Summary: In both neurotypical males and people on the autism spectrum, researchers found a reduction in resting-state brain function in the default mode network. Additionally, connectivity between the two hemispheres in the visual cortex is reduced in women with ASD.
Source: The Child Mind Institute
Around three times as many males are diagnosed with autism than females. This suggests that biological sex factors may play a role in the development and presentation of autism.
Studies on the neurobiology (brain biology) of males and females with autism have begun to examine brain networks but results have been mixed. This is largely due to the limited availability of data from autistic females.
In response, researchers from Child Mind Institute and colleagues involved in the AIMS2TRIALS, have combined thousands of MRI data openly available for scientific discovery in the Autism Brain Imaging Exchange (ABIDE) repository to explore brain network differences between autistic and neurotypical control males and females.
They used the ABIDE sample for discovery of new information and two additional large samples to see if those findings could be repeated (i.e., replicated). These included one sample derived from the Gender Explorations of Neurogenetics and Development to Advance Autism Research made available through the National Database for Autism Research and another one shared by the collaborators of the AIMS2TRIALS.
Across these three samples, the researchers found that both neurotypical males and autistic people showed reduced resting-state brain function in the so-called ‘default network’, a network that is active when we engage in social cognition or thoughts about ourselves.
Additionally, in the discovery sample and in one of the largest of the two replication samples, it was shown that connections between hemispheres (the two halves of the brain) in the visual cortex are reduced in autistic females, while autistic males are not different from males who are not autistic.
The results suggest that many autistic people may have different interactions between the two hemispheres of their brain when compared to non-autistic people. This reflects a combination of effects, including some that appear to be unrelated to sex, and some in which there is an interaction between sex and autism diagnosis. Each of these effects appears specific to a different system in the brain.
This study highlights the importance of data sharing and collaboration for implementing discovery science and addressing critical challenges related to reproducibility of findings – which affect all of fields of science.
The researchers suggest that there remains an urgent need for more research with similarly large groups of participants, as only then do studies have enough statistical power to reliably account for sources of variability and therefore generate robust conclusions. Until now, limited replication of imaging findings has hampered brain imaging research in autism.
The open sharing policies of the Autism Brain Imaging Data Exchange and the NIMH Data Archive, through which the Gender Explorations of Neurogenetics Development to Advance Autism Research was made available, are particularly promising for accelerating the pace of advancement.
Funding: The study was funded by Autism Science Foundation, NIH, Gifts to the Child Mind Institute from Phyllis Green Randolph Cowen, and Joseph Healey, Dr. John and Consuela Phelan Scholarships, Ontario Brain Institute via the Province of Ontario Neurodevelopmental Disorders Network, Slifka-Ritvo Award for Innovation in Autism Research from the International Society for Autism Research, The Alan B. Slifka Foundation, The Academic Scholars Award from the Department of Psychiatry University of Toronto, The O’Brien Scholars Program in the Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health (CAMH), The Hospital for Sick Children, The Slaight Family Child and Youth Mental Health Innovation Fund from CAMH Foundation, The Canadian Institutes of Health Research Sex and Gender Science Chair, The Innovative Medicines Initiative 2 Joint, The European Union’s Horizon 2020 research and innovation program, EFPIA, AUTISM SPEAKS, Autistica, SFARI, The NIHR Maudsley Biomedical Research Centre, The Autism Research Trust.
About this autism research news
Source: The Child Mind Institute Contact: Press Office – The Child Mind Institute Image: The image is in the public domain
Original Research: Open access. “Towards robust and replicable sex differences in the intrinsic brain function of autism” by Dorothea L. Floris, José O. A. Filho, Meng-Chuan Lai, Steve Giavasis, Marianne Oldehinkel, Maarten Mennes, Tony Charman, Julian Tillmann, Guillaume Dumas, Christine Ecker, Flavio Dell’Acqua, Tobias Banaschewski, Carolin Moessnang, Simon Baron-Cohen, Sarah Durston, Eva Loth, Declan G. M. Murphy, Jan K. Buitelaar, Christian F. Beckmann, Michael P. Milham & Adriana Di Martino. Molecular Autism
Towards robust and replicable sex differences in the intrinsic brain function of autism
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.
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.
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.
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.
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.