Protocol Update: The Normative Modelling Paradigm for Computational Psychiatry

de Boer, A. A. A.; Bayer, J. M. M.; Fraza, C.; Chavanne, A.; Rehak Buckova, B.; Tsilimparis, K.; Serin, E.; Bernas, A.; Cirstian, R.; Zabihi, M.; Rutherford, S.; Al Khaledi, A.; Wolfers, T.; Beckmann, C.; Marquand, A. F.

doi:10.64898/2026.02.17.706268

bioRxiv · 10.64898/2026.02.17.706268

Protocol Update: The Normative Modelling Paradigm for Computational Psychiatry

de Boer, A. A. A.·Bayer, J. M. M.·Fraza, C.·Chavanne, A.·Rehak Buckova, B.·Tsilimparis, K.·Serin, E.·Bernas, A.·Cirstian, R.·Zabihi, M.·Rutherford, S.·Al Khaledi, A.·Wolfers, T.·Beckmann, C.·Marquand, A. F.

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Abstract

Normative Modelling ( brain growth charting) is now a well-established method for computational psychiatry and involves charting centiles of variation across a population in terms of mappings between biology and behavior, providing statistical inferences at the level of the individual. These models have helped the field to move away from case-control analysis toward individual-level analysis. Correspondingly, normative modelling has now been applied to chart brain development and ageing in many populations and has been used to quantify individual deviations across various neurological and psychiatric conditions. This has been supported by large-scale models that are openly accessible for diverse brain imaging modalities. As normative modelling continues to grow, several recent methodological developments, such as non-Gaussian models, longitudinal models, and federated learning, have been implemented in different software tools, including the Predictive Clinical Neuroscience toolkit (PCNtoolkit). In this protocol update, we provide: (i) a revised overview of this methodological landscape; (ii) an update to our 2022 standardised analytical protocol for normative modelling of neuroimaging data, including options for federated and longitudinal normative models; (iii) practical guidance suited to both novice and experienced practitioners supported by open-source code examples implemented in the refactored version of PCNtoolkit; and (iv) updated models for cortical thickness, surface area, volumetric data, functional connectivity and diffusion-weighted imaging for use by the community.

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de Boer, A. A. A., Bayer, J. M. M., Fraza, C., Chavanne, A., Rehak Buckova, B., Tsilimparis, K., Serin, E., Bernas, A., Cirstian, R., Zabihi, M., Rutherford, S., Al Khaledi, A., Wolfers, T., Beckmann, C., Marquand, A. F.. 2026-02-18. Protocol Update: The Normative Modelling Paradigm for Computational Psychiatry. https://doi.org/10.64898/2026.02.17.706268

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