Er vindt onderhoud plaats aan de Radboud Repository. Het is mogelijk dat uw zoekactie incomplete resultaten oplevert. Indien u publicaties wilt uploaden kunt u dit doen via de Upload Full Text button. Radboud Repository is undergoing maintenance. Please note that your search may produce incomplete results. If you would like to upload publications, you can do so by means of the Upload Full Text button.
Towards robust and replicable sex differences in the intrinsic brain function of autism
SourceMolecular Autism, 12, 1, (2021), article 19
Article / Letter to editor
Display more detailsDisplay less details
PI Group Statistical Imaging Neuroscience
PI Group Memory & Emotion
Subject130 000 Cognitive Neurology & Memory; 220 Statistical Imaging Neuroscience; Radboudumc 13: Stress-related disorders DCMN: Donders Center for Medical Neuroscience; Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience
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 < 0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research. RESULTS: Discovery analyses in ABIDE revealed significant main effects of diagnosis and sex across the intrinsic functional connectivity of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples-EU-AIMS LEAP. LIMITATIONS: Given the lack of a priori harmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability. CONCLUSIONS: Atypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies.
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.