences.

White matter organization in developmental coordination disorder: A pilot study exploring the added value of constrained spherical deconvolution.

Previous studies of white matter organization in sensorimotor tracts in developmental coordination disorder (DCD) have adopted diffusion tensor imaging (DTI), a method unable to reconcile pathways with 'crossing fibres'. In response to limitations of the commonly adopted DTI approach, the present study employed a framework that can reconcile the 'crossing fibre' problem (i.e., constrained spherical deconvolution- CSD) to characterize white matter tissue organization of sensorimotor tracts in young adults with DCD. Participants were 19 healthy adults aged 18-46: 7 met diagnostic criteria for DCD (4 females) and 12 were controls (3 females). All underwent high angular diffusion MRI. After preprocessing, the left and right corticospinal tracts (CST) and superior longitudinal fasciculi (SLF) were delineated and all tracts were then generated using both CSD and DTI tractography respectively. Based on the CSD model, individuals with DCD demonstrated significantly decreased mean apparent fibre density (AFD) in the left SLF relative to controls (with large effect size, Cohen's d = 1.32) and a trend for decreased tract volume of the right SLF (with medium-large effect size, Cohen's d = 0.73). No differences in SLF microstructure were found between groups using DTI, nor were differences in CST microstructure observed across groups regardless of hemisphere or diffusion model. Our data are consistent with the view that motor impairment characteristic of DCD may be subserved by white matter abnormalities in sensorimotor tracts, specifically the left and right SLF. Our data further highlight the benefits of higher order diffusion MRI (e.g. CSD) relative to DTI for clarifying earlier inconsistencies in reports speaking to white matter organization in DCD, and its contribution to poor motor skill in DCD.

HTLV-1 infection-induced motor dysfunction, memory impairment, depression, and brain tissues oxidative damage in female BALB/c mice.

AIMS: The HTLV-1 infection is associated with a neuro-inflammatory disease. In the present study, the behavioral consequences and brain oxidative damages were evaluated in HTLV-1-infected BALB/c mice. MATERIAL AND METHODS: 20 female BALB/c mice were divided into two groups comprising control and HTLV-1-infected. The HTLV-1-infected group was inoculated with a 106 MT-2 HTLV-1-infected cell line. Two months later, the behavioral tests were conducted. Finally, oxidative stress was assessed in the cortex and hippocampus tissues. KEY FINDINGS: In the HTLV-1-infected group, running time and latency to fall, travel distance and time spent in the peripheral zone, total crossing number and total traveled distance in open field test, the latency of entrance into the dark compartment in the passive avoidance test, the new object exploration percentage, and discrimination ratio were significantly lower than in the control group. The immobility time, time spent in the dark compartment in passive avoidance test, and total exploration time significantly increased in the HTLV-1-infected group compared to the control group. In the cortical tissue of the HTLV-1 group, the malondialdehyde levels were elevated while the total thiol levels decreased in comparison to the control group. The activity of superoxide dismutase in the cortical and hippocampal tissues, and catalase activity in cortical tissue significantly decreased in the HTLV-1 group in comparison to the control group. SIGNIFICANCE: The HTLV-1 infection seems to induce depression-like behavior, motor dysfunction, disruption in working and fear memory and also oxidative stress in the cortex and hippocampus.

Extensive somatosensory and motor corticospinal sprouting occurs following a central dorsal column lesion in monkeys.

The corticospinal tract (CST) forms the major descending pathway mediating voluntary hand movements in primates, and originates from ∼nine cortical subdivisions in the macaque. While the terminals of spared motor CST axons are known to sprout locally within the cord in response to spinal injury, little is known about the response of the other CST subcomponents. We previously reported that following a cervical dorsal root lesion (DRL), the primary somatosensory (S1) CST terminal projection retracts to 60% of its original terminal domain, while the primary motor (M1) projection remains robust (Darian-Smith et al., J. Neurosci., 2013). In contrast, when a dorsal column lesion (DCL) is added to the DRL, the S1 CST, in addition to the M1 CST, extends its terminal projections bilaterally and caudally, well beyond normal range (Darian-Smith et al., J. Neurosci., 2014). Are these dramatic responses linked entirely to the inclusion of a CNS injury (i.e., DCL), or do the two components summate or interact? We addressed this directly, by comparing data from monkeys that received a unilateral DCL alone, with those that received either a DRL or a combined DRL/DCL. Approximately 4 months post-lesion, the S1 hand region was mapped electrophysiologically, and anterograde tracers were injected bilaterally into the region deprived of normal input, to assess spinal terminal labeling. Using multifactorial analyses, we show that following a DCL alone (i.e., cuneate fasciculus lesion), the S1 and M1 CSTs also sprout significantly and bilaterally beyond normal range, with a termination pattern suggesting some interaction between the peripheral and central lesions.

