1. {{Erratum: Relation Between Infant Microbiota and Autism? Results from a National Cohort Sibling Design Study}}. {Epidemiology (Cambridge, Mass)}. 2019.
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2. Barchel D, Stolar O, De-Haan T, Ziv-Baran T, Saban N, Fuchs DO, Koren G, Berkovitch M. {{Oral Cannabidiol Use in Children With Autism Spectrum Disorder to Treat Related Symptoms and Co-morbidities}}. {Frontiers in pharmacology}. 2018; 9: 1521.
Objective: Children with autism spectrum disorder (ASD) commonly exhibit comorbid symptoms such as aggression, hyperactivity and anxiety. Several studies are being conducted worldwide on cannabidiol use in ASD; however, these studies are still ongoing, and data on the effects of its use is very limited. In this study we aimed to report the experience of parents who administer, under supervision, oral cannabinoids to their children with ASD. Methods: After obtaining a license from the Israeli Ministry of Health, parents of children with ASD were instructed by a nurse practitioner how to administer oral drops of cannabidiol oil. Information on comorbid symptoms and safety was prospectively recorded biweekly during follow-up interviews. An independent group of specialists analyzed these data for changes in ASD symptoms and drug safety. Results: 53 children at a median age of 11 (4-22) year received cannabidiol for a median duration of 66 days (30-588). Self-injury and rage attacks (n = 34) improved in 67.6% and worsened in 8.8%. Hyperactivity symptoms (n = 38) improved in 68.4%, did not change in 28.9% and worsened in 2.6%. Sleep problems (n = 21) improved in 71.4% and worsened in 4.7%. Anxiety (n = 17) improved in 47.1% and worsened in 23.5%. Adverse effects, mostly somnolence and change in appetite were mild. Conclusion: Parents’ reports suggest that cannabidiol may improve ASD comorbidity symptoms; however, the long-term effects should be evaluated in large scale studies.
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3. Burling JM, Kadambi A, Safari T, Lu H. {{The Impact of Autistic Traits on Self-Recognition of Body Movements}}. {Front Psychol}. 2018; 9: 2687.
Despite the sparse visual information and paucity of self-identifying cues provided by point-light stimuli, as well as a dearth of experience in seeing our own-body movements, people can identify themselves solely based on the kinematics of body movements. The present study found converging evidence of this remarkable ability using a broad range of actions with whole-body movements. In addition, we found that individuals with a high degree of autistic traits showed worse performance in identifying own-body movements, particularly for simple actions. A Bayesian analysis showed that action complexity modulates the relationship between autistic traits and self-recognition performance. These findings reveal the impact of autistic traits on the ability to represent and recognize own-body movements.
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4. Chen F, Wang L, Peng G, Yan N, Pan X. {{Development and evaluation of a 3-D virtual pronunciation tutor for children with autism spectrum disorders}}. {PLoS One}. 2019; 14(1): e0210858.
The deficit in speech sound production in some children with autism spectrum disorder (ASD) adds to their communication barriers. The 3-D virtual environments have been implemented to improve their communication abilities. However, there were no previous studies on the use of a 3-D virtual pronunciation tutor designed specifically to train pronunciation for children with ASD. To fill this research gap, the current study developed and evaluated a 3-D virtual tutor which served as a multimodal and real-data-driven speech production tutor to present both places and manners of Mandarin articulation. Using an eye-tracking technique (RED 5 Eye Tracker), Experiment 1 objectively investigated children’s gauged attention distribution online while learning with our computer-assisted 3-D virtual tutor in comparison to a real human face (HF) tutor. Eye-tracking results indicated most participants showed more interests in the visual speech cues of the 3-D tutor, and paid some degree of absolute attention to the additional visual speech information of both articulatory movements and airflow changes. To further compare treatment outcomes, training performance was evaluated in Experiment 2 with the ASD learners divided into two groups, with one group learning from the HF tutor and the other from the 3-D tutor (HF group vs. 3-D group). Both groups showed improvement with the help of computer-based training in the post-intervention test based on the calculation of a 5-point Likert scale. However, the 3-D group showed much higher gains in producing Mandarin stop and affricate consonants, and apical vowels. We conclude that our 3-D virtual imitation intervention system provides an effective approach of audiovisual pronunciation training for children with ASD.
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5. Eskow KG, Chasson GS, Summers JA. {{The Role of Choice and Control in the Impact of Autism Waiver Services on Family Quality of Life and Child Progress}}. {J Autism Dev Disord}. 2019.
