{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:02:39Z","timestamp":1790089359583,"version":"4.0.1"},"reference-count":6,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000026","name":"U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA000641"],"award-info":[{"award-number":["DA000641"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neuropsychopharmacol."],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Functional magnetic resonance imaging (fMRI) is widely used to investigate brain function. However, interpretation of the blood oxygen level-dependent (BOLD) signal is complicated by the fact that it reflects both neuronal activity and vascular physiology. This problem is especially relevant in neuropsychopharmacology research because pharmacological and psychiatric effects on brain function are often accompanied by physiological shifts. Here, we discuss recent evidence for an approach to disentangling neuronal and physiological components of the BOLD signal that enhances the interpretability and clinical utility of fMRI. Converging findings suggest that the systemic low-frequency oscillation (sLFO), a major component of the global signal, indexes cardiovascular manifestations of arousal rather than neuronal function. As such, retaining the sLFO in fMRI data can substantially distort functional connectivity estimates, leading to the misinterpretation of physiological fluctuations in arousal as neuronal effects. At the same time, the sLFO itself tracks physiological arousal level, behavioral performance, drug craving, pharmacological modulation, and large-scale brain network organization. Collectively, we suggest that when interpreting fMRI data, sLFO-indexed physiological arousal should both be modeled and considered separately, as extracting this signal from fMRI data provides dual benefits: a cleaner neuronal signal and a complementary index of behaviorally relevant physiology.<\/jats:p>","DOI":"10.1038\/s41386-026-02512-0","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T05:26:52Z","timestamp":1785821212000},"page":"1914-1915","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A non-neuronal fMRI signal: both a confound and an opportunity for insight"],"prefix":"10.1038","volume":"51","author":[{"given":"Amy C.","family":"Janes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2562-9617","authenticated-orcid":false,"given":"Cole","family":"Korponay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianye","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5832-5279","authenticated-orcid":false,"given":"Blaise B.","family":"Frederick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"2512_CR1","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1038\/s41593-025-01945-y","volume":"28","author":"T Bolt","year":"2025","unstructured":"Bolt T, Wang S, Nomi JS, Setton R, Gold BP, Frederick BB, et al. Autonomic physiological coupling of the global fMRI signal. Nat Neurosci. 2025;28:1327\u201335.","journal-title":"Nat Neurosci"},{"key":"2512_CR2","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1038\/s41562-024-01908-6","volume":"8","author":"C Korponay","year":"2024","unstructured":"Korponay C, Janes AC, Frederick BB. Brain-wide functional connectivity artifactually inflates throughout functional magnetic resonance imaging scans. Nat Hum Behav. 2024;8:1568\u201380.","journal-title":"Nat Hum Behav"},{"key":"2512_CR3","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.70561","volume":"47","author":"T Zhai","year":"2026","unstructured":"Zhai T, Gu H, Holton A, Chang E, Frederick BB, Ross TJ, et al. Benchmarking fMRI denoising pipelines. Hum Brain Mapp. 2026;47:e70561.","journal-title":"Hum Brain Mapp"},{"key":"2512_CR4","doi-asserted-by":"publisher","first-page":"106004","DOI":"10.1117\/1.JBO.17.10.106004","volume":"17","author":"Y Tong","year":"2012","unstructured":"Tong Y, Hocke LM, Licata SC, Frederick B. Low-frequency oscillations measured in the periphery with near-infrared spectroscopy are strongly correlated with blood oxygen level-dependent functional magnetic resonance imaging signals. J Biomed Opt. 2012;17:106004.","journal-title":"J Biomed Opt"},{"key":"2512_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpsgos.2026.100720","volume":"6","author":"JC Welsh","year":"2026","unstructured":"Welsh JC, Korponay C, Zhai T, Hill JA, Salmeron BJ, Frederick BB, et al. Functional magnetic resonance imaging signal typically viewed as \u201cnoise\u201d has clinical relevance in psychiatry. Biol Psychiatry Glob Open Sci. 2026;6:100720.","journal-title":"Biol Psychiatry Glob Open Sci"},{"key":"2512_CR6","doi-asserted-by":"publisher","unstructured":"Hill JA, Zhai T, Korponay C, Welsh JC, Salmeron BJ, Ross TJ, et al. Physiological arousal as a predominant source of individual differences in functional brain networks. Commun Biol. 2026. https:\/\/doi.org\/10.1038\/s42003-026-10624-y.","DOI":"10.1038\/s42003-026-10624-y"}],"container-title":["Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02512-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02512-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02512-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:23:31Z","timestamp":1790087011000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02512-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":6,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["2512"],"URL":"https:\/\/doi.org\/10.1038\/s41386-026-02512-0","relation":{},"ISSN":["0893-133X","1740-634X"],"issn-type":[{"value":"0893-133X","type":"print"},{"value":"1740-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]},"assertion":[{"value":"27 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 July 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}