Data-driven identification of subtypes of executive function across typical development, attention deficit hyperactivity disorder, and autism spectrum disorders / Chandan J. VAIDYA in Journal of Child Psychology and Psychiatry, 61-1 (January 2020)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 61-1 (January 2020) . - p.51-61 Titre : Data-driven identification of subtypes of executive function across typical development, attention deficit hyperactivity disorder, and autism spectrum disorders Type de document : texte imprimé Auteurs : Chandan J. VAIDYA, Auteur ; Xiaozhen YOU, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Francisco PEREIRA, Auteur ; Madison M. BERL, Auteur ; Lauren KENWORTHY, Auteur Article en page(s) : p.51-61 Langues : Anglais (eng) Mots-clés : Attention deficit hyperactivity disorder  autism spectrum disorders  functional MRI (fMRI)  individual differences  machine learning Index. décimale : PER Périodiques Résumé : BACKGROUND: Impairment of executive function (EF), the goal-directed regulation of thoughts, actions, and emotions, drives negative outcomes and is common across neurodevelopmental disorders including attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). A primary challenge to its amelioration is heterogeneity in symptom expression within and across disorders. Parsing this heterogeneity is necessary to attain diagnostic precision, a goal of the NIMH Research Domain Criteria Initiative. We aimed to identify transdiagnostic subtypes of EF that span the normal to impaired spectrum and establish their predictive and neurobiological validity. METHODS: Community detection was applied to clinical parent-report measures in 8-14-year-old children with and without ADHD and ASD from two independent cohorts (discovery N = 320; replication N = 692) to identify subgroups with distinct behavioral profiles. Support vector machine (SVM) classification was used to predict subgroup membership of unseen cases. Preliminary neurobiological validation was obtained with existing functional magnetic resonance imaging (fMRI) data on a subsample (N = 84) by testing hypotheses about sensitivity of EF subgroups versus DSM categories. RESULTS: We observed three transdiagnostic EF subtypes characterized by behavioral profiles that were defined by relative weakness in: (a) flexibility and emotion regulation; (b) inhibition; and (c) working memory, organization, and planning. The same tripartite structure was also present in the typically developing children. SVM trained on the discovery sample and tested on the replication sample classified subgroup membership with 77.0% accuracy. Split-half SVM classification on the combined sample (N = 1,012) yielded 88.9% accuracy (this SVM is available for public use). As hypothesized, frontal-parietal engagement was better distinguished by EF subtype than DSM diagnosis and the subgroup characterized with inflexibility failed to modulate right IPL activation in response to increased executive demands. CONCLUSIONS: The observed transdiagnostic subtypes refine current diagnostic nosology and augment clinical decision-making for personalizing treatment of executive dysfunction in children. En ligne : http://dx.doi.org/10.1111/jcpp.13114 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=413 [article] Data-driven identification of subtypes of executive function across typical development, attention deficit hyperactivity disorder, and autism spectrum disorders [texte imprimé] / Chandan J. VAIDYA, Auteur ; Xiaozhen YOU, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Francisco PEREIRA, Auteur ; Madison M. BERL, Auteur ; Lauren KENWORTHY, Auteur . - p.51-61. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 61-1 (January 2020) . - p.51-61 Mots-clés : Attention deficit hyperactivity disorder  autism spectrum disorders  functional MRI (fMRI)  individual differences  machine learning Index. décimale : PER Périodiques Résumé : BACKGROUND: Impairment of executive function (EF), the goal-directed regulation of thoughts, actions, and emotions, drives negative outcomes and is common across neurodevelopmental disorders including attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). A primary challenge to its amelioration is heterogeneity in symptom expression within and across disorders. Parsing this heterogeneity is necessary to attain diagnostic precision, a goal of the NIMH Research Domain Criteria Initiative. We aimed to identify transdiagnostic subtypes of EF that span the normal to impaired spectrum and establish their predictive and neurobiological validity. METHODS: Community detection was applied to clinical parent-report measures in 8-14-year-old children with and without ADHD and ASD from two independent cohorts (discovery N = 320; replication N = 692) to identify subgroups with distinct behavioral profiles. Support vector machine (SVM) classification was used to predict subgroup membership of unseen cases. Preliminary neurobiological validation was obtained with existing functional magnetic resonance imaging (fMRI) data on a subsample (N = 84) by testing hypotheses about sensitivity of EF subgroups versus DSM categories. RESULTS: We observed three transdiagnostic EF subtypes characterized by behavioral profiles that were defined by relative weakness in: (a) flexibility and emotion regulation; (b) inhibition; and (c) working memory, organization, and planning. The same tripartite structure was also present in the typically developing children. SVM trained on the discovery sample and tested on the replication sample classified subgroup membership with 77.0% accuracy. Split-half SVM classification on the combined sample (N = 1,012) yielded 88.9% accuracy (this SVM is available for public use). As hypothesized, frontal-parietal engagement was better distinguished by EF subtype than DSM diagnosis and the subgroup characterized with inflexibility failed to modulate right IPL activation in response to increased executive demands. CONCLUSIONS: The observed transdiagnostic subtypes refine current diagnostic nosology and augment clinical decision-making for personalizing treatment of executive dysfunction in children. En ligne : http://dx.doi.org/10.1111/jcpp.13114 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=413

Neural correlates of schema-dependent episodic memory and association with behavioral flexibility in autism spectrum disorders and typical development / Kevin M. COOK in Journal of Neurodevelopmental Disorders, 13 (2021)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 13 (2021) Titre : Neural correlates of schema-dependent episodic memory and association with behavioral flexibility in autism spectrum disorders and typical development Type de document : texte imprimé Auteurs : Kevin M. COOK, Auteur ; Xiaozhen YOU, Auteur ; Joseph Bradley CHERRY, Auteur ; Junaid S. MERCHANT, Auteur ; Mary SKAPEK, Auteur ; Meredith D. POWERS, Auteur ; Cara E. PUGLIESE, Auteur ; Lauren KENWORTHY, Auteur ; Chandan J. VAIDYA, Auteur Langues : Anglais (eng) Mots-clés : Adult  Autism Spectrum Disorder  Child  Humans  Memory, Episodic  Mental Recall  Prefrontal Cortex/diagnostic imaging  Recognition, Psychology  Associative memory  Behavioral flexibility  Medial temporal lobe  Executive function  Prefrontal cortex  fMRI  Executive Function. The other authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Conceptual knowledge frameworks termed schemas facilitate memory formation and are posited to support flexible behavior. In adults, the medial temporal lobe (MTL) and medial prefrontal cortex (mPFC) trade-off in supporting schema-based memory formation, such that encoding of subsequently remembered schema-congruent information relies on mPFC, whereas schema-incongruent information relies on MTL. Whether this is true in the immature brain and relates to behavioral flexibility is unknown. In this preliminary investigation, we aimed to replicate the adult findings in typically developing (TD) children and to investigate the relevance to behavioral flexibility by examining a disorder with pathognomonic behavioral rigidity, autism spectrum disorder (ASD). METHODS: Children completed an associative subsequent memory paradigm, encoding object-scene pairs in an MRI scanner and subsequently completing a recognition test outside the scanner after a delay. Recognition performance was back sorted to construct remembered vs forgotten contrasts. One-way ANOVAS were conducted in MTL and mPFC masks for schema-congruency, followed by congruency by flexibility scores. Exploratory analyses were then conducted within the whole brain. RESULTS: As reported in adults, episodic memory was strongest for schema-congruent object-scene pairs, followed by intermediate pairs, and lowest for schema-incongruent pairs in both TD and ASD groups. However, the trade-off between mPFC and MTL in TD children differed from adult reports such that mPFC supported memory for intermediate schema-congruency and left anterior MTL supported memory for schema-congruent pairs. In ASD, mPFC engagement interacted with flexibility such that activation supporting memory for intermediate schema-congruency varied with parent-reported flexibility and was higher in those with more flexible behavior. A similar interaction was also observed in both the left dorsolateral and rostrolateral PFC in whole-brain analysis. CONCLUSION: Our findings provide the first preliminary evidence for the association of schema-based episodic memory formation and behavioral flexibility, an executive function impaired in multiple developmental disorders. Upon replication, this line of research holds promise for memory-based interventions addressing executive problems of behavioral rigidity. En ligne : https://dx.doi.org/10.1186/s11689-021-09388-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Neural correlates of schema-dependent episodic memory and association with behavioral flexibility in autism spectrum disorders and typical development [texte imprimé] / Kevin M. COOK, Auteur ; Xiaozhen YOU, Auteur ; Joseph Bradley CHERRY, Auteur ; Junaid