3 recherche sur le mot-clé 'publication. Competing interests: The authors declare no competing interests.'

Pupil responses to social stimuli are associated with adaptive behaviors across the first 24 months of life / Rebecca GRZADZINSKI in Journal of Neurodevelopmental Disorders, 17 (2025)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 17 (2025) Titre : Pupil responses to social stimuli are associated with adaptive behaviors across the first 24 months of life Type de document : texte imprimé Auteurs : Rebecca GRZADZINSKI, Auteur ; Raymond S. 3rd CARPENTER, Auteur ; Josh RUTSOHN, Auteur ; Alapika JATKAR, Auteur ; Kattia MATA, Auteur ; Ambika BHATT, Auteur ; Maria M. ORTIZ-JUZA, Auteur ; Madison R. DENNEHEY, Auteur ; Donna GILLESKIE, Auteur ; Jed T. ELISON, Auteur ; Nicolas PÉGARD, Auteur ; Jose RODRIGUEZ-ROMAGUERA, Auteur Langues : Anglais (eng) Mots-clés : Autism  Autism-spectrum disorder  Eye-tracking  Pupil change  Pupil dynamics  Pupillometry  Social arousal  Social attention  approved by the Institutional Review Board at the University of North Carolina at  Chapel Hill (IRB #21-1704). A parent or legal guardian provided written informed  consent. Consent for publication: All authors have approved the manuscript for  publication. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Pupil changes in response to well-controlled stimuli can be used to understand processes that regulate attention, learning, and arousal. This study investigates whether pupil dynamics to social stimuli are associated with concurrent adaptive behavior in typically developing infants. To accomplish this, we developed and assessed pupillary responses to Stimuli for Early Social Arousal and Motivation in Infants (SESAMI). METHODS: A sample of forty-six typically developing children aged six to twenty-four months were exposed to SESAMI. Infants were presented with either dynamic social faces or non-social stimuli that controlled for luminance, motion, and auditory exposure. A multi-level mixed effects model was used to fit pupillary response functions (PRFs) that measure the change in pupil size over time as the infants fixate on either a socially dynamic face or a non-social control. This model produces separate social and non-social PRFs for both the population and each individual. An average individual deviation score from the population PRF was calculated separately for social and non-social trials yielding the pupil response index (PRI). Vineland Adaptive Behavior Scales (VABS) were regressed on social and non-social individual PRIs while controlling for age and average fixation time. We tested whether the social PRI was a statistically significant predictor of adaptive behavior by comparing the model predicted VABS scores with observed scores. RESULTS: An increase in PRI to social stimuli was significantly associated with better adaptive behaviors in typically developing children between 6 and 24 months of age. CONCLUSIONS: SESAMI combined with pupillometry and multi-level mixed effects modeling, provides a novel and scalable framework for quantifying individual differences in pupil changes in response to social stimuli relative to a population-level baseline. By demonstrating that pupil response indices during social fixations predict adaptive behaviors, we lay the foundation to test how these measures may help identify infants with intellectual and developmental disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09628-2. En ligne : https://dx.doi.org/10.1186/s11689-025-09628-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Pupil responses to social stimuli are associated with adaptive behaviors across the first 24 months of life [texte imprimé] / Rebecca GRZADZINSKI, Auteur ; Raymond S. 3rd CARPENTER, Auteur ; Josh RUTSOHN, Auteur ; Alapika JATKAR, Auteur ; Kattia MATA, Auteur ; Ambika BHATT, Auteur ; Maria M. ORTIZ-JUZA, Auteur ; Madison R. DENNEHEY, Auteur ; Donna GILLESKIE, Auteur ; Jed T. ELISON, Auteur ; Nicolas PÉGARD, Auteur ; Jose RODRIGUEZ-ROMAGUERA, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 17 (2025) Mots-clés : Autism  Autism-spectrum disorder  Eye-tracking  Pupil change  Pupil dynamics  Pupillometry  Social arousal  Social attention  approved by the Institutional Review Board at the University of North Carolina at  Chapel Hill (IRB #21-1704). A parent or legal guardian provided written informed  consent. Consent for publication: All authors have approved the manuscript for  publication. