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Alterations in electrophysiological indices of perceptual processing and discrimination are associated with co-occurring emotional and behavioural problems in adolescents with autism spectrum disorder / Virginia CARTER LENO in Molecular Autism, 9 (2018)
[article]
Titre : Alterations in electrophysiological indices of perceptual processing and discrimination are associated with co-occurring emotional and behavioural problems in adolescents with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Virginia CARTER LENO, Auteur ; S. CHANDLER, Auteur ; P. WHITE, Auteur ; I. YORKE, Auteur ; Tony CHARMAN, Auteur ; A. PICKLES, Auteur ; E. SIMONOFF, Auteur Article en page(s) : 50p. Langues : Anglais (eng) Mots-clés : asd Comorbidity eeg erp IAMHealth Perceptual processing Psychopathology Sensory approved by Camden and King's Cross Ethics Sub-Committee (14/LO/2098).Not applicable.AP receives royalties from the Social Communication Questionnaire. The other authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Many young people with autism spectrum disorder (ASD) experience emotional and behavioural problems. However, the causes of these co-occurring difficulties are not well understood. Perceptual processing atypicalities are also often reported in individuals with ASD, but how these relate to co-occurring emotional and behavioural problems remains unclear, and few studies have used objective measurement of perceptual processing. Methods: Event-related potentials (ERPs) were recorded in response to both standard and deviant stimuli (which varied in pitch) in an auditory oddball paradigm in adolescents (mean age of 13.56 years, SD = 1.12, range = 11.40-15.70) with ASD (n = 43) with a wide range of IQ (mean IQ of 84.14, SD = 24.24, range 27-129). Response to deviant as compared to standard stimuli (as indexed by the mismatch negativity (MMN)) and response to repeated presentations of standard stimuli (habituation) were measured. Multivariate regression tested the association between neural indices of perceptual processing and co-occurring emotional and behavioural problems. Results: Greater sensitivity to changes in pitch in incoming auditory information (discrimination), as indexed by increased MMN amplitude, was associated with higher levels of parent-rated behaviour problems. MMN amplitude also showed a trend positive correlation with parent-rated sensory hyper-sensitivity. Conversely, greater habituation at the later N2 component was associated with higher levels of emotional problems. Upon more detailed analyses, this appeared to be driven by a selectively greater ERP response to the first (but not the second or third) standard stimuli that followed deviant stimuli. A similar pattern of association was found with other measures of anxiety. All results remained in covariation analyses controlling for age, sex and IQ, although the association between MMN amplitude and behaviour problems became non-significant when controlling for ASD severity. Conclusions: Findings suggest that alterations in mechanisms of perceptual processing and discrimination may be important for understanding co-occurring emotional and behavioural problems in young people with ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0236-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371
in Molecular Autism > 9 (2018) . - 50p.[article] Alterations in electrophysiological indices of perceptual processing and discrimination are associated with co-occurring emotional and behavioural problems in adolescents with autism spectrum disorder [Texte imprimé et/ou numérique] / Virginia CARTER LENO, Auteur ; S. CHANDLER, Auteur ; P. WHITE, Auteur ; I. YORKE, Auteur ; Tony CHARMAN, Auteur ; A. PICKLES, Auteur ; E. SIMONOFF, Auteur . - 50p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 50p.