S. MERCHANT, Auteur ; Mary SKAPEK, Auteur ; Meredith D. POWERS, Auteur ; Cara E. PUGLIESE, Auteur ; Lauren KENWORTHY, Auteur ; Chandan J. VAIDYA, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 13 (2021) Mots-clés : Adult  Autism Spectrum Disorder  Child  Humans  Memory, Episodic  Mental Recall  Prefrontal Cortex/diagnostic imaging  Recognition, Psychology  Associative memory  Behavioral flexibility  Medial temporal lobe  Executive function  Prefrontal cortex  fMRI  Executive Function. The other authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Conceptual knowledge frameworks termed schemas facilitate memory formation and are posited to support flexible behavior. In adults, the medial temporal lobe (MTL) and medial prefrontal cortex (mPFC) trade-off in supporting schema-based memory formation, such that encoding of subsequently remembered schema-congruent information relies on mPFC, whereas schema-incongruent information relies on MTL. Whether this is true in the immature brain and relates to behavioral flexibility is unknown. In this preliminary investigation, we aimed to replicate the adult findings in typically developing (TD) children and to investigate the relevance to behavioral flexibility by examining a disorder with pathognomonic behavioral rigidity, autism spectrum disorder (ASD). METHODS: Children completed an associative subsequent memory paradigm, encoding object-scene pairs in an MRI scanner and subsequently completing a recognition test outside the scanner after a delay. Recognition performance was back sorted to construct remembered vs forgotten contrasts. One-way ANOVAS were conducted in MTL and mPFC masks for schema-congruency, followed by congruency by flexibility scores. Exploratory analyses were then conducted within the whole brain. RESULTS: As reported in adults, episodic memory was strongest for schema-congruent object-scene pairs, followed by intermediate pairs, and lowest for schema-incongruent pairs in both TD and ASD groups. However, the trade-off between mPFC and MTL in TD children differed from adult reports such that mPFC supported memory for intermediate schema-congruency and left anterior MTL supported memory for schema-congruent pairs. In ASD, mPFC engagement interacted with flexibility such that activation supporting memory for intermediate schema-congruency varied with parent-reported flexibility and was higher in those with more flexible behavior. A similar interaction was also observed in both the left dorsolateral and rostrolateral PFC in whole-brain analysis. CONCLUSION: Our findings provide the first preliminary evidence for the association of schema-based episodic memory formation and behavioral flexibility, an executive function impaired in multiple developmental disorders. Upon replication, this line of research holds promise for memory-based interventions addressing executive problems of behavioral rigidity. En ligne : https://dx.doi.org/10.1186/s11689-021-09388-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

PAC1R Genotype to Phenotype Correlations in Autism Spectrum Disorder / Meredith GOODRICH in Autism Research, 12-2 (February 2019)  

Public ISBD [article]  inAutism Research > 12-2 (February 2019) . - p.200-211 Titre : PAC1R Genotype to Phenotype Correlations in Autism Spectrum Disorder Type de document : texte imprimé Auteurs : Meredith GOODRICH, Auteur ; Anna Chelsea ARMOUR, Auteur ; Karuna PANCHAPAKESAN, Auteur ; Xiaozhen YOU, Auteur ; Joseph DEVANEY, Auteur ; Susan KNOBLACH, Auteur ; Catherine A.W. SULLIVAN, Auteur ; Maria Jesus HERRERO, Auteur ; Abha R. GUPTA, Auteur ; Chandan J. VAIDYA, Auteur ; Lauren KENWORTHY, Auteur ; Joshua G. CORBIN, Auteur Article en page(s) : p.200-211 Langues : Anglais (eng) Mots-clés : Pac1r  amygdala  autism  genetic modifier  neuroimaging Index. décimale : PER Périodiques Résumé : Amygdala dysfunction has been implicated in numerous neurodevelopmental disorders, including autism spectrum disorder (ASD). Previous studies in mice and humans, respectively, have linked Pac1r/PAC1R function to social behavior and PTSD-susceptibility. Based on this connection to social and emotional processing and the central role played by the amygdala in ASD, we examined a putative role for PAC1R in social deficits in ASD and determined the pattern of gene expression in the developing mouse and human amygdala. We reveal that Pac1r/PAC1R is expressed in both mouse and human amygdala from mid-neurogenesis through early postnatal stages, critical time points when altered brain trajectories are hypothesized to unfold in ASD. We further find that parents of autistic children carrying a previously identified PTSD-risk genotype (CC) report greater reciprocal social deficits compared to those carrying the non-risk GC genotype. Additionally, by exploring resting-state functional connectivity differences in a subsample of the larger behavioral sample, we find higher functional connectivity between the amygdala and right middle temporal gyrus in individuals with the CC risk genotype. Thus, using multimodal