1. Caeyenberghs K, Taymans T, Wilson PH, Vanderstraeten G, Hosseini H, van Waelvelde H. {{Neural signature of developmental coordination disorder in the structural connectome independent of comorbid autism}}. {Dev Sci}. 2016.
Children with autism spectrum disorders (ASD) often exhibit motor clumsiness (Developmental Coordination Disorder, DCD), i.e. they struggle with everyday tasks that require motor coordination like dressing, self-care, and participating in sport and leisure activities. Previous studies in these neurodevelopmental disorders have demonstrated functional abnormalities and alterations of white matter microstructural integrity in specific brain regions. These findings suggest that the global organization of brain networks is affected in DCD and ASD and support the hypothesis of a ‘dys-connectivity syndrome’ from a network perspective. No studies have compared the structural covariance networks between ASD and DCD in order to look for the signature of DCD independent of comorbid autism. Here, we aimed to address the question of whether abnormal connectivity in DCD overlaps that seen in autism or comorbid DCD-autism. Using graph theoretical analysis, we investigated differences in global and regional topological properties of structural brain networks in 53 children: 8 ASD children with DCD (DCD+ASD), 15 ASD children without DCD (ASD), 11 with DCD only, and 19 typically developing (TD) children. We constructed separate structural correlation networks based on cortical thickness derived from Freesurfer. The children were assessed on the Movement-ABC and the Beery Test of Visual Motor Integration. Behavioral results demonstrated that the DCD group and DCD+ASD group scored on average poorer than the TD and ASD groups on various motor measures. Furthermore, although the brain networks of all groups exhibited small-world properties, the topological architecture of the networks was significantly altered in children with ASD compared with DCD and TD. ASD children showed increased normalized path length and higher values of clustering coefficient. Also, paralimbic regions exhibited nodal clustering coefficient alterations in singular disorders. These changes were disorder-specific, and included alterations in clustering coefficient in the isthmus of the right cingulate gyrus and the pars orbitalis of the right inferior frontal gyrus in ASD children, and DCD-related increases in the lateral orbitofrontal cortex. Children meeting criteria for both DCD and ASD exhibited topological changes that were more widespread from those seen in children with only DCD, i.e. children with DCD+ASD showed alterations of clustering coefficient in (para)limbic regions, primary areas, and association areas. The DCD+ASD group showed changes in clustering coefficient in the left association cortex relative to the ASD group. Finally, the DCD+ASD group shared ASD-specific abnormalities in the pars orbitalis of right inferior frontal gyrus, which was hypothesized to reflect atypical emotional-cognitive processing. Our results provide evidence that DCD and ASD are neurodevelopmental disorders with a low degree of overlap in abnormalities in connectivity. The co-occurrence of DCD+ASD was also associated with a distinct topological pattern, highlighting the unique neural signature of comorbid neurodevelopmental disorders.
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2. Fadda R, Parisi M, Ferretti L, Saba G, Foscoliano M, Salvago A, Doneddu G. {{Exploring the Role of Theory of Mind in Moral Judgment: The Case of Children with Autism Spectrum Disorder}}. {Front Psychol}. 2016; 7: 523.
This paper adds to the growing research on moral judgment (MJ) by considering whether theory of mind (ToM) might foster children’s autonomous MJ achievement. A group of 30 children with autism spectrum disorder (ASD) was compared in MJ and ToM with 30 typically developing (TD) children. Participants were tested for MJ with a classical Piaget’s task and for ToM with a second order False Belief task. In the moral task, children were told two versions of a story: in one version the protagonist acted according to a moral intention but the action resulted in a harmful consequence; in the other version the protagonist acted according to an immoral intention, but the action resulted in a harmless consequence. Children were asked which of the two protagonists was the « naughtier. » In line with previous studies, the results indicated that, while the majority of TD participants succeeded in the second order False Belief task, only few individuals with ASD showed intact perspective taking abilities. The analysis of the MJ in relation to ToM showed that children with ASD lacking ToM abilities judged guilty the protagonists of the two versions of the story in the moral task because both of them violated a moral rule or because they considered the consequences of the actions, ignoring any psychological information. These results indicate a heteronomous morality in individuals with ASD, based on the respect of learned moral rules and outcomes rather than others’ subjective states.