Home and Community-Based Services (HCBS) Waivers provide support and services to families with a child/youth with autism spectrum disorder (ASD). Research indicates HCBS Waivers are positively related to family quality of life (FQoL) and Child Progress. This study replicated and expanded prior research using propensity score matching of 460 families. Results support prior findings that HCBS waivers have a positive impact on FQoL and aspects of child progress. This study also found that having choices in the selection of services and service providers, as well as control over day-to-day provision of services, strengthened both the child and family impacts of the Waiver services. In addition, the study provides preliminary evidence for psychometric properties of a quick and inexpensive parent-report of ASD severity.
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6. Finke EH, Kremkow JMD, Drager KDR, Murillo A, Richardson L, Serpentine EC. {{« I Would Like for My Child to be Happy with His Life »: Parental Hopes for Their Children with ASD Across the Lifespan}}. {J Autism Dev Disord}. 2019.
The purpose of this project was to understand the hopes of parents with children with ASD. Particularly understudied are the hopes parents have for long-term outcomes for their child. A cross-sectional focus group design was used and six focus groups were completed. These groups included parents of (1) preschool aged children who were recently diagnosed, (2) children in early elementary school, (3) children in later elementary school, (4) children in middle school, (5) children in high school, and (6) children who are adults with ASD. Results indicated 77.4% of the data were devoted to hopes for the children’s independence, happiness, and skill improvement; increased authentic socially significant relationships; and future employment.
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7. Foti F, Piras F, Vicari S, Mandolesi L, Petrosini L, Menghini D. {{Observational Learning in Low-Functioning Children With Autism Spectrum Disorders: A Behavioral and Neuroimaging Study}}. {Front Psychol}. 2018; 9: 2737.
New skills may be learned from the outcomes of their own internally generated actions (experiential learning) or from the observation of the consequences of externally generated actions (observational learning). Observational learning requires the coordination of cognitive functions and the processing of social information. Due to the « social » abilities underlying observational learning, the study of this process in individuals with limited social abilities such as those affected by Autism Spectrum Disorders (ASD) is worthy of being investigated. We asked a group of 16 low-functioning young children with ASD and group of 16 sex- and mental age-matched typically developing (TD) children to build a house with a set of bricks after a video-demonstration showing an actor who built the house (observational task – OBS task) and then to build by trial and error another house (experiential task – EXP task). For ASD group, performances in learning tasks were correlated with measures of cortical thickness of specific Regions of Interest (ROI) and volume of deep gray matter structures known to be related with such kinds of learning. According to our a priori hypothesis, for OBS task we selected the following ROI: frontal lobe (pars opercularis, pars triangularis, and premotor area), parietal lobe (inferior parietal gyrus), temporal lobe (superior temporal gyrus), cerebellar hemispheres. For EXP task, we selected the following ROI: precentral frontal gyrus and superior frontal gyrus, cerebellar hemispheres, basal ganglia, thalamus. Although performances of ASD and TD children improved in both OBS and EXP tasks, children with ASD obtained lower scores of goal achievement than TD children in both learning tasks. Only in ASD group, goal achievement scores positively correlated with hyperimitations indicating that children with ASD tended to have a « copy-all » approach that facilitated the goal achievement. Moreover, the marked hyperimitative tendencies of children with ASD were positively associated with the thickness of left pars opercularis, left premotor area, and right superior temporal gyrus, areas belonging to mirror neuron system, and with the volume of both cerebellar hemispheres. These findings suggest that in children with ASD the hyperimitation can represent a learning strategy that might be related to the mirror neuron system.
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8. Franck N, Bon L, Dekerle M, Plasse J, Massoubre C, Pommier R, Legros-Lafarge E, Jaafari N, Guillard-Bouhet N, Quiles C, Couhet G, Verdoux H, Gouache B, Martin B, Cervello S, Demily C, Dubreucq J. {{Satisfaction and Needs in Serious Mental Illness and Autism Spectrum Disorder: The REHABase Psychosocial Rehabilitation Project}}. {Psychiatr Serv}. 2019: appips201800420.