approaches, our data reveal that the amygdala-expressed PAC1R gene may be linked to severity of ASD social phenotype and possible alterations in brain connectivity, therefore potentially acting as a modifier of amygdala-related phenotypes. Autism Res 2019, 12: 200-211 (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this multimodal study across mouse and human, we examined expression patterns of Pac1r/PAC1R, a gene implicated in social behavior, and further explored whether a previously identified human PTSD-linked mutation in PAC1R can predict brain connectivity and social deficits in ASD. We find that PAC1R is highly expressed in the both the mouse and human amygdala. Furthermore, our human data suggest that PAC1R genotype is linked to severity of social deficits and functional amygdala connectivity in ASD. En ligne : http://dx.doi.org/10.1002/aur.2051 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=383 [article] PAC1R Genotype to Phenotype Correlations in Autism Spectrum Disorder [texte imprimé] / Meredith GOODRICH, Auteur ; Anna Chelsea ARMOUR, Auteur ; Karuna PANCHAPAKESAN, Auteur ; Xiaozhen YOU, Auteur ; Joseph DEVANEY, Auteur ; Susan KNOBLACH, Auteur ; Catherine A.W. SULLIVAN, Auteur ; Maria Jesus HERRERO, Auteur ; Abha R. GUPTA, Auteur ; Chandan J. VAIDYA, Auteur ; Lauren KENWORTHY, Auteur ; Joshua G. CORBIN, Auteur . - p.200-211. Langues : Anglais (eng) in Autism Research > 12-2 (February 2019) . - p.200-211 Mots-clés : Pac1r  amygdala  autism  genetic modifier  neuroimaging Index. décimale : PER Périodiques Résumé : Amygdala dysfunction has been implicated in numerous neurodevelopmental disorders, including autism spectrum disorder (ASD). Previous studies in mice and humans, respectively, have linked Pac1r/PAC1R function to social behavior and PTSD-susceptibility. Based on this connection to social and emotional processing and the central role played by the amygdala in ASD, we examined a putative role for PAC1R in social deficits in ASD and determined the pattern of gene expression in the developing mouse and human amygdala. We reveal that Pac1r/PAC1R is expressed in both mouse and human amygdala from mid-neurogenesis through early postnatal stages, critical time points when altered brain trajectories are hypothesized to unfold in ASD. We further find that parents of autistic children carrying a previously identified PTSD-risk genotype (CC) report greater reciprocal social deficits compared to those carrying the non-risk GC genotype. Additionally, by exploring resting-state functional connectivity differences in a subsample of the larger behavioral sample, we find higher functional connectivity between the amygdala and right middle temporal gyrus in individuals with the CC risk genotype. Thus, using multimodal approaches, our data reveal that the amygdala-expressed PAC1R gene may be linked to severity of ASD social phenotype and possible alterations in brain connectivity, therefore potentially acting as a modifier of amygdala-related phenotypes. Autism Res 2019, 12: 200-211 (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this multimodal study across mouse and human, we examined expression patterns of Pac1r/PAC1R, a gene implicated in social behavior, and further explored whether a previously identified human PTSD-linked mutation in PAC1R can predict brain connectivity and social deficits in ASD. We find that PAC1R is highly expressed in the both the mouse and human amygdala. Furthermore, our human data suggest that PAC1R genotype is linked to severity of social deficits and functional amygdala connectivity in ASD. En ligne : http://dx.doi.org/10.1002/aur.2051 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=383

Probing heterogeneity to identify individualized treatment approaches in autism: Specific clusters of executive function challenges link to distinct co-occurring mental health problems / Cara E. PUGLIESE in Autism, 28-11 (November 2024)  

Public ISBD [article]  inAutism > 28-11 (November 2024) . - p.2834 - 2847 Titre : Probing heterogeneity to identify individualized treatment approaches in autism: Specific clusters of executive function challenges link to distinct co-occurring mental health problems Type de document : texte imprimé Auteurs : Cara E. PUGLIESE, Auteur ; Rebecca HANDSMAN, Auteur ; Xiaozhen YOU, Auteur ; Laura G. ANTHONY, Auteur ; Chandan VAIDYA, Auteur ; Lauren KENWORTHY, Auteur Article en page(s) : p.2834 - 2847 Langues : Anglais (eng) Mots-clés : anxiety  autism spectrum disorders  depression  executive function  psychiatric comorbidity Index. décimale : PER Périodiques Résumé : Mental health conditions such as anxiety, depression, aggression, and inattention are common in autistic youth and are challenging to treat by community providers. We aim to parse the heterogeneity of autism based on dimensions of executive function and determine whether specific executive function profiles are differentially related to psychiatric symptoms. Parents of 397 well-characterized 8 - 14-year-old autistic children without