Atypical brain lateralisation in the auditory cortex and language performance in 3- to 7-year-old children with high-functioning autism spectrum disorder: a child-customised magnetoencephalography (MEG) study / Yuko YOSHIMURA in Molecular Autism, (October 2013)  

Public ISBD [article]  inMolecular Autism > (October 2013) Titre : Atypical brain lateralisation in the auditory cortex and language performance in 3- to 7-year-old children with high-functioning autism spectrum disorder: a child-customised magnetoencephalography (MEG) study Type de document : Texte imprimé et/ou numérique Auteurs : Yuko YOSHIMURA, Auteur ; Mitsuru KIKUCHI, Auteur ; Kiyomi SHITAMICHI, Auteur ; Sanae UENO, Auteur ; Toshio MUNESUE, Auteur ; Yasuki ONO, Auteur ; Tsunehisa TSUBOKAWA, Auteur ; Yasuhiro HARUTA, Auteur ; Manabu OI, Auteur ; Yo NIIDA, Auteur ; Gerard REMIJN, Auteur ; Tsutomu TAKAHASHI, Auteur ; Michio SUZUKI, Auteur ; Haruhiro HIGASHIDA, Auteur ; Yoshio MINABE, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Magnetoencephalography (MEG) is used to measure the auditory evoked magnetic field (AEF), which reflects language-related performance. In young children, however, the simultaneous quantification of the bilateral auditory-evoked response during binaural hearing is difficult using conventional adult-sized MEG systems. Recently, a child-customised MEG device has facilitated the acquisition of bi-hemispheric recordings, even in young children. Using the child-customised MEG device, we previously reported that language-related performance was reflected in the strength of the early component (P50m) of the auditory evoked magnetic field (AEF) in typically developing (TD) young children (2 to 5 years old) [Eur J Neurosci 2012, 35:644-650]. The aim of this study was to investigate how this neurophysiological index in each hemisphere is correlated with language performance in autism spectrum disorder (ASD) and TD children. We used magnetoencephalography (MEG) to measure the auditory evoked magnetic field (AEF), which reflects language-related performance. We investigated the P50m that is evoked by voice stimuli (/ne/) bilaterally in 33 young children (3 to 7 years old) with ASD and in 30 young children who were typically developing (TD). The children were matched according to their age (in months) and gender. Most of the children with ASD were high-functioning subjects. The results showed that the children with ASD exhibited significantly less leftward lateralisation in their P50m intensity compared with the TD children. Furthermore, the results of a multiple regression analysis indicated that a shorter P50m latency in both hemispheres was specifically correlated with higher language-related performance in the TD children, whereas this latency was not correlated with non-verbal cognitive performance or chronological age. The children with ASD did not show any correlation between P50m latency and language-related performance; instead, increasing chronological age was a significant predictor of shorter P50m latency in the right hemisphere. Using a child-customised MEG device, we studied the P50m component that was evoked through binaural human voice stimuli in young ASD and TD children to examine differences in auditory cortex function that are associated with language development. Our results suggest that there is atypical brain function in the auditory cortex in young children with ASD, regardless of language development. En ligne : http://dx.doi.org/10.1186/2040-2392-4-38 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Atypical brain lateralisation in the auditory cortex and language performance in 3- to 7-year-old children with high-functioning autism spectrum disorder: a child-customised magnetoencephalography (MEG) study [Texte imprimé et/ou numérique] / Yuko YOSHIMURA, Auteur ; Mitsuru KIKUCHI, Auteur ; Kiyomi SHITAMICHI, Auteur ; Sanae UENO, Auteur ; Toshio MUNESUE, Auteur ; Yasuki ONO, Auteur ; Tsunehisa TSUBOKAWA, Auteur ; Yasuhiro HARUTA, Auteur ; Manabu OI, Auteur ; Yo NIIDA, Auteur ; Gerard REMIJN, Auteur ; Tsutomu TAKAHASHI, Auteur ; Michio SUZUKI, Auteur ; Haruhiro HIGASHIDA, Auteur ; Yoshio MINABE, Auteur. Langues : Anglais (eng) in Molecular Autism > (October 2013) Index. décimale : PER Périodiques Résumé : Magnetoencephalography (MEG) is used to measure the auditory evoked magnetic field (AEF), which reflects language-related performance. In young children, however, the simultaneous quantification of the bilateral auditory-evoked response during binaural hearing is difficult using conventional adult-sized MEG systems. Recently, a child-customised MEG device has facilitated the acquisition of bi-hemispheric recordings, even in young children. Using the child-customised MEG device, we previously reported that language-related performance was reflected in the strength of the early component (P50m) of the auditory evoked magnetic field (AEF) in typically developing (TD) young children (2 to 5 years old) [Eur J Neurosci 2012, 35:644-650]. The aim of this study was to investigate how this neurophysiological index in each hemisphere is correlated with language performance in autism spectrum disorder (ASD) and TD children. We used magnetoencephalography (MEG) to measure the auditory evoked magnetic field (AEF), which reflects language-related performance. We investigated the P50m that is evoked by voice stimuli (/ne/) bilaterally in 33 young children (3 to 7 years old) with ASD and in 30 young children who were typically developing (TD). The children were matched according to their age (in months) and gender. Most of the children with ASD were high-functioning subjects. The results showed that the children with ASD exhibited significantly less leftward lateralisation in their P50m intensity compared with the TD children. Furthermore, the results of a multiple regression analysis indicated that a shorter P50m latency in both hemispheres was specifically correlated with higher language-related performance in the TD children, whereas this latency was not correlated with non-verbal cognitive performance or chronological age. The children with ASD did not show any correlation between P50m latency and language-related performance; instead, increasing chronological age was a significant predictor of shorter P50m latency in the right hemisphere. Using a child-customised MEG device, we studied the P50m component that was evoked through binaural human voice stimuli in young ASD and TD children to examine differences in auditory cortex function that are associated with language development. Our results suggest that there is atypical brain function in the auditory cortex in young children with ASD, regardless of language development. En ligne : http://dx.doi.org/10.1186/2040-2392-4-38 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