OBJECTIVE:: The REHABase project is a French observational, prospective, and multicenter cohort study of serious mental illness and autism spectrum disorder (ASD), launched in 2016 for a planned minimum duration of 15 years. The aim is to characterize the care and quality-of-life needs of participants. This article presents initial results from data collection. METHODS:: Psychosocial, cognitive, and functional data were collected at baseline, annually, and after rehabilitation care. Data from the baseline evaluation on diagnoses, medications, well-being, insight, life satisfaction, and care needs are presented. The clinical profiles of REHABase participants with serious mental illness or ASD were assessed in relation to their level of satisfaction with life and well-being in nine life dimensions and their needs, according to their stage of recovery in a five-stage model. RESULTS:: Baseline data were collected for 1,397 participants between January 2016 and August 2018. Main diagnoses were schizophrenia spectrum disorder (49%); ASD (13%); and personality (12%), bipolar (9%), and major depressive (6%) disorders. More than 50% of participants reported needs for care or interventions in four of nine dimensions: employment, cognitive functioning, symptom management, and interpersonal relationships. Nearly half of participants were not in the active stages of recovery (stages 4 and 5), and even those considered to have reached the final stage continued to require help in several areas. CONCLUSIONS:: Most participants had already received psychiatric care for several years, and most remained dissatisfied with their social and emotional life and their psychological well-being.
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9. Fulceri F, Grossi E, Contaldo A, Narzisi A, Apicella F, Parrini I, Tancredi R, Calderoni S, Muratori F. {{Motor Skills as Moderators of Core Symptoms in Autism Spectrum Disorders: Preliminary Data From an Exploratory Analysis With Artificial Neural Networks}}. {Front Psychol}. 2018; 9: 2683.
Motor disturbances have been widely observed in children with autism spectrum disorder (ASD), and motor problems are currently reported as associated features supporting the diagnosis of ASD in the current Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Studies on this issue reported disturbances in different motor domains, including both gross and fine motor areas as well as coordination, postural control, and standing balance. However, they failed to clearly state whether motor impairments are related to demographical and developmental features of ASD. Both the different methodological approaches assessing motor skills and the heterogeneity in clinical features of participants analyzed have been implicated as contributors to variance in findings. However, the non-linearity of the relationships between variables may account for the inability of the traditional analysis to grasp the core problem suggesting that the « single symptom approach analysis » should be overcome. Artificial neural networks (ANNs) are computational adaptive systems inspired by the functioning processes of the human brain particularly adapted to solving non-linear problems. This study aimed to apply the ANNs to reveal the entire spectrum of the relationship between motor skills and clinical variables. Thirty-two male children with ASD [mean age: 48.5 months (SD: 8.8); age range: 30-60 months] were recruited in a tertiary care university hospital. A multidisciplinary comprehensive diagnostic evaluation was associated with a standardized assessment battery for motor skills, the Peabody Developmental Motor Scale-Second Edition. Exploratory analyses were performed through the ANNs. The findings revealed that poor motor skills were a common clinical feature of preschoolers with ASD, relating both to the high level of repetitive behaviors and to the low level of expressive language. Moreover, unobvious trends among motor, cognitive and social skills have been detected. In conclusion, motor abnormalities in preschoolers with ASD were widespread, and the degree of impairment may inform clinicians about the severity of ASD core symptoms. Understanding motor disturbances in children with ASD may be relevant to clarify neurobiological basis and ultimately to guide the development of tailored treatments.
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10. Graciarena M, Seiffe A, Nait-Oumesmar B, Depino AM. {{Hypomyelination and Oligodendroglial Alterations in a Mouse Model of Autism Spectrum Disorder}}. {Frontiers in cellular neuroscience}. 2018; 12: 517.
Autism spectrum disorders (ASDs) are neuropsychiatric diseases characterized by impaired social interaction, communication deficits, and repetitive and stereotyped behaviors. ASD etiology is unknown, and both genetic and environmental causes have been proposed. Different brain structures are believed to play a role in ASD-related behaviors, including medial prefrontal cortex (mPFC), hippocampus, piriform cortex (Pir), basolateral amygdala (BLA) and Cerebellum. Compelling evidence suggests a link between white matter modifications and ASD symptoms in patients. Besides, an hypomyelination of the mPFC has been associated in rodents to social behavior impairment, one of the main symptoms of ASD. However, a comparative analysis of myelination as well as oligodendroglial (OL)-lineage cells in brain regions associated to social behaviors in animal models of ASD has not been performed so far. Here, we investigated whether OL-lineage cells and myelination are altered in a murine model of ASD induced by the prenatal exposure to valproic acid (VPA). We showed an hypomyelination in the BLA and Pir of adult VPA-exposed mice. These results were accompanied by a decrease in the number of OL-lineage cells and of mature OLs in the Pir, in addition to the mPFC, where myelination presented no alterations. In these regions the number of oligodendrocyte progenitors (OPCs) remained unaltered. Likewise, activation of histone deacetylases (HDACs) on OL-lineage cells in adulthood showed no differences. Overall, our results reveal OL-lineage cell alterations and hypomyelination as neuropathological hallmarks of ASD that have been overlooked so far.
