{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T06:22:06Z","timestamp":1793946126593,"version":"4.8.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000027","name":"U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01AA029137"],"award-info":[{"award-number":["R01AA029137"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2013-07434"],"award-info":[{"award-number":["2013-07434"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","award":["Clinical Scholar Grant"],"award-info":[{"award-number":["Clinical Scholar Grant"]}],"id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["668863-SyBil-AA"],"award-info":[{"award-number":["668863-SyBil-AA"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neuropsychopharmacol."],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The Neural Craving Signature (NCS), a machine learning derived neuroimaging biomarker, differentiates individuals with from those without substance use disorders (SUDs), but has not been evaluated for predicting clinical outcomes. In a secondary analysis, we applied the NCS to fMRI cue-reactivity data from 39 participants in a published, negative RCT of repetitive transcranial magnetic stimulation (rTMS) for Alcohol Use Disorder (AUD). NCS scores predicted craving [Penn Alcohol Craving Scale (PACS)], both at the time of fMRI (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.29, 95%, CI [0.27, 0.73], t(36)\u2009=\u20093.86,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0005), and during repeated study visits (\u03b2\u2009=\u20094.6, SE\u2009=\u20095.3, t(39.15)\u2009=\u20091.17,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). NCS also classified AUD severity (Addiction Severity Index, ASI, alcohol subscale\u2014\u03b2\u2009=\u20090.14,\n                    <jats:italic>SE<\/jats:italic>\n                    \u2009=\u20090.04,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0016,\n                    <jats:italic>R\u00b2<\/jats:italic>\n                    \u2009=\u20090.24; Alcohol Use Disorder Identification Test, AUDIT, \u03b2\u2009=\u20095.32,\n                    <jats:italic>SE<\/jats:italic>\n                    \u2009=\u20091.46,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0025,\n                    <jats:italic>R\u00b2<\/jats:italic>\n                    \u2009=\u20090.22). Most importantly, the NCS predicted alcohol use, both measured by self-reported percent heavy drinking days (HDD%; \u03b2\u2009=\u200910.19, SE\u2009=\u20094.46, t(38.23)\u2009=\u20092.28,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.028) and the biomarker phosphatidyl ethanol (PEth; \u03b2\u2009=\u20090.32, SE\u2009=\u20090.15, t(37.10)\u2009=\u20092.15,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.038). Participants with below median NCS scores had a lower likelihood of relapse than those above median (Cox regression\u2014HR\u2009=\u20090.35, 95% CI [0.16\u20130.80],\n                    <jats:italic>p\u2009<\/jats:italic>\n                    =\u20090.013). NCS identified relapse cases with an area under the curve of 0.79 (SE\u2009=\u20090.077, z\u2009=\u20093.8,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0001), achieving 66.7% sensitivity and 77.8% specificity at optimal NCS score. These findings provide initial support for the NCS as a predictor of clinical outcomes in AUD.\n                  <\/jats:p>","DOI":"10.1038\/s41386-026-02369-3","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T12:52:37Z","timestamp":1772023957000},"page":"1237-1244","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The neurobiological cravings signature (NCS) as a predictive neuromarker of clinical outcomes in alcohol use disorder"],"prefix":"10.1038","volume":"51","author":[{"given":"Andreas","family":"L\u00f6fberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Harp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5972-0913","authenticated-orcid":false,"given":"Irene","family":"Perini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1107-5644","authenticated-orcid":false,"given":"Robin","family":"K\u00e4mpe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Karlsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Pietrzak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9893-1046","authenticated-orcid":false,"given":"Hedy","family":"Kober","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Heilig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"2369_CR1","unstructured":"World Health Organization. (World Health Organization, Geneva, 2024)."