Intra-Sessional Autonomic Arc Detection Using Continuous HRV and EDA Monitoring in Adults Undergoing Ketamine-Assisted Therapy for PTSD: A Prospective Observational Signal Characterisation Pilot Study

Post-traumatic stress disorder (PTSD) affects an estimated 9.2% of Canadians over a lifetime, with particularly high prevalence among first responders, veterans, and survivors of interpersonal violence. Conventional first-line treatments leave a significant proportion of patients with residual symptoms, and access to evidence-based care remains limited in rural and remote settings. Ketamine-assisted therapy (KAT) has demonstrated rapid anxiolytic and antidepressant effects in multiple randomised controlled trials and represents a promising approach for treatment-refractory PTSD. However, the mechanisms through which KAT produces therapeutic change, and the conditions that determine whether a given session produces durable benefit, are incompletely understood.

The REBUS (Relaxed Beliefs Under Psychedelics) account provides the theoretical foundation for this study. Under this framework, ketamine temporarily reduces the precision-weighting of high-confidence predictive priors - including deeply entrenched trauma-related threat appraisals - creating a window of increased neuroplasticity during which the generative model is most available for revision. This window is hypothesised to correspond to a specific autonomic configuration: a shift from peak sympathetic activation toward increasing ventral vagal dominance, characterised by falling electrodermal activity, rising HRV coherence, and emerging parasympathetic predominance. This configuration is referred to as the Transition Window. The Transition Window is theoretically critical because articulation of psychological content delivered during this state is predicted to produce genuine prior-precision reduction, whereas identical articulation delivered outside this window is predicted to produce verbal acknowledgement without the underlying autonomic reorganisation that constitutes genuine release.

The foundational challenge for testing this prediction empirically is that no validated method has existed for detecting the Transition Window in real time. This study addresses that gap by applying the JungleCODE arc-position detection algorithm to continuous intra-sessional physiological data from KAT participants.

JungleCODE (Open Medicine Studio; patent pending, PCT filed) is a proprietary signal processing algorithm that analyses continuous heart rate variability (HRV) time-series data - and, where available, electrodermal activity (EDA) - to estimate arc position on a clinically defined aporia-to-ataraxia spectrum. Aporia refers to the state of peak arousal, maximal predictive prior precision, and high sympathetic drive. Ataraxia refers to the state of regulatory restoration, reduced prior precision, and ventral vagal dominance. Unlike single-biomarker threshold approaches, JungleCODE is a trajectory detection algorithm: it identifies where in a continuous arc the person is located based on the directional pattern of change over time, not the absolute value at any given moment. The algorithm outputs arc-position scores at 30-second intervals along with transition event flags, trajectory classification, and autonomic phase designation.

This study is observational and non-interventional. Participants independently arrange their own ketamine-assisted therapy sessions with a licensed British Columbia physician or nurse practitioner. The researcher does not administer ketamine or any other substance and has no clinical role during the session. All clinical decisions and safety oversight during the KAT session remain entirely with the licensed treating provider. The researcher's role is continuous physiological monitoring via an EmbracePlus wrist-worn wearable biosensor and a structured post-session interview.