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11. Jure R. {{Autism Pathogenesis: The Superior Colliculus}}. {Front Neurosci}. 2018; 12: 1029.
After been exposed to the visual input, in the first year of life, the brain experiences subtle but massive changes apparently crucial for communicative/emotional and social human development. Its lack could be the explanation of the very high prevalence of autism in children with total congenital blindness. The present theory postulates that the superior colliculus is the key structure for such changes for several reasons: it dominates visual behavior during the first months of life; it is ready at birth for complex visual tasks; it has a significant influence on several hemispheric regions; it is the main brain hub that permanently integrates visual and non-visual, external and internal information (bottom-up and top-down respectively); and it owns the enigmatic ability to take non-conscious decisions about where to focus attention. It is also a sentinel that triggers the subcortical mechanisms which drive social motivation to follow faces from birth and to react automatically to emotional stimuli. Through indirect connections it also activates simultaneously several cortical structures necessary to develop social cognition and to accomplish the multiattentional task required for conscious social interaction in real life settings. Genetic or non-genetic prenatal or early postnatal factors could disrupt the SC functions resulting in autism. The timing of postnatal biological disruption matches the timing of clinical autism manifestations. Astonishing coincidences between etiologies, clinical manifestations, cognitive and pathogenic autism theories on one side and SC functions on the other are disclosed in this review. Although the visual system dependent of the SC is usually considered as accessory of the LGN canonical pathway, its imprinting gives the brain a qualitatively specific functions not supplied by any other brain structure.
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12. Kazeminejad A, Sotero RC. {{Topological Properties of Resting-State fMRI Functional Networks Improve Machine Learning-Based Autism Classification}}. {Front Neurosci}. 2018; 12: 1018.
Automatic algorithms for disease diagnosis are being thoroughly researched for use in clinical settings. They usually rely on pre-identified biomarkers to highlight the existence of certain problems. However, finding such biomarkers for neurodevelopmental disorders such as Autism Spectrum Disorder (ASD) has challenged researchers for many years. With enough data and computational power, machine learning (ML) algorithms can be used to interpret the data and extract the best biomarkers from thousands of candidates. In this study, we used the fMRI data of 816 individuals enrolled in the Autism Brain Imaging Data Exchange (ABIDE) to introduce a new biomarker extraction pipeline for ASD that relies on the use of graph theoretical metrics of fMRI-based functional connectivity to inform a support vector machine (SVM). Furthermore, we split the dataset into 5 age groups to account for the effect of aging on functional connectivity. Our methodology achieved better results than most state-of-the-art investigations on this dataset with the best model for the >30 years age group achieving an accuracy, sensitivity, and specificity of 95, 97, and 95%, respectively. Our results suggest that measures of centrality provide the highest contribution to the classification power of the models.
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13. Liu F, Li J, Wu F, Zheng H, Peng Q, Zhou H. {{Altered composition and function of intestinal microbiota in autism spectrum disorders: a systematic review}}. {Translational psychiatry}. 2019; 9(1): 43.
At present, the pathophysiology of autism spectrum disorder (ASD) remains unclear. Increasing evidence suggested that gut microbiota plays a critical role in gastrointestinal symptoms and behavioral impairment in ASD patients. The primary aim of this systematic review is to investigate potential evidence for the characteristic dysbiosis of gut microbiota in ASD patients compared with healthy controls (HCs). The MEDLINE, EMBASE, Web of Science and Scopus were systematically searched before March 2018. Human studies that compared the composition of gut microbiota in ASD patients and HCs using culture-independent techniques were included. Independent data extraction and quality assessment of studies were conducted according to PRISMA statement and Newcastle-Ottawa Scale. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to infer biological functional changes of the shifted microbiota with the available data in four studies. Sixteen studies with a total sample size of 381 ASD patients and 283 HCs were included in this systematic review. The quality of the studies was evaluated as medium to high. The overall changing of gut bacterial community in terms of beta-diversity was consistently observed in ASD patients compared with HCs. Furthermore, Bifidobacterium, Blautia, Dialister, Prevotella, Veillonella, and Turicibacter were consistently decreased, while Lactobacillus, Bacteroides, Desulfovibrio, and Clostridium were increased in patients with ASD relative to HCs in certain studies. This systematic review demonstrated significant alterations of gut microbiota in ASD patients compared with HCs, strengthen the evidence that dysbiosis of gut microbiota may correlate with behavioral abnormality in ASD patients. However, results of inconsistent changing also existed and further big-sampled well-designed studies are needed. Generally, as a potential mediator of risk factors, the gut microbiota could be a novel target for ASD patients in the future.