Mots-clés : asd Comorbidity eeg erp IAMHealth Perceptual processing Psychopathology Sensory approved by Camden and King's Cross Ethics Sub-Committee (14/LO/2098).Not applicable.AP receives royalties from the Social Communication Questionnaire. The other authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Many young people with autism spectrum disorder (ASD) experience emotional and behavioural problems. However, the causes of these co-occurring difficulties are not well understood. Perceptual processing atypicalities are also often reported in individuals with ASD, but how these relate to co-occurring emotional and behavioural problems remains unclear, and few studies have used objective measurement of perceptual processing. Methods: Event-related potentials (ERPs) were recorded in response to both standard and deviant stimuli (which varied in pitch) in an auditory oddball paradigm in adolescents (mean age of 13.56 years, SD = 1.12, range = 11.40-15.70) with ASD (n = 43) with a wide range of IQ (mean IQ of 84.14, SD = 24.24, range 27-129). Response to deviant as compared to standard stimuli (as indexed by the mismatch negativity (MMN)) and response to repeated presentations of standard stimuli (habituation) were measured. Multivariate regression tested the association between neural indices of perceptual processing and co-occurring emotional and behavioural problems. Results: Greater sensitivity to changes in pitch in incoming auditory information (discrimination), as indexed by increased MMN amplitude, was associated with higher levels of parent-rated behaviour problems. MMN amplitude also showed a trend positive correlation with parent-rated sensory hyper-sensitivity. Conversely, greater habituation at the later N2 component was associated with higher levels of emotional problems. Upon more detailed analyses, this appeared to be driven by a selectively greater ERP response to the first (but not the second or third) standard stimuli that followed deviant stimuli. A similar pattern of association was found with other measures of anxiety. All results remained in covariation analyses controlling for age, sex and IQ, although the association between MMN amplitude and behaviour problems became non-significant when controlling for ASD severity. Conclusions: Findings suggest that alterations in mechanisms of perceptual processing and discrimination may be important for understanding co-occurring emotional and behavioural problems in young people with ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0236-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 Intestinal dysmotility in a zebrafish (Danio rerio) shank3a;shank3b mutant model of autism / D. M. JAMES in Molecular Autism, 10 (2019)
[article]
Titre : Intestinal dysmotility in a zebrafish (Danio rerio) shank3a;shank3b mutant model of autism Type de document : Texte imprimé et/ou numérique Auteurs : D. M. JAMES, Auteur ; R. A. KOZOL, Auteur ; Y. KAJIWARA, Auteur ; A. L. WAHL, Auteur ; E. C. STORRS, Auteur ; Joseph D. BUXBAUM, Auteur ; M. KLEIN, Auteur ; B. MOSHIREE, Auteur ; J. E. DALLMAN, Auteur Article en page(s) : 3 p. Langues : Anglais (eng) Mots-clés : *Digestive transit *Enteroendocrine *Peristaltic rate *Phelan-McDermid syndrome approved by the Institutional Animal Care and Use Committee of University of Miami.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background and aims: Autism spectrum disorder (ASD) is currently estimated to affect more than 1% of the world population. For people with ASD, gastrointestinal (GI) distress is a commonly reported but a poorly understood co-occurring symptom. Here, we investigate the physiological basis for GI distress in ASD by studying gut function in a zebrafish model of Phelan-McDermid syndrome (PMS), a condition caused by mutations in the SHANK3 gene. Methods: To generate a zebrafish model of PMS, we used CRISPR/Cas9 to introduce clinically related C-terminal frameshift mutations in shank3a and shank3b zebrafish paralogues (shank3abDeltaC). Because PMS is caused by SHANK3 haploinsufficiency, we assessed the digestive tract (DT) structure and function in zebrafish shank3abDeltaC (+/-) heterozygotes. Human SHANK3 mRNA was then used to rescue DT phenotypes in larval zebrafish. Results: Significantly slower rates of DT peristaltic contractions (p < 0.001) with correspondingly prolonged passage time (p < 0.004) occurred in shank3abDeltaC (+/-) mutants. Rescue injections of mRNA encoding the longest human SHANK3 isoform into shank3abDeltaC (+/-) mutants produced larvae with intestinal bulb emptying similar to wild type (WT), but still deficits in posterior intestinal motility. Serotonin-positive enteroendocrine cells (EECs) were significantly reduced in both shank3abDeltaC (+/-) and shank3abDeltaC (-/-) mutants (p < 0.05) while enteric neuron counts and overall structure of the DT epithelium, including goblet cell number, were unaffected in shank3abDeltaC (+/-) larvae. Conclusions: Our data and rescue experiments support mutations in SHANK3 as causal for GI transit and motility abnormalities. Reductions in serotonin-positive EECs and serotonin-filled ENS boutons suggest an endocrine/neural component to this dysmotility. This is the first study to date demonstrating DT dysmotility in a zebrafish single gene mutant model of ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0250-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389
in Molecular Autism > 10 (2019) . - 3 p.[article] Intestinal dysmotility in a zebrafish (Danio rerio) shank3a;shank3b mutant model of autism [Texte imprimé et/ou numérique] / D. M. JAMES, Auteur ; R. A. KOZOL, Auteur ; Y. KAJIWARA, Auteur ; A. L. WAHL, Auteur ; E. C. STORRS, Auteur ; Joseph D. BUXBAUM, Auteur ; M. KLEIN, Auteur ; B. MOSHIREE, Auteur ; J. E. DALLMAN, Auteur . - 3 p.
