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Altered frontal connectivity as a mechanism for executive function deficits in fragile X syndrome / Lauren M. SCHMITT in Molecular Autism, 13 (2022)
[article]
Titre : Altered frontal connectivity as a mechanism for executive function deficits in fragile X syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Lauren M. SCHMITT, Auteur ; Joy LI, Auteur ; Rui LIU, Auteur ; Paul S. HORN, Auteur ; John A. SWEENEY, Auteur ; Craig A. ERICKSON, Auteur ; Ernest V. PEDAPATI, Auteur Article en page(s) : 47 p. Langues : Anglais (eng) Mots-clés : Child Male Humans Female Fragile X Syndrome Executive Function Autism Spectrum Disorder Electroencephalography/methods Brain Connectivity Eeg Electroencephalography Fxs Fragile X syndrome commercial or financial relationships that could be construed as a potential conflict of interest for the current manuscript. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the leading inherited monogenic cause of intellectual disability and autism spectrum disorder. Executive function (EF), necessary for adaptive goal-oriented behavior and dependent on frontal lobe function, is impaired in individuals with FXS. Yet, little is known how alterations in frontal lobe neural activity is related to EF deficits in FXS. METHODS: Sixty-one participants with FXS (54% males) and 71 age- and sex-matched typically-developing controls (TDC; 58% males) completed a five-minute resting state electroencephalography (EEG) protocol and a computerized battery of tests of EF, the Test of Attentional Performance for Children (KiTAP). Following source localization (minimum-norm estimate), we computed debiased weighted phase lag index (dWPLI), a phase connectivity value, for pairings between 18 nodes in frontal regions for gamma (30-55Â Hz) and alpha (10.5-12.5Â Hz) bands. Linear models were generated with fixed factors of group, sex, frequency, and connection. Relationships between frontal connectivity and EF variables also were examined. RESULTS: Individuals with FXS demonstrated increased gamma band and reduced alpha band connectivity across all frontal regions and across hemispheres compared to TDC. After controlling for nonverbal IQ, increased error rates on EF tasks were associated with increased gamma band and reduced alpha band connectivity. LIMITATIONS: Frontal connectivity findings are limited to intrinsic brain activity during rest and may not generalize to frontal connectivity during EF tasks or everyday function. CONCLUSIONS: We report gamma hyper-connectivity and alpha hypo-connectivity within source-localized frontal brain regions in FXS compared to TDC during resting-state EEG. For the first time in FXS, we report significant associations between EF and altered frontal connectivity, with increased error rate relating to increased gamma band connectivity and reduced alpha band connectivity. These findings suggest increased phase connectivity within gamma band may impair EF performance, whereas greater alpha band connectivity may provide compensatory support for EF. Together, these findings provide important insight into neurophysiological mechanisms of EF deficits in FXS and provide novel targets for treatment development. En ligne : http://dx.doi.org/10.1186/s13229-022-00527-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 47 p.[article] Altered frontal connectivity as a mechanism for executive function deficits in fragile X syndrome [Texte imprimé et/ou numérique] / Lauren M. SCHMITT, Auteur ; Joy LI, Auteur ; Rui LIU, Auteur ; Paul S. HORN, Auteur ; John A. SWEENEY, Auteur ; Craig A. ERICKSON, Auteur ; Ernest V. PEDAPATI, Auteur . - 47 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 47 p.