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14. Nevill RE, Havercamp SM. {{Effects of mindfulness, coping styles and resilience on job retention and burnout in caregivers supporting aggressive adults with developmental disabilities}}. {J Intellect Disabil Res}. 2019.
BACKGROUND: Considering the growing body of studies investigating the effects of mindfulness-based interventions on caregivers supporting people with developmental disabilities, the current study aimed to explore the role that the cognitive processes of mindfulness, coping style and resilience played in predicting caregiver retention and burnout among a sample of direct support professionals working with aggressive adults with developmental disabilities. METHODS: Ninety-seven direct support professionals were surveyed to determine level of mindfulness, coping styles, resilience and burnout and were interviewed 3 months later to determine if they were still working with the aggressive adult. RESULTS: Mindfulness skills of describing non-judgmentally and observing one’s environment, as well as problem-focused coping, emerged as protective factors against burnout, while avoidance-focused and maladaptive coping emerged as risk factors. Mindful openness acted as the only predictor of job retention. CONCLUSIONS: These results support that paid caregivers should receive trainings in mindfulness and positive coping mechanisms as part of their job trainings, to promote positive outcomes for both themselves and the people they support.
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15. Raza S, Zwaigenbaum L, Sacrey LR, Bryson S, Brian J, Smith IM, Reid K, Roberts W, Szatmari P, Vaillancourt T, Roncadin C, Garon N. {{Brief Report: Evaluation of the Short Quantitative Checklist for Autism in Toddlers (Q-CHAT-10) as a Brief Screen for Autism Spectrum Disorder in a High-Risk Sibling Cohort}}. {J Autism Dev Disord}. 2019.
This study examined the potential of the short form of the Quantitative Checklist for Autism in Toddlers (Q-CHAT-10) to identify autism spectrum disorder (ASD) in a high-risk sibling cohort. High-risk (HR; siblings of children diagnosed with ASD) and low-risk (LR; no family history of ASD) toddlers were assessed prospectively at 18 and 24 months of age using the Q-CHAT-10 and underwent blind diagnostic assessment for ASD at 36 months of age. The results indicated that at 18 and 24 months, total score differentiated between HR toddlers subsequently diagnosed with ASD from other HR and LR toddlers. The sensitivity at both time points was acceptable; however, the specificity was below the level recommended for clinical application.
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16. Reisinger DL, Shaffer RC, Pedapati EV, Dominick KC, Erickson CA. {{A Pilot Quantitative Evaluation of Early Life Language Development in Fragile X Syndrome}}. {Brain Sci}. 2019; 9(2).
Language delay and communication deficits are a core characteristic of the fragile X syndrome (FXS) phenotype. To date, the literature examining early language development in FXS is limited potentially due to barriers in language assessment in very young children. The present study is one of the first to examine early language development through vocal production and the language learning environment in infants and toddlers with FXS utilizing an automated vocal analysis system. Child vocalizations, conversational turns, and adult word counts in the home environment were collected and analyzed in a group of nine infants and toddlers with FXS and compared to a typically developing (TD) normative sample. Results suggest infants and toddlers with FXS are exhibiting deficits in their early language skills when compared to their chronological expectations. Despite this, when accounting for overall developmental level, their early language skills appear to be on track. Additionally, FXS caregivers utilize less vocalizations around infants and toddlers with FXS; however, additional research is needed to understand the true gap between FXS caregivers and TD caregivers. These findings provide preliminary information about the early language learning environment and support for the feasibility of utilizing an automated vocal analysis system within the FXS population that could ease data collection and further our understanding of the emergence of language development.
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17. Rose SA, Wass S, Jankowski JJ, Feldman JF, Djukic A. {{Attentional shifting and disengagement in Rett syndrome}}. {Neuropsychology}. 2019.