Langues : Anglais (eng)
in Molecular Autism > 10 (2019) . - 3 p.
Mots-clés : *Digestive transit *Enteroendocrine *Peristaltic rate *Phelan-McDermid syndrome approved by the Institutional Animal Care and Use Committee of University of Miami.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background and aims: Autism spectrum disorder (ASD) is currently estimated to affect more than 1% of the world population. For people with ASD, gastrointestinal (GI) distress is a commonly reported but a poorly understood co-occurring symptom. Here, we investigate the physiological basis for GI distress in ASD by studying gut function in a zebrafish model of Phelan-McDermid syndrome (PMS), a condition caused by mutations in the SHANK3 gene. Methods: To generate a zebrafish model of PMS, we used CRISPR/Cas9 to introduce clinically related C-terminal frameshift mutations in shank3a and shank3b zebrafish paralogues (shank3abDeltaC). Because PMS is caused by SHANK3 haploinsufficiency, we assessed the digestive tract (DT) structure and function in zebrafish shank3abDeltaC (+/-) heterozygotes. Human SHANK3 mRNA was then used to rescue DT phenotypes in larval zebrafish. Results: Significantly slower rates of DT peristaltic contractions (p < 0.001) with correspondingly prolonged passage time (p < 0.004) occurred in shank3abDeltaC (+/-) mutants. Rescue injections of mRNA encoding the longest human SHANK3 isoform into shank3abDeltaC (+/-) mutants produced larvae with intestinal bulb emptying similar to wild type (WT), but still deficits in posterior intestinal motility. Serotonin-positive enteroendocrine cells (EECs) were significantly reduced in both shank3abDeltaC (+/-) and shank3abDeltaC (-/-) mutants (p < 0.05) while enteric neuron counts and overall structure of the DT epithelium, including goblet cell number, were unaffected in shank3abDeltaC (+/-) larvae. Conclusions: Our data and rescue experiments support mutations in SHANK3 as causal for GI transit and motility abnormalities. Reductions in serotonin-positive EECs and serotonin-filled ENS boutons suggest an endocrine/neural component to this dysmotility. This is the first study to date demonstrating DT dysmotility in a zebrafish single gene mutant model of ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0250-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 Links between looking and speaking in autism and first-degree relatives: insights into the expression of genetic liability to autism / K. NAYAR in Molecular Autism, 9 (2018)
[article]
Titre : Links between looking and speaking in autism and first-degree relatives: insights into the expression of genetic liability to autism Type de document : Texte imprimé et/ou numérique Auteurs : K. NAYAR, Auteur ; P. C. GORDON, Auteur ; G. E. MARTIN, Auteur ; A. L. HOGAN, Auteur ; C. LA VALLE, Auteur ; W. MCKINNEY, Auteur ; M. LEE, Auteur ; E. S. NORTON, Auteur ; M. LOSH, Auteur Article en page(s) : 51p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder Broad autism phenotype Endophenotype Eye movement Eye-voice span Gaze Language Rapid automatized naming Restricted and repetitive behaviors Social communication standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.Not applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Rapid automatized naming (RAN; naming of familiar items presented in an array) is a task that taps fundamental neurocognitive processes that are affected in a number of complex psychiatric conditions. Deficits in RAN have been repeatedly observed in autism spectrum disorder (ASD), and also among first-degree relatives, suggesting that RAN may tap features that index genetic liability to ASD. This study used eye tracking to examine neurocognitive mechanisms related to RAN performance in ASD and first-degree relatives, and investigated links to broader language and clinical-behavioral features. Methods: Fifty-one individuals with ASD, biological parents of individuals with ASD (n = 133), and respective control groups (n = 45 ASD controls; 58 parent controls) completed RAN on an eye tracker. Variables included naming time, frequency of errors, and measures of eye movement during RAN (eye-voice span, number of fixations and refixations). Results: Both the ASD and parent-ASD groups showed slower naming times, more errors, and atypical eye-movement patterns (e.g., increased fixations and refixations), relative to controls, with differences persisting after accounting for spousal resemblance. RAN ability and associated eye movement patterns were correlated with increased social-communicative impairment and increased repetitive behaviors in ASD. Longer RAN times and greater refixations in the parent-ASD group were driven by the subgroup who showed clinical-behavioral features