Atypical lateralization of motor circuit functional connectivity in children with autism is associated with motor deficits / D. L. FLORIS in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 35p. Titre : Atypical lateralization of motor circuit functional connectivity in children with autism is associated with motor deficits Type de document : Texte imprimé et/ou numérique Auteurs : D. L. FLORIS, Auteur ; A. D. BARBER, Auteur ; M. B. NEBEL, Auteur ; M. MARTINELLI, Auteur ; Meng-Chuan LAI, Auteur ; D. CROCETTI, Auteur ; Simon BARON-COHEN, Auteur ; J. SUCKLING, Auteur ; J. J. PEKAR, Auteur ; S. H. MOSTOFSKY, Auteur Article en page(s) : 35p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/physiopathology  Brain/diagnostic imaging/physiopathology  Case-Control Studies  Child  Female  Functional Laterality/physiology  Humans  Image Processing, Computer-Assisted  Language  Magnetic Resonance Imaging  Male  Neuropsychological Tests  Autism  Hemispheric specialization  Intrinsic functional connectivity  Lateralization  Motor deficits Index. décimale : PER Périodiques Résumé : BACKGROUND: Atypical lateralization of language-related functions has been repeatedly found in individuals with autism spectrum conditions (ASC). Few studies have, however, investigated deviations from typically occurring asymmetry of other lateralized cognitive and behavioural domains. Motor deficits are among the earliest and most prominent symptoms in individuals with ASC and precede core social and communicative symptoms. METHODS: Here, we investigate whether motor circuit connectivity is (1) atypically lateralized in children with ASC and (2) whether this relates to core autistic symptoms and motor performance. Participants comprised 44 right-handed high-functioning children with autism (36 males, 8 females) and 80 typically developing control children (58 males, 22 females) matched on age, sex and performance IQ. We examined lateralization of functional motor circuit connectivity based on homotopic seeds derived from peak activations during a finger tapping paradigm. Motor performance was assessed using the Physical and Neurological Examination for Subtle Signs (PANESS). RESULTS: Children with ASC showed rightward lateralization in mean motor circuit connectivity compared to typically developing children, and this was associated with poorer performance on all three PANESS measures. CONCLUSIONS: Our findings reveal that atypical lateralization in ASC is not restricted to language functions but is also present in circuits subserving motor functions and may underlie motor deficits in children with ASC. Future studies should investigate whether this is an age-invariant finding extending to adolescents and adults and whether these asymmetries relate to atypical lateralization in the language domain. En ligne : http://dx.doi.org/10.1186/s13229-016-0096-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Atypical lateralization of motor circuit functional connectivity in children with autism is associated with motor deficits [Texte imprimé et/ou numérique] / D. L. FLORIS, Auteur ; A. D. BARBER, Auteur ; M. B. NEBEL, Auteur ; M. MARTINELLI, Auteur ; Meng-Chuan LAI, Auteur ; D. CROCETTI, Auteur ; Simon BARON-COHEN, Auteur ; J. SUCKLING, Auteur ; J. J. PEKAR, Auteur ; S. H. MOSTOFSKY, Auteur . - 35p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 35p. Mots-clés : Autism Spectrum Disorder/physiopathology  Brain/diagnostic imaging/physiopathology  Case-Control Studies  Child  Female  Functional Laterality/physiology  Humans  Image Processing, Computer-Assisted  Language  Magnetic Resonance Imaging  Male  Neuropsychological Tests  Autism  Hemispheric specialization  Intrinsic functional connectivity  Lateralization  Motor deficits Index. décimale : PER Périodiques Résumé : BACKGROUND: Atypical lateralization of language-related functions has been repeatedly found in individuals with autism spectrum conditions (ASC). Few studies have, however, investigated deviations from typically occurring asymmetry of other lateralized cognitive and behavioural domains. Motor deficits are among the earliest and most prominent symptoms in individuals with ASC and precede core social and communicative symptoms. METHODS: Here, we investigate whether motor circuit connectivity is (1) atypically lateralized in children with ASC and (2) whether this relates to core autistic symptoms and motor performance. Participants comprised 44 right-handed high-functioning children with autism (36 males, 8 females) and 80 typically developing control children (58 males, 22 females) matched on