},{"key":"2369_CR2","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/S0140-6736(19)31775-1","volume":"394","author":"AF Carvalho","year":"2019","unstructured":"Carvalho AF, Heilig M, Perez A, Probst C, Rehm J. Alcohol use disorders. Lancet. 2019;394:781\u201392.","journal-title":"Lancet"},{"key":"2369_CR3","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1001\/jama.2014.3628","volume":"311","author":"DE Jonas","year":"2014","unstructured":"Jonas DE, Amick HR, Feltner C, Bobashev G, Thomas K, Wines R, et al. Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis. JAMA. 2014;311:1889\u2013900.","journal-title":"JAMA"},{"key":"2369_CR4","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1021\/acschemneuro.5b00067","volume":"6","author":"ND Volkow","year":"2015","unstructured":"Volkow ND, Koob G, Baler R. Biomarkers in substance use disorders. ACS Chem Neurosci. 2015;6:522\u20135.","journal-title":"ACS Chem Neurosci"},{"key":"2369_CR5","doi-asserted-by":"crossref","unstructured":"Ekhtiari H, Sangchooli A, Carmichael O, Moeller FG, O\u2019Donnell P, Oquendo M, et al. Neuroimaging biomarkers in addiction. Nat Mental Health 2024;2:1498\u2013517.","DOI":"10.1038\/s44220-024-00334-x"},{"key":"2369_CR6","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1007\/s00702-024-02766-2","volume":"131","author":"NR Harp","year":"2024","unstructured":"Harp NR, Wager TD, Kober H. Neuromarkers in addiction: definitions, development strategies, and recent advances. J Neural Transm. 2024;131:509\u201323.","journal-title":"J Neural Transm"},{"key":"2369_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1046\/j.1359-6357.2003.00586.x","volume":"98","author":"FK Del Boca","year":"2003","unstructured":"Del Boca FK, Darkes J. The validity of self-reports of alcohol consumption: state of the science and challenges for research. Addiction. 2003;98:1\u201312.","journal-title":"Addiction"},{"key":"2369_CR8","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.tics.2009.06.004","volume":"13","author":"RZ Goldstein","year":"2009","unstructured":"Goldstein RZ, Craig AD, Bechara A, Garavan H, Childress AR, Paulus MP, et al. The neurocircuitry of impaired insight in drug addiction. Trends Cogn Sci. 2009;13:372\u201380.","journal-title":"Trends Cogn Sci"},{"key":"2369_CR9","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1038\/nrn3119","volume":"12","author":"RZ Goldstein","year":"2011","unstructured":"Goldstein RZ, Volkow ND. Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Nat Rev Neurosci. 2011;12:652\u201369.","journal-title":"Nat Rev Neurosci"},{"key":"2369_CR10","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1001\/jamapsychiatry.2022.1240","volume":"79","author":"N Vafaie","year":"2022","unstructured":"Vafaie N, Kober H. Association of drug cues and craving with drug use and relapse: a systematic review and meta-analysis. JAMA psychiatry. 2022;79:641\u201350.","journal-title":"JAMA psychiatry"},{"key":"2369_CR11","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1046\/j.1360-0443.1999.9433273.x","volume":"94","author":"BL Carter","year":"1999","unstructured":"Carter BL, Tiffany ST. Meta-analysis of cue-reactivity in addiction research. Addiction. 1999;94:327\u201340.","journal-title":"Addiction"},{"key":"2369_CR12","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1038\/s41596-021-00649-4","volume":"17","author":"H Ekhtiari","year":"2022","unstructured":"Ekhtiari H, Zare-Bidoky M, Sangchooli A, Janes AC, Kaufman MJ, Oliver JA, et al. A methodological checklist for fMRI drug cue reactivity studies: development and expert consensus. Nat Protoc. 2022;17:567\u201395.","journal-title":"Nat Protoc"},{"key":"2369_CR13","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1001\/jamapsychiatry.2023.5483","volume":"81","author":"ACRI","year":"2024","unstructured":"ACRI. Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity: A Systematic Review. JAMA Psychiatry. 2024;81:414\u201325.","journal-title":"JAMA Psychiatry"},{"key":"2369_CR14","unstructured":"FDA-NIH Biomarker Working Group. (ed Food and Drug Administration (US)) (Silver Spring (MD), Co-published by National Institutes of Health (US), Bethesda (MD), 2016)."