BioFormer: Rethinking Cross-Subject Generalization via Spectral Structural Alignment in Biomedical Time-Series

Cross-subject generalization in biomedical time-series (BTS) refers to training on data from some subjects and testing on unseen subjects. The key challenge is to suppress subject-specific variability in BTS representations. Most existing methods implicitly suppress the variability through model building or subject adversarial learning, but rarely model it explicitly. We introduce \textit{\textbf{spectral drift}} as a new perspective to characterize subject-specific variability. Specifically, BTS signals under the same label often share consistent oscillatory structure, yet exhibit subject-dependent magnitude or phase shifts in specific frequency components, which we interpret as subject-specific variability. Building on this insight, we propose \textbf{BioFormer}. At its core is a Frequency-Band Alignment Module (FBAM) that generates band-wise modulation factors from the spectral distribution and adaptively adjusts amplitude and phase to align spectral structure, thereby mitigating variability. We further pair FBAM with Sample-Conditional Layer Normalization, which infers normalization parameters from intrinsic signal statistics rather than subject identity, stabilizing cross-subject representations. Extensive experiments on six datasets demonstrate that BioFormer outperforms 12 baselines, yielding absolute F1-score improvements of 6\%.