{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:48:51Z","timestamp":1782103731718,"version":"3.54.5"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Entropy"],"abstract":"<jats:p>This paper presents a computational model of delirium in the Intensive Care Unit (ICU), in which delirium is defined as the endpoint of a self-reinforcing cycle of predictive failure between two bidirectionally coupled agents: the patient and the ICU room environment. Drawing on the active inference framework and the free energy principle, the paper proposes that delirium is not a property of the patient in isolation but a relational phenomenon that emerges when the environment persistently fails to predict the patient\u2019s internal state. This failure triggers a causal feedback mechanism in which desynchronization pressure progressively sharpens the patient\u2019s prior beliefs\u2014implementing precision rigidity in the correct active inference sense: not a brain overwhelmed by noise but a brain locked into a state that incoming observations can no longer update. The model is implemented as a two-agent POMDP in which both agents maintain generative models and continuously attempt to predict each other\u2019s states. The room agent (R)\u2014understood as the environment-side sensing\u2013inference\u2013actuation loop, whether instantiated by clinical staff or by an automated monitoring system\u2014infers the patient (P)\u2019s latent parameters (\u03b8cog,\u03b8emo) over time and builds a progressively personalized generative model of the patient. Synchronization is operationalized via two commensurable directional surprisal metrics: SR\u2192P=\u2212lnQR(s*), the room\u2019s surprisal at the patient\u2019s true state, and SP\u2192R=\u2212lnP(oR\u2223QP), the patient\u2019s surprisal at the room\u2019s observations. A systematic ablation study across four model variants shows that room inference is the architectural component necessary to reproduce the synchronization\u2013delirium relationship: when the room infers, the association between synchronization and declared delirium is strong and stable, whereas a non-inferring room collapses to ceiling delirium rates and a weak association. \u03b8 learning and the prior-sharpening feedback do not increase the strength of this association; instead they shape the phenotypic gradient, reducing ceiling effects in vulnerable phenotypes and amplifying the separation between them. The model is presented as a computational hypothesis generator rather than a calibrated clinical predictor, and its implications for ICU design are discussed.<\/jats:p>","DOI":"10.3390\/e28060702","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:49:42Z","timestamp":1781743782000},"page":"702","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ICU Delirium as a Failure of Predictive Synchronization: A Two-Agent Active Inference Model"],"prefix":"10.3390","volume":"28","author":[{"given":"Luca M.","family":"Possati","sequence":"first","affiliation":[{"name":"Faculty of Behavioural, Management and Social Sciences, Philosophy Section, University of Twente, Drienerlolaan 5, 7522 NB Enschede, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1001\/jama.286.21.2703","article-title":"Delirium in mechanically ventilated patients","volume":"286","author":"Ely","year":"2001","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S0140-6736(13)60688-1","article-title":"Delirium in elderly people","volume":"383","author":"Inouye","year":"2014","journal-title":"Lancet"},{"key":"ref_3","unstructured":"Namjoshi, S.V. 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