{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:33:55Z","timestamp":1777858435637,"version":"3.51.4"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25wm0625322"],"award-info":[{"award-number":["JP25wm0625322"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25wm0625210"],"award-info":[{"award-number":["JP25wm0625210"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJMS2024\\u20139"],"award-info":[{"award-number":["JPMJMS2024\\u20139"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJCR25Q2"],"award-info":[{"award-number":["JPMJCR25Q2"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23KJ1293"],"award-info":[{"award-number":["23KJ1293"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neuroscience Research"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.neures.2026.105021","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T16:45:11Z","timestamp":1767804311000},"page":"105021","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Gradual proactive regulation of body state by reinforcement learning of homeostasis"],"prefix":"10.1016","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2786-0306","authenticated-orcid":false,"given":"Mana","family":"Fujiwara","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honda","family":"Naoki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.neures.2026.105021_bib1","series-title":"Design for a brain: The origin of adaptive behaviour","author":"Ashby","year":"1960"},{"key":"10.1016\/j.neures.2026.105021_bib2","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/nrn3950","article-title":"Interoceptive predictions in the brain","volume":"16","author":"Barrett","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.neures.2026.105021_bib3","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/S0006-3223(02)01546-9","article-title":"Context, ambiguity, and unlearning: sources of relapse after behavioral extinction","volume":"52","author":"Bouton","year":"2002","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.neures.2026.105021_bib4","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.biopsych.2005.12.015","article-title":"Contextual and temporal modulation of extinction: behavioral and biological mechanisms","volume":"60","author":"Bouton","year":"2006","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.neures.2026.105021_bib5","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1097\/00000441-193212000-00028","article-title":"The wisdom of the body","volume":"184","author":"Cannon","year":"1932","journal-title":"Am. J. Med. Sci."},{"key":"10.1016\/j.neures.2026.105021_bib6","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12967-019-02184-z","article-title":"Reduced heart rate variability predicts fatigue severity in individuals with chronic fatigue syndrome\/myalgic encephalomyelitis","volume":"18","author":"Escorihuela","year":"2020","journal-title":"J. Transl. Med."},{"key":"10.1016\/j.neures.2026.105021_bib7","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adg6086","article-title":"Pavlovian-conditioned opioid tolerance","volume":"9","author":"Farahbakhsh","year":"2023","journal-title":"Sci. Adv."},{"key":"10.1016\/j.neures.2026.105021_bib8","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0002-9343(97)00087-9","article-title":"Does the chronic fatigue syndrome involve the autonomic nervous system?","volume":"102","author":"Freeman","year":"1997","journal-title":"Am. J. Med."},{"key":"10.1016\/j.neures.2026.105021_bib9","doi-asserted-by":"crossref","DOI":"10.1098\/rsif.2014.1383","article-title":"Knowing one\u2019s place: a free-energy approach to pattern regulation","volume":"12","author":"Friston","year":"2015","journal-title":"J. R. Soc. Interface"},{"key":"10.1016\/j.neures.2026.105021_bib10","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s11229-007-9237-y","article-title":"Free-energy and the brain","volume":"159","author":"Friston","year":"2007","journal-title":"Synthese"},{"key":"10.1016\/j.neures.2026.105021_bib11","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/s12967-019-1935-y","article-title":"Orthostatic intolerance in chronic fatigue syndrome","volume":"17","author":"Garner","year":"2019","journal-title":"J. Transl. Med."},{"key":"10.1016\/j.neures.2026.105021_bib12","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abo5627","article-title":"Coordinated activity of a central pathway drives associative opioid analgesic tolerance","volume":"9","author":"Hou","year":"2023","journal-title":"Sci. Adv."