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Pupil changes in response to well-controlled stimuli can be used to understand processes that regulate attention, learning, and arousal. This study investigates whether pupil dynamics to social stimuli are associated with concurrent adaptive behavior in typically developing infants. To accomplish this, we developed and assessed pupillary responses to Stimuli for Early Social Arousal and Motivation in Infants (SESAMI). METHODS: A sample of forty-six typically developing children aged six to twenty-four months were exposed to SESAMI. Infants were presented with either dynamic social faces or non-social stimuli that controlled for luminance, motion, and auditory exposure. A multi-level mixed effects model was used to fit pupillary response functions (PRFs) that measure the change in pupil size over time as the infants fixate on either a socially dynamic face or a non-social control. This model produces separate social and non-social PRFs for both the population and each individual. An average individual deviation score from the population PRF was calculated separately for social and non-social trials yielding the pupil response index (PRI). Vineland Adaptive Behavior Scales (VABS) were regressed on social and non-social individual PRIs while controlling for age and average fixation time. We tested whether the social PRI was a statistically significant predictor of adaptive behavior by comparing the model predicted VABS scores with observed scores. RESULTS: An increase in PRI to social stimuli was significantly associated with better adaptive behaviors in typically developing children between 6 and 24 months of age. CONCLUSIONS: SESAMI combined with pupillometry and multi-level mixed effects modeling, provides a novel and scalable framework for quantifying individual differences in pupil changes in response to social stimuli relative to a population-level baseline. By demonstrating that pupil response indices during social fixations predict adaptive behaviors, we lay the foundation to test how these measures may help identify infants with intellectual and developmental disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09628-2. En ligne : https://dx.doi.org/10.1186/s11689-025-09628-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

Brain volumes, cognitive, and adaptive skills in school-age children with Down syndrome / Rebecca GRZADZINSKI in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : Brain volumes, cognitive, and adaptive skills in school-age children with Down syndrome Type de document : texte imprimé Auteurs : Rebecca GRZADZINSKI, Auteur ; Kattia MATA, Auteur ; Ambika S. BHATT, Auteur ; Alapika JATKAR, Auteur ; Dea GARIC, Auteur ; Mark D. SHEN, Auteur ; Jessica B. GIRAULT, Auteur ; Tanya ST JOHN, Auteur ; Juhi PANDEY, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; Annette ESTES, Auteur ; Audrey M. SHEN, Auteur ; Stephen DAGER, Auteur ; Robert SCHULTZ, Auteur ; Kelly BOTTERON, Auteur ; Natasha MARRUS, Auteur ; Martin STYNER, Auteur ; Alan EVANS, Auteur ; Sun Hyung KIM, Auteur ; Robert MCKINSTRY, Auteur ; Guido GERIG, Auteur ; Joseph PIVEN, Auteur ; Heather HAZLETT, Auteur ; IBIS NETWORK, Auteur Langues : Anglais (eng) Mots-clés : Humans  Down Syndrome/diagnostic imaging/physiopathology/pathology  Male  Female  Child  Magnetic Resonance Imaging  Adaptation, Psychological/physiology  Cognition/physiology  Brain/diagnostic imaging/pathology/physiopathology  Autism Spectrum Disorder/diagnostic imaging/physiopathology/pathology  Organ Size  Cerebellum/diagnostic imaging/pathology/physiopathology  Adaptive  Autism spectrum disorder  Brain volumes  Cognitive  Cortical volumes  Down syndrome  Intellectual disability  Mri  Neurobehavioral/behavioral profiles  Neurodevelopmental disorder  Neuroimaging  School-age children  in this work was approved by the local Institutional Review Board. Consent for  publication: All authors have reviewed the manuscript and approved it for  publication. