Autonomic-salience stability as a candidate Gate for awake low-dose ketamine: a systems neuroscience framework with a clinical anchor
Frontiers in Systems Neuroscience July 1, 2026 Kei Torii, Maho Jinno
Ketamine's effects vary across patients and sessions, so dose alone does not explain them. A Gate-Amplifier-Reintegration framework proposes that awake low-dose ketamine amplifies transient network flexibility, while autonomic-salience stability acts as a Gate that may steer this flexibility toward reintegration or dysphoric dissociation. The three-step sequence involves Gate (candidate autonomic-salience stability), Amplifier (ketamine under conditions preserving vigilance), and Reintegration (organizing flexibility into language, attention, and action). Heart-rate variability serves as a peripheral state-verification proxy. The framework is informed by nonrandomized clinical observations from a single-center outpatient chronic pain care pathway, which provide clinical provenance but not comparative efficacy evidence. Falsifiable predictions include prospective Gate manipulation altering pre-dose autonomic state and randomized designs testing mediation of tolerability and clinical change.