},{"key":"2369_CR15","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/nn.2303","volume":"12","author":"N Kriegeskorte","year":"2009","unstructured":"Kriegeskorte N, Simmons WK, Bellgowan PS, Baker CI. Circular analysis in systems neuroscience: the dangers of double dipping. Nat Neurosci. 2009;12:535\u201340.","journal-title":"Nat Neurosci"},{"key":"2369_CR16","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1056\/NEJMoa1204471","volume":"368","author":"TD Wager","year":"2013","unstructured":"Wager TD, Atlas LY, Lindquist MA, Roy M, Woo C-W, Kross E. An fMRI-based neurologic signature of physical pain. N Engl J Med. 2013;368:1388\u201397.","journal-title":"N Engl J Med"},{"key":"2369_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2023.119990","volume":"271","author":"SP Speer","year":"2023","unstructured":"Speer SP, Keysers C, Barrios JC, Teurlings CJ, Smidts A, Boksem MA, et al. A multivariate brain signature for reward. NeuroImage. 2023;271:119990.","journal-title":"NeuroImage"},{"key":"2369_CR18","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1038\/s41593-022-01082-w","volume":"25","author":"M \u010ceko","year":"2022","unstructured":"\u010ceko M, Kragel PA, Woo C-W, L\u00f3pez-Sol\u00e0 M, Wager TD. Common and stimulus-type-specific brain representations of negative affect. Nat Neurosci. 2022;25:760\u201370.","journal-title":"Nat Neurosci"},{"key":"2369_CR19","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/s41593-022-01228-w","volume":"26","author":"L Koban","year":"2023","unstructured":"Koban L, Wager TD, Kober H. A neuromarker for drug and food craving distinguishes drug users from non-users. Nat Neurosci. 2023;26:316\u201325.","journal-title":"Nat Neurosci"},{"key":"2369_CR20","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2024.1254341","volume":"11","author":"CE Wiers","year":"2024","unstructured":"Wiers CE, Manza P, Wang G-J, Volkow ND. Ketogenic diet reduces a neurobiological craving signature in inpatients with alcohol use disorder. Front Nutr. 2024;11:1254341.","journal-title":"Front Nutr"},{"key":"2369_CR21","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1038\/s41386-019-0565-7","volume":"45","author":"I Perini","year":"2020","unstructured":"Perini I, Kampe R, Arlestig T, Karlsson H, Lofberg A, Pietrzak M, et al. Repetitive transcranial magnetic stimulation targeting the insular cortex for reduction of heavy drinking in treatment-seeking alcohol-dependent subjects: a randomized controlled trial. Neuropsychopharmacology. 2020;45:842\u201350.","journal-title":"Neuropsychopharmacology"},{"key":"2369_CR22","unstructured":"APA. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. 4th ed. American Psychiatric Association (APA): Washington, DC; 1994."},{"key":"2369_CR23","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.drugalcdep.2013.02.036","volume":"132","author":"WM Compton","year":"2013","unstructured":"Compton WM, Dawson DA, Goldstein RB, Grant BF. Crosswalk between DSM-IV dependence and DSM-5 substance use disorders for opioids, cannabis, cocaine and alcohol. Drug Alcohol Depend. 2013;132:387\u201390.","journal-title":"Drug Alcohol Depend"},{"key":"2369_CR24","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1111\/j.1532-5415.1992.tb01992.x","volume":"40","author":"TN Tombaugh","year":"1992","unstructured":"Tombaugh TN, McIntyre NJ. The mini-mental state examination: a comprehensive review. J Am Geriatr Soc. 1992;40:922\u201335.","journal-title":"J Am Geriatr Soc"},{"key":"2369_CR25","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1111\/j.1360-0443.1993.tb02093.x","volume":"88","author":"JB Saunders","year":"1993","unstructured":"Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption\u2013II. Addiction. 1993;88:791\u2013804.","journal-title":"Addiction"},{"key":"2369_CR26","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1037\/0021-843X.91.3.199","volume":"91","author":"HA Skinner","year":"1982","unstructured":"Skinner HA, Allen BA. Alcohol dependence syndrome: measurement and validation. J Abnorm Psychol. 