1. Han J, Zeng K, Kang J, Tong Z, Cai E, Chen H, Ding M, Gu Y, Ouyang G, Li X. {{Development of Brain Network in Children with Autism from Early Childhood to Late Childhood}}. {Neuroscience}. 2017; 367: 134-46.
Extensive studies have indicated brain function connectivity abnormalities in autism spectrum disorder (ASD). However, there is a lack of longitudinal or cross-sectional research focused on tracking age-related developmental trends of autistic children at an early stage of brain development or based on a relatively large sample. The present study examined brain network changes in a total of 186 children both with and without ASD from 3 to 11years, an early and key development period when significant changes are expected. The study aimed to investigate possible abnormal connectivity patterns and topological properties of children with ASD from early childhood to late childhood by using resting-state electroencephalographic (EEG) data. The main findings of the study were as follows: (1) From the connectivity analysis, several inter-regional synchronizations with reduction were identified in the younger and older ASD groups, and several intra-regional synchronization increases were observed in the older ASD group. (2) From the graph analysis, a reduced clustering coefficient and enhanced mean shortest path length in specific frequencies was observed in children with ASD. (3) Results suggested an age-related decrease of the mean shortest path length in the delta and theta bands in TD children, whereas atypical age-related alteration was observed in the ASD group. In addition, graph measures were correlated with ASD symptom severity in the alpha band. These results demonstrate that abnormal neural communication is already present at the early stages of brain development in autistic children and this may be involved in the behavioral deficits associated with ASD.
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2. Ikuse D, Tani M, Itahashi T, Yamada H, Ohta H, Morita T, Arai G, Saga N, Tokumasu T, Ohta M, Sato A, Iwanami A. {{The effect of visual cues on performance in the ultimatum game in individuals with autism spectrum disorder}}. {Psychiatry Res}. 2017; 259: 176-83.
The Ultimatum Game (UG) allows for the assessment of altruistic behavior as well as the perception of fairness. We examined the effects of visual social cues (gaze of others), factors associated with autism, and trust on UG performance in typical adults (TAs) and individuals with autism spectrum disorder (ASD). We hypothesized that individuals with ASD would be less affected by visual social cues than TAs. We recruited 30 TAs and 30 individuals with ASD. Participants completed 30 trials of the UG, during which the visual background was altered to include either stylized eyespots, flowers, or a neutral background. Reaction times and money distributed in each condition were recorded. Reaction times did not vary among background conditions in either group, although individuals with ASD responded more slowly overall. TAs distributed less money in the neutral background and flowers conditions than in the eyespots condition, while no significant differences in the amount of money distributed were observed among background conditions for individuals with ASD, who also distributed more money overall than TAs. Such findings may be due to decreased susceptibility to social cues among individuals with ASD.
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3. Mithyantha R, Kneen R, McCann E, Gladstone M. {{Current evidence-based recommendations on investigating children with global developmental delay}}. {Arch Dis Child}. 2017; 102(11): 1071-6.
INTRODUCTION: Global developmental delay (GDD) affects 1%-3% of the population of children under 5 years of age, making it one of the most common conditions presenting in paediatric clinics; causes are exogenous, genetic (non-metabolic) or genetic (metabolic). Recent advances in biotechnology and genetic testing mean that the investigations available to perform for children under 5 years are increasing and are more sensitive than previously. This change in availability and type of testing necessitates an update in the recommendations for investigating GDD. METHODS: We conducted a review of the literature from 2006 to 2016 to identify articles with evidence relating to the investigation of developmental delay in children under the age of 5 years. We collated the evidence into first-line and second-line investigations and, where available, on their yield and cost implications. RESULTS: We have provided up-to-date guidance for first-line and second-line investigations for children with GDD under the age of 5 years. Recent evidence demonstrates that genetic testing for all children with unexplained GDD should be first line, if an exogenous cause is not already established. Our review of the literature demonstrates that all patients, irrespective of severity of GDD, should have investigations for treatable conditions. Evidence demonstrates that the yield for treatable conditions is higher than previously thought and that investigations for these metabolic conditions should be considered as first line. Additional second-line investigations can be led by history, examination and developmental trajectories. DISCUSSION: We may need to update present recommendations in the UK for investigation of developmental delay. This would include microarray testing as first line and a more thorough approach to investigations for metabolic disorders that can be treated. Clinical assessment remains vital for guiding investigations.
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4. Zhou JH, Wang XT, Zhou L, Xu FX, Su LD, Wang H, Jia F, Xu FQ, Chen GQ, De Zeeuw CI, Shen Y. {{Ablation of TFR1 in Purkinje Cells Inhibits mGlu1 Trafficking and Impairs Motor Coordination, But Not Autistic-Like Behaviors}}. {J Neurosci}. 2017; 37(47): 11335-52.
Group 1 metabotropic glutamate receptors (mGlu1/5s) are critical to synapse formation and participate in synaptic LTP and LTD in the brain. mGlu1/5 signaling alterations have been documented in cognitive impairment, neurodegenerative disorders, and psychiatric diseases, but underlying mechanisms for its modulation are not clear. Here, we report that transferrin receptor 1 (TFR1), a transmembrane protein of the clathrin complex, modulates the trafficking of mGlu1 in cerebellar Purkinje cells (PCs) from male mice. We show that conditional knock-out of TFR1 in PCs does not affect the cytoarchitecture of PCs, but reduces mGlu1 expression at synapses. This regulation by TFR1 acts in concert with that by Rab8 and Rab11, which modulate the internalization and recycling of mGlu1, respectively. TFR1 can bind to Rab proteins and facilitate their expression at synapses. PC ablation of TFR1 inhibits parallel fiber-PC LTD, whereas parallel fiber-LTP and PC intrinsic excitability are not affected. Finally, we demonstrate that PC ablation of TFR1 impairs motor coordination, but does not affect social behaviors in mice. Together, these findings underscore the importance of TFR1 in regulating mGlu1 trafficking and suggest that mGlu1- and mGlu1-dependent parallel fiber-LTD are associated with regulation of motor coordination, but not autistic behaviors.SIGNIFICANCE STATEMENT Group 1 metabotropic glutamate receptor (mGlu1/5) signaling alterations have been documented in cognitive impairment, neurodegenerative disorders, and psychiatric diseases. Recent work suggests that altered mGlu1 signaling in Purkinje cells (PCs) may be involved in not only motor learning, but also autistic-like behaviors. We find that conditional knock-out of transferrin receptor 1 (TFR1) in PCs reduces synaptic mGlu1 by tethering Rab8 and Rab11 in the cytosol. PC ablation of TFR1 inhibits parallel fiber-PC LTD, whereas parallel fiber-PC LTP and PC intrinsic excitability are intact. Motor coordination is impaired, but social behaviors are normal in TFR1flox/flox;pCP2-cre mice. Our data reveal a new regulator for trafficking and synaptic expression of mGlu1 and suggest that mGlu1-dependent LTD is associated with motor coordination, but not autistic-like behaviors.
