2026/07/31 by Kunkun Zhang, Qianwei Zhou
Biochemistry, Genetics and Molecular Biology · Computer Science · #q-bio.QM #cs.AI
arxiv created 2026/07/31 · arxiv updated 2026/08/05
Decoders of anesthetic state from cortical activity fail across drug classes, most notoriously ketamine, but reported accuracy cannot say whether the neural representation or only the decision threshold has failed; we separate the two in a controlled preparation with ground-truth labels. We decoded awake versus anesthetized from mouse electrocorticography (the 250-Hz-bandlimited local field potential, sampled at 1875 Hz) under leave-one-anesthetic-out evaluation across five mechanistically distinct anesthetics (isoflurane, dexmedetomidine, ketamine, propofol, and midazolam), comparing a spatially blind band-power decoder, covariance/Riemannian representations, and Riemannian domain adaptation, with all statistics at the session level and mouse-level cluster bootstrapping for the ketamine fold. The representation transfers: band-power ranks awake versus anesthetized at a session AUROC of at least 0.96 on every held-out drug, ketamine included (0.980, cluster confidence interval 0.821 to 1.000). The failure is confined to the threshold: across three representations the ketamine ranking is near-invariant while its balanced accuracy swings from chance to high, and a permutation test is significant for ranking (p = 0.0025) but not for fixed-threshold accuracy (p = 0.3795). Riemannian domain adaptation is net-negative. A causal, label-free threshold anchored to the subject's own pre-induction baseline fixes ketamine (balanced accuracy 0.50 to 0.85) and dominates domain adaptation. Because the ketamine test sessions come from three mice that also contribute training drugs, this is within-subject cross-drug transfer; we do not claim population-level transfer across subjects. In cross-drug state decoding the actionable failure is calibration, not representation.