of the broad autism phenotype (BAP). Finally, parent-child dyad correlations revealed associations between naming time and refixations in parents with the BAP and increased repetitive behaviors in their child with ASD. Conclusions: Differences in RAN performance and associated eye movement patterns detected in ASD and in parents, and links to broader social-communicative abilities, clinical features, and parent-child associations, suggest that RAN-related abilities might constitute genetically meaningful neurocognitive markers that can help bridge connections between underlying biology and ASD symptomatology. En ligne : https://dx.doi.org/10.1186/s13229-018-0233-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371
in Molecular Autism > 9 (2018) . - 51p.[article] Links between looking and speaking in autism and first-degree relatives: insights into the expression of genetic liability to autism [Texte imprimé et/ou numérique] / K. NAYAR, Auteur ; P. C. GORDON, Auteur ; G. E. MARTIN, Auteur ; A. L. HOGAN, Auteur ; C. LA VALLE, Auteur ; W. MCKINNEY, Auteur ; M. LEE, Auteur ; E. S. NORTON, Auteur ; M. LOSH, Auteur . - 51p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 51p.
Mots-clés : Autism spectrum disorder Broad autism phenotype Endophenotype Eye movement Eye-voice span Gaze Language Rapid automatized naming Restricted and repetitive behaviors Social communication standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.Not applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Rapid automatized naming (RAN; naming of familiar items presented in an array) is a task that taps fundamental neurocognitive processes that are affected in a number of complex psychiatric conditions. Deficits in RAN have been repeatedly observed in autism spectrum disorder (ASD), and also among first-degree relatives, suggesting that RAN may tap features that index genetic liability to ASD. This study used eye tracking to examine neurocognitive mechanisms related to RAN performance in ASD and first-degree relatives, and investigated links to broader language and clinical-behavioral features. Methods: Fifty-one individuals with ASD, biological parents of individuals with ASD (n = 133), and respective control groups (n = 45 ASD controls; 58 parent controls) completed RAN on an eye tracker. Variables included naming time, frequency of errors, and measures of eye movement during RAN (eye-voice span, number of fixations and refixations). Results: Both the ASD and parent-ASD groups showed slower naming times, more errors, and atypical eye-movement patterns (e.g., increased fixations and refixations), relative to controls, with differences persisting after accounting for spousal resemblance. RAN ability and associated eye movement patterns were correlated with increased social-communicative impairment and increased repetitive behaviors in ASD. Longer RAN times and greater refixations in the parent-ASD group were driven by the subgroup who showed clinical-behavioral features of the broad autism phenotype (BAP). Finally, parent-child dyad correlations revealed associations between naming time and refixations in parents with the BAP and increased repetitive behaviors in their child with ASD. Conclusions: Differences in RAN performance and associated eye movement patterns detected in ASD and in parents, and links to broader social-communicative abilities, clinical features, and parent-child associations, suggest that RAN-related abilities might constitute genetically meaningful neurocognitive markers that can help bridge connections between underlying biology and ASD symptomatology. En ligne : https://dx.doi.org/10.1186/s13229-018-0233-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 Sparsifying machine learning models identify stable subsets of predictive features for behavioral detection of autism / S. LEVY in Molecular Autism, 8 (2017)
[article]
Titre : Sparsifying machine learning models identify stable subsets of predictive features for behavioral detection of autism Type de document : Texte imprimé et/ou numérique Auteurs : S. LEVY, Auteur ; M. DUDA, Auteur ; N. HABER, Auteur ; Dennis P. WALL, Auteur Article en page(s) : 65p. Langues : Anglais (eng) Mots-clés : Asd Autism Autism diagnosis Autism screening Autism spectrum disorder Machine learning Sparse machine learning company focused on building digital solutions for child health.