Cross-cohort validation of EEG biomarkers using a pre-registered three-criterion framework: a demonstration in amyotrophic lateral sclerosis

Background. Despite decades of EEG biomarker development for amyotrophic lateral sclerosis (ALS), no candidate has progressed to clinical deployment, partly because cross-cohort validation is rare. We aimed to develop and demonstrate a pre-registered three-criterion screening framework to identify which candidate EEG features show the combined properties required for biomarker translation: cross-sectional discrimination, within-subject reliability, and cross-cohort effect consistency. Methods. We pre-registered a validation framework adapted from FDA-NIH BEST principles and applied it to 18 EE

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