Pubmed du 28/11/17

mardi 28 novembre 2017

1. Correction : Detection of atypical network development patterns in children with autism spectrum disorder using magnetoencephalography. PLoS One. 2017 ; 12(11) : e0188813.

[This corrects the article DOI : 10.1371/journal.pone.0184422.].

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2. Abbott AE, Linke A, Nair A, Jahedi A, Alba LA, Keown CL, Fishman I, Muller RA. Repetitive behaviors in autism are linked to imbalance of corticostriatal connectivity:A functional connectivity MRI study. Soc Cogn Affect Neurosci. 2017.

The neural underpinnings of repetitive behaviors (RBs) in autism spectrum disorders (ASDs), ranging from cognitive to motor characteristics, remain unknown. We assessed RB symptomatology in 50 ASD and 52 typically developing (TD) children and adolescents (ages 8-17 years), examining intrinsic functional connectivity (iFC) of corticostriatal circuitry, which is important for reward-based learning and integration of emotional, cognitive, and motor processing, and considered impaired in ASDs. Connectivity analyses were performed for three functionally distinct striatal seeds (limbic, frontoparietal, motor). Functional connectivity with cortical regions of interest was assessed for corticostriatal circuit connectivity indices and ratios, testing the balance of connectivity between circuits. Results showed corticostriatal overconnectivity of limbic and frontoparietal seeds, but underconnectivity of motor seeds. Correlations with RBs were found for connectivity between the striatal motor seeds and cortical motor clusters from the whole-brain analysis, and for frontoparietal/limbic and motor/limbic connectivity ratios. Division of ASD participants into high (n=17) and low RB subgroups (n=19) showed reduced frontoparietal/limbic and motor/limbic circuit ratios for high RB compared to low RB and TD groups in the right hemisphere. Results suggest an association between RBs and an imbalance of corticostriatal iFC in ASD, being for limbic, but reduced for frontoparietal and motor circuits.

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3. Adorjan I, Ahmed B, Feher V, Torso M, Krug K, Esiri M, Chance SA, Szele FG. Calretinin interneuron density in the caudate nucleus is lower in autism spectrum disorder. Brain. 2017 ; 140(7) : 2028-40.

Autism spectrum disorder is a debilitating condition with possible neurodevelopmental origins but unknown neuroanatomical correlates. Whereas investigators have paid much attention to the cerebral cortex, few studies have detailed the basal ganglia in autism. The caudate nucleus may be involved in the repetitive movements and limbic changes of autism. We used immunohistochemistry for calretinin and neuropeptide Y in 24 age- and gender-matched patients with autism spectrum disorder and control subjects ranging in age from 13 to 69 years. Patients with autism had a 35% lower density of calretinin+ interneurons in the caudate that was driven by loss of small calretinin+ neurons. This was not caused by altered size of the caudate, as its cross-sectional surface areas were similar between diagnostic groups. Controls exhibited an age-dependent increase in the density of medium and large calretinin+ neurons, whereas subjects with autism did not. Diagnostic groups did not differ regarding ionized calcium-binding adapter molecule 1+ immunoreactivity for microglia, suggesting chronic inflammation did not cause the decreased calretinin+ density. There was no statistically significant difference in the density of neuropeptide Y+ neurons between subjects with autism and controls. The decreased calretinin+ density may disrupt the excitation/inhibition balance in the caudate leading to dysfunctional corticostriatal circuits. The description of such changes in autism spectrum disorder may clarify pathomechanisms and thereby help identify targets for drug intervention and novel therapeutic strategies.

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4. Carvalho Pereira A, Violante IR, Mouga S, Oliveira G, Castelo-Branco M. Medial Frontal Lobe Neurochemistry in Autism Spectrum Disorder is Marked by Reduced N-Acetylaspartate and Unchanged Gamma-Aminobutyric Acid and Glutamate + Glutamine Levels. J Autism Dev Disord. 2017.

