{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:19:18Z","timestamp":1785410358479,"version":"3.56.0"},"posted":{"date-parts":[[2025,3,31]]},"group-title":"Neuroscience","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"award":["Z1A-DA000587"],"award-info":[{"award-number":["Z1A-DA000587"]}],"id":[{"id":"https:\/\/ror.org\/00fq5cm18","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>The orbitofrontal cortex (OFC) is critical to identifying task structure and to generalizing appropriately across task states with similar underlying or hidden causes. This capability is at the heart of OFCs proposed role in a network responsible for cognitive mapping, and its loss can explain many deficits associated with OFC damage or inactivation. Substance use disorder is defined by behaviors that share much in common with these deficits, such as an inability to modify learned behaviors in the face of new information about undesired consequences. One explanation for this similarity would be if addictive drugs impacted the ability of OFC to recognize underlying similarities, hidden states, that allow information learned in one setting to be used in another. To explore this possibility, we trained rats to self-administer cocaine and then recorded single unit activity in lateral OFC as these rats performed in an odor sequence task consisting of unique and shared positions. In well-trained controls, we observed chance decoding of sequence at shared positions and near chance decoding even at unique positions, reflecting the irrelevance of distinguishing these positions in the task. By contrast, in cocaine-experienced rats, decoding remained significantly elevated, particularly at the positions that had superficial sensory differences that were collapsed in controls across learning. These neural differences were accompanied by increases in behavioral variability at these positions. A tensor component analysis showed that this effect of reduced generalization after cocaine use also extended across positions in the sequences. These results show that prior cocaine use disrupts the normal identification of hidden states by OFC.<\/jats:p>","DOI":"10.1101\/2025.03.28.645972","type":"posted-content","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T02:38:04Z","timestamp":1743475084000},"source":"Crossref","is-referenced-by-count":0,"title":["Prior cocaine use disrupts identification of hidden states by single units and neural ensembles in orbitofrontal cortex"],"prefix":"10.64898","author":[{"given":"Wenhui","family":"Zong","sequence":"first","affiliation":[{"name":"National Institute on Drug Abuse, Intramural Research Program, Baltimore MD 21224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren E.","family":"Mueller","sequence":"additional","affiliation":[{"name":"National Institute on Drug Abuse, Intramural Research Program, Baltimore MD 21224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhewei","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Institute on Drug Abuse, Intramural Research Program, Baltimore MD 21224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfeng","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University & Chinese Institute of Brain Research, Beijing 100875, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8180-0701","authenticated-orcid":false,"given":"Geoffrey","family":"Schoenbaum","sequence":"additional","affiliation":[{"name":"National Institute on Drug Abuse, Intramural Research Program, Baltimore MD 21224"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041201365015000_2025.03.28.645972v4.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2024.10.005"},{"key":"2026041201365015000_2025.03.28.645972v4.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-024-00893-z"},{"key":"2026041201365015000_2025.03.28.645972v4.3","doi-asserted-by":"publisher","DOI":"10.1038\/S41593-022-01149-8"},{"key":"2026041201365015000_2025.03.28.645972v4.4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0134-15.2015"},{"key":"2026041201365015000_2025.03.28.645972v4.5","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.22177"},{"key":"2026041201365015000_2025.03.28.645972v4.6","doi-asserted-by":"crossref","first-page":"5283","DOI":"10.1038\/s41467-024-49652-9","article-title":"Hippocampal and orbitofrontal neurons contribute to complementary aspects of associative structure","volume":"15","year":"2024","journal-title":"Nature Communications"},{"key":"2026041201365015000_2025.03.28.645972v4.7","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEURON.2016.08.019"},{"key":"2026041201365015000_2025.03.28.645972v4.