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Down syndrome (DS) is the most common congenital neurodevelopmental disorder, present in about 1 in every 700 live births. Despite its prevalence, literature exploring the neurobiology underlying DS and how this neurobiology is related to behavior is limited. This study fills this gap by examining cortical volumes and behavioral correlates in school-age children with DS. METHODS: School-age children (mean = 9.7 years ± 1.1) underwent comprehensive assessments, including cognitive and adaptive assessments, as well as an MRI scan without the use of sedation. Children with DS (n = 35) were compared to available samples of typically developing (TD; n = 80) and ASD children (n = 29). ANOVAs were conducted to compare groups on cognitive and adaptive assessments. ANCOVAs (covarying for age, sex, and total cerebral volume; TCV) compared cortical brain volumes between groups. Correlations between behavioral metrics and cortical and cerebellar volumes (separately for gray (GM) and white matter (WM)) were conducted separately by group. RESULTS: As expected, children with DS had significantly lower cognitive skills compared to ASD and TD children. Daily Living adaptive skills were comparable between ASD children and children with DS, and both groups scored lower than TD children. Children with DS exhibited a smaller TCV compared to ASD and TD children. Additionally, when controlling for TCV, age, and sex, children with DS had significantly smaller total GM and tissue volumes. Cerebellum volumes were significantly correlated with Daily Living adaptive behaviors in the DS group only. CONCLUSIONS: Despite children with DS exhibiting lower cognitive skills and smaller brain volume overall than children with ASD, their deficits in Socialization and Daily Living adaptive skills are comparable. Differences in lobar volumes (e.g., Right Frontal GM/WM, Left Frontal WM, and Left and Right Temporal WM) were observed above and beyond overall differences in total volume. The correlation between cerebellum volumes and Daily Living adaptive behaviors in the DS group provides a novel area to explore in future research. En ligne : https://dx.doi.org/10.1186/s11689-024-09581-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Brain volumes, cognitive, and adaptive skills in school-age children with Down syndrome [texte imprimé] / Rebecca GRZADZINSKI, Auteur ; Kattia MATA, Auteur ; Ambika S. BHATT, Auteur ; Alapika JATKAR, Auteur ; Dea GARIC, Auteur ; Mark D. SHEN, Auteur ; Jessica B. GIRAULT, Auteur ; Tanya ST JOHN, Auteur ; Juhi PANDEY, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; Annette ESTES, Auteur ; Audrey M. SHEN, Auteur ; Stephen DAGER, Auteur ; Robert SCHULTZ, Auteur ; Kelly BOTTERON, Auteur ; Natasha MARRUS, Auteur ; Martin STYNER, Auteur ; Alan EVANS, Auteur ; Sun Hyung KIM, Auteur ; Robert MCKINSTRY, Auteur ; Guido GERIG, Auteur ; Joseph PIVEN, Auteur ; Heather HAZLETT, Auteur ; IBIS NETWORK, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Humans  Down Syndrome/diagnostic imaging/physiopathology/pathology  Male  Female  Child  Magnetic Resonance Imaging  Adaptation, Psychological/physiology  Cognition/physiology  Brain/diagnostic imaging/pathology/physiopathology  Autism Spectrum Disorder/diagnostic imaging/physiopathology/pathology  Organ Size  Cerebellum/diagnostic imaging/pathology/physiopathology  Adaptive  Autism spectrum disorder  Brain volumes  Cognitive  Cortical volumes  Down syndrome  Intellectual disability  Mri  Neurobehavioral/behavioral profiles  Neurodevelopmental disorder  Neuroimaging  School-age children  in this work was approved by the local Institutional Review Board. Consent for  publication: All authors have reviewed the manuscript and approved it for  publication. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Down syndrome (DS) is the most common congenital neurodevelopmental disorder, present in about 1 in every 700 live births. Despite its prevalence, literature exploring the neurobiology underlying DS and how this neurobiology is related to behavior is limited. This study fills this gap by examining cortical volumes and behavioral correlates in school-age children with DS. METHODS: School-age children (mean = 9.7 years ± 1.1) underwent comprehensive assessments, including cognitive and adaptive assessments, as well as an MRI scan without the use of sedation. Children with DS (n = 35) were compared to available samples of typically developing (TD; n = 80) and ASD children (n = 29). ANOVAs were conducted to compare groups on cognitive and adaptive assessments. ANCOVAs (covarying for age, sex, and total cerebral volume; TCV) compared cortical brain volumes between groups. Correlations between behavioral metrics and cortical and cerebellar volumes (separately for gray (GM) and white matter (WM)) were conducted separately by group. RESULTS: As expected, children with DS had significantly lower cognitive skills compared to ASD and TD children. Daily Living adaptive skills were comparable between ASD children and children with DS, and both groups scored lower than TD children. Children with DS exhibited a smaller TCV compared to ASD and TD children. Additionally, when controlling