age, sex and performance IQ. We examined lateralization of functional motor circuit connectivity based on homotopic seeds derived from peak activations during a finger tapping paradigm. Motor performance was assessed using the Physical and Neurological Examination for Subtle Signs (PANESS). RESULTS: Children with ASC showed rightward lateralization in mean motor circuit connectivity compared to typically developing children, and this was associated with poorer performance on all three PANESS measures. CONCLUSIONS: Our findings reveal that atypical lateralization in ASC is not restricted to language functions but is also present in circuits subserving motor functions and may underlie motor deficits in children with ASC. Future studies should investigate whether this is an age-invariant finding extending to adolescents and adults and whether these asymmetries relate to atypical lateralization in the language domain. En ligne : http://dx.doi.org/10.1186/s13229-016-0096-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin / C. M. PRETZSCH in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 49 p. Titre : Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin Type de document : Texte imprimé et/ou numérique Auteurs : C. M. PRETZSCH, Auteur ; D. L. FLORIS, Auteur ; B. VOINESCU, Auteur ; M. ELSAHIB, Auteur ; M. A. MENDEZ, Auteur ; R. WICHERS, Auteur ; L. AJRAM, Auteur ; G. IVIN, Auteur ; M. HEASMAN, Auteur ; E. PRETZSCH, Auteur ; S. WILLIAMS, Auteur ; D. G. M. MURPHY, Auteur ; Eileen DALY, Auteur ; G. M. MCALONAN, Auteur Article en page(s) : 49 p. Langues : Anglais (eng) Mots-clés : Autism spectrum condition  Autism spectrum disorder  Cbdv  Cannabidivarin  Functional connectivity  Striatum Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) has a high cost to affected individuals and society, but treatments for core symptoms are lacking. To expand intervention options, it is crucial to gain a better understanding of potential treatment targets, and their engagement, in the brain. For instance, the striatum (caudate, putamen, and nucleus accumbens) plays a central role during development and its (atypical) functional connectivity (FC) may contribute to multiple ASD symptoms. We have previously shown, in the adult autistic and neurotypical brain, the non-intoxicating cannabinoid cannabidivarin (CBDV) alters the balance of striatal 'excitatory-inhibitory' metabolites, which help regulate FC, but the effects of CBDV on (atypical) striatal FC are unknown. METHODS: To examine this in a small pilot study, we acquired resting state functional magnetic resonance imaging data from 28 men (15 neurotypicals, 13 ASD) on two occasions in a repeated-measures, double-blind, placebo-controlled study. We then used a seed-based approach to (1) compare striatal FC between groups and (2) examine the effect of pharmacological probing (600 mg CBDV/matched placebo) on atypical striatal FC in ASD. Visits were separated by at least 13 days to allow for drug washout. RESULTS: Compared to the neurotypicals, ASD individuals had lower FC between the ventral striatum and frontal and pericentral regions (which have been associated with emotion, motor, and vision processing). Further, they had higher intra-striatal FC and higher putamenal FC with temporal regions involved in speech and language. In ASD, CBDV reduced hyperconnectivity to the neurotypical level. LIMITATIONS: Our findings should be considered in light of several methodological aspects, in particular our participant group (restricted to male adults), which limits the generalizability of our findings to the wider and heterogeneous ASD population. CONCLUSION: In conclusion, here we show atypical striatal FC with regions commonly associated with ASD symptoms. We further provide preliminary proof of concept that, in the adult autistic brain, acute CBDV administration can modulate atypical striatal circuitry towards neurotypical function. Future studies are required to determine whether modulation of striatal FC is associated with a change in ASD symptoms. TRIAL REGISTRATION: clinicaltrials.gov, Identifier: NCT03537950. Registered May 25th, 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03537950?term=NCT03537950&draw=2&rank=1 . En ligne : http://dx.doi.org/10.1186/s13229-021-00454-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin [Texte imprimé et/ou numérique] / C. M. PRETZSCH, Auteur ; D. L. FLORIS, Auteur ; B. VOINESCU, Auteur ; M. ELSAHIB, Auteur ; M. A. MENDEZ, Auteur ; R. WICHERS, Auteur ; L. AJRAM, Auteur ; G. IVIN, Auteur ; M. HEASMAN, Auteur ; E. PRETZSCH, Auteur ; S. WILLIAMS, Auteur ; D. G. M. MURPHY, Auteur ; Eileen DALY, Auteur ; G. M. MCALONAN, Auteur . - 49 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 49 p. Mots-clés : Autism spectrum condition  Autism spectrum disorder  Cbdv  Cannabidivarin  Functional connectivity  Striatum Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) has a high cost to affected individuals and society, but treatments for core symptoms are lacking. To expand intervention options, it is crucial to gain a better understanding of potential treatment targets, and their engagement, in the brain. For instance, the striatum (caudate, putamen, and nucleus accumbens) plays a central role during development and its (atypical) functional connectivity (FC) may contribute to multiple ASD symptoms. We have previously shown, in the adult autistic and neurotypical brain, the non-intoxicating cannabinoid cannabidivarin (CBDV) alters the balance of striatal 'excitatory-inhibitory' metabolites, which help regulate FC, but the effects of CBDV on (atypical) striatal FC are unknown. METHODS: To examine this in a small pilot study, we acquired resting state functional magnetic resonance imaging data from 28 men (15 neurotypicals, 13 ASD) on two occasions in a repeated-measures, double-blind, placebo-controlled study. We then used a seed-based approach to (1) compare striatal FC between groups and (2) examine the effect of pharmacological probing (600 mg CBDV/matched placebo) on atypical striatal FC in ASD. Visits were separated by at least 13 days to allow for drug washout. RESULTS: Compared to the neurotypicals, ASD individuals had lower FC between the ventral striatum and frontal and pericentral regions (which have been associated with emotion, motor, and vision processing). Further, they had higher intra-striatal FC and higher putamenal FC with temporal regions involved in speech and language. In ASD, CBDV reduced hyperconnectivity to the neurotypical level. LIMITATIONS: Our findings should be considered in light of several methodological aspects, in particular our participant group (restricted to male adults), which limits the generalizability of our findings to the wider and heterogeneous ASD population. CONCLUSION: In conclusion, here we show atypical striatal FC with regions commonly associated with ASD symptoms. We further provide preliminary proof of concept that, in the adult autistic brain, acute CBDV administration can modulate atypical striatal circuitry towards neurotypical function. Future studies are required to determine whether modulation of striatal FC is associated with a change in ASD symptoms. TRIAL REGISTRATION: clinicaltrials.gov, Identifier: NCT03537950. Registered May 25th, 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03537950?term=NCT03537950&draw=2&rank=1 . En ligne : http://dx.doi.org/10.1186/s13229-021-00454-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Network-specific sex differentiation of intrinsic brain function in males with autism / D. L. FLORIS in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 17p. Titre : Network-specific sex differentiation of intrinsic brain function in males with autism Type de document : Texte imprimé et/ou numérique Auteurs : D. L. FLORIS, Auteur ; Meng-Chuan LAI, Auteur ; T. NATH, Auteur ; M. P. MILHAM, Auteur ; Adriana DI MARTINO, Auteur Article en page(s) : 17p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Extreme Male Brain  Gender Incoherence  Resting-state fMRI  Sex differentiation  Sex mosaicism Index. décimale : PER Périodiques Résumé : Background: The male predominance in the prevalence of autism spectrum disorder (ASD) has motivated research on sex differentiation in ASD. Multiple sources of evidence have suggested a neurophenotypic convergence of ASD-related characteristics and typical sex differences. Two existing, albeit competing, models provide predictions on such neurophenotypic convergence. These two models are testable with neuroimaging. Specifically, the Extreme Male Brain (EMB) model predicts that ASD is associated with enhanced brain maleness in both males and females with ASD (i.e., a shift-towards-maleness). In contrast, the Gender Incoherence (GI) model predicts a shift-towards-maleness in females, yet a shift-towards-femaleness in males with ASD. Methods: To clarify whether either model applies to the intrinsic functional properties of the brain in males with ASD, we measured the statistical overlap between typical sex differences and ASD-related atypicalities in resting-state fMRI (R-fMRI) datasets largely available in males. Main analyses focused on two large-scale R-fMRI samples: 