Atypical development of the central auditory system in young children with Autism spectrum disorder / Yuko YOSHIMURA in Autism Research, 9-11 (November 2016)  

Public ISBD [article]  inAutism Research > 9-11 (November 2016) . - p.1216-1226 Titre : Atypical development of the central auditory system in young children with Autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Yuko YOSHIMURA, Auteur ; Mitsuru KIKUCHI, Auteur ; Hirotoshi HIRAISHI, Auteur ; Chiaki HASEGAWA, Auteur ; Tetsuya TAKAHASHI, Auteur ; Gerard B. REMIJN, Auteur ; Manabu OI, Auteur ; Toshio MUNESUE, Auteur ; Haruhiro HIGASHIDA, Auteur ; Yoshio MINABE, Auteur ; Haruyuki KOJIMA, Auteur Article en page(s) : p.1216-1226 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  magnetoencephalography  P1m  young children Index. décimale : PER Périodiques Résumé : The P1m component of the auditory evoked magnetic field is the earliest cortical response associated with language acquisition. However, the growth curve of the P1m component is unknown in both typically developing (TD) and atypically developing children. The aim of this study is to clarify the developmental pattern of this component when evoked by binaural human voice stimulation using child-customized magnetoencephalography. A total of 35 young TD children (32–121 months of age) and 35 children with autism spectrum disorder (ASD) (38–111 months of age) participated in this study. This is the first report to demonstrate an inverted U-shaped growth curve for the P1m dipole intensity in the left hemisphere in TD children. In addition, our results revealed a more diversified age-related distribution of auditory brain responses in 3- to 9-year-old children with ASD. These results demonstrate the diversified growth curve of the P1m component in ASD during young childhood, which is a crucial period for first language acquisition. En ligne : http://dx.doi.org/10.1002/aur.1604 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=297 [article] Atypical development of the central auditory system in young children with Autism spectrum disorder [Texte imprimé et/ou numérique] / Yuko YOSHIMURA, Auteur ; Mitsuru KIKUCHI, Auteur ; Hirotoshi HIRAISHI, Auteur ; Chiaki HASEGAWA, Auteur ; Tetsuya TAKAHASHI, Auteur ; Gerard B. REMIJN, Auteur ; Manabu OI, Auteur ; Toshio MUNESUE, Auteur ; Haruhiro HIGASHIDA, Auteur ; Yoshio MINABE, Auteur ; Haruyuki KOJIMA, Auteur . - p.1216-1226. Langues : Anglais (eng) in Autism Research > 9-11 (November 2016) . - p.1216-1226 Mots-clés : autism spectrum disorder  magnetoencephalography  P1m  young children Index. décimale : PER Périodiques Résumé : The P1m component of the auditory evoked magnetic field is the earliest cortical response associated with language acquisition. However, the growth curve of the P1m component is unknown in both typically developing (TD) and atypically developing children. The aim of this study is to clarify the developmental pattern of this component when evoked by binaural human voice stimulation using child-customized magnetoencephalography. A total of 35 young TD children (32–121 months of age) and 35 children with autism spectrum disorder (ASD) (38–111 months of age) participated in this study. This is the first report to demonstrate an inverted U-shaped growth curve for the P1m dipole intensity in the left hemisphere in TD children. In addition, our results revealed a more diversified age-related distribution of auditory brain responses in 3- to 9-year-old children with ASD. These results demonstrate the diversified growth curve of the P1m component in ASD during young childhood, which is a crucial period for first language acquisition. En ligne : http://dx.doi.org/10.1002/aur.1604 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=297

Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism / Shiro SUDA in Molecular Autism, (August 2011)  

Public ISBD [article]  inMolecular Autism > (August 2011) . - 5 p. Titre : Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism Type de document : Texte imprimé et/ou numérique Auteurs : Shiro SUDA, Auteur ; Keiko IWATA, Auteur ; Chie SHIMMURA, Auteur ; Yosuke KAMENO, Auteur ; Ayyappan ANITHA, Auteur ; Ismail THANSEEM, Auteur ; Kazuhiko NAKAMURA, Auteur ; Hideo MATSUZAKI, Auteur ; Kenji J. TSUCHIYA, Auteur ; Genichi SUGIHARA, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Keita KOIZUMI, Auteur ; Haruhiro HIGASHIDA, Auteur ; Nori TAKEI, Auteur ; Norio MORI, Auteur Année de publication : 2011 Article en page(s) : 5 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND:Axon-guidance proteins play a crucial role in brain development. As the dysfunction of axon-guidance signaling is thought to underlie the microstructural abnormalities of the brain in people with autism, we examined the postmortem brains of people with autism to identify any changes in the expression of axon-guidance proteins.RESULTS:The mRNA and protein expression of axon-guidance proteins, including ephrin (EFN)A4, eEFNB3, plexin (PLXN)A4, roundabout 2 (ROBO)2 and ROBO3, were examined in the anterior cingulate cortex and primary motor cortex of autistic brains (n = 8 and n = 7, respectively) and control brains (n = 13 and n = 8, respectively) using real-time reverse-transcriptase PCR (RT-PCR) and western blotting. Real-time RT-PCR revealed that the relative expression levels of EFNB3, PLXNA4A and ROBO2 were significantly lower in the autistic group than in the control group. The protein levels of these three genes were further analyzed by western blotting, which showed that the immunoreactive values for PLXNA4 and ROBO2, but not for EFNB3, were significantly reduced in the ACC of the autistic brains compared with control brains.CONCLUSIONS:In this study, we found decreased expression of axon-guidance proteins such as PLXNA4 and ROBO2 in the brains of people with autism, and suggest that dysfunctional axon-guidance protein expression may play an important role in the pathophysiology of autism. En ligne : http://dx.doi.org/10.1186/2040-2392-2-14 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=149 [article] Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism [Texte imprimé et/ou numérique] / Shiro SUDA, Auteur ; Keiko IWATA, Auteur ; Chie SHIMMURA, Auteur ; Yosuke KAMENO, Auteur ; Ayyappan ANITHA, Auteur ; Ismail THANSEEM, Auteur ; Kazuhiko NAKAMURA, Auteur ; Hideo MATSUZAKI, Auteur ; Kenji J. TSUCHIYA, Auteur ; Genichi SUGIHARA, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Keita KOIZUMI, Auteur ; Haruhiro HIGASHIDA, Auteur ; Nori TAKEI, Auteur ; Norio MORI, Auteur . - 2011 . - 5 p. Langues : Anglais (eng) in Molecular Autism > (August 2011) . - 5 p. Index. décimale : PER Périodiques Résumé : BACKGROUND:Axon-guidance proteins play a crucial role in brain development. As the dysfunction of axon-guidance signaling is thought to underlie the microstructural abnormalities of the brain in people with autism, we examined the postmortem brains of people with autism to identify any changes in the expression of axon-guidance proteins.RESULTS:The mRNA and protein expression of axon-guidance proteins, including ephrin (EFN)A4, eEFNB3, plexin (PLXN)A4, roundabout 2 (ROBO)2 and ROBO3, were examined in the anterior cingulate cortex and primary motor cortex of autistic brains (n = 8 and n = 7, respectively) and control brains (n = 13 and n = 8, respectively) using real-time reverse-transcriptase PCR (RT-PCR) and western blotting. Real-time RT-PCR revealed that the relative expression levels of EFNB3, PLXNA4A and ROBO2 were significantly lower in the autistic group than in the control group. The protein levels of these three genes were further analyzed by western blotting, which showed that the immunoreactive values for PLXNA4 and ROBO2, but not for EFNB3, were significantly reduced in the ACC of the autistic brains compared with control brains.CONCLUSIONS:In this study, we found decreased expression of axon-guidance proteins such as PLXNA4 and ROBO2 in the brains of people with autism, and suggest that dysfunctional axon-guidance protein expression may play an important role in the pathophysiology of autism. En ligne : http://dx.doi.org/10.1186/2040-2392-2-14 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=149

