ArticleProceedings of the National Academy of Sciences of the United States of America2024
Deep learning models reveal replicable, generalizable, and behaviorally relevant sex differences in human functional brain organization.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 54 citations in OpenAlex.
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- Early life phthalate and replacement plasticizer exposures and changes in early childhood brain functional connectivity and structural morphology.Environment international · 2026Article
- The progression of sex differences in brain networks across the lifespan.bioRxiv : the preprint server for biology · 2026Article
- Lifestyle and Transcriptional Signatures Associated with Ethnicity/Race-Related Variations in the Functional Connectome.Research (Washington, D.C.) · 2026Article
- Critical role of EEG signals in assessment of sex-specific insights in neurological diagnostics via machine learning approach.Scientific reports · 2025Article
- Identification and External Validation of a Problem Cannabis Risk Network.Biological psychiatry · 2025Article
- Emotion, attention and stress regulation as markers of resilience in male and female Israeli soldiers during the Israel-Hamas war.European archives of psychiatry and clinical neuroscience · 2025Article
- Reproducible sex differences in personalised functional network topography in youth.The British journal of psychiatry : the journal of mental science · 2025Article
- White matter volume and microstructural integrity are associated with fatigue in relapsing multiple sclerosis.Scientific reports · 2025Article
- "Precision Medicine" and the Failed Search for Binary Brain Sex Differences to Address Gender Behavioral Health Disparities.American journal of human biology : the official journal of the Human Biology Council · 2025Review
- Protective role of parenthood on age-related brain function in mid- to late-life.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Analysis of functional connectivity changes from childhood to old age: A study using HCP-D, HCP-YA, and HCP-A datasets.Imaging neuroscience (Cambridge, Mass.) · 2025Article
- Mine water inflow prediction model based on variational mode decomposition and gated recurrent units optimized by improved chimp optimization algorithm.Scientific reports · 2025Article
- Reply to Lockhart et al.: Advancing the understanding of sex differences in functional brain organization with innovative AI tools.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Not so binary or generalizable: Brain sex differences with artificial neural networks.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Artificial Intelligence in Obsessive-Compulsive Disorder: A Systematic Review.Current treatment options in psychiatry · 2025Review
- Women, intuition, and management-the Yin and Yang of nonconscious thought.Frontiers in psychology · 2025Article
- Unique models of embodied cognition and eco-social niches proposed to validate hypothesis of social attunement and mis-attunement with a focus on autism.Frontiers in psychiatry · 2025Article
- Topological signatures of brain dynamics: persistent homology reveals individuality and brain-behavior links.Frontiers in human neuroscience · 2025Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
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Abstract
Sex plays a crucial role in human brain development, aging, and the manifestation of psychiatric and neurological disorders. However, our understanding of sex differences in human functional brain organization and their behavioral consequences has been hindered by inconsistent findings and a lack of replication. Here, we address these challenges using a spatiotemporal deep neural network (stDNN) model to uncover latent functional brain dynamics that distinguish male and female brains. Our stDNN model accurately differentiated male and female brains, demonstrating consistently high cross-validation accuracy (>90%), replicability, and generalizability across multisession data from the same individuals and three independent cohorts (N ~ 1,500 young adults aged 20 to 35). Explainable AI (XAI) analysis revealed that brain features associated with the default mode network, striatum, and limbic network consistently exhibited significant sex differences (effect sizes > 1.5) across sessions and independent cohorts. Furthermore, XAI-derived brain features accurately predicted sex-specific cognitive profiles, a finding that was also independently replicated. Our results demonstrate that sex differences in functional brain dynamics are not only highly replicable and generalizable but also behaviorally relevant, challenging the notion of a continuum in male-female brain organization. Our findings underscore the crucial role of sex as a biological determinant in human brain organization, have significant implications for developing personalized sex-specific biomarkers in psychiatric and neurological disorders, and provide innovative AI-based computational tools for future research.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.