Mots-clés : Child Male Humans Female Fragile X Syndrome Executive Function Autism Spectrum Disorder Electroencephalography/methods Brain Connectivity Eeg Electroencephalography Fxs Fragile X syndrome commercial or financial relationships that could be construed as a potential conflict of interest for the current manuscript. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the leading inherited monogenic cause of intellectual disability and autism spectrum disorder. Executive function (EF), necessary for adaptive goal-oriented behavior and dependent on frontal lobe function, is impaired in individuals with FXS. Yet, little is known how alterations in frontal lobe neural activity is related to EF deficits in FXS. METHODS: Sixty-one participants with FXS (54% males) and 71 age- and sex-matched typically-developing controls (TDC; 58% males) completed a five-minute resting state electroencephalography (EEG) protocol and a computerized battery of tests of EF, the Test of Attentional Performance for Children (KiTAP). Following source localization (minimum-norm estimate), we computed debiased weighted phase lag index (dWPLI), a phase connectivity value, for pairings between 18 nodes in frontal regions for gamma (30-55Â Hz) and alpha (10.5-12.5Â Hz) bands. Linear models were generated with fixed factors of group, sex, frequency, and connection. Relationships between frontal connectivity and EF variables also were examined. RESULTS: Individuals with FXS demonstrated increased gamma band and reduced alpha band connectivity across all frontal regions and across hemispheres compared to TDC. After controlling for nonverbal IQ, increased error rates on EF tasks were associated with increased gamma band and reduced alpha band connectivity. LIMITATIONS: Frontal connectivity findings are limited to intrinsic brain activity during rest and may not generalize to frontal connectivity during EF tasks or everyday function. CONCLUSIONS: We report gamma hyper-connectivity and alpha hypo-connectivity within source-localized frontal brain regions in FXS compared to TDC during resting-state EEG. For the first time in FXS, we report significant associations between EF and altered frontal connectivity, with increased error rate relating to increased gamma band connectivity and reduced alpha band connectivity. These findings suggest increased phase connectivity within gamma band may impair EF performance, whereas greater alpha band connectivity may provide compensatory support for EF. Together, these findings provide important insight into neurophysiological mechanisms of EF deficits in FXS and provide novel targets for treatment development. En ligne : http://dx.doi.org/10.1186/s13229-022-00527-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 Reduced mismatch negativity in children and adolescents with autism spectrum disorder is associated with their impaired adaptive functioning / Jonathan LASSEN in Autism Research, 15-8 (August 2022)
[article]
Titre : Reduced mismatch negativity in children and adolescents with autism spectrum disorder is associated with their impaired adaptive functioning Type de document : Texte imprimé et/ou numérique Auteurs : Jonathan LASSEN, Auteur ; Bob ORANJE, Auteur ; Martin VESTERGAARD, Auteur ; Malene FOLDAGER, Auteur ; Troels W. KJAER, Auteur ; Sidse ARNFRED, Auteur ; Bodil AGGERNAES, Auteur Article en page(s) : p.1469-1481 Langues : Anglais (eng) Mots-clés : Acoustic Stimulation/methods Adolescent Autism Spectrum Disorder/complications Autistic Disorder Brain Child Electroencephalography/methods Humans Asd Eeg adaptive behavior autism mismatch negativity Index. décimale : PER Périodiques Résumé : Children and adolescents on the autism spectrum display sensory disturbances, rigid and repetitive behavior, social communication problems and a high prevalence of impaired adaptive functioning. Autism is associated with slowed behavioral and neural habituation to repeated sensory input and decreased responses to sensory deviations. Mismatch negativity (MMN) reflects a pre-attentive difference in the neural response to sensory deviations relative to regularities and studies overall suggest that children and adolescents with autism tend to have smaller MMN. However, it remains unclear whether reduced MMN in autism is coupled to severity of specific autistic symptoms or more generally to lower level of adaptive functioning. To address these questions, the present study used electroencephalography (EEG) to assess whether auditory MMN in 59 children and adolescents with autism aged 7-14years compared to 59 typically developing children and adolescents were related to specific autistic symptoms or level in adaptive functioning. As hypothesized, the autism group had a lower MMN amplitude than controls. Smaller MMN amplitudes were specifically associated with lower adaptive functioning in the autistic subjects but not in controls while no apparent relationships were observed with autistic-like social interaction and communication problems, atypical language, rigidity, stereotypy or sensory sensitivity symptoms. Our findings indicate that a blunted response to changes in sensory input may underlie or contribute to the generalized difficulties with adapting to daily life circumstances seen in children and adolescents with autism. LAY SUMMARY: Children and adolescents on the autism spectrum have a high prevalence of impaired adaptive functioning. Neuroimaging studies have reported that children and adolescents with autism display attenuated brain activity when discriminating sensory input. However, it is unknown whether this attenuation is related to autistic symptoms and/or adaptive functioning. The present study used electroencephalogram (EEG) to show that attenuated brain response in discrimination of novel compared to repetitive sounds in children and adolescents with autism is related to their impaired adaptive functioning. En ligne : http://dx.doi.org/10.1002/aur.2738 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=483
in Autism Research > 15-8 (August 2022) . - p.1469-1481[article] Reduced mismatch negativity in children and adolescents with autism spectrum disorder is associated with their impaired adaptive functioning [Texte imprimé et/ou numérique] / Jonathan LASSEN, Auteur ; Bob ORANJE, Auteur ; Martin VESTERGAARD, Auteur ; Malene FOLDAGER, Auteur ; Troels W. KJAER, Auteur ; Sidse ARNFRED, Auteur ; Bodil AGGERNAES, Auteur . - p.1469-1481.