an intellectual disability reported on their child?s executive function skills and psychiatric symptoms. We applied a data-driven, graph theory-based, community-detection approach to a common executive function measure, revealing three distinct executive function profile subgroups. Despite having similar social challenges, the executive function subgroups differed on anxiety, aggression, affect, and inattention symptoms. Results support the need for more intensive subtyping with autistic youth to develop appropriate, individualized mental health treatments and supports. Characterizing youth through neurocognitive strengths and challenges can guide the development of precision medicine, allowing for more meaningful, specialized treatment. Lay Abstract Many autistic people struggle with mental health problems like anxiety, depression, inattention, and aggression, which can be challenging to treat. Executive function challenges, which impact many autistic individuals, may serve as a risk factor for mental health problems or make treating mental health conditions more difficult. While some people respond well to medication or therapy, others do not. This study tried to understand if there are different subgroups of autistic young people who may have similar patterns of executive function strengths and challenges-like flexibility, planning, self-monitoring, and emotion regulation. Then, we investigated whether executive function subgroups were related to mental health problems in autistic youth. We found three different types of executive function subgroups in autistic youth, each with different patterns of mental health problems. This helps us identify specific profiles of executive function strengths and challenges that may be helpful with identifying personalized supports, services, and treatment strategies for mental health conditions. En ligne : https://dx.doi.org/10.1177/13623613241246091 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=537 [article] Probing heterogeneity to identify individualized treatment approaches in autism: Specific clusters of executive function challenges link to distinct co-occurring mental health problems [texte imprimé] / Cara E. PUGLIESE, Auteur ; Rebecca HANDSMAN, Auteur ; Xiaozhen YOU, Auteur ; Laura G. ANTHONY, Auteur ; Chandan VAIDYA, Auteur ; Lauren KENWORTHY, Auteur . - p.2834 - 2847. Langues : Anglais (eng) in Autism > 28-11 (November 2024) . - p.2834 - 2847 Mots-clés : anxiety  autism spectrum disorders  depression  executive function  psychiatric comorbidity Index. décimale : PER Périodiques Résumé : Mental health conditions such as anxiety, depression, aggression, and inattention are common in autistic youth and are challenging to treat by community providers. We aim to parse the heterogeneity of autism based on dimensions of executive function and determine whether specific executive function profiles are differentially related to psychiatric symptoms. Parents of 397 well-characterized 8 - 14-year-old autistic children without an intellectual disability reported on their child?s executive function skills and psychiatric symptoms. We applied a data-driven, graph theory-based, community-detection approach to a common executive function measure, revealing three distinct executive function profile subgroups. Despite having similar social challenges, the executive function subgroups differed on anxiety, aggression, affect, and inattention symptoms. Results support the need for more intensive subtyping with autistic youth to develop appropriate, individualized mental health treatments and supports. Characterizing youth through neurocognitive strengths and challenges can guide the development of precision medicine, allowing for more meaningful, specialized treatment. Lay Abstract Many autistic people struggle with mental health problems like anxiety, depression, inattention, and aggression, which can be challenging to treat. Executive function challenges, which impact many autistic individuals, may serve as a risk factor for mental health problems or make treating mental health conditions more difficult. While some people respond well to medication or therapy, others do not. This study tried to understand if there are different subgroups of autistic young people who may have similar patterns of executive function strengths and challenges-like flexibility, planning, self-monitoring, and emotion regulation. Then, we investigated whether executive function subgroups were related to mental health problems in autistic youth. We found three different types of executive function subgroups in autistic youth, each with different patterns of mental health problems. This helps us identify specific profiles of executive function strengths and challenges that may be helpful with identifying personalized supports, services, and treatment strategies for mental health conditions. En ligne : https://dx.doi.org/10.1177/13623613241246091 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=537

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