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3. Fujiwara T, Morisaki N, Honda Y, Sampei M, Tani Y. {{Chemicals, Nutrition, and Autism Spectrum Disorder: A Mini-Review}}. {Front Neurosci}. 2016; 10: 174.
The rapid increase of the prevalence of autism spectrum disorder (ASD) suggests that exposure to chemicals may impact the development of ASD. Therefore, we reviewed literature on the following chemicals, nutrient to investigate their association with ASD: (1) smoke/tobacco, (2) alcohol, (3) air pollution, (4) pesticides, (5) endocrine-disrupting chemicals, (6) heavy metals, (7) micronutrients, (8) fatty acid, and (9) parental obesity as a proxy of accumulation of specific chemicals or nutritional status. Several chemical exposures such as air pollution (e.g., particular matter 2.5), pesticides, bisphenol A, phthalates, mercury, and nutrition deficiency such as folic acid, vitamin D, or fatty acid may possibly be associated with an increased risk of ASD, whereas other traditional risk factors such as smoking/tobacco, alcohol, or polychlorinated biphenyls are less likely to be associated with ASD. Further research is needed to accumulate evidence on the association between chemical exposure and nutrient deficiencies and ASD in various doses and populations.
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4. Hames EC, Murphy B, Rajmohan R, Anderson RC, Baker M, Zupancic S, O’Boyle M, Richman D. {{Visual, Auditory, and Cross Modal Sensory Processing in Adults with Autism: An EEG Power and BOLD fMRI Investigation}}. {Front Hum Neurosci}. 2016; 10: 167.
Electroencephalography (EEG) and blood oxygen level dependent functional magnetic resonance imagining (BOLD fMRI) assessed the neurocorrelates of sensory processing of visual and auditory stimuli in 11 adults with autism (ASD) and 10 neurotypical (NT) controls between the ages of 20-28. We hypothesized that ASD performance on combined audiovisual trials would be less accurate with observable decreased EEG power across frontal, temporal, and occipital channels and decreased BOLD fMRI activity in these same regions; reflecting deficits in key sensory processing areas. Analysis focused on EEG power, BOLD fMRI, and accuracy. Lower EEG beta power and lower left auditory cortex fMRI activity were seen in ASD compared to NT when they were presented with auditory stimuli as demonstrated by contrasting the activity from the second presentation of an auditory stimulus in an all auditory block vs. the second presentation of a visual stimulus in an all visual block (AA2-VV2).We conclude that in ASD, combined audiovisual processing is more similar than unimodal processing to NTs.
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5. Jimenez-Barron LT, O’Rawe JA, Wu Y, Yoon M, Fang H, Iossifov I, Lyon GJ. {{Genome-wide variant analysis of simplex autism families with an integrative clinical-bioinformatics pipeline}}. {Cold Spring Harb Mol Case Stud}. 2015; 1(1): a000422.
Autism spectrum disorders (ASDs) are a group of developmental disabilities that affect social interaction and communication and are characterized by repetitive behaviors. There is now a large body of evidence that suggests a complex role of genetics in ASDs, in which many different loci are involved. Although many current population-scale genomic studies have been demonstrably fruitful, these studies generally focus on analyzing a limited part of the genome or use a limited set of bioinformatics tools. These limitations preclude the analysis of genome-wide perturbations that may contribute to the development and severity of ASD-related phenotypes. To overcome these limitations, we have developed and utilized an integrative clinical and bioinformatics pipeline for generating a more complete and reliable set of genomic variants for downstream analyses. Our study focuses on the analysis of three simplex autism families consisting of one affected child, unaffected parents, and one unaffected sibling. All members were clinically evaluated and widely phenotyped. Genotyping arrays and whole-genome sequencing were performed on each member, and the resulting sequencing data were analyzed using a variety of available bioinformatics tools. We searched for rare variants of putative functional impact that were found to be segregating according to de novo, autosomal recessive, X-linked, mitochondrial, and compound heterozygote transmission models. The resulting candidate variants included three small heterozygous copy-number variations (CNVs), a rare heterozygous de novo nonsense mutation in MYBBP1A located within exon 1, and a novel de novo missense variant in LAMB3. Our work demonstrates how more comprehensive analyses that include rich clinical data and whole-genome sequencing data can generate reliable results for use in downstream investigations.
