AI Discovery of Mechanisms of Consciousness, Its Disorders, and Their Treatment | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Biological Sciences - Article AI Discovery of Mechanisms of Consciousness, Its Disorders, and Their Treatment Daniel Toker, Zhong Zheng, Jasmine Thum, Jing Guang, Jitka Annen, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6866175/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Mar, 2026 Read the published version in Nature Neuroscience → Version 1 posted You are reading this latest preprint version Abstract Understanding disorders of consciousness (DOC) remains one of the most challenging problems in neuroscience, hindered by the lack of experimental models for probing mechanisms or testing interventions. To address this, we introduce a generative adversarial AI framework that pits deep neural networks—trained to detect consciousness across over 680,000 neuroelectrophysiology samples and validated on 565 patients, healthy volunteers, and animals—against interpretable, machine learning-driven neural field models. This adversarial architecture produces biologically realistic simulations of both conscious and comatose brains that recapitulate empirical neurophysiological features across humans, monkeys, rats, and bats. Without explicit programming, the AI model retrodicts known DOC responses to brain stimulation and generates testable predictions about unconsciousness mechanisms. Two such predictions are validated here: selective disruption of the basal ganglia indirect pathway, supported by diffusion MRI in 51 DOC patients; and increased cortical inhibitory-to-inhibitory synaptic coupling, supported by RNA sequencing from resected brain tissue in six human coma patients and a rat stroke model. The model also identifies high-frequency subthalamic nucleus stimulation as a promising DOC intervention, supported here using electrophysiology data from human patients. This work introduces an AI framework for causal inference and therapeutic discovery in consciousness research and complex systems more broadly. Biological sciences/Neuroscience/Diseases of the nervous system Biological sciences/Computational biology and bioinformatics/Computational models disorders of consciousness artificial intelligence neural field theory deep brain stimulation Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SimulatingConsciousnessSupplementaryNature.pdf AI Discovery of Mechanisms of Consciousness, Its Disorders, and Their Treatment Cite Share Download PDF Status: Published Journal Publication published 24 Mar, 2026 Read the published version in Nature Neuroscience → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6866175","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":473254586,"identity":"7eed269e-b29a-4be7-aa91-d1ea0dd332b1","order_by":0,"name":"Daniel 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