1982;91:199\u2013209.","journal-title":"J Abnorm Psychol"},{"key":"2369_CR27","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1080\/10550490500528316","volume":"15","author":"AT McLellan","year":"2006","unstructured":"McLellan AT, Cacciola JC, Alterman AI, Rikoon SH, Carise D. The Addiction Severity Index at 25: origins, contributions and transitions. Am J Addict. 2006;15:113\u201324.","journal-title":"Am J Addict"},{"key":"2369_CR28","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1046\/j.1360-0443.2000.95341912.x","volume":"95","author":"CS Rosen","year":"2000","unstructured":"Rosen CS, Henson BR, Finney JW, Moos RH. Consistency of self-administered and interview-based Addiction Severity Index composite scores. Addiction. 2000;95:419\u201325.","journal-title":"Addiction"},{"key":"2369_CR29","unstructured":"First MB. Structured clinical interview for DSM-IV axis I disorders. Biometrics Research Department. 1997."},{"key":"2369_CR30","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1111\/j.1600-0447.1994.tb01480.x","volume":"89","author":"P Svanborg","year":"1994","unstructured":"Svanborg P, Asberg M. A new self-rating scale for depression and anxiety states based on the Comprehensive Psychopathological Rating Scale. Acta Psychiatr Scand. 1994;89:21\u20138.","journal-title":"Acta Psychiatr Scand"},{"key":"2369_CR31","doi-asserted-by":"crossref","unstructured":"Guy W. ECDEU assessment manual for psychopharmacology. US Department of Health, Education, and Welfare, Public Health Service 1976.","DOI":"10.1037\/e591322011-001"},{"key":"2369_CR32","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1006\/nimg.2002.1179","volume":"17","author":"AR Hariri","year":"2002","unstructured":"Hariri AR, Tessitore A, Mattay VS, Fera F, Weinberger DR. The amygdala response to emotional stimuli: a comparison of faces and scenes. Neuroimage. 2002;17:317\u201323.","journal-title":"Neuroimage"},{"key":"2369_CR33","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.addbeh.2009.09.006","volume":"35","author":"C Pulido","year":"2010","unstructured":"Pulido C, Brown SA, Cummins K, Paulus MP, Tapert SF. Alcohol cue reactivity task development. Addictive Behav. 2010;35:84\u201390.","journal-title":"Addictive Behav"},{"key":"2369_CR34","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/s41592-018-0235-4","volume":"16","author":"O Esteban","year":"2019","unstructured":"Esteban O, Markiewicz CJ, Blair RW, Moodie CA, Isik AI, Erramuzpe A, et al. fMRIPrep: a robust preprocessing pipeline for functional MRI. Nat methods. 2019;16:111\u201316.","journal-title":"Nat methods"},{"key":"2369_CR35","doi-asserted-by":"crossref","unstructured":"Gorgolewski K, Burns CD, Madison C, Clark D, Halchenko YO, Waskom ML, et al. Nipype: a flexible, lightweight and extensible neuroimaging data processing framework in python. Front Neuroinformatics. 2011;5:13.","DOI":"10.3389\/fninf.2011.00013"},{"key":"2369_CR36","unstructured":"Socialstyrelsen. (2024)."},{"key":"2369_CR37","doi-asserted-by":"crossref","unstructured":"Sobell LC. Timeline follow-back in Measuring alcohol consumption. New Jersey: Humana Press. 1992:41-72.","DOI":"10.1007\/978-1-4612-0357-5_3"},{"key":"2369_CR38","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1111\/j.1530-0277.1999.tb04349.x","volume":"23","author":"BA Flannery","year":"1999","unstructured":"Flannery BA, Volpicelli JR, Pettinati HM. Psychometric properties of the Penn Alcohol Craving Scale. Alcohol Clin Exp Res. 1999;23:1289\u201395.","journal-title":"Alcohol Clin Exp Res"},{"key":"2369_CR39","doi-asserted-by":"publisher","first-page":"2060","DOI":"10.1111\/acer.12851","volume":"39","author":"FM Wurst","year":"2015","unstructured":"Wurst FM, Thon N, Yegles M, Schr\u00fcck A, Preuss UW, Weinmann W. Ethanol metabolites: their role in the assessment of alcohol intake. Alcohol: Clin Exp Res. 2015;39:2060\u201372.","journal-title":"Alcohol: Clin Exp Res"},{"key":"2369_CR40","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1093\/alcalc\/agad015","volume":"58","author":"RB Skr\u00e5stad","year":"2023","unstructured":"Skr\u00e5stad RB, Aamo TO, Andreassen TN, Havnen H, Hveem K, Krokstad S, et al. Quantifying alcohol consumption in the general population by analysing phosphatidylethanol concentrations in whole blood: results from 24,574 subjects included in the HUNT4 study. Alcohol Alcohol. 