Digital Twin Brain simulation and manipulation of a functional brain network underlying mental illness

作者：Yunman Xia, Songjun Peng, Juergen Dukart, Y. Xie, Shitong Xiang, Spase Petkoski, Zilin Li, Joerg F. Hipp, Suresh Muthukumaraswamy, Anna Forsyth, Tianye Jia, Nilakshi Vaidya, Tristram A. Lett, Liyi Qian, Xiao Chang, Yuxiang Dai, T Banaschewski, G Barker, Arun L. W. Bokde, R Bruhl, Sylvane Desrivières, Herta Flor, Penny Gowland, Antoine Grigis, Andreas Heinz, Hervé Lemaître, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise Poustka, Michael N. Smolka, Sarah Hohmann, Henrik Walter, Robert Whelan, Paul Wirsching, Z Zhang, Lauren Robinson, Jeanne Winterer, Yuning Zhang, Hedi Kebir, Ulrike Schmidt, Julia Sinclair, Ying Liu, Jiexiang Wang, Fei Dai, Longbin Zeng, Yubo Hou, Huarui Wang, Leijun Ye, Chunhe Li, Qibao Zheng, Andre Marquand, Changsong Zhou, Viktor Jirsa, Jianfeng Feng, Lu Wf, Gunter Schumann · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2026 · DOI：10.64898/2026.03.06.710030 · 被引用次数：2 · 研究领域：Functional Brain Connectivity Studies、EEG and Brain-Computer Interfaces、Mental Health Research Topics

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.