The nature of neurochemical changes in autism spectrum disorder (ASD) remains controversial. We compared medial prefrontal cortex (mPFC) neurochemistry of twenty high-functioning children and adolescents with ASD without associated comorbidities and fourteen controls. We observed reduced total N-acetylaspartate (tNAA) and total creatine, increased Glx/tNAA but unchanged glutamate + glutamine (Glx) and unchanged absolute or relative gamma-aminobutyric acid (GABA+) in the ASD group. Importantly, both smaller absolute and relative GABA+ levels were associated with worse communication skills and developmental delay scores assessed by the autism diagnostic interview-revised (ADI-R). We conclude that tNAA is reduced in the mPFC in ASD and that glutamatergic metabolism may be altered due to unbalanced Glx/tNAA. Moreover, GABA+ is related to autistic symptoms assessed by the ADI-R.

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5. Delemere E, Dounavi K. Parent-Implemented Bedtime Fading and Positive Routines for Children with Autism Spectrum Disorders. J Autism Dev Disord. 2017.

Sleep disorders affect a large portion of those with autism spectrum disorder. Behavioural interventions have been found to increase appropriate sleep behaviours. This study sought to examine the efficacy of two stimulus control interventions (bedtime fading and positive routines) on total sleep duration, sleep onset latency and frequency and duration of night wakings for children with autism using two multiple baseline designs. Secondary dependent variables, namely, educational opportunities, challenging behaviours, parent acceptance and social validity were also analysed. Results suggest some efficacy for both interventions. Increased total sleep duration and decreased sleep onset latency were achieved with bedtime fading. Positive routines showed mixed results with decreased sleep onset latency and increased total sleep duration for two of three participants.

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6. Edmiston EK, Muscatello RA, Corbett BA. Altered Pre-Ejection Period Response to Social Evaluative Threat in Adolescents with Autism Spectrum Disorder. Res Autism Spectr Disord. 2017 ; 36 : 57-65.

Introduction : The autonomic nervous system (ANS) is involved in regulating social behavior ; Autism Spectrum Disorder (ASD) is characterized by alterations in social behavior and reduced physiological response to threat. We hypothesized that adolescents with ASD would show reduced ANS response to social threat. Methods : Eighteen males with ASD and thirteen males with typical development (TD), ages 12 to 17, completed a social threat paradigm while wearing an impedance cardiography apparatus. We calculated pre-ejection period (PEP) and tested for between-group differences in PEP response to social threat. We also conducted correlation analyses between PEP change scores and clinical symptom scales. Results : There was an effect of diagnosis on change in PEP from baseline to the onset of social threat (F=7.60, p=0.01), with greater changes in PEP in TD compared to ASD. PEP change score and the Social Communication Questionnaire (r=0.634, p=0.005) and the ADHD Problems Subscale of the Child Behavior Checklist (r=0.568, p=0.014) were correlated. Conclusions : These findings suggest reduced arousal in response to social threat in ASD, with preliminary evidence that reduced sympathetic activation is associated with increased social behavior symptoms.

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7. Gouleme N, Scheid I, Peyre H, Seassau M, Maruani A, Clarke J, Delorme R, Bucci MP. Postural Control and Emotion in Children with Autism Spectrum Disorders. Transl Neurosci. 2017 ; 8 : 158-66.

Autism Spectrum Disorders subjects (ASD) are well known to have deficits in social interaction. We recorded simultaneously eye movements and postural sway during exploration of emotional faces in children with ASD and typically developing children (TD). We analyzed several postural and ocular parameters. The results showed that all postural parameters were significantly greater in children with ASD ; ASD made significantly fewer saccades and had shorter fixation time than TD, particularly in the eyes, and especially for unpleasant emotions. These results suggest that poor postural control of ASD and their impaired visual strategies could be due to a lack of interest in social cognition, causing a delay in the development of the cortical areas, and thus could have an effect on their postural control.

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8. Hamm J, Yun J. Influence of physical activity on the health-related quality of life of young adults with and without autism spectrum disorder. Disabil Rehabil. 2017 : 1-7.

