{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:54:46Z","timestamp":1787032486333,"version":"build-2736575974"},"posted":{"date-parts":[[2026,3,10]]},"group-title":"Neuroscience","reference-count":106,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Linking synaptic-level perturbations to distributed brain-network dynamics remains a central challenge for understanding and treating mental illness. Although recent whole-brain models can reproduce individual brain activity patterns, they largely function as descriptive simulators rather than mechanistic, intervention-capable systems. Here we present an intervention-capable digital twin of the human brain, integrating individual neuroanatomy and task-evoked dynamics within a neuronal-scale framework. Individualised digital twin brains recapitulate a participant-specific compact cortico-subcortical network phenotype that captures transdiagnostic psychopathology across population and clinical cohorts. In silico modulation of excitatory and inhibitory synaptic conductance produces bidirectional, heterogeneous network responses across individuals. Population-scale simulations stratify individuals and predict longitudinal symptom trajectories from DTB-derived response profiles. Independent pharmacological functional MRI data further validate the predicted baseline-dependent network responses in vivo. Together, these findings establish digital brain models as experimental platforms for mechanistic perturbation, behavioural prediction and stratification, providing a foundation for precision neuroscience and psychiatry.<\/jats:p>","DOI":"10.64898\/2026.03.06.710030","type":"posted-content","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T12:25:14Z","timestamp":1773145514000},"source":"Crossref","is-referenced-by-count":2,"title":["Digital Twin Brain simulation and manipulation of a functional brain network underlying mental illness"],"prefix":"10.64898","author":[{"given":"Yunman","family":"Xia","sequence":"first","affiliation":[{"name":"Centre for Population Neuroscience and Stratified Medicine (PONS), Department of Psychiatry and Neuroscience, Charite-Universitaetsmedizin Berlin, Germany"},{"name":"PONS, Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songjun","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Physics, Hong Kong Baptist University, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Dukart","sequence":"additional","affiliation":[{"name":"Institute of Neurosciences and Medicine, Brain & Behaviour (INM-7), Research Centre Juelich, Juelich, Germany"},{"name":"Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Psychological and Cognitive Sciences, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shitong","family":"Xiang","sequence":"additional","affiliation":[{"name":"Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China"},{"name":"Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spase","family":"Petkoski","sequence":"additional","affiliation":[{"name":"Institut de Neurosciences des Syst\u00e8mes (INS) UMR1106, Aix Marseille Universit\u00e9, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Hipp","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Neuroscience and Rare Diseases, Roche Innovation Center Basel, F. 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