Altered functional organization within the insular cortex in adult males with high-functioning autism spectrum disorder: evidence from connectivity-based parcellation / T. YAMADA in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 41p. Titre : Altered functional organization within the insular cortex in adult males with high-functioning autism spectrum disorder: evidence from connectivity-based parcellation Type de document : Texte imprimé et/ou numérique Auteurs : T. YAMADA, Auteur ; T. ITAHASHI, Auteur ; M. NAKAMURA, Auteur ; H. WATANABE, Auteur ; M. KURODA, Auteur ; H. OHTA, Auteur ; C. KANAI, Auteur ; N. KATO, Auteur ; R. I. HASHIMOTO, Auteur Article en page(s) : 41p. Langues : Anglais (eng) Mots-clés : Adult  Autism Spectrum Disorder/diagnostic imaging/pathology/physiopathology  Brain Mapping/methods  Case-Control Studies  Cerebral Cortex/diagnostic imaging/pathology/physiopathology  Cluster Analysis  Functional Laterality  Humans  Image Interpretation, Computer-Assisted  Magnetic Resonance Imaging  Male  Middle Aged  Nerve Net/diagnostic imaging/pathology/physiopathology  Neural Pathways/diagnostic imaging/pathology/physiopathology  Autism spectrum disorder  Connectivity-based functional parcellation  Insula  Resting-state functional magnetic resonance imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: The insular cortex comprises multiple functionally differentiated sub-regions, each of which has different patterns of connectivity with other brain regions. Such diverse connectivity patterns are thought to underlie a wide range of insular functions, including cognitive, affective, and sensorimotor processing, many of which are abnormal in autism spectrum disorder (ASD). Although past neuroimaging studies of ASD have shown structural and functional abnormalities in the insula, possible alterations in the sub-regional organization of the insula and the functional characteristics of each sub-region have not been examined in the ASD brain. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 36 adult males with ASD and 38 matched typically developed (TD) controls. A data-driven clustering analysis was applied to rs-fMRI data of voxels in the left and right insula to automatically group voxels with similar intrinsic connectivity pattern into a cluster. After determining the optimal number of clusters based on information theoretic measures of variation of information and mutual information, functional parcellation patterns in both the left and the right insula were compared between the TD and ASD groups. Furthermore, functional profiles of each sub-region were meta-analytically decoded using Neurosynth and were compared between the groups. RESULTS: We observed notable alterations in the anterior sector of the left insula and the middle ventral sub-region of the right insula in the ASD brain. Meta-analytic decoding revealed that whereas the anterior sector of the left insula contained two functionally differentiated sub-regions for cognitive, sensorimotor, and emotional/affective functions in TD brain, only a single functional cluster for cognitive and sensorimotor functions was identified in the anterior sector in the ASD brain. In the right insula, the middle ventral sub-region, which is primarily specialized for sensory- and auditory-related functions, showed a significant volumetric increase in the ASD brain compared with the TD brain. CONCLUSIONS: The results indicate an altered organization of sub-regions in specific parts of the left and right insula of the ASD brain. The alterations in the left and right insula may constitute neural substrates underlying abnormalities in emotional/affective and sensory functions in ASD. En ligne : http://dx.doi.org/10.1186/s13229-016-0106-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Altered functional organization within the insular cortex in adult males with high-functioning autism spectrum disorder: evidence from connectivity-based parcellation [Texte imprimé et/ou numérique] / T. YAMADA, Auteur ; T. ITAHASHI, Auteur ; M. NAKAMURA, Auteur ; H. WATANABE, Auteur ; M. KURODA, Auteur ; H. OHTA, Auteur ; C. KANAI, Auteur ; N. KATO, Auteur ; R. I. HASHIMOTO, Auteur . - 41p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 41p. Mots-clés : Adult  Autism Spectrum Disorder/diagnostic imaging/pathology/physiopathology  Brain Mapping/methods  Case-Control Studies  Cerebral Cortex/diagnostic imaging/pathology/physiopathology  Cluster Analysis  Functional Laterality  Humans  Image Interpretation, Computer-Assisted  Magnetic Resonance Imaging  Male  Middle Aged  Nerve Net/diagnostic imaging/pathology/physiopathology  Neural Pathways/diagnostic imaging/pathology/physiopathology  Autism spectrum disorder  Connectivity-based functional parcellation  Insula  Resting-state functional magnetic resonance imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: The insular cortex comprises multiple functionally differentiated sub-regions, each of which has different patterns of connectivity with other brain regions. Such diverse connectivity patterns are thought to underlie a wide range of insular functions, including cognitive, affective, and sensorimotor processing, many of which are abnormal in autism spectrum disorder (ASD). Although past neuroimaging studies of ASD have shown structural and functional abnormalities in the insula, possible alterations in the sub-regional organization of the insula and the functional characteristics of each sub-region have not been examined in the ASD brain. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 36 adult males with ASD and 38 matched typically developed (TD) controls. A data-driven clustering analysis was applied to rs-fMRI data of voxels in the left and right insula to automatically group voxels with similar intrinsic connectivity pattern into a cluster. After determining the optimal number of clusters based on information theoretic measures of variation of information and mutual information, functional parcellation patterns in both the left and the right insula were compared between the TD and ASD groups. Furthermore, functional profiles of each sub-region were meta-analytically decoded using Neurosynth and were compared between the groups. RESULTS: We observed notable alterations in the anterior sector of the left insula and the middle ventral sub-region of the right insula in the ASD brain. Meta-analytic decoding revealed that whereas the anterior sector of the left insula contained two functionally differentiated sub-regions for cognitive, sensorimotor, and emotional/affective functions in TD brain, only a single functional cluster for cognitive and sensorimotor functions was identified in the anterior sector in the ASD brain. In the right insula, the middle ventral sub-region, which is primarily specialized for sensory- and auditory-related functions, showed a significant volumetric increase in the ASD brain compared with the TD brain. CONCLUSIONS: The results indicate an altered organization of sub-regions in specific parts of the left and right insula of the ASD brain. The alterations in the left and right insula may constitute neural substrates underlying abnormalities in emotional/affective and sensory functions in ASD. En ligne : http://dx.doi.org/10.1186/s13229-016-0106-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms / Y. KATO in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 15 p. Titre : Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms Type de document : Texte imprimé et/ou numérique Auteurs : Y. KATO, Auteur ; H. KUWABARA, Auteur ; T. OKADA, Auteur ; T. MUNESUE, Auteur ; S. BENNER, Auteur ; M. KURODA, Auteur ; M. KOJIMA, Auteur ; W. YASSIN, Auteur ; Y. ERIGUCHI, Auteur ; Y. KAMENO, Auteur ; C. MURAYAMA, Auteur ; T. NISHIMURA, Auteur ; K. TSUCHIYA, Auteur ; Kiyoto KASAI, Auteur ; N. OZAKI, Auteur ; H. KOSAKA, Auteur ; H. YAMASUE, Auteur Article en page(s) : 15 p. Langues : Anglais (eng) Mots-clés : Administration, Intranasal  Adolescent  Adult  Autistic Disorder/blood/drug therapy/metabolism/psychology  Double-Blind Method  Facial Expression  Humans  Male  Metabolomics  Middle Aged  Oxytocin/administration & dosage/blood/pharmacokinetics  Sarcosine/analogs & derivatives/blood  Social Behavior  Treatment Outcome  Young Adult  Asperger  Autism  Clinical trial  Developmental disorders  Facial expression  N,N-Dimethylglycine  Neuropeptide  Oxytocin  Plasticity  collection, management, analysis, and interpretation of the data  preparation,  review, or approval of the manuscript  or decision to submit the manuscript for  publication. There are no conflicts of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. METHODS: The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6-week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N?=?106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial. RESULTS: Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (false discovery rate (FDR) corrected P?=?0.043, d?=?0.74, N?=?83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (P(FDR)?=?0.004, d?=?1.13, N?=?60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (P(FDR)?=?0.006, r?=?-?0.485, N?=?43) and deteriorations between 2 and 4 weeks (P(FDR)?=?0.032, r?=?0.415, N?=?37). LIMITATIONS: The metabolites changes caused by oxytocin administration were quantified using peripheral blood and therefore may not directly reflect central nervous system changes. CONCLUSION: Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-methyl-D-aspartate receptor and neural plasticity to the time-course change in oxytocin's efficacy. TRIAL REGISTRATION: A multi-center, parallel-group, placebo-controlled, double-blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders (the date registered: 30 October 2014; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703 ) (UMIN000015264). En ligne : http://dx.doi.org/10.1186/s13229-021-00423-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms [Texte imprimé et/ou numérique] / Y. KATO, Auteur ; H. KUWABARA, Auteur ; T. OKADA, Auteur ; T. MUNESUE, Auteur ; S. BENNER, Auteur ; M. KURODA, Auteur ; M. KOJIMA, Auteur ; W. YASSIN, Auteur ; Y. ERIGUCHI, Auteur ; Y. KAMENO, Auteur ; C. MURAYAMA, Auteur ; T. NISHIMURA, Auteur ; K. TSUCHIYA, Auteur ; Kiyoto KASAI, Auteur ; N. OZAKI, Auteur ; H. KOSAKA, Auteur ; H. YAMASUE, Auteur . - 15 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 15 p. Mots-clés : Administration, Intranasal  Adolescent  Adult  Autistic Disorder/blood/drug therapy/metabolism/psychology  Double-Blind Method  Facial Expression  Humans  Male  Metabolomics  Middle Aged  Oxytocin/administration & dosage/blood/pharmacokinetics  Sarcosine/analogs & derivatives/blood  Social Behavior  Treatment Outcome  Young Adult  Asperger  Autism  Clinical trial  Developmental disorders  Facial expression  N,N-Dimethylglycine  Neuropeptide  Oxytocin  Plasticity  collection, management, analysis, and interpretation of the data  preparation,  review, or approval of the manuscript  or decision to submit the manuscript for  publication. There are no conflicts of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. METHODS: The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6-week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N?=?106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial. RESULTS: Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (false discovery rate (FDR) corrected P?=?0.043, d?=?0.74, N?=?83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (P(FDR)?=?0.004, d?=?1.13, N?=?60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (P(FDR)?=?0.006, r?=?-?0.485, N?=?43) and deteriorations between 2 and 4 weeks (P(FDR)?=?0.032, r?=?0.415, N?=?37). LIMITATIONS: The metabolites changes caused by oxytocin administration were quantified using peripheral blood and therefore may not directly reflect central nervous system changes. CONCLUSION: Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-methyl-D-aspartate receptor and neural plasticity to the time-course change in oxytocin's efficacy. TRIAL REGISTRATION: A multi-center, parallel-group, placebo-controlled, double-blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders (the date registered: 30 October 2014; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703 ) (UMIN000015264). En ligne : http://dx.doi.org/10.1186/s13229-021-00423-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

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