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.11.005"},{"key":"2026041201365015000_2025.03.28.645972v4.9","doi-asserted-by":"publisher","DOI":"10.1037\/bne0000463"},{"key":"2026041201365015000_2025.03.28.645972v4.10","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005483"},{"key":"2026041201365015000_2025.03.28.645972v4.11","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1038\/s41386-024-01858-7","article-title":"The selective D3-receptor antagonist VK4-116 reverses loss of insight caused by self-administration of cocaine in rats","volume":"49","year":"2024","journal-title":"Neuropsychopharmacology"},{"key":"2026041201365015000_2025.03.28.645972v4.12","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-007-1051-1"},{"key":"2026041201365015000_2025.03.28.645972v4.13","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf3700"},{"key":"2026041201365015000_2025.03.28.645972v4.14","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4305-05.2006"},{"key":"2026041201365015000_2025.03.28.645972v4.15","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhh216"},{"key":"2026041201365015000_2025.03.28.645972v4.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(01)00355-4"},{"key":"2026041201365015000_2025.03.28.645972v4.17","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2017.159"},{"key":"2026041201365015000_2025.03.28.645972v4.18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061355"},{"key":"2026041201365015000_2025.03.28.645972v4.19","doi-asserted-by":"publisher","DOI":"10.1037\/a0029534"},{"key":"2026041201365015000_2025.03.28.645972v4.20","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.121.3.543"},{"key":"2026041201365015000_2025.03.28.645972v4.21","doi-asserted-by":"publisher","DOI":"10.1101\/lm.534807"},{"key":"2026041201365015000_2025.03.28.645972v4.22","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-013-3222-6"},{"key":"2026041201365015000_2025.03.28.645972v4.23","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3763"},{"key":"2026041201365015000_2025.03.28.645972v4.24","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr138"},{"key":"2026041201365015000_2025.03.28.645972v4.25","doi-asserted-by":"publisher","DOI":"10.1038\/nn1931"},{"key":"2026041201365015000_2025.03.28.645972v4.26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2012.08211.x"},{"key":"2026041201365015000_2025.03.28.645972v4.27","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhh136"},{"key":"2026041201365015000_2025.03.28.645972v4.28","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhw312"},{"key":"2026041201365015000_2025.03.28.645972v4.29","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1755-20.2020"},{"key":"2026041201365015000_2025.03.28.645972v4.30","doi-asserted-by":"crossref","first-page":"5223","DOI":"10.1016\/j.cub.2024.09.064","article-title":"Prior cocaine use diminishes encoding of latent information by orbitofrontal, but not medial, prefrontal ensembles","volume":"34","year":"2024","journal-title":"Current Biology"},{"key":"2026041201365015000_2025.03.28.645972v4.31","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.neuron.2018.11.025","article-title":"Expectancy-related changes in dopaminergic error signals are impaired by cocaine self-administration","volume":"101","year":"2019","journal-title":"Neuron"},{"key":"2026041201365015000_2025.03.28.645972v4.32","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2777-14.2015"},{"key":"2026041201365015000_2025.03.28.645972v4.33","doi-asserted-by":"crossref","unstructured":"Konova, A.B. , Ceceli, A.O. , Horga, G. , Moeller, S.J. , Alia-Klein, N. , and Goldstein, R.Z. (pending - 2022). Reduced neural encoding of utility prediction errors in cocaine addiction. Neuron.","DOI":"10.1016\/j.neuron.2023.09.015"},{"key":"2026041201365015000_2025.03.28.645972v4.34","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3014"},{"key":"2026041201365015000_2025.03.28.645972v4.35","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/10.3.318"},{"key":"2026041201365015000_2025.03.28.645972v4.36","doi-asserted-by":"crossref","first-page":"100143","DOI":"10.1016\/j.addicn.2024.100143","article-title":"The utility of a latent-cause framework for understanding addiction phenomena","volume":"10","year":"2024","journal-title":"Addiction Neuroscience"},{"key":"2026041201365015000_2025.03.28.645972v4.37","doi-asserted-by":"publisher","DOI":"10.1037\/bne0000451"},{"key":"2026041201365015000_2025.03.28.645972v4.38","doi-asserted-by":"publisher","DOI":"10.1038\/35084134"},{"key":"2026041201365015000_2025.03.28.645972v4.39","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200108080-00060"},{"key":"2026041201365015000_2025.03.28.645972v4.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2019.03.011"},{"key":"2026041201365015000_2025.03.28.645972v4.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.05.015"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.03.28.645972","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:12:18Z","timestamp":1782277938000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.03.28.645972"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,31]]},"references-count":41,"URL":"https:\/\/doi.org\/10.1101\/2025.03.28.645972","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.7554\/eLife.109883","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.109883.3","asserted-by":"object"}],"has-version":[{"id-type":"doi","id":"10.7554\/eLife.109883.2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.109883.1","asserted-by":"object"}]},"subject":[],"published":{"date-parts":[[2025,3,31]]},"subtype":"preprint"}}