{ "abstract": "It is often assumed that phenotypic heterogeneity in autism reflects underlying pathobiological variation. However, direct evidence supporting this link is lacking. Leveraging cross-species functional neuroimaging, we show that brain dysconnectivity patterns in autism can be parsed into biologically dissociable subtypes. Specifically, we found that functional magnetic resonance imaging (fMRI) connectivity alterations in 20 distinct genetic mouse models of autism cluster into hypoconnectivity-dominant and hyperconnectivity-dominant subtypes. These subtypes are linked to distinct biological pathways, with hypoconnectivity being associated with synaptic dysfunction and hyperconnectivity reflecting transcriptional and immune-related alterations. Here we identified analogous hypoconnectivity and hyperconnectivity subtypes in a multicenter human fMRI dataset of n = 940 individuals with idiopathic autism and n = 1,036 neurotypical individuals. The human autism subtypes are highly replicable, are associated with distinct functional network architectures and behavioral profiles and recapitulate the synaptic and immune-related pathways identified in the rodent dataset. Our work provides a new empirical framework for targeted subtyping of the autism spectrum.", "abstract_shown": true, "affiliations": [ "Autism Center, Child Mind Institute, New York, NY, USA", "Functional Neuroimaging Laboratory, Istituto Italiano di Tecnologia, Center for Neuroscience and Cognitive Systems, CNCS@UNITN, Rovereto, Italy", "IMT School for Advanced Studies, Lucca, Italy", "Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland", "Department of Psychiatry, University of Geneva, Geneva, Switzerland", "Center for Mind and Brain Sciences (CIMeC), University of Trento, Rovereto, Italy", "Adaptive Decisions Lab, Blizard Institute, Queen Mary University of London, London, UK", "Brain Research Institute, University of Zurich, Zurich, Switzerland", "Department of Pharmacology, University of Oxford, Oxford, UK", "Synaptic Plasticity of Inhibitory Networks, Istituto Italiano di Tecnologia, Genova, Italy", "Centre for Craniofacial and Regenerative Biology, King's College London, London, UK", "Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK", "Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada", "Boston Children's Hospital, Harvard Medical School, Boston, MA, USA", "International Research Center for Neurointelligence, University of Tokyo, Tokyo, Japan", "Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada", "Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario, Canada", "Oxford Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK", "Department of Biomedical Sciences, Humanitas University, Milan, Italy", "IRCCS Humanitas Research Hospital, Milan, Italy", "IRCCS Ospedale Policlinico San Martino, Genova, Italy", "Department of Cellular, Computational and Integrative Biology. University of Trento, Trento, Italy", "National Center for Rare Diseases, Istituto Superiore di Sanità, Rome, Italy", "Neural Control of Movement Lab, ETH Zürich, Zurich, Switzerland", "Center for Integrative Developmental Neuroscience, Child Mind Institute, New York, NY, USA", "Laboratory for Autism and Neurodevelopmental Disorders, Istituto Italiano di Tecnologia, Center for Neuroscience and Cognitive Systems, Rovereto, Italy", "Center for Biomedical Imaging and Neuromodulation, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA", "Functional Neuroimaging Laboratory, Istituto Italiano di Tecnologia, Center for Neuroscience and Cognitive Systems, CNCS@UNITN, Rovereto, Italy. alessandro.gozzi@iit.it" ], "article_type": null, "arxiv": null, "author_total": 23, "authors": [ { "affs": [ 0, 1, 2 ], "name": "Marco Pagani", "orcid": "0000-0002-6052-6931" }, { "affs": [ 3, 4 ], "name": "Valerio Zerbi", "orcid": "0000-0001-7984-9565" }, { "affs": [ 5, 1 ], "name": "Silvia Gini", "orcid": "0009-0001-2757-3306" }, { "affs": [ 1 ], "name": "Filomena Grazia Alvino", "orcid": "0000-0002-5669-4369" }, { "affs": [ 6, 7, 8 ], "name": "Abhishek Banerjee", "orcid": "0000-0002-5649-6469" }, { "affs": [ 9 ], "name": "Andrea Barberis", "orcid": "0000-0002-5054-6517" }, { "affs": [ 10, 11 ], "name": "M. Albert Basson", "orcid": "0000-0001-9834-7528" }, { "affs": [ 5 ], "name": "Yuri Bozzi", "orcid": "0000-0002-1496-9889" }, { "affs": [ 1 ], "name": "Alberto Galbusera", "orcid": "0000-0001-7213-0013" }, { "affs": [ 12 ], "name": "Jacob Ellegood", "orcid": "0000-0003-1504-3321" }, { "affs": [ 13, 14 ], "name": "Michela Fagiolini", "orcid": "0000-0003-2807-803X" }, { "affs": [ 15, 16, 17 ], "name": "Jason P. Lerch", "orcid": "0000-0001-6164-2881" }, { "affs": [ 18, 19 ], "name": "Michela Matteoli", "orcid": "0000-0002-3569-7843" }, { "affs": [ 1, 20 ], "name": "Caterina Montani", "orcid": "0000-0002-3150-0302" }, { "affs": [ 19 ], "name": "Davide Pozzi", "orcid": "0000-0001-6436-0556" }, { "affs": [ 21 ], "name": "Giovanni Provenzano", "orcid": "0000-0001-7160-4184" }, { "affs": [ 22 ], "name": "María Luisa Scattoni", "orcid": "0000-0002-6659-0280" }, { "affs": [ 23 ], "name": "Nicole Wenderoth", "orcid": "0000-0002-3246-9386" }, { "affs": [ 24 ], "name": "Ting Xu", "orcid": "0000-0002-0065-3832" }, { "affs": [ 25 ], "name": "Michael Vincent Lombardo", "orcid": "0000-0001-6780-8619" }, { "affs": [ 26, 24 ], "name": "Michael Peter Milham", "orcid": "0000-0003-3532-1210" }, { "affs": [ 0 ], "name": "Adriana Di Martino", "orcid": "0000-0001-6927-290X" }, { "affs": [ 27 ], "name": "Alessandro Gozzi", "orcid": "0000-0002-5731-4137" } ], "bibtex": "https://research.draconitic.com/paper/45066dsy9x8xt.bib", "cited_by": 33, "doi": "10.1038/s41593-026-02287-z", "fulltext_url": null, "id": "45066dsy9x8xt", "issns": [ "1097-6256", "1546-1726" ], "landing_url": "https://doi.org/10.1038/s41593-026-02287-z", "language": "en", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2805|Autism Spectrum Disorder Research" ] ], "openalex": "W7161263408", "pdf_url": "https://www.nature.com/articles/s41593-026-02287-z.pdf", "pmcid": "PMC13246445", "pmid": "42141307", "published": "2026-05-15", "publisher": "Nature Portfolio", "ris": "https://research.draconitic.com/paper/45066dsy9x8xt.ris", "sources": [ { "first_seen": "2026-10-30T13:26:53Z", "native_id": "W7161263408", "source": "openalex", "url": "https://doi.org/10.1038/s41593-026-02287-z" } ], "subjects": [ { "field": "biology", "origin": "openalex:2805|Autism Spectrum Disorder Research", "subfield": "neuroscience" } ], "title": "Autism subtypes identified using cross-species functional connectivity analyses", "title_text": "Autism subtypes identified using cross-species functional connectivity analyses", "type": "peer-reviewed", "updated_at": "2026-11-08T13:20:48Z", "url": "https://research.draconitic.com/paper/45066dsy9x8xt", "venue": "Nature Neuroscience", "versions": [] }