for TCV, age, and sex, children with DS had significantly smaller total GM and tissue volumes. Cerebellum volumes were significantly correlated with Daily Living adaptive behaviors in the DS group only. CONCLUSIONS: Despite children with DS exhibiting lower cognitive skills and smaller brain volume overall than children with ASD, their deficits in Socialization and Daily Living adaptive skills are comparable. Differences in lobar volumes (e.g., Right Frontal GM/WM, Left Frontal WM, and Left and Right Temporal WM) were observed above and beyond overall differences in total volume. The correlation between cerebellum volumes and Daily Living adaptive behaviors in the DS group provides a novel area to explore in future research. En ligne : https://dx.doi.org/10.1186/s11689-024-09581-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

UBE3A reinstatement restores behaviorand proteome in an Angelman syndrome mouse model of imprinting defects / Claudia MILAZZO in Molecular Autism, 16 (2025)  

Public ISBD [article]  inMolecular Autism > 16 (2025) . - 45 Titre : UBE3A reinstatement restores behaviorand proteome in an Angelman syndrome mouse model of imprinting defects Type de document : texte imprimé Auteurs : Claudia MILAZZO, Auteur ; Ramanathan NARAYANAN, Auteur ; Solveig BADILLO, Auteur ; Silvia WANG, Auteur ; Rosaisela ALMAND, Auteur ; Roos MONSHOUWER, Auteur ; Manuel TZOUROS, Auteur ; Sabrina GOLLING, Auteur ; Edwin J. MIENTJES, Auteur ; Stormy J. CHAMBERLAIN, Auteur ; Thomas KREMER, Auteur ; Ype ELGERSMA, Auteur ; Claudia MILAZZO, Auteur ; Ramanathan NARAYANAN, Auteur ; Solveig BADILLO, Auteur ; Silvia WANG, Auteur ; Rosaisela ALMAND, Auteur ; Roos MONSHOUWER, Auteur ; Manuel TZOUROS, Auteur ; Sabrina GOLLING, Auteur ; Edwin J. MIENTJES, Auteur ; Stormy J. CHAMBERLAIN, Auteur ; Thomas KREMER, Auteur ; Ype ELGERSMA, Auteur Article en page(s) : 45 Langues : Anglais (eng) Mots-clés : Animals  Angelman Syndrome/genetics/metabolism  Ubiquitin-Protein Ligases/genetics/metabolism  Genomic Imprinting  Disease Models, Animal  Mice  Proteome/metabolism  Behavior, Animal  Male  Female  Oligonucleotides, Antisense  Angelman syndrome  Antisense oligonucleotide  Behavior  Imprinting defects  Mouse model  Proteome  were conducted in accordance with the European Commission Council Directive  2010/63/EU (CCD license AVD101002016791 and AVD10100202216352). Consent for  publication: All authors have approved the final manuscript and consent for  publication. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman Syndrome (AS) is a severe neurodevelopmental disorder with only symptomatic treatment currently available. The primary cause of AS is loss of functional UBE3A protein. This can be caused by deletions in the maternal 15q11-q13 region, maternal AS-imprinting center defects (mICD), paternal uniparental disomy of chromosome 15 (UPD) or mutations within the UBE3A gene. Current mouse models are Ube3a-centric and do not address expression changes of other genes in the 15q11-q13 locus on the pathophysiology of AS. This limits the ability to discern differences in therapeutic responses to current UBE3A-targeting strategies and hampers the identification of novel therapeutics/co-therapeutics. METHODS: Using a mouse line that harbors a maternally inherited mutation affecting the AS-PWS imprinting center ('mICD mice'), we studied the impact of the mICD or UPD AS subtype on behavior, seizure susceptibility and proteome. Additionally, by using mice overexpressing two copies of Ube3a or antisense oligonucleotide (ASO) targeting Ube3a-ATS, we analyzed the impact of bi-allelic Ube3a activation on behavior and proteome. RESULTS: mICD mice showed 80% reduction in UBE3A protein, bi-allelic expression of Ube3a-ATS and Mkrn3-Snord115 gene cluster, leading to robust AS behavioral deficits and proteome alterations similar to Ube3a(m-/p+) mice. Genetic UBE3A overexpression in mICD mice, mimicking therapeutic strategies that effectively activate the biallelic silenced Ube3a gene, resulted in a complete rescue of all behavioral phenotypes, seizure susceptibility and proteome alterations. Subsequently, treatment with an antisense oligonucleotide (ASO) to directly activate the biallelic silenced Ube3a gene in mICD mice also resulted in efficient reinstatement of UBE3A, 30% higher relative to WT, alongside a partial rescue of behavioral phenotypes. LIMITATIONS: Despite using a highly robust AS-specific behavioral battery, we did not investigate readouts such as neuronal activity and sleep, for which impairments in Ube3a(m-/p+) mice were