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6. Marraffa C. {{Social communication in autism spectrum disorder not improved by Theory of Mind interventions}}. {J Paediatr Child Health}. 2016; 52(4): 461-3.
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7. Napoli E, Ross-Inta C, Song G, Wong S, Hagerman R, Gane LW, Smilowitz JT, Tassone F, Giulivi C. {{Premutation in the Fragile X Mental Retardation 1 (FMR1) Gene Affects Maternal Zn-milk and Perinatal Brain Bioenergetics and Scaffolding}}. {Front Neurosci}. 2016; 10: 159.
Fragile X premutation alleles have 55-200 CGG repeats in the 5′ UTR of the FMR1 gene. Altered zinc (Zn) homeostasis has been reported in fibroblasts from >60 years old premutation carriers, in which Zn supplementation significantly restored Zn-dependent mitochondrial protein import/processing and function. Given that mitochondria play a critical role in synaptic transmission, brain function, and cognition, we tested FMRP protein expression, brain bioenergetics, and expression of the Zn-dependent synaptic scaffolding protein SH3 and multiple ankyrin repeat domains 3 (Shank3) in a knock-in (KI) premutation mouse model with 180 CGG repeats. Mitochondrial outcomes correlated with FMRP protein expression (but not FMR1 gene expression) in KI mice and human fibroblasts from carriers of the pre- and full-mutation. Significant deficits in brain bioenergetics, Zn levels, and Shank3 protein expression were observed in the Zn-rich regions KI hippocampus and cerebellum at PND21, with some of these effects lasting into adulthood (PND210). A strong genotype x age interaction was observed for most of the outcomes tested in hippocampus and cerebellum, whereas in cortex, age played a major role. Given that the most significant effects were observed at the end of the lactation period, we hypothesized that KI milk might have a role at compounding the deleterious effects on the FMR1 genetic background. A higher gene expression of ZnT4 and ZnT6, Zn transporters abundant in brain and lactating mammary glands, was observed in the latter tissue of KI dams. A cross-fostering experiment allowed improving cortex bioenergetics in KI pups nursing on WT milk. Conversely, WT pups nursing on KI milk showed deficits in hippocampus and cerebellum bioenergetics. A highly significant milk type x genotype interaction was observed for all three-brain regions, being cortex the most influenced. Finally, lower milk-Zn levels were recorded in milk from lactating women carrying the premutation as well as other Zn-related outcomes (Zn-dependent alkaline phosphatase activity and lactose biosynthesis-whose limiting step is the Zn-dependent beta-1,4-galactosyltransferase). In premutation carriers, altered Zn homeostasis, brain bioenergetics and Shank3 levels could be compounded by Zn-deficient milk, increasing the risk of developing emotional and neurological/cognitive problems and/or FXTAS later in life.
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8. Ronconi L, Molteni M, Casartelli L. {{Building Blocks of Others’ Understanding: A Perspective Shift in Investigating Social-Communicative Deficit in Autism}}. {Front Hum Neurosci}. 2016; 10: 144.
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9. Yau SH, Brock J, McArthur G. {{The relationship between spoken language and speech and nonspeech processing in children with autism: a magnetic event-related field study}}. {Dev Sci}. 2016.
It has been proposed that language impairments in children with Autism Spectrum Disorders (ASD) stem from atypical neural processing of speech and/or nonspeech sounds. However, the strength of this proposal is compromised by the unreliable outcomes of previous studies of speech and nonspeech processing in ASD. The aim of this study was to determine whether there was an association between poor spoken language and atypical event-related field (ERF) responses to speech and nonspeech sounds in children with ASD (n = 14) and controls (n = 18). Data from this developmental population (ages 6-14) were analysed using a novel combination of methods to maximize the reliability of our findings while taking into consideration the heterogeneity of the ASD population. The results showed that poor spoken language scores were associated with atypical left hemisphere brain responses (200 to 400 ms) to both speech and nonspeech in the ASD group. These data support the idea that some children with ASD may have an immature auditory cortex that affects their ability to process both speech and nonspeech sounds. Their poor speech processing may impair their ability to process the speech of other people, and hence reduce their ability to learn the phonology, syntax, and semantics of their native language.