Grey-matter network disintegration as predictor of cognitive and motor function with aging.

Loss of grey-matter volume with advancing age affects the entire cortex. It has been suggested that atrophy occurs in a network-dependent manner with advancing age rather than in independent brain areas. The relationship between networks of structural covariance (SCN) disintegration and cognitive functioning during normal aging is not fully explored. We, therefore, aimed to (1) identify networks that lose GM integrity with advancing age, (2) investigate if age-related impairment of integrity in GM networks associates with cognitive function and decreasing fine motor skills (FMS), and (3) examine if GM disintegration is a mediator between age and cognition and FMS. T1-weighted scans of n = 257 participants (age range: 20-87) were used to identify GM networks using independent component analysis. Random forest analysis was implemented to examine the importance of network integrity as predictors of memory, executive functions, and FMS. The associations between GM disintegration, age and cognitive performance, and FMS were assessed using mediation analyses. Advancing age was associated with decreasing cognitive performance and FMS. Fourteen of 20 GM networks showed integrity changes with advancing age. Next to age and education, eight networks (fronto-parietal, fronto-occipital, temporal, limbic, secondary somatosensory, cuneal, sensorimotor network, and a cerebellar network) showed an association with cognition and FMS (up to 15.08%). GM networks partially mediated the effect between age and cognition and age and FMS. We confirm an age-related decline in cognitive functioning and FMS in non-demented community-dwelling subjects and showed that aging selectively affects the integrity of GM networks. The negative effect of age on cognition and FMS is associated with distinct GM networks and is partly mediated by their disintegration.

Disruption to functional networks in neonates with perinatal brain injury predicts motor skills at 8 months.

Objective: Functional connectivity magnetic resonance imaging (fcMRI) of neonates with perinatal brain injury could improve prediction of motor impairment before symptoms manifest, and establish how early brain organization relates to subsequent development. This cohort study is the first to describe and quantitatively assess functional brain networks and their relation to later motor skills in neonates with a diverse range of perinatal brain injuries. Methods: Infants (n = 65, included in final analyses: n = 53) were recruited from the neonatal intensive care unit (NICU) and were stratified based on their age at birth (premature vs. term), and on whether neuropathology was diagnosed from structural MRI. Functional brain networks and a measure of disruption to functional connectivity were obtained from 14 min of fcMRI acquired during natural sleep at term-equivalent age. Results: Disruption to connectivity of the somatomotor and frontoparietal executive networks predicted motor impairment at 4 and 8 months. This disruption in functional connectivity was not found to be driven by differences between clinical groups, or by any of the specific measures we captured to describe the clinical course. Conclusion: fcMRI was predictive over and above other clinical measures available at discharge from the NICU, including structural MRI. Motor learning was affected by disruption to somatomotor networks, but also frontoparietal executive networks, which supports the functional importance of these networks in early development. Disruption to these two networks might be best addressed by distinct intervention strategies.

Do subjects with minimal motor features have prodromal Parkinson disease?