Langues : Anglais (eng)
in Autism Research > 15-8 (August 2022) . - p.1469-1481
Mots-clés : Acoustic Stimulation/methods Adolescent Autism Spectrum Disorder/complications Autistic Disorder Brain Child Electroencephalography/methods Humans Asd Eeg adaptive behavior autism mismatch negativity Index. décimale : PER Périodiques Résumé : Children and adolescents on the autism spectrum display sensory disturbances, rigid and repetitive behavior, social communication problems and a high prevalence of impaired adaptive functioning. Autism is associated with slowed behavioral and neural habituation to repeated sensory input and decreased responses to sensory deviations. Mismatch negativity (MMN) reflects a pre-attentive difference in the neural response to sensory deviations relative to regularities and studies overall suggest that children and adolescents with autism tend to have smaller MMN. However, it remains unclear whether reduced MMN in autism is coupled to severity of specific autistic symptoms or more generally to lower level of adaptive functioning. To address these questions, the present study used electroencephalography (EEG) to assess whether auditory MMN in 59 children and adolescents with autism aged 7-14years compared to 59 typically developing children and adolescents were related to specific autistic symptoms or level in adaptive functioning. As hypothesized, the autism group had a lower MMN amplitude than controls. Smaller MMN amplitudes were specifically associated with lower adaptive functioning in the autistic subjects but not in controls while no apparent relationships were observed with autistic-like social interaction and communication problems, atypical language, rigidity, stereotypy or sensory sensitivity symptoms. Our findings indicate that a blunted response to changes in sensory input may underlie or contribute to the generalized difficulties with adapting to daily life circumstances seen in children and adolescents with autism. LAY SUMMARY: Children and adolescents on the autism spectrum have a high prevalence of impaired adaptive functioning. Neuroimaging studies have reported that children and adolescents with autism display attenuated brain activity when discriminating sensory input. However, it is unknown whether this attenuation is related to autistic symptoms and/or adaptive functioning. The present study used electroencephalogram (EEG) to show that attenuated brain response in discrimination of novel compared to repetitive sounds in children and adolescents with autism is related to their impaired adaptive functioning. En ligne : http://dx.doi.org/10.1002/aur.2738 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=483 Resting state EEG power spectrum and functional connectivity in autism: a cross-sectional analysis / Pilar GARCES in Molecular Autism, 13 (2022)
[article]
Titre : Resting state EEG power spectrum and functional connectivity in autism: a cross-sectional analysis Type de document : Texte imprimé et/ou numérique Auteurs : Pilar GARCES, Auteur ; Sarah BAUMEISTER, Auteur ; Luke MASON, Auteur ; Christopher H. CHATHAM, Auteur ; Stefan HOLIGA, Auteur ; Juergen DUKART, Auteur ; Emily J. H. JONES, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sven BÖLTE, Auteur ; Jan K. BUITELAAR, Auteur ; Sarah DURSTON, Auteur ; Bob ORANJE, Auteur ; Antonio M. PERSICO, Auteur ; Christian F. BECKMANN, Auteur ; Thomas BOUGERON, Auteur ; Flavio DELL'ACQUA, Auteur ; Christine ECKER, Auteur ; Carolin MOESSNANG, Auteur ; Tony CHARMAN, Auteur ; Julian TILLMANN, Auteur ; Declan G. M. MURPHY, Auteur ; Mark H. JOHNSON, Auteur ; Eva LOTH, Auteur ; Daniel BRANDEIS, Auteur ; Joerg F. HIPP, Auteur Article en page(s) : 22 p. Langues : Anglais (eng) Mots-clés : Adolescent Adult Autism Spectrum Disorder/diagnosis Autistic Disorder Brain/diagnostic imaging Brain Mapping/methods Child Cross-Sectional Studies Electroencephalography/methods Humans Magnetic Resonance Imaging/methods Reproducibility of Results Autism spectrum disorder Eeg Functional connectivity Power spectrum Resting state Index. décimale : PER Périodiques Résumé : BACKGROUND: Understanding the development of the neuronal circuitry underlying autism spectrum disorder (ASD) is critical to shed light into its etiology and for the development of treatment options. Resting state EEG provides a window into spontaneous local and long-range neuronal synchronization and has been investigated in many ASD studies, but results are inconsistent. Unbiased investigation in large and comprehensive samples focusing on replicability is needed. METHODS: We quantified resting state EEG alpha peak metrics, power spectrum (PS, 2-32 Hz) and functional connectivity (FC) in 411 children, adolescents and adults (n=212 ASD, n=199 neurotypicals [NT], all with IQ?