Atypical cerebellar functional connectivity at 9 months of age predicts delayed socio-communicative profiles in infants at high and low risk for autism / Nana J. OKADA in Journal of Child Psychology and Psychiatry, 63-9 (September 2022)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 63-9 (September 2022) . - p.1002-1016 Titre : Atypical cerebellar functional connectivity at 9 months of age predicts delayed socio-communicative profiles in infants at high and low risk for autism Type de document : Texte imprimé et/ou numérique Auteurs : Nana J. OKADA, Auteur ; Janelle LIU, Auteur ; Tawny TSANG, Auteur ; Erin NOSCO, Auteur ; Nicole M. MCDONALD, Auteur ; Kaitlin K. CUMMINGS, Auteur ; Jiwon JUNG, Auteur ; Genevieve PATTERSON, Auteur ; Susan Y. BOOKHEIMER, Auteur ; Shulamite A. GREEN, Auteur ; Shafali S JESTE, Auteur ; Mirella DAPRETTO, Auteur Article en page(s) : p.1002-1016 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/diagnostic imaging  Autistic Disorder  Cerebellum/diagnostic imaging  Communication  Humans  Infant  Magnetic Resonance Imaging  Autism spectrum disorder  fMRI  infancy  social communication Index. décimale : PER Périodiques Résumé : BACKGROUND: While the cerebellum is traditionally known for its role in sensorimotor control, emerging research shows that particular subregions, such as right Crus I (RCrusI), support language and social processing. Indeed, cerebellar atypicalities are commonly reported in autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by socio-communicative impairments. However, the cerebellum's contribution to early socio-communicative development remains virtually unknown. METHODS: Here, we characterized functional connectivity within cerebro-cerebellar networks implicated in language/social functions in 9-month-old infants who exhibit distinct 3-year socio-communicative developmental profiles. We employed a data-driven clustering approach to stratify our sample of infants at high (n=82) and low (n=37) familial risk for ASD into three cohorts-Delayed, Late-Blooming, and Typical-who showed unique socio-communicative trajectories. We then compared the cohorts on indices of language and social development. Seed-based functional connectivity analyses with RCrusI were conducted on infants with fMRI data (n=66). Cohorts were compared on connectivity estimates from a-priori regions, selected on the basis of reported coactivation with RCrusI during language/social tasks. RESULTS: The three trajectory-based cohorts broadly differed in social communication development, as evidenced by robust differences on numerous indices of language and social skills. Importantly, at 9months, the cohorts showed striking differences in cerebro-cerebellar circuits implicated in language/social functions. For all regions examined, the Delayed cohort exhibited significantly weaker RCrusI connectivity compared to both the Late-Blooming and Typical cohorts, with no significant differences between the latter cohorts. CONCLUSIONS: We show that hypoconnectivity within distinct cerebro-cerebellar networks in infancy predicts altered socio-communicative development before delays overtly manifest, which may be relevant for early detection and intervention. As the cerebellum is implicated in prediction, our findings point to probabilistic learning as a potential intermediary mechanism that may be disrupted in infancy, cascading into alterations in social communication. En ligne : http://dx.doi.org/10.1111/jcpp.13555 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486 [article] Atypical cerebellar functional connectivity at 9 months of age predicts delayed socio-communicative profiles in infants at high and low risk for autism [Texte imprimé et/ou numérique] / Nana J. OKADA, Auteur ; Janelle LIU, Auteur ; Tawny TSANG, Auteur ; Erin NOSCO, Auteur ; Nicole M. MCDONALD, Auteur ; Kaitlin K. CUMMINGS, Auteur ; Jiwon JUNG, Auteur ; Genevieve PATTERSON, Auteur ; Susan Y. BOOKHEIMER, Auteur ; Shulamite A. GREEN, Auteur ; Shafali S JESTE, Auteur ; Mirella DAPRETTO, Auteur . - p.1002-1016. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 63-9 (September 2022) . - p.1002-1016 Mots-clés : Autism Spectrum Disorder/diagnostic imaging  Autistic Disorder  Cerebellum/diagnostic imaging  Communication  Humans  Infant  Magnetic Resonance Imaging  Autism spectrum disorder  fMRI  infancy  social communication Index. décimale : PER Périodiques Résumé : BACKGROUND: While the cerebellum is traditionally known for its role in sensorimotor control, emerging research shows that particular subregions, such as right Crus I (RCrusI), support language and social processing. Indeed, cerebellar atypicalities are commonly reported in autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by socio-communicative impairments. However, the cerebellum's contribution to early socio-communicative development remains virtually unknown. METHODS: Here, we characterized functional connectivity within cerebro-cerebellar networks implicated in language/social functions in 9-month-old infants who exhibit distinct 3-year socio-communicative developmental profiles. We employed a data-driven clustering approach to stratify our sample of infants at high (n=82) and low (n=37) familial risk for ASD into three cohorts-Delayed, Late-Blooming, and Typical-who showed unique socio-communicative trajectories. We then compared the cohorts on indices of language and social development. Seed-based functional connectivity analyses with RCrusI were conducted on infants with fMRI data (n=66). Cohorts were compared on connectivity estimates from a-priori regions, selected on the basis of reported coactivation with RCrusI during language/social tasks. RESULTS: The three trajectory-based cohorts broadly differed in social communication development, as evidenced by robust differences on numerous indices of language and social skills. Importantly, at 9months, the cohorts showed striking differences in cerebro-cerebellar circuits implicated in language/social functions. For all regions examined, the Delayed cohort exhibited significantly weaker RCrusI connectivity compared to both the Late-Blooming and Typical cohorts, with no significant differences between the latter cohorts. CONCLUSIONS: We show that hypoconnectivity within distinct cerebro-cerebellar networks in infancy predicts altered socio-communicative development before delays overtly manifest, which may be relevant for early detection and intervention. As the cerebellum is implicated in prediction, our findings point to probabilistic learning as a potential intermediary mechanism that may be disrupted in infancy, cascading into alterations in social communication. En ligne : http://dx.doi.org/10.1111/jcpp.13555 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486

Atypical early neural responses to native and non-native language in infants at high likelihood for developing autism / Megan BANCHIK ; Tawny TSANG ; Nana J OKADA ; Rebecca ALTSHULER ; Nicole MCDONALD ; Susan Y BOOKHEIMER ; Shafali S JESTE ; Shulamite GREEN ; Mirella DAPRETTO in Molecular Autism, 16 (2025)  

Public ISBD [article]  inMolecular Autism > 16 (2025) . - 6 Titre : Atypical early neural responses to native and non-native language in infants at high likelihood for developing autism Type de document : Texte imprimé et/ou numérique Auteurs : Megan BANCHIK, Auteur ; Tawny TSANG, Auteur ; Nana J OKADA, Auteur ; Rebecca ALTSHULER, Auteur ; Nicole MCDONALD, Auteur ; Susan Y BOOKHEIMER, Auteur ; Shafali S JESTE, Auteur ; Shulamite GREEN, Auteur ; Mirella DAPRETTO, Auteur Article en page(s) : 6 Langues : Anglais (eng) Mots-clés : Humans  Infant  Male  Magnetic Resonance Imaging  Female  Language  Autism Spectrum Disorder/physiopathology/diagnostic imaging  Brain/diagnostic imaging/physiopathology  Autistic Disorder/physiopathology  Brain Mapping  Speech  Autism  Language  Native language  fMRI  obtained from all participants' caregivers and/or legal guardians. All study  protocols were approved by the UCLA Institutional Review Board. Consent for  publication: Not applicable. Competing interests: The authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Language difficulties are common in autism spectrum disorder (ASD), a neurodevelopmental condition characterized by impairments in social communication as well as restricted and repetitive behaviors. Amongst infant siblings of children with an ASD diagnosis - who are at higher likelihood for developing ASD - a high proportion also show difficulties and delays in language acquisition. METHODS: In this study, we used functional magnetic resonance imaging (fMRI) to examine differences in language processing in 9-month-old infants at high (HL) and typical (TL) familial likelihood for ASD. Infants were presented with native (English) and novel (Japanese) speech while sleeping naturally in the scanner. Whole-brain and a priori region-of-interest analyses were conducted to evaluate neural differences in language processing based on likelihood group and language condition. RESULTS: HL infants showed attenuated responses to speech in general, particularly in left temporal