OBJECTIVE: Understanding the pathological changes underlying mild motor features of the eldery and defining a patient population with prodromal Parkinson disease (PD) are of great clinical importance. It remains unclear, however, how to accurately and specifically diagnose prodromal PD. We examined whether older adults with minimal parkinsonian motor features have nigrostriatal degeneration and α-synuclein pathology consistent with prodromal PD. METHODS: Brain sections were obtained from older adults with a clinical diagnosis of PD (n = 21) and without a clinical diagnosis of PD (n = 27) who underwent motor examination proximate to death. Cases without PD were further dichotomized into no motor deficit (n = 9) or minimal motor features (n = 18) groups using a modified Unified Parkinson's Disease Rating Scale. We performed quantitative unbiased stereological analyses of dopaminergic neurons/terminals and α-synuclein accumulation in the nigrostriatal system. RESULTS: In all subjects with minimal motor features, there were significant reductions in dopaminergic neurons and terminals in the substantia nigra and putamen that were intermediate between subjects with no motor deficit and PD. Phosphorylated α-synuclein inclusions were observed in the substantia nigra that were of similar density to what was seen in PD. Furthermore, there was greater Lewy neuritic pathology in the putamen relative to PD patients. Lastly, neurons with α-synuclein inclusions displayed reductions in tyrosine hydroxylase expression that were comparable in subjects with both minimal motor features and PD. INTERPRETATION: Minimal motor features in older adults may represent prodromal PD and identify at-risk individuals for testing putative neuroprotective interventions that could slow or prevent PD progression. Ann Neurol 2018;83:562-574.

Low, but not high, dose triptolide controls neuroinflammation and improves behavioral deficits in toxic model of multiple sclerosis by dampening of NF-κB activation and acceleration of intrinsic myelin repair.

Cuprizone (Cup) is a copper chelating agent frequently used to study factors that affect oligodendrocytes (OLGs) death and acute demyelination. Triptolide (TP), a nuclear factor-kappaB (NF-κB) blocker, is a major bioactive component of Tripterygium wilfordii Hook f. (TWHf) with various therapeutic activities. In this study, we examined the effects of TP on neuroglia activation, inflammation, apoptosis, demyelination, and behavioral deficits in the Cup-induced toxic model of multiple sclerosis (MS). C57BL/6 J mice were fed with chow containing 0.2% Cup for 6 weeks to induce detectable neuroinflammation and myelin loss. TP was administered intraperitoneally at different doses (125, 250 or 500 µg/kg/day) during the last week of the Cup challenge. Although TP substantially decreased Cup-induced NF-κB extra activation, TNF-α and IL-1 over expression, and gliosis in a dose-dependent manner, only low dose of TP (TP-125) was able to raise the number of OLGs precursor cells (NG-2+/O4+), reduce Bax/Bcl-2 ratio and improve behavioral deficits. In addition, TP-125 decreased NF-κB activation on GFAP+ astrocytes more than MAC-3+ microglial and MOG+ oligodendrocytes which suggested the possibility of specific dampening of NF-κB signaling in reactive astrocytes. Behavioral assessments by open-field and rota-rod tests showed that only TP-125 notably improved motor function and motor coordination compared to the Cup group. These findings highlight the pivotal role of NF-κB signaling in the oligodendrogenesis and lesion reduction in demyelination diseases such as MS.

Oculomotor atypicalities in Developmental Coordination Disorder.

Children with Developmental Coordination Disorder (DCD) fail to acquire adequate motor skill, yet surprisingly little is known about the oculomotor system in DCD. Successful completion of motor tasks is supported by accurate visual feedback. The purpose of this study was to determine whether any oculomotor differences can distinguish between children with and without a motor impairment. Using eye tracking technology, visual fixation, smooth pursuit, and pro- and anti-saccade performance were assessed in 77 children that formed three groups: children with DCD (aged 7-10), chronologically age (CA) matched peers, and a motor-match (MM) group (aged 4-7). Pursuit gain and response preparation in the pro- and anti-saccade tasks were comparable across groups. Compared to age controls, children with DCD had deficits in maintaining engagement in the fixation and pursuit tasks, and made more anti-saccade errors. The two typically developing groups performed similarly, except on the fast speed smooth pursuit and antisaccade tasks, where the CA group outperformed the younger MM group. The findings suggest that children with DCD have problems with saccadic inhibition and maintaining attention on a visual target. Developmental patterns were evident in the typically developing groups, suggesting that the pursuit system and cognitive control develop with age. This study adds to the literature by being the first to systematically identify specific oculomotor differences between children with and without a motor impairment. Further examination of oculomotor control may help to identify underlying processes contributing to DCD. A video abstract of this article can be viewed at: https://youtu.be/NinXa2KlB4M. [Correction added on 27 January 2017, after first online publication: The video abstract link was added.].

Atypical inter-hemispheric communication correlates with altered motor inhibition during learning of a new bimanual coordination pattern in developmental coordination disorder.

Impairment 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.