Decreased homotopic interhemispheric functional connectivity in children with autism spectrum disorder / S. YAO in Autism Research, 14-8 (August 2021)  

Public ISBD [article]  inAutism Research > 14-8 (August 2021) . - p.1609-1620 Titre : Decreased homotopic interhemispheric functional connectivity in children with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : S. YAO, Auteur ; M. ZHOU, Auteur ; Y. ZHANG, Auteur ; F. ZHOU, Auteur ; Q. ZHANG, Auteur ; Z. ZHAO, Auteur ; X. JIANG, Auteur ; X. XU, Auteur ; B. BECKER, Auteur ; K. M. KENDRICK, Auteur Article en page(s) : p.1609-1620 Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Autism Spectrum Disorder/diagnostic imaging  Brain/diagnostic imaging  Brain Mapping  Child  Child, Preschool  Corpus Callosum/diagnostic imaging  Humans  Magnetic Resonance Imaging  Neural Pathways/diagnostic imaging  autism spectrum disorder  children  corpus callosum  homotopic interhemispheric functional connectivity  resting-state Index. décimale : PER Périodiques Résumé : While several functional and structural changes occur in large-scale brain networks in autism spectrum disorder (ASD), reduced interhemispheric resting-state functional connectivity (rsFC) between homotopic regions may be of particular importance as a biomarker. ASD is an early-onset developmental disorder and neural alterations are often age-dependent. Although there is some evidence for homotopic interhemispheric rsFC alterations in language processing regions in ASD children, wider analyses using large data sets have not been performed. The present study, therefore, conducted a voxel-based homotopic interhemispheric rsFC analysis in 146 ASD and 175 typically developing children under-age 10 and examined associations with symptom severity in the autism brain imaging data exchange data sets. Given the role of corpus callosum (CC) in interhemispheric connectivity and reported CC volume changes in ASD we additionally examined whether there were parallel volumetric changes. Results demonstrated decreased homotopic rsFC in ASD children in the posterior cingulate cortex (PCC) and precuneus of the default mode network, the precentral gyrus of the mirror neuron system, and the caudate of the reward system. Homotopic rsFC of the PCC was associated with symptom severity. Furthermore, although no significant CC volume changes were found in ASD children, there was a significant negative correlation between the anterior CC volumes and homotopic rsFC strengths in the caudate. The present study shows that a reduced pattern of homotopic interhemispheric rsFC in ASD adults/adolescents is already present in children of 5-10?years old and further supports their potential use as a general ASD biomarker. LAY SUMMARY: Homotopic interhemispheric functional connectivity plays an important role in synchronizing activity between the two hemispheres and is altered in adults and adolescents with autism spectrum disorder (ASD). In the present study focused on children with ASD, we have observed a similar pattern of decreased homotopic connectivity, suggesting that alterations in homotopic interhemispheric connectivity may occur early in ASD and be a useful general biomarker across ages. En ligne : http://dx.doi.org/10.1002/aur.2523 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449 [article] Decreased homotopic interhemispheric functional connectivity in children with autism spectrum disorder [Texte imprimé et/ou numérique] / S. YAO, Auteur ; M. ZHOU, Auteur ; Y. ZHANG, Auteur ; F. ZHOU, Auteur ; Q. ZHANG, Auteur ; Z. ZHAO, Auteur ; X. JIANG, Auteur ; X. XU, Auteur ; B. BECKER, Auteur ; K. M. KENDRICK, Auteur . - p.1609-1620. Langues : Anglais (eng) in Autism Research > 14-8 (August 2021) . - p.1609-1620 Mots-clés : Adolescent  Adult  Autism Spectrum Disorder/diagnostic imaging  Brain/diagnostic imaging  Brain Mapping  Child  Child, Preschool  Corpus Callosum/diagnostic imaging  Humans  Magnetic Resonance Imaging  Neural Pathways/diagnostic imaging  autism spectrum disorder  children  corpus callosum  homotopic interhemispheric functional connectivity  resting-state Index. décimale : PER Périodiques Résumé : While several functional and structural changes occur in large-scale brain networks in autism spectrum disorder (ASD), reduced interhemispheric resting-state functional connectivity (rsFC) between homotopic regions may be of particular importance as a biomarker. ASD is an early-onset developmental disorder and neural alterations are often age-dependent. Although there is some evidence for homotopic interhemispheric rsFC alterations in language processing regions in ASD children, wider analyses using large data sets have not been performed. The present study, therefore, conducted a voxel-based homotopic interhemispheric rsFC analysis in 146 ASD and 175 typically developing children under-age 10 and examined associations with symptom severity in the autism brain imaging data exchange data sets. Given the role of corpus callosum (CC) in interhemispheric connectivity and reported CC volume changes in ASD we additionally examined whether there were parallel volumetric changes. Results demonstrated decreased homotopic rsFC in ASD children in the posterior cingulate cortex (PCC) and precuneus of the default mode network, the precentral gyrus of the mirror neuron system, and the caudate of the reward system. Homotopic rsFC of the PCC was associated with symptom severity. Furthermore, although no significant CC volume changes were found in ASD children, there was a significant negative correlation between the anterior CC volumes and homotopic rsFC strengths in the caudate. The present study shows that a reduced pattern of homotopic interhemispheric rsFC in ASD adults/adolescents is already present in children of 5-10?years old and further supports their potential use as a general ASD biomarker. LAY SUMMARY: Homotopic interhemispheric functional connectivity plays an important role in synchronizing activity between the two hemispheres and is altered in adults and adolescents with autism spectrum disorder (ASD). In the present study focused on children with ASD, we have observed a similar pattern of decreased homotopic connectivity, suggesting that alterations in homotopic interhemispheric connectivity may occur early in ASD and be a useful general biomarker across ages. En ligne : http://dx.doi.org/10.1002/aur.2523 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449