A Missense Mutation in CD38 Associated with Autism Spectrum Disorder in Three Pedigrees / Haruhiro HIGASHIDA  

Public ISBD in Autism - A Neurodevelopmental Journey from Genes to Behaviour / Valsamma EAPEN   Titre : A Missense Mutation in CD38 Associated with Autism Spectrum Disorder in Three Pedigrees Type de document : Texte imprimé et/ou numérique Auteurs : Haruhiro HIGASHIDA, Auteur ; Toshio MUNESUE, Auteur ; Shigeru YOKOYAMA, Auteur ; Minako HASHII, Auteur ; Keita KOIZUMI, Auteur ; Akihiro MATSUSHIMA, Auteur Année de publication : 2011 Importance : p.183-196 Langues : Anglais (eng) Index. décimale : AUT-B AUT-B - L'Autisme - Ouvrages généraux et scientifiques En ligne : http://dx.doi.org/10.5772/17774 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=143 in Autism - A Neurodevelopmental Journey from Genes to Behaviour / Valsamma EAPEN   A Missense Mutation in CD38 Associated with Autism Spectrum Disorder in Three Pedigrees [Texte imprimé et/ou numérique] / Haruhiro HIGASHIDA, Auteur ; Toshio MUNESUE, Auteur ; Shigeru YOKOYAMA, Auteur ; Minako HASHII, Auteur ; Keita KOIZUMI, Auteur ; Akihiro MATSUSHIMA, Auteur . - 2011 . - p.183-196. Langues : Anglais (eng) Index. décimale : AUT-B AUT-B - L'Autisme - Ouvrages généraux et scientifiques En ligne : http://dx.doi.org/10.5772/17774 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=143

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Non-synonymous single-nucleotide variations of the human oxytocin receptor gene and autism spectrum disorders: a case–control study in a Japanese population and functional analysis / Wen-Jie MA in Molecular Autism, (July 2013)  