BACKGROUND : Health-related quality of life constructs has been used to understand the multiple dimensions (i.e., physical health, psychological, environment and social relationships) that affect a person’s health status. In order to improve health-related quality of life for young adults, it is important to understand the factors that influence each dimension. The purpose of this paper was to examine the influence of the presence of autism spectrum disorder and physical activity on the multiple domains of health-related quality of life for young adults. METHODS : Three-hundred and twenty participants, including young adults with ASD, completed a questionnaire about their physical activity and health-related quality of life. RESULTS : Five multiple regressions revealed that the presence of autism spectrum disorder significantly predicted overall health-related quality of life, the physical health domain, psychological domain, and the environment domain. Additionally, physical activity significantly predicted each domain and overall health-related quality of life regardless of the presence of autism spectrum disorder. CONCLUSION : Practitioners should recognize the limitations that individuals with autism spectrum disorder may experience regarding their health-related quality of life, and utilize physical activity as a tool for improving health-related quality of life. Implications for Rehabilitation In order to address an individual’s overall health, practitioners must consider multiple dimensions of health-related quality of life. Autism spectrum disorders influence how people perceive multiple dimensions of their health. Physical activity is a tool for improving perceptions of the multiple dimensions of health for individuals with and without autism spectrum disorders.

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9. Jyonouchi H, Geng L, Streck DL, Dermody JJ, Toruner GA. MicroRNA expression changes in association with changes in interleukin-1ss/interleukin10 ratios produced by monocytes in autism spectrum disorders : their association with neuropsychiatric symptoms and comorbid conditions (observational study). J Neuroinflammation. 2017 ; 14(1) : 229.

BACKGROUND : MicroRNAs (miRNAs) play a major role in regulating immune responses at post-transcriptional levels. Previously, we have reported fluctuating interlukine-1ss (IL-1ss)/IL-10 ratios produced by peripheral blood monocytes (PBMo) in some patients with autism spectrum disorders (ASD). This study examined whether changes in miRNA expression by PBMo are associated with changes in IL-1ss/IL-10 ratios and how such changes are associated with ASD clinical features. METHODS : miRNA expression by purified PBMo from ASD subjects (N = 69) and non-ASD controls (N = 27) were determined by high-throughput sequencing. Cytokine production by PBMo in responses to stimuli of innate immunity, and behavioral symptoms [assessed by aberrant behavioral checklist (ABC)] were also evaluated at the same time of sample obtainment. RESULTS : As a whole, there was no difference in miRNA expression between ASD and control non-ASD PBMo. However, when ASD cells were subdivided into 3 groups with high, normal, or low IL-1ss/IL-10 ratios as defined in the "Results" section, in comparison with the data obtained from non-ASD controls, we observed marked changes in miRNA expression. Namely, over 3-fold changes in expression of miR-181a, miR-93, miR-223, miR-342, and miR-1248 were observed in ASD PBMo with high or low IL-1ss/IL-10 ratios, but not in ASD PBMo with normal ratios. These miRNAs that had altered in expression are those closely associated with the regulation of key signaling pathways. With changes in IL-1ss/IL-10 ratios, we also observed changes in the production of cytokines (IL-6, TNF-alpha, and TGF-ss) other than IL-1ss/IL-10 by ASD PBMo. The association between behavioral symptoms and cytokine levels was different when ASD cells exhibit high/low IL-1ss/IL-10 ratios vs. when ASD cells exhibited normal ratios. Non-IgE-mediated food allergy was also observed at higher frequency in ASD subjects with high/low IL-1ss/IL-10 ratios than with normal ratios. CONCLUSIONS : Changes in cytokine profiles and miRNA expression by PBMo appear to be associated with changes in ASD behavioral symptoms. miRNAs that are altered in expression in ASD PBMo with high/low IL-1ss/IL-10 ratios are those associated with inflammatory responses. Changes in IL-1ss/IL-10 ratios along with changes in miRNA expression may serve as biomarkers for immune-mediated inflammation in ASD.

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10. Khatri N, Gilbert JP, Huo Y, Sharaflari R, Nee M, Qiao H, Man HY. The autism protein Ube3A/E6AP remodels neuronal dendritic arborization via caspase-dependent microtubule destabilization. J Neurosci. 2017.