2023;58:258\u201365.","journal-title":"Alcohol Alcohol"},{"key":"2369_CR41","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.3758\/s13428-016-0809-y","volume":"49","author":"SG Luke","year":"2017","unstructured":"Luke SG. Evaluating significance in linear mixed-effects models in R. Behav Res Methods. 2017;49:1494\u2013502.","journal-title":"Behav Res Methods"},{"key":"2369_CR42","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1097\/JTO.0b013e3181ec173d","volume":"5","author":"JN Mandrekar","year":"2010","unstructured":"Mandrekar JN. Receiver operating characteristic curve in diagnostic test assessment. J Thorac Oncol. 2010;5:1315\u201316.","journal-title":"J Thorac Oncol"},{"key":"2369_CR43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2017\/3762651","volume":"2017","author":"I Unal","year":"2017","unstructured":"Unal I. Defining an optimal cut-point value in ROC analysis: an alternative approach. Comput Math Methods Med. 2017;2017:1\u201314.","journal-title":"Comput Math Methods Med"},{"key":"2369_CR44","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-022-01676-9","volume":"22","author":"F Barto\u0161","year":"2022","unstructured":"Barto\u0161 F, Aust F, Haaf JM. Informed Bayesian survival analysis. BMC Med Res Methodol. 2022;22:238.","journal-title":"BMC Med Res Methodol"},{"key":"2369_CR45","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1001\/jamapsychiatry.2013.762","volume":"70","author":"D Seo","year":"2013","unstructured":"Seo D, Lacadie CM, Tuit K, Hong K-I, Constable RT, Sinha R. Disrupted ventromedial prefrontal function, alcohol craving, and subsequent relapse risk. JAMA psychiatry. 2013;70:727\u201339.","journal-title":"JAMA psychiatry"},{"key":"2369_CR46","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1007\/s00406-021-01259-7","volume":"271","author":"P Bach","year":"2021","unstructured":"Bach P, Weil G, Pompili E, Hoffmann S, Hermann D, Vollst\u00e4dt-Klein S, et al. FMRI-based prediction of naltrexone response in alcohol use disorder: a replication study. Eur Arch Psychiatry Clin Neurosci. 2021;271:915\u201327.","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"2369_CR47","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1111\/j.1467-9280.2007.01882.x","volume":"18","author":"MS Fritz","year":"2007","unstructured":"Fritz MS, Mackinnon DP. Required sample size to detect the mediated effect. Psychol Sci. 2007;18:233\u20139.","journal-title":"Psychol Sci"},{"key":"2369_CR48","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-018-0578-7","volume":"18","author":"L Lapointe-Shaw","year":"2018","unstructured":"Lapointe-Shaw L, Bouck Z, Howell NA, Lange T, Orchanian-Cheff A, Austin PC, et al. Mediation analysis with a time-to-event outcome: a review of use and reporting in healthcare research. BMC Med Res Methodol. 2018;18:118.","journal-title":"BMC Med Res Methodol"},{"key":"2369_CR49","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1126\/science.278.5335.45","volume":"278","author":"AI Leshner","year":"1997","unstructured":"Leshner AI. Addiction is a brain disease, and it matters. Science. 1997;278:45\u201347.","journal-title":"Science"},{"key":"2369_CR50","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1038\/s41386-020-00950-y","volume":"46","author":"M Heilig","year":"2021","unstructured":"Heilig M, MacKillop J, Martinez D, Rehm J, Leggio L, Vanderschuren LJ. Addiction as a brain disease revised: why it still matters, and the need for consilience. Neuropsychopharmacology. 2021;46:1715\u201323.","journal-title":"Neuropsychopharmacology"},{"key":"2369_CR51","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/bs.pbr.2015.07.023","volume":"224","author":"M Heilig","year":"2016","unstructured":"Heilig M, Leggio L. What the alcohol doctor ordered from the neuroscientist: Theragnostic biomarkers for personalized treatments. Prog Brain Res. 2016;224:401\u201318.","journal-title":"Prog Brain Res"},{"key":"2369_CR52","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.neubiorev.2021.02.006","volume":"124","author":"DG Nielsen","year":"2021","unstructured":"Nielsen DG, Andersen K, Nielsen AS, Juhl C, Mellentin A. Consistency between self-reported alcohol consumption and biological markers among patients with alcohol use disorder\u2013a systematic review. Neurosci Biobehav Rev. 2021;124:370\u201385.","journal-title":"Neurosci Biobehav Rev"},{"key":"2369_CR53","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1037\/0033-295X.97.2.147","volume":"97","author":"ST Tiffany","year":"1990","unstructured":"Tiffany ST. A cognitive model of drug urges and drug-use behavior: role of automatic and nonautomatic processes. Psychol Rev. 1990;97:147\u201368.","journal-title":"Psychol Rev"},{"key":"2369_CR54","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1037\/0893-164X.15.2.159","volume":"15","author":"AI Alterman","year":"2001","unstructured":"Alterman AI, Bovasso GB, Cacciola JS, McDermott PA. A comparison of the predictive validity of four sets of baseline ASI summary indices. Psychol Addict Behav. 