q-bio.QMJul 31, 2026

Cross-Anesthetic ECoG State Decoding Fails at the Decision Threshold, Not the Representation

Authors: Kunkun Zhang, Qianwei Zhou

Abstract

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.

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