UBE3A gene copy number variation and the resulting overexpression of the protein E6AP is directly linked to autism spectrum disorders (ASDs), however the underlying cellular and molecular neurobiology remains less clear. Here we report the role of ASD-related increased dosage of Ube3A/E6AP in dendritic arborization during brain development. We show that increased E6AP expression in primary cultured neurons leads to a reduction in dendritic branch number and length. The E6AP-dependent remodeling of dendritic arborization results from retraction of dendrites by thinning and fragmentation at the tips of dendrite branches, leading to shortening or removal of dendrites. This remodeling effect is mediated by the ubiquitination and degradation of XIAP by E6AP, which leads to activation of caspase-3 and cleavage of microtubules. In vivo, male and female Ube3A 2X ASD mice show decreased XIAP levels, increased caspase-3 activation, and elevated levels of tubulin cleavage. Consistently, dendritic branching and spine density are reduced in cortical neurons of Ube3A 2X ASD mice. Our findings reveal an important role for Ube3A/E6AP in ASD-related developmental alteration in dendritic arborization and synapse formation, which provide new insights into the pathogenesis of Ube3A/E6AP-dependent ASD.SIGNIFICANCE STATEMENTCopy number variation of the UBE3A gene and aberrant overexpression of the gene product E6AP protein is a common cause in autism spectrum disorders (ASDs). As a major event during brain development, dendritic growth and remodeling play a crucial role in neuronal connectivity and information integration. We found that in primary neurons and in Ube3A transgenic autism mouse brain, overexpression of E6AP leads to significant loss of dendritic arborization. This effect is mediated by the ubiquitination of XIAP by E6AP, subsequent activation of caspases, and the eventual cleavage of microtubules, leading to local degeneration and retraction at the tips of dendritic branches. These findings demonstrate dysregulation in neuronal structural stability as a major cellular neuropathology in ASD.

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11. Mossa A, Giona F, Pagano J, Sala C, Verpelli C. SHANK genes in autism : Defining therapeutic targets. Prog Neuropsychopharmacol Biol Psychiatry. 2017.

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12. Potvin MC, Prelock PA, Savard L. Supporting Children with Autism and Their Families : A Culturally Responsive Family-Driven Interprofessional Process. Pediatr Clin North Am. 2018 ; 65(1) : 47-57.

This article describes the Coaching in Context (CinC) process, a family-driven, culturally responsive structure that facilitates family identification and achievement of goals. CinC focuses on modification of the demands of an activity with guidance from a health care professional who coaches the family to increase their participation in everyday activities. An interprofessional team is key in this process. Working as a team and communicating effectively across professions supports the health professional who serves as the coach. Effective interprofessional team collaboration is possible ; health professions share values for the delivery of the highest quality of care.

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13. Salomone E, Leadbitter K, Aldred C, Barrett B, Byford S, Charman T, Howlin P, Green J, Le Couteur A, McConachie H, Parr JR, Pickles A, Slonims V. The Association Between Child and Family Characteristics and the Mental Health and Wellbeing of Caregivers of Children with Autism in Mid-Childhood. J Autism Dev Disord. 2017.

We examined predictors of mental health difficulties and wellbeing in caregivers of children with autism in the Pre-school Autism Communication Trial cohort in middle childhood (N = 104). Child’s intellectual disability, daily living skills impairment, elevated emotional and behavioural difficulties, high educational level of caregiver and household income below the median significantly predicted caregivers’ mental health difficulties, but autism severity, child communication skills and family circumstances did not. Lower caregiver mental wellbeing was predicted by elevated child emotional and behavioural difficulties. The need to support the mental health and wellbeing of caregivers of children with autism is discussed in light of the results.

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14. Servadio M, Manduca A, Melancia F, Leboffe L, Schiavi S, Campolongo P, Palmery M, Ascenzi P, di Masi A, Trezza V. Impaired repair of DNA damage is associated with autistic-like traits in rats prenatally exposed to valproic acid. Eur Neuropsychopharmacol. 2017.