OBJECTIVE: The purpose of the present study was to deepen our understanding of attention (a core cognitive ability) in Rett syndrome (RTT), an x-linked neurodevelopmental disorder caused by mutations in the MECP2 gene. We focused on 2 key aspects of visual orienting-shifting and disengaging attention-both of which are critical for exploring the visual world. We used gaze-based measures and eye-tracking technology to minimize demands on the limited verbal and motor abilities associated with RTT. METHOD: Shifting and disengaging attention were examined in 31 children (2-12 years) with Rett Syndrome (RTT) and 31 age-matched typically developing (TD) controls. Using the gap-overlap paradigm, the frequency and speed of shifting attention from a central to peripheral target were compared on Baseline trials, where the central stimulus disappears as the peripheral target appears, and Overlap trials, where the central stimulus remains, thus requiring disengagement. RESULTS: Our findings revealed that children with RTT had more « sticky fixations » (p < .001). That is, they had fewer saccades to the peripheral target than TD children, and this was true on both baseline (77% vs. 95%), and overlap trials (63% vs. 90%). The younger children in the RTT group also had slower saccadic RTs (SRTs) than their TD counterparts (p = .04). Within the RTT group, SRTs correlated with symptom severity. Surprisingly, disengagement cost (the relative difference between gap and overlap SRTs) did not differ across groups. CONCLUSION: Our results suggest that children with Rett have difficulty shifting attention and, to a lesser extent, disengaging attention, whereas with other disorders, problems with disengagement are paramount. (PsycINFO Database Record (c) 2019 APA, all rights reserved). Lien vers le texte intégral (Open Access ou abonnement)
18. Rosenthal IA, Hutcherson CA, Adolphs R, Stanley DA. {{Deconstructing Theory-of-Mind Impairment in High-Functioning Adults with Autism}}. {Current biology : CB}. 2019.
Inferring the beliefs, desires, and intentions of other people (« theory of mind, » ToM) requires specialized psychological processes that represent the minds of others as distinct from our own [1-3]. ToM is engaged ubiquitously in our everyday social behavior and features a specific developmental trajectory [4] that is notably delayed in children with autism spectrum disorder (ASD) [5, 6]. In healthy individuals, model-based analyses of social learning and decision-making have successfully elucidated specific computational components of ToM processing [7-11]. However, the use of this approach to study ToM impairment in ASD has been extremely limited [10, 12]. To better characterize specific ToM impairment in ASD, we developed a novel learning task and applied model-based analyses in high-functioning adults with ASD and matched healthy controls. After completing a charitable donation task, participants performed a « mentalizer » task in which they observed another person (the agent) complete the same charity task. The mentalizer task probed the participants’ ability to acquire and use ToM representations. To accurately predict agent behavior, participants needed to dynamically track the agent’s beliefs (true or false) about an experimental context that varied over time and use that information to infer the agent’s intentions from their actions. ASD participants were specifically impaired at using their estimates of agent belief to learn agent intentions, though their ability to track agent belief was intact and their reasoning about belief and intentions was rational. Furthermore, model parameters correlated with aspects of social functioning, e.g., ADOS severity scores [13]. Together, these results identify novel, and more specific, targets for future research.
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19. Shams S, Foley KA, Kavaliers M, MacFabe DF, Ossenkopp KP. {{Systemic treatment with the enteric bacterial metabolic product propionic acid results in reduction of social behavior in juvenile rats: Contribution to a rodent model of autism spectrum disorder}}. {Dev Psychobiol}. 2019.
The role of the gut microbiome and its enteric metabolites, such as short-chain fatty acids (SCFAs), in the etiology of autism spectrum disorders (ASDs) has recently received increased attention. Of particular interest has been the SCFA, propionic acid (PPA). Several different rodent models have been developed using PPA treatment to examine behaviors of relevance to ASD. The effects of systemic (intraperitoneal, i.p.) administration of PPA on social behavior, anxiety-related behavior, and locomotor activity in juvenile male rats (age 35 days) were examined in this study. Rats received seven i.p. injections of buffered PPA (500 mg/kg) or phosphate-buffered saline. Behavior was video-recorded during social interaction in a large open field (first four injections) or assessed in an automated activity system (individual animals, last three injections). PPA treatment significantly reduced social interaction, increased anxiety-related behavior, and produced hypoactivity and increased abnormal motor movements. These findings suggest that PPA alters behaviors of relevance to ASD in juvenile rats. These results contribute to the behavioral validity of the rodent model of ASD with systemic PPA treatment.
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20. Shiohama T, Levman J, Takahashi E. {{Surface- and voxel-based brain morphologic study in Rett and Rett-like syndrome with MECP2 mutation}}. {Int J Dev Neurosci}. 2019.
