Brain structure plays a pivotal role in shaping neural dynamics. Current models lack the anatomical and functional resolution needed to accurately capture both structural and dynamical features of the human brain. Here, we introduce the FEDE (high FidElity Digital brain modEl) pipeline, generating anatomically accurate brain digital twins from imaging data. Using advanced techniques of anatomical tissue segmentation and finite-element analysis, FEDE reconstructs brain structure with high spatial resolution, while also replicating whole-brain neural activity. We demonstrated its application by creating the first brain digital twin of a toddler with autism spectrum disorder (ASD). Through parameter optimization, FEDE replicated both time-frequency and spatial features of recorded neural activity. Notably, FEDE predicted patient-specific aberrant values of excitation to inhibition ratio, coherently with ASD pathophysiology. FEDE represents a significant leap forward in brain modeling, paving the way for more effective applications of digital twin in experimental and clinical settings.

The authors have declared no competing interest.

LGA, AAV and AM were supported by #NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project EBRAINS Italy (IR0000011) European Brain ReseArch INfrastructureS Italy (DN. 101 16.06.2022), project MNESYS (PE0000006). A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022), and project Fit4MedRob Fit for Medical Robotics Grant (# PNC0000007). LM and JC were supported by #NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006) A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022), AR was partly funded by the National Institute for Nuclear Physics (INFN, CSN5) within the next_AIM project and by the European Commission under the NextGeneration EU with the PNRR M4C2 Inv. 1.3, PE00000013 FAIR project (Spoke 8). SC was partially supported by the Italian Ministry of Health (Grant Ricerca Corrente 2025). EB and SC were partially supported by the Italian Ministry of Health (Grant Ricerca Corrente 2025).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was conducted in accordance with the Declaration of Helsinki and approved by the Regional Ethical Committee of Meyer Hospital in Florence Italy number 131/2024

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Code and patient data can be transmitted upon reasonable request to alberto.mazzoni@santannapisa.it