Prenatal exposure to the antiepileptic and mood stabilizer valproic acid (VPA) is an environmental risk factor for autism spectrum disorders (ASD), although recent epidemiological studies show that the public awareness of this association is still limited. Based on the clinical findings, prenatal VPA exposure in rodents is a widely used preclinical model of ASD. However, there is limited information about the precise biochemical mechanisms underlying the link between ASD and VPA. Here, we tested the effects of increasing doses of VPA on behavioral features resembling core and secondary symptoms of ASD in rats. Only when administered prenatally at the dose of 500mg/kg, VPA induced deficits in communication and social discrimination in rat pups, and altered social behavior and emotionality in the adolescent and adult offspring in the absence of gross malformations. This dose of VPA inhibited histone deacetylase in rat embryos and favored the formation of DNA double strand breaks (DSB), but impaired their repair. The defective DSB response was no more visible in one-day-old pups, thus supporting the hypothesis that unrepaired VPA-induced DNA damage at the time of neural tube closure may underlie the autistic-like traits displayed in the course of development by rats prenatally exposed to VPA. These experiments help to understand the neurodevelopmental trajectories affected by prenatal VPA exposure and identify a biochemical link between VPA exposure during gestation and ASD.

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15. Sitzmann AF, Hagelstrom RT, Tassone F, Hagerman RJ, Butler MG. Rare FMR1 gene mutations causing fragile X syndrome : A review. Am J Med Genet A. 2017.

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, typically due to CGG-repeat expansions in the FMR1 gene leading to lack of expression. We identified a rare FMR1 gene mutation (c.413G>A), previously reported in a single patient and reviewed the literature for other rare FMR1 mutations. Our patient at 10 years of age presented with the classical findings of FXS including intellectual disability, autism, craniofacial findings, hyperextensibility, fleshy hands, flat feet, unsteady gait, and seizures but without the typical CGG-repeat expansion. He had more features of FXS than the previously reported patient with the same mutation. Twenty individuals reported previously with rare missense or nonsense mutations or other coding disturbances of the FMR1 gene ranged in age from infancy to 50 years ; most were verbal with limited speech, had autism and hyperactivity, and all had intellectual disability. Four of the 20 individuals had a mutation within exon 15, three within exon 5, and two within exon 2. The FMR1 missense mutation (c.413G>A) is the same as in a previously reported male where it was shown that there was preservation of the post-synaptic function of the fragile X mental retardation protein (FMRP), the encoded protein of the FMR1 gene was preserved. Both patients with this missense mutation had physical, cognitive, and behavioral features similarly seen in FXS.

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16. Smerbeck A. The Survey of Favorite Interests and Activities : Assessing and understanding restricted interests in children with autism spectrum disorder. Autism. 2017 : 1362361317742140.

Restricted interests are an established diagnostic symptom of autism spectrum disorder. While there is considerable evidence that these interests have maladaptive consequences, they also provide a range of benefits. This article introduces a new instrument, the Survey of Favorite Interests and Activities, and uses it to examine the nature of restricted interests in autism spectrum disorder. Respondents report substantial benefits of restricted interests as well as areas of difficulty. The Survey of Favorite Interests and Activities assesses Social Flexibility, Perseveration, Respondent Discomfort, Adaptive Coping, and Atypicality. All scales have Cronbach’s alpha > 0.70. Age and socioeconomic status have little effect on Survey of Favorite Interests and Activities scales ; nor does gender with the exception of interest Atypicality. The expected pattern of correlations with existing scales was found. Research and clinical implications are discussed.

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17. Trevisan DA, Roberts N, Lin C, Birmingham E. How do adults and teens with self-declared Autism Spectrum Disorder experience eye contact ? A qualitative analysis of first-hand accounts. PLoS One. 2017 ; 12(11) : e0188446.

A tendency to avoid eye contact is an early indicator of Autism Spectrum Disorder (ASD), and difficulties with eye contact often persist throughout the lifespan. Eye contact difficulties may underlie social cognitive deficits in ASD, and can create significant social and occupational barriers. Thus, this topic has received substantial research and clinical attention. In this study, we used qualitative methods to analyze self-reported experiences with eye contact as described by teens and adults with self-declared ASD. Results suggest people with a self- declared ASD diagnosis experience adverse emotional and physiological reactions, feelings of being invaded, and sensory overload while making eye contact, in addition to difficulties understanding social nuances, and difficulties receiving and sending nonverbal information. Some data support existing mindblindness frameworks, and hyperarousal or hypoarousal theories of eye contact, but we also present novel findings unaccounted for by existing frameworks. Additionally, we highlight innovative strategies people with self-declared ASD have devised to overcome or cope with their eye contact difficulties.