Duloxetine ameliorates valproic acid-induced hyperactivity, anxiety-like behavior, and social interaction deficits in zebrafish / T. P. JOSEPH in Autism Research, 15-1 (January 2022)  

Public ISBD [article]  inAutism Research > 15-1 (January 2022) . - p.27-41 Titre : Duloxetine ameliorates valproic acid-induced hyperactivity, anxiety-like behavior, and social interaction deficits in zebrafish Type de document : Texte imprimé et/ou numérique Auteurs : T. P. JOSEPH, Auteur ; F. ZHOU, Auteur ; L. Y. SAI, Auteur ; H. CHEN, Auteur ; S. L. LIN, Auteur ; M. SCHACHNER, Auteur Article en page(s) : p.27-41 Langues : Anglais (eng) Mots-clés : Animals  Anxiety/chemically induced/drug therapy  Autism Spectrum Disorder/drug therapy  Behavior, Animal  Disease Models, Animal  Duloxetine Hydrochloride  Prenatal Exposure Delayed Effects  Social Behavior  Social Interaction  Valproic Acid  Zebrafish  L1cam  autism spectrum disorder  duloxetine  social preference  valproic acid  zebrafish Index. décimale : PER Périodiques Résumé : Syndromic autism spectrum disorders (ASDs) are characterized by impaired social communication and repetitive/stereotyped behaviors. Currently available therapeutic agents against ASD have limited efficacy. Thus, searching for novel and effective drugs ameliorating core symptoms, in particular social deficits, is of utmost importance. Duloxetine (DLX), an antidepressant that has been identified as an agonist mimetic for the cell adhesion molecule L1, exhibits beneficial functions in vitro and in vivo. Therefore, in this study, we focused on the rapid and persistent neuroprotective function of DLX following valproic acid (VPA)-triggered hyperactivity, anxiety-like behavior and social deficits in zebrafish. Embryonic exposure to VPA reduced survival in a dose- and time-dependent manner, delayed hatching, and also resulted in a significant number of malformed larvae. After initial dose-response experiments in zebrafish larvae, 10 ?M VPA exposure between 0.33 and 4.5?days post fertilization (dpf) was identified as an effective concentration that led to an early and persistent ASD-like phenotype in zebrafish. ASD-like elevated acetylcholine esterase (AChE) activity and reduced Akt-mTOR signaling was observed in zebrafish whole brain. Acute administration of DLX (4.5-6 dpf) reduced the VPA-induced ASD-like phenotype in zebrafish larvae. Additionally, such early-life acute DLX treatment had long-term effects in ameliorating social impairments, hyperactivity, and anxiety-like behaviors through adulthood. This was accompanied by reduced AChE activity and by normalized Akt-mTOR signaling. Overall, DLX treatment showed a long-term therapeutic effect on autistic-like behaviors, and alteration of AChE activity and Akt-mTOR signaling were identified as crucial in the VPA-induced ASD zebrafish model. En ligne : http://dx.doi.org/10.1002/aur.2620 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450 [article] Duloxetine ameliorates valproic acid-induced hyperactivity, anxiety-like behavior, and social interaction deficits in zebrafish [Texte imprimé et/ou numérique] / T. P. JOSEPH, Auteur ; F. ZHOU, Auteur ; L. Y. SAI, Auteur ; H. CHEN, Auteur ; S. L. LIN, Auteur ; M. SCHACHNER, Auteur . - p.27-41. Langues : Anglais (eng) in Autism Research > 15-1 (January 2022) . - p.27-41 Mots-clés : Animals  Anxiety/chemically induced/drug therapy  Autism Spectrum Disorder/drug therapy  Behavior, Animal  Disease Models, Animal  Duloxetine Hydrochloride  Prenatal Exposure Delayed Effects  Social Behavior  Social Interaction  Valproic Acid  Zebrafish  L1cam  autism spectrum disorder  duloxetine  social preference  valproic acid  zebrafish Index. décimale : PER Périodiques Résumé : Syndromic autism spectrum disorders (ASDs) are characterized by impaired social communication and repetitive/stereotyped behaviors. Currently available therapeutic agents against ASD have limited efficacy. Thus, searching for novel and effective drugs ameliorating core symptoms, in particular social deficits, is of utmost importance. Duloxetine (DLX), an antidepressant that has been identified as an agonist mimetic for the cell adhesion molecule L1, exhibits beneficial functions in vitro and in vivo. Therefore, in this study, we focused on the rapid and persistent neuroprotective function of DLX following valproic acid (VPA)-triggered hyperactivity, anxiety-like behavior and social deficits in zebrafish. Embryonic exposure to VPA reduced survival in a dose- and time-dependent manner, delayed hatching, and also resulted in a significant number of malformed larvae. After initial dose-response experiments in zebrafish larvae, 10 ?M VPA exposure between 0.33 and 4.5?days post fertilization (dpf) was identified as an effective concentration that led to an early and persistent ASD-like phenotype in zebrafish. ASD-like elevated acetylcholine esterase (AChE) activity and reduced Akt-mTOR signaling was observed in zebrafish whole brain. Acute administration of DLX (4.5-6 dpf) reduced the VPA-induced ASD-like phenotype in zebrafish larvae. Additionally, such early-life acute DLX treatment had long-term effects in ameliorating social impairments, hyperactivity, and anxiety-like behaviors through adulthood. This was accompanied by reduced AChE activity and by normalized Akt-mTOR signaling. Overall, DLX treatment showed a long-term therapeutic effect on autistic-like behaviors, and alteration of AChE activity and Akt-mTOR signaling were identified as crucial in the VPA-induced ASD zebrafish model. En ligne : http://dx.doi.org/10.1002/aur.2620 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450

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