Rett syndrome (RTT) is a rare congenital disorder which in most cases (95%) is caused by methyl-CpG binding protein 2 (MECP2) mutations. RTT is characterized by regression in global development, epilepsy, autistic features, acquired microcephaly, habitual hand clapping, loss of purposeful hand skills, and autonomic dysfunctions. Although the literature has demonstrated decreased volumes of the cerebrum, cerebellum, and the caudate nucleus in RTT patients, surface-based brain morphology including cortical thickness and cortical gyrification analyses are lacking in RTT. We present quantitative surface- and voxel-based morphological measurements in young children with RTT and Rett-like syndrome (RTT-l) with MECP2 mutations. The 8 structural T1-weighted MR images were obtained from 7 female patients with MECP2 mutations (3 classic RTT, 2 variant RTT, and 2 RTT-l) (mean age 5.2 [standard deviation 3.3] years old). Our analyses demonstrated decreased total volumes of the cerebellum in RTT/RTT-l compared to gender- and age-matched controls (t (22)=-2.93, p = .008, Cohen’s d = 1.27). In contrast, global cerebral cortical surface areas, global/regional cortical thicknesses, the degree of global gyrification, and global/regional gray and white matter volumes were not statistically significantly different between the two groups. Our findings, as well as literature findings, suggest that early brain abnormalities associated with RTT/RTT-l (with MECP2 mutations) can be detected as regionally decreased cerebellar volumes. Decreased cerebellar volume may be helpful for understanding the etiology of RTT/RTT-l.
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21. Soda T, Mapelli L, Locatelli F, Botta L, Goldfarb M, Prestori F, D’Angelo E. {{Hyper-excitability and hyper-plasticity disrupt cerebellar signal transfer in the IB2 KO mouse model of autism}}. {J Neurosci}. 2019.
Autism spectrum disorders (ASD) are pervasive neurodevelopmental conditions that often involve mutations affecting synaptic mechanisms. Recently, the involvement of cerebellum in ASD has been suggested but the underlying functional alterations remained obscure. We investigated single-neuron and microcircuit properties in IB2 KO mice of either sex. The IB2 gene (chr22q13.3 terminal region) deletion occurs in virtually all cases of Phelan-McDermid syndrome, causing autistic symptoms and a severe delay in motor skill acquisition. IB2 KO granule cells showed a larger NMDA receptor-mediated current and enhanced intrinsic excitability raising the excitatory/inhibitory balance. Furthermore, the spatial organization of granular layer responses to mossy fibers shifted from a Mexican hat to stovepipe hat profile, with stronger excitation in the core and weaker inhibition in the surround. Finally, the size and extension of long-term synaptic plasticity was remarkably increased. These results show for the first time that hyper-excitability and hyper-plasticity disrupt signal transfer in the granular layer of IB2 KO mice supporting cerebellar involvement in the pathogenesis of ASD.SIGNIFICANCE STATEMENTThis paper shows for the first time a complex set of alterations in the cerebellum granular layer of a mouse model (IB2 KO) of autism spectrum disorders. The IB2 KO in mice mimics the deletion of the corresponding gene in the Phelan McDermid syndrome in humans. The changes reported here are centered on NMDA receptor hyper-activity, hyper -plasticity and hyper-excitability. These, in turn, increase the excitatory/inhibitory balance and alter the shape of center/surround structures that emerge in the granular layer in response to mossy fiber activity. These results supports recent theories suggesting the involvement of cerebellum in autism spectrum disorders.
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22. Thabtah F, Peebles D. {{A new machine learning model based on induction of rules for autism detection}}. {Health informatics journal}. 2019: 1460458218824711.
Autism spectrum disorder is a developmental disorder that describes certain challenges associated with communication (verbal and non-verbal), social skills, and repetitive behaviors. Typically, autism spectrum disorder is diagnosed in a clinical environment by licensed specialists using procedures which can be lengthy and cost-ineffective. Therefore, scholars in the medical, psychology, and applied behavioral science fields have in recent decades developed screening methods such as the Autism Spectrum Quotient and Modified Checklist for Autism in Toddlers for diagnosing autism and other pervasive developmental disorders. The accuracy and efficiency of these screening methods rely primarily on the experience and knowledge of the user, as well as the items designed in the screening method. One promising direction to improve the accuracy and efficiency of autism spectrum disorder detection is to build classification systems using intelligent technologies such as machine learning. Machine learning offers advanced techniques that construct automated classifiers that can be exploited by users and clinicians to significantly improve sensitivity, specificity, accuracy, and efficiency in diagnostic discovery. This article proposes a new machine learning method called Rules-Machine Learning that not only detects autistic traits of cases and controls but also offers users knowledge bases (rules) that can be utilized by domain experts in understanding the reasons behind the classification. Empirical results on three data sets related to children, adolescents, and adults show that Rules-Machine Learning offers classifiers with higher predictive accuracy, sensitivity, harmonic mean, and specificity than those of other machine learning approaches such as Boosting, Bagging, decision trees, and rule induction.