language areas, as well as a lack of neural discrimination between the native and novel languages compared to the TL group. Importantly, we also demonstrate that HL infants show distinctly atypical patterns of lateralization for speech processing, particularly during native speech processing, suggesting a failure to left-lateralize. LIMITATIONS: The sample size, particularly for the TL group, is relatively modest because of the challenges inherent to collecting auditory stimulus-evoked data from sleeping participants, as well as retention and follow-up difficulties posed by the COVID-19 pandemic. The groups were not matched on some demographic variables, but the present findings held even after accounting for these differences. CONCLUSIONS: To our knowledge, this is the first fMRI study to directly measure autism-associated atypicalities in native language uptake during infancy. These findings provide a better understanding of the neurodevelopmental underpinnings of language delay in ASD, which is a prerequisite step for developing earlier and more effective interventions for autistic children and HL siblings who experience language impairments. En ligne : https://dx.doi.org/10.1186/s13229-025-00640-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555 [article] Atypical early neural responses to native and non-native language in infants at high likelihood for developing autism [Texte imprimé et/ou numérique] / Megan BANCHIK, Auteur ; Tawny TSANG, Auteur ; Nana J OKADA, Auteur ; Rebecca ALTSHULER, Auteur ; Nicole MCDONALD, Auteur ; Susan Y BOOKHEIMER, Auteur ; Shafali S JESTE, Auteur ; Shulamite GREEN, Auteur ; Mirella DAPRETTO, Auteur . - 6. Langues : Anglais (eng) in Molecular Autism > 16 (2025) . - 6 Mots-clés : Humans  Infant  Male  Magnetic Resonance Imaging  Female  Language  Autism Spectrum Disorder/physiopathology/diagnostic imaging  Brain/diagnostic imaging/physiopathology  Autistic Disorder/physiopathology  Brain Mapping  Speech  Autism  Language  Native language  fMRI  obtained from all participants' caregivers and/or legal guardians. All study  protocols were approved by the UCLA Institutional Review Board. Consent for  publication: Not applicable. Competing interests: The authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Language difficulties are common in autism spectrum disorder (ASD), a neurodevelopmental condition characterized by impairments in social communication as well as restricted and repetitive behaviors. Amongst infant siblings of children with an ASD diagnosis - who are at higher likelihood for developing ASD - a high proportion also show difficulties and delays in language acquisition. METHODS: In this study, we used functional magnetic resonance imaging (fMRI) to examine differences in language processing in 9-month-old infants at high (HL) and typical (TL) familial likelihood for ASD. Infants were presented with native (English) and novel (Japanese) speech while sleeping naturally in the scanner. Whole-brain and a priori region-of-interest analyses were conducted to evaluate neural differences in language processing based on likelihood group and language condition. RESULTS: HL infants showed attenuated responses to speech in general, particularly in left temporal language areas, as well as a lack of neural discrimination between the native and novel languages compared to the TL group. Importantly, we also demonstrate that HL infants show distinctly atypical patterns of lateralization for speech processing, particularly during native speech processing, suggesting a failure to left-lateralize. LIMITATIONS: The sample size, particularly for the TL group, is relatively modest because of the challenges inherent to collecting auditory stimulus-evoked data from sleeping participants, as well as retention and follow-up difficulties posed by the COVID-19 pandemic. The groups were not matched on some demographic variables, but the present findings held even after accounting for these differences. CONCLUSIONS: To our knowledge, this is the first fMRI study to directly measure autism-associated atypicalities in native language uptake during infancy. These findings provide a better understanding of the neurodevelopmental underpinnings of language delay in ASD, which is a prerequisite step for developing earlier and more effective interventions for autistic children and HL siblings who experience language impairments. En ligne : https://dx.doi.org/10.1186/s13229-025-00640-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555