>?75). We performed analyses in source-space using individual head models derived from the participants' MRIs. We tested for differences in mean and variance between the ASD and NT groups for both PS and FC using linear mixed effects models accounting for age, sex, IQ and site effects. Then, we used machine learning to assess whether a multivariate combination of EEG features could better separate ASD and NT participants. All analyses were embedded within a train-validation approach (70%-30% split). RESULTS: In the training dataset, we found an interaction between age and group for the reactivity to eye opening (p=.042 uncorrected), and a significant but weak multivariate ASD vs. NT classification performance for PS and FC (sensitivity 0.52-0.62, specificity 0.59-0.73). None of these findings replicated significantly in the validation dataset, although the effect size in the validation dataset overlapped with the prediction interval from the training dataset. LIMITATIONS: The statistical power to detect weak effects-of the magnitude of those found in the training dataset-in the validation dataset is small, and we cannot fully conclude on the reproducibility of the training dataset's effects. CONCLUSIONS: This suggests that PS and FC values in ASD and NT have a strong overlap, and that differences between both groups (in both mean and variance) have, at best, a small effect size. Larger studies would be needed to investigate and replicate such potential effects. En ligne : http://dx.doi.org/10.1186/s13229-022-00500-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 22 p.[article] Resting state EEG power spectrum and functional connectivity in autism: a cross-sectional analysis [Texte imprimé et/ou numérique] / Pilar GARCES, Auteur ; Sarah BAUMEISTER, Auteur ; Luke MASON, Auteur ; Christopher H. CHATHAM, Auteur ; Stefan HOLIGA, Auteur ; Juergen DUKART, Auteur ; Emily J. H. JONES, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sven BÖLTE, Auteur ; Jan K. BUITELAAR, Auteur ; Sarah DURSTON, Auteur ; Bob ORANJE, Auteur ; Antonio M. PERSICO, Auteur ; Christian F. BECKMANN, Auteur ; Thomas BOUGERON, Auteur ; Flavio DELL'ACQUA, Auteur ; Christine ECKER, Auteur ; Carolin MOESSNANG, Auteur ; Tony CHARMAN, Auteur ; Julian TILLMANN, Auteur ; Declan G. M. MURPHY, Auteur ; Mark H. JOHNSON, Auteur ; Eva LOTH, Auteur ; Daniel BRANDEIS, Auteur ; Joerg F. HIPP, Auteur . - 22 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 22 p.
Mots-clés : Adolescent Adult Autism Spectrum Disorder/diagnosis Autistic Disorder Brain/diagnostic imaging Brain Mapping/methods Child Cross-Sectional Studies Electroencephalography/methods Humans Magnetic Resonance Imaging/methods Reproducibility of Results Autism spectrum disorder Eeg Functional connectivity Power spectrum Resting state Index. décimale : PER Périodiques Résumé : BACKGROUND: Understanding the development of the neuronal circuitry underlying autism spectrum disorder (ASD) is critical to shed light into its etiology and for the development of treatment options. Resting state EEG provides a window into spontaneous local and long-range neuronal synchronization and has been investigated in many ASD studies, but results are inconsistent. Unbiased investigation in large and comprehensive samples focusing on replicability is needed. METHODS: We quantified resting state EEG alpha peak metrics, power spectrum (PS, 2-32 Hz) and functional connectivity (FC) in 411 children, adolescents and adults (n=212 ASD, n=199 neurotypicals [NT], all with IQ?>?75). We performed analyses in source-space using individual head models derived from the participants' MRIs. We tested for differences in mean and variance between the ASD and NT groups for both PS and FC using linear mixed effects models accounting for age, sex, IQ and site effects. Then, we used machine learning to assess whether a multivariate combination of EEG features could better separate ASD and NT participants. All analyses were embedded within a train-validation approach (70%-30% split). RESULTS: In the training dataset, we found an interaction between age and group for the reactivity to eye opening (p=.042 uncorrected), and a significant but weak multivariate ASD vs. NT classification performance for PS and FC (sensitivity 0.52-0.62, specificity 0.59-0.73). None of these findings replicated significantly in the validation dataset, although the effect size in the validation dataset overlapped with the prediction interval from the training dataset. LIMITATIONS: The statistical power to detect weak effects-of the magnitude of those found in the training dataset-in the validation dataset is small, and we cannot fully conclude on the reproducibility of the training dataset's effects. CONCLUSIONS: This suggests that PS and FC values in ASD and NT have a strong overlap, and that differences between both groups (in both mean and variance) have, at best, a small effect size. Larger studies would be needed to investigate and replicate such potential effects. En ligne : http://dx.doi.org/10.1186/s13229-022-00500-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477