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23. Wang M, Wan J, Rong H, He F, Wang H, Zhou J, Cai C, Wang Y, Xu R, Yin Z, Zhou W. {{Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder}}. {mSystems}. 2019; 4(1).
Changes in the gut microenvironment may influence the pathogenesis of autism spectrum disorders (ASD). Here, we investigated the composition of the gut microbiota and metabolites in children with ASD. Ninety-two children with ASD and 42 age-matched children exhibiting typical development (TD) were enrolled in the two-stage study. In the discovery stage, shotgun metagenomic sequencing and liquid chromatography-mass spectrometry (LC-MS) were performed simultaneously on fecal samples obtained from 43 children in the ASD group and 31 children in the TD group. Systematic bioinformatic analyses were performed to identify gut metabolites associated with altered gut microbiota composition. At the validation stage, differential metabolites were tested using LC-MS with an additional 49 and 11 children in the ASD and TD groups, respectively. Altered glutamate metabolites were found in the ASD group, along with a decline in 2-keto-glutaramic acid and an abundance of microbiota associated with glutamate metabolism. These changes in glutamate metabolism were correlated with lower levels of the highly abundant bacteria Bacteroides vulgatus and higher levels of the potentially harmful Eggerthella lenta and Clostridium botulinum. Lower gut cortisol levels have also been identified in the ASD group and associated with changes in gut microbiota glutamate metabolism. Finally, gut 2-keto-glutaramic acid was validated as a potential biomarker for ASD. The significant changes in the gut microenvironment in children with ASD may provide new insight into the cause of ASD and aid in the search for diagnostic and therapeutic approaches. IMPORTANCE Multiple lines of evidence suggest that the gut microbiota may play an important role in the pathogenesis of ASD, but the specific mechanism is still unclear. Through a comprehensive gut metagenomic and metabolome study of children with ASD, alterations in gut metabolite composition were found in children with ASD, and these alterations were linked to changes in gut microbiota composition. This may give us a deeper understanding of the role of gut microbiota in the pathogenesis of ASD.
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24. Zapata-Fonseca L, Dotov D, Fossion R, Froese T, Schilbach L, Vogeley K, Timmermans B. {{Multi-Scale Coordination of Distinctive Movement Patterns During Embodied Interaction Between Adults With High-Functioning Autism and Neurotypicals}}. {Front Psychol}. 2018; 9: 2760.
Autism Spectrum Disorder (ASD) can be understood as a social interaction disorder. This requires researchers to take a « second-person » stance and to use experimental setups based on bidirectional interactions. The present work offers a quantitative description of movement patterns exhibited during computer-mediated real-time sensorimotor interaction in 10 dyads of adult participants, each consisting of one control individual (CTRL) and one individual with high-functioning autism (HFA). We applied time-series analyses to their movements and found two main results. First, multi-scale coordination between participants was present. Second, despite this dyadic alignment and our previous finding that individuals with HFA can be equally sensitive to the other’s presence, individuals’ movements differed in style: in contrast to CTRLs, HFA participants appeared less inclined to sustain mutual interaction and instead explored the virtual environment more generally. This finding is consistent with social motivation deficit accounts of ASD, as well as with hypersensitivity-motivated avoidance of overstimulation. Our research demonstrates the utility of time series analyses for the second-person stance and complements previous work focused on non-dynamical and performance-based variables.
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25. Zheng R, Naiman ID, Skultety J, Passmore SR, Lyons J, Glazebrook CM. {{The Impact of Different Movement Types on Motor Planning and Execution in Individuals With Autism Spectrum Disorder}}. {Motor control}. 2019: 1-20.
Although there are consistent reports that motor skills are affected in individuals with autism, the details are still debated; specifically, why individuals spend more time preparing movements and whether or not movement execution takes longer. The present study investigated if the conflicting reports were related to: (a) differences in movement type and (b) if longer reaction times were related to the time for motor planning or for force-generation processes. Participants performed three different movement types. People with autism had longer premotor reaction times and movement times for the three-dimensional movements only. We suggest individuals with autism have difficulty planning and executing unconstrained reaching movements specifically. The present results are consistent with evidence that autistic individuals have more difficulty effectively using visual feedback but can use tactile feedback to execute reaching movements efficiently and accurately.