Concomitant medication use in children with autism spectrum disorder: Data from the Autism Biomarkers Consortium for Clinical Trials / Logan SHURTZ in Autism, 27-4 (May 2023)  

Public ISBD [article]  inAutism > 27-4 (May 2023) . - p.952-966 Titre : Concomitant medication use in children with autism spectrum disorder: Data from the Autism Biomarkers Consortium for Clinical Trials Type de document : Texte imprimé et/ou numérique Auteurs : Logan SHURTZ, Auteur ; Chloe SCHWARTZ, Auteur ; Charlotte DISTEFANO, Auteur ; James C MCPARTLAND, Auteur ; April R LEVIN, Auteur ; Geraldine DAWSON, Auteur ; Natalia M KLEINHANS, Auteur ; Susan FAJA, Auteur ; Sara J WEBB, Auteur ; Frederick SHIC, Auteur ; Adam J NAPLES, Auteur ; Helen SEOW, Auteur ; Raphael A BERNIER, Auteur ; Katarzyna CHAWARSKA, Auteur ; Catherine A SUGAR, Auteur ; James DZIURA, Auteur ; Damla SENTURK, Auteur ; Megha SANTHOSH, Auteur ; Shafali S JESTE, Auteur Article en page(s) : p.952-966 Langues : Anglais (eng) Mots-clés : aberrant behavior checklist,antipsychotics,autism spectrum disorders,clinical trials,medications,Vineland Adaptive Behavior Scales Index. décimale : PER Périodiques Résumé : Children with autism spectrum disorder are prescribed various medications to address behavior and mood. In clinical trials, individuals taking concomitant psychotropic medications often are excluded to maintain homogeneity and prevent contamination of clinical endpoints. However, this choice may compromise the representativeness of the sample. In a recent study designed to identify biomarkers and endpoints for clinical trials (the Autism Biomarkers Consortium for Clinical Trials), school-age children with autism spectrum disorder were enrolled without excluding for medications, providing the opportunity to examine characteristics of psychotropic medication use and guide future decisions on medication-related inclusion criteria. The aims of the current analysis were (1) to quantify the frequency and type of psychotropic medications reported in school-age children enrolled in the study and (2) to examine behavioral features of children with autism spectrum disorder based on medication classes. Of the 280 children with autism spectrum disorder in the cohort, 42.5% were taking psychotropic medications, with polypharmacy in half. The most commonly reported psychotropic medications included melatonin, stimulants, selective serotonin reuptake inhibitors, alpha agonists, and antipsychotics. Our findings suggest that exclusion of children taking concomitant psychotropic medications could limit the representativeness of the study population, perhaps even excluding children who may most benefit from new treatment options.Lay abstractChildren with autism spectrum disorder are prescribed a variety of medications that affect the central nervous system (psychotropic medications) to address behavior and mood. In clinical trials, individuals taking concomitant psychotropic medications often are excluded to maintain homogeneity of the sample and prevent contamination of biomarkers or clinical endpoints. However, this choice may significantly diminish the clinical representativeness of the sample. In a recent multisite study designed to identify biomarkers and behavioral endpoints for clinical trials (the Autism Biomarkers Consortium for Clinical Trials), school-age children with autism spectrum disorder were enrolled without excluding for medications, thus providing a unique opportunity to examine characteristics of psychotropic medication use in a research cohort and to guide future decisions on medication-related inclusion criteria. The aims of the current analysis were (1) to quantify the frequency and type of psychotropic medications reported in school-age children enrolled in the ABC-CT and (2) to examine behavioral features of children with autism spectrum disorder based on medication classes. Of the 280 children with autism spectrum disorder in the cohort, 42.5% were taking psychotropic medications, with polypharmacy in half of these children. The most commonly reported psychotropic medications included melatonin, stimulants, selective serotonin reuptake inhibitors, alpha agonists, and antipsychotics. Descriptive analysis showed that children taking antipsychotics displayed a trend toward greater overall impairment. Our findings suggest that exclusion of children taking concomitant psychotropic medications in trials could limit the clinical representativeness of the study population, perhaps even excluding children who may most benefit from new treatment options. En ligne : https://doi.org/10.1177/13623613221121425 