Network-specific sex differentiation of intrinsic brain function in males with autism
Abstract 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, albe...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-03-01
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| Series: | Molecular Autism |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13229-018-0192-x |
| _version_ | 1811288443688321024 |
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| author | Dorothea L. Floris Meng-Chuan Lai Tanmay Nath Michael P. Milham Adriana Di Martino |
| author_facet | Dorothea L. Floris Meng-Chuan Lai Tanmay Nath Michael P. Milham Adriana Di Martino |
| author_sort | Dorothea L. Floris |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T03:36:51Z |
| format | Article |
| id | doaj.art-9cbee2c81e914bfeb8077eaf38f2fe2c |
| institution | Directory Open Access Journal |
| issn | 2040-2392 |
| language | English |
| last_indexed | 2024-04-13T03:36:51Z |
| publishDate | 2018-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Autism |
| spelling | doaj.art-9cbee2c81e914bfeb8077eaf38f2fe2c2022-12-22T03:04:18ZengBMCMolecular Autism2040-23922018-03-019111210.1186/s13229-018-0192-xNetwork-specific sex differentiation of intrinsic brain function in males with autismDorothea L. Floris0Meng-Chuan Lai1Tanmay Nath2Michael P. Milham3Adriana Di Martino4Hassenfeld Children’s Hospital at NYU Langone Health, Department of Child and Adolescent Psychiatry, Child Study CenterChild and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health and The Hospital for Sick Children, Department of Psychiatry, University of TorontoHassenfeld Children’s Hospital at NYU Langone Health, Department of Child and Adolescent Psychiatry, Child Study CenterCenter for the Developing Brain, Child Mind InstituteHassenfeld Children’s Hospital at NYU Langone Health, Department of Child and Adolescent Psychiatry, Child Study CenterAbstract 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.http://link.springer.com/article/10.1186/s13229-018-0192-xAutism spectrum disorderResting-state fMRISex differentiationSex mosaicismExtreme Male BrainGender Incoherence |
| spellingShingle | Dorothea L. Floris Meng-Chuan Lai Tanmay Nath Michael P. Milham Adriana Di Martino Network-specific sex differentiation of intrinsic brain function in males with autism Molecular Autism Autism spectrum disorder Resting-state fMRI Sex differentiation Sex mosaicism Extreme Male Brain Gender Incoherence |
| title | Network-specific sex differentiation of intrinsic brain function in males with autism |
| title_full | Network-specific sex differentiation of intrinsic brain function in males with autism |
| title_fullStr | Network-specific sex differentiation of intrinsic brain function in males with autism |
| title_full_unstemmed | Network-specific sex differentiation of intrinsic brain function in males with autism |
| title_short | Network-specific sex differentiation of intrinsic brain function in males with autism |
| title_sort | network specific sex differentiation of intrinsic brain function in males with autism |
| topic | Autism spectrum disorder Resting-state fMRI Sex differentiation Sex mosaicism Extreme Male Brain Gender Incoherence |
| url | http://link.springer.com/article/10.1186/s13229-018-0192-x |
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