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) diagnosis can be delayed due in part to the time required for administration of standard exams, such as the Autism Diagnostic Observation Schedule (ADOS). Shorter and potentially mobilized approaches would help to alleviate bottlenecks in the healthcare system. Previous work using machine learning suggested that a subset of the behaviors measured by ADOS can achieve clinically acceptable levels of accuracy. Here we expand on this initial work to build sparse models that have higher potential to generalize to the clinical population. Methods: We assembled a collection of score sheets for two ADOS modules, one for children with phrased speech (Module 2; 1319 ASD cases, 70 controls) and the other for children with verbal fluency (Module 3; 2870 ASD cases, 273 controls). We used sparsity/parsimony enforcing regularization techniques in a nested cross validation grid search to select features for 17 unique supervised learning models, encoding missing values as additional indicator features. We augmented our feature sets with gender and age to train minimal and interpretable classifiers capable of robust detection of ASD from non-ASD. Results: By applying 17 unique supervised learning methods across 5 classification families tuned for sparse use of features and to be within 1 standard error of the optimal model, we find reduced sets of 10 and 5 features used in a majority of models. We tested the performance of the most interpretable of these sparse models, including Logistic Regression with L2 regularization or Linear SVM with L1 regularization. We obtained an area under the ROC curve of 0.95 for ADOS Module 3 and 0.93 for ADOS Module 2 with less than or equal to 10 features. Conclusions: The resulting models provide improved stability over previous machine learning efforts to minimize the time complexity of autism detection due to regularization and a small parameter space. These robustness techniques yield classifiers that are sparse, interpretable and that have potential to generalize to alternative modes of autism screening, diagnosis and monitoring, possibly including analysis of short home videos. En ligne : http://dx.doi.org/10.1186/s13229-017-0180-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330
in Molecular Autism > 8 (2017) . - 65p.[article] Sparsifying machine learning models identify stable subsets of predictive features for behavioral detection of autism [Texte imprimé et/ou numérique] / S. LEVY, Auteur ; M. DUDA, Auteur ; N. HABER, Auteur ; Dennis P. WALL, Auteur . - 65p.
Langues : Anglais (eng)
in Molecular Autism > 8 (2017) . - 65p.
Mots-clés : Asd Autism Autism diagnosis Autism screening Autism spectrum disorder Machine learning Sparse machine learning company focused on building digital solutions for child health.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) diagnosis can be delayed due in part to the time required for administration of standard exams, such as the Autism Diagnostic Observation Schedule (ADOS). Shorter and potentially mobilized approaches would help to alleviate bottlenecks in the healthcare system. Previous work using machine learning suggested that a subset of the behaviors measured by ADOS can achieve clinically acceptable levels of accuracy. Here we expand on this initial work to build sparse models that have higher potential to generalize to the clinical population. Methods: We assembled a collection of score sheets for two ADOS modules, one for children with phrased speech (Module 2; 1319 ASD cases, 70 controls) and the other for children with verbal fluency (Module 3; 2870 ASD cases, 273 controls). We used sparsity/parsimony enforcing regularization techniques in a nested cross validation grid search to select features for 17 unique supervised learning models, encoding missing values as additional indicator features. We augmented our feature sets with gender and age to train minimal and interpretable classifiers capable of robust detection of ASD from non-ASD. Results: By applying 17 unique supervised learning methods across 5 classification families tuned for sparse use of features and to be within 1 standard error of the optimal model, we find reduced sets of 10 and 5 features used in a majority of models. We tested the performance of the most interpretable of these sparse models, including Logistic Regression with L2 regularization or Linear SVM with L1 regularization. We obtained an area under the ROC curve of 0.95 for ADOS Module 3 and 0.93 for ADOS Module 2 with less than or equal to 10 features. Conclusions: The resulting models provide improved stability over previous machine learning efforts to minimize the time complexity of autism detection due to regularization and a small parameter space. These robustness techniques yield classifiers that are sparse, interpretable and that have potential to generalize to alternative modes of autism screening, diagnosis and monitoring, possibly including analysis of short home videos. En ligne : http://dx.doi.org/10.1186/s13229-017-0180-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330