2001;15:159\u201362.","journal-title":"Psychol Addict Behav"},{"key":"2369_CR55","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1037\/0893-164X.15.3.171","volume":"15","author":"G Bovasso","year":"2001","unstructured":"Bovasso G, Alterman AI, Cacciola J, Cook TG. Predictive validity of the addiction severity index\u2019s composite scores in the assessment of 2-year outcomes in a methadone maintenance population. Psychol Addict Behav. 2001;15:171\u201376.","journal-title":"Psychol Addict Behav"},{"key":"2369_CR56","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1111\/j.1530-0277.2002.tb02534.x","volume":"26","author":"DF Reinert","year":"2002","unstructured":"Reinert DF, Allen JP. The alcohol use disorders identification test (AUDIT): a review of recent research. Alcohol: Clin Exp Res. 2002;26:272\u201379.","journal-title":"Alcohol: Clin Exp Res"},{"key":"2369_CR57","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.jneumeth.2015.01.001","volume":"242","author":"I Reinhard","year":"2015","unstructured":"Reinhard I, Lemenager T, Fauth-B\u00fchler M, Hermann D, Hoffmann S, Heinz A, et al. A comparison of region-of-interest measures for extracting whole brain data using survival analysis in alcoholism as an example. J Neurosci methods. 2015;242:58\u201364.","journal-title":"J Neurosci methods"},{"key":"2369_CR58","doi-asserted-by":"publisher","first-page":"e1002180","DOI":"10.1371\/journal.pbio.1002180","volume":"13","author":"LJ Chang","year":"2015","unstructured":"Chang LJ, Gianaros PJ, Manuck SB, Krishnan A, Wager TD. A sensitive and specific neural signature for picture-induced negative affect. PLoS Biol. 2015;13:e1002180.","journal-title":"PLoS Biol"},{"key":"2369_CR59","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1093\/cercor\/bhaa290","volume":"31","author":"W Zhao","year":"2021","unstructured":"Zhao W, Palmer CE, Thompson WK, Chaarani B, Garavan HP, Casey B, et al. Individual differences in cognitive performance are better predicted by global rather than localized BOLD activity patterns across the cortex. Cereb Cortex. 2021;31:1478\u201388.","journal-title":"Cereb Cortex"},{"key":"2369_CR60","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12717","volume":"25","author":"P Bach","year":"2020","unstructured":"Bach P, Weil G, Pompili E, Hoffmann S, Hermann D, Vollst\u00e4dt-Klein S, et al. Incubation of neural alcohol cue reactivity after withdrawal and its blockade by naltrexone. Addict Biol. 2020;25:e12717.","journal-title":"Addict Biol"}],"container-title":["Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02369-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02369-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02369-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T16:02:53Z","timestamp":1779811373000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02369-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":60,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["2369"],"URL":"https:\/\/doi.org\/10.1038\/s41386-026-02369-3","relation":{},"ISSN":["0893-133X","1740-634X"],"issn-type":[{"value":"0893-133X","type":"print"},{"value":"1740-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]},"assertion":[{"value":"26 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 January 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"MH has received speaker\u2019s fees, research funding and\/ or scientific advisory board compensation from Lundbeck, Aelis Farma, Indivior, Brainsway Technologies, Accord Pharma, Nordic Drugs, Idorsia and Janssen Pharmaceuticals; and is a Senior Editor at Neuropsychopharmacology. The remaining authors have nothing to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}