},{"key":"10.1016\/j.neures.2026.105021_bib13","doi-asserted-by":"crossref","DOI":"10.1164\/rccm.201206-1138ED","article-title":"Trajectories of recovery and dysfunction after acute illness, with implications for clinical trial design","author":"Iwashyna","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.neures.2026.105021_bib14","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.04811","article-title":"Homeostatic reinforcement learning for integrating reward collection and physiological stability","volume":"3","author":"Keramati","year":"2014","journal-title":"Elife"},{"key":"10.1016\/j.neures.2026.105021_bib15","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1037\/rev0000046","article-title":"Cocaine addiction as a homeostatic reinforcement learning disorder","volume":"124","author":"Keramati","year":"2017","journal-title":"Psychol. Rev."},{"key":"10.1016\/j.neures.2026.105021_bib16","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/s43588-023-00439-w","article-title":"Decoding reward-curiosity conflict in decision-making from irrational behaviors","volume":"3","author":"Konaka","year":"2023","journal-title":"Nat. Comput. Sci."},{"key":"10.1016\/j.neures.2026.105021_bib17","doi-asserted-by":"crossref","DOI":"10.1126\/science.493999","article-title":"Conditioned tolerance to the hypothermic effect of ethyl alcohol","author":"Le","year":"1979","journal-title":"Science"},{"key":"10.1016\/j.neures.2026.105021_bib18","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1005099","article-title":"Uncertainty-dependent extinction of fear memory in an amygdala-mPFC neural circuit model","volume":"12","author":"Li","year":"2016","journal-title":"PLoS Comput. Biol."},{"key":"10.1016\/j.neures.2026.105021_bib19","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.3389\/fpsyg.2014.01301","article-title":"Striatal direct and indirect pathways control decision-making behavior","volume":"5","author":"Macpherson","year":"2014","journal-title":"Front. Psychol."},{"key":"10.1016\/j.neures.2026.105021_bib20","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1037\/h0077824","article-title":"Conditioning and extinction of tolerance to the hypothermic effect of ethanol in rats","volume":"94","author":"Mansfield","year":"1980","journal-title":"J. Comp. Physiol. Psychol."},{"key":"10.1016\/j.neures.2026.105021_bib21","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/BF00427791","article-title":"Response specificity of behaviorally augmented tolerance to ethanol supports a learning interpretation","volume":"79","author":"Mansfield","year":"1983","journal-title":"Psychopharmacology"},{"key":"10.1016\/j.neures.2026.105021_bib22","series-title":"in: Reference Module in Neuroscience and Biobehavioral Psychology","article-title":"Stress: Homeostasis, Rheostasis, Reactive Scope, Allostasis and Allostatic Load\u2606","author":"McEwen","year":"2017"},{"key":"10.1016\/j.neures.2026.105021_bib23","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/S0896-6273(02)01064-4","article-title":"Behavioral and neural analysis of extinction","volume":"36","author":"Myers","year":"2002","journal-title":"Neuron"},{"key":"10.1016\/j.neures.2026.105021_bib24","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1037\/0097-7403.18.2.182","article-title":"Rapid reacquisition in conditioning of the rabbit\u2019s nictitating membrane response","volume":"18","author":"Napier","year":"1992","journal-title":"J. Exp. Psychol. Anim. Behav. Process"},{"key":"10.1016\/j.neures.2026.105021_bib25","article-title":"Evidence of altered cardiac autonomic regulation in myalgic encephalomyelitis\/chronic fatigue syndrome: A systematic review and meta-analysis","volume":"98","author":"Nelson","year":"2019","journal-title":"Med. (Baltim. )"},{"key":"10.1016\/j.neures.2026.105021_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopsycho.2023.108741","article-title":"Active inference as a theory of sentient behavior","volume":"186","author":"Pezzulo","year":"2024","journal-title":"Biol. Psychol."},{"key":"10.1016\/j.neures.2026.105021_bib27","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1037\/0033-295X.98.3.390","article-title":"Homeostatic theory of drug tolerance: A general model of physiological adaptation","volume":"98","author":"Poulos","year":"1991","journal-title":"Psychol. Rev."},{"key":"10.1016\/j.neures.2026.105021_bib28","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/sj.npp.1301555","article-title":"Neural mechanisms of extinction learning and retrieval","volume":"33","author":"Quirk","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.neures.2026.105021_bib29","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1037\/a0035942","article-title":"Clarifying the roles of homeostasis and allostasis in physiological regulation","volume":"121","author":"Ramsay","year":"2014","journal-title":"Psychol. Rev."