357 neurotypical (NT) males and 471 NT females from the 1000 Functional Connectome Project and 360 males with ASD and 403 NT males from the Autism Brain Imaging Data Exchange. Results: Across all R-fMRI metrics, results revealed coexisting, but network-specific, shift-towards-maleness and shift-towards-femaleness in males with ASD. A shift-towards-maleness mostly involved the default network, while a shift-towards-femaleness mostly occurred in the somatomotor network. Explorations of the associated cognitive processes using available cognitive ontology maps indicated that higher-order social cognitive functions corresponded to the shift-towards-maleness, while lower-order sensory motor processes corresponded to the shift-towards-femaleness. Conclusions: The present findings suggest that atypical intrinsic brain properties in males with ASD partly reflect mechanisms involved in sexual differentiation. A model based on network-dependent atypical sex mosaicism can synthesize prior competing theories on factors involved in sex differentiation in ASD. En ligne : http://dx.doi.org/10.1186/s13229-018-0192-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354 [article] Network-specific sex differentiation of intrinsic brain function in males with autism [Texte imprimé et/ou numérique] / D. L. FLORIS, Auteur ; Meng-Chuan LAI, Auteur ; T. NATH, Auteur ; M. P. MILHAM, Auteur ; Adriana DI MARTINO, Auteur . - 17p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 17p. Mots-clés : Autism spectrum disorder  Extreme Male Brain  Gender Incoherence  Resting-state fMRI  Sex differentiation  Sex mosaicism Index. décimale : PER Périodiques Résumé : Background: The male predominance in the prevalence of autism spectrum disorder (ASD) has motivated research on sex differentiation in ASD. Multiple sources of evidence have suggested a neurophenotypic convergence of ASD-related characteristics and typical sex differences. Two existing, albeit competing, models provide predictions on such neurophenotypic convergence. These two models are testable with neuroimaging. Specifically, the Extreme Male Brain (EMB) model predicts that ASD is associated with enhanced brain maleness in both males and females with ASD (i.e., a shift-towards-maleness). In contrast, the Gender Incoherence (GI) model predicts a shift-towards-maleness in females, yet a shift-towards-femaleness in males with ASD. Methods: To clarify whether either model applies to the intrinsic functional properties of the brain in males with ASD, we measured the statistical overlap between typical sex differences and ASD-related atypicalities in resting-state fMRI (R-fMRI) datasets largely available in males. Main analyses focused on two large-scale R-fMRI samples: 357 neurotypical (NT) males and 471 NT females from the 1000 Functional Connectome Project and 360 males with ASD and 403 NT males from the Autism Brain Imaging Data Exchange. Results: Across all R-fMRI metrics, results revealed coexisting, but network-specific, shift-towards-maleness and shift-towards-femaleness in males with ASD. A shift-towards-maleness mostly involved the default network, while a shift-towards-femaleness mostly occurred in the somatomotor network. Explorations of the associated cognitive processes using available cognitive ontology maps indicated that higher-order social cognitive functions corresponded to the shift-towards-maleness, while lower-order sensory motor processes corresponded to the shift-towards-femaleness. Conclusions: The present findings suggest that atypical intrinsic brain properties in males with ASD partly reflect mechanisms involved in sexual differentiation. A model based on network-dependent atypical sex mosaicism can synthesize prior competing theories on factors involved in sex differentiation in ASD. En ligne : http://dx.doi.org/10.1186/s13229-018-0192-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354

Towards robust and replicable sex differences in the intrinsic brain function of autism / D. L. FLORIS in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 19 p. Titre : Towards robust and replicable sex differences in the intrinsic brain function of autism Type de document : Texte imprimé et/ou numérique Auteurs : D. L. FLORIS, Auteur ; J. O. A. FILHO, Auteur ; Meng-Chuan LAI, Auteur ; S. GIAVASIS, Auteur ; M. OLDEHINKEL, Auteur ; M. MENNES, Auteur ; Tony CHARMAN, Auteur ; J. TILLMANN, Auteur ; G. DUMAS, Auteur ; C. ECKER, Auteur ; F. DELL'ACQUA, Auteur ; Tobias BANASCHEWSKI, Auteur ; C. MOESSNANG, Auteur ; Simon BARON-COHEN, Auteur ; S. DURSTON, Auteur ; E. LOTH, Auteur ; D. G. M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur ; Christian F. BECKMANN, Auteur ; M. P. MILHAM, Auteur ; Adriana DI MARTINO, Auteur Article en page(s) : 19 p. Langues : Anglais (eng) Mots-clés : Adolescent  Autistic Disorder/diagnostic imaging/physiopathology  Brain/diagnostic imaging/physiopathology  Child  Female  Humans  Magnetic Resonance Imaging  Male  Sex Characteristics  Autism spectrum disorder  Replication  Resting-state functional connectivity  Robustness  Sex differences  Voxel-mirrored homotopic connectivity  Responsiveness Scale—Child Version by Organization Speciali, Italy. JKB has been a  consultant to, advisory board member of, and a speaker for Takeda/Shire, Medice,  Roche, and Servier. He is not an employee of any of these companies and not a stock  shareholder of any of these companies. He has no other financial or material  support, including expert testimony, patents, or royalties. CFB is director and  shareholder in SBGneuro Ltd. TC has received consultancy from Roche and Servier and  received book royalties from Guildford Press and Sage. DM has been a consultant to,  and advisory board member, for Roche and Servier. He is not an employee of any of  these companies, and not a stock shareholder of any of these companies. TB served in  an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals,  Oberberg GmbH, Shire, and Infectopharm. He received conference support or speaker’s  fee by Lilly, Medice, and Shire. He received royalties from Hogrefe, Kohlhammer, CIP  Medien, Oxford University Press  the present work is unrelated to these  relationships. JT is a consultant to Roche. The remaining authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Marked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data. METHODS: We addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7-18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z?>?3.1, cluster-level P? En ligne : http://dx.doi.org/10.1186/s13229-021-00415-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Towards robust and replicable sex differences in the intrinsic brain function of autism [Texte imprimé et/ou numérique] / D. L. FLORIS, Auteur ; J. O. A. FILHO, Auteur ; Meng-Chuan LAI, Auteur ; S. GIAVASIS, Auteur ; M. OLDEHINKEL, Auteur ; M. MENNES, Auteur ; Tony CHARMAN, Auteur ; J. TILLMANN, Auteur ; G. DUMAS, Auteur ; C. ECKER, Auteur ; F. DELL'ACQUA, Auteur ; Tobias BANASCHEWSKI, Auteur ; C. MOESSNANG, Auteur ; Simon BARON-COHEN, Auteur ; S. DURSTON, Auteur ; E. LOTH, Auteur ; D. G. M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur ; Christian F. BECKMANN, Auteur ; M. P. MILHAM, Auteur ; Adriana DI MARTINO, Auteur . - 19 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 19 p. Mots-clés : Adolescent  Autistic Disorder/diagnostic imaging/physiopathology  Brain/diagnostic imaging/physiopathology  Child  Female  Humans  Magnetic Resonance Imaging  Male  Sex Characteristics  Autism spectrum disorder  Replication  Resting-state functional connectivity  Robustness  Sex differences  Voxel-mirrored homotopic connectivity  Responsiveness Scale—Child Version by Organization Speciali, Italy. JKB has been a  consultant to, advisory board member of, and a speaker for Takeda/Shire, Medice,  Roche, and Servier. He is not an employee of any of these companies and not a stock  shareholder of any of these companies. He has no other financial or material  support, including expert testimony, patents, or royalties. CFB is director and  shareholder in SBGneuro Ltd. TC has received consultancy from Roche and Servier and  received book royalties from Guildford Press and Sage. DM has been a consultant to,  and advisory board member, for Roche and Servier. He is not an employee of any of  these companies, and not a stock shareholder of any of these companies. TB served in  an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals,  Oberberg GmbH, Shire, and Infectopharm. He received conference support or speaker’s  fee by Lilly, Medice, and Shire. He received royalties from Hogrefe, Kohlhammer, CIP  Medien, Oxford University Press  the present work is unrelated to these  relationships. JT is a consultant to Roche. The remaining authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Marked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data. METHODS: We addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7-18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z?>?3.1, cluster-level P? En ligne : http://dx.doi.org/10.1186/s13229-021-00415-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

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