described. CONCLUSIONS: Taken together, these findings demonstrate that the loss of UBE3A protein is the primary factor underlying AS phenotypes in this mICD/UPD mouse model of AS, while the biallelic expressed genes in this locus play either a marginal or yet unidentified role. These findings also corroborate UBE3A reinstatement as an attractive therapeutic strategy for AS individuals carrying an mICD or UPD mutation. En ligne : https://dx.doi.org/10.1186/s13229-025-00675-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=569 [article] UBE3A reinstatement restores behaviorand proteome in an Angelman syndrome mouse model of imprinting defects [texte imprimé] / Claudia MILAZZO, Auteur ; Ramanathan NARAYANAN, Auteur ; Solveig BADILLO, Auteur ; Silvia WANG, Auteur ; Rosaisela ALMAND, Auteur ; Roos MONSHOUWER, Auteur ; Manuel TZOUROS, Auteur ; Sabrina GOLLING, Auteur ; Edwin J. MIENTJES, Auteur ; Stormy J. CHAMBERLAIN, Auteur ; Thomas KREMER, Auteur ; Ype ELGERSMA, Auteur ; Claudia MILAZZO, Auteur ; Ramanathan NARAYANAN, Auteur ; Solveig BADILLO, Auteur ; Silvia WANG, Auteur ; Rosaisela ALMAND, Auteur ; Roos MONSHOUWER, Auteur ; Manuel TZOUROS, Auteur ; Sabrina GOLLING, Auteur ; Edwin J. MIENTJES, Auteur ; Stormy J. CHAMBERLAIN, Auteur ; Thomas KREMER, Auteur ; Ype ELGERSMA, Auteur . - 45. Langues : Anglais (eng) in Molecular Autism > 16 (2025) . - 45 Mots-clés : Animals  Angelman Syndrome/genetics/metabolism  Ubiquitin-Protein Ligases/genetics/metabolism  Genomic Imprinting  Disease Models, Animal  Mice  Proteome/metabolism  Behavior, Animal  Male  Female  Oligonucleotides, Antisense  Angelman syndrome  Antisense oligonucleotide  Behavior  Imprinting defects  Mouse model  Proteome  were conducted in accordance with the European Commission Council Directive  2010/63/EU (CCD license AVD101002016791 and AVD10100202216352). Consent for  publication: All authors have approved the final manuscript and consent for  publication. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman Syndrome (AS) is a severe neurodevelopmental disorder with only symptomatic treatment currently available. The primary cause of AS is loss of functional UBE3A protein. This can be caused by deletions in the maternal 15q11-q13 region, maternal AS-imprinting center defects (mICD), paternal uniparental disomy of chromosome 15 (UPD) or mutations within the UBE3A gene. Current mouse models are Ube3a-centric and do not address expression changes of other genes in the 15q11-q13 locus on the pathophysiology of AS. This limits the ability to discern differences in therapeutic responses to current UBE3A-targeting strategies and hampers the identification of novel therapeutics/co-therapeutics. METHODS: Using a mouse line that harbors a maternally inherited mutation affecting the AS-PWS imprinting center ('mICD mice'), we studied the impact of the mICD or UPD AS subtype on behavior, seizure susceptibility and proteome. Additionally, by using mice overexpressing two copies of Ube3a or antisense oligonucleotide (ASO) targeting Ube3a-ATS, we analyzed the impact of bi-allelic Ube3a activation on behavior and proteome. RESULTS: mICD mice showed 80% reduction in UBE3A protein, bi-allelic expression of Ube3a-ATS and Mkrn3-Snord115 gene cluster, leading to robust AS behavioral deficits and proteome alterations similar to Ube3a(m-/p+) mice. Genetic UBE3A overexpression in mICD mice, mimicking therapeutic strategies that effectively activate the biallelic silenced Ube3a gene, resulted in a complete rescue of all behavioral phenotypes, seizure susceptibility and proteome alterations. Subsequently, treatment with an antisense oligonucleotide (ASO) to directly activate the biallelic silenced Ube3a gene in mICD mice also resulted in efficient reinstatement of UBE3A, 30% higher relative to WT, alongside a partial rescue of behavioral phenotypes. LIMITATIONS: Despite using a highly robust AS-specific behavioral battery, we did not investigate readouts such as neuronal activity and sleep, for which impairments in Ube3a(m-/p+) mice were described. CONCLUSIONS: Taken together, these findings demonstrate that the loss of UBE3A protein is the primary factor underlying AS phenotypes in this mICD/UPD mouse model of AS, while the biallelic expressed genes in this locus play either a marginal or yet unidentified role. These findings also corroborate UBE3A reinstatement as an attractive therapeutic strategy for AS individuals carrying an mICD or UPD mutation. En ligne : https://dx.doi.org/10.1186/s13229-025-00675-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=569