},{"key":"10.1016\/j.neures.2026.105021_bib30","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1037\/0097-7403.1.1.88","article-title":"Reinstatement of fear to an extinguished conditioned stimulus","volume":"1","author":"Rescorla","year":"1975","journal-title":"J. Exp. Psychol. Anim. Behav. Process"},{"key":"10.1016\/j.neures.2026.105021_bib31","doi-asserted-by":"crossref","DOI":"10.3109\/16066350109141767","article-title":"Pavlovian Conditioning and Drug Overdose: When Tolerance Fails","author":"Siegel","year":"2001","journal-title":"Addict. Res. Theory"},{"key":"10.1016\/j.neures.2026.105021_bib32","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/j.0963-7214.2005.00384.x","article-title":"Drug tolerance, drug addiction, and drug anticipation","volume":"14","author":"Siegel","year":"2005","journal-title":"Curr. Dir. Psychol. Sci."},{"key":"10.1016\/j.neures.2026.105021_bib33","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1177\/0963721418806510","article-title":"The psychological and neural basis of loss aversion","volume":"28","author":"Sokol-Hessner","year":"2019","journal-title":"Curr. Dir. Psychol. Sci."},{"key":"10.1016\/j.neures.2026.105021_bib34","doi-asserted-by":"crossref","first-page":"550","DOI":"10.3389\/fnhum.2016.00550","article-title":"Allostatic self-efficacy: A metacognitive theory of dyshomeostasis-induced fatigue and depression","volume":"10","author":"Stephan","year":"2016","journal-title":"Front. Hum. Neurosci."},{"key":"10.1016\/j.neures.2026.105021_bib35","series-title":"Allostasis, Homeostasis, and the Costs of Physiological Adaptation","first-page":"17","article-title":"Principles of allostasis: Optimal design, predictive regulation, pathophysiology, and rational therapeutics","author":"Sterling","year":"2004"},{"key":"10.1016\/j.neures.2026.105021_bib36","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.physbeh.2011.06.004","article-title":"Allostasis: a model of predictive regulation","volume":"106","author":"Sterling","year":"2012","journal-title":"Physiol. Behav."},{"key":"10.1016\/j.neures.2026.105021_bib37","series-title":"Handbook of Life Stress, Cognition and Health","first-page":"629","article-title":"Allostasis: A New Paradigm to Explain Arousal Pathology","author":"Sterling","year":"1988"},{"key":"10.1016\/j.neures.2026.105021_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopsycho.2022.108266","article-title":"Simulating homeostatic, allostatic and goal-directed forms of interoceptive control using active inference","volume":"169","author":"Tschantz","year":"2022","journal-title":"Biol. Psychol."},{"key":"10.1016\/j.neures.2026.105021_bib39","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2022.857009","article-title":"Computational Mechanisms of Osmoregulation: A Reinforcement Learning Model for Sodium Appetite","volume":"16","author":"Uchida","year":"2022","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.neures.2026.105021_bib40","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13613-022-01038-0","article-title":"Chronic critical illness and post-intensive care syndrome: from pathophysiology to clinical challenges","volume":"12","author":"Voiriot","year":"2022","journal-title":"Ann. Intensive Care"},{"key":"10.1016\/j.neures.2026.105021_bib41","doi-asserted-by":"crossref","first-page":"4156","DOI":"10.1038\/s41467-021-24068-x","article-title":"Central amygdala micro-circuits mediate fear extinction","volume":"12","author":"Whittle","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.neures.2026.105021_bib42","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1006122","article-title":"Identification of animal behavioral strategies by inverse reinforcement learning","volume":"14","author":"Yamaguchi","year":"2018","journal-title":"PLoS Comput. Biol."},{"key":"10.1016\/j.neures.2026.105021_bib43","doi-asserted-by":"crossref","DOI":"10.1093\/pnasnexus\/pgae540","article-title":"Modeling long-term nutritional behaviors using deep homeostatic reinforcement learning","volume":"3","author":"Yoshida","year":"2024","journal-title":"PNAS Nexus"}],"container-title":["Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168010226000088?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168010226000088?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:13:05Z","timestamp":1777507985000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168010226000088"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":43,"alternative-id":["S0168010226000088"],"URL":"https:\/\/doi.org\/10.1016\/j.neures.2026.105021","relation":{},"ISSN":["0168-0102"],"issn-type":[{"value":"0168-0102","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Gradual proactive regulation of body state by reinforcement learning of homeostasis","name":"articletitle","label":"Article Title"},{"value":"Neuroscience Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.neures.2026.105021","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"105021"}}