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18. Wu DM, Wen X, Han XR, Wang S, Wang YJ, Shen M, Fan SH, Zhuang J, Li MQ, Hu B, Sun CH, Bao YX, Yan J, Lu J, Zheng YL. Relationship Between Neonatal Vitamin D at Birth and Risk of Autism Spectrum Disorders : the NBSIB Study. J Bone Miner Res. 2017.

Previous studies suggested that lower vitamin D might be a risk factor for autism spectrum disorders (ASDs). The aim of this study was to estimate the prevalence of ASDs in 3-year-old Chinese children and to examine the association between neonatal vitamin D status and risk of ASDs. We conducted a study of live births who had taken part in expanded newborn screening (NBS), with outpatient follow-up when the children 3-year old. The children were confirmed for ASDs in outpatient by the Autism Diagnostic Interview-Revised and Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria. Intellectual disability (ID) status was defined by the intelligence quotient (IQ < 80) for all the participants. The study design included a 1:4 case to control design. The concentration of 25-hydroxyvitamin D3 [25(OH)D3] in children with ASD and controls were assessed from neonatal dried blood samples. A total of 310 children were diagnosed as having ASDs ; thus, the prevalence was 1.11% (95% CI, 0.99% to 1.23%). The concentration of 25(OH)D3 in 310 ASD and 1240 controls were assessed. The median 25(OH)D3 level was significantly lower in children with ASD as compared to controls (p < 0.0001). Compared with the fourth quartiles, the relative risk (RR) of ASDs was significantly increased for neonates in each of the three lower quartiles of the distribution of 25(OH)D3, and increased risk of ASDs by 260% (RR for lowest quartile : 3.6 ; 95% CI, 1.8 to 7.2 ; p < 0.001), 150% (RR for second quartile : 2.5 ; 95% CI, 1.4 to 3.5 ; p = 0.024), and 90% (RR for third quartile : 1.9 ; 95% CI, 1.1 to 3.3 ; p = 0.08), respectively. Furthermore, the nonlinear nature of the ID-risk relationship was more prominent when the data were assessed in deciles. This model predicted the lowest relative risk of ID in the 72rd percentile (corresponding to 48.1 nmol/L of 25(OH)D3). Neonatal vitamin D status was significantly associated with the risk of ASDs and intellectual disability. The nature of those relationships was nonlinear. (c) 2017 American Society for Bone and Mineral Research.

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19. Zeng K, Kang J, Ouyang G, Li J, Han J, Wang Y, Sokhadze EM, Casanova MF, Li X. Disrupted Brain Network in Children with Autism Spectrum Disorder. Sci Rep. 2017 ; 7(1) : 16253.

Alterations in brain connectivity have been extensively reported in autism spectrum disorder (ASD), while their effects on the topology of brain network are still unclear. This study investigated whether and how the brain networks in children with ASD were abnormally organized with resting state EEG. Temporal synchronization analysis was first applied to capture the aberrant brain connectivity. Then brain network topology was characterized by three graph analysis methods including the commonly-used weighted and binary graph, as well as minimum spanning tree (MST). Whole brain connectivity in ASD group was found to be significantly reduced in theta and alpha band compared to typically development children (TD). Weighted graph found significantly decreased path length together with marginally significantly decreased clustering coefficient in ASD in alpha band, indicating a loss of small-world architecture to a random network. Such abnormal network topology was also demonstrated in the binary graph. In MST analysis, children with ASD showed a significant lower leaf fractions with a decrease trend of tree hierarchy in the alpha band, suggesting a shift towards line-like decentralized organization in ASD. The altered brain network may offer an insight into the underlying pathology of ASD and possibly serve as a biomarker that may aid in diagnosis of ASD.

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