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=499 [article] Concomitant medication use in children with autism spectrum disorder: Data from the Autism Biomarkers Consortium for Clinical Trials [Texte imprimé et/ou numérique] / Logan SHURTZ, Auteur ; Chloe SCHWARTZ, Auteur ; Charlotte DISTEFANO, Auteur ; James C MCPARTLAND, Auteur ; April R LEVIN, Auteur ; Geraldine DAWSON, Auteur ; Natalia M KLEINHANS, Auteur ; Susan FAJA, Auteur ; Sara J WEBB, Auteur ; Frederick SHIC, Auteur ; Adam J NAPLES, Auteur ; Helen SEOW, Auteur ; Raphael A BERNIER, Auteur ; Katarzyna CHAWARSKA, Auteur ; Catherine A SUGAR, Auteur ; James DZIURA, Auteur ; Damla SENTURK, Auteur ; Megha SANTHOSH, Auteur ; Shafali S JESTE, Auteur . - p.952-966. Langues : Anglais (eng) in Autism > 27-4 (May 2023) . - p.952-966 Mots-clés : aberrant behavior checklist,antipsychotics,autism spectrum disorders,clinical trials,medications,Vineland Adaptive Behavior Scales Index. décimale : PER Périodiques Résumé : Children with autism spectrum disorder are prescribed various medications to address behavior and mood. In clinical trials, individuals taking concomitant psychotropic medications often are excluded to maintain homogeneity and prevent contamination of clinical endpoints. However, this choice may compromise the representativeness of the sample. In a recent study designed to identify biomarkers and endpoints for clinical trials (the Autism Biomarkers Consortium for Clinical Trials), school-age children with autism spectrum disorder were enrolled without excluding for medications, providing the opportunity to examine characteristics of psychotropic medication use and guide future decisions on medication-related inclusion criteria. The aims of the current analysis were (1) to quantify the frequency and type of psychotropic medications reported in school-age children enrolled in the study and (2) to examine behavioral features of children with autism spectrum disorder based on medication classes. Of the 280 children with autism spectrum disorder in the cohort, 42.5% were taking psychotropic medications, with polypharmacy in half. The most commonly reported psychotropic medications included melatonin, stimulants, selective serotonin reuptake inhibitors, alpha agonists, and antipsychotics. Our findings suggest that exclusion of children taking concomitant psychotropic medications could limit the representativeness of the study population, perhaps even excluding children who may most benefit from new treatment options.Lay abstractChildren with autism spectrum disorder are prescribed a variety of medications that affect the central nervous system (psychotropic medications) to address behavior and mood. In clinical trials, individuals taking concomitant psychotropic medications often are excluded to maintain homogeneity of the sample and prevent contamination of biomarkers or clinical endpoints. However, this choice may significantly diminish the clinical representativeness of the sample. In a recent multisite study designed to identify biomarkers and behavioral endpoints for clinical trials (the Autism Biomarkers Consortium for Clinical Trials), school-age children with autism spectrum disorder were enrolled without excluding for medications, thus providing a unique opportunity to examine characteristics of psychotropic medication use in a research cohort and to guide future decisions on medication-related inclusion criteria. The aims of the current analysis were (1) to quantify the frequency and type of psychotropic medications reported in school-age children enrolled in the ABC-CT and (2) to examine behavioral features of children with autism spectrum disorder based on medication classes. Of the 280 children with autism spectrum disorder in the cohort, 42.5% were taking psychotropic medications, with polypharmacy in half of these children. The most commonly reported psychotropic medications included melatonin, stimulants, selective serotonin reuptake inhibitors, alpha agonists, and antipsychotics. Descriptive analysis showed that children taking antipsychotics displayed a trend toward greater overall impairment. Our findings suggest that exclusion of children taking concomitant psychotropic medications in trials could limit the clinical representativeness of the study population, perhaps even excluding children who may most benefit from new treatment options. En ligne : https://doi.org/10.1177/13623613221121425 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=499

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