Public ISBD [article]  inMolecular Autism > (July 2013) . - 14 p. Titre : Non-synonymous single-nucleotide variations of the human oxytocin receptor gene and autism spectrum disorders: a case–control study in a Japanese population and functional analysis Type de document : Texte imprimé et/ou numérique Auteurs : Wen-Jie MA, Auteur ; Minako HASHII, Auteur ; Toshio MUNESUE, Auteur ; Kenshi HAYASHI, Auteur ; Kunimasa YAGI, Auteur ; Masakazu YAMAGISHI, Auteur ; Haruhiro HIGASHIDA, Auteur ; Shigeru YOKOYAMA, Auteur Année de publication : 2013 Article en page(s) : 14 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorders  Inositol-1,4,5-trisphosphate  Intracellular free calcium  Oxytocin  Oxytocin receptor  Single-nucleotide variation Index. décimale : PER Périodiques Résumé : Background The human oxytocin receptor (hOXTR) is implicated in the etiology of autism spectrum disorders (ASDs) and is a potential target for therapeutic intervention. Several studies have reported single-nucleotide polymorphisms (SNPs) of the OXTR gene associated with ASDs. These SNPs, however, reside outside the protein-coding region. Not much is known about genetic variations that cause amino acid substitutions that alter receptor functions. Methods Variations in the OXTR gene were analyzed in 132 ASD patients at Kanazawa University Hospital in Japan and 248 unrelated healthy Japanese volunteers by re-sequencing and real-time polymerase chain reaction-based genotyping. Functional changes in variant OXTRs were assessed by radioligand binding assay and measurements of intracellular free calcium concentrations ([Ca2+]i) and inositol 1,4,5-trisphosphate (IP3) levels. Results Six subjects (4.5%) in the ASD group and two in the control group (0.8%) were identified as heterozygotes carrying the R376G variation (rs35062132; c.1126C>G); one individual from the ASD group (0.8%) and three members of the control group (1.2%) were found to be carrying R376C (c.1126C>T). The C/G genotype significantly correlated with an increased risk of ASDs (odds ratio (OR) = 5.83; 95% confidence interval (CI) = 1.16 to 29.33; P = 0.024, Fisher’s exact test). Consistently, the G allele showed a correlation with an increased likelihood of ASDs (OR = 5.73; 95% CI = 1.15 to 28.61; P = 0.024, Fisher’s exact test). The frequencies of the C/T genotype and the T allele in the ASD and control groups did not differ significantly. We also examined changes in agonist-induced cellular responses mediated by the variant receptors hOXTR-376G and hOXTR-376C. OXT-induced receptor internalization and recycling were faster in hOXTR-376G-expressing HEK-293 cells than in cells expressing hOXTR-376R or hOXTR-376C. In addition, the elevation in [Ca2+]i and IP3 formation decreased in the cells expressing hOXTR-376G and hOXTR-376C tagged with enhanced green fluorescent protein (EGFP), in comparison with the cells expressing the common-type hOXTR-376R tagged with EGFP. Conclusions These results suggest that the rare genetic variation rs35062132 might contribute to the pathogenesis of ASDs, and could provide a molecular basis of individual differences in OXTR-mediated modulation of social behavior. En ligne : http://dx.doi.org/10.1186/2040-2392-4-22 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211 [article] Non-synonymous single-nucleotide variations of the human oxytocin receptor gene and autism spectrum disorders: a case–control study in a Japanese population and functional analysis [Texte imprimé et/ou numérique] / Wen-Jie MA, Auteur ; Minako HASHII, Auteur ; Toshio MUNESUE, Auteur ; Kenshi HAYASHI, Auteur ; Kunimasa YAGI, Auteur ; Masakazu YAMAGISHI, Auteur ; Haruhiro HIGASHIDA, Auteur ; Shigeru YOKOYAMA, Auteur . - 2013 . - 14 p. Langues : Anglais (eng) in Molecular Autism > (July 2013) . - 14 p. Mots-clés : Autism spectrum disorders  Inositol-1,4,5-trisphosphate  Intracellular free calcium  Oxytocin  Oxytocin receptor  Single-nucleotide variation Index. décimale : PER Périodiques Résumé : Background The human oxytocin receptor (hOXTR) is implicated in the etiology of autism spectrum disorders (ASDs) and is a potential target for therapeutic intervention. Several studies have reported single-nucleotide polymorphisms (SNPs) of the OXTR gene associated with ASDs. These SNPs, however, reside outside the protein-coding region. Not much is known about genetic variations that cause amino acid substitutions that alter receptor functions. Methods Variations in the OXTR gene were analyzed in 132 ASD patients at Kanazawa University Hospital in Japan and 248 unrelated healthy Japanese volunteers by re-sequencing and real-time polymerase chain reaction-based genotyping. Functional changes in variant OXTRs were assessed by radioligand binding assay and measurements of intracellular free calcium concentrations ([Ca2+]i) and inositol 1,4,5-trisphosphate (IP3) levels. Results Six subjects (4.5%) in the ASD group and two in the control group (0.8%) were identified as heterozygotes carrying the R376G variation (rs35062132; c.1126C>G); one individual from the ASD group (0.8%) and three members of the control group (1.2%) were found to be carrying R376C (c.1126C>T). The C/G genotype significantly correlated with an increased risk of ASDs (odds ratio (OR) = 5.83; 95% confidence interval (CI) = 1.16 to 29.33; P = 0.024, Fisher’s exact test). Consistently, the G allele showed a correlation with an increased likelihood of ASDs (OR = 5.73; 95% CI = 1.15 to 28.61; P = 0.024, Fisher’s exact test). The frequencies of the C/T genotype and the T allele in the ASD and control groups did not differ significantly. We also examined changes in agonist-induced cellular responses mediated by the variant receptors hOXTR-376G and hOXTR-376C. OXT-induced receptor internalization and recycling were faster in hOXTR-376G-expressing HEK-293 cells than in cells expressing hOXTR-376R or hOXTR-376C. In addition, the elevation in [Ca2+]i and IP3 formation decreased in the cells expressing hOXTR-376G and hOXTR-376C tagged with enhanced green fluorescent protein (EGFP), in comparison with the cells expressing the common-type hOXTR-376R tagged with EGFP. Conclusions These results suggest that the rare genetic variation rs35062132 might contribute to the pathogenesis of ASDs, and could provide a molecular basis of individual differences in OXTR-mediated modulation of social behavior. En ligne : http://dx.doi.org/10.1186/2040-2392-4-22 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211

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