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From early to contemporary normative modeling: Mapping individual differences in neurophysiological signals
Francesco Antonio Mallus1,2, Yanwu Yang1,3,4, Richard Dinga5
1Department of Psychiatry and Psychotherapy, University Hospital Tübingen, Tübingen, Germany.
Abstract:
Normative modeling has become a cornerstone of computational neuroscience, offering a powerful framework for detecting individual deviations from typical brain function. This review traces its trajectory in electrophysiology of the brain, from early studies in the 1970s, through a period of relative neglect, to its recent revival driven by machine learning advances and the availability of large-scale datasets. We provide a structured overview of this evolution, showing the shift from small, site-specific age-based models to increasingly harmonized approaches that integrate diverse biological and methodological innovations. Key studies are compared with respect to cohort composition, modeling strategies, and validation procedures, situating each within the broader arc of methodological progress. Despite this momentum, significant challenges remain, such as a lack of standardized practices, limited comparability across studies, and the need for richer integration of complex neurophysiological signals. Looking ahead, we argue that the future of electrophysiological normative modeling lies in scaling and unifying efforts, through international collaborations, standardized pipelines, and the incorporation of novel features. By coupling machine learning with both cross-sectional and longitudinal designs, the field can progress from proof-of-concept demonstrations to precise, individualized brain mapping. Ultimately, such advances will provide the foundation for clinical applications, enabling cost-effective personalized